The reaction of electrophiles with models of iron–iron hydrogenase: A switch in regioselectivity Jesse W. Tye, Marcetta Y. Darensbourg * , Michael B. Hall ** Department of Chemistry, Texas A&M University, College Station, TX 77843-3255, USA Available online 1 April 2006 Abstract Simple dithiolate-bridged dinuclear iron clusters of the form (m-S(CH 2 ) x S)[Fe(CO) 2 (PR 3 )] 2 act as models of the active site of the enzyme iron-iron hydrogenase ([FeFe]H 2 ase). These complexes have been shown react with the electrophilic species, H C and Et C ðEt C ZCH 3 CH C 2 Þ with differing regioselectivity; H C reacts to form a 3c–2e K Fe–H–Fe bond, while Et C reacts to form a new C–S bond. We have used density functional theory (DFT) calculations to examine the reaction of these two electrophilic species using the computational model (m-SCH 2 CH 2 S)[Fe(CO) 2 (PH 3 )] 2 . In agreement with the experimental results, protonation of the Fe–Fe bond density is found to yield a much more stable complex than protonation of a bridging sulfur atom, while alkylation of a sulfur atom of the bridging thiolate is found to yield a much more stable complex than alkylation of the iron centers. Additional computations show that a mononuclear iron(II) complex with an Fe–E bond (EZH or Et) is significantly more stable than its constitutional isomer with iron(0) and an S–E bond. The instability of a bridging ethyl complex is attributed to the inability of the ethyl group, in contrast to a hydride, to form a stable 3c–2e K bond with the two iron centers. q 2006 Elsevier B.V. All rights reserved. Keywords: Hydrogenase; Enzyme model complexes; Iron–carbonyl complexes 1. Introduction The iron-iron hydrogenase enzymes ([FeFe]H 2 ases) facili- tate the reversible oxidation of dihydrogen to protons and electrons, H 2 /2H C C2e K [1–3]. The active site of these enzymes consists of a dithiolate bridged dinuclear iron assembly [4–6], which is similar in structure and composition to simple dithiolate-bridged dinuclear iron complexes of the form (m-SRS)[Fe(CO) 2 L] 2 as shown in Fig. 1 [7,8]. The reactions of models of [FeFe]H 2 ase with electrophilic species are important for a number of reasons. First, the reaction of these complexes with H C is a critical step in the electrocatalysis of H 2 . Second, the iron-based reaction of the formally Fe I Fe I complexes with certain electrophiles, generates the corresponding formally Fe II Fe II complexes, which are capable of binding and activating H 2 [9]. Third, the reaction of these complexes with various alkylating agents tunes the reactivity of the resulting di-iron complexes by modulating the donor ability of the bridging sulfur atoms. Finally, the reaction of these complexes with electrophiles provide another point of attachment (in addition to the S-to-S linker and donor ligands) for pendant functionalities, which may be used to attach potential electrocatalysts to the surface of an electrode. Dithiolate-bridged dinuclear iron complexes have been shown to react with a range of electrophilic species. The two main targets for electrophilic attack are the sulfur lone pairs of the bridging dithiolate ligand and the Fe–Fe bond, Scheme 1. Most common is the reaction of an electrophile, E C , with the Fe–Fe bond density to generate the corresponding [(m-E) (m-SRS)[Fe(CO) 2 L] 2 ] 1C [10]. In a few cases, however, the electrophile adds to a sulfur atom of the dithiolate bridge to form the corresponding [(m-SRSE)[Fe(CO) 2 L] 2 ] 1C complex. Specifically, the (m-SCH 2 CH 2 S)[Fe(CO) 2 (PMe 3 )] 2 complex reacts differently with the electrophiles H C and Et C , as determined by single-crystal X-ray diffraction and 1 H NMR and IR spectral studies on the resulting products [11,12]. The reaction of (m-SCH 2 CH 2 S)[Fe(CO) 2 (PMe 3 )] 2 with H C leads to the protonation of the Fe–Fe bond density (Scheme 1) generating the corresponding bridging hydride species [(m-H))(m-SCH 2 CH 2 S)[Fe(CO) 2 (PMe 3 )] 2 ] 1C , while its reaction with Et C leads to alkylation of a sulfur atom of the S-to-S linker (Scheme 1) generating the corresponding bridging thioether/bridging thiolate complex [(m-SCH 2 CH 2 SEt)[Fe(CO) 2 (PMe 3 )] 2 ] 1C . Journal of Molecular Structure: THEOCHEM 771 (2006) 123–128 www.elsevier.com/locate/theochem 0166-1280/$ - see front matter q 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2006.03.022 * Corresponding authors. Fax: C1 979 845 0158. ** Fax: C1 979 845 2971. E-mail addresses: marcetta@mail.chem.tamu.edu (M.Y. Darensbourg), mbhall@tamu.edu (M.B. Hall).