Polyphosphazenes hydrolytic sensitivity

A substantial number of bioactive molecules, such as polypeptides, N-acetyl-DL-penicillamine, p-(dipropylsulfamoyl)benzoic acid, and nicotinic acid, contain a carboxylic acid function, and this provides a site for linkage to a polyphosphazene chain. A number of prototype polymers have been synthesized in which pendent amino groups provide coupling sites for the carboxylic acid (34). The amide linkages so formed are potentially bioerodible, but the use of a hydrolytic sensitizing cosubstituent would be expected to accelerate the process. 

The parent polymer by itself is not a useful material owing to the extreme hydrolytic sensitivity of the P-Cl bond. However, this feature has been turned around and used as an advantage. Nucleophilic substitution of the chlorines in the polymer results in substituted polyphosphazenes which are hydrolytically stable. Also, using this method the polymer architecture and properties are readily fine-tuned by a subtle variation of the substituent. Over three hundred types of polyphosphazenes have been synthesised by this method. Assembly of organic polymers containing cyclo-phosphazenes as pendant groups is another approach that is gaining importance [6]. 

Although the hydrolytic stability of some phosphazene polymer makes them attractive as structural materials, it is possible to create hydrolytically sensitive phosphazenes that may be useful medically as slow-rdease drugs. Steroids, antibiotics. and catecholamines (e.g., dopamine and epinephrine) have been linked to a polyphosphazene skeleton (Fig. 16.27) with the intention that slow hydrolysis would provide these drugs in a therapeutic steady state. 

RS(0)=N]n and classical polyphosphazenes, [R2P=N]n 1 [20,21]. The first well-characterized examples of these materials, polythiophosphazenes, were also reported by Allcock et al. [22]. These polymers were prepared via the thermal ROP of a cyclothiophosphazene. This yielded the hydrolytically sensitive polythio-phosphazene 12 with a backbone of three-coordinate sulfur(IV), nitrogen, and phosphorus atoms. Although reaction of 12 with nucleophiles such as aryloxides yielded materials 13 with improved hydrolytic stability, degradation in the presence of moisture was still rapid except where very bulky substituents such as o-phenylphenoxy were present ... 

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] ... 

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