Electrochemical and electron spin resonance studies of selected benzazolo[3,2‐a]quinolinium salts

Abstract

The electrochemical reduction of the chloride or perchlorate salts of benzazolo[3,2‐a]quinolinium ion and several of its analogues is reported. The compounds studied are the perchlorate salt of 3‐nitrobenzothiazolo‐and 3‐nitro‐9‐methoxybenzothiazolo[3,2‐a]quinolinium, and the chloride salts of 7‐ethyl‐, 3‐nitro‐7‐methyl‐, 3‐nitro‐7‐ethyl‐, 3‐nitro‐7‐isopropyl‐, 3‐nitro‐7‐butyl‐ and 3‐nitro‐7‐benzylbenzimidazolo[3,2‐a]‐quinolinium, respectively. Cyclic voltammetry of the corresponding 3‐nitrobenzothiazolo[3,2‐a]quinolinium derivatives in N,N‐dimethylformamide shows an irreversible peak potential at ‐0.6 and a quasi‐reversible peak at ‐(1.2–1.3) volts, respectively, relative to the standard calomel electrode. In contrast, the corresponding 3‐nitrobenzimidazolo[3,2‐a]quinolinium derivatives show, in general, reversible peaks at near ‐0.8 and ‐(1.2–1.4) volts, respectively. Upon electrolytic reduction, only the nitro‐substituted derivatives produced observable electron paramagnetic resonance electron spin resonance spectra. This observation is explained in terms of the stabilization of the radicals produced by the nitro group. Theoretical MM+/AM1/UHF calculations support the idea that the larger nitrogen splitting is caused by N‐12 and the minor splittings by N‐7 in the benzimidazolo[3,2‐a]quinolinium ion series.

Comparison of the nucleic acid covalent binding capacity of two nitro-substituted benzazolo[3,2-a]quinolinium salts upon enzymatic reduction

“…Of these, 3-nitrobenzothiazolo[3,2-a]quinolinium chloride (NBQ-2) has shown potential as an anticancer agent (Cox et al, 1982). It has been shown that these planar heterocyclic cationic nitroarenes can be reduced electrochemically or bioreduced in the presence of HX/XO (Cox et al, 1999,Alegria et al, 1993,Alegria et al, 2004. However, nothing is known regarding the possibility of DNA alkylation mediated through nitro reduction by this family of compounds.…”