Semiempirical method for examining asynchronicity in metal-oxido-mediated C-H bond activation

The oxidation of substrates via the cleavage of thermodynamically strong C-H bonds is an essential part of mammalian metabolism. These reactions are predominantly carried out by enzymes that produce high-valent metal-oxido species, which are directly responsible for cleaving the C-H bonds. While much is known about the identity of these transient intermediates, the mechanistic factors that enable metal-oxido species to accomplish such difficult reactions are still incomplete. For synthetic metal-oxido species, C-H bond cleavage is often mechanistically described as synchronous, proton-coupled electron transfer (PCET). However, data have emerged that suggest that the basicity of the M-oxido unit is the key determinant in achieving enzymatic function, thus requiring alternative mechanisms whereby proton transfer (PT) has a more dominant role than electron transfer (ET). To bridge this knowledge gap, the reactivity of a monomeric MnIV-oxido complex with a series of external substrates was studied, resulting in a spread of over 104 in their second-order rate constants that tracked with the acidity of the C-H bonds. Mechanisms that included either synchronous PCET or rate-limiting PT, followed by ET, did not explain our results, which led to a proposed PCET mechanism with asynchronous transition states that are dominated by PT. To support this premise, we report a semiempirical free energy analysis that can predict the relative contributions of PT and ET for a given set of substrates. These findings underscore why the basicity of M-oxido units needs to be considered in C-H functionalization.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:118

Enthalten in:

Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 36 vom: 07. Sept.

Sprache:

Englisch

Beteiligte Personen:

Barman, Suman K [VerfasserIn]
Yang, Meng-Yin [VerfasserIn]
Parsell, Trenton H [VerfasserIn]
Green, Michael T [VerfasserIn]
Borovik, A S [VerfasserIn]

Links:

Volltext

Themen:

C–H bond activation
Journal Article
Metal–oxido complexes
PCET
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 06.12.2021

Date Revised 01.03.2022

published: Print

Citation Status PubMed-not-MEDLINE

doi:

10.1073/pnas.2108648118

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330083082