Preshendren Govender

Next generation PhotoCORMs: polynuclear tricarbonylmanganese(I)-functionalized polypyridyl metallodendrimers.

The first CO-releasing metallodendrimers, based on polypyridyl dendritic scaffolds functionalized with Mn(CO)3 moieties, of the general formula [DAB-PPI-{MnBr(bpy(CH3,CH═N))(CO)3}n], where DAB = 1,4-diaminobutane, PPI = poly(propyleneimine), bpy = bipyridyl, and n = 4 for first- or n = 8 for second-generation dendrimers, were synthesized and comprehensively characterized by analytical (HR-ESI mass spectrometry and elemental analysis) and spectroscopic ((1)H, (13)C{(1)H}-NMR, infrared, and UV/vis spectroscopy) methods. The CO-release properties of these compounds were investigated in pure buffer and using the myoglobin assay. Both metallodendrimer generations are stable in the dark in aqueous buffer for up to 16 h but show photoactivated CO release upon excitation at 410 nm, representing a novel class of macromolecular photoactivatable CO-releasing molecules (PhotoCORMs). No scaling effects were observed since both metallodendrimers release ∼65% of the total number of CO ligands per molecule, regardless of the generation number. In addition, the mononuclear model complex [MnBr(bpy(CH3,CH═NCH2CH2CH3))(CO)3] was prepared and comprehensively studied, including DFT/TDDFT calculations. These metallodendrimer-based PhotoCORMs afford new methods of targeted delivery of large amounts of carbon monoxide to cellular systems.

Antimalarial activity of ruthenium( ii ) and osmium( ii ) arene complexes with mono- and bidentate chloroquine analogue ligands

Eight new ruthenium and five new osmium p-cymene half-sandwich complexes have been synthesized, characterized and evaluated for antimalarial activity. All complexes contain ligands that are based on a 4-chloroquinoline framework related to the antimalarial drug chloroquine. Ligands HL(1-8) are salicylaldimine derivatives, where HL(1) = N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine, and HL(2-8) contain non-hydrogen substituents in the 3-position of the salicylaldimine ring, viz. F, Cl, Br, I, NO2, OMe and (t)Bu for HL(2-8), respectively. Ligand HL(9) is also a salicylaldimine-containing ligand with substitutions in both 3- and 5-positions of the salicylaldimine moiety, i.e. N-(2-((2-hydroxy-3,5-di-tert-butylphenyl)methyl-imino)ethyl)-7-chloroquinolin-4-amine, while HL(10) is N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) The half sandwich metal complexes that have been investigated are [Ru(η(6)-cym)(L(1-8))Cl] (Ru-1-Ru-8, cym = p-cymene), [Os(η(6)-cym)(L(1-3,5,7))Cl] (Os-1-Os-3, Os-5, and Os-7), [M(η(6)-cym)(HL(9))Cl2] (M = Ru, Ru-HL(9); M = Os, Os-HL(9)) and [M(η(6)-cym)(L(10))Cl]Cl (M = Ru, Ru-10; M = Os, Os-10). In complexes Ru-1-Ru-8 and Ru-10, Os-1-Os-3, Os-5 and Os-7 and Os-10, the ligands were found to coordinate as bidentate N,O- and N,N-chelates, while in complexes Ru-HL(9) and Os-HL(9), monodentate coordination of the ligands through the quinoline nitrogen was established. The antimalarial activity of the new ligands and complexes was evaluated against chloroquine sensitive (NF54 and D10) and chloroquine resistant (Dd2) Plasmodium falciparum malaria parasite strains. Coordination of ruthenium and osmium arene moieties to the ligands resulted in lower antiplasmodial activities relative to the free ligands, but the resistance index is better for the ruthenium complexes compared to chloroquine. Overall, osmium complexes appeared to be less active than the corresponding ruthenium complexes.

Regulating the anticancer properties of organometallic dendrimers using pyridylferrocene entities: synthesis, cytotoxicity and DNA binding studies

A new series of eight first- and second-generation heterometallic ferrocenyl-derived metal-arene metallodendrimers, containing ruthenium(ii)-p-cymene, ruthenium(ii)-hexamethylbenzene, rhodium(iii)-cyclopentadienyl or iridium(iii)-cyclopentadienyl moieties have been prepared. The metallodendrimers were synthesized by first reacting DAB-(NH2)n (where n = 4 or 8, DAB = diaminobutane) with salicylaldehyde, and then the Schiff-base dendritic ligands were reacted in a one-pot reaction with the appropriate [(η(6)-p-iPrC6H4Me)RuCl2]2, [(η(6)-C6Me6)RuCl2]2, [(η(5)-C5Me5)IrCl2]2 or [(η(5)-C5Me5)RhCl2]2 dimers, in the presence of 4-pyridylferrocene. Heterometallic binuclear analogues were prepared as models of the larger metallodendrimers. All complexes have been characterized using analytical and spectroscopic methods. The cytotoxicity of the heterometallic metallodendrimers and their binuclear analogues were evaluated against A2780 cisplatin-sensitive and A2780cisR cisplatin-resistant human ovarian cancer cell lines and against a non-tumorigenic HEK-293 human embryonic kidney cell line. The second generation Ru(ii)-η(6)-C6Me6 metallodendrimer is the most cytotoxic and selective compound. DNA binding experiments reveal that a possible mode-of-action of these compounds involves non-covalent interactions with DNA.

Cyclometalated Benzaldimine-Terminated Rhodium and Iridium Dendrimers: Synthesis, Characterization and Molecular Structures of Mononuclear Analogues

Monomeric and dendritic benzaldimine ligands were reacted with either [Rh(η5-C5Me5)Cl2]2 or [Ir(η5-C5Me5)Cl2]2 via a bridge-splitting reaction, to produce a series of new mono- and polynuclear rhodium(III) and iridium(III) cyclometalated complexes. All of the complexes were characterized using various spectroscopic and analytical techniques including 1H NMR, 13C{1H} NMR and FT-IR spectroscopy, mass spectrometry and elemental analysis. The molecular structures of the mononuclear complexes were determined using single crystal X-ray crystallography.