Water-soluble and degradable polyphosphorodiamidates via thiol-ene polyaddition

Water-soluble polyphosphorodiamidates (PPDAs) and structural analog polyphosphates (PPEs) are synthesized by the metal-free radical thiol-ene polyaddition. To ensure complete water-solubility, we transform the thioether functionalities in the polymer backbone to sulfones by oxidation with peroxide. Due to a significant difference in the hydrolytic stability of P-N and P-O bonds, the chemical structure around the phosphorus atom in the main chain controls the degradation kinetics. The pendant ester group is used to further control the degradation rates of the polymers. Under acidic conditions, PPDAs show a fast and pH-dependent hydrolysis rate of the main chain, while PPEs are stable under such conditions, which was monitored by NMR spectroscopy. Under basic conditions, in contrast, the P-O-bonds can be hydrolyzed, while the P-amides are relatively stable. This set of hydrophilic and degradable polymers enlarges the family of phosphorus-containing polymers and might be useful in the field of drug delivery or tissue engineering and to date is the only route to prepare PPDAs by thiol-ene polymerization.