Nickel pincer model of the active site of lactate racemase involves ligand participation in hydride transfer

Abstract

Lactate racemase is the first enzyme known to possess a metal pincer active site. The enzyme interconverts d- and l-lactic acid, which is important for the assembly of cell walls in many microorganisms. Here, we report a synthetic model of the active site of lactate racemase, which features a pyridinium-based SCS pincer ligand framework bound to nickel. The model complex mediates the dehydrogenation of alcohols, a reaction relevant to lactate racemization. Experimental and computational data indicate ligand participation in the dehydrogenation reaction.

Keywords: biomimetic chemistry; hydride transfer; lactate racemase; nickel; pincer ligands.

Fig. 1.

Proposed catalytic mechanism of lactate racemase.

Fig. 2.

Synthesis of the pincer ligands and complexes.

Fig. 3.

Solid-state structure of complexes 5 (A) and 7 (B). The thermal ellipsoids are displayed at 50% probability.

Fig. 4.

Alcohol oxidation mediated by Ni pincer complexes. The reactions were conducted under N₂, and the yields were determined by GC using n-decane as the internal standard.

Fig. 5.

Potential mechanisms for the dehydrogenation of benzyl alcohol mediated by complex 7.

Fig. 6.

Computed Gibbs free-energy profiles of possible mechanistic pathway for alcohol dehydrogenations by 7 and 5. Reported free energies, in kilocalorie per mole, computed at the PBE0-dDsC/TZ2P//M06/def2-SVP level including solvation corrections in acetonitrile.