H-Atom Abstraction Reactivity through the Lens of Asynchronicity and Frustration with Their Counteracting Effects on Barriers

0564247 - ÚFCH JH 2023 RIV US eng J - Journal Article
Maldonado-Domínguez, Mauricio - Srnec, Martin
H-Atom Abstraction Reactivity through the Lens of Asynchronicity and Frustration with Their Counteracting Effects on Barriers.
Inorganic Chemistry. Roč. 61, č. 47 (2022), s. 18811-18822. ISSN 0020-1669. E-ISSN 1520-510X
R&D Projects: GA ČR(CZ) GA21-10383S
Grant - others:Ministerstvo školství, mládeže a tělovýchovy - GA MŠk(CZ) LM2018140
Institutional support: RVO:61388955
Keywords : hydrogen atom abstraction * chemical reactions * thermodynamics
OECD category: Physical chemistry
Impact factor: 4.6, year: 2022
Method of publishing: Limited access

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.
Permanent Link: https://hdl.handle.net/11104/0335951