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

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, ¹H and ¹³C 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 ≈ −0.575 V) that were more anodic than those registered for their 4-nitro analogues (E_1/2 ≈ −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 L₆ 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 [(η⁵-C₅H₄)-C₆H₄-N=CH-(C₄H₂S)] system.