WO2002077037A2 - Biaryl monomers and dendritic polymers derived therefrom - Google Patents

Abstract

Globular dendritic polymers having functional groups oriented on the exterior and interior surfaces of the polymer are disclosed (Fig 1). The inventive polymers are composed of biaryl monomer units having at least two substituents. One of the substituents orients toward the exterior surface of the globular dendritic polymer and the other substituent orients toward the interior surface of the polymer. Each substituent can be selected to have an affinity for a solvent having a particular solvent property, such as, for example, hydrophobicity, hydrophilicity, solvent polarity, pH, ionic strength. When the polymer is dissolved in a solvent having a solvent having a solvent parameter for which a substituent has an affinity, that substituent orients toward the external surface of the polymer. When one substituent is hydrophilic and one substituent is hydrophobic, the polymers are facially amphiphilic. The dendeitic polymers are useful for encapsulation and controlled release of phamraceutical and agrochemical agents, catalysis, and targeted drug delivery.

Description

BIARYL MONOMERS AND DENDRITIC POLYMERS DERIVED

THEREFROM

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to United States Provisional

Application for Patent Serial No. 60/277,887 filed on March 22, 2001. FIELD OF THE INVENTION

This invention relates generally to biaryl monomers and hyperbranched polymers, dendrons, and dendrimers derived therefrom. More particularly this invention relates to biaryl monomers that are capable of bonding to three other monomers and hyperbranched polymers, dendrons and dendrimers derived therefrom. BACKGROUND OF THE INVENTION

The concave nature of the binding sites in enzymes and nucleic acids has long inspired chemists to design new host materials with recognition sites at their concave face (see e.g., Cram, Nature, 1992, 356:39-36, and Breslow et al , Chem. Rev. , 1998, 98:1997-2011, the relevant disclosures of which are incorporated herein by reference). The globular architecture of dendritic polymers such as dendrons and dendrimers presents a number of possibilities for such recognition sites (see e.g., Newkome, Moorefield, and

Vδgtle, Dendrimers and Dendrons Concepts, Syntheses, Applications, Wiley- NCH, Weinheim, Germany, 2001, hereinafter referred to as Newkome et al., the relevant disclosures of which are incorporated herein by reference). In fact, Smith et al. , Chem. Eur. J. , 1998, 4:1353-1361, incorporated herein by reference, have referred to dendrimers as possible globular protein mimics.

A promising approach to gaining control over the orientation and spacial disposition of functional groups within a dendritic polymer involves rendering the polymer amphiphilic (see, e.g., Newkome et al. , at pages 59-68; 234-236; and 415-416, incorporated herein by reference). In reported examples of amphiphilic dendritic polymers, however, the amphiphilicity is the result of the difference in hydrophobicity between the macromolecular backbone and the peripheral moieties, or between different peripheral moieties. The functional groups are not directed toward the interiors of the globular dendritic polymer. In fact, functionalization of dendrons and dendrimers is often only practically achievable at the peripheral monomers of the dendritic structure.

Functionality has been introduced into the interior of a dendrimer by functionalization of the core monomer, as for example, utilizing a porphyrin group as the core monomer to allow sequestration of a metal ion in the core of a dendrimer (see e.g., Newkome et al. at pages 475-476, incorporated herein by reference). However, such an approach allows only limited control over the functional environment within the globular interior of a dendrimer. An advantage of globular dendritic materials is that these molecules can act as nanoscale containers. Since dendrimers may be synthesized in globular sizes in the range of about 2 to about 15 nm in diameter, these materials are useful as host molecules for a number of guest substances. For example, in controlled drug release a non-polar drug can be encapsulated within these globular containers. The drugs can then be slowly released by diffusion.

Similarly, in the synthesis of nanoparticles, the size of the nanoparticle can be directly controlled by controlling the size of the globular dendrimer host in which the particle is assembled.

To fully realize dendritic structures as potential biological mimics, however, requires the ability to incorporate functional structural elements into the dendrimer molecular structure in a controlled and selective manner. A useful feature to incorporate into a dendrimer structure would be a functionalized interior region. It would be desirable to be able to selectively incorporate either hydrophobic or hydrophilic functionality, for example, on the exterior surface or interior region of a globular dendrimer. Such selective functionalization allows, for example, tailoring of the dendritic molecular structure to accommodate guest molecules in the interior of a dendrimer or binding of the exterior of a dendrimer to various substrates.

It would be highly desirable to construct a dendritic polymer in which the functional environment of the globular interior^' and exterior surfaces of the polymer could be predictably controlled and manipulated by environmental factors such as solvent polarity, pH, solution ionic strength, and the like. The currently known amphiphilic dendritic polymers fall short of this goal. Generally, these materials adopt either globular or open structures, depending on the solvent environment in which they are found. These materials, for example, generally do not have the capability of forming globular structures in which the interior functionality can be changed from hydrophobic (i.e. , lipophilic) to hydrophilic within a single dendritic molecular structure.

There is an ongoing need therefore, for a globular dendritic material in which the functionality of the interior and exterior surfaces of the globular dendrimer can be controlled and manipulated in a predictable fashion. The dendritic polymers of the present invention fulfill this need.

SUMMARY OF THE INVENTION

A dendritic polymer of the present invention comprises at least one biaryl monomer unit having at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group. The first aryl group of the biaryl monomer defines a plane, and the second aryl group includes a first functional substituent and a second functional substituent. The first and second functional substituents are bonded to the second aryl group such that the substituents are oriented on opposite sides of the plane defined by the first aryl group. When the first functional substituent is hydrophilic and the second functional substituent is hydrophobic the hydrophilic and hydrophobic substituents are oriented on opposite sides of the plane defined by the first aryl group. In addition, the first aryl group has first and second branching substituents, each adapted for bonding to another monomer unit, and at least one of the first and second aryl group has a third branching substituent adapted for bonding to a third monomer unit.

In solution, the dendritic polymers of the present invention adopt a globular conformation having an exterior surface and an interior surface. The bi- planar nature of the biaryl monomer units of the polymer necessarily orients the first and second functional substituents opposite surfaces of the globular polymer. When the first functional substituent of a monomer unit is directed to the exterior surface, the second functional substituent is directed toward the interior surface. The first and second functional substituents can be selected such that specific groups will orient to specific surfaces of the polymer. For example, if the first functional substituent is hydrophilic and the second functional substituent is hydrophobic, the hydrophobic substituents will orient toward the interior surface of the polymer when the polymer is dissolved in a hydrophilic solvent such as water.

The ability of a preferred embodiment of the dendritic polymer of the present invention to spontaneously orient functional groups according to the hydrophobic or hydrophilic nature of the solvent (i.e., the solvent polarity) in which the dendritic polymer is dissolved provides distinct advantages and improvements over conventional amphiphilic dendritic materials. Facially amphiphilic dendritic polymers have a functionalized interior region capable of selectively encapsulating guest materials and capable of releasing such materials by inversion of the dendritic polymer if the solvent polarity or the functional group hydrophilicity/hydrophobicity changes. The functionality of the interior region of conventional amphiphilic dendrimers is not generally affected by the solvent polarity. The chemical nature and identity of the hydrophilic and hydrophobic substituents of the dendritic polymers of the invention can be selected to achieve a desired functional environment on the exterior surface of the globular polymer, the interior cavity of the polymer, or both. The dendritic polymers of the present invention are useful, for example, as agents for targeted delivery of pharmaceuticals; for encapsulation and controlled release of drugs and other chemical active agents such as pesticides; as solubilizing agents fbr pharmaceuticals, agrochemicals and dyes, as carriers for fluorescent imaging agents, and as demulsifiers. BRIEF DESCRIPTION OF THE DRAWINGS

In the Drawings, FIGURE 1 diagrammatically illustrates the bi- planar nature of the biaryl monomers of the present invention and the resulting facial orientation of functional groups on the monomer;

FIGURE 2 depicts functional group orientation of a conventional amphiphilic dendritic material (A) and two possible facial orientations of functional groups in the facially amphiphilic dendritic polymers of the invention (B, and B₂); FIGURE 3 depicts the manner in which biaryl monomers affect functional group orientation;

FIGURE 4 depicts d e branching pattern of a 5th generation dendron derived from AB₂ monomers; FIGURE 5 diagrammatically illustrates a method for fluorocarbon solvent-based phase transfer catalysis utilizing a dendritic polymer of the invention; and

FIGURE 6 diagrammatically illustrates a method for pH controlled delivery and release of a pharmaceutical agent into a tumor cell. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The dendritic polymers of the present invention are derived from functionalized biaryl AB₂ monomers. These functionalized biaryl monomers are useful for the preparation dendritic polymers (e.g., hyperbranched polymers, dendrons and dendrimers) that have functional substituents oriented on the exterior and interior surfaces of the dendritic polymer when the polymer adopts a globular conformation in solution. The inventive polymers can be rendered facially amphiphilic when the biaryl monomer includes both hydrophilic and hydrophobic functional groups. These facially amphiphilic dendritic polymers have both hydrophilic and hydrophobic functional groups that are facially orientable and can be distributed throughout the dendritic structure. Dendritic polymers naturally adopt globular conformations in solution, having an external globular surface exposed to the solvent, and an interior region that can be substantially free of solvent. Globular dendritic polymers can be thought of as monomolecular micelles. Because the aryl groups in biaryl compounds, such as biphenyl, tend to orient themselves in substantially perpendicular planes, functional groups such as hydrophilic and hydrophobic groups on one aryl group can be oriented above and below the plane of the other aryl group of the biaryl, as illustrated in FIG. 1.

In solution, the functional groups of the amphiphilic biaryl-based dendritic polymers of the present invention orient themselves with substantially all of one type of functional group (e.g. , hydrophilic or hydrophobic) on the globular exterior and the other type of functional group in the interior, depending on the hydrophilic or hydrophobic character of the solvent in which the dendritic polymer is dissolved. This orientation is due to the bi-planar nature of the biaryl monomer units, which necessarily orient functional groups in a plane perpendicular to the plane of the dendrimer backbone. For example, FIGS. 2 and 3 illustrate functional group orientation of a conventional amphiphilic dendritic polymer and a facially amphiphilic dendritic polymer of the invention. In FIG. 2, configuration A illustrates a conventional dendritic material having a hydrophilic macromolecular backbone and hydrophobic end capping groups, whereas configurations _λ and B₂ illustrate two possible orientations of a facially amphiphilic biaryl dendritic polymer of the present invention. Orientation B_x is typical of the functional group orientation of the facially amphiphilic dendritic polymer in a hydrophilic solvent such as water, wherein the hydrophilic functional groups are oriented on the external globular surface of the polymer, whereas the hydrophobic functional groups are oriented toward the interior of the globular macromolecule. Likewise, orientation B₂ illustrates the functional group orientation of the same dendritic polymer of the present invention dissolved in a hydrophobic solvent such as a hydrocarbon, wherein the hydrophobic groups are oriented on the globular exterior and the hydrophilic groups are oriented on the interior. FIG. 3 illustrates the manner in which the bi-planar nature of the biaryl monomer units of the inventive dendritic polymers necessarily orients the hydrophobic and hydrophilic substituents to opposite surfaces of the polymer. The functional groups can be oriented above and below the plane of the backbone aryl groups. Like functional groups tend to orient on the same face of the polymer. In a hydrophilic solvent, the natural tendency of dendritic materials to fold in on themselves to form globular structures in solution leads to a globular dendritic polymer with hydrophilic substituents distributed over the exterior surface of the polymer and hydrophobic substituents lining the interior of the polymer. As used herein, the term "dendritic polymer" and grammatical variations thereof refers to hyperbranched polymers, dendrons and dendrimers, including such hyperbranched polymers, dendrons and dendrimers that are bound to a solid support such as polystyrene resins, and like materials.

The term "hyperbranched polymer" and grammatical variations thereof, refers to a polymer derived, at least in part, from a single polymerization reaction of monomers capable of bonding to three or more other monomers, which polymerization results in a high degree of branch points within the polymer. Hyperbranched polymers are typically poly disperse materials.

The term "dendron" and grammatical variations thereof, is used herein to refer to oligomeric and polymeric materials substantially entirely composed of monomers having three or more functional groups capable of bonding to other monomers. Dendrons are typically prepared in a convergent fashion, utilizing several individual chemical reactions, to afford substantially monodisperse oligomers or polymers. Dendrons generally can be described as macromolecules that originate at a single core monomer unit having two or more points of connectivity available for addition of other monomers. Another multifunctional monomer is bound to each connection point of the core monomer, such that each additional monomer has two or more connection points available for further reaction. The resulting macromolecule is branched substantially at each subsequent monomer unit, such that at each successive generation or tier of monomers the number of monomer units increases geometrically according to the degree of connectivity of the monomer units. FIG. 4 illustrates an example of the branching pattern of a dendron derived from an AB₂ monomer (e.g. , a monomer that has two points of connectivity available at each successive tier or generatibn of monomers). In FIG. 4, the number of monomers doubles in each successive tier (labeled 1, 2, 3, etc.). Thus by generation 5 there are 63 total monomer units in the dendron (including the core monomer). By the 6th generation, there are a total of 127 monomer units in such a dendron. In the case of an AB₃ monomer, for example, each successive tier of monomers would triple in its number of monomers units. As used herein, the term "dendrimer" refers to a polymer composed of a plurality of dendrons attached to a core molecule. Typically, dendrimers are composed of two, three, or four dendron segments attached to a central core monomer, although more are possible. For example, a dendrimer composed of three 6th generation, AB₂ -derived dendron units attached to a trivalent core monomer would have 382 total monomer units (127 x 3 + 1).

Monomers and polymers of the present invention that have acidic substituents such as C(=O)OH, SO₃H, PO₃H₂, and like substituents also include alkali metal, alkaline earth metal, and ammonium salts of the acidic substituents. Monomers and polymers of the present invention that have basic substituents such as amino groups, nitrogen-heterocyclic groups, and like substituents also include organic acid and mineral acid of the basic substituents. A dendritic polymer of the present invention comprises at least one biaryl monomer unit having at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group. The first aryl group of the biaryl monomer defines a plane, and the second aryl group includes a first functional substituent and a second functional substituent. Biaryl compounds naturally adopt a bi-planar conformation, with one aryl group defining a plane and the other aryl group oriented so as to roughly bisect the plane of the first aryl group. The substituents are bonded to the second aryl group such that the first and second functional substituents are oriented on opposite sides of the plane defined by the first aryl group, as illustrated in FIG. 1, for example. In addition, the first aryl group has first and second branching substituents, each adapted for bonding to another monomer unit and at least one of the first and second aryl group has a third branching substituent adapted for bonding to a third monomer unit.

As used herein in relation to the first and second aryl groups of the biaryl monomers and monomer units in dendritic polymers of the present invention, the term aryl includes C₆ - C₂₅ aromatic hydrocarbon groups such as phenyl, naphthyl, anthracenyl, triphenylenyl, phenanthrenyl, pyrenyl, and the like; and C₃ - C₉ oxygen, sulfur and nitrogen heteroaromatic groups such as a furan, an imidazole, a pyrrole, a thiophene, a thiazole, an azole, an oxazole, a pyridine, a pyrazine, a pyrimidine, an indole, a benzofuran, a benzothiophene, a benzothiazole, a benzoxazole, a quinoline, an isoquinoline, and like heterocyclic groups. Preferably, the aryl groups are phenyl or naphthyl groups. More preferably, at least one of the aryl groups is a phenyl group, e.g., the biaryl is a biphenyl or a phenylnaphthyl compound. Most preferably, both aryl groups of the biaryl are phenyl groups, e.g., the biaryl is a biphenyl.

The dendritic polymers of the present invention can be hyperbranched polymers, dendrons, or dendrimers. Hyperbranched polymer embodiments of the dendritic polymers of the present invention can be prepared by a polymerization of biaryl monomers having reactive branching substituents. Such hyperbranched polymers can be made in a single polymerization reaction and are typically polydisperse polymers, consisting of a large number of macromolecular structures of varying degrees of polymerization and varying degrees of branching. Because of the relatively simple manufacturing processes used to prepare hyperbranched polymers, these materials can be economically feasible for use in applications requiring low-cost materials. Synthetic strategies for the production of hyperbranched polymers are well known in the polymer art, and are extensively discussed in chapters 3 and 4 and 6, pages 51 - 190 and 331-

394, of Newkome et al. , the relevant disclosures of which are incorporated herein by reference.

Reactive functional groups capable of participating in polymerization reactions to form hyperbranched polymers include, without being limited to, acids, acid halides, amines, alcohols, haloalkyl groups, sulfonyl halides, and like functional groups that are capable of participating in condensation reactions to form ester, amide, ether, or sulfonamide bonds, for example.

Preferably, the dendritic polymers of the present invention are prepared by a convergent manufacturing strategy, to produce dendrons and dendrimers. Convergent methodologies for the synthesis of dendrons and dendrimers are extensively discussed in chapter 5 of Newkome et al. , the relevant disclosures of which are incorporated herein by reference. Further illustration of such methods as applied to the synthesis of facially amphiphilic dendrons and dendrimers is provided below in the experimental methods section.

Convergent synthetic methods require a plurality of individual synthetic reactions to produce a single polymeric material. One distinct advantage of convergent synthetic methods is that the dendritic polymers obtained by such methods can be substantially monodisperse, consisting essentially of a single chemical entity of well defined molecular structure. Dendrons and dendrimers derived from convergent syntheses can be ideally suited for pharmaceutical applications, or other applications that require, or preferably utilize substantially pure, monodisperse materials.

The dendritic polymers of the present invention can be homopolymers, consisting essentially of monomer units having a single molecular structure, or the inventive polymers can be copolymers consisting of monomer units having a plurality of molecular structures. In one preferred embodiment the facially amphiphilic dendritic polymers of the present invention are homopolymers.

A preferred dendritic polymer of the present invention comprises at least one biaryl monomer unit having the following structure (I):

wherein

A¹ and A² are each independently phenyl or naphthyl;

X¹, X², Y¹, and Y² are each independently OH, O, NHR¹, NR\ SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², SO₂, E^ E'L², P(L²)₂,

E³R\ or E⁴R⁴; D is C(=O) or C(R^!)(R²);

Z is OH, O, NHR¹, NR¹-, SH, S, a covalent bond, CI, Br, I, or OSO₂-R⁵;

Z² is CI, Br, I, or OSO₂-R⁵;

E¹ is CH₂ or CF₂;

E² is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O); E³ is CHR⁷, CF₂, or CFR⁷;

E⁴ is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O); L¹ is H, C_rC₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl;

L² is C₄-C₂₀ alkyl, phenyl, -C^ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl;

R¹ and R² are each independently H or C_rC₂₀ alkyl;

R³ is OH, NH_2ι C(=O)OH, -SO₃H, or PO₃R⁷H;

R⁴ is H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxy lie acid-substituted

C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted Cι_C₁₀ alkyl, a phosphonic acid-substituted C_rCι₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C,-C₁₀ alkyl, or a trialkylammonium-substituted

C_rC₁₀ alkyl;

R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃;

R⁶ is H, C_rC₂₀ alkyl, or C_rC₂₀ perfluoroalkyl;

R⁷ is H or C_rC₃ alkyl; R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; x is an integer having a value in the range of 0 to about 20; with the proviso that: when X¹ is OH * O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y¹ and Y² are

E'V, E²L², P(L²)₂, E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y² is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X¹ and X² are E V, E²L², P(L²)₂, E³R³ or E R⁴; when A¹ is phenyl, A² is in the 1 position of the phenyl ring, X¹ is in the 2 or 3 position of the phenyl ring, and X² is in the 5 or 6 position of the phenyl ring; when A¹ is naphthyl, A² is in the 1 position of the naphthyl ring, X¹ is in the 2 or 3 position of the naphthyl ring, and X² is in the 6 or 7 position of the naphthyl ring; when A² is phenyl, A¹ is in the 1 position of the phenyl ring, Y¹ is in the 2 or 3 position of the phenyl ring, and Y² is in the 5 or 6 position of the phenyl ring; and when A² is naphthyl, A¹ is in the 1 or 8 position of the naphthyl ring, Y¹ is in the 2 or 3 position of the naphthyl ring, and Y² is in the 6 or 7 position of the naphthyl ring.

In a particularly preferred embodiment of the polymer, when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y² is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is E^lV, E²L², or P(L )₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; and when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E^¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂. Particularly preferred dendritic polymers of the present invention the biaryl monomer units of structure (I) can comprise any of the following structures (II), (III), (IV), (V), (VI) and (VII).

Generally, both X groups in the structures (I), (II), (III), (IN), (V), (VI) and (VII) are functional substituents, or both X groups are branching substituents. When the X groups are functional substituents, the Y groups are both branching substituents. When the X groups are branching substituents, both Y groups are functional substituents. Branching substituents include OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², and SO₂; and functional substituents include E^¹, E²L², or P(L²)₂, E³R\ and E⁴R⁴.

wherein X¹ is in the 2 or 3 position, and X² is in the 5 or 6 position; Y¹ is in the 2' or 3' position, and Y² is in the 5' or 6" position, as the positions are indicated numerically in the structure;

wherein X¹ is in the 2 or 3 position, and'X² is in the 5 or 6 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures;

wherein X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the 2' or 3' position, and Y² is in the 5' or 6' position, as the positions are indicated numerically in the structure;

X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures;. In each of structures (II), (III), (IV), (V), (VI) and (VII), the substituents X¹, X², Y¹, Y², D and Z are defined as, and have the same limitations as described for structure (I) above.

Optionally, structures (I), (II), (III), (IV), (V), (VI) and (VII) can include a third functional substituent on the aryl group bearing the first and second functional substituents. The third functional substituent can, for example, be a substrate binding substituent capable of binding to a pharmaceutical agent, agrochemical, or other useful materials. Biaryl monomers, useful for the preparation of the dendritic polymers of the present invention comprise at least one biaryl monomer unit having at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group. The first aryl group of the biaryl monomer defines a plane, and the second aryl group has a first functional substituent and a second functional substituent. The first and second functional substituents are oriented on opposite sides of the plane defined by the first aryl group in the normal, bi-planar conformation adopted by biaryl compounds. In addition, the first aryl group has first and second branching substituents, each adapted for bonding to another monomer unit and at least one of the first and second aryl group has a third branching substituent adapted for bonding to a third monomer unit.

Optionally, the second aryl group can include a third functional substituent, bound to the aryl group on the same side as the second functional substituent.

The aryl groups can be C₆ - C₂₅ aromatic hydrocarbon groups such as phenyl, naphthyl, anthracenyl, triphenylenyl, phenanthrenyl, pyrenyl, and the like; and C₃ - C₉ oxygen, sulfur and nitrogen heteroaromatic groups such as a furan, an imidazole, a pyrrole, a thiophene, a thiazole, an azole, an oxazole, a pyridine, a pyrazine, a pyrimidine, an indole, a benzofuran, a benzomiophene, a benzothiazole, a benzoxazole, a quinoline, an isoquinoline, and like heterocyclic groups. Preferably, the aryl groups are phenyl or naphthyl units. More preferably, at least one of the aryl groups is a phenyl group, e.g., the biaryl is a biphenyl or a phenylnaphthyl compound. Most preferably, both aryl groups of the biaryl are phenyl groups, e.g., the biaryl is a biphenyl.

Preferred biaryl monomers, useful for the preparation of the dendritic polymers of the present invention have the following structure (VIII):

wherein

A¹ and A² are each independently phenyl or naphthyl; X³, X⁴, Y³, and Y⁴ are each independently OH, ΝHR¹, SH, C(=O)OH,

C(=O)Z², SO₃H, SO₂Z², E'L¹, E L², P(L²)₂, E³R³, or E⁴R⁴;

D is C(=O) or C(R¹)(R²);

Z* is OH, ΝHR¹, SH, CI, Br, I, or OSO₂-R⁵;

Z² is CI, Br, I, or OSO₂-R⁵; E¹ is CH₂ or CF₂;

E² is ΝR⁶, O, S, Ν(R⁶)C(=O), OC(=O) or SC(=O);

E³ is CHR⁷, CF₂, or CFR⁷;

E⁴ is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O);

L¹ is H, C_x-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl;

L² is C₄-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl; R¹ and R² are each independently H or C_rC₂₀ alkyl;

R³ is OH, NH_2ι C(=O)OH, SO₃H, or PO₃R⁷H;

R⁴ is H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰;

(CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C^C^ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C,-C₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl;

R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃; R⁶ is H, C_rC₂₀ alkyl, or C_rC₂₀ perfluoroalkyl; R⁷ is H or C_rC₃ alkyl;

R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; x is an integer having a value in the range of 0 to about 20; with the proviso that: when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X²is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y¹ and Y² are E^lL\ E²L², P(L²)₂, E³R³ or E⁴R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X¹ and X² are E^lV, E²L², P(L²)₂, E³R³ or E⁴R⁴; when A¹ is phenyl, A² is in the 1 position of the phenyl ring, X³ is in the 2 or 3 position of the phenyl ring, and X⁴ is in the 5 or 6 position of the phenyl ring; when A¹ is naphthyl, A² is in the 1 position of the naphthyl ring, X³ is in the 2 or 3 position of the naphthyl ring, and X⁴ is in the 6 or 7 position of the naphthyl ring ; when A² is phenyl, A¹ is in the 1 position of the phenyl ring, Y³ is in me 2 or 3 position of the phenyl ring, and Y⁴ is in the 5 or 6 position of the phenyl ring; and when A² is naphthyl, A¹ is in the 1 or 8 position of the naphthyl ring, Y³ is in the 2 or 3 position of the naphthyl ring, and Y⁴ is in the 6 or 7 position of the naphthyl ring.

In a particularly preferred embodiment of the monomers of structure (VIII), when X³ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, SO₂Z², X⁴ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, SO₂Z², one of Y³ and Y⁴ is

E^¹, E²L², or P(L²)₂ , and one of Y³ and Y⁴ is E³R³ or E⁴R⁴; when Y³ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, SO₂Z², Y⁴is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, SO₂Z², one of X³ and X⁴ is E'L¹, E²L², or P(L²)₂, and one of X³ and X⁴ is E³R³ or E⁴R⁴; and when one of X³ and X⁴ is E³R³ or E⁴R⁴, one of X³ and X⁴ is also E^]L\ E²L², or P(L²)₂, and Y³ and Y⁴ are each independently OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, SO₂Z²;

Particularly preferred biaryl monomers of the present invention comprise biaryl monomer units having any of the following structures (IX), (X), (XI), (XII), (XIII) and (XIV):

wherein X³ is in the 2 or 3 position, and X⁴ is in the 5 or 6 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 5' or 6' position, as the positions are indicated numerically in the structure;

wherein X³ is in the 2 or 3 position, and X⁴ is in the 5 or 6 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 6' or 7' position, as the positions are indicated numerically in the structures;

wherein X³ is in the 2 or 3 position, and X⁴ is in the 6 or 7 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 5' or 6' position, as the positions are indicated numerically in the structure;

wherein X³ is in the 2 or 3 position, and X⁴ is in the 6 or 7 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 6' or 7' position, as the positions are indicated numerically in the structures; and in each of structures (IX), (X), (XI), (XII), (XIII) and (XIV), the substituents X³, X⁴, Y³, Y⁴, D and Z* are defined as, and have the same limitations as described for structure (Nffl) above.

Generally, both X groups in the structures (I), (II), (III), (IV), (V), (VI) and (VII) are functional substituents, or both X groups are branching substituents. When the X groups are functional substituents, the Y groups are both branching substituents. When the X groups are branching substituents, both Y groups are functional substituents. Branching substituents include OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, and SO₂Z²; and functional substituents include E Λ E²L², or P(L )₂, E³R³, and E⁴R⁴.

Optionally, structures (I), (II), (III), (IV), (V), (VI) and (VII) can include a third functional substituent on the aryl group bearing the first and second functional substituents. The third functional substituent can, for example, be a substrate binding substituent capable of binding to a pharmaceutical agent, agrochemical, or other useful materials. By way of illustration, specific biphenyl monomer-based examples f the present invention are provided below:

10

30 In one preferred embodiment of the invention, the dendritic polymer is a dendron having any of the following structures (XVI), (XVII), or (XVIII) and other dendrons and dendrimers derived therefrom.

(XVIII)

wherein, in each of structures (XVI), (XVII) and (XVIII),

D is C(=O) or CH₂;

L^w, L^x, L^γ, and L^z, at each occurrence, are each independently C₄-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl;

G^w, G^x, G^γ and G^z, at each occurrence, are each independently H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C C₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl; T¹ and T², at each occurrence, are each independently H, C_rC₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_x-C₂₀ perfluoroalkyl, C_rC₂₀ perfluoroalkyl-substituted phenyl;

(3-OR^π,5-OR¹²)-benzyl, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted Cj-C₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rCι₀ alkyl, a sulfonic acid-substituted C^C^ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted C C₁₀ alkyl, or a triall ^lammonium-substituted C_rC₁₀ alkyl;

Z is OH, NHR¹, SH, CI, Br, I, or OSO₂-R⁵; R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃; R⁶ is H, C C₂₀ alkyl, or C_rC₂₀ perfluoroalkyl; R⁷ is H or C_rC₃ alkyl; R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl;

R¹¹ and R¹² at each occurrence, are each independently H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted^' C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted -C_JQ alkyl, a phosphonic acid-substituted C_J- _Q alkyl, a trialkylammonium-substituted C_rC₁₀ alkyl, C_rC₂₀ alkyl, phenyl, C C₂₀ alkyl-substituted phenyl, benzyl, a diphenylphosphine-substituted C_rC₂₀ alkyl, C_ΓC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl; and x is an integer having a value in the range of 0 to about 20.

In another preferred embodiment of the dendrons having structures (XVI), (XVII and (XVIII), L^w, L^x , V, and L^z are each independently (CH₂CH₂O)_x-CH₃ or carboxylic acid-substituted C_rC₂₀ alkyl; G , G^x, G^γ, and G^z are each independently C_rC₂₀ alkyl; each of T¹ and T² is (3-OL^x,5-OG^x)-benzyl; D is CH₂; Z is OH or Br; and x is an integer in the range of about 1 to about 20. Such dendrons are exemplified by compounds 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, and 29 described below.

The dendritic polymers of the present invention are useful in a variety of applications including pH controlled targeted delivery of pharmaceutical agents, encapsulation of hydrophilic and hydrophobic pharmaceutical and agrochemical agents, controlled release of pharmaceutical, agrochemical and like active agents, phase transfer and other catalytic processes, as solubilizing agents for pharmaceuticals, agrochemicals, and medical diagnostic agents such as fluorescent imaging agents; as cell-cell adhesion agents in tissue engineering applications, as exipients for the preparation of nanoparticles, as demulsifying agents and for encapsulation of pharmaceutical agents, agrochemicals and dyes.

A preferred embodiment of the present invention is a globular dendritic polymer having an external surface and an interior surface. The polymer is composed of a plurality of biaryl monomer units. Each of the biaryl monomer units comprises at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group. The first aryl group defines a plane. The second aryl group generally adopts a conformation that approximately bisects the plane of the first aryl group. The second aryl group includes a first substituent and a second substituent. The first substituent has an affinity for a solvent having a first solvent property and the second substituent has an affinity for a solvent having a second solvent property. The first and second substituents are bound to the second aryl group such that the first and second substituents are oriented on opposite sides of the plane defined by the first aryl group. The first aryl group has first and second branching substituents each adapted for bonding to another monomer unit; and at least one of said first and second aryl groups has a third branching substituent adapted for bonding to a third monomer unit.

When the polymer is dissolved in a solvent having the first solvent property, the first substituent is oriented to the external surface of the polymer. In contrast, when the polyrrier is dissolved in a solvent having the second solvent property the second substituent is oriented to the external surface of the polymer. Each substituent can be selected to have an affinity for a solvent having a particular solvent property, such as, for example, hydrophobicity, hydrophilicity, solvent polarity, pH, ionic strength.

The process whereby the exterior and interior surfaces exchange, due to change in pH or any other solvent parameter, is referred to herein as inversion. The term inversion also includes the adoption of a random, non- globular conformation, from a globular conformation, or the adoption of a globular conformation from a random, non-globular conformation. In one preferred embodiment, the first functional substituent is a hydrophilic substituent and second functional substituent is a hydrophobic substituent. In this embodiment, the dendritic polymer is facially amphiphilic in solution. In another preferred embodiment of the present invention, the first functional substituent is a perfluorinated substituent having an affinity for fluorocarbon solvents, and the second functional substituent can be either hydrophobic or hydrophilic in nature. Alternatively, the dendritic polymers of this embodiment can be copolymers comprising some biaryl monomer units having a hydrophobic second functional substituent and some biaryl monomer units having a hydrophilic second functional monomer. Alternatively, the second aryl group can comprise a perfluorinated first functional substituent, a hydrophilic second functional substituent and a hydrophobic third functional substituent. The second and third functional substituents both being bonded to the second aryl group on the side of the aryl group opposite the first functional substituent.

Preferred perfluorinated substituent groups include C_rC₂₀ perfluoroalkyl and

perfluoroalkyl-substituted phenyl.

In another preferred embodiment, the dendritic polymer is a copolymer having at least one biaryl monomer in which the first substituent of the polymer is a fluorocarbon substituent (fluorophilic) that provides solubility of the dendritic polymer in fluorocarbon or carbon dioxide solvents and the second substituent is hydrophobic; and at least one biaryl monomer unit in which the first substituent is fluorophilic and the second substituent is hydrophilic. The hydrophobic and the hydrophilic substituents can be directed to the interior of the polymer. The interior substituents act as solubilizing agents for polar and apolar solutes. In this manner, mutually reactive solutes can be brought together within the interior of the globular dendritic polymer, thus facilitating reactions between the solutes in a fluorocarbon or carbon dioxide solvent system. Dendritic polymers of the present invention which have biaryl monomers with a first substituent that is a C C₂₀ perfluoroalkyl hydrophobic substituent and a second substituent that is either hydrophobic or hydrophilic are useful for solubilization and phase transfer catalysis of hydrophilic and hydrophobic solutes in fluorocarbon solvents and in liquid or supercritical carbon dioxide. FIG. 5 illustrates such a use. A globular dendritic polymer has fluorophilic moieties (fluorocarbon substituents) on its exterior surface and the interior surface includes both lipophilic (Hydrophobic) and hydrophilic moieties.

The polymer is dissolved in a fluorocarbon solvent. Hydrophilic and lipophilic substrates in a fluorocarbon solvent are encapsulated by the dendritic polymer, which then facilitates chemical reactions between the substrates to for a reaction product. These polymers can be used for the destruction of chemical warfare agents by encapsulating the agent and a reagent that can react to detoxify the agent, or the polymers can be used as recyclable reaction catalysts, since the fluorocarbon solvent can be easily evaporated to recover the polymer.

In another preferred embodiment the inventive dendritic polymer is a pH sensitive globular dendritic polymer having an external surface and an interior region comprising a plurality of biaryl monomer units. Each of the biaryl monomer units comprises at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group. The first aryl group defines a plane, and the second aryl group can be oriented so as to roughly bisect the plane of the first aryl group. The second aryl group has a first substituent and a second substituent, each of the first and second substituents having hydrophilic properties at selected pH values. The first substituent is substantially more hydrophilic than the second substituent in solution having a first pH value, and the second substituent is substantially more hydrophilic than the first substituent in a solution having a second pH value. The first and second substituents are bound to the second aryl group such that they are oriented on opposite sides of the plane defined by the first aryl group. The first aryl group has first and second branching substituents that are each adapted for bonding to another monomer unit; and at least one of said first and second aryl groups has a third branching substituent adapted for bonding to a third monomer unit. When the pH sensitive globular dendritic polymer is dissolved in a solution having the first pH value, the first substituent of the second aryl group is oriented to the exterior surface of the polymer, and the second substituent is oriented in the interior surface of the polymer. In a solution having the second pH value, the polymer inverts, and the first substituent becomes oriented on the interior surface of the polymer and the second substituent is oriented on the exterior surface of the polymer. Alternatively, the polymer can adopt a random, non-globular conformation at the second pH, such that both the first and second substituents are exposed to the solvent (i.e., there is no "interior" surface, both surfaces are "exterior").

Preferably the pH sensitive dendritic polymer has a second substituent comprising a basic functional group that has a pK_b in the range of about y to about z and which is oriented to the interior surface of the polymer at a pH of about w or greater; wherein y has a numerical value in the range of about 3 to about 8, w has a numerical value at least about 0.5 greater than z; z has a numerical value least about 1 greater than y.

Preferably the basic functional group is an amino or nitrogen- heterocyclic functional group selected from primary, secondary or tertiary amino, amino-substituted O_rC₁₀ alkyl, amino-aryl, nitrogen-heterocycle, nitrogen- heterocycle-substituted C_rC₁₀ alkyl, basic amino acids and basic peptides. The first substituent preferably is selected from oligomeric polyoxyethylene groups, carboxylic acids, and acidic or neutral polypeptides. Polypeptides that bind to proteins that are overexpressed on tumor cell surfaces are particularly useful as the first substituent, in that they can aid in targeting the dendritic polymer to the tumor.

High molecular weight materials up to 800 KDa have been reported to be capable of entering tumors. Tumor vessels are leaky, and thus allow macromolecular uptake that is generally not seen in healthy tissues.

Tumors typically also lack effective lymphatic drainage, promoting the accumulation of macromolecular materials in tumors. For example, macromolecule-drug conjugates have been reported to have a higher retention rate in tumors than the free drugs. The pH sensitive dendritic polymers of the present invention as described above are useful for delivering drugs or prodrugs to tumors. The pH of a healthy cell is about 7.4, whereas the pH of the interstitial space between tumor cells is about 6.7 and the pH of the tumor cell lysosome is about 5. FIG. 6 illustrates the process of drug delivery to the tumor cell and release in the lysosome, in which the drug molecule has been covalently bound to the dendritic polymer. Cleavage of the drug from the polymer is achieved through natural enzymatic processes within the cell. Alternatively, the drug can be encapsulated without being covalently bound to the dendritic polymer. A prodrug can be utilized in place of a drug, as well.

For weak bases, the pH at which half of the base is protonated is approximately equal to the pK_b of the base. Thus, basic substituents such as amino and heterocyclic substituents, having pK_b values in the range of about 5 to about 6.5 will have less than about half of the basic functional groups protonated at a pH in the range of about of 6.7 to about 7.4. For delivery of a drug to a tumor, the amino and nitrogen-heterocyclic substituents will preferably have a pK_b in the range of about 5 to about 6.5, more preferably about 5 to about 6.

Preferably, in each monomer unit of the polymer, the first and the second aryl groups are phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group of the monomer unit; and the second functional substituent is at the 5 or 6 position relative to the first aryl group of the monomer unit.

Another aspect of the present invention is a method of delivering an anti-tumor drug to a tumor utilizing a pH sensitive dendritic polymer of the invention. A drug or prodrug is encapsulated or chemically bound to the dendritic polymer. If the drug is chemically bound to the polymer, binding can be through one of the functional substituents, or through an additional binding substituent that is attached to the second aryl group of the polymer on the same side of the aryl group as the basic substituent.

A preferred embodiment of the anti-tumor drug delivery method involves utilization of a dendritic polymer having a pH sensitive functional substituent and comprises the sequential steps of: (a) binding or encapsulating an anti-tumor drug or prodrug in the interior region of a pH sensitive dendritic polymer in an aqueous solution having a pH, w, of greater than about 7 to form a polymer-drug conjugate;

(b) preparing a solution of the polymer-drug conjugate in a pharmaceutically acceptable carrier having a pH of greater than about 7;

(c) administering the solution of the polymer-drug conjugate to a patient having a tumor so as to contact the polymer-drug conjugate with the tumor.

Upon contacting the tumor, it is believed that the polymer-drug conjugate can enter the interstitial space between the tumor cells or the lysosome of a tumor cell, and a substantial portion of amino or nitrogen-heterocyclic functional groups of the dendritic polymer are protonated upon entering the interstitial space or lysosome. Protonation of the functional groups render the basic functional group more hydrophilic than the first functional group, and the polymer inverts so that the drug released. When the drug is covalently bound to the interior surface of the polymer, release of the drug is achieved by enzymatic cleavage after the polymer has inverted, exposing the bound drug or prodrug to the enzymes present in the lysosome, as is illustrated in FIG. 6. Upon inversion of the polymer, the drug is exposed to enzymes n the lysosome that can cleave the drug from the polymer to release the drug.

Another method aspect of the present invention is a method of encapsulating a solute in the inventive dendritic polymers. A dendritic polymer having a functional substituent that has a binding affinity for a solute is utilized in this embodiment. The polymer and solute are brought into contact in a solvent in which the substituent with the binding affinity is oriented on the exterior surface of the polymer, or where the polymer adopts a random, non-globular conformation. Upon contact, the solute is bound to the substituent. When a solvent parameter is changed that causes the polymer to invert, the solute becomes encapsulated in the interior of the polymer. Each substituent can be selected to have an affinity for a solvent having a particular solvent property, such as, for example, hydrophobicity, hydrophilicity, solvent polarity, pH, ionic strength. After encapsulation, the polymer-encapsulated solute can be separated from the solution by a size dependent separation method, for example. Preferred size dependent separation methods include membrane filtration, size exclusion chromatography, and ultracentrifugation. Alternatively, the polymer- encapsulated solute can be separated by precipitation. Preferably, in each monomer unit of the polymer, the first and the second aryl groups are phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group of the monomer unit; and the second functional substituent is at the 5 or 6 position relative to the first aryl group of the monomer unit. A preferred embodiment of the encapsulation method involves utilization of a dendritic polymer having functional substituent sensitive to a solvent parameter and comprises the sequential steps of:

(a) contacting a solute in an aqueous solution with a solvent parameter sensitive dendritic polymer in a solution having a first solvent parameter value; and

(b) adjusting the solvent parameter of the solution to a second solvent parameter value to form a polymer-encapsulated solute, and optionally

(c) separating the polymer-encapsulated solute from the solution. The first substituent of the second aryl group of the polymer has a binding affinity for the solute and is substantially more hydrophilic than the second substituent in an aqueous solution having the first solvent parameter value. The second substituent is substantially more hydrophilic than the first substituent in an aqueous solution having the second solvent parameter value. The first substituent is oriented at the external surface of the dendritic polymer and binds to the solute when the polymer contacts the solute. The dendritic polymer inverts upon adjustment of the solvent parameter to the second solvent parameter value, thereby encapsulating the solute by bringing the solute and the first substituent to which the solute is bound into the interior region of the polymer. The sensitive substituent can be selected to have an affinity for a solvent having a particular solvent parameter, such as, for example, hydrophobicity, hydrophilicity, solvent polarity, pH, ionic strength. Preferably the substituent is sensitive to pH. Solutes that can be encapsulated include heavy metal ions, dyes, and recyclable catalysts, for example. A basic functional groups that has an affinity for a heavy metals include, chelating functional groups such as poly amino compounds, and chelating nitrogen-heterocyclic groups such as bipyridines. Such basic functional groups are effective when the first pH is more acidic than the second pH. Alternatively, the chelating acidic functional groups can be utilized to bind to the solute, such as poly carboxylic acids. Acidic functional groups are useful when the first pH is less acidic than the second pH.

Dendritic polymers of the present invention having first and second substituents with cell surface adhesion affinity. Preferred substituents with cell adhesion affinity include polypeptides such as such as the tripeptide Arg-Gly-Asp (also abbreviated referred to as RGD peptide), the tetrapeptide Gly-Arg-Gly-Asp (GRGD, SEQ ID NO: 1) and pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS, SEQ ID NO: 2) are useful for tissue engineering applications wherein the cell surface affinity agent causes the dendritic polymer to adhere to a tissue surface and to promote binding between different tissues, for example in transplant applications. Multiple cell adhesion substituents on both surfaces of the dendritic polymer can act as a cell-cell binding agent. Such dendritic polymers can also be used to deliver pharmaceutically active agents to specific tissue sites. Preferably, in each monomer unit of the polymer, the first and the second aryl groups are phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group of the monomer unit; and the second functional substituent is at the 5 or 6 position relative to the first aryl group of the monomer unit. Optionally, the dendritic polymers of the present invention can be bound to a solid support, such as a polystyrene resin, or like material. Suitable support resins and methods of binding dendritic polymers to supports are disclosed in Lebreton et al. , Aldrichimica Acta, 2001, 34 (3):75-83, the relevant disclosures of which are incorporated herein by reference. Resin bound dendritic polymers are particularly useful as recyclable catalysts, carriers for reagents, scavengers in parallel solution-phase synthesis, and affinity chromatography supports, for example. The following non-limiting examples illustrate the preparation of dendritic polymers of the present invention. Scheme 1 depicts the synthesis of the aryl boronic acid 5, a key intermediate for the synthesis of biphenyl or phenylnaphthyl monomers. 3,5-Dihydroxybenzoic acid 1 was reacted with three equivalents of tert-butyldimethylsilyl chloride (TBDMSC1) and imidazole in dimethylformamide (DMF) solvent to afford the trisilyl derivative 2 in about 81 % yield. Compound 2 was converted to the acid chloride 3 by reaction with thionyl chloride and catalytic trimethylamine hydrochloride in dichloromethane solvent. The dichloromethane solvent was removed in vacuo and the crude acid chloride 3 was dissolved in bromotrichloromethane and reacted with catalytic

2,2'azobisisobutyronitrile (AIBN) and 2-mercaptopyridine-N-oxide sodium salt to afford the 5-bromoresorcinol derivative 4 in about 62% overall yield from the trisilyl derivative 2. Boronic acid 5 was prepared in substantially quantitative yield by reaction of bromo compound 4 with tert-butyl lithium and trimethyl borate, followed by an aqueous work-up with saturated aqueous ammonium chloride.

Scheme 2 illustrates the synthesis of bromobenzene intermediate 10. 4-Bromo-3,5-dihydroxybenzoic acid 6 was esterified by refluxing in ethanol containing a catalytic amount of fuming sulfuric acid to afford ester 7 in about 95% yield. Ester 7 was alkylated with a sub-stoichiometric amount of butyl iodide with potassium carbonate and 18-crown-6 in acetone to afford butyl ether 8 in about 46% yield. The remaining phenolic hydroxyl group of 8 was ethoxylated with methyltriethylene glycol (TEG) tosylate 9 in the presence of potassium carbonate and 18-crown-6, in acetone, to afford bromobenzoate ester 10 in about 92% yield.

Scheme 3 depicts the preparation of benzyl bromide intermediate 14. 3 ,5-Dihydroxybenzyl alcohol 11 was reacted with a sub-stoichiometric amount of butyl iodide, following the procedure for the alkylation of 7 above to afford butyl ether 12 in about 54% yield. Compound 12 was then reacted with TEG tosylate 9, as described above for triethoxylation of compound 8, to provide benzyl alcohol 13 in about 69% yield. Compound 13 was then converted to the benzyl bromide 14 in about 82% yield by reaction with triphenylphosphine and carbon tetrabromide in tetrahydrofuran (THF) solvent.

The synthesis of a functionalized biphenyl monomer 17 is illustrated in Scheme 4. Boronic acid 4 was coupled to bromobenzoate 10 by Suzuki coupling (catalytic tetrakis-triphenylphosphine palladium and potassium phosphate in dimethoxyethane (DME) solvent) to afford biphenyl ester 15 in about 45% yield. The ethyl ester moiety of 15 was reduced with lithium borohydride in THF solvent to afford benzylic alcohol 16 in about 88% yield. Compound 16 was desilylated by treatment with tetrabutylammonium fluoride (TBAF) in THF to provide about a 91 % yield of core monomer unit 17.

The convergent synthesis of first, second, third, and fourth generation dendrons having a core monomer derived from 17 is illustrated in Scheme 5. A trimeric first generation dendron 18 was prepared by alkylation of the two phenolic hydroxyl groups of 17 with benzylbromide 14, in the presence of potassium carbonate and 18-crown-6 as base, in about 72% yield. The benzylic alcohol 18 was converted to benzylic bromide 19 by treatment with triphenylphosphine and carbon tetrabromide in THF. The crude bromide 19 was then converted to second generation dendritic alcohol 20 in about 61 % overall yield by alkylation of 17 with 2 equivalents of 19. The benzylic alcohol group of 20 was converted to a benzylic bromide by treatment with triphenylphosphine and carbon tetrabromide in THF to provide the second generation dendritic bromide 21 which was utilized without purification. Two equivalents of dendron 21 were reacted with monomer 17, by the procedure described above, to afford (15-mer) third generation dendritic alcohol 22 in about 21 % yield from 20. Following similar procedures, 22 was converted to the bromide 23. Core monomer 17 was alkylated with two equivalents of 23 to provide fourth generation dendritic alcohol 24 in about 39% yield.

Second generation dendrons 20 and 21 comprise 3 monomer units of the present invention (i.e. , a core biphenyl unit and 2 branch biphenyl units). In addition, the peripheral dendrimer units are further capped with two functionalized benzylic groups, thus these dendrons can also be referred to as septimeric (7-mer) dendrons (i.e., a core, plus two biphenyl units, plus four benzylic capping units). Third generation dendrons 22 and 23 comprise 7 biaryl monomer units of the present invention (i.e. , a core biphenyl unit, 2 first branch biphenyl units, and 4 second branch biphenyl units) as well as 8 benzylic capping units (i.e., a 15-mer). Fourth generation dendron 24 comprises 15 biaryl monomer units of the present invention (i.e., a core biphenyl unit, 2 first branch biphenyl units, 4 second branch biphenyl units and 8 third branch biphenyl units), as well as, 16 benzylic capping units for a total of 31 monomer units (i.e., a 31- mer).

Scheme 1

Scheme 2

to Scheme 3

11 12

13

14 Scheme 4

10

LiBH,

16 17 Scheme 5

Scheme 5 cont.

18-crown-6

21

Dendrons having structures (XVI), such as 20 and 21, (XVII), such as 22 and 23 and (XVIII), such as 24, are useful for the synthesis of larger dendritic polymers such as other dendrons or dendrimers. For example, reaction of 2 equivalents of compound 24 with a monomer 17 will provide a fifth generation dendron. Likewise, reaction of three equivalents of dendron 24 with a trifunctional core monomer will result in a dendrimer comprising 45 biaryl monomer units of the present invention.

Other dendritic materials prepared by the methods described above include compounds 25 - 29 below.

^■10

Second generation dendrons 28 and 29 were subsequently converted to the third and fourth generation dendrons by the methods described above for the synthesis of dendrons 22, 23, and 24. Hydrolysis of the ester groups of dendron 25 affords a dendron having a carboxylic acid-substituted alkyl substituent.

Analytical Procedures and Methods. ^JH-NMR spectra were recorded on a 400 MHz or a 500 MHz FT NMR spectrometer using the residual proton resonance of the solvent as the internal standard. Chemical shifts are reported in parts per million (ppm). When peak multiplicities are given, the following abbreviations are used: s, singlet; d, doublet; t, triplet; q, quartet; d of d, doublet of a doublet; m, multiplet; b, broad. ¹³C-NMR spectra were proton decoupled and recorded on a 400 MHz or a 500 MHz FT NMR spectrometer using the carbon signal of the deuterated solvent as the internal standard. MALDI ToF mass spectra was obtained at the Coordinated Instrumentation Facility of Tulane University or at the mass spectrometric facility at the University of Notre Dame. Flash chromatography was performed with EM Science 37-75 mm silica gel. Analytical thin layer chromatography was performed on EM Science silica plates with F-254 indicator and the visualization was accomplished by UV lamp or using the molybdic acid stain mixture. THF was distilled over Na / Ph₂CO ketyl. All other chemicals obtained from commercial sources were used without further purification, unless otherwise mentioned.

Silylation of 3,5-dihydroxybenzoic acid: 3,5-Dihydroxybenzoic acid 1 (1.00 g, 6.49 mmol) was dissolved in DMF (15 mL)/CH₂Cl₂ (15 mL) and then tert-butyldimethylsilyl chloride (3.42 g, 22.70 mmol) and imidazole (1.55 g, 22.70 mmol) were added to this solution. The resulting reaction mixture was stirred at ambient temperature under nitrogen for about 16 hours. Water was added to reaction mixture and the organic phase was separated. The aqueous layer was extracted with CH₂C1₂ ( 3 x 15 mL). The combined organic phase was dried over anhydrous MgSO₄ and the solvent was removed in vacuo. The crude product was column purified using silica gel and ethyl acetate/hexane (20:80) mixture as eluent to afford 2.61 g (81 %) of the ester 2 as a white solid. ^JH NMR

(400 MHz, CDC1₃) 6.99 (d, J=2.0 Hz, 2H), 6.36 (t, J=2.0 Hz, Η), 0.77 (s, 27H), 0.00 (s, 18H). ¹³C NMR (100 MHz, CDC1₃) 172.4, 157.0, 131.2, 118.2, 115.4, 25.9, 18.5, -4.1. GC/MS rή/z (r. i.): 496 (3, M+), 481 (3), 442 (5), 441 (20), 440 (42), 439 (100), 397 (7), 323 (4), 147 (6), 133 (6), 73 (54), 57 (11). Synthesis of bis-(O-t-butyldimethylsilyl)-5-bromoresorcinol 4:

Distilled dichloromethane (15 mL) was added to a flask containing the silyl ester 2 (10 g, 4.23 mmol) and trimethylamine hydrochloride (0.01 g, 0.08 mmol). Distilled thionyl chloride (0.38 mL, 5.08 mmol) was added dropwise to this solution under nitrogen. After the addition was complete, the reaction mixture was heated at reflux for about 3 hours. Solvent was removed in vacuo and the residue was vacuum dried (190 °C/6mm Hg). The crude acid chloride 3 thus obtained was dissolved in bromotrichloromethane (15 mL) along with 2,2 '-azobisisobutyromtrile (0.10 g, 0.63 mmol). This homogeneous solution was added dropwise to a refluxing solution of 2-mercaptopyridine N-oxide sodium salt hydrate (0.76 g, 5.08 mmol) in bromotrichloromethane (10 mL). After heating at reflux for about 2 hours, the solvent was removed in vacuo. The mixture was purified by silica gel chromatography using hexane as eluent to afford about 10 g (62% ) of the bis-(O-t-butyldimethylsilyl)-5-bromoresorcinol 4 as a yellow liquid. Η NMR (400 MHz, CDC1₃) 6.47 (s, 2H), 6.10 (s, ^XH), 0.81 (s, 18H), 0.03 (s, 12H). ¹³C NMR (100 MHz CDC1₃) 161.5, 126.7, 121.4, 115.6, 30.1, 22.6, 0.0. GC/MS m/z (r. i.): 418 (16, M+), 416 (14), 361 (55), 359 (51), 319 (66), 317 (61) 280 (23), 265 (56), 223 (13), 137 (16), 73

(100), 41 (14).

Preparation of boronic acid 5: t-Butyl lithium ( 111.12 mmol, 65.4 mL of 1.7 M pentane solution) was added to a solution of bis-(O-t-butyldimethylsilyl)-5-bromo-resorcinol 4 (31.77 mmol, 13.27 g) in THF (about 300 mL) at about -78 °C and was stirred at this temperature for about 15 minutes. Trimethyl borate (B(OMe)₃; 62 mmol, 6.9 mL) was added to the reaction mixture, which was stirred at a temperature of about -78 to about 20 °C for about 8 hours. The reaction was quenched with a saturated NH₄C1 solution and extracted with ethyl acetate. The solvent was removed in vacuo and the crude boronic acid 5 was utilized without further purification or characterization.

Synthesis of ethyl- 4-bromo-3,5-dihydroxybenzoate 7: About 8 to 10 drops of fuming sulfuric acid was added to a solution of ' 4-bromo-3,5-dihydroxybenzoic acid 6 (6.83 g, 0.Θ3 mol) in ethyl alcohol (80 mL). The mixture was refluxed overnight and subsequently was concentrated in vacuo. The crude product was dissolved in ether and washed with aqueous sodium bicarbonate aqueous solution. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated to afford about 7.28 g (95 %) of the ester 7 as a white solid. ^JH NMR (400 MHz, Acetone-d₆) 9.07 (s, 2H); 7.16 (s, 2H); 4.28 (q, J=7.2 Hz, 2H); 1.32 (t, J=7.2 Hz, 3H). ¹³C NMR (100 MHz, Acetone-d₆) 165.5, 155.5, 130.8,108.0, 103.7, 61.0, 13.9. GC/MS m/z (r. i.):

262 (47), 260 (46, M+), 234 (30), 232 (30), 217 (100), 215 (97), 190 (27), 189 (28), 188 (29), 187 (26), 108 (19), 107 (12), 79 (22), 51 (25). Synthesis of ethyl-4-bromo-3-hydroxy-5-butyloxy-benzoate 8:

Ethyl-4-bromo-3,5-dihydroxybenzoate 7 (7.05 g, 0.03 mol), potassium carbonate (3.73 g, 0.03 mol), 18-crown-6 (0.36 g, 1.35 mmol), and 1-iodobutane (2.46 mL, 0.02 mol) were all dissolved in 100 mL of acetone. The resulting mixture was refluxed under nitrogen for about 12 hours, after which the reaction mixture was concentrated in vacuo. The resulting residue was purified by silica gel chromatography using ethyl acetate/CH₂Cl₂ (5:95) to afford about 2.92 g (46%) of the butyl ether 8 as a white solid. Η NMR (400 MHz, CDC1₃) 7.32 (s, Η); 7.11 (s, 1H); 5.85 (s, Η); 4.35 (q, J=7.2 Hz, 2H); 4.07 (t, J=6.4 Hz, 2H); 1.81 (m, 2H); 1.53 (m, 2H); 1.37 (t, J=7.2 Hz, 3H); 0.98 (t, J=7.2 Hz, 3H). ¹³C

NMR (100 MHz, CDC1₃) 166.2, 156.2, 153.5, 131.2, 109.6, 105.8, 105.4, 69.4, 61.6, 31.2, 19.4, 14.4, 14.0. GC/MS m/z (r. L): 318 (36), 316 (35, M+), 262 (99), 260 (100), 234 (75), 232 (77), 218 (47), 217 (81), 216 (54), 215 (83), 190 (37), 188 (42). Synthesis of triethoxylated bromoester 10:

Ethyl-4-bromo-3-hydroxy-5-butyloxy-benzoate 8 (14.04 g, 0.04 mol), potassium carbonate (9.18 g, 0.07 mol), 18-crown-6 (0.59 g, 2.20 mmol), and triethyleneglycol monomethyl ether tosylate 9 (14.11 g, 0.04 mol) were dissolved in about 150 mL of acetone. The resulting solution was refluxed under nitrogen for about 12 hours. The reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography using ethyl acetate/CH₂Cl₂ (20:80) to afford about 18.86 (92%) of triethoxylated bromide 10 as a colorless liquid. Η NMR (400 MHz, CDC1₃) 7.18 (s, 2H); 4.34 (q, J=7.2^*Hz, 2H); 4.21 (t, J=5.2 Hz, 2H); 4.05 (t, J=6.4 Hz, 2H); 3.90 (t, J=4.8 Hz, 2H); 3.77 (m, 2H); 3.6V3.66 (m, 4H); 3.51 (m, 2H); 3.34 (s, 3H); 1.78 (m, 2H); 1.50 (m,

2H); 1.36 (t, J=6.8 Hz, 3H); 0.95 (t, J=7.2 Hz, 3H). ¹³C NMR (100 MHz, CDC1₃) 165.9, 156.5, 156.2, 130.2,107.6, 106.6, 106.4, 71.8, 71.0, 70.6, 70.4, 69.3, 69.2, 69.1, 61.3, 58.9, 31.0, 19.1, 14.3, 13.7. GC/MS m/z (r. i.): 464 (0.3), 462 (0.3, M+), 360 (1), 351 (3), 318 (19), 316 (19), 263 (17), 262 (25), 260 (24), 234 (11), 232 (11), 136 (12), 59 (100), 45 (19), 41 (14).

Synthesis of 3-hydroxy-5-butyloxy-benzyl alcohol 12: Following the procedure for the synthesis of ethyl-4-bromo-3-hydroxy-5-butyloxy-benzoate 8, 3,5-dihydroxybenzyl alcohol 11 (20.00 g, 0.14 mol) was butylated to afford about 12.20 g (54%) of 3-hydroxy-5-butoxy-benzyl alcohol 12 as a yellow liquid after silica gel chromatographic purification utilizing ethyl acetate/CH₂Cl₂ (25:75) as the eluent. Η NMR (400 MHz, CDC1₃) 6.42 (s, Η); 6.40 (s, Η); 6.34 (s, Η); 4.51 (s, 2H); 3.86 (t, J=6.4 Hz, 2H); 1.72 (m, 2H); 1.46 (m, 2H); 0.99 (t,

J=7.2 Hz, 3H). ¹³C NMR (100 MHz, CDC1₃) 160.6, 157.4, 143.0, 106.6, 105.7, 101.5, 68.0, 65.1, 31.4, 19.4, 14.1. GC/MS m/z (r. i.): 196 (57, M+), 140 (100), 122 (38), 111 (77), 94 (22), 65 (15), 41 (21).

Synthesis of 3-butyIoxy-5-triethylenoxy-benzyl alcohol 13: Following the procedure for the synthesis of compound 10,

3-hydroxy-5-butyloxy-benzyl alcohol 12 (12.20 g, 62.18 mmol) was triethoxylated to afford about 14.69 (69%) of the benzyl alcohol 13 as a colorless liquid after silica gel chromatographic purification utilizing ethyl acetate/CH₂Cl₂ (35:75) as eluent. Η NMR (400 MHz, CDC1₃) 6.45 (t, J=2.4 Hz, 2H); 6.33 (t, J=2.4 Hz, Η); 4.54 (d, J=4.8 Hz, 2H); 4.05 (t, J=5.2 Hz, 2H); 3.87 (t, J=6.4

Hz, 2H); 3.77 (t, J=4.8 Hz, 2H); 3.67 (m, 2H); 3.57^~3.62 (m, 4H); 3.48 (m, 2H); 3.31 (s, 3H); 1.69 (m, 2H); 1.41 (m, 2H); 0.90 (t, J=7.6 Hz, 3H). ¹³C NMR (100 MHz, CDC1₃) 160.7, 160.3, 143.5, 105.6, 105.2, 100.9, 72.1, 71.0, 70.9, 70.8, 69.9, 68.0, 67.7, 65.5, 59.3, 31.5, 19.5, 14.1. GC/MS m/z (r. i.): 342 (22, M+), 310 (3), 266 (5), 240 (5), 220 (7), 196 (47), 165 (38), 141 (59),

140 (43), 123 (24), 111 (27), 59 (100), 45 (25), 41 (20).

Synthesis of 3-butyloxy-5-triethylenoxy-benzylbromide 14: A solution of triphenylphosphine (PPh₃,17.89 g, 68.22 mmol) in THF (about 20 mL) was added to a stirring solution of 3-butyloxy-5-triethylenoxy-benzyl alcohol 13 (14.60 g, 42.64 mmol) and carbon tetrabromide (CBr₄, 22.63 g, 68.22 mmol) in a minimal amount of THF (about 10 mL) at a temperature of about 0 °C. The resulting mixture was allowed to warm to ambient room temperature over a period of about 10 minutes, and then was stirred for about 2 hours. Subsequently, additional triphenylphosphine (2.24 g, 8.54 mmol) and CBr₄ (2.83 g, 8.54 mmol) were added to force the reaction to completion. The mixture was stirred for another hour and separated between dichloromethane and water. The organic layer was concentrated and the residue was purified by silica gel chromatography to afford about 14.06 g (82%) of benzyl bromide 14 as an oil, after silica gel chromatographic purification utilizing ethyl acetate/CH₂Cl₂ (20:80) as eluent. Η NMR (400 MHz, CDC1₃) 6.57 (d, J = 1.6 Hz, 2H); 6.45 (t, J=2.4 Hz, Η); 4.44 (s, 2H); 4.15 (t, J=4.8 Hz, 2H); 3.98 (t, J=6.4 Hz, 2H); 3.89 (t, J=4.8 Hz, 2H); 3.77 (m, 2H); 3.69^~3.74 (m, 4H); 3.60 (m, 2H); 3.43

(s, 3H); 1.79 (m, 2H); 1.53 (m, 2H); 1.02 (t, J=7.2 Hz, 3H). ¹³C NMR (100 MHz, CDC1₃) 160.6, 160.2, 139.8,108.0, 107.6, 101.8, 72.1, 71.0, 70.9, 70.8, 69.9, 68.0, 67.7, 59.3, 33.9, 31.5, 19.4, 14.1. GC/MS m/z (r. i.): 406 (2), 404 (2, M+), 348 (1), 346 (1), 293 (9), 261 (10), 260 (10), 259 (9), 258 (9), 205 (65), 179 (71), 151 (36), 149 (39), 123 (26), 77 (15), 59 (100), 45 (33).

Suzuki coupling of boronic acid 5 and bromide 10: Tetrakis- triphenylphosphine palladium (Pd(PPh₃)₄; 3.17 mmol, 3.66 g) was added to a solution of the crude boronic acid 5 (31.77 mmol), bromoester 10 (24.8 mmol, 11.5 g) and K₃PO₄ (95.31 mmol, 20.23 g) in DME (about 200 mL) and the mixture was refluxed for about 30 hours. The solvent was removed in vacuo and the residue is purified by silica gel column chromatography using ethyl acetate/hexane (20:80) as eluent to afford about 7.55 g (42%) of the biphenyl ester 15. Η-NMR (400 MHz, CDC1₃) 7.29 (s, 2H), 6.40 (d, J=1.76 Hz, 2H), 6.29 (t, J= 1.72 Hz, Η), 4.39 (q, J=7.12 Hz, 2H), 4.08 (t, J=5.1 Hz, 2H), 3.93 (t, J=6.40 Hz, 2H), 3.68 (t, J=5.07 Hz, 2H), 3.60-3.50 (m, 8H), 3.36 (s,

3H), 1.59 (m, 2H), 1.41 (t, J=6.62 Hz, 3H), 1.29 (m, 2H), 0.98 (s, 18H), 0.85 (t, J=7.37 Hz, 3H), 0.18 (s, 12H); ¹³C-NMR (100 MHz, CDC1₃) 166.2, 156.9, 156.5, 155.4, 135.1, 130.3, 125.0, 115\7, 110.7, 106.7, 71.7, 69.1, 68.8, 68.3, 60.9, 58.8, 30.9, 25.5, 18.9, 18.0, 14.2, 13.5, -4.5. Reduction of ester 15 to alcohol 16: A solution of lithium borohydride (1.31 g, 60 mmol) in THF (150 mL) was refluxed for about 1 hour, then cooled to room temperature, and a solution of ester 15 (10 mmol, 7.21 g) in THF ( 20 mL) was added dropwise to the borohydride solution. After the addition was complete the resulting reaction mixture was refluxed for about 12 hours, after which the reaction was quenched with ethyl acetate. Solvent was removed in vacuo, the residue was treated with a saturated NH₄C1 solution and the resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic extract was dried over anhydrous MgSO₄ and the filtered organic layer was evaporated to dryness. The crude product was purified by silica gel column chromatography to afford about 5.97 g (88%) of the alcohol 16. Η-NMR (100 MHz, CDC1₃) 6.49 (s, Η), 6.46 (s, ¹H), 6.23 (d, J= 1.74 Hz, 2H), 6.09 (t, J=1.73 Hz, ¹H), 4.51 (s, 2H), 3.92 (t, J=5.1 Hz, 2H), 3.85

(t, J=6.4 Hz, 2H), 3.50-3.30 (m, 8H), 3.21 (s, 3H), 1.41(m, J= 1.94, 2H), 1.05 (m, J=7.41 Hz, 2H), 0.8 (s, 18H), 0.65 (s, 12H). ¹³C-NMR (100 MHz, CDC1₃) 157.5, 157.2, 155.6, 142.1, 136.1, 120.0, 116.5, 110.7, 104.7, 104.5, 72.0, 71.0, 70.8, 70.5, 69.6, 69.1, 68.6, 65.4, 60.6, 59.1, 31.4, 25.9, 19.3, 13.9, 18.0. EI-MS (m z) 679 (M+), 622.

Desilylation of 16: Tetrabutylammonium fluoride (TBAF; 60 mmol, 60 mL of 1.0 M THF solution) was added to the solution of alcohol 16 (7 mmol, 4.75 g) in THF (125 mL) and the resulting mixture was stirred at room temperature under nitrogen for about 20 hours. The solvent was removed in vacuo, the residue was treated with 10% aqueous HC1 (50 mL), and the product was extracted with ethyl acetate. The crude product was isolated by evaporation of the ethyl acetate and the resulting residue was column chromatographed utilizing hexane/ethyl acetate (20:80) mixture as eluent to provide about 2.87g of compound 17 in about 91 % yield. Η-NMR (400 MHz, CDC1₃) 7.4 (broad singlet, 2H), 6.21-6.53 9 (m, 5H), 4.5 (s, 2H), 4.02 (t, J=5.Ηz, 2H), 3.81(t,

J=6.4 Hz, 2H), 3.71 (t, J=5.06 Hz, 2H), 3.60-3.40 (m, 8H), 3.21 (s, 3H), 1.51 (m, 2H), 1.24 (m, 2H), 0.7 (t, J=7.33 Hz, 3H). ¹³C-NMR (100 MHz, CDC1₃) 157.2, 157.0, 156.7, 141.8, 136.0, 119.5, 110!6, 104.1, 101.6, 71.8, 71.0, 70.7, 70.3, 69.6, 68.9, 65.1, 60.7, 58.9, 31.3, 19.2, 13.9. EI-MS (m/z) 450 (M+).

General procedure A for the synthesis of dendritic hydroxymethyl compounds: A mixture of the appropriate (bromomethyl compound (1 eq.), compound 17 (0.5 eq), potassium carbonate (10-15 eq.) and 18-crown-6 (10-15 mol %) in THF is heated at reflux and stirred vigorously under nitrogen for about 36 hours. The mixture is allowed to cool and ^• evaporated to dryness under reduced pressure. The residue is treated with water and the product is extracted with ethyl acetate. The aqueous layer is extracted with ethyl acetate and combined extracts are dried over anhydrous MgSO₄ and concentrated. The crude product is purified by silica gel column chromatography.

General procedure B for the synthesis of dendritic bromomethyl compounds: To a solution of the appropriate dendritic benzyl alcohol in the minimum amount of dry THF is added PPh₃ and CBr₄. The reaction mixture is stirred at room temperature under nitrogen and is monitored by TLC. The reaction mixture is treated with water and extracted with ethyl acetate. The combined extracts are dried over MgSO₄ and the solvent are evaporated. The crude product is purified by silica gel column chromatography.

Synthesis of first generation dendron alcohol 18: A mixture of benzyl bromide compound 14 (1 eq., 5.64 g, 14 mmol), compound 17 (0.5 eq, 3.15 g, 6.99 mmol), potassium carbonate (10-15 eq.) and 18-crown-6 (10-15 mol %) in THF (about 50 mL) was heated at reflux and stirred vigorously under nitrogen for about 36 hours. The mixture is allowed to cool to room temperature and was evaporated to dryness under reduced pressure. The residue was treated with water and the product is extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic extract was dried over anhydrous MgSO₄ and concentrated. The crude product was purified by silica gel column chromatography using ethyl acetate/ 1,4-dioxane

(90:10) mixture as eluent. Dendron 18 was obtained in about 72% yield (about 5.53 g). Η-NMR (400 MHz, CDC1₃) 6.60-6.37 (m, 11H), 4.88 (s, 4H), 4.59 (s, 2H), 4.07 (t, J=5.13 Hz, 6H), 3.99 (t, J=6.41 Hz, 6H), 3.89-3.77 (m, 14H), 3.67-3.57 (m, 8H), 3.49-3.39 (m, 8H), 3.32 (s, 3H), 3.30(s, 3H), 3.24 (s, 3H), 1.72-1.69 (m,4H), 1.57-1.53 (m, 4H), 1.33-1.27 (m, 4H). 0.91 (t, 6H, J=7.42

Hz), 0.81 (t, 3H, J=7.32 Hz). ¹³C-NMR (100 MHz, CDC1₃) 160.6, 160.2, 159.2, 157.4, 157.1, 142.4, 139.2, 119.4, 110.5, 106.3, 105.8, 104.4, 101.0, 72.1, 72.0, 70.9, 70.9, 70.8, 70.7, 70.5, 70.1, 69.8, 69.7, 69.0, 68.5, 67.9, 67.6, 59.2, 59.1, 31.4, 31.3, 19.4, 19.4, 14.0, 13.9. Synthesis of first generation dendron bromide 19: PPh₃ (5.63 g,

21.45 mmol) and CBr₄ (7.11 g, 21.45 mmol) were added to a solution of the dendron alcohol 18 (14.3 mmol) in the minimum amount of dry THF (about 20 mL). The resulting reaction mixture was stirred at room temperature under nitrogen and was monitored by thin layer chromatography (TLC). Upon apparent completion of the reaction, as judged by TLC, the reaction mixture was treated with water and extracted with ethyl acetate. The combined organic extract was dried over MgSO₄ and the solvent was removed by evaporation. The crude product was purified by silica gel column chromatography using ethyl acetate/ 1,4-dioxane (80:20) mixture as eluent to afford about 11.47 g of dendron bromide 19 (69%). Η-NMR (400 MHz, CDC1₃) 6.63-6.39 (m, 11H), 4.90 (s, 4H), 4.46 (s, 2H), 4.09 (t, J=4.09 Hz, 6H), 4.02 (t, J=4.29 Hz, 6H), 3.91-3.61 (m, 14H), 3.53-3.44 (m, 8H), 3.38 (s, 3H), 3.33 (s, 3H), 3.28 (s, 3H),

1.75-1.69 (m, 4H), 1.60-1.55 (m 4H), 1.36-1.29 (m 4H), 0.94 (t, J=7.41 Hz, 6H), 0.83 (t, J=7.21 Hz, 3H). ¹³C-NMR (100 MHz, CDC1₃) 160.6, 160.2,

159.2, 157.4, 157.1, 139.5, 138.4, 135.7, 120.5, 110.3, 106.7, 106.3, 105.8, 101.1, 100.9, 72.1, 72.0, 70.9, 70.8, 70.7, 70.5, 70.1, 69.8, 69.6, 69.0, 68.6, 67.9, 67.9, 67.6, 67.2, 59.2, 59.1, 34.2, 31.4, 31.2, 19.4, 19.3, 14.0, 13.9.

Synthesis of second generation dendron alcohol 20: Dendron 20 was prepared following the procedure for the preparation of 18 above. The reaction was carried out utilizing about 1.4 mmol of 17 and about 2.8 mmol of 19. Crude dendron 20 was chromatographically purified on silica gel using ethyl acetate/ 1,4-dioxane (80:20) as eluent to afford about 2.95 g, 88% yield of dendron 20. Η-NMR (400 MHz, CDC1₃) 6.61-6.38 (m, 27H), 4.98 (s, 4H), 4.90 (s, 8H), 4.67 (s, 2H), 4.06 (t, J=5.3 Hz, 14H), 3.98 (t, J=6.1 Hz, 14H), 3.90- 3.79(m, 14H), 3.69-3.67 (m, 32H), 3.64-3.59 (m, 16H), 3.50-3.41 (m, 8H), 3.32 (s, 18H), 3.29 (s, 3H), 1.70 (m, 8H), 1.54 (m, 6H), 1.44 (m, 8H), 1.30 (m,6H), 0.92 (t, J=7.11 Hz, 18H), 0.82 (t, J=7.22 Hz, 3H). ¹³C-NMR

(100 MHz, CDC1₃) 160.3, 159.9, 159.0, 158.9, 157.1, 156.9, 156.8, 142.5,

139.3, 137.8, 136.1, 135.8, 119.6, 117.4, 115.5, 110.1, 106.1, 105.6, 105.0, 104.9, 104.6, 104.3, 100.7, 71.8, 71.9, 71.7, 70.7, 70.5, 70.4, 70.3, 70.2, 69.8, 69.6, 69.3, 68.7, 68.3, 67.6, 67.3, 65.3, 60.3, 58.9, 58.8, 31.1, 31.0, 30.8, 19.1, 14.1, 13.7, 13.7. MALDI-TOF 2635.18 (Calcd. for C₁₄₄H₂₁₀O₄₂

(M+Na+)= 2635.82). Synthesis of second generation dendron bromide 21: Following the general procedure for the preparation of 19 above, 0.531 mmol of 20 was brominated to afford about 0.6 g (42%) of bromide 21. Η-NMR (400 MHz, CDC1₃) 6.61-6.38 (m, 27H), 4.99 (s, 4H), 4.92 (s, 8H), 4.01 (t, J=5.11 Hz, 8H), 3.94 (t, J=6.6 Hz, 8H), 3.90- 3.79(m, 14H), 3.69-3.67 (m, 14H),

3.64-3.59 (m, 24H), 3.50-3.41 (m, 32H), 3.32 (s, 18H), 3.29 (s, 3H), 1.70 (m, 8H), 1.54 (m, 6H), 1.44 (m, 8H), 1.30 (m,6H), 0.92 (t, J=7.43 Hz, 18H), 0.82 (t, J=7.11 Hz, 3H). ¹³C-NMR (100 MHz, CDC1₃) 160.2, 159.8, 158.9, 158.8, 157.1, 156.8, 139.2, 137.9, 137.7, 135.7, 135.6, 120.1, 119.6, 110.1, 110.0, 106.1, 106.0, 105.5, 105.0, 104.8, 100.8, 100.6, 71.7, 71.6, 70.6, 70.4, 70.3,

70.2, 70.1, 69.7, 69.5, 69.3, 69.2, 68.7, 68.2, 67.5, 67.2, 58.8, 58.7, 46.4, 31.1, 30.9, 19.0, 13.7, 13.6. MALDI-TOF: 2698.65 (Calcd: for C₁₄₄H₂₀₉BrO₄₁ (M+Na+ =2698.08).

Synthesis of third generation dendron alcohol 22: Dendron 22 was prepared following the procedure for the preparation of 18 above. The reaction was carried out utilizing about 0.106 mmol of 17 and about 0.212 mmol of 21. Crude dendron 22 was chromatographically purified on silica gel using ethyl acetate/ 1,4-dioxane (80:20) as eluent to afford about 0.3 g, 50% yield of 22. ^αH-NMR (400 MHz, CDC1₃) 6.69-6.37 (m, 59H), 4.97 (s, 12H), 4.89 (s, 16H), 4.64 (s, 2H), 4.06 (t, J=5.11 Hz, 30H), 3.98 (t, J=6.34 Hz,

30H), 3.90- 3.79 (m, 30H), 3.69-3.67 (m, 96H), 3.64-3.59 (m, 16H), 3.50-3.41 (m, 8H), 3.32 (s, 42H), 3.29 (s, 3H), 1.70 (m, 30H), 1.54 (m, 16H), 1.44 (m, 8H), 1.30 (m,6H), 0.92 (t, J=7.11 Hz, 36E), 0.82 (t, J=7.22 Hz, 9H). ¹³C-NMR (100 MHz, CDC1₃) 160.1, 159.6, 159.1, 158.9, 157.2, 156.9, 139.3, 137.7, 136.0, 135.8, 119.7, 110.1, 106.1, 105.6, 105.2, 105.0, 100.7, 71.8,

71.7, 70.7, 70.6, 70.5, 70.3, 70.2, 69.8, 69.6, 69.4, 69.3, 68.8, 68.3, 67.6,

67.3, 58.9, 58.8, 31.2, 31.1, 31.0, 19.2, 19.1, 13.7, 13.6. MALDI-TOF: 5662.38 (Calcd: for C₃₁₂H₄₅₀0₉₀ (M+Na+) 5662.86).

Synthesis of third generation dendron bromide 23: Following the general procedure for the preparation of 19 above, 0.049 mmol of 22 was brominated to afford about 0.2 g (76%) of bromide 23. Η-NMR (400 MHz, CDC1₃) 6.69-6.37 (m, 59H), 4.95(s, 12H), 4.87 (s, 16H), 4.41 (s, 2H), 4.06 (t, J=5.11 Hz, 30H), 3.98 (t, J=6.34 Hz, 30H), 3.91- 3.80(m, 30H), 3.68-3.65 (m, 96H), 3.63-3.59 (m, 16H), 3.51-3.40 (m, 8H), 3.33 (s, 42H), 3.28 (s, 3H), 1.71 (m, 30H), 1.54 (m, 16H), 1.44 (m, 8H), 1.30 (m,6H), 0.92 (t, J=7.11 Hz, 36H), 0.82 (t, J=7.22 Hz, 9H). ¹³C-NMR (100 MHz, CDC1₃) 160.3, 159.7, 158.8, 158.8, 157.1, 156.8, 139.2, 137.9, 137.7, 135.7, 135.6, 120.1, 119.6,

110.1, 110.0, 106.1, 106.0, 105.5, 105.0, 104.8, 100.8, 100.6, 71.7, 71.6,

70.6, 70.4, 70.3, 70.2, 70.1, 69.7, 69.5, 69.3, 69.2, 68.7, 68.2, 67.5, 67.2,

58.7, 58.6, 46.5, 31.1, 30.8, 19.0, 13.6, 13.5.

Synthesis of fourth generation dendron 24: Dendron 24 was prepared following the procedure for the preparation of 18 above. The reaction was carried out utilizing about 0.0105 mmol of 17 and about 0.021 mmol of 23. Crude dendron 24 was chromatographically purified on silica gel using ethyl acetate/ 1,4-dioxane (80:20) as eluent to afford about 0.061 g, 51 % yield of dendron 24. Η-NMR (400 MHz, CDC1₃) 6.69-6.37 (m, 123H), 4.97(s, 28H), 4.89 (s, 32H), 4.60 (s, 2H), 4.04 (t, J=5.33 Hz, 62H), 3.98 (t,

J=6.13 Hz, 62H), 3.90- 3.79(m, 62H), 3.69-3.67 (m, 56H), 3.64-3.59 (m, 194H), 3.50-3.41 (m, 34H), 3.32 (s, 18H), 3.29 (s, 86H), 1.70 (m, 16H), 1.54 (m, 24H), 1.44 (m, 32H), 1.30 (m,24H), 0.92 (t, J=7.11 Hz, 72H), 0.82 (t, J=7.22 Hz, 12H). ¹³C-NMR (100 MHz, CDC1₃) 160.3, 159.9, 159.0, 158.9, 157.2, 156.9, 139.3, 137.7, 136.0, 135.8, 119.7, 110.1, 106.1, 105.6, 105.2,

105.0, 100.7, 71.8, 71.7, 70.7, 70.6, 70.5, 70.3, 70.2, 69.8, 69.6, 69.4, 69.3,

68.8, 68.3, 67.6, 67.3, 58.9, 58.8, 31.2, 31.1, 31.0, 19.2, 19.1, 13.8, 13.7. ' MALDI-TOF: 11695.0, (Calcd: for C₆₄₈H₉₃₀0₁₈₆ 11696.2).

Dendrons 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, and 29 are soluble in, for example, dichloromethane, chloroform, ethyl acetate, acetonitrile,

DMF, THF, and acetone.

Numerous variations and modifications of the embodiments described above can be effected without departing from the spirit and scope of the novel features of the invention. No limitations with respect to the specific embodiments illustrated herein are intended or should be inferred. The above description is intended to cover by the appended claims all such modifications as fall within the scope of the claims.

Claims

WE CLAIM:

1. A dendritic polymer comprising at least one biaryl monomer unit wherein the biaryl monomer unit comprises at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group, the first aryl group defining a plane; the second aryl group having a first functional substituent and a second functional substituent, the first and second functional substituents being bonded to the second aryl group such that the first and second functional substituents are oriented on opposite sides of the plane defined by the first aryl group; the first aryl group having first and second branching substituents each adapted for bonding to another monomer unit and at least one of the first and second aryl groups having a third branching substituent adapted for bonding to a third monomer unit.

2. A dendritic polymer of claim 1 wherein the first and second aryl groups are each independently selected from a phenyl group and a naphthyl group.

3. A dendritic polymer of claim 1 wherein the first functional substituent is a hydrophilic substituent and the second functional substituent is a hydrophobic substituent.

4. A dendritic polymer of claim 1 wherein the first aryl group is a first phenyl group, the second aryl group is bound to tlie 1 position of the first phenyl group; the first branching substituent is bound to the 2 or 3 position of the first phenyl group; and the second branching substituent is boun to the 5 or 6 position of the first phenyl group.

5. A dendritic polymer of claim 4 wherein the second aryl group is a second phenyl group, the first functional substituent is bound to the 2 or 3 position of the second phenyl group; and the second functional substituent is bound to the 5 or 6 position of the second phenyl group.

6. A dendritic polymer of claim 4 wherein the second aryl group is a naphthyl group; the first functional substituent is bound to the 2 or 3 position of the naphthyl group; and the second functional substituent is bound to the 6 or 7 position of the naphthyl group.

7. A dendritic polymer of claim 1 wherein the first aryl group is a first naphthyl group; the second aryl group is bound to the 1 position of the first naphthyl group; the first branching substituent is bound to the 2 or 3 position of the first naphthyl group; and the second branching substituent is bound to the 6 or 7 position of the first naphthyl group.

8. A dendritic polymer of claim 7 wherein the second aryl group is a phenyl group; the first functional substituent is bound to the 2 or 3 position of the phenyl group; and the second functional substituent is bound to the 5 or 6 position of the phenyl group.

9. A dendritic polymer of claim 7 wherein the second aryl group is a second naphthyl group; the first functional substituent is bound to the 2 or 3 position of the second naphthyl group; and the second functional substituent is bound to the 6 or 7 position of the second naphthyl group.

10. A dendritic polymer of claim 1 wherein the at least one biaryl monomer unit has the structure (I):

wherein

A¹ and A² are each independently phenyl or naphthyl;

X¹, X², Y¹, and Y² are each independently OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², SO₂, ET.¹, E²L², P(L²)₂,

E³R³, or E⁴R⁴;

D is C(=O) or C(R^!)(R²);

Z is OH, O, NHR¹, NR¹-, SH, S, a covalent bond, CI, Br, I, or OSO₂-R⁵;

Z² is CI, Br, I, or OSO₂-R⁵;

E¹ is CH₂ or CF₂;

E² is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O); E³ is CHR⁷, CF₂, or CFR⁷;

E⁴ is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O);

L¹ is H, C_J-C_JO alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or Cj- o perfluoroalkyl-substituted phenyl;

L² is C₄-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted -C^ alkyl, C_]-C₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl;

R¹ and R² are each independently H or C_rC₂₀ alkyl; R³ is OH, NH_2ι C(=O)OH, -SO₃H, or PO₃R⁷H;

R⁴ is H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰;

(CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted

C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C,.C₁₀ alkyl, a phosphonic acid-substituted C_rCι₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C,-C₁₀ alkyl, or a trialkylammonium-substituted

C_rC₁₀ alkyl;

R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃; R⁶ is H, C_J- _JO alkyl, or C_rC₂₀ perfluoroalkyl;

R⁷ is H or C_rC₃ alkyl;

R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; x is an integer having a value in the range of 0 to about 20; with the proviso that: when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, and Y¹ and Y² are each independently ET.¹, E²L², P(L²)₂, E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, and X¹ and X² are each independently ET.¹, E²L², P(L²)₂, E³R³ or E⁴R⁴; when A¹ is phenyl, A² is in the 1 position of the phenyl ring, X¹ is in the 2 or 3 position of the phenyl ring, and X² is in the 5 or 6 position of the phenyl ring; when A¹ is naphthyl, A² is in the 1 position of the naphthyl ring, X¹ is in the 2 or 3 position of the naphthyl ring, and X² is in the 6 or 7 position of the naphthyl ring; when A² is phenyl, A¹ is in the 1 position of the phenyl ring, Y¹ is in the 2 or 3 position of the phenyl ring, and Y² is in the 5 or 6 position of the phenyl ring; and when A² is naphthyl, A¹ is in the 1 or 8 position of the naphthyl ring, Y¹ is in the 2 or 3 position of the naphthyl ring, and Y² is in the 6 or 7 position of the naphthyl ring.

11. A dendritic polymer of claim 10 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^lV, E L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is E^lV, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E¹L¹,'E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

12. A dendritic polymer of claim 10 wherein the biaryl monomer unit has the structure (II):

wherein X¹ is in the 2 or 3 position, and X² is in the 5 or 6 position; Y¹ is in the

2' or 3' position, and Y² is in the 5' or 6' position, as the positions are indicated numerically in the structure.

13. A dendritic polymer of claim 12 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^λV, E L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is E E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also ET.¹, E²L², or P(L²)₂ , and V and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

14. A dendritic polymer of claim 10 wherein the biaryl monomer unit has either of the structures (III) or (IV):

wherein, in each of structures (III) and (JV), X¹ is in the 2 or 3 position, and X² is in the 5 or 6 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures.

15. A dendritic polymer of claim 14 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^¹, E L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is E E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E^lV, E²L², or P(L²)₂ , and Y^{1 '}and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

16. A dendritic polymer of claim 10 wherein the biaryl monomer unit has the structure (V):

wherein X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the 2' or 3' position, and Y² is in the 5' or 6' position, as the positions are indicated numerically in the structure.

17. The dendritic polymer of claim 16 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and X² is E'L¹, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E'L¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

18. A dendritic polymer of claim 10 wherein the biaryl monomer unit has either of the structures (VI) or (Nil):

wherein, in each of structures (NI) and (Nil), X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures.

19. The dendritic polymer of claim 18 wherein when X¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E^lV, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y² is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and X² is E'V, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E¹^, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

20. A dendritic polymer of claim 1 useful for encapsulation of pharmaceutical and agrochemical active agents, wherein the first and second aryl groups are each independently selected from phenyl and naphthyl; the first functional substituent is selected from oligomeric polyoxyethylene groups, carboxylic acids, and acidic or neutral polypeptides; and the second functional substituent is selected from an amino or nitrogen-heterocyclic functional group selected from primary, secondary or tertiary amino, amino-substituted -C^ alkyl, amino-aryl, nitrogen-heterocycle, nitrogen-heterocycle-substituted C_rCι₀ alkyl, basic amino acids and basic peptides.

21. A dendritic polymer of claim 20 wherein the first and second aryl groups are both phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group; and the second functional substituent is at the 5 or 6 position relative to the first aryl group.

22. A dendritic polymer of claim 1 useful as a phase transfer catalyst in a fluorocarbon solvent, wherein the first functional substituent is a C_rC₂₀ perfluoroalkyl or C_rC₂₀ perfluoroalkyl-substituted phenyl, and the second functional substituent is selected from a hydrophobic substituent and a hydrophilic substituent.

23. A dendritic polymer of claim 22 wherein in each monomer unit, the first and the second aryl groups are phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group of the monomer unit; and the second functional substituent is at the 5 or 6 position relative to the first aryl group of the monomer unit.

24. A dendritic polymer of claim 1 useful for pH controlled encapsulation and release of pharmaceutical active agents, wherein the first and second aryl groups are each independently selected from phenyl and naphthyl; the first functional substituent is selected from oligomeric polyoxyethylene groups, carboxylic acids, and acidic or neutral polypeptides; and the second functional substituent is selected from primary, secondary or tertiary amino, amino-substituted^*Cι-C₁₀ alkyl, amino-aryl, nitrogen-heterocycle, nitrogen- heterocycle-substituted C_rC₁₀ alkyl, basic amino acids and basic polypeptides.

25. A dendritic polymer of claim 24 wherein the first and second aryl groups are both phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group; and the second functional substituent is at the 5 or 6 position relative to the first aryl group.

26. A dendritic polymer of claim 1 useful for promoting cell- cell adhesion in a biological tissue, wherein the first and second aryl groups are each independently selected from phenyl and naphthyl; and the first and second functional substituents are selected from tripeptide Arg-Gly-Asp (RGD), the tetrapeptide Gly-Arg-Gly-Asp (GRGD, SEQ ID NO: 1), and pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS, SEQ ID NO: 2).

27. A dendritic polymer of claim 26 wherein in each monomer unit, the first and the second aryl groups are phenyl groups; the first functional substituent is at the 2 or 3 position relative to the first aryl group of the monomer unit; and the second functional substituent is at the 5 or 6 position relative to the first aryl group of the monomer unit.

28. A dendritic polymer comprising at least one biaryl monomer unit having the structure (I):

wherein

A¹ and A² are each independently phenyl or naphthyl;

X¹, X², Y¹, and Y² are each independently OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², SO₂, ET E²L², P(L²)₂,

E³R³, or E R⁴;

D is C(=O) or C(R¹)(R²);

Z is OH, O, NHR¹, NR¹-, SH, S, a covalent bond, CI, Br, I, or OSO₂-R⁵;

Z² is CI, Br, I, or OSO₂-R⁵;

E¹ is CH₂ or CF₂;

E² is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O);

E³ is CHR⁷, CF₂, or CFR⁷;

E⁴ is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O);

L¹ is H, C_rC₂₀ alkyl, phenyl, C,-C₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C]-C₂₀ perfluoroalkyl-substituted phenyl; L² is C₄-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or

C_rC₂₀ perfluoroalkyl-substituted phenyl;

R¹ and R² are each independently H or Cι-C₂₀ alkyl; R³ is OH, NH_2j C(=O)OH, -SO₃H, or PO₃R⁷H;

R⁴ is H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰;

(CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted

C_rC₁₀ alkyl, an amino-substituted C,-C₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted Cι_C₁₀ alkyl, a phosphonic acid-substituted - Q alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted

C_rC₁₀ alkyl;

R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃; R⁶ is H, C_rC₂₀ alkyl, or - _Q perfluoroalkyl;

R⁷ is H or C_rC₃ alkyl;

R⁸, R⁹, and R¹⁰are each independently H or C_rC₃ alkyl; x is an integer having a value in the range of 0 to about 20; with the proviso that: when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, and Y¹ and Y² are each independently E'L¹, E²L², P(L²)₂, E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, and X¹ and X² are each independently E^lV, E²L², P(L²)₂, E³R³ or E⁴R⁴; when A¹ is phenyl, A² is in the 1 position of the phenyl ring, X¹ is in the 2 or 3 position of the phenyl ring, and X² is in the 5 or 6 position of the phenyl ring; when A¹ is naphthyl, A² is in the 1 position of the naphthyl ring, X¹ is in the 2 or 3 position of the naphthyl ring, and X² is in the 6 or 7 position of the naphthyl ring; when A² is phenyl, A¹ is in the 1 position of the phenyl ring, Y¹ is in the 2 or 3 position of the phenyl ring, and Y² is in the 5 or 6 position of the phenyl ring; and when A² is naphthyl, A¹ is in the 1 or 8 position of the naphthyl ring, Y¹ is in the 2 or 3 position of the naphthyl ring, and Y² is in the 6 or 7 position of the naphthyl ring.

29. A dendritic polymer of claim 28 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X² is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is ET.¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and X² is tfL¹, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E^lV, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹,

NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

30. A dendritic polymer of claim 28 wherein the biaryl monomer unit has the structure (II):

wherein X¹ is in the 2 or 3 position, and X² is in the 5 or 6 position; Y¹ is in the

2' or 3' position, and Y² is in the 5' or 6' position, as the positions are indicated numerically in the structure.

31. A dendritic polymer of claim 30 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E'L¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is E^lV, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E R⁴, one of X¹ and X² is also E¹-.¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

32. A dendritic polymer of claim 28 wherein the biaryl monomer unit has either of the structures (III) or (JN):

wherein, in each of structures (III) and (IN), X¹ is in the 2 or 3 position, and X² is in the 5 or 6 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures.

33. A dendritic polymer of claim 32 wherein when X¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is ElΛ E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O,

C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and X² is E^lV, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E¹! , E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, ΝHR¹,

ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

34. A dendritic polymer of claim 28 wherein the biaryl monomer unit has the structure (V):

wherein X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the

2' or 3' position, and Y² is in the 5' or 6' position, as the positions are indicated numerically in the structure.

35. A dendritic polymer of claim 34 wherein when X¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, NHR¹, NR¹, SH, S,

C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E¹- , E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and

X² is ET E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E^¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, NHR¹, NR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

36. A dendritic polymer of claim 28 wherein the biaryl • monomer unit has either of the structures (VI) or (VII):

wherein, in each of structures (NI) and (Nil), X¹ is in the 2 or 3 position, and X² is in the 6 or 7 position; Y¹ is in the 2' or 3' position, and Y² is in the 6' or 7' position, as the positions are indicated numerically in the structures.

37. A dendritic polymer of claim 36 wherein when X¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, X²is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of Y¹ and Y² is E'L¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E R⁴; when Y¹ is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, Y²is OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂, one of X¹ and X² is E'V, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also ET.¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, O, ΝHR¹, ΝR¹, SH, S, C(=O)OH, C(=O)O, C(=O)Z², C(=O), SO₃H, SO₂Z², or SO₂.

38. A globular dendritic polymer having an external surface and an interior surface comprising a plurality of biaryl monomer units wherein each of the plurality of biaryl monomer units comprises at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group, the first aryl group defining a plane, the second aryl group having a first substituent and a second substituent, the first substituent having an affinity for a solvent having a first solvent property and the second substituent having an affinity for a solvent having a second solvent property; the first and second substituents being bound to the second aryl group such that the first and second substituents are oriented on opposite sides of the plane defined by the first aryl group; the first aryl group having first and second branching substituents each adapted for bonding to another monomer unit; and at least one of said first and second aryl groups having a third branching substituent adapted for bonding to a third monomer unit; whereby the first substituent is oriented to the external surface of the polymer in a solvent having the first solvent property, and the polymer inverts in a solvent having the second solvent property.

39. The method of claim 38 wherein the first and second solvent parameters are selected from hydrophobicity, hydrophilicity, solvent polarity, pH, and ionic strength.

40. A globular dendritic polymer having an external surface and an interior surface comprising a plurality of biaryl monomer units wherein each of the plurality of biaryl monomer units comprises at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group, the first aryl group defining a plane, the second aryl group having a first substituent and a second substituent, each of the first and second substituents having hydrophilic properties at selected pH values, the first substituent being substantially more hydrophilic than the second substituent in solution having a first pH value, the second substituent being substantially more hydrophilic than the first substituent in a solution having a second pH value; the first and second substituents being bound to the second aryl group such that the first and second substituents are oriented on opposite sides of the plane defined by the first aryl group; the first aryl group having first and second branching substituents each adapted for bonding to another monomer unit; and at least one of said first and second aryl groups having a third branching substituent adapted for bonding to a third monomer unit; whereby the first substituent of the second aryl group is oriented on the exterior surface of the polymer in a solution having the first pH value, and the polymer inverts in a solution having the second pH value.

41. A globular dendritic polymer of claim 40 wherein the second substituent comprises a basic functional group that has a pK_b in the range of about y to about z; and the value of the first pH is greater than about w; wherein y and z each have a numerical value in the range of about 3 to about 8, w has a numerical value at least about 0.5 greater than z; z has a numerical value at least about 1 greater than y.

42. A dendritic polymer according to claim 41 wherein the basic functional group is an amino or nitrogen-heterocyclic functional group selected from primary, secondary or tertiary amino, amino-substituted C_rC₁₀ alkyl, amino-aryl, nitrogen-heterocycle, nitrogen-heterocycle-substituted C_rC₁₀ alkyl, basic amino acids and basic polypeptides; and the first substituent is selected from oligomeric polyoxyethylene groups, carboxylic acids, and acidic or neutral polypeptides.

43. A dendritic polymer according to claim 42 wherein w is about 7.4, y is about 5 and z is about 6.7.

44. A method of delivering an anti-tumor drug to a tumor comprising the sequential steps of:

(a) binding or encapsulating an anti-tumor drug or prodrug in the interior region of a dendritic polymer of claim 43 in an aqueous solution having a pH, w, of greater than about 7 to form a polymer-drug conjugate;

(b) preparing a solution of the polymer-drug conjugate in a pharmaceutically acceptable carrier having a pH of greater than about 7; and

(c) administering the solution of the polymer-drug conjugate to a patient having a tumor so as to contact the polymer-drug conjugate with the tumor; whereby the drug or prodrug is released into the tumor.

45. A method of encapsulating a solute comprising the sequential steps of:

(a) contacting a solute in an aqueous solution with a dendritic polymer of claim 38 in a solution having a first solvent parameter value; and

(b) adjusting the solvent parameter of the solution to a second solvent parameter value to form a polymer-encapsulated solute; wherein the first substituent of the second aryl group of the polymer has a binding affinity for the solute; the first substituent is substantially more hydrophilic than the second substituent in an aqueous solution having the first solvent parameter value, and the second substituent is substantially more hydrophilic than the first substituent in an aqueous solution having the second solvent parameter value.

46. A method according to claim 45 including the additional step (c) of separating the polymer-encapsulated solute from the solution.

47. A method according to claim 46 wherein the step (c) of separating the polymer-encapsulated solute from the solution is accomplished by a size dependent separation method or by precipitation.

48. A method of the method according to claim 45 wherein the first solvent parameter is a first pH and the second solvent parameter is a second PH.

49. A dendron having the following structure (XNI), and other dendrons and dendrimers derived therefrom:

wherein

D is C(=O) or CH₂; L^w, L^x, L^γ, and L^z, at each occurrence, are each independently C₄-C₂₀ alkyl, phenyl,

C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or - _Q perfluoroalkyl-substituted phenyl; G , G^x, G^γ and G^z, at each occurrence, are each independently H,

(CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted

C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC_I0 alkyl; T¹ and T², at each occurrence, are each independently H, C_rC₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, C_rC₂₀ perfluoroalkyl-substituted phenyl;

(3-ORⁿ,5-OR¹²)-benzyl, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, bibtin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C C_l0 alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted .C_JQ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted C C₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl; Z is OH, NHR¹, SH, CI, Br, I, or OSO₂-R⁵; R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃;

R⁶ is H, C_rC₂₀ alkyl, or C_rC₂₀ perfluoroalkyl; R⁷ is H or C_rC₃ alkyl;

R^s, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; R¹¹ and R¹² at each occurrence, are each independently H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C,-C₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl,- a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted Cι-C₁₀ alkyl, a phosphonic acid-substituted C_J-C_JQ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC_ω alkyl, a trialkylammonium-substituted C_rC₁₀ alkyl, C_rC₂₀ alkyl, phenyl, C_J-C_JO alkyl-substituted phenyl, benzyl, a diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl; and x is an integer having a value in the range of 0 to about 20.

50. A dendron according to claim 49, wherein D is CH₂; each of L^x and L^γ is (CH₂CH₂O)_x-CH₃ or carboxylic acid-substituted C,-Cι₀ alkyl; each of G^x and G^γ is C_I-C₂₀ alkyl; each of T¹ and T² is (3-OL^x,5-OG^x )-benzyl;

Z is -OH or -Br; and x is an integer in the range of about 1 to about 20.

51. A dendron having the following structure (XNII), and other dendrons and dendrimers derived therefrom:

wherein

D is C(=O) or CH₂; L^w, L^x, L^γ, and L^z, at each occurrence, are each independently C₄-C₂₀ alkyl, phenyl,

Cj- o alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl; G , G^x, G^γ and G^z, at each occurrence, are each independently H,

(CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted -C^ alkyl, a phosphinic acid-substimted C_rC₁₀ alkyl, a phosphonic acid-substituted

C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl; T¹ and T², at each occurrence, are each independently H, C_rC₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, C_rC₂₀ perfluoroalkyl-substituted phenyl;

(3-OR^π,5-OR¹²)-benzyl, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted .Cio alkyl, a phosphinic acid-substimted C_rC₁₀ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl; Z is OH, NHR¹, SH, CI, Br, I, or OSO₂-R⁵; R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃;

R⁶ is H, C_rC₂₀ alkyl, or C_rC₂₀ perfluoroalkyl; R⁷ is H or C C₃ alkyl;

R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; R¹¹ and R¹² at each occurrence, are each independently H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rCι₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted Cι-C₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, a trialkylammonium-substituted C,-C₁₀ alkyl, -C_JO alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, a diphenylphosphine-substituted C_rC₂₀ alkyl,

C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl; and x is an integer having a value in the range of 0 to about 20.

52. A dendron according to claim 51, wherein D is CH₂; each of L^x and L^γ is (CH₂CH₂O)_x-CH₃ or carboxylic acid-substituted C,-C₁₀ alkyl; each of G^x and G^γ is C_rC₂₀ alkyl; each of T¹ and T² is (3-OL^x,5-OG^x )-benzyl;

Z is -OH or -Br; and x is an integer in the range of about 1 to about 20.

53. A dendron having the following structure (XNIII), and other dendrons and dendrimers derived therefrom:

(XNIII)

wherein

D is C(=O) or CH₂;

L , L^x, L^γ, and L^z, at each occurrence, are each independently C₄-C₂₀ alkyl, phenyl,

C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl;

G^w, G^x, G^γ and G^z, at each occurrence, are each independently H,

(CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-ΝR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C C_w alkyl, a phosphinic acid-substituted C,-C_]0 alkyl, a phosphonic acid-substituted

C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substituted C_rC₁₀ alkyl;

T¹ and T², at each occurrence, are each independently H, C_rC₂₀ alkyl, phenyl, - o alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, C_rC₂₀ perfluoroalkyl-substituted phenyl;

(3-OR^π,5-OR¹²)-benzyl, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted Cι_C₁₀ alkyl, a phosphinic acid-substituted C_rC₁₀ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, or a trialkylammonium-substitoted C_rC₁₀ alkyl; Z is OH, NHR¹, SH, CI, Br, I, or OSO₂-R⁵; R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃; R⁶ is H, C_j- o alkyl, or C_rC₂₀ perfluoroalkyl; R⁷ is H or C_rC₃ alkyl;

R⁸, R⁹, and R¹⁰are each independently H or C_rC₃ alkyl; R¹¹ and R¹² at each occurrence, are each independently H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substimted C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted C C₁₀ alkyl, a phosphonic acid-substituted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substituted C_rC₁₀ alkyl, a trialkylammonium-substituted C_rC_I0 alkyl, C_rC₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, a diphenylphosphine-substituted C_rC₂₀ alkyl,

C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl; and x is an integer having a value in the range of 0 to about 20.

54. A dendron according to claim 53, wherein D is CH₂; each of L^x and L^γ is (CH₂CH₂O)_x-CH₃ or carboxylic acid-substituted C_rC₁₀ alkyl; each of G^x and G^γ is C_rC₂₀ alkyl; each of T¹ and T² is (3-OL^x,5-OG^x )-benzyl;

Z is -OH or -Br; and x is an integer in the range of about 1 to about 20.

55. A biaryl monomer comprising at least a first aryl group and a second aryl group directly covalently bonded to the first aryl group, the first aryl group defining a plane; the second aryl group having a first functional substituent and a second functional substituent, the first and second functional substituents being bonded to the second aryl group such that the first and second functional substituents are oriented on opposite sides of the plane defined by the first aryl group; the first aryl group having first and second branching substituents each adapted for bonding to another monomer and at least one of the first and second aryl groups having a third branching substituent adapted for bonding to a third monomer.

56. A monomer of claim 55 wherein the first and second aryl groups are each independently selected from a phenyl group and a naphthyl group.

57. A monomer of claim 55 wherein the first functional substituent is a hydrophilic substituent and the second functional substituent is a hydrophobic substituent.

58. A monomer of claim 55 wherein the first aryl group is a first phenyl group, the second aryl group is bound to the 1 position of the first phenyl group; the first branching substituent is bound to the 2 or 3 position of the first phenyl group; and the second branching substituent is bound to the 5 or 6 position of the first phenyl group.

59. A monomer of claim 58 wherein the second aryl group is a second phenyl group, the first functional substituent is bound to the 2 or 3 position of the second phenyl group; and the second functional substituent is bound to the 5 or 6 position of the second phenyl group.

60. A monomer of claim 58 wherein the second aryl group is a naphthyl group; the first functional substituent is bound to the 2 or 3 position of the naphthyl group; and the second functional substituent is bound to the 6 or 7 position of the naphthyl group.

61. • A monomer of claim 55 wherein the first aryl group is a first naphthyl group; the second aryl group is bound to the 1 position of the first naphthyl group; the first branching substituent is bound to the 2 or 3 position of the first naphthyl group; and the second branching substituent is bound to the 6 or 7 position of the first naphthyl group.

62. A monomer of claim 61 wherein the second aryl group is a phenyl group; the first functional substitoent is bound to the 2 or 3 position of the phenyl group; and the second functional substituent is bound to the 5 or 6 position of the phenyl group.

63. A monomer of claim 61 wherein the second aryl group is a second naphthyl group; the first functional substitoent is bound to the 2 or 3 position of the second naphthyl group; and the second functional substituent is bound to the 6 or 7 position of the second naphthyl group.

64. A biaryl monomer having the structure (NIII):

wherein

A¹ and A² are each independently phenyl or naphthyl;

X³, X⁴, Y³, and Y⁴ are each independently OH, ΝHR¹, SH, C(=O)OH,

C(=O)Z², SO₃H, SO₂Z², E'L¹, E²L², P(L )₂, E³R³, or E⁴R⁴;

D is C(=O) or C(R^])(R²);

Z* is OH, ΝHR¹, SH, CI, Br, I, or OSO₂-R⁵;

Z² is CI, Br, I, or OSO₂-R⁵;

E¹ is CH₂ or CF₂;

E² is ΝR⁶, O, S, Ν(R⁶)C(=O), OC(=O) or SC(=O);

E³ is CHR⁷, CF₂, or CFR⁷;

E⁴ is NR⁶, O, S, N(R⁶)C(=O), OC(=O) or SC(=O);

L¹ is H, C_rC₂₀ alkyl, phenyl, - _Q alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC_2Q perfluoroalkyl, or

C_ΓC₂₀ perfluoroalkyl-substituted phenyl;

L² is C₄-C₂₀ alkyl, phenyl, C_rC₂₀ alkyl-substituted phenyl, benzyl, diphenylphosphine-substituted C_rC₂₀ alkyl, C_rC₂₀ perfluoroalkyl, or C_rC₂₀ perfluoroalkyl-substituted phenyl;

R¹ and R² are each independently H or C_rC₂₀ alkyl;

R³ is OH, NH_2ι C(=O)OH, SO₃H, or PO₃R⁷H;

R⁴ is H, (CH₂CH₂O)_x-R⁸, (CH₂CH₂O)_x-CH₂CH₂-NR⁹R¹⁰; (CH₂CH₂O)_x-C(=O)NR⁹R¹⁰, an amino acid, a polypeptide, a nucleic acid, a polynucleic acid, biotin, sugar, a polysaccharide, a carboxylic acid-substituted

C_rC₁₀ alkyl, an amino-substituted C_rC₁₀ alkyl, a hydroxy-substituted C_rC₁₀ alkyl, a sulfonic acid-substituted C_rC₁₀ alkyl, a phosphinic acid-substituted .C_JO alkyl, a phosphonic acid-substitoted C_rC₁₀ alkyl, a nitrogen-heterocycle, a nitrogen-heterocycle-substitoted C_rC₁₀ alkyl, or a trialkylammonium-substituted

C_rC₁₀ alkyl;

R⁵ is C_rC₂₀ alkyl, phenyl, methylphenyl, or CF₃;

R⁶ is H, C_rC₂₀ alkyl, or C_rC₂₀ perfluoroalkyl;

R⁷ is H or C_rC₃ alkyl; R⁸, R⁹, and R¹⁰ are each independently H or C_rC₃ alkyl; x is an integer having a value in the range of 0 to about 20; with the proviso that: when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or

SO₂Z², X² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², and Y¹ and Y² are each independently ET.¹, E²L², P(L )₂, E³R³ or E⁴R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or

SO₂Z², Y² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², and X¹ and X² are each independently ET.¹, E²L², P(L²)₂, E³R³ or E⁴R⁴; when A¹ is phenyl, A² is in the 1 position of the phenyl ring, X³ is in the 2 or 3 position of the phenyl ring, and X⁴ is in the 5 or 6 position of the phenyl ring; when A¹ is naphthyl, A² is in the 1 position of the naphthyl ring,

X³ is in the 2 or 3 position of the naphthyl ring, and X⁴ is in the 6 or 7 position of the naphthyl ring; when A² is phenyl, A¹ is in the 1 position of the phenyl ring, Y³ is in the 2 or 3 position of the phenyl ring, and Y⁴ is in the 5 or 6 position of the phenyl ring; and when A² is naphthyl, A¹ is in the 1 or 8 position of the naphthyl ring, Y³ is in the 2 or 3 position of the naphthyl ring, and Y⁴ is in the 6 or 7 position of the naphthyl ring.

65. A monomer of claim 64 wherein when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of Y¹ and Y² is E'L¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y²is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of X¹ and X² is ET.¹, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also ET.¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z².

66. A biaryl monomer according to claim 64 having the structure (IX):

wherein X³ is in the 2 or 3 position, and X⁴ is in the 5 or 6 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 5' or 6' position , as the positions are indicated numerically in the structure.

67. A monomer of claim 66 wherein when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of Y¹ and Y² is E^V, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of X¹ and X² is ET.¹, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E'L¹, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z².

68. A biaryl monomer according to claim 64 having either of the structures (X) or (XI):

wherein X³ is in the 2 or 3 position, and X⁴ is in the 5 or 6 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 6' or 7' position, as the positions are indicated numerically in the structures.

69. A monomer claim 68 wherein when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of Y¹ and Y² is ET.¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y²is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of X¹ and X² is E^lV, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E^lV, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z².

70. A biaryl monomer according to claim 64 having the structure (XII):

wherein X³ is in the 2 or 3 position, and X⁴ is in the 6 or 7 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 5' or 6* position, as the positions are indicated numerically in the structure.

71. A monomer of claim 70 wherein when X¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X²is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of Y¹ and Y² is ET.¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y² is OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of X¹ and X² is E^!L\ E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also ET.¹, E L², or P(L²)₂ , and Y¹ and Y² are each independently OH, NHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z².

72. A biaryl monomer according to claim 64 having either of the structures (XIII) or (XIN):

wherein X³ is in the 2 or 3 position, and X⁴ is in the 6 or 7 position; Y³ is in the 2' or 3' position, and Y⁴ is in the 6' or 7' position, as the positions are indicated numerically in the structures.

73. A monomer of claim 72 wherein when X¹ is OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², X is OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of Y¹ and Y² is ET.¹, E²L², or P(L²)₂ , and one of Y¹ and Y² is E³R³ or E⁴R⁴; when Y¹ is OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², Y² is OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z², one of X¹ and X² is ET.¹, E²L², or P(L²)₂ , and one of X¹ and X² is E³R³ or E⁴R⁴; when one of X¹ and X² is E³R³ or E⁴R⁴, one of X¹ and X² is also E¹^, E²L², or P(L²)₂ , and Y¹ and Y² are each independently OH, ΝHR¹, SH, C(=O)OH, C(=O)Z², SO₃H, or SO₂Z².