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

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.