Gajendra Gupta

Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes

Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III) complexes of the type (C5Me5)2Rh2(μ-SR)2Cl2 (R = CH2Ph, 1; R = CH2CH2Ph, 2) and cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes of the type [(C5Me5)2M2(μ-SR)3](+) (M = Rh, R = CH2Ph, 3; M = Rh, R = CH2CH2Ph, 5; M = Rh, R = CH2C6H4-p-(t)Bu, 7: M = Ir, R = CH2Ph, 4; M = Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-(t)Bu, 8) have been synthesized from the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers (C5Me5)2M2(μ-Cl)2Cl2 by reaction with the corresponding thiol derivative (RSH). Complexes 3-8 were isolated as chloride salts. All complexes were obtained in good yield and were fully characterized by spectroscopic methods. The molecular structures of the neutral complexes (1 and 2) show interesting features: the two rhodium atoms are bridged by two thiolato ligands with no metal-metal bonds and the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each other, an uncommon conformation for such dinuclear complexes. These structural features were rationalized using DFT calculations. Additionally, the antiproliferative activity of the complexes was evaluated against the cancerous A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian cell lines and on the noncancerous HEK293 human embryonic kidney cells. All complexes were found to be active and the cationic iridium complexes , and are particularly cytotoxic, with IC50 values in the nanomolar range (IC50 < 0.1 μM). The catalytic activity of the complexes for the oxidation of glutathione (GSH) to GSSG was evaluated by NMR spectroscopy.

Biological studies of chalcogenolato-bridged dinuclear half-sandwich complexes.

A series of cationic chalcogenolato-bridged diruthenium complexes [(η(6)-p-MeC6H4Pr(i))2Ru2(μ-EC6H5)3](+) (E = S, 1; E = Se, 2; E = Te, 3) has been obtained in ethanol from the reaction of (η(6)-p-MeC6H4Pr(i))2Ru2(μ-Cl)2Cl2 with benzenethiol, benzeneselenol, and sodium tellurophenolate, respectively. The thiolato and selenolato derivatives are isolated in good yield as the chloride salts, while the tellurolato analogue is isolated as the hexafluorophosphate salt. Similarly, the dinuclear pentamethylcyclopentadienyl (C5Me5) rhodium and iridium complexes (η(5)-C5Me5)2M2(μ-Cl)2Cl2 react with benzenethiol, benzeneselenol, and sodium tellurophenolate in ethanol to give the corresponding cationic dinuclear complexes of the general formula [(η(5)-C5Me5)2M2(μ-EC6H5)3](+) (M = Rh, E = S, 4; E = Se, 5; E = Te, 6; M = Ir, E = S, 7; E = Se, 8; E = Te, 9). In addition, cationic dinuclear complexes with mixed thiolato-selenolato and thiolato-tellurolato bridges have been prepared, [(η(6)-p-MeC6H4Pr(i))2Ru2(μ-EC6H5)(μ-SCH2C6H4-p-Bu(t))2](+) (E = Se, 10; E = Te, 11) and [(η(5)-C5Me5)2M2(μ-EC6H5)(μ-SCH2C6H5)2](+) (M = Rh, E = Se, 12; E = Te, 13; M = Ir, E = Se, 14; E = Te, 15), starting from the neutral dinuclear complexes (η(6)-p-MeC6H4Pr(i))2Ru2Cl2(μ-SCH2C6H4-p-Bu(t))2 and (η(5)-C5Me5)2M2Cl2(μ-SCH2C6H5)2. All complexes are highly cytotoxic showing activity in the submicromolar range. The nature of the chalcogenolato bridges seems to have an impact on the activity, while the nature of the metal center plays a minor role. Among the complexes tested, the dinuclear complexes 1, 4, and 7 with the thiolato bridges show the highest activity on cancer cells and the best affinity for CT-DNA as demonstrated by cell biology and biophysical experiments.

Syntheses, characterization and molecular structures of novel Ru(II), Rh(III) and Ir(III) complexes and their possible roles as antitumour and cytotoxic agents

A series of organometallic arene platinum group metal complexes of the type [(η6-arene)Ru(L)Cl]PF6 {arene = benzene; p-cymene and hexamethylbenzene, L = N, N′ ligands} and [(η5-Cp*)M(L)Cl]PF6 (where M = Rh(III) and Ir(III), L = N, N′ ligands) were synthesized. All complexes were isolated as hexafluoridophosphate salts and characterised by elemental analysis, infrared and NMR spectroscopy. The molecular structures of three representative complexes 1, 4 and 9 were determined by single crystal X-ray crystallography. They have a “piano stool” geometry with η5 and η6 coordination of the arene ligands. Trypan blue exclusion and DNA fragmentation assays of the synthesized complexes displayed the potent anticancer properties of complexes 5, 6 and 9. Compound 6 shows the highest antitumor activity with a T/C value of 211%.

Self-Assembled Novel BODIPY-Based Palladium Supramolecules and Their Cellular Localization

Four new palladium metal supramolecules with triangular/square architectures derived from boron dipyrromethane (BODIPY) ligands were synthesized by self-assembly and fully characterized by 1H and 31P NMR, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction. These supramolecules were more cytotoxic to brain cancer (glioblastoma) cells than to normal lung fibroblasts. Their cytotoxicity to the glioblastoma cells was higher than that of a benchmark metal-based chemotherapy drug, cisplatin. The characteristic green fluorescence of the BODIPY ligands in these supramolecules permitted their intracellular visualization using confocal microscopy, and the compounds were localized in the cytoplasm and on the plasma membrane.

Facile synthesis of hexagonal Sb2Te3 nanoplates using Ph2SbTeR (R = Et, Ph) single source precursors

Two new antimony telluride single source precursors (SSPs), Ph2SbTeR (R = Et, Ph), have been used to synthesise pure and defect free hexagonal Sb2Te3 nanoplates by thermal decomposition in an organic solvent. The chemical composition of the SSPs plays an important role in the formation of antimony telluride nanocrystals.

Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles

The neutral dinuclear complexes [(η5-C5Me5)2Rh2(μ-dhnq)Cl2] (1) and [(η5-C5Me5)2Ir2(μ-dhnq)Cl2] (2) (dhnqH2 = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of [(η5-C5Me5)M(μ-Cl)Cl]2 (M = Rh, Ir) with dhnqH2 in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4′-bipyridine or 1,2-bis(4-pyridyl)ethylene), in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles [(η5-C5Me5)4M4(μ-dhnq)2(μ-L)2]4+ (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4′-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridyl)ethylene, M = Rh, 7; M = Ir, 8). All complexes were isolated as their triflate salts and were fully characterized by infrared, 1H and 13C NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3–8 was evaluated against the human ovarian A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range.

Anticancer activity of large metalla-assemblies built from half-sandwich complexes

A series of octanuclear p-cymene ruthenium and pentamethylcyclopentadienyl rhodium and iridium metalla-assemblies has been prepared from tetrapyridyl porphyrin (tpp) panels and the corresponding dinuclear clips, (η6-MeC6H4Pri)2Ru2(μ4-C6HRO4)Cl2 (R = C11H23) and (η5-C5Me5)2M2(μ4-C6HRO4)Cl2 (M = Rh, Ir). All complexes were isolated in good yield as their triflate salts, [(η6-MeC6H4Pri)8Ru8(μ4-tpp)2(μ4-C6HRO4)4][CF3SO3]8 (1), [(η5-C5Me5)8Rh8(μ4-tpp)2(μ4-C6HRO4)4][CF3SO3]8 (2) and [(η5-C5Me5)8Ir8(μ4-tpp)2(μ4-C6HRO4)4][CF3SO3]8 (3), and fully characterized by spectroscopic methods. The antiproliferative activity of the complexes was evaluated on the cancerous (MCF-7, B16 and A549) and non-cancerous (NIH 3T3) cell lines, showing in all cases IC50 values around 0.1 μM. Further biological studies suggest that apoptosis is induced by the complexes and that interaction with DNA can be in part responsible for the high cytotoxicity.

Facile solution routes for the syntheses of GeTe nanocrystals

Solution-based synthetic routes are attractive strategies for synthesizing GeTe materials, because they have the potential to impart morphology control on the crystallites and permit liquid-based processing of films and patterned structures. Two liquid phase reaction systems for GeTe nanoparticles (NPs) have been studied using GeCl2·dioxane and trioctylphosphine-tellurium (TOP-Te) in oleylamine (OLA) as solvent and reducing agent and using GeCl2·dioxane and (Et3Si)2Te in trioctylphosphine oxide (TOPO) without the use of any reducing agent. The morphology of the GeTe powders had a strong dependence on the Te source and reaction medium. The SEM image of NPs obtained by the reaction of GeCl2·dioxane and (Et3Si)2Te reveals that with an increase in reaction time (2, 10, 15 and 30 min), the size of the NPs increases and their shape becomes uniform. However, it is interesting to observe that after 30 min, the morphology of the nanoparticles was maintained even after longer reaction times i.e., the duration of heating had no pronounced influence on the size and morphology of the nanocrystals after a particular period of time. Reaction with TOP-Te leads to the formation of irregular GeTe nanocrystals through the so called Ostwald-ripening process. However, with (Et3Si)2Te as Te source, a ligand exchange reaction mechanism has been proposed leading to the formation of well-dispersed GeTe nanoparticles of uniform shape.

Hydroxylation of azomethine carbon: isolation of complexes of η5 and η6-cyclic hydrocarbon platinum group metals with a new Schiff-base ligand

A new Schiff base, (pyridin-2-yl)-N-(3,5-di(pyridin-2-yl)-4H-1,2,4-triazol-4-yl)methanimine, (L), was synthesized. Reaction of [(η6-arene)Ru(µ-Cl)Cl]2 and [Cp*M(µ-Cl)Cl]2 (M = Rh and Ir) with one equivalent of L in the presence of NH4PF6 in methanol yielded dinuclear complexes, [(η6-arene)2Ru2(L-OH)Cl](PF6)2 {arene = C6H6 (1), p-iPrC6H4Me (p-cymene) (2) and C6Me6 (3)}, and [Cp*2M2(L-OH)Cl](PF6)2 [M = Rh (4) and Ir (5)], respectively, leading to the formation of five new chiral complexes with –OH on the azomethine carbon. L is a pentadentate ligand where one of the metal centers is coordinated to two nitrogen atoms in a bidentate chelating fashion while the other metal is bonded tridentate to three nitrogen atoms. Although the ligand is neutral before coordination, after complexation it is anionic (uni-negative) with negative charge on the azo nitrogen {see the structures: N(5) in 2[PF6]2 and N(3) for 4[PF6]2}. The complexes have been characterized by various spectroscopic methods including infrared and 1H NMR and the molecular structures of the representative complexes are established by single-crystal X-ray diffraction studies.

Syntheses and structural studies of mononuclear arene ruthenium complexes with nitrogen-based chelating ligands

Dinuclear arene ruthenium complexes [(η6-arene)Ru(μ-Cl)Cl]2 (arene = C6H6; p iPrC6H4Me; C6Me6) and monomeric cyclopentadienyl complexes [(η5-Cp)Ru(PPh3)2Cl] (Cp = cyclopentadienyl) react with polypyridyl nitrogen ligands L1 (3-(pyridin-2-yl)-1H-1,2,4-triazole) and L2 (1,3-bis(di-2-pyridylaminomethyl)benzene) in methanol to afford cationic mononuclear compounds [(η6-arene)Ru(L1)Cl]+ (arene = C6H6, 1; p iPrC6H4Me, 2; C6Me6, 3), [(η6arene)Ru(L2)Cl]+ (arene = C6H6, 4; p iPrC6H4Me, 5; C6Me6, 6), [(η5-Cp)Ru(L1)(PPh3)]+ (7), and [(η5Cp)Ru(L2)(PPh3)]+ (8). All cationic mononuclear compounds were isolated as their hexafluorophosphate salts and characterized by elemental analyses, NMR, and IR spectroscopic methods and some representative complexes by UV-Vis spectroscopy. The solid state structures of two derivatives, [6]PF6 and [7]PF6, have been determined by the X-ray structure analysis.