The University of Kansas, Department of Chemistry and Center for Environmentally Beneficial Catalysis, 1567 Irving Hill Road, Lawrence, Kansas 66045, United States.
J Am Chem Soc. 2021 Sep 22;143(37):15159-15175. doi: 10.1021/jacs.1c06199. Epub 2021 Sep 8.
The enzymes manganese lipoxygenase (MnLOX) and manganese superoxide dismutase (MnSOD) utilize mononuclear Mn centers to effect their catalytic reactions. In the oxidized Mn state, the active site of each enzyme contains a hydroxo ligand, and X-ray crystal structures imply a hydrogen bond between this hydroxo ligand and a carboxylate ligand. While hydrogen bonding is a common feature of enzyme active sites, the importance of this particular hydroxo-carboxylate interaction is relatively unexplored. In this present study, we examined a pair of Mn-hydroxo complexes that differ by a single functional group. One of these complexes, [Mn(OH)(PaPyN)], contains a naphthyridinyl moiety capable of forming an intramolecular hydrogen bond with the hydroxo ligand. The second complex, [Mn(OH)(PaPyQ)], contains a quinolinyl moiety that does not permit any intramolecular hydrogen bonding. Spectroscopic characterization of these complexes supports a common structure, but with perturbations to [Mn(OH)(PaPyN)], consistent with a hydrogen bond. Kinetic studies using a variety of substrates with activated O-H bonds, revealed that [Mn(OH)(PaPyN)] is far more reactive than [Mn(OH)(PaPyQ)], with rate enhancements of 15-100-fold. A detailed analysis of the thermodynamic contributions to these reactions using DFT computations reveals that the former complex is significantly more basic. This increased basicity counteracts the more negative reduction potential of this complex, leading to a stronger O-H BDFE in the [Mn(OH)(PaPyN)] product. Thus, the differences in reactivity between [Mn(OH)(PaPyQ)] and [Mn(OH)(PaPyN)] can be understood on the basis of thermodynamic considerations, which are strongly influenced by the ability of the latter complex to form an intramolecular hydrogen bond.
酶锰过氧化物歧化酶 (MnSOD) 和锰过氧化物酶 (MnLOX) 利用单核锰中心来实现其催化反应。在氧化的 Mn 状态下，每个酶的活性位点都含有一个羟基金属配体，X 射线晶体结构表明该羟基金属配体与一个羧酸配体之间存在氢键。虽然氢键是酶活性位点的一个常见特征，但这种特殊的羟-羧酸盐相互作用的重要性尚未得到充分研究。在本研究中，我们研究了一对仅在一个官能团上有所不同的 Mn-羟基金属配合物。这些配合物之一，[Mn(OH)(PaPyN)]，含有一个能够与羟基金属配体形成分子内氢键的萘啶基部分。第二个配合物，[Mn(OH)(PaPyQ)]，含有一个不允许任何分子内氢键形成的喹啉基部分。对这些配合物的光谱特征进行了表征，支持了一个共同的结构，但对于 [Mn(OH)(PaPyN)]，存在与氢键一致的扰动。使用具有活化 O-H 键的各种底物进行的动力学研究表明，[Mn(OH)(PaPyN)]的反应性远远高于 [Mn(OH)(PaPyQ)]，反应速率提高了 15-100 倍。使用密度泛函理论计算对这些反应的热力学贡献进行了详细分析，结果表明前者的配合物具有更高的碱性。这种增加的碱性抵消了该配合物更负的还原电位，导致 [Mn(OH)(PaPyN)]产物中 O-H BDFE 更强。因此，[Mn(OH)(PaPyQ)]和[Mn(OH)(PaPyN)]之间的反应性差异可以基于热力学考虑来理解，这受到后者配合物形成分子内氢键的能力的强烈影响。
