Hyperconjugation-mediated solvent effects in phosphoanhydride bonds.
Hyperconjugation-mediated solvent effects in phosphoanhydride bonds.
复制标题
磷酸酐键中超共轭介导的溶剂效应。
DOI：
10.1021/jp306607k
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Chapman,MichaelS
中科院分区：
文献类型：
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作者：
Summerton,JeanC;Evanseck,JeffreyD;Chapman,MichaelS
密度泛函理论和自然键轨道分析被用来探索溶剂对三磷酸甲酯超共轭的影响，三磷酸甲酯是一种“能量丰富”的磷酸酐键的模型，如在ATP中发现的。正如预期的那样，二面角旋转的羟基邻的磷酸酐键揭示了异头效应的构象依赖性涉及调制的供体和受体轨道之间的轨道重叠。然而，在溶剂氢键的旋转中观察到构象独立性。当一个孤对轨道旋转远离最佳反周面取向时，异头效应的整体幅度大约被另一孤对轨道补偿，因为它变得更加反周面。此外，溶剂调制的异头效应并不限于反peripanimal孤对;氢键涉及的左孤对也影响异头相互作用和强度的磷酸酐键。反溶剂氢键和反溶剂氢键都延长了非桥O-P键，增加了给体和受体轨道之间的距离，减少了轨道重叠，这导致了异头效应的降低。溶剂效应是加和的，在增加水配位时，异头效应的降低更大。通过控制活性位点中底物的配位环境，激酶、磷酸酶和在代谢和信号传导中重要的其他酶可能具有通过立体电子效应调节单个磷酸酐键的稳定性的潜力。
Density functional theory and natural bond orbital analysis are used to explore the impact of solvent on hyperconjugation in methyl triphosphate, a model for “energy rich” phosphoanhydride bonds, such as found in ATP. As expected, dihedral rotation of a hydroxyl group vicinal to the phosphoanhydride bond reveals that the conformational dependence of the anomeric effect involves modulation of the orbital overlap between the donor and acceptor orbitals. However, a conformational independence was observed in the rotation of a solvent hydrogen bond. As one lone pair orbital rotates away from an optimal antiperiplanar orientation, the overall magnitude of the anomeric effect is compensated approximately by the other lone pair as it becomes more antiperiplanar. Furthermore, solvent modulation of the anomeric effect is not restricted to the antiperiplanar lone pair; hydrogen bonds involving gauche lone pairs also affect the anomeric interaction and the strength of the phosphoanhydride bond. Both gauche and anti solvent hydrogen bonds lengthen nonbridging O–P bonds, increasing the distance between donor and acceptor orbitals and decreasing orbital overlap, which leads to a reduction of the anomeric effect. Solvent effects are additive with greater reduction in the anomeric effect upon increasing water coordination. By controlling the coordination environment of substrates in an active site, kinases, phosphatases, and other enzymes important in metabolism and signaling may have the potential to modulate the stability of individual phosphoanhydride bonds through stereoelectronic effects.