Experimental and theoretical approach to hydrogen-bonded diastereomeric interactions in a model complex
Experimental and theoretical approach to hydrogen-bonded diastereomeric interactions in a model complex
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DOI：
10.1021/ja970503d
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发表时间：
1997-08-13
影响因子：
15
通讯作者：
vanGunsteren, WF
中科院分区：
文献类型：
--
作者：
Hunenberger, PH;Granwehr, JK;vanGunsteren, WF
用微量热法测定了298K时(R，R)-1，2-环己二胺(R)与(R，R)-1，2-环戊二醇(R-5)和(S，S)-1，2-环戊二醇(S-5)以及相应的环己二醇(R-6和S-6)在苯和四氯化碳中的结合亲和力，并观察到非对映异构体配合物之间的意外差异。报道了两种较小的非对映化合物R/R-5和R/S-5在简化溶剂模型中的长时间尺度(0.1MU S)分子动力学模拟。直接自由能计算的结果与第一对在苯中测量的实验值很好地吻合，但对于第二对的结果几乎相同，这与实验不同。对模型参数对模拟结果的影响进行了系统的分析，发现没有通过调整参数来提高对映体选择性的可能性。造成差异的其他可能原因是特定的溶质-溶剂或溶剂-溶剂相互作用，电子电荷重新分布效应，或形成两个以上分子的团簇。由于达到了很长的时间尺度，动力学得到了一个很好的收敛图像，并且可以详细地研究处于平衡状态的物种。络合物的平均寿命约为200ps，而氢键的平均寿命仅约为5ps。除了非结合态，在模拟中观察到的两个非对映异构体对的主要物种都是单氢键络合物，明显倾向于O到N而不是N到O的氢键。许多其他氢键模式(桥联、双键)也有少量观察到。
Binding affinities of (R,R)-1,2-cyclohexanediamine (R) to (R,R)-1,2-cyclopentanediol (R-5) and (S,S)-1,2-cyclopentanediol (S-5) and to the corresponding cyclohexanediols (R-6 and S-6) have been measured in benzene and in CCl4 at 298 K by microcalorimetry, and unexpected differences between the diastereomeric complexes are observed. Long time scale (0.1 mu s) molecular-dynamics simulations of the two smaller diastereomeric complexes, R/R-5 and R/S-5, in a simplified solvent model are reported. A direct free energy calculation gives results in good agreement with the experimental values measured in benzene for the first pair, but nearly identical results for the second pair, which is at variance with experiment. A systematic analysis of the dependence of simulation results on model parameters is performed, and no possibility is found to improve the enantioselectivity by parameter tuning. Other possible causes for discrepancies are specific solute-solvent or solvent-solvent interactions, electronic charge redistribution effects, or formation of clusters of more than two molecules. Owing to the long time scales reached, a well-converged picture of the dynamics is obtained, and the species present at equilibrium can be studied in detail. The average lifetime of the complex is found to be about 200 ps, whereas that of a hydrogen bond is only about 5 ps. Besides the unbound state, the dominant species observed in the simulations for both diastereomeric pairs are singly hydrogen-bonded complexes, with a clear preference for a O to N over the N to O hydrogen bond. Many other hydrogen-bonding patterns (bridged, double) are also observed in minor amounts.