Synthetic Poly(phosphoester)s with Defined Charge Patterns

Sequence-defined poly(phosphodiester)s, synthesized by solid-phase phosphoramidite chemistry, are inherently polyanionic due to their negatively charged phosphate repeat units. This study introduces a method for precisely controlling the charge distribution of these polymers. The approach uses two non-natural phosphoramidite monomers with distinct phosphorus protecting groups, namely, cyanoethyl or methyl. Optimizing solid-phase synthesis conditions, in particular, during oxidation and cleavage, enables the selective deprotection of cyanoethyl units. This selective process allows for the synthesis of oligomers and polymers with precise sequences of ionic or methylated phosphates. Ion-exchange HPLC and mass spectrometry analyses confirmed the formation of macromolecules with well-defined charge patterns. Additionally, these polymers exhibited robust structural stability in water.