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

Abstract

The synthesis of unsymmetrical ferrocenyl and cyrhetrenyl azines [(h5-C5H4)-CR¼N-N¼CH-2-C4H2X-5-NO2]M (M¼Re(CO)3, Fe(h5-C5H5); R¼H, CH3,X¼O, S) has led to the development of new derivativesof 5-nitroheterocycles as potential anti-trypanosomal agents. The structures of compounds have beenconfirmed using conventional spectroscopic techniques (FT-IR,1H and13C NMR), mass spectrometry,including single-crystal X-ray diffraction analysis of compounds2NTand4NT. Based on the chemicalshifts of the iminic carbons (C6,C7) and the reduction potential of the nitro group (E1/2 NO2), an extensivep-conjugation of the azine bridge (-C(R)¼N-N¼CH-) was observed along with a correlation between theopposing electronic effects of the cyrhetrenyl and ferrocenyl fragments. It was established that the ex-istence of an electron-withdrawing group (cyrhetrene) could facilitate the generation of radical species(RNO2to RNO2 ) through the azine bridge. The organometallic azines were evaluated for anti-trypanosomal activityin vitroagainst the epimastigote form of the Dm28c strain ofT. cruzi, yieldingIC50values in the low micromolar range.