Beyond the classical thermodynamic contributions to hydrogen atom abstraction reactivity

Abstract

Hydrogen atom abstraction (HAA) reactions are cornerstones of chemistry. Various (metallo)enzymes performing the HAA catalysis evolved in nature and inspired the rational development of multiple synthetic catalysts. Still, the factors determining their catalytic efficiency are not fully understood. Herein, we define the simple thermodynamic factor η by employing two thermodynamic cycles: one for an oxidant (catalyst), along with its reduced, protonated, and hydrogenated form; and one for the substrate, along with its oxidized, deprotonated, and dehydrogenated form. It is demonstrated that η reflects the propensity of the substrate and catalyst for (a)synchronicity in concerted H+/e− transfers. As such, it significantly contributes to the activation energies of the HAA reactions, in addition to a classical thermodynamic (Bell–Evans–Polanyi) effect. In an attempt to understand the physicochemical interpretation of η, we discovered an elegant link between η and reorganization energy λ from Marcus theory. We discovered computationally that for a homologous set of HAA reactions, λ reaches its maximum for the lowest |η|, which then corresponds to the most synchronous HAA mechanism. This immediately implies that among HAA processes with the same reaction free energy, ΔG0, the highest barrier (≡ΔG≠) is expected for the most synchronous proton-coupled electron (i.e., hydrogen) transfer. As proof of concept, redox and acidobasic properties of nonheme FeIVO complexes are correlated with activation free energies for HAA from C−H and O−H bonds. We believe that the reported findings may represent a powerful concept in designing new HAA catalysts.

Regulating the Basicity of Metal–Oxido Complexes with a Single Hydrogen Bond and Its Effect on C–H Bond Cleavage

“…A similar premise has recently been reported for a Co III –oxido complexes 30 and found from theoretical analyzes of [Fe III H 3 buea(O)] 2- and Fe IV –oxido complexes. 55,56…”

“…Results from our experimental investigations indicate that our systems do not follow any of these mechanisms which prompted us to consider other possibilities. Asynchronous processes 55,56 in which the proton and electron are transferred unequally to a M–oxido unit at the transition state have also been touted as relevant pathways for C–H bond activation. Our results with 1 - 5 fit this type of description and offer support of the premise that asynchronous mechanistic routes are important in the activation of C–H bond activation by M-oxido complexes.…”

From Synthetic to Biological Fe4S4 Complexes: Redox Properties Correlated to Function of Radical S‐Adenosylmethionine Enzymes

“…As demonstrated in Refs. [37][38][39][40][41][42][43][44], H-atom-abstraction (HAA) reactivity and selectivity are strongly influenced by the interplay of redox and acidobasic components of the HAA thermodynamic force, which are usually inter-dependent so that a lower E°is compensated to some extent by a higher pK a and vice versa. Thus, to probe the 5'-dAdo * properties relevant for enzymatic HAA reactivity, we first analyze electrochemical behavior of 5'-dAdo * in aqueous solution and then we compare it with its behavior in models of the [Fe 4…”

“…force, which would steer the asynchronicity between proton and electron transfers in favor of proton transfer (for the definition of asynchronicity and its effect on the HAA barrier see Ref. [37]). This is currently a matter of undergoing research in our laboratory.…”

Radiolysis generates a complex organosynthetic chemical network

“…Radical reactions can proceed via low barriers without requiring further activation by a catalyst 7 . Radicals can exhibit powerful electrochemical potentials (far greater than even the most potent combinations of geochemical substrates 8 ) and can be readily sourced from both organic and inorganic substrates to drive a wide array of organic redox reactions 9 – 11 . Indeed, a number of enzyme-facilitated biochemical redox potentials exceed tabulated geochemical potentials, indicating that non-enzymatic predecessors of these reactions, for kinetic reasons alone, may have required radiolysis, photolysis or extremely powerful phosphorylating intermediates to drive protometabolism 12 .…”