Poly(phosphorodiamidate)s by Olefin Metathesis Polymerization with Precise Degradation

Abstract

Degradable polymers are a currently growing field of research for biomedical and materials science applications. The majority of such compounds are based on polyesters and polyamides. In contrast, their phosphorus-containing counterparts are much less studied, in spite of their potential precise degradation profile and biocompatibility. Herein, the first library of poly(phosphorodiamidate)s (PPDAs) with two P-N bonds forming the polymer backbone and a pendant P-OR group is prepared through acyclic diene metathesis polymerization. They are designed to vary in their hydrophilicity and are compared with the structural analogues poly(phosphoester)s (PPEs) with respect to their thermal properties and degradation profiles. The degradation of PPDAs can be controlled precisely by the pH: under acidic conditions the P-N linkages in the polymer backbone are cleaved, whereas under basic conditions the pendant ester is cleaved selectively and almost no backbone degradation occurs. The PPDAs exhibit distinctively higher thermal stability (from thermogravimetric analysis (TGA)) and higher glass transition and/or melting temperatures (from differential scanning calorimetry (DSC)) compared with analogous PPEs. This renders this exotic class of phosphorus-containing polymers as highly promising for the development of future drug carriers or tissue engineering scaffolds.

Molecular Firefighting—How Modern Phosphorus Chemistry Can Help Solve the Challenge of Flame Retardancy

“…Biodegradable PUs are commonly synthesized with hydrolyzable soft segments 51. The use of P‐FRs could achieve both, since these materials demonstrate good FR properties and can be both biocompatible and degradable 52. Chiu et al 51.…”

Functional biodegradable polymers via ring-opening polymerization of monomers without protective groups

“…10 Contrary, polyphosphoramidates undergo hydrolysis in basic and acidic media. [11][12][13][14][15] While hydrolysis almost exclusively proceeds at the P-N bond under acidic and nearly neutral conditions, P-O, as well as P-N bond cleavage, occurs under basic conditions, still with a higher probability for P-N cleavage. 14 94% cleavage of mainchain polyphosphoramidates to diesters has been shown at pH 3.0 within 12.5 days.…”

Stimuli‐Responsive Phosphorus‐Based Polymers

“…In contrast to polyphosphazenes, a significantly faster rate of cleavage is usually observed under basic conditions, whereas under acidic conditions cleavage of pendant methyl moieties tends to occur first, followed by slower main‐chain degradation . Interestingly, poly(phosphorodiamidate)s, recently prepared via olefin metathesis polymerization, are reported to be quite stable under basic conditions but can be degraded by acidic hydrolysis as a result of their having P–N bonds as oppose to P‐O bond in the main‐chain. Furthermore, recently polyphosphoramidates have also been designed to undergo rapid main‐chain cleavage at acidic pH values.…”