Unstable, Metastable, or Stable Halogen Bonding Interaction Involving Negatively Charged Donors? A Statistical and Computational Chemistry Study

doi:10.1021/jp50629

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	Unstable, Metastable, or Stable Halogen Bonding Interaction Involving Negatively Charged Donors? A Statistical and Computational Chemistry Study
	Yang, Zhuo 1; Xu, Zhijian1,2 ; Liu, Yingtao 1; Wang, Jinan 1; Shi, Jiye 3; Chen, Kaixian1 ; Zhu, Weiliang1
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2014-12-11
卷号	118 期号:49 页码:14223-14233
ISSN号	1520-6106
DOI	10.1021/jp50629
文献子类	Article
英文摘要	The noncovalent halogen bonding could be attributed to the attraction between the positively charged s-hole and a nucleophile. Quantum mechanics (QM) calculation indicated that the negatively charged organohalogens have no positively charged s-hole on their molecular surface, leading to a postulation of repulsion between negatively charged organohalogens and nucleophiles in vacuum. However, PDB survey revealed that 24% of the ligands with halogen bonding geometry could be negatively charged. Moreover, 36% of ionizable drugs in CMC (Comprehensive Medicinal Chemistry) are possibly negatively charged at pH 7.0. QM energy scan showed that the negatively charged halogen bonding is probably metastable in vacuum. However, the QM calculated bonding energy turned negative in various solvents, suggesting that halogen bonding with negatively charged donors should be stable in reality. Indeed, QM/MM calculation on three crystal structures with negatively charged ligands revealed that the negatively charged halogen bonding was stable. Hence, we concluded that halogen bonding with negatively charged donors is unstable or metastable in vacuum but stable in protein environment, and possesses similar geometric and energetic characteristics as conventional halogen bonding. Therefore, negatively charged organohalogens are still effective halogen bonding donors for medicinal chemistry and other applications.
资助项目	NNSF[81273435] ; NNSF[81302699] ; National Science & Technology Major Project[2013ZX09103001-001] ; National Science & Technology Major Project[2012ZX09301-001-004] ; Ministry of Science and Technology[2012AA01A305] ; Ministry of Science and Technology[2012AA020302] ; State Key Laboratory of Medicinal Chemical Biology, Nankai University[20130265]
WOS关键词	DENSITY-FUNCTIONAL THEORY ; DRUG-LIKE MOLECULES ; DIELECTRIC-CONSTANT ; PK(A) VALUES ; SUPRAMOLECULAR CHEMISTRY ; NONCOVALENT INTERACTIONS ; BINDING-AFFINITY ; M06 SUITE ; PROTEIN ; PREDICTION
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000349059700027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276805]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Shi, Jiye
作者单位	1.Chinese Acad Sci, Drug Discovery & Design Ctr, Key Lab Receptor Res, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China; 3.UCB Pharma, Dept Informat, Slough SL1 4EN, Berks, England
推荐引用方式 GB/T 7714	Yang, Zhuo,Xu, Zhijian,Liu, Yingtao,et al. Unstable, Metastable, or Stable Halogen Bonding Interaction Involving Negatively Charged Donors? A Statistical and Computational Chemistry Study[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2014,118(49):14223-14233.
APA	Yang, Zhuo.,Xu, Zhijian.,Liu, Yingtao.,Wang, Jinan.,Shi, Jiye.,...&Zhu, Weiliang.(2014).Unstable, Metastable, or Stable Halogen Bonding Interaction Involving Negatively Charged Donors? A Statistical and Computational Chemistry Study.JOURNAL OF PHYSICAL CHEMISTRY B,118(49),14223-14233.
MLA	Yang, Zhuo,et al."Unstable, Metastable, or Stable Halogen Bonding Interaction Involving Negatively Charged Donors? A Statistical and Computational Chemistry Study".JOURNAL OF PHYSICAL CHEMISTRY B 118.49(2014):14223-14233.