Ferrocenyl and cyrhetrenyl azines containing a 5-nitroheterocyclic moiety: synthesis, structural characterization, electrochemistry and evaluation as anti-Trypanosoma cruzi agents

The synthesis of unsymmetrical ferrocenyl and cyrhetrenyl azines [(η-CH)-CR=N-N=CH-2-CHX-5-NO]M (M=Re(CO), Fe(η-CH); R = H, CH, X = O, S) has led to the development of new derivatives of 5-nitroheterocycles as potential anti-trypanosomal agents. The structures of compounds have been confirmed using conventional spectroscopic techniques (FT-IR, H and C NMR), mass spectrometry, including single-crystal X-ray diffraction analysis of compounds 2NT and 4NT. Based on the chemical shifts of the iminic carbons (C, C) and the reduction potential of the nitro group (E), an extensive π-conjugation of the azine bridge (-C(R)=N-N=CH-) was observed along with a correlation between the opposing electronic effects of the cyrhetrenyl and ferrocenyl fragments. It was established that the existence of an electron-withdrawing group (cyrhetrene) could facilitate the generation of radical species (RNO to RNO ) through the azine bridge. The organometallic azines were evaluated for anti-trypanosomal activity in vitro against the epimastigote form of the Dm28c strain of T. cruzi, yielding IC values in the low micromolar range.A.H.K. wishes to acknowledge FONDECYT-Chile (Projects 1150601 and 1110669), FONDEQUIP (Project EQM 130154) and D.I. Pontificia Universidad Católica de Valparaíso; J.G. wishes to acknowledge CONICYT and D.I. Pontificia Universidad Católica de Valparaíso for a postdoctoral position