Drug reservoir mechanism of Pt(II)-sulfur chelates based on pharmacokinetics of Pt(II) complex with thiols & thio-ethers: An experimental and theoretical approach
| Autor: | Rituparna Bhaduri, Sankar Ch. Moi, Subhajit Mukherjee, Swarup Kumar Tarai, Venkata Pera Reddy B, Saikat Mandal |
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| Rok vydání: | 2021 |
| Předmět: |
Denticity
010405 organic chemistry Ligand Chemistry Thio Entropy of activation Associative substitution 010402 general chemistry 01 natural sciences Medicinal chemistry 0104 chemical sciences Inorganic Chemistry Materials Chemistry Electronic effect Reactivity (chemistry) Chelation Physical and Theoretical Chemistry |
| Zdroj: | Inorganica Chimica Acta. 517:120202 |
| ISSN: | 0020-1693 |
| DOI: | 10.1016/j.ica.2020.120202 |
| Popis: | Dichloro Pt(II) complex, Cis-[Pt(AEP)Cl2], C-1 was synthesized with bidentate chelating ligand 1-(2-Aminoethyl)-pyrrolidine (AEP) and hydrolyzed to the corresponding complex [Pt(AEP)(OH2)2](ClO4)2, C-2 to investigate their pharmacokinetics and theoretical study. Bio-relevant tri-peptide glutathione (GSH) and amino acid dl -methionine ( dl -meth) substituted complex [Pt(AEP)(GSH)] C-3 and [Pt(AEP)( dl -meth)]2+ C-4 were synthesized and characterized as model sulfur chelated anticancer agent. To observe the role of steric and electronic effect of the ligand in pharmacokinetics, at pseudo-first-order reaction condition and at pH 4.0, in vitro reactions of complex C-2 with GSH and dl -meth for bio-transformation to C-3 & C-4 respectively, were studied. To evaluate the mechanistic pathway of ‘drug reservoir’ activity. Two-step rate constants (k1 and k2) and activation parameters were assessed, which reflect the high and negative value of entropy of activation (ΔSǂ) and low and positive value of enthalpy of activation (ΔHǂ) to support an associative mechanism. A theoretical investigation was executed, which mainly emphasized on structural optimization, HOMO-LUMO energy, TD-DFT, IR simulations and reactivity parameters to observe a detailed insight into the electronic structure and bonding mode as well as bonding parameters of the complexes. Bonding mode of thiol and thio-ether in C-3 and C-4 were established with FT-IR spectroscopy and NBO analysis with all possible chelation in the substituted complexes which clearly reveals to the formation of C-3 and C-4 through (S, O), rather than C-3‘ and C-4‘ through (S, N) or (N, O). |
| Databáze: | OpenAIRE |
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