Cyrhetrenylaniline and new organometallic phenylimines derived from 4 and 5 nitrothiophene: synthesis, characterization, X-Ray structures, electrochemistry and in vitro anti-T. brucei activity

Abstract

A novel series of cyrhetrenyl (3a-4a) and ferrocenyl (3b-4b) Schiff bases were synthesized through a condensation reaction, between the known 4-ferrocenylaniline (2b) or the unreported 4-cyhretrenylaniline (2a) with 4-or 5-nitrothiophenecarboxaldehyde. The structure of 2a and the new Schiff bases have been elucidated using conventional spectroscopic techniques (FT-IR, H-1 and C-13 NMR), mass spectrometry, and single-crystal X-ray diffraction analysis of compounds 2a, 4a and 3b. Cyclic voltammetry of organometallic phenylimines derived from 5-nitrothiophene showed NO2 group reduction potentials (E-1/2 approximate to 0.575 V) that were more anodic than those registered for their 4-nitro analogues (E-1/2 approximate to 0.981 V). All organometallic imines were tested against the bloodstream form of Trypanosoma brucei. Evaluation indicated that the most active complexes are the 5-nitrothiophene derivatives, 4a, which were remarkably more active than nifurtimox. In addition, complex 4b resulted in less toxicity to host L-6 cells than nifurtimox. The results revealed that the electronic effects of cyrhetrene and ferrocene are not an influential factor in E-1/2 and anti-Trypanosoma brucei activity for these new imines, which is probably due to the non-coplanarity of the[(eta(5)-C5H4)-C6H4-N=CH-(C4H2S)] system.