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.

Automated summary

The study reported the synthesis and crystal structures of four imidazo[4,5-f]1,10-phenanthroline type compounds, characterized by NMR spectroscopy. Some of the compounds were found to exist in two tautomeric forms. The mode of binding and intrinsic binding constant of these compounds to DNA were also investigated, showing differences in binding mechanisms among the compounds.