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.

The selective functionalization of C–H bonds is one of the Grails of synthetic chemistry. In this work, we demonstrate that the selectivity toward fast hydroxylation or radical diffusion (known as the OH-rebound and dissociation mechanisms) following H-atom abstraction (HAA) from a substrate C–H bond by high-valent iron-oxo oxidants is already encoded in the HAA step when the post-HAA barriers are much lower than the preceding one. By applying the reactive mode composition factor (RMCF) analysis, which quantifies the kinetic energy distribution (KED) at the reactive mode (RM) of transition states, we show that reactions following the OH-rebound coordinate concentrate the RM kinetic energy on the motion of the reacting oxygen atom and the nascent substrate radical, whereas reactions following the dissociation channel localize most of their kinetic energy in H-atom motion. These motion signatures serve to predict the post-HAA selectivity, and since KED is affected by the free energy of reaction and asynchronicity (factor η) of HAA, we show that bimolecular HAA reactions in solution that are electron transfer-driven and highly exergonic have the lowest fraction of KED on the transferred H-atom and the highest chance to follow rebound hydroxylation. Finally, the RMCF analysis predicts that the H/D primary kinetic isotope effect can serve as a probe for these mechanisms, as confirmed in virtually all reported examples in the literature.

The kinetic energy distribution in the reactive mode in transition states correlates the asynchronicity of CPET with relative kinetic isotope effects.

The adsorption of surfactants (DTAB, SDS, and CAPB) at the calcite-water interface was studied through surface zeta potential measurements and multiscale molecular dynamics. The ground-state polarization of surfactants proved to be a key factor for the observed behavior; correlation was found between adsorption and the hard or soft charge distribution of the amphiphile. SDS exhibits a steep aggregation profile, reaching saturation and showing classic ionic-surfactant behavior. In contrast, DTAB and CAPB featured diversified adsorption profiles, suggesting interplay between supramolecular aggregation and desorption from the solid surface and alleviating charge buildup at the carbonate surface when bulk concentration approaches CMC. This manifests as an adsorption profile with a fast initial step, followed by a metastable plateau and finalizing with a sharp decrease and stabilization of surface charge. Suggesting this competition of equilibria, elicited at the CaCO3 surface, this study provides atomistic insight into the adsorption mechanism for ionic surfactants on calcite, which is in accordance with experimental evidence and which is a relevant criterion for developing enhanced oil recovery processes.

Hydrogen atom abstraction (HAA) is central to life, and its importance in synthetic chemistry continues to grow. Enzymes rely on HAA to trigger life-sustaining reaction cascades, and greener synthetic routes are attainable by in situ capture of the carbon-centered radicals generated by HAA. Despite the potential of HAA for the diversification of molecular complexity and the late-stage functionalization of bioactive compounds, readily applicable and reliable models translating experimentally or computationally accessible thermodynamic quantities into relative free energy barriers are missing. In this work, we discovered a complete thermodynamic basis for the description of HAA reactivity, which consists of three components. Besides, the traditional linear free energy relationship and the recently introduced factor of asynchronicity (Srnec et al., PNAS 2018, 115, E10287-E10294), we present the third thermodynamic component of H atom abstraction reactions: the factor of frustration that arises from the dissimilarity of the species competing over a hydrogen atom in their overall ability to acquire an electron and proton. Incorporating these nonclassical descriptors into a Marcus-type model, the approach herein presented allows nearly quantitative prediction of relative barriers in six sets of metal-oxo-mediated HAA reactions, outperforming existing methods even in a stringent test with >200 computational HAA reactions.