John Alex, Shaikh Mobin M, Ghosh Prasenjit
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400 076, India.
Dalton Trans. 2008 Jun 7(21):2815-24. doi: 10.1039/b801496e. Epub 2008 Apr 18.
A structural and functional mimic of the galactose oxidase (GOase) enzyme active-site by a copper complex supported over a sterically demanding ligand having [N2O2] donor sites is reported. Specifically, the binding of the histidine (496 and 581) and tyrosine (272 and 495) residues to the copper center in a square-pyramidal fashion in the active-site of galactose oxidase (GOase) enzyme has been modeled in a copper complex, ([(3-tert-butyl-5-methyl-2-hydoxybenzyl)(3'-tert-butyl-5'-methyl-2'-oxobenzyl)(2-pyridylmethyl)]amine)Cu(OAc)) (1b), stabilized over a sterically demanding ligand in which the two phenolate-O atoms mimicked the tyrosine binding while an amine-N and pyridyl-N atoms emulated the histidine binding to the metal center, similar to that in the enzyme active-site. Furthermore, the copper complex 1b is found to be an effective functional model of the enzyme as it efficiently catalyzed the chemoselective oxidation of primary alcohols to aldehydes in high turnover numbers under ambient conditions. An insight into the nature of the active-species was obtained by EPR and CV studies, which in conjunction with the DFT studies, revealed that the active-species is an anti-ferromagnetically coupled diamagnetic radical cation, (1)1b+, obtained by one electron oxidation at the equatorial phenolate-O atom of the ligand in the 1b complex.
报道了一种负载在具有[N2O2]供体位点的空间位阻配体上的铜配合物对半乳糖氧化酶（GOase）酶活性位点的结构和功能模拟。具体而言，在半乳糖氧化酶（GOase）酶活性位点中，组氨酸（496和581）和酪氨酸（272和495）残基以方锥形式与铜中心的结合已在一种铜配合物（[(3-叔丁基-5-甲基-2-羟基苄基)(3'-叔丁基-5'-甲基-2'-氧代苄基)(2-吡啶甲基)]胺）Cu(OAc)) (1b)中进行了模拟，该配合物稳定在一个空间位阻配体上，其中两个酚盐 - O原子模拟酪氨酸结合，而一个胺 - N和吡啶 - N原子模拟组氨酸与金属中心的结合，类似于酶活性位点中的情况。此外，发现铜配合物1b是该酶的有效功能模型，因为它在环境条件下以高周转数有效地催化了伯醇向醛的化学选择性氧化。通过电子顺磁共振（EPR）和循环伏安法（CV）研究深入了解了活性物种的性质，结合密度泛函理论（DFT）研究表明，活性物种是一种反铁磁耦合的抗磁性自由基阳离子(1)1b +，它是通过在1b配合物中配体的赤道酚盐 - O原子上进行单电子氧化获得的。
