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

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 (C20H17N5O3) 1a , (indole)imidazo[4,5-f]1,10-phenanthroline ethanol monosolvate monohydrate (C23H21N5O2) 2a , (benzo[b]thiophene)imidazo[4,5-f]1,10-phenanthroline (C21H12N4S)(3) , and (4,5-dimethylthiophene)imidazo[4,5-f]1,10-phenanthroline (C19H14N4S)(4) , are reported. The compounds were characterized in dimethyl sulfoxide-d(6) (DMSO-d(6)) solution by H-1 and C-13 NMR spectroscopy and in the solid-state by C-13 NMR spectroscopy using the cross-polarisation magic angle spinning (CP/MAS) technique. H-1 and C-13 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 H-1 spectra. This tautomeric effect was not observed in 3 and 4 . 1a crystallised in the triclinic space group, P (1) over bar with one molecule and one solvent water molecule in the asymmetric unit while 2a crystallised in the monoclinic space group, P2(1)/c, with one molecule and two solvate molecules (CH3CH2OH and H2O) in the asymmetric unit. 3 and 4 both crystallised in the monoclinic space group, P2(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 pi-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 pi-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 x 10(3) - 1.7 x 10(4) M-1. (C) 2021 Elsevier B.V. All rights reserved.