Glyoxalase I-type hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex

Article abstract of DOI:10.1021/ja0601336

The synthesis, characterization, and hemithioacetal isomerization reactivity of a mononuclear Ni(II) deprotonated amide complex, [(bppppa ^-)Ni]ClO₄·CH₃OH (1, bppppa^- = monoanion of N,N-bis-[(6-phenyl-2-pyridyl)methyl]-N-[(6-pivaloylamido-2- pyridyl)methyl]amine), are reported. Complex 1 was characterized by X-ray crystallography, ¹H NMR, UV-vis, FTIR, and elemental analysis. Treatment of 1 with an equimolar amount of the hemithioacetal PhC(O)CH(OH)SCD₃ in dry acetonitrile results in the production of the thioester PhCH(OH)C(O)SCD₃ in ～60% yield. This reaction is conveniently monitored via ²H NMR spectroscopy. A protonated analogue of 1, [(bppppa)Ni](ClO₄)₂ (2), is unreactive with the hemithioacetal, thus indicating the requirement of the anionic chelate ligand in 1 for hemithioacetal isomerization reactivity. Complex 1 is unreactive with the thioester product, PhCH(OH)C(OH)SCD₃, which indicates that the pK_a value for the PhCH(OH)C(O)SCD₃ proton of the thioester must be significantly higher than the pK_a value of the C-H proton of the hemithioacetal (PhC(O)CH(OH)SCD₃). Complex 1 is the first well-characterized Ni(II) coordination complex to exhibit reactivity relevant to Ni(II)-containing E. coli glyoxalase I. Treatment of NiBr₂-2H ₂O with PhC(O)CH(OH)SCD₃ in the presence of 1-methylpyrrolidine also yields thioester product, albeit the reaction is slower and involves the formation of multiple -SCD₃ labeled species, as detected by ₂H NMR spectroscopy. The results of this study provide the first insight into hemithioacetal isomerization promoted by a synthetic Ni(II) coordination complex versus a simple Ni(II) ion.