title: Stability and Characteristics of the Halogen Bonding Interaction in an Anion-Anion Complex: A Computational Chemistry Study.
abstract: Halogen bonding is the noncovalent interaction between the positively charged σ-hole of organohalogens and nucleophiles. In reality, both the organohalogen and nucleophile could be deprotonated to form anions, which may lead to the vanishing of the σ-hole and possible repulsion between the two anions. However, our database survey in this study revealed that there are halogen bonding-like interactions between two anions. Quantum mechanics calculations with small model complexes composed of halobenzoates and propiolate indicated that the anion-anion halogen bonding is unstable in vacuum but attractive in solvents. Impressively, the QM optimized halogen bonding distance between the two anions is shorter than that in a neutral system, indicating a possibly stronger halogen bonding interaction, which is verified by the calculated binding energies. Furthermore, natural bond orbital and quantum theory of atoms in molecule analyses also suggested stronger anion-anion halogen bonding than that of the neutral one. 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 by the QM/MM method demonstrated that the anion-anion halogen bonding could contribute to the ligands' binding affinity up to ∼3 kcal/mol. Therefore, anion-anion halogen bonding is stable and applicable in reality.
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 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 Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Jinan
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Cai
authors.affiliation: UCB Biopharma SPRL , Chemin du Foriest, Braine-l'Alleud, Belgium.
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu