Dataset of "Elucidation of factors shaping reactivity of 5'-deoxyadenosyl – a prominent organic radical in biology"

This study investigates the factors modulating the reactivity of 5'-deoxyadenosyl (5'dAdo•) radical, a potent hydrogen atom abstractor, present in the active sites of radical SAM enzymes, but otherwise undergoing a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5'dAdo• in aqueous solution and in two enzymatic microenvironments and reveal that HAA efficiency of 5'dAdo• depends on (i) formation of 5'dAdo• in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5'dAdo• complex formation, (ii) hindering the conformational change associated with self-decay by performing the reaction in a tight cavity. The enzymatic cavity, however, does not have a strong effect on the HAA activity of 5'dAdo•. We performed an analysis of HAA performed by 5'dAdo• based on the three-component thermodynamic model incorporating the diagonal effect of the free energy of reaction, and the off-diagonal effect of asynchronicity and frustration. The study is based on the straightforward relationship between the off-diagonal thermodynamic effects and the electronic-structure descriptor – the redistribution of charge between the reactants during the reaction. It allows to access HAA-competent redox and acidobasic properties of 5'dAdo• that are otherwise unavailable due to its instability upon one-electron reduction and protonation. The results show that all reactions feature a favourable thermodynamic driving force and tunneling, the latter of which lowers systematically barriers by ~2 kcal mol-1. In addition, most of the reaction experience a favourable off-diagonal thermodynamic contribution. In HAA reactions, 5'dAdo• acts as a weak oxidant as well as a base, also 5'dAdo•-promoted HAA reactions proceed with quite low degree of asynchronicity of proton and electron transfer. Finally, the study elucidates the crucial and dual role of asynchronicity. It directly lowers the barrier as a part of the off-diagonal thermodynamic contribution, but also indirectly increases the non-thermodynamic part of the barrier by controlling the adiabatic coupling between proton and electron transfer. The latter signals that the reaction proceeds as a hydrogen atom transfer rather than a proton-coupled electron transfer.