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 [(eta(5)-C5H4)-CR = N-N = CH-2-C4H2X-5-NO2]M (M = Re(CO)(3), Fe(eta(5)-C5H5); R = H, CH3, 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-1 and C-13 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-6, C-7) and the reduction potential of the nitro group (E-1/2 (NO2)), an extensive p-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 (RNO2 to RNO2-) through the azine bridge. The organometallic azines were evaluated for antitrypanosomal activity in vitro against the epimastigote form of the Dm28c strain of T. cruzi, yielding IC50 values in the low micromolar range. (C) 2017 Elsevier B.V. All rights reserved.