Glyoxalase I-type Hemithioacetal Isomerization Reactivity of a Mononuclear Ni(II) Deprotonated Amide Complex

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(O)SCD3, which indicates that the pKa
value for the PhCH(OH)C(O)SCD3 proton of the thioester must be significantly higher than the pKa 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 NiBr2·2H2O 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.

本文报道了单核Ni(II)去质子化酰胺配合物[(bppppa⁻)Ni]ClO4·CH3OH（记为1，其中bppppa⁻为N,N-双[(6-苯基-2-吡啶基)甲基]-N-[(6-新戊酰氨基-2-吡啶基)甲基]胺的单阴离子形式）的合成、表征及其半硫缩醛异构化反应活性。配合物1通过X射线晶体衍射（X-ray crystallography）、氢核磁共振（¹H NMR）、紫外-可见吸收光谱（UV−vis）、傅里叶变换红外光谱（FTIR）以及元素分析进行了表征。将1与等摩尔量的半硫缩醛PhC(O)CH(OH)SCD3在干燥乙腈中反应，可得到硫酯PhCH(OH)C(O)SCD3，产率约为60%。该反应可通过氘核磁共振（²H NMR）光谱便捷监测。配合物1的质子化类似物[(bppppa)Ni](ClO4)2（记为2）与该半硫缩醛不发生反应，这表明配合物1中带负电荷的螯合配体是半硫缩醛异构化反应活性所必需的。配合物1与硫酯产物PhCH(OH)C(O)SCD3不发生反应，这说明该硫酯的PhCH(OH)C(O)SCD3质子的酸解离常数（pKa）显著高于半硫缩醛PhC(O)CH(OH)SCD3的C-H质子的酸解离常数。配合物1是首个被充分表征的、展现出与含Ni(II)的大肠杆菌（E. coli）乙醛酸酶I（glyoxalase I）相关反应活性的Ni(II)配位配合物。将二水合溴化镍（NiBr2·2H2O）与PhC(O)CH(OH)SCD3在1-甲基吡咯烷存在下反应，同样可得到硫酯产物，不过反应速率较慢，且通过氘核磁共振光谱检测发现会生成多种-SCD3标记的物种。本研究结果首次为合成Ni(II)配位配合物而非简单Ni(II)离子促进的半硫缩醛异构化反应提供了相关认知。