Hydrophobic pockets built in polymer micelles enhance the reactivity of Cu2+ ions

Abstract

We report the hydrophobicity-enhanced reactivity of Cu²⁺ ions as an ester hydrolase. Using a dipicolylamine (DPA) containing reversible addition–fragmentation chain transfer agent, the synthetic sequence, either hydrophobic or hydrophilic first in amphiphilic block copolymers of polystyrene-block-poly(N′N-dimethylacrylamide) (PS-b-PDMA), was varied to control the location of the binding motif, DPA, in the hydrophobic core or on the hydrated corona of polymer micelles. The hydrophobicity of Cu²⁺ sites showed a significant impact (as large as 60 times more activity) on their catalytic efficiency towards ester hydrolase. With two different kinetic modes, including Michaelis–Menten and the reverse saturation kinetics models, the binding constant K_b of the substrates to Cu²⁺ sites were quantitatively analyzed and we demonstrate that hydrophobicity favors the binding of the substrates to Cu²⁺ sites at polymer micelles with smaller sizes, however, K_b decays exponentially with micellar diameters. Despite the diffusion barrier, hydrophobicity shows a profound impact on the catalytic rate constant k_c that measures the single conversion rate of bound substrates to products. There is a 16–20 times kinetic enhancement in the hydrolase activity, completely endowed by the hydrophobic microenvironment of Cu²⁺ sites compared to micelles with similar sizes. Our results indicate how the hydrophobicity of Cu²⁺-containing micelles can impact the catalytic efficiency and potentially illustrate a promising way toward the design of bioinspired catalysts.