Tripodal Bis(imidazole) Thioether Copper(I) Complexes: Mimics of the Cu_M Site of Copper Hydroxylase Enzymes

Tripodal bis(imidazole) thioether ligands, (N-methyl-4,5-diphenyl-2-imidazolyl)2C(OR)C(CH3)2SR‘ (BITOR,SR‘; R = H, CH3; R‘ = CH3, C(CH3)3, C(C6H5)3), have been prepared, offering the same N2S donor atom set as the CuM binding site of the hydroxylase enzymes, dopamine beta hydroxylase and peptidylglycine hydroxylating monooxygenase. Isolable copper(I) complexes of the type [(BITOR,SMe)Cu(CO)]PF6 (3a and 3b) are produced in reactions of the respective tripodal ligands 1a (R = H) and 1b (R = Me) with [Cu(CH3CN)4]PF6 in CH2Cl2 under CO (1 atm); the pyramidal structure of 3a has been determined crystallographically. The infrared (IR) ν(CO)'s of 3a and 3b (L = CO) are comparable to those of the CuM-carbonylated enzymes, indicating similar electronic character at the copper centers. The reaction of [(BITOH,SMe)Cu(CH3CN)]PF6 (2a) with dioxygen produces [(BITO,SOMe)2Cu2(DMF)2](PF6)2 (4), whose X-ray structure revealed the presence of bridging BIT−alkoxo ligands and terminal −SOMe groups. In contrast, oxygenation of 2b (R = Me) affords crystallographically defined [(BITOMe,SMe)2Cu2(μ-OH)2](OTf)2 (5), in which the copper centers are oxygenated without accompanying sulfur oxidation. Complex 5 in DMF is transformed into five-coordinate, mononuclear [CuII(BITOMe,SMe)(DMF)2](PF6)2 (6). The sterically hindered BITOR,SR‘ ligands 9 and 10 (R‘ = t-Bu; R = H, Me) and 11 and 12 (R‘ = CPh3; R = H, Me) were also prepared and examined for copper coordination/oxygenation. Oxygenation of copper(I) complex 13b derived from the BITOMe,SBu-t ligand is slow, relative to 2b, producing a mixture of (BITOMe,SBu-t)2Cu2(μ-OH)2-type complexes 14b and 15b in which the −SBu-t group is uncoordinated; one of these complexes (15b) has been ortho-oxygenated on a neighboring aryl group according to the X-ray analysis and characterization of the free ligand. Oxygenation of the copper(I) complex derived from BITOMe,SCPh3 ligand 12 produces a novel dinuclear disulfide complex, [(BITOMe,S)2Cu2(μ-OH)2](PF6)2 (17), which is structurally characterized. Reactivity studies under anaerobic conditions in the presence of t-BuNC indicate that 17 is the result of copper(I)-induced detritylation followed by oxygenation of a highly reactive copper(I)−thiolate complex.三脚架型双(咪唑)硫醚配体（tripodal bis(imidazole) thioether ligands），通式为(N-甲基-4,5-二苯基-2-咪唑基)₂C(OR)C(CH₃)₂SR'（BITOR,SR'；R=H、CH₃；R'=CH₃、叔丁基、三苯甲基），已被成功合成。该类配体具备与羟化酶——多巴胺β羟化酶（dopamine β-hydroxylase）与肽基甘氨酸羟化单加氧酶（peptidylglycine α-hydroxylating monooxygenase）——的CuM结合位点完全一致的N₂S供原子配位环境。通过三脚架型配体1a（R=H）与1b（R=CH₃）分别与四(乙腈)合铜(I)六氟磷酸盐（tetrakis(acetonitrile)copper(I) hexafluorophosphate, [Cu(CH3CN)4]PF6）在二氯甲烷（dichloromethane, CH2Cl2）溶剂中、1atm一氧化碳氛围下反应，可得到可分离的[(BITOR,SMe)Cu(CO)]PF6型铜(I)配合物（3a与3b）；配合物3a的锥状结构已通过单晶X射线衍射解析确定。配合物3a与3b（配体L=CO）的红外CO伸缩振动频率（infrared ν(CO)）与CuM羰基化酶的数值相近，表明二者铜中心具有相似的电子特性。[(BITOH,SMe)Cu(CH3CN)]PF6（2a）与氧气的反应产物为[(BITO,SOMe)2Cu2(DMF)2](PF6)2（4），其中DMF即N,N-二甲基甲酰胺（N,N-dimethylformamide），其单晶X射线衍射结构显示体系中存在桥联BIT-烷氧基配体与端基-SOMe基团。与之相反，2b（R=CH₃）的氧化反应得到经单晶X射线衍射确证的[(BITOMe,SMe)2Cu2(μ-OH)2](OTf)2（5），其中OTf即三氟甲磺酸盐（triflate），该配合物的铜中心被氧化，但硫原子未发生氧化。配合物5在N,N-二甲基甲酰胺（DMF）中可转化为五配位单核铜(II)配合物[CuII(BITOMe,SMe)(DMF)2](PF6)2（6）。空间位阻型BITOR,SR'配体9、10（R'=叔丁基；R=H、CH₃）与11、12（R'=三苯甲基；R=H、CH₃）也已被合成，并用于铜配位与氧化反应的研究。由BITOMe,SBu-t配体衍生的铜(I)配合物13b的氧化反应相较于2b更为缓慢，反应生成(BITOMe,SBu-t)2Cu2(μ-OH)2型配合物14b与15b的混合物，其中-SBu-t基团未参与配位；通过游离配体的X射线衍射分析与表征可知，其中配合物15b的邻位芳基发生了氧化修饰。由BITOMe,SCPh3配体12衍生的铜(I)配合物经氧化后得到一种新型双核二硫配合物[(BITOMe,S)2Cu2(μ-OH)2](PF6)2（17），其结构已通过单晶X射线衍射解析确证。在无氧条件下以叔丁基异腈（tert-butyl isocyanide, t-BuNC）为探针的反应活性研究表明，配合物17是铜(I)诱导的脱三苯甲基反应，随后高活性铜(I)-硫醇盐配合物发生氧化的产物。