Roles of Noncovalent Interactions in Phosphoester Hydrolysis Catalyzed by Binuclear (Fe(III)-Zn(II)) Metal Complexes

In this study, the roles of noncovalent interactions (NCIs) and the interplay between them have been investigated in the activities of three distinct Fe(III)-Zn(II) core-containing complexes (¹L, ²L, and ⁰L). The effects of NCIs were incorporated by attaching one, two, and zero pyrene molecule(s) through diamino-butyl, HN(CH₂)₄NH linker in ¹L, ²L, and ⁰L, respectively. These complexes interact with the bis(4-nitrophenyl)phosphate (BNPP) substrate through different types of NCIs, i.e., ¹L (2 hydrogen bonds and 1 π-π interaction), ²L (1 hydrogen bond and 2 π-π interactions), and ⁰L (1 hydrogen bond and 1 H-π interaction). BNPP coordinates to ¹L, ²L, and ⁰L with binding energies of -25.0, -28.4, and -16.8 kcal/mol, respectively. The binding energies of these complexes are in agreement with the measured K_ass values. However, in contrast to ⁰L, due to the presence of the linker, the phosphoester bonds of BNPP are not located in an in-line attack position of the nucleophile in ¹L and ²L. These complexes can catalyze BNPP hydrolysis through two distinct pathways: (1) Dissociative-associative and (2) associative (AS). The chemical nature of the linker is found to determine the preference of the pathway, i.e., the DA pathway for ¹L and ⁰L, while AS for ²L. Their rate-determining barriers follow the ⁰L (10.1 kcal/mol) < ¹L (22.0 kcal/mol) < ²L (25.4 kcal/mol) order. These variances in barriers are explained in terms of the effects of the distinct NCIs provided by these complexes. The measured kinetics and k_H/k_D values support these findings, offering insight into the roles NCIs play in controlling the reactivity of metal complexes. This understanding will pave the way toward the design of more efficient catalysts for multiple critical reactions.