Half-sandwich ruthenium(II), rhodium(III) and iridium(III) fluorescent metal complexes containing pyrazoline based ligands: DNA binding, cytotoxicity and antibacterial activities.

A series of nine new complexes of ruthenium(II), rhodium(III), and iridium(III) incorporated with pyrazoline-based ligands were synthesized and characterized by various spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, UV-Vis spectroscopy, ESI-MS spectrometry and X-ray crystallographic studies. All the synthesized compounds were assessed for their antibacterial abilities against Gram-positive and Gram-negative bacterial strains. The compounds showed better antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus Thuringiensis), with activities superior to standard kanamycin. Antioxidant studies revealed the mild radical scavenging proficiency of the compounds. DNA binding studies using fluorescence spectroscopy showed that the compounds could bind to Salmon Milt DNA electrostatically via external contact and groove surface binding with moderate affinity. The synthesized complexes were tested for anticancer activity using cell cytotoxicity and apoptosis assays in Dalton's lymphoma (DL) cell lines. The findings were compared to cisplatin (the standard drug) under identical experimental conditions. The cell viability results showed that complex 7 induced higher cytotoxicity in the DL cell line than the other tested compounds. The results of the molecular docking analysis further suggest that selective complexes have complete contact with the active amino acids sites of anti-apoptotic Bcl-2 family protein.

Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents.

Reaction of salicylaldehyde-2-picolinylhydrazone (HL) Schiff base ligand with precursor compounds [{(p-cymene)RuCl2}2] 1, [{(C6H6)RuCl2}2] 2, [{Cp*RhCl2}2] 3 and [{Cp*IrCl2}2] 4 yielded the corresponding neutral mononuclear compounds 5-8, respectively. The in vitro antitumor evaluation of the compounds 1-8 against Dalton's ascites lymphoma (DL) cells by fluorescence-based apoptosis study and by their half-maximal inhibitory concentration (IC50) values revealed the high antitumor activity of compounds 3, 4, 5 and 6. Compounds 1-8 render comparatively lower apoptotic effect than that of cisplatin on model non-tumor cells, i.e., peripheral blood mononuclear cells (PBMC). The antibacterial evaluation of compounds 5-8 by agar well-diffusion method revealed that compound 6 is significantly effective against all the eight bacterial species considered with zone of inhibition up to 35 mm. Fluorescence imaging study of compounds 5-8 with plasmid circular DNA (pcDNA) and HeLa RNA demonstrated their fluorescence imaging property upon binding with nucleic acids. The docking study with some key enzymes associated with the propagation of cancer such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed strong interactions between proteins and compounds 5-8. Conformational analysis by density functional theory (DFT) study has corroborated our experimental observation of the N, N binding mode of ligand. Compounds 5-8 exhibited a HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital) energy gap 2.99-3.04 eV. Half-sandwich ruthenium, rhodium and iridium compounds were obtained by treatment of metal precursors with salicylaldehyde-2-picolinylhydrazone (HL) by in situ metal-mediated deprotonation of the ligand. Compounds under investigation have shown potential antitumor, antibacterial and fluorescence imaging properties. Arene ruthenium compounds exhibited higher activity compared to that of Cp*Rh/Cp*Ir in inhibiting the cancer cells growth and pathogenic bacteria. At a concentration 100 µg/mL, the apoptosis activity of arene ruthenium compounds, 5 and 6 (~30 %) is double to that of Cp*Rh/Cp*Ir compounds, 7 and 8 (~12 %). Among the four new compounds 5-8, the benzene ruthenium compound, i.e., compound 6 is significantly effective against the pathogenic bacteria under investigation.

Substitution reactions in dinuclear Ru-Hbpp complexes: an evaluation of through-space interactions.

The synthesis of new dinuclear complexes of the general formula in,in-{[Ru(II)(trpy)(L)](µ-bpp)[Ru(II)(trpy)(L')]}(3+) [bpp(-) is the bis(2-pyridyl)-3,5-pyrazolate anionic ligand; trpy is the 2,2':6',2″-terpyridine neutral meridional ligand, and L and L' are monodentate ligands; L = L' = MeCN, 3a(3+); L = L' = 3,5-lutidine (Me(2)-py), 3c(3+); L = MeCN, L' = pyridine (py), 4(3+)], have been prepared and thoroughly characterized. Further, the preparation and isolation of dinuclear complexes containing dinitrile bridging ligands of the general formula in,in-{[Ru(II)(trpy)](2)(µ-bpp)(µ-L-L)}(3+) [µ-L-L = 1,4-dicyanobutane (adiponitrile, adip), 6a(3+); 1,3-dicyanopropane (glutaronitrile, glut), 6b(3+); 1,2-dicyanoethane (succinonitrile; succ), 6c(3+)] have also been carried out. In addition, a number of homologous dinuclear complexes previously described, containing the anionic bis(pyridyl)indazolate (bid(-)) tridentate meridional ligand in lieu of trpy, have also been prepared for comparative purposes. In the solid state, six complexes have been characterized by X-ray crystallography, and in solution, all of them have been spectroscopically characterized by NMR and UV-vis spectroscopy. In addition, their redox properties have also been investigated by means of cyclic voltammetry and differential pulse voltammetry and show the existence of two one-electron waves assigned to the formation of the II,III and III,III species. Dinitrile complexes 6a(3+), 6b(3+), and 6c(3+) display a dynamic behavior involving their enantiomeric interconversion. The energy barrier for this interconversion can be controlled by the number of methylenic units between the dinitrile ligand. On the other hand, pyridyl complexes in,in-{[Ru(II)(T)(py)](2)(µ-bpp)}(n+) (T = trpy, n = 3, 3b(3+); T = bid(-), n = 1, 3b'(+)) and 3c(3+) undergo two consecutive substitution reactions of their monodentate ligands by MeCN.The substitution kinetics have been monitored by (1)H NMR and UV-vis spectroscopy and follow first-order behavior with regard to the initial ruthenium complex. For the case of 3b(3+), the first-order rate constant k(1) = (2.9 ± 0.3) × 10(-5) s(-1), whereas for the second substitution, the k obtained is k(2) = (1.7 ± 0.7) × 10(-6) s(-1), both measured at 313 K. Their energies of activation at 298 K are 114.7 and 144.3 kJ mol(-1), respectively. Density functional theory (DFT) calculations have been performed for two consecutive substitution reactions, giving insight into the nature of the intermediates. Furthermore, the energetics obtained by DFT calculations of the two consecutive substitution reactions agree with the experimental values obtained. The kinetic properties of the two consecutive substitution reactions are rationalized in terms of steric crowding and also in terms of through-space interactions.