Work

A Synthetic Iron Model of Carbon–Sulfur Bond Activation by the Nitrogenase-Family Enzyme Methylthio-Alkane Reductase

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide The all-iron (FeFe) nitrogenase utilizes a complex iron–sulfur cluster to catalyze the reduction of dinitrogen to ammonia (N 2 R). Recently, it has been found that methylthio-alkane reductase ( mar ), which reduces methyl thioalkanes to methanethiol and hydrocarbon fragments, has a structurally similar active site. In this report, we explore the reactivity of a trisphosphine boratrane iron complex ([Fe]), an N 2 R catalyst, with thioalkanes as a functional model system. Reacting the neutral iron dinitrogen complex ([Fe(N 2 )]) with dimethyl sulfide (Me 2 S) yields a 1:1 mixture of iron methyl ([FeMe]) and iron methyl thiolate ([Fe(SMe)]) products. Subsequent protonation forms methane and methanethiol, the products of Me 2 S reduction by mar . Kinetic studies, including kinetic isotope effects (KIE), pre-equilibrium Van’t Hoff parameters, and Eyring analysis, as well as the reactivity with a broad scope of thioalkanes, point to [Fe(SMe 2 )], formed via an uphill pre-equilibrium with [Fe(N 2 )] as a key intermediate. In [Fe(SMe 2 )], the C–S bond strength decreases by 44 kcal mol –1, priming it for bond homolysis. We propose that homolytic C–S bond cleavage occurs with the released alkyl radical being trapped by a second equivalent of iron. Comparisons of N 2 and thioalkane reduction by [Fe] suggest similar modes of substrate activation at Fe, namely, backbonding into a π* orbital of N≡N and a C–S σ* orbital of Me 2 S, setting the substrates up for N–H bond formation and homolytic C–S bond cleavage, respectively.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.6c05863

Authors: Christian M. Johansen, Derek R. Kuno-Williams, John M. Ovian, Jonas C. Peters

Institution: California Institute of Technology

Language: English

Topic: Metalloenzymes and iron-sulfur proteins

Subfield: Renewable Energy, Sustainability and the Environment

Field: Energy

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: Resnick Sustainability Institute for Science, Energy and Sustainability, California Institute of Technology, National Institutes of Health, National Institute of General Medical Sciences