Liu Tao, Li Hua, Huang Ming-Bao, Duan Yong, Wang Zhi-Xiang
College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
J Phys Chem A. 2008 Jun 19;112(24):5436-47. doi: 10.1021/jp712052e. Epub 2008 May 27.
Ab initio calculations up to MP2/aug-cc-pVTZ//MP2/cc-pVTZ level, including natural charge population and natural resonance theory analyses, have been carried out to study the two-way effects between hydrogen bond (H-bond) and the intramolecular resonance effect by using the H-bonded complexes of formamide ( FAO) and its derivatives ( FAXs, X represents the heavy atoms in the substituent groups, CH 2, NH, SiH 2, PH, and S) with water as models. Unlike NH 3 and NH 2CH 3 which prefer being H-bond acceptors ( HA) to form H-bond with water, the amino groups in the six monomers, because of the resonance effect, prefer being H-bond donors ( HD) rather HA. Six monomers can all form HD complexes with water, and only two ( FAC and FASi) with the weakest resonance effect are able to form HA complexes with water. The HD H-bond and resonance effect enhance each other (positive two-way effects) whereas the HA H-bond and resonance effect weaken each other (negative two-way effects). The H-bond energies in the six HD complexes are nearly linearly correlated with the weights of the dipolar resonance in Pauling's model and the N-C bond lengths; the correlation coefficients are 0.91 and 0.93, respectively. The positive two-way effects also happens in FAO-water complex, in which the FAO CO group serves as HA ( HA co ). Interestingly, when the HD and HA co H-bonds are present in FAO H-bond complex simultaneously, the enhancements are much more significant, and the energies of the two types of H-bonds are much larger than those when only one type of H-bond is present, reflecting the cooperative effects. By using the knowledge to the two-way effects, we computationally designed a molecule ( FAO- BH 3 ) to increase H-bond energy. Because of the oxygen lone pair donation to the empty pi orbital of BH 3, FAO- BH 3 has a much stronger resonance effect than FAO. As a result, the H-bond energy (-5.55 kcal/mol) in HD H 2O ... FAO- BH 3 complex is much greater than the -3.30 kcal/mol in the HD H 2O...FAO complex. The two-way effects can be rationalized as follows: the resonance effect leads to intramolecular charge shifts in the monomers which facilitate or prevent the charge donation or acceptation of their H-bond partners. Therefore, the H-bonds are strengthened or weakened. In reverse, the charge donations or acceptations of their H-bond partners facilitate or prevent the intramolecular charge shifts in the monomer moieties, which enhance or weaken the resonance effect. The understanding to the two-way effects may be helpful in drug design and refinement by modulating the H-bond strength and in building empirical H-bond models to study large biological molecules. The study supports Pauling's resonance model.
以甲酰胺（FAO）及其衍生物（FAXs，X代表取代基中的重原子，CH₂、NH、SiH₂、PH和S）与水形成的氢键复合物为模型，进行了高达MP2/aug-cc-pVTZ//MP2/cc-pVTZ水平的从头算计算，包括自然电荷布居和自然共振理论分析，以研究氢键（H键）与分子内共振效应之间的双向影响。与NH₃和NH₂CH₃倾向于作为氢键受体（HA）与水形成氢键不同，由于共振效应，六个单体中的氨基更倾向于作为氢键供体（HD）而非HA。六个单体都能与水形成HD复合物，只有两个共振效应最弱的（FAC和FASi）能够与水形成HA复合物。HD氢键和共振效应相互增强（正向双向效应），而HA氢键和共振效应相互减弱（负向双向效应）。六个HD复合物中的氢键能与鲍林模型中偶极共振的权重和N-C键长几乎呈线性相关，相关系数分别为0.91和0.93。正向双向效应也发生在FAO-水复合物中，其中FAO的CO基团作为HA（HAco）。有趣的是，当HD和HAco氢键同时存在于FAO氢键复合物中时，增强作用更为显著，两种类型氢键的能量比仅存在一种类型氢键时大得多，这反映了协同效应。利用对双向效应的认识，我们通过计算设计了一种分子（FAO-BH₃）以增加氢键能。由于氧孤对电子向BH₃的空π轨道供电子，FAO-BH₃的共振效应比FAO强得多。结果，HD H₂O…FAO-BH₃复合物中的氢键能（-5.55 kcal/mol）远大于HD H₂O…FAO复合物中的-3.30 kcal/mol。双向效应可如下解释：共振效应导致单体分子内电荷转移，这促进或阻碍了其氢键伙伴的电荷供体或受体作用。因此，氢键被增强或减弱。反之，其氢键伙伴的电荷供体或受体作用促进或阻碍了单体部分的分子内电荷转移，从而增强或减弱了共振效应。对双向效应的理解可能有助于通过调节氢键强度进行药物设计和优化，以及构建经验性氢键模型来研究大型生物分子。该研究支持了鲍林的共振模型。
