Mono- and polynuclear Ferrocenyl-derived complexes: synthesis, characterisation and biological evaluation as antimycobacterial and antiplasmodial agents

Ferrocene-containing precursors, vinylferrocene and (E)-4-vinylferrocenylbenzaldehyde were prepared, by a Wittig olefination reaction and Heck cross-coupling reaction, respectively. Mononuclear ferrocenyl-derived imino complexes were synthesised by Schiff-base condensation reactions of (E)-4-vinylferrocenylbenzaldehyde with various amines. This included the preparation of a silicon-containing derivative and its carbon analogue, to determine the effect of the lipophilic moiety on the biological activity. In addition, polynuclear ferrocenyl-derived imino complexes based on the tris(2-aminoethyl)amine scaffold and the polypropyleneimine (PPI) first- and second-generation scaffolds were also synthesised using Schiff-base chemistry. These polynuclear complexes were prepared using template chemical procedures to that of the mononuclear complexes. The corresponding mono- and polynuclear ferrocenyl-derived amino complexes were synthesised via reductive amination reactions from the (E)-4-vinylferrocenylbenzaldehyde. The imine moiety was hydrogenated in order to compare the effect on the biological activity. The imino and amino complexes were isolated in moderate to high yields. A second series of ferrocenyl complexes was also prepared incorporating a thiosemicarbazone moiety, as this is a known pharmacophore and may confer favourable properties in terms of biological activity as well as solubility. Methyl hydrazinecarbodithioate was synthesised and reacted with the previously synthesised (E)-4-vinylferrocenylbenzaldehyde by a Schiff-base condensation reaction to afford a ferrocenyl dithiocarbamate. The dithiocarbamate was reacted with various amines via nucleophilic substitution reactions to give mono- and polynuclear ferrocenylthiosemicarbazone complexes. These complexes were isolated in low to moderate yields

Synthesis, characterization and antimicrobial evaluation of mono- and polynuclear ferrocenyl-derived amino and imino complexes

A series of ferrocenyl mono- and polynuclear complexes conjugated to imino and amino scaffolds was prepared. The imino complexes were prepared via a Schiff base condensation reaction between (E)-4-vinylferrocenylbenzaldehyde and various amines. The amino complexes were prepared by reductive amination reactions using the same precursors. The compounds were characterized using standard spectroscopic and analytical techniques including Nuclear Magnetic Resonance (NMR) spectroscopy, Infrared (IR) spectroscopy and mass spectrometry. The compounds were screened against Mycobacterium tuberculosis as well as the NF54 chloroquine-sensitive (CQS) strain of Plasmodium falciparum. Overall, the complexes showed moderate in vitro biological activity, with the ferrocenylimines exhibiting enhanced activity against M. tuberculosis compared to the corresponding amines. The ferrocenylimines also displayed moderate activity against P. falciparum, with the second-generation polyimine complex exhibiting the highest activity in vitro. The ferrocenylamines exhibit promising antiplasmodial activity, enhanced compared to the imines, with the silicon-containing derivative and the second-generation dendrimer showing good activity

Synthesis, characterization, antiplasmodial evaluation and electrochemical studies of water-soluble heterobimetallic ferrocenyl complexes

Three new ferrocenyl-containing heterobimetallic complexes were synthesized using a sodium sulfonate-salicylaldimine mononuclear ferrocenyl complex and various metal precursors. Complexation with ruthenium(II), rhodium(III) and iridium(III) precursors yielded the heterobimetallic complexes, which display good water-solubility. The ferrocenyl ligand acts as a N,O-bidentate chelating ligand, coordinating to the metal center via the imine nitrogen and the deprotonated phenolic oxygen. The complexes were characterized using analytical and spectroscopic techniques. The compounds were evaluated for in vitro antiplasmodial activity against the NF54 chloroquine-sensitive strain of Plasmodium falciparum. The mono- and bimetallic complexes exhibit enhanced activity compared to the salicylaldimine hydrazone. The compounds were evaluated for their ability to inhibit β-haematin formation but were inactive, suggesting an alternative reason for their antiplasmodial activity. Electrochemical studies on the bimetallic complexes revealed a voltammetric wave corresponding to the oxidation of the ferrocenyl group and another at a more positive potential which inhibited the reversibility of the ferrocenyl oxidation

Mono- and polynuclear ferrocenylthiosemicarbazones: Synthesis, characterisation and antimicrobial evaluation

A series of mono- and polynuclear ferrocenylthiosemicarbazone complexes were prepared via nucleophilic substitution reactions of various amine scaffolds with a ferrocenyl dithiocarbamate. The dithiocarbamate was prepared via a Schiff base condensation reaction. The compounds were characterised using various spectroscopic and analytical techniques including Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectroscopy, mass spectrometry and elemental analysis. The ferrocenyl dithiocarbamate and thiosemicarbazone compounds were screened for their preliminary antimicrobial activity against the H37Rv strain of Mycobacterium tuberculosis and the chloroquine-sensitive (CQS) NF54 strain of Plasmodium falciparum. Against M. tuberculosis, the compounds displayed moderate to low activity. The mononuclear and octanuclear complexes were the most active, exhibiting similar MIC values. All compounds displayed moderate activity in the antiplasmodial screening. The mononuclear and trinuclear complexes exhibited enhanced activity compared to the complexes with higher nuclearity