Crystal Structures,ct-DNA/BSA Binding Properties and Antibacterial Activities of Halogenated Pyridyl Hydrazones

Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9Cl2N3O, 3 a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9BrClN3O, 3 b) and 4-iodobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone(C(13)H9ClIN3O, 3 c), have been synthesized and characterized by elemental analysis, IR, 1 H NMR, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that 3 a^3 c crystallize in monoclinic with space group Cc. The units of 3 a ~ 3 c were linked by intermolecular N–H...X(X = Cl, Br, I) hydrogen bonds into 2 D layered structures, which were further extended into 3 D networks by a series of π-π stacking interactions. Thermogravimetric analysis showed that all of them possessed higher thermal stabilities. The reactivities toward calf thymus DNA(ct-DNA) and bovine serum albumin(BSA) of 3 a^3 c were investigated by UV-vis and fluorescent spectroscopy as well as molecular docking simulation. Both theoretical and experimental results indicated that 3 a^3 c bound to ct-DNA in the mode of minor groove binding, and interacted with BSA through the hydrophobic cavity near TRP213. Besides, the orders of binding affinities of 3 a^3 c to ct-DNA and BSA were both 3 c > 3 b > 3 a, which were the same as that of antibacterial activities. Thus, the interactions of iodinated acylhydrazone with biological targets were stronger than that of chlorinated and brominated acylhydrazones, which provided a representative case for halogenation of lead compounds in rational drug design.