title: How Do Distance and Solvent Affect Halogen Bonding Involving Negatively Charged Donors?
abstract: 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.
authors: 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.
authors: Zhaoqiang
authors: Z
authors: Chen
authors: 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.
authors: Guimin
authors: G
authors: Wang
authors: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050, China.|University of Chinese Academy of Sciences , No.19A Yuquan Road, Beijing 100049, China.
authors: Zhijian
authors: Z
authors: Xu
authors: 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.
authors: Jinan
authors: J
authors: Wang
authors: 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.
authors: Yuqi
authors: Y
authors: Yu
authors: 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.
authors: Tingting
authors: T
authors: Cai
authors: 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.
authors: Qiang
authors: Q
authors: Shao
authors: UCB Biopharma SPRL , Chemin du Foriest, Braine-l'Alleud B-1420, Belgium.
authors: Jiye
authors: J
authors: Shi
authors: 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.
authors: Weiliang
authors: W
authors: Zhu