Polyhydroxamicalkanoate as a bioinspired acetylcholinesterase-based catalyst for acetylthiocholine hydrolysis and organophosphorus dephosphorylation: experimental studies and theoretical insights

Acetylcholinesterase (AChE)-based biosensing methods are limited due to facile denaturation and leakage during the immobilization process. Accordingly, enzyme mimics have demonstrated extensive potential in versatile catalysis applications, since they provide desirable advantages over natural enzymes, including low-cost scalable production combined with flexible experimental conditions. Herein, we investigate the performance of a functionalized polyacrylamide, polyhydroxamicalkanoate (PHA) for the hydrolysis of the acetylthiocholine (ATCh) substrate as well as paraoxon-ethyl dephosphorylation. Polyhydroxamicalkanoate contains hydroxamic and carboxyl groups inserted along its backbone acting as an active site. This mimetic model exhibited significant rate enhancements for ATCh hydrolysis of over 10(8)-fold in pH 7.0 and over 10(7)-fold in pH 8.0. In this contribution, density functional theory calculations were employed to explore, at the atomistic level, the interactions between the bio-inspired AChE material with ATCh in addition to paraoxon- ethyl. Vibrational analysis validates our structural models for ATCh, paraoxon- ethyl and PHA. Remarkably, the adsorption energy of paraoxon- ethyl-PHA is 3-fold higher than that of ATCh-PHA. The foregoing result implies that paraoxon- ethyl strongly inhibits the polymeric active site in comparison with ATCh due to a covalent bond between the phosphorus atom in the pesticide and the oxygen atom in the hydroxamate moiety in PHA, releasing p-nitrophenolate. This study sheds light on the interaction mechanism that an AChE-based bioinspired polymer undergoes in ATCh hydrolysis and paraoxon- ethyl dephosphorylation. The modeling strategy consolidates the experimental outcomes which reveals the potential application of this biomimetic PHA polymer as an alternative for biosensing approaches. (AU)