Synthesis, characterization and DNA binding of four imidazo[4,5-f]1,10-phenanthroline derivatives

Abstract

The synthesis and crystal structures of four imidazo[4,5- f ]1,10-phenanthroline type compounds, namely 2,6-(dimethoxypyridyl)imidazo[4,5- f ]1,10-phenanthroline monohydrate (C 20 H 17 N 5 O 3 ) 1a , (indole)imidazo[4,5- f ]1,10-phenanthroline ethanol monosolvate monohydrate (C 23 H 21 N 5 O 2 ) 2a , (benzo[b]thiophene)imidazo[4,5- f ]1,10-phenanthroline (C 21 H 12 N 4 S) 3 , and (4,5-dimethylthiophene)imidazo[4,5- f ]1,10-phenanthroline (C 19 H 14 N 4 S) 4 , are reported. The compounds were characterized in dimethyl sulfoxide- d 6 (DMSO- d 6 ) solution by 1 H and 13 C NMR spectroscopy and in the solid-state by 13 C NMR spectroscopy using the cross-polarisation magic angle spinning (CP/MAS) technique. 1 H and 13 C liquid-state NMR spectra of 1 and 2 exhibit a sharpening of peaks upon heating, suggesting the presence of two tautomeric forms of 1 and 2 , this is confirmed by the presence of two distinct signals for the N-H protons in the 1 H spectra. This tautomeric effect was not observed in 3 and 4. 1a crystallised in the triclinic space group, P 1 ¯ with one molecule and one solvent water molecule in the asymmetric unit while 2a crystallised in the monoclinic space group, P 2 1 / c, with one molecule and two solvate molecules (CH 3 CH 2 OH and H 2 O) in the asymmetric unit. 3 and 4 both crystallised in the monoclinic space group, P 2 1 / n, each with one molecule in the asymmetric unit. 4 displays a positional disorder on the 4,5-thiophene moiety in a 60:40 ratio. When a drug candidate binds to DNA via intercalation, a hypochromic effect is observed in the spectra due to stabilised π-interactions between the base pairs of the DNA structure and the drug candidate. Contrastingly, if a drug candidate binds to DNA via electrostatic attraction, a hyperchromic effect is observed. The mode of binding as well as intrinsic binding constant (K b ) of 1a – 4 are reported herein. The spectra of 1a, 2a and 4 exhibit a hypochromic effect, thus interaction via π-interactions is suggested and the spectrum of 3 exhibits a hyperchromic shift, suggesting that the mode of binding of 3 occurs via electrostatic attraction. The K b values for 1a–4 range from 1.5 × 10 3 – 1.7 × 10 4 M −1 .