The synthesis, characterization and biological activity of six bioorganometallic conjugates of ciprofloxacin with ferrocenyl, ruthenocenyl and cymantrenyl entities are described. Their antimicrobial activities were investigated against Gram-positive bacteria, Gram-negative bacteria and bloodstream forms of Trypanosoma brucei. Furthermore, the morphological changes of bacterial cells upon treatment with the conjugates were examined by scanning electron microscopy. In addition, the cytotoxicity of the conjugates against tumor and normal mammalian cells was also investigated. The results showed that conjugation of an organometallic moiety can significantly enhance the antimicrobial activity of the antibiotic ciprofloxacin drug. It was found that N-alkyl cymantrenyl and ruthenocenyl ciprofloxacin conjugates were the most effective derivatives although other conjugates also showed significant antimicrobial activity. The increase in the antimicrobial activity was most likely due to two independent mechanisms of action. The first mechanism is due to the bacterial topoisomerase inhibitory activity of ciprofloxacin while the second mechanism can be attributed to the generation of reactive oxygen species caused by the organometallic moiety. The presence of two modes of action enables the conjugates to kill bacteria in their stationary growth phase and to overcome the drug resistance of S. aureus strains. In addition, the conjugates showed promising selectivity toward bacterial and parasitic cells over mammalian cells.

Luminescent fac -[Re(CO) ₃ (phen)(aspirin)]: insights into in vitro anticancer activity and confocal microscopy imaging in HeLa cells.

In order to determine the influence of the ortho- and meta- halogen substituents in the phenyl ring of benzoic acid on the formation of C–H⋯X hydrogen bonds and X⋯O halogen bonds in crystal packing where the halogen (X) is a fluorine, chlorine, bromine or iodine atom, we synthesized and structurally characterized a series of nine co-crystals formed from acridine and benzoic acids: acridine·benzoic acid (1), acridine·2-fluorobenzoic acid (2), acridine·2-chlorobenzoic acid (3), acridine·2-bromobenzoic acid (4), acridine·2-iodobenzoic acid (5), acridine·3-fluorobenzoic acid (6), acridine·3-chlorobenzoic acid (7), acridine·3-bromobenzoic acid (8) and acridine·3-iodobenzoic acid (9). The number, type and strength of the hydrogen and halogen bonds, and the melting points of co-crystals 1–9 were compared. Systematic analysis of the intermolecular interactions taking place in the co-crystals of the title compounds indicates that competition between halogen and hydrogen bonding depends on the position and type of halo-substituent.

Two new neutral fac-[Re(CO)₃(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O₂C(CH₂)₅CH₃ or O₂C(CH₂)₄C≡CH, were synthetized in one-pot procedures from fac-[Re(CO)₃(phen)Cl] and the corresponding carboxylic acids, and were fully characterized by IR and UV-Vis absorption spectroscopy, ¹H- and ¹³C-NMR, mass spectrometry and X-ray crystallography. The compounds, which display orange luminescence, were used as probes for living cancer HeLa cell staining. Confocal microscopy revealed accumulation of both dyes in mitochondria. To investigate the mechanism of mitochondrial staining, a new non-emissive compound, fac-[Re(CO)₃(phen)L], with L = O₂C(CH₂)₃((C₅H₅)Fe(C₅H₄), i.e., containing a ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible when ferrocene-containing ligand dissociates from the metal center to produce a species containing the luminescent fac­[Re(CO)₃(phen)]⁺ core. The release of ligands from the Re center was verified in vitro through the conjugation with model proteins. These findings suggest that the mitochondria accumulation of compounds 1–3 is due to the formation of luminescent fac-[Re(CO)₃(phen)]⁺ products, which react with cellular matrix molecules giving secondary products and are uptaken into the negatively charged mitochondrial membranes. Thus, reported compounds feature a rare dissociation-driven mechanism of action with great potential for biological applications.