Chen Zhaoqiang, Wang Guimin, Xu Zhijian, Wang Jinan, Yu Yuqi, Cai Tingting, Shao Qiang, Shi Jiye, Zhu Weiliang
CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
University of Chinese Academy of Sciences , No.19A Yuquan Road, Beijing 100049, China.
J Phys Chem B. 2016 Sep 1;120(34):8784-93. doi: 10.1021/acs.jpcb.6b05027. Epub 2016 Aug 22.
It was reported that negatively charged donors can form halogen bonding, which is stable, especially, in a polar environment. On the basis of a survey of the Protein Data Bank, we noticed that the distance between the negative charge center and the halogen atom of an organohalogen may vary greatly. Therefore, a series of model systems, composed of 4-halophenyl-conjugated polyene acids and ammonia, were designed to explore the potential effect of distance on halogen bonding in different solvents. Quantum mechanics (QM) calculations demonstrated that the longer the distance, the stronger the bonding. The energy decomposition analysis on all of the model systems demonstrated that electrostatic interaction contributes the most (44-56%) to the overall binding, followed by orbital interaction (42-36%). Natural bond orbital calculations showed that electron transfer takes place from the acceptor to the donor, whereas the halogen atom becomes more positive during the bonding, which is in agreement with the result of neutral halogen bonding. QM/molecular mechanics calculations demonstrated that the polarity of binding pockets makes all of the interactions attractive in a protein system. Hence, the strength of halogen bonding involving negatively charged donors could be adjusted by changing the distance between the negative charge center and halogen atom and the environment in which the bonding exists, which may be applied in material and drug design for tuning their function and activity.
据报道，带负电荷的供体可以形成卤键，这种卤键是稳定的，尤其是在极性环境中。基于对蛋白质数据库的调查，我们注意到有机卤化物的负电荷中心与卤原子之间的距离可能有很大差异。因此，设计了一系列由4-卤苯基共轭多烯酸和氨组成的模型系统，以探索距离对不同溶剂中卤键的潜在影响。量子力学（QM）计算表明，距离越长，键越强。对所有模型系统的能量分解分析表明，静电相互作用对整体结合的贡献最大（44-56%），其次是轨道相互作用（42-36%）。自然键轨道计算表明，电子从受体转移到供体，而在键合过程中卤原子变得更正电，这与中性卤键的结果一致。QM/分子力学计算表明，结合口袋的极性使蛋白质系统中的所有相互作用都具有吸引力。因此，涉及带负电荷供体的卤键强度可以通过改变负电荷中心与卤原子之间的距离以及键合存在的环境来调节，这可应用于材料和药物设计中以调节其功能和活性。
