Synthesis, reactivity, and pH-responsive assembly of new double hydrophilic block copolymers of carboxymethyldextran and poly(ethylene glycol)

Double hydrophilic block copolymers (DHBC) were prepared by end-to-end coupling of two biocompatible water-soluble homopolymers: the polysaccharide dextran (Mw 8300 or 14,700 g mol−1) and ω-amino poly(ethylene glycol) (PEG–NH2, Mw 3000 or 7000 g mol−1). The synthesis involved, first, specific oxidation of the dextran terminal aldehyde group and, second, covalent linkage of PEG–NH2 via a lactone aminolysis reaction. The diblock copolymers dextran–PEG (DEX–PEG) were converted in high yield into the corresponding carboxymethyldextran–PEG (CMD–PEG) derivatives with control over the degree of substitution, from 30 to 85 mol% CH2COOH groups per glucopyranosyl unit. Further modifications of a CMD–PEG block copolymer led to N-(2-aminoethyl)carbamidomethyldextran–PEG yielding a pair of oppositely-charged DHBC of identical charge density, chain length, and neutral block/charged block content. The properties of CMD–PEG in aqueous solutions were studied by static and dynamic light scattering as a function of solution pH, providing evidence of the pH-sensitive assembly of the copolymers driven by inter- and intra-chain hydrogen-bond formation.