Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design

Molecules

卷:24

Kenta Sasaki¹  Yuji Sumii¹  Norio Shibata¹  Seiji Tsuzuki² 

[1] Department of Nanopharmaceutical Sciences, and Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan;

[2] Research Center for Computational Design of Advanced Functional Materials, AIST, Tsukuba, Ibaraki 305-8568, Japan;

关键词: halogen bonding;    fluorine;    iodine;    pentafluorosulfanyl;    titration;    ab initio calculation;    nmr study;    drug design;   

DOI  :  10.3390/molecules24193610

来源: DOAJ

【 摘 要 】

The activation of halogen bonding by the substitution of the pentafluoro-λ⁶-sulfanyl (SF₅) group was studied using a series of SF₅-substituted iodobenzenes. The simulated electrostatic potential values of SF₅-substituted iodobenzenes, the ab initio molecular orbital calculations of intermolecular interactions of SF₅-substituted iodobenzenes with pyridine, and the ¹³C-NMR titration experiments of SF₅-substituted iodobenzenes in the presence of pyridine or tetra (n-butyl) ammonium chloride (TBAC) indicated the obvious activation of halogen bonding, although this was highly dependent on the position of SF₅-substitution on the benzene ring. It was found that 3,5-bis-SF₅-iodobenzene was the most effective halogen bond donor, followed by o-SF₅-substituted iodobenzene, while the m- and p-SF₅ substitutions did not activate the halogen bonding of iodobenzenes. The similar ortho-effect was also confirmed by studies using a series of nitro (NO₂)-substituted iodobenzenes. These observations are in good agreement with the corresponding Mulliken charge of iodine. The 2:1 halogen bonding complex of 3,5-bis-SF₅-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF₅-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF₅-iodobenzene unit may be an attractive fragment of rational drug design capable of halogen bonding with biomolecules.

【 授权许可】

Unknown