Controlling the Reactivity of a Metal-Hydroxo Adduct with a Hydrogen Bond

Abstract

The enzymes manganese lipoxygenase (MnLOX) and manganese superoxide dismutase (MnSOD) utilize mononuclear Mn centers to effect their catalytic reactions. In the oxidized Mn III state, the active site of each enzyme contains a hydroxo ligand, and X-ray crystal structures imply a hydrogen bond between this hydroxo ligand and a cis carboxylate ligand. While hydrogen bonding is a common feature of enzyme active sites, the importance of this particular hydroxo-carboxylate interaction is relatively unexplored. In this present study, we examined a pair of Mn III -hydroxo complexes that differ by a single functional group. One of these complexes, [Mn III (OH)(PaPy 2 N)] + , contains a naphthyridinyl moiety capable of forming an intramolecular hydrogen bond with the hydroxo ligand. The second complex, [Mn III (OH)(PaPy 2 Q)] + , contains a quinolinyl moiety that does not permit any intramolecular hydrogen bonding. Spectroscopic characterization of these complexes supports a common structure, but with perturbations to [Mn III (OH)(PaPy 2 N)] + , consistent with a hydrogen bond. Kinetic studies using a variety of substrates with activated O−H bonds, revealed that [Mn III (OH)(PaPy 2 N)] + is far more reactive than [Mn III (OH)(PaPy 2 Q)] + , with rate enhancements of 15−100-fold. A detailed analysis of the thermodynamic contributions to these reactions using DFT computations reveals that the former complex is significantly more basic. This increased basicity counteracts the more negative reduction potential of this complex, leading to a stronger O−H BDFE in the [Mn II (OH 2 )(PaPy 2 N)] + product. Thus, the differences in reactivity between [Mn III (OH)(PaPy 2 Q)] + and [Mn III (OH)(PaPy 2 N)] + can be understood on the basis of thermodynamic considerations, which are strongly influenced by the ability of the latter complex to form an intramolecular hydrogen bond.

Synthetic Advances for Mechanistic Insights: Metal–Oxygen Intermediates with a Macrocyclic Pyridinophane System

“…The interaction of the metal core with the secondary coordination sphere, such as a hydrogen bond, has been known to influence the chemical behaviors of metal–oxygen intermediates. − In this regard, we suggest another effect of the ligand architecture, that is, different bond strengths of the substituted groups in the secondary coordination sphere where the high-valent manganese­(IV)–hydroxo species have different stabilities toward the intramolecular C–H bond activation.…”

Aliphatic and Aromatic C–H Bond Oxidation by High-Valent Manganese(IV)-Hydroxo Species

“…Recently, metal-hydroxo species have also been recognized as critical intermediates in the catalytic event of metalloenzymes such as lipoxygenase (LOX). ,− Mn-LOX enzyme is proposed to oxidize C–H bonds of polyunsaturated fatty acids, where Mn III -hydroxo species performs the rate-determining hydrogen atom abstraction. Several mid- and high-valent metal-hydroxo complexes have been synthesized and spectroscopically characterized.…”

Oxidative versus basic asynchronous hydrogen atom transfer reactions of Mn(iii)-hydroxo and Mn(iii)-aqua complexes

“…Mechanisms of hydrogen atom transfer (HAT) reactions from organic substrates (SH) to metal-oxygen complexes, such as metal-oxo, metal-hydroxo, [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] metal-(hydro)peroxo [40][41][42][43][44] and metal-superoxo, [45][46][47][48][49][50][51][52][53][54] have been investigated extensively, as summarized in Scheme 1. HAT proceeds via the transfer of both a proton and an electron which can be transferred simul-spectrum of "asynchronicity", in which the transition state for the HAT reaction can contain either more PT or more ET character (Scheme 1).…”

“…Mechanisms of hydrogen atom transfer (HAT) reactions from organic substrates (SH) to metal–oxygen complexes, such as metal-oxo, 1–23 metal-hydroxo, 24–39 metal-(hydro)peroxo 40–44 and metal-superoxo, 45–54 have been investigated extensively, as summarized in Scheme 1. HAT proceeds via the transfer of both a proton and an electron which can be transferred simultaneously in a coupled fashion (concerted proton–electron transfer, CPET) or a stepwise fashion (proton transfer–electron transfer, PT/ET, or electron transfer–proton transfer, ET/PT) (Scheme 1).…”