Synthesis and pH-dependent micellization of sulfonamide-modified diblock copolymer

Abstract

The main objective of this study was to develop and characterize pH-sensitive biodegradable polymeric materials. For pH-sensitivity, we employed three kinds of moieties: 2-amino-3-(1H-imidazol-4-yl)-propionic acid (H),N-[4-(4,6-dimethyl-pyrimidin-2ylsulfamoyl)-phenyl]succinamic acid (SM), and 2-{3-[4-(4,6-dimethyl-pyrimidin-2-ylsulfamoyl)-phenylcarbamoyl]-propionylamino}-3-(3H-imidazol-4-yl)-propionic acid (SH). The pH-sensitive diblock copolymers were synthesized by ring opening polymerization and coupling reaction from poly(ethylene glycol) (MPEG), e-caprolactone (CL), D,L-lactide (LA) and pH-sensitive moieties. The pH-sensitive SH molecule was synthesized in a two-step reaction. The first step involved the synthesis of SHM, a methyl ester derivative of SH, by coupling reaction of SM and L-histidine methyl ester dihydrochloride, whereas the second step involved the hydrolysis of the same. The synthesized SM, SHM and SH molecules were characterized by FTIR,1H-NMR and13C-NMR spectroscopy, whereas diblock copolymers and pH-sensitive diblock copolymer were characterized by 1H-NMR and GPC analysis. The critical micelle concentrations were determined at various pH conditions by fluorescence technique using pyrene as a probe. The micellization and demicellization studies of pH-sensitive diblock copolymers were also done at different pH conditions. The pH-sensitivity was further established by acid-based titration and DLS analysis.