Syntheses, characterization, density functional theory calculations, and activity of tridentate SNS zinc pincer complexes

A series of tridentate SNS ligand precursors were metallated with ZnCl₂ to give new tridentate SNS pincer zinc complexes. The zinc complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH) and were characterized with single crystal X-ray diffraction, ¹H, ¹³C, and HSQC NMR spectroscopies and electrospray mass spectrometry. The bond lengths and bond angles of the zinc complexes correlate well to those in horse LADH. The zinc complexes feature SNS donor atoms and pseudotetrahedral geometry about the zinc center, as is seen for liver alcohol dehydrogenase. The SNS ligand precursors were characterized with ¹H, ¹³C, and HSQC NMR spectroscopies and cyclic voltammetry, and were found to be redox active. Gaussian calculations were performed and agree quite well with the experimentally observed oxidation potential for the pincer ligand. The zinc complexes were screened for the reduction of electron poor aldehydes in the presence of a hydrogen donor, 1-benzyl-1,4-dihydronicotinamide (BNAH). The zinc complexes enhance the reduction of electron poor aldehydes. Density functional theory calculations were performed to better understand why the geometry about the zinc center is pseudo-tetrahedral rather than pseudo-square planar, which is seen for most pincer complexes. For the SNS tridentate pincer complexes, the data indicate that the pseudo-tetrahedral geometry was 43.8 kcal/mol more stable than the pseudo-square planar geometry. Density functional theory calculations were also performed on zinc complexes with monodentate ligands and the data indicate that the pseudo-tetrahedral geometry was 30.6 kcal/mol more stable than pseudo-square planar geometry. Overall, the relative stabilities of the pseudo-tetrahedral and pseudo-square planar systems are the same for this coordination environment whether the ligand set is a single tridentate SNS system or is broken into three separate units. The preference of a d¹⁰ Zn center to attain a tetrahedral local environment trumps any stabilization gained by removal of constraints within the ligand set.