Ly Hong Giang T, Mihaylov Tzvetan, Absillis Gregory, Pierloot Kristine, Parac-Vogt Tatjana N
Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
Inorg Chem. 2015 Dec 7;54(23):11477-92. doi: 10.1021/acs.inorgchem.5b02122. Epub 2015 Nov 24.
Detailed kinetic studies on the hydrolysis of glycylglycine (Gly-Gly) in the presence of the dimeric tetrazirconium(IV)-substituted Wells-Dawson-type polyoxometalate Na14[Zr4(P2W16O59)2(μ3-O)2(OH)2(H2O)4] · 57H2O (1) were performed by a combination of (1)H, (13)C, and (31)P NMR spectroscopies. The catalyst was shown to be stable under a broad range of reaction conditions. The effect of pD on the hydrolysis of Gly-Gly showed a bell-shaped profile with the fastest hydrolysis observed at pD 7.4. The observed rate constant for the hydrolysis of Gly-Gly at pD 7.4 and 60 °C was 4.67 × 10(-7) s(-1), representing a significant acceleration as compared to the uncatalyzed reaction. (13)C NMR data were indicative for coordination of Gly-Gly to 1 via its amide oxygen and amine nitrogen atoms, resulting in a hydrolytically active complex. Importantly, the effective hydrolysis of a series of Gly-X dipeptides with different X side chain amino acids in the presence of 1 was achieved, and the observed rate constant was shown to be dependent on the volume, chemical nature, and charge of the X amino acid side chain. To give a mechanistic explanation of the observed catalytic hydrolysis of Gly-Gly, a detailed quantum-chemical study was performed. The theoretical results confirmed the nature of the experimentally suggested binding mode in the hydrolytically active complex formed between Gly-Gly and 1. To elucidate the role of 1 in the hydrolytic process, both the uncatalyzed and the polyoxometalate-catalyzed reactions were examined. In the rate-determining step of the uncatalyzed Gly-Gly hydrolysis, a carboxylic oxygen atom abstracts a proton from a solvent water molecule and the nascent OH nucleophile attacks the peptide carbon atom. Analogous general-base activity of the free carboxylic group was found to take place also in the case of polyoxometalate-catalyzed hydrolysis as the main catalytic effect originates from the -C═O···Zr(IV) binding.
通过结合¹H、¹³C和³¹P核磁共振光谱，对在二聚四锆（IV）取代的韦尔斯-道森型多金属氧酸盐Na₁₄[Zr₄(P₂W₁₆O₅₉)₂(μ₃ - O)₂(OH)₂(H₂O)₄]·57H₂O（1）存在下甘氨酰甘氨酸（Gly - Gly）的水解进行了详细的动力学研究。结果表明，该催化剂在广泛的反应条件下是稳定的。pD对Gly - Gly水解的影响呈现钟形曲线，在pD 7.4时观察到最快的水解反应。在pD 7.4和60°C下，Gly - Gly水解的观测速率常数为4.67×10⁻⁷ s⁻¹，与未催化反应相比有显著加速。¹³C核磁共振数据表明Gly - Gly通过其酰胺氧原子和胺氮原子与1配位，形成了具有水解活性的配合物。重要的是，在1存在下实现了一系列具有不同X侧链氨基酸的Gly - X二肽的有效水解，并且观测到的速率常数显示取决于X氨基酸侧链的体积、化学性质和电荷。为了对观测到的Gly - Gly催化水解给出机理解释，进行了详细的量子化学研究。理论结果证实了实验所提出的Gly - Gly与1形成的水解活性配合物中结合模式的性质。为了阐明1在水解过程中的作用，研究了未催化反应和多金属氧酸盐催化反应。在未催化的Gly - Gly水解的速率决定步骤中，一个羧基氧原子从溶剂水分子中夺取一个质子，新生的OH亲核试剂攻击肽碳原子。在多金属氧酸盐催化水解的情况下，也发现了游离羧基类似的广义碱活性，因为主要的催化作用源于 - C═O···Zr(IV)键合。
