Proton-Coupled OAT Triggers C2H2 Activation in a Bioinspired Molybdenum Complex.

Understanding acetylene coordination to group VI metals is crucial for elucidating the long-standing mechanistic ambiguities of tungstoenzyme acetylene hydratase (AH), for which several contrasting pathways have been proposed. Motivated by a recently hypothesized mechanism (Biochemistry2025, 64, 10, 2154-2172.) involving one-electron oxidation of the tungsten center, we explore the reactivity of the acetylene ligand in Mo- and W-AH models bearing 4,6-dimethylpyrimidine-2-thiolate (PymS) ligands, chosen to mimic the sulfur-rich environment of the AH active site. To trigger the redox chemistry and provide protons, half an equivalent of trimethylamine-N-oxide dihydrate (TMAO·2H2O) was added to the [MoO(C2H2)(PymS)2], yielding two distinct vinylated products: 4,6-dimethyl-1-vinylpyrimidine-2(1H)-thione and 4,6-dimethyl-2-(vinylthio)pyrimidine, which could be interpreted as acetaldehyde surrogates. In this transformation, TMAO serves as an oxygen atom donor, accepting electrons from Mo(IV), and triggers the formation of the μ-oxido Mo(V) dimer, which destabilizes the coordinated C2H2 and promotes the reaction with the neighboring ligand. The presence of a Mo(V) species was detected by EPR spectroscopy, supporting a radical nature of the reaction. In contrast, the C2H2 ligand in the tungsten analogue does not undergo vinylation, likely due to its ligand environment not stabilizing the +V oxidation state. These observations may be extended to the biochemistry of the AH active site, where the W(V) oxidation state would be more readily accessible. Finally, our data provide experimental evidence for potential redox events during biological acetylene hydration and additionally suggest that acetylene coordination is essential to the process.