Computational calculations of pKa values of imidazole in Cu(II) complexes of biological relevance
Computational calculations of pKa values of imidazole in Cu(II) complexes of biological relevance
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DOI：
10.1039/c0cp02319a
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Sodupe, Mariona
中科院分区：
文献类型：
--
作者：
Ali-Torres, Jorge;Rodriguez-Santiago, Luis;Sodupe, Mariona
咪唑环是组氨酸侧链的一部分。这种氨基酸的主要特征之一是能够配位铜，特别是Cu 2+，因为其咪唑环的中间基性质，具有很大的生物相关性。蛋白质如细胞色素c氧化酶（呼吸链中的关键酶）和β-淀粉样肽（与阿尔茨海默病的病理学有关）是在其配位领域中含有组氨酸的蛋白质的实例。几项研究表明，这种金属离子的存在会导致组氨酸咪唑环的pK（a）降低。然而，还没有关于这些类型的金属阳离子络合物中pK（a）变化的系统研究的报道。本文利用密度泛函理论研究了咪唑pK（a）与咪唑环数目在Cu ~（2+）配位环境中的关系。用具有不同交换率的B3 LYP和MPWB 1 K泛函和高相关CCSD（T）方法研究了咪唑（ImH）和咪唑在Cu ~（2+）（ImH）（m）（H_2O）（4-m）（m = 1-3）配合物中的pK（a）.结果表明，咪唑pK（a）下降2和7个单位之间，这取决于所采用的方法和咪唑环配位的金属阳离子的数量。考虑到咪唑的pK（a）为14，这种降低可能与生物过程有关。
The imidazole ring is part of the lateral chain of histidine. One of the main features of this amino acid is the ability to coordinate copper, especially Cu2+, because of the intermediate base nature of its imidazole ring, which has a great biological relevance. Proteins such as cytochrome c oxidase, a crucial enzyme in the respiratory chain, and beta-amyloid peptide, implicated in the pathology of Alzheimer's disease, are examples of proteins containing histidines in their coordination sphere. Several studies indicate that the presence of this metal ion produces a decrease in the pK(a) of the imidazole ring of histidine. However, there are no reports of systematic studies of pK(a) variation in these types of metal cation complexes. In this work we use density functional theory to study the dependence of imidazole pK(a) with the number of imidazole rings in Cu2+ coordination environments. The pK(a) of isolated imidazole (ImH), and the pK(a) of imidazole in Cu2+(ImH)(m)(H2O)(4-m) (m = 1-3) complexes have been studied using two different functionals, B3LYP and MPWB1K, which have different percentage of exact exchange, and the highly-correlated CCSD(T) method. Results show that imidazole pK(a) decreases between 2 and 7 units depending on the method employed and the number of imidazole rings coordinating the metal cation. Taking into account that the pK(a) of imidazole is 14, this decrease could be relevant in biological processes.