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

五氟硫基芳基碘化物诱导卤键的研究:合理药物设计中潜在的卤键供体。

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Abstract

The activation of halogen bonding by the substitution of the pentafluoro-λ(6)-sulfanyl (SF(5)) group was studied using a series of SF(5)-substituted iodobenzenes. The simulated electrostatic potential values of SF(5)-substituted iodobenzenes, the ab initio molecular orbital calculations of intermolecular interactions of SF(5)-substituted iodobenzenes with pyridine, and the (13)C-NMR titration experiments of SF(5)-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 SF(5)-substitution on the benzene ring. It was found that 3,5-bis-SF(5)-iodobenzene was the most effective halogen bond donor, followed by o-SF(5)-substituted iodobenzene, while the m- and p-SF(5) substitutions did not activate the halogen bonding of iodobenzenes. The similar ortho-effect was also confirmed by studies using a series of nitro (NO(2))-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(5)-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF(5)-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF(5)-iodobenzene unit may be an attractive fragment of rational drug design capable of halogen bonding with biomolecules.

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