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

The activation of halogen bonding by the substitution of the pentafluoro-λ-sulfanyl (SF) group was studied using a series of SF-substituted iodobenzenes. The simulated electrostatic potential values of SF-substituted iodobenzenes, the ab initio molecular orbital calculations of intermolecular interactions of SF-substituted iodobenzenes with pyridine, and the C-NMR titration experiments of SF-substituted iodobenzenes in the presence of pyridine or tetra (-butyl) ammonium chloride (TBAC) indicated the obvious activation of halogen bonding, although this was highly dependent on the position of SF-substitution on the benzene ring. It was found that 3,5-bis-SF-iodobenzene was the most effective halogen bond donor, followed by -SF-substituted iodobenzene, while the - and -SF substitutions did not activate the halogen bonding of iodobenzenes. The similar -effect was also confirmed by studies using a series of nitro (NO)-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-SF-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF-iodobenzene unit may be an attractive fragment of rational drug design capable of halogen bonding with biomolecules.