Micellization kinetics of a novel multi-responsive double hydrophilic diblock copolymer studied by stopped-flow pH and temperature jump

Double hydrophilic diblock copolymer, poly(N-isopropylacrylamide)-block- poly(2-diethylamino ethyl methacrylate) (PNIPAM-b-PDEA), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Containing the well-known thermo-responsive PNIPAM block and pH-responsive PDEA block, this novel diblock copolymer exhibits intriguing " schizophrenic" micellization behavior in aqueous solution, forming PDEA-core micelles at alkaline pH and room temperature, and PNIPAM-core micelles at acidic pH and elevated temperatures. The kinetics of the pH- and thermo-responsive micellization processes were studied in detail using a stopped-flow apparatus equipped with a newly developed millisecond temperature jump (mT-jump) accessory. Upon a pH jump from 4 to 12 at 25 °C, the early stages of relaxation curves monitoring the formation PDEA-core micelles can be well-fitted using a double-exponential function, leading to two characteristic relaxation time constants, τ₁ and τ₂. As τ₂ decreases with increasing polymer concentration, the slow process is thus expected to proceed via micelle fusion/fission mechanism, approaching the final equilibrium state. Upon a temperature jump from 20 to 45 °C at pH 4, the relaxation curves monitoring the formation PNIPAM-core micelles can also be well-fitted using a double-exponential function. The fast process (τ₁) is associated with the quick association of unimers into a large amount of small micelles and the formation of quasi-equilibrium micelles. τ₂ is almost independent of polymer concentration, suggesting that unimer insertion/expulsion is the main mechanism for the slow process. The protonated PDEA corona of quasiequilibrium micelles renders the micelle fusion/fission mechanism less favorable due to electrostatic repulsion.