Structural and functional synthetic model of mono-iron hydrogenase featuring an anthracene scaffold

Abstract

Mono-iron hydrogenase was the third type of hydrogenase discovered. Its Lewis acidic iron(II) centre promotes the heterolytic cleavage of the H-H bond and this non-redox H activation distinguishes it from the well-studied dinuclear [FeFe] and [NiFe] hydrogenases. Cleavage of the H-H bond is followed by hydride transfer to the enzyme's organic substrate, HMPT, which serves as a CO 'carrier' in methanogenic pathways. Here we report a scaffold-based synthetic approach by which to model mono-iron hydrogenase using an anthracene framework, which supports a biomimetic fac-C,N,S coordination motif to an iron(II) centre. This arrangement includes the biomimetic and organometallic Fe-C σ bond, which enables bidirectional activity reminiscent of the native enzyme: the complex activates H under mild conditions, and catalyses C-H hydride abstraction plus H generation from a model substrate. Notably, neither H activation nor C-H hydride abstraction was observed in the analogous complex with a pincer-type mer-C,N,S ligation, emphasizing the importance of the fac-C,N,S-iron(II) motif in promoting enzyme-like reactivity.

Biomimetic Hydrogenation Catalyzed by a Manganese Model of [Fe]‐Hydrogenase

“…However, the Fe‐acyl moiety was prone to decomposition via decarbonylation so that catalysis could not be achieved. Two Fe models supported by an anthracene‐bridged NCS ligand could also activate H 2 . Notably these two models contained a carbamoyl donor, instead of the acyl donor found in the enzyme.…”

“…In this context, we examined the hydrogenation of substrates similar to the native substrate of [Fe]‐hydrogenase, namely, methenyl‐H 4 MPT + . The hydrogenation of the 1,3‐bis(2,6‐difluorophenyl)‐2‐(4‐tolyl)imidazolinium cation (in its bromide salt 9 a ), a previously reported model of methenyl‐H 4 MPT + , was first tested. After optimizing conditions (see Table S2 in the Supporting Information), we obtained a yield of 92 % for the hydrogenation of 9 a to generate 10 a using 2.5 mol % of 5 as catalyst (Scheme ).…”

Functional Hydride Transfer by a Thiolate‐Containing Model of Mono‐Iron Hydrogenase featuring an Anthracene Scaffold

“…We previously reported using a1 ,8-anthracene scaffold bearing at hioether moiety in af unctional modeling study (H 2 activation, H-D scrambling,a nd CÀH hydride abstraction-but no hydride transfer). [9] Thep roposed structure was supported by spectroscopy and theoretical calculation, [9,11] but direct structural evidence (X-ray) for the fac-CNS chelating motif remained elusive.H erein, we report the structural characterization of as ynthetic model derived from the anthracene scaffold that exhibits H 2 activation and hydride transfer activity.…”

Functional Hydride Transfer by a Thiolate‐Containing Model of Mono‐Iron Hydrogenase featuring an Anthracene Scaffold

“…[8] We reasoned that an asymmetric anthracenebased ligand could support af acial set of biomimetic donors (Figure 1, right). [9] Thep roposed structure was supported by spectroscopy and theoretical calculation, [9,11] but direct structural evidence (X-ray) for the fac-CNS chelating motif remained elusive.H erein, we report the structural characterization of as ynthetic model derived from the anthracene scaffold that exhibits H 2 activation and hydride transfer activity. [9] Thep roposed structure was supported by spectroscopy and theoretical calculation, [9,11] but direct structural evidence (X-ray) for the fac-CNS chelating motif remained elusive.H erein, we report the structural characterization of as ynthetic model derived from the anthracene scaffold that exhibits H 2 activation and hydride transfer activity.…”

“…[9,10] Thek ey breakthrough herein is the inclusion of the aryl thiolate with abulky dimethylphenyl unit at the ortho position to maintain mononuclearity.T he bulky synthon was prepared by base-catalyzed ring-opening of 2-amino-6-bromobenzothiazole followed by treatment with MeI. Thea symmetric aminopyridine synthon Anth·py NH 2 ·Cl was obtained utilizing Pd 2 -(dba) 3 /SPhos as catalyst.…”