Aminated polyphosphazenes

Aminated polyphosphazenes present amines with a low value of pKa as side groups, and constitute the most studied class of bioresorbable polyphosphazenes. Amino acid ester and imidazole-substituted polyphosphazenes appear to be two good candidates for drug delivery applications, because of their good hydrolysis degradation and low... 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

The design of single-component polymer transport materials continues to interest researchers in this field. The use of such materials will completely eliminate solvent extraction, diffusional instability, and crystallization of the small molecules. One obvious route that has not been successful to date is the design of yet another aromatic-amine-containing carbon-backbone polymer. An alternative may be to explore the large class of glassy silicon-backbone polymers, such as polysilylenes (14) and polyphosphazenes (iS). 

In order to prepare hydrolytically stable polythionyiphosphazenes the perchlo-rinated polymers were reacted with nucleophiles to substitute the hydrolytically sensitive main group-element halogen bonds [2]. This type of post-polymerization structural modification is well-established in polyphosphazene chemistry [2,8]. Thus, aryloxide nucleophiles or primary amines were used to substitute the polymers leading to poly(aryloxythionylphosphazenes) 24 and poly(amino-thionylphosphazenes) 25 respectively [35,37] ... 

Single-handed helicity induction was also achieved in gels and films of polyphenylacetylene derivatives. Gels obtained by copolymerization of (4-carboxyphenyl)acetylene with a bis(phe-nylacetylene) or by cross-linking of 168 responded to chirality to nonracemic amines in DMSO and alkaline water. Compound 174 formed an optically active gel upon complexation with optically active bis (amino acid)s. A cast film of 168 exhibited ICD in response to the chirality of liquid and solid chiral amines. Polydiacetylenes with a 4-carboxyIphenyI functions also showed ICD in the presence of optically active amines in dispersion and in the solid state. Helicity induction was also realized for polyphosphazene derivative 185 as (P)-phenethylamine as the chiral additive. ... 

Polyphosphazenes that bear -D-glucosyl side groups cosubstituted with methyl-amine, alkoxy or aryloxy side groups have been symthesized (Allcock et al, 1991) (Figure 22) resulting in a range of polymers with varying water solubility, hydrophilic-ity or hydrophobicity. 

A large variety of drugs and other bioactive molecules have been covalently linked to the polyphosphazene chain. Steroids were covalently linked by reaction of the sodium salt of steroidal alcohol functional groups with poly [ (dichloro) phosphazene ] (Allcock et al, 1980). Remaining chlorine side groups were replaced with methyl-amine, a side group which promotes the water solubility of the resulting polymer. 

A significant amoimt of research was devoted to post-functionahzation of aryloxy- or methyl-substituted polyphosphazenes. In the first case, electrophihc aromatic substitution reactions were used to obtain sulfonated (113-116), car-boxylated (117) nitrated (aminated) (118,119) and phosphonated (120,121) products (Fig. 7a). Alternatively, methyl substituents were deprotonated with n-BuLi and subsequently treated with a desired nucleophile (Fig. 7b). Using this method, polyphosphazenes bearing carboxylic (122), alcohol (123,124), ester (125), and other (63,126) groups became available. Numerous studies have been devoted... 

FIGURE 1.7 Fluoroalkylamino groups can be linked to the polyphosphazene chain. These reactions are facilitated by the presence of nonlluorinated tertiary amines as hydrochloride aeceptors. 

Although fluorinated alkoxy and aryloxy polyphosphazenes have been investigated in some detail, fluorinated aminophosphazene polymers have received less attention. A possible reason is the lower reactivity of these amines compared to the fluo-roalkoxides. However, an example of this class has been investigated recently with the synthesis of 2,2,2-trifluoroethylamino derivatives (Figure 1.7) [33]. 

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