阴离子——阴离子型卤键作用的理论研究
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- 英文论文题名：Stability and Characteristics of the Halogen Bonding Interaction inan Anion-Anion Complex:A Computational Chemistry Study
- 论文作者：王桂敏 ; 陈照强 ; 徐志建 ; 王进安 ; 杨洋 ; 蔡婷婷 ; 施继烨 ; 朱维良
- 英文论文作者：Guimin Wang ; Zhaoqiang Chen ; Zhijian Xu ; Jinan Wang ; Yang Yang ; Tingting Cai ; Jiye Shi ; Weiliang Zhu ; CAS Key Laboratory of Receptor Research ; Drug Discovery and Design Center ; Shanghai Institute of Materia Medica ; ChineseAcademy of Sciences ; UCB Biopharma SPRL ; Chemin du Foriest
- 年：2016
- 作者机构：中国科学院受体结构与功能重点实验室中科院上海药物研究所药物发现与设计中心;UCB生物制药公司;
- 论文关键词：卤键 ; 阴离子 ; 量子力学/分子力学 ; 药物设计
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
- 语种：中文
- 分类号：O641.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：400k
- 原文格式：D
- 会议级别：全国
摘要
卤键是卤素原子的σ-空穴(σ-hole)与亲核试剂之间形成的非共价相互作用。在生理条件下,药物分子可能呈现出不同的质子化状态。含卤小分子去质子化后,卤素头部正电性的σ-空穴会消失,可能与同样带负电荷的亲核分子相互排斥。经过数据库搜寻,我们发现带负电荷的分子之间存在具有卤键几何特征的作用模式。基于对卤苯甲酸和丙炔酸的复合物的量化计算表明阴离子-阴离子型卤键在真空中是不稳定的,而在溶剂中可以稳定存在。卤键作用距离和能量均说明阴离子-阴离子型卤键较中性分子间的卤键更强,自然键轨道(NBO)和分子中的原子的量化理论(QTAIM)的分析同样证实了上述结论。运用对称性匹配微扰理论(SAPT)进行能量分解后,我们发现诱导作用对分子间的相互吸引贡献很大。我们从蛋白晶体数据库(PDB)中选取了4个蛋白-配体复合物,利用量子力学/分子力学杂交方法进行了计算,结果提示阴离子-阴离子型卤键可以提高配体的亲和力,最大作用能接近3kcal/mol。
Halogen bonding is the noncovalent interaction between the positively charged o-hole of organohalogens and nucleophiles.In reality,both the organohalogen and nucleophile could be deprotonated,which may lead to the vanishing of the o-hole and possible repulsion between the two anions.However,our database survey revealed that there are halogen bonding-like interactions between two anions.Quantum mechanics calculations with halobenzoates and propiolate indicated that the anion-anion halogen bonding is unstable in vacuum but attractive in solvents.Furthermore,natural bond orbital and quantum theory of atoms in molecule analyses suggested stronger anion-anion halogen bonding than that of the neutral one,which is consistent with the distance and binding energy.Energy decomposition by symmetry adapted perturbation theory revealed that the strong binding might be attributed to large induction energy.The calculations on 4 protein-ligand complexes from PDB demonstrated that the anion-anion halogen bonding could contribute to the ligands' binding affinity up to ~3kcal/mol.
Halogen bonding is the noncovalent interaction between the positively charged o-hole of organohalogens and nucleophiles.In reality,both the organohalogen and nucleophile could be deprotonated,which may lead to the vanishing of the o-hole and possible repulsion between the two anions.However,our database survey revealed that there are halogen bonding-like interactions between two anions.Quantum mechanics calculations with halobenzoates and propiolate indicated that the anion-anion halogen bonding is unstable in vacuum but attractive in solvents.Furthermore,natural bond orbital and quantum theory of atoms in molecule analyses suggested stronger anion-anion halogen bonding than that of the neutral one,which is consistent with the distance and binding energy.Energy decomposition by symmetry adapted perturbation theory revealed that the strong binding might be attributed to large induction energy.The calculations on 4 protein-ligand complexes from PDB demonstrated that the anion-anion halogen bonding could contribute to the ligands' binding affinity up to ~3kcal/mol.
引文
[1]Wang,G.;Chen,Z.;Xu,Z.;Wang,J.;Yang,Y.;Cai,T.;Shi,J.;Zhu,W.J.Phys.Chem.B 2016,120(4):610.