Mononuclear η6-arene ruthenium(II) complexes with pyrazolyl-pyridazine ligands: synthesis, CT-DNA binding, reactivity towards glutathione, and cytotoxicity.

Organometallic η6-arene ruthenium(II) complexes with 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (Ru1, Ru2, and Ru5) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (Ru3-4) N,N' heterocyclic and η6-arene (cymene (Ru1-4) or toluene (Ru 5)) have been synthesized. The ruthenium(II) complexes have common "three-legged piano-stool" pseudo-octahedral structures known for half-sandwich complexes. Evolution of their UV-Visible absorption spectra in PBS buffer or DMSO over 24 h confirmed their good solvolysis stability. Titrations of the complexes with the calf thymus DNA (CT-DNA) were monitored using UV-Visible absorption and fluorescence spectroscopies. The complexes interact moderately with CT-DNA and their binding constants are in the order of 104 M-1. Competitive binding of the complexes to a DNA-Hoechst 33,258 depicted competitive displacement of Hoechst from DNA's minor grooves. These complexes bind to glutathione forming GSH-adducts through S coordination by replacement of a halide, with the iodo-analogues having higher binding constants than the chloro-complexes. Cyclic voltammograms of the complexes exhibited one electron-transfer quasi-reversible process. Trends in the molecular docking data of Ru1-5/DNA were similar to those for DNA binding constants. Of the five, only Ru1, Ru3 and Ru5 showed some activity (moderate) against the MCF-7 breast cancer cells with IC50 values in the range of 59.2-39.9 for which Ru5 was the most active. However, the more difficult-to-treat cell line, MDA-MB 231 cell was recalcitrant to the treatment by these complexes.

Mechanistic elucidation of linker and ancillary ligand substitution reactions in Pt(II) dinuclear complexes.

The rate of substitution of aqua ligands by three nucleophiles, thiourea (TU), N,N-dimethylthiourea (DMTU) and N,N,N,N-tetramethylthiourea (TMTU), for the complexes [cis-{PtOH2(NH3)2}2-µ-pyrazine](ClO4)2 (pzn), [cis-{PtOH2(NH3)2}2-µ-2,3-dimethylpyrazine](ClO4)2 (2,3pzn), [cis-{PtOH2(NH3)2}2-µ-2,5-pyrazine](ClO4)2 (2,5pzn) and [cis-{PtOH2(NH3)2}2-µ-2,6-dimethylpyrazine](ClO4)2 (2,6pzn) was investigated under pseudo first-order conditions as a function of concentration and temperature by stopped-flow and UV-Visible spectrophotometry. The reaction proceeded in three consecutive steps; each step follows first order kinetics with respect to each complex and nucleophile. The pseudo first-order rate constants, k(obs(1/2/3)), for sequential substitution of the aqua ligands and subsequent displacement of the linker obeyed the rate law: k(obs(1/2/3)) = k((1/2/3))[nucleophile]. The steric hindrance properties of the pyrazine-bridging ligand control the overall reaction pattern. The order of reactivity of the complexes is 2,3pzn ≈ 2,5pzn < 2,6pzn < pzn. The difference in reactivity attributed to the steric crowding at the Pt(II) centre imposed by the methyl groups reduces the lability of the aqua complexes. The order of reactivity of the nucleophiles decreases with the increase in steric demand TU > DMTU > TMTU. 1H and 195Pt NMR spectroscopic results confirmed the observed dissociation of the bridging ligand from the metal centre of the cis-dinuclear complexes and its derivatives in the third step. The dissociation process is accelerated by the introduction of the steric effect on the linker in conjunction with the increased ligand field strength imparted by additional thiourea ligands at each metal centre. The large negative entropy of activation ΔS(≠) values in all cases support an associative substitution mechanism.

The π-acceptor effect in the substitution reactions of tridentate N-donor ligand complexes of platinum(II): a detailed kinetic and mechanistic study.

The nucleophilic substitution reactions of complexes [Pt{4'-(2'''-CH(3)-phenyl)-2,2':6',2''-terpyridine}Cl]CF(3)SO(3), [CH(3)PhPtCl], [Pt{4'-(2'''-CH(3)-phenyl)-6-(3''-isoquinoyl)-2,2'bipyridine}Cl]SbF(6), [CH(3)PhisoqPtCl], [Pt{2-(2'-pyridyl)-1,10-phenanthroline}Cl]Cl, [pyPhenPtCl], and [Pt(terpyridine)Cl](+), [PtCl] with a series of nucleophiles: thiourea (TU), N,N-dimethylthiourea (DMTU), N,N,N,N-tetramethylthiourea (TMTU), I(-), Br(-), and SCN(-) were studied in 0.1 M LiCF(3)SO(3) in methanol (in the presence of 10 mM LiCl). The reactivity of the investigated complexes follows the order pyPhenPtCl > PtCl > CH(3)PhPtCl > CH(3)PhisoqPtCl. The lability of the chloride ligand is dependent on the strength of π-backbonding properties of the spectator ligands around the platinum centre. The experimental data is strongly supported by DFT calculations. The dependence of the second-order rate constants on concentration of the nucleophiles as well as the large negative values reported for the activation entropy (ΔS(‡)) confirmed an associative mechanism of substitution.

Studies of chromium removal from tannery wastewaters by algae biosorbents, Spirogyra condensata and Rhizoclonium hieroglyphicum.

Chromium in the effluent is a major concern for tanning industry. Chemical precipitation methods are commonly employed for the removal of chromium but this leads to formation of chrome-bearing solid waste, plus it is uneconomical when the concentration of chromium in the effluent is low. Ion exchange and membrane separation methods are relatively expensive. In this study, two algae namely, Spirogyra condensata and Rhizoclonium hieroglyphicum have been employed to remove chromium from tannery effluent. The effect of pH and chromium concentration showed S. condensata to exhibit maximum uptake of about 14 mg Cr(III)/g of algae at optimum pH of 5.0 whereas R. hieroglyphicum had 11.81 mg of Cr(III)/g of algae at pH of 4.0. Langmuir and Freundlich models were applied. Increase of initial concentration of Cr resulted to a decrease in adsorption efficiency. Dilute sulphuric acid (0.1M) showed good desorption efficiency (>75%). Interference from cations negatively impacted on biosorption of chromium. Immobilized algae on Amberlite XAD-8 in a glass column, gave better recovery of chromium in tannery effluent compared to a batch method with unimmobilized algae. Fourier transform infra red (FT-IR) analysis of the two algae revealed the presence of carboxyl groups as possible binding sites.