Goutam Kr. Ghosh

Ligand substitution reaction on a platinum(II) complex with bio-relevant thiols: kinetics, mechanism and bioactivity in aqueous medium

The kinetics of the interaction between [Pt(pic)(H2O)2](ClO4)2, cis-diaqua(2-aminomethylpyridine)platinum(II) perchlorate 1 and selected thiols (L-cysteine and N-acetyl-L-cysteine) has been studied spectrophotometrically in aqueous medium as a function of complex and thiol concentrations, pH, and temperature at constant ionic strength. The observed pseudo-first-order rate constants kobs (s−1) obeyed the equation kobs = k1[thiol]. At pH = 4.0, complex 1 interacts with the thiols via two distinct consecutive steps. The first step is dependent while the second step is independent of ligand concentration. The rate constants for the process are of the order: k1 ≈ 10−3 M−1 s−1 and k2 ≈ 10−5 s−1. The association equilibrium constant (KE) for the outer sphere complex formation has been evaluated together with the rate constants for the two subsequent steps. Both the steps are ligand-assisted anation and the final step is the ring closure process. The activation parameters for both steps were evaluated using Eyrings equation. The low ΔH‡1 = (34.91 ± 0.97 kJ mol−1) and ΔH‡2 = (29.10 ± 0.72 kJ mol−1) values and large negative values of ΔS‡1 = (−174.68 ± 2.18 J K−1 mol−1) and ΔS‡2 = (−233.74 ± 2.4 J K−1 mol−1) for both the anation steps were evaluated. On the basis of the kinetic observations, evaluated activation parameters and spectroscopic data, a plausible associative mechanism is proposed for both processes. Antibacterial properties on both gram positive and gram negative bacteria and anticancer properties of complex 1 and its substituted complexes 2 and 3 on HeLa cells have been investigated. Complexes 1 to 3 show remarkable growth inhibition of bacteria. They also show anticancer activity of about 70% when compared to cis-platin. The complexes bind to DNA and change its electrophoretic mobilization pattern in agarose gel.

Interaction of bio-relevant thio-ether and thiols with dinuclear Pd(II) complex: kinetics, mechanism, bioactivity in aqueous medium and molecular docking

The kinetics of interaction between [Pd(pic)(OH)]2(ClO4)2, 2 (pic = 2-aminomethylpyridine) with the selected ligands (L) DL-methionine (DL-meth), L-cysteine (L-cys) and N-acetyl-L-cysteine (N-ac-L-cys) have been studied under pseudo-first order conditions using a stopped-flow spectrophotometer in aqueous medium as a function of [complex 2] as well as [ligand], pH, and temperature at constant ionic strength. The ligand dependent second order reaction is found to take place in two consecutive steps in accordance with the rate law, k(obs) = k1[L]2 in which all these three reactions follow the third order kinetics. The first step of the reaction is dependent, while the second step is independent of [ligand] in all the cases. The activation parameters, ΔH‡ and ΔS‡ for the two-step reactions are evaluated from the Eyring equation. An associative mode of activation (an associative mechanism) in the transition state is proposed for all these substitution processes. Complex 2 and its substituted products [Pd(pic)DL-meth]+ 3; [Pd(pic)L-cys] 4; and [Pd(pic)N-ac-L-cys] 5 are characterized by UV-Vis, FT-IR, 1H-NMR and ESI-mass spectroscopic methods. Complex 2–5 show remarkable anticancer properties on HeLa cells of about 70% at high concentration when compared to cis-platin and antibacterial properties on both the Gram positive (Bacillus subtilis) and Gram negative (E. coli Dh5α) bacteria. In addition, DNA interaction with plasmid DNA is observed and computational molecular docking studies were carried out with an aim to establish the binding mode of complex 2 with B-DNA.

Interaction of Glutathione With Cis-(2-Aminomethylpyridine)diaqua platinum(II) Perchlorate in Aqueous Medium: Their Kinetics and Mechanism

The kinetic interaction of glutathione with cis-[Pt(pic)(OH2)2] (ClO4)2 (pic = 2-Aminomethylpyridine) has been studied spectrophotometrically as a function of cis-[Pt(pic)(OH2)2]2+, glutathione concentration, and temperature at pH 4.0, where the complex exists predominantly as the diaqua species and glutathione as a zwitter ion. The substitution reaction shows two distinct consecutive steps: the first is the ligand assisted anation and the second is the chelation step. The association equilibrium constant (KE ) for the outer sphere complex formation has been evaluated with rate constants k1 (≈10−3) for the first step. The activation parameters for both the steps were evaluated using Eyring equation. The low ΔH1 ≠ = (52.37 ± 2.10 kJmol−1) and large negative value of ΔS1 ≠ = (−112.35 ± 2.98 JK−1mol−1) as well as ΔH2 ≠ = (37.29 ± 1.84 kJmol−1) and ΔS2 ≠ = (−130.12 ± 3.16 JK−1mol−1) indicate an associative mode of activation for both the aqua ligand substitution processes.

An experimental and theoretical approach on the kinetics and mechanism for the formation of a four-membered (S, S) chelated Pt(II) complex

The interaction of a chemoprotective agent, diethyldithiocarbamate (DDTC), with cis-[Pt(pic)(H2O)2]2+, 2 (where pic = 2-aminomethylpyridine), in aqueous medium was investigated experimentally and theoretically. The equilibrium constant (KE) for the formation of the outer sphere association complex and the rate constants for both steps have been evaluated experimentally, and were compared with the theoretically determined values. The activation parameters (ΔHǂ, ΔSǂ and ΔGǂ) for both the steps were calculated and an associative mechanism is proposed. The bonding modes of the product [Pt(pic)(DDTC)]+, 3, were confirmed by spectroscopic measurements and supported by Time Dependent Density Functional Theory (TD-DFT) and Natural Bond Orbital (NBO) calculations. Penta coordinated platinum transition state geometries for both the steps were fully optimized and confirmed by frequency analysis and an intrinsic reaction coordinate method molecular docking study has been performed to understand the binding interaction of complex 2 with B-DNA. The anticancer properties of 2 and 3 were investigated on a HeLa cell line, and they showed remarkable activity of about 70% compared to cisplatin at 50 μM concentration.

Kinetics and mechanism of biphasic substitution reactions of a platinum(II) complex with thioglycollic acid and 4-methyl-3-thiosemicarbazide in aqueous solution

The kinetics of interactions between cis-diaqua(2-aminomethylpyridine)platinum(II) perchlorate (1) [Pt(pic)(OH2)2](ClO4)2, thioglycollic acid (TGA), and 4-methyl-3-thiosemicarbazide (MTSC) have been studied spectrophotometrically in aqueous medium as a function of the [complex (1)] as well as [TGA] or [MTSC], pH and temperature at constant ionic strength. The observed pseudo-first-order rate constants were proportional to [TGA] or [MTSC]. At pH 4.0, the interactions of (1) with both TGA and MTSC show two distinct consecutive steps; the first step is dependent and second independent of [TGA] or [MTSC]. The association equilibrium constant (KE) for the outer sphere complex formation has been evaluated, along with the rate constants for the two steps. The first step is assigned to ligand-assisted anation and the second to chelation of TGA or MTSC. The activation parameters for both the steps were evaluated using Eyring’s equation. On the basis of the kinetic observations and evaluated activation parameters, an associative mechanism is proposed for both the reactions.

Kinetics and Mechanism of the Interaction of DL-methionine with Di-μ-Hydroxobis(1,10-Phenanthroline)Dipalladium(II) Ion in Aqueous Solution

The kinetics of interaction between DL-methionine with the di-μ-hydroxobis(1,10-phenanthroline)dipalladium(II) ion complex has been studied spectrophotometrically, in pseudo-first-order conditions in aqueous solution as a function of [complex], [ligand], pH and temperature at constant ionic strength. At pH 6.5 the interaction of DL-methionine with the complex shows two distinct consecutive steps, i.e., it shows linear dependence on the concentration of DL-methionine. Both the steps are [ligand] dependent. The second order rate constants for the two steps are in the order of k1 ≈10 −5 dm 3 mol −1 s −1 and k 2 ≈ 10dm 3 mol −1 s −1 . The activation parameters are calculated from Eyring equation are found, ΔH‡ 1 = 73.16 ± 2.5KJ mol −1 , ΔS‡ 1 = −93.03 ±4.45 JK −1 mol −1 , ΔH‡ 2 = 66.50 ± 3.35 KJ mol −1 , ΔS‡2= − 63.21 ± 4.2 JK −1 mole −1 . On the basis of the kinetic data and thermodynamical activation parameters an associative mechanism is proposed for the interaction process.

Kinetics and mechanism of interaction of Pt(II) complex with bio-active ligands and in vitro Pt(II)-sulfur adduct formation in aqueous medium: bio-activity and computational study

Abstract Kinetics of interaction between [Pt(pic)(H2O)2](ClO4)2, 2 (where pic = 2-aminomethylpyridine) with the selected ligands DL-methionine (DL-meth) and DL-penicillamine (DL-pen) have been studied spectrophotometrically in aqueous medium separately as a function of [2] as well as [ligand], pH and temperature at constant ionic strength. The association equilibrium constants (KE) for the outer sphere complex formation have been evaluated together with the rate constants for the two subsequent steps. Activation parameters (enthalpy of activation ΔH≠ and entropy of activation ΔS≠) were calculated from the Eyring equation. An associative mechanism of substitution is proposed for both reactions on the basis of the kinetic observations, evaluated activation parameters, and spectroscopic data. Structural optimizations, HOMO-LUMO energy calculation, and Natural Bond Orbital (NBO) analysis of 2–4 were carried out with Density Functional Theory. Bonding mode of thiol and thio-ether is confirmed by spectroscopic analyses and NBO calculation. Cytotoxic properties of 2–4 were explored on A549 carcinoma cell lines; DNA-binding properties of the complexes were also investigated by gel electrophoresis.

Kinetics and Mechanism of Interaction of Thiosemicarbazide with Di-μ-hydroxobis(1,10-phenanthroline) Dipalladium(II) Perchlorate in Aqueous Solution

The kinetics and mechanism of the interaction between thiosemicarbazide with di-μ-hydroxobis(1,10-phenanthroline)dipalladium(II) ion complex has been followed spectrophotometrically in pseudo first order conditions in aqueous solution as a function of [Pd(1,10-phen)(H2O)2]2+, [thiosemicarbazide], pH, and temperature. The reaction of thiosemicarbazide (TSC) at pH 6.5 has been monitored at 240 nm. The reaction rate increases linearly with increasing thiosemicarbazide concentration in the studied concentration range. The second order rate constants 102k2 are 27.01, 33.78, 40.23, and 50.46 dm3 mol−1 s−1 at 20, 25, 30, and 35○C, respectively, have been calculated from the slope of k versus [thiosemicarbazide] plot by using the Origin6.0 software. From the experimental findings, an associative mechanism for the substitution reaction is proposed. The activation parameters calculated from Eyring equation are ΔH# 1= 46.72 ± 1.8 kJ mol−1, ΔS# 1= −100.38 ± 3.1JK−1mole−1support the proposition. On the basis of the kinetic and activation parameters, an associative mechanism is proposed for the interaction process. Quantum chemically obtained structures and geometrical parameters of the Pd(II) complex have been reported.