化学
咪唑酯
脱质子化
咪唑
铜
齿合度
铜蛋白
组氨酸
氧化还原
光化学
组合化学
立体化学
无机化学
有机化学
金属
酶
离子
作者
Tao A. G. Large,William Keown,J. Brannon Gary,Linus Chiang,T. Daniel P. Stack
标识
DOI:10.1002/anie.202416967
摘要
Imidazole ligation of metals through histidine is extensive among metalloproteins and enzymes, yet the role of the imidazolate conjugate base is often neglected, despite its potential accessibility when bonded to a highly oxidized metal center. Using synthetic models of oxygenated tyrosinase enzymes with exclusive monodentate imidazole ligation, we find that deprotonation of the μ2‐η2:η2‐peroxidodicopper(II) species triggers redox isomerization to an imidazolate‐ligated bis(μ2‐oxido)dicopper(III) species. Formal two‐electron oxidation to Cu(III) remains unprecedented in biological systems, yet is effected readily by addition of base in these model systems. Spectrophotometric titrations by UV/visible/near‐IR and copper K‐edge X‐ray absorption spectroscopies are interpreted most simply as two cooperative, 2H+ transformations in which the peroxide O‐O is cleaved in the first step. Elaboration from simple imidazoles to a protected histidine extends this isomerization into an amino acid environment. The role of phenolate as a base suggests this four‐electron reduction of O2 is energetically viable in a biological context and requires only two copper centers, which act as two‐electron shuttles when imidazole deprotonation assists. This existential precedent of viable imidazolate intermediates invites speculation into an alternative mechanism for phenol hydroxylation not previously considered at Type 3 copper sites such a tyrosinases.
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