New Monomeric Cobalt(II) and Zinc(II) Complexes of a Mixed N,S(alkylthiolate) Ligand: Model Complexes of (His)(His)(Cys) Metalloprotein Active Sites

The new N2S(alkylthiolate) ligand 2-methyl-1-[methyl-(2-pyridin-2-ylethyl)amino]propane-2-thiolate, PATH (1), has
been prepared and reacted with zinc(II) and cobalt(II) to give the monomeric complexes [(PATH)ZnBr] (2), [(PATH)ZnNCS] (3), [(PATH)CoBr] (4), and [(PATH)CoNCS] (5). The molecular structures of 4 and 5 have been determined
by X-ray diffraction. Each complex displays a distorted tetrahedral geometry at the metal center, with the PATH
ligand providing the N2S(alkylthiolate) donors. These complexes are close structural mimics of the active site of
metalloproteins with a His2Cys−MII site such as that found in peptide deformylase. Complexes 4 and 5 are the first
examples of crystallographically characterized CoII complexes with an N2SL (L ≠ N,S) donor set. Only one
diastereomer for 2−5 is observed in the solid state, and simple molecular mechanics (Chem3D) calculations suggest
this isomer is stable because of a favorable ligand conformation. NMR studies in the case of ZnII and UV−vis
studies in the case of CoII provide strong evidence that their solid-state structures are retained in solution. Cyclic
voltammetry reveals processes for both the CoII/I (4, − 1.51 V; 5, − 1.49 V) and CoIII/II (4, + 0.9 V; 5, + 0.9 V)
couples. The UV−vis data for the cobalt complexes are consistent with a monomeric, four-coordinate geometry
regardless of the nature of the solvent (i.e., donating (MeOH, CH3CN) vs nondonating (CH2Cl2)) and are compared
with other cobalt complexes as well as cobalt-substituted His2Cys metalloproteins (peptide deformylase and blue-copper proteins). In addition, reaction of the bromide complexes 2 and 4 with hydroxide anion leads to the formation
of 1:1 hydroxide:MII complexes which have been characterized in situ by 1H NMR and UV−vis spectroscopy,
respectively.

新型N₂S(烷基硫代盐)配体2-甲基-1-[甲基-(2-吡啶-2-基乙基)氨基]丙烷-2-硫代盐（PATH，1）已被合成，并分别与锌(II)、钴(II)反应，得到单核配合物[(PATH)ZnBr]（2）、[(PATH)ZnNCS]（3）、[(PATH)CoBr]（4）与[(PATH)CoNCS]（5）。配合物4和5的分子结构经X射线衍射（X-ray diffraction）表征。所有配合物的金属中心均呈现畸变四面体几何构型，PATH配体提供N₂S(烷基硫代盐)配位位点。此类配合物是具有His₂Cys−MⅡ活性位点的金属蛋白酶活性中心的精准结构模拟物，例如肽脱甲酰基酶（peptide deformylase）中的活性位点。配合物4和5是首例经晶体学表征的、带有N₂SL（L≠N,S）配位环境的CoⅡ配合物。固态下仅观测到2~5的一种非对映异构体，通过简单分子力学（Chem3D）计算可知，该异构体因配体构象有利而具有更高稳定性。针对锌(II)配合物的核磁共振（NMR）研究，以及针对钴(II)配合物的紫外-可见（UV−vis）光谱研究，均提供了强有力证据，证明二者在溶液中保留了固态结构。循环伏安法（cyclic voltammetry）检测到了CoⅡ/Ⅰ（4：-1.51 V；5：-1.49 V）与CoⅢ/Ⅱ（4：+0.9 V；5：+0.9 V）的氧化还原电对过程。钴配合物的紫外-可见光谱数据显示，无论溶剂性质如何（即给电子溶剂如甲醇(MeOH)、乙腈(CH₃CN)，与非给电子溶剂如二氯甲烷(CH₂Cl₂)），其均为单核四配位几何构型；研究团队还将该数据与其他钴配合物，以及钴取代的His₂Cys金属蛋白酶（肽脱甲酰基酶与蓝铜蛋白）的相关数据进行了对比。此外，溴化物配合物2和4分别与氢氧根阴离子反应，生成了1:1的氢氧根:MⅡ配合物，二者分别通过¹H核磁共振（¹H NMR）与紫外-可见光谱完成了原位表征。