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.com
Volume 5, Issue 3 (Suppl)
Mod Chem Appl, an open access journal
ISSN: 2329-6798
Global Chemistry 2017
September 04-06, 2017
September 04-06, 2017 | London, UK
5
th
Global Chemistry Congress
Mod Chem Appl 2017, 5:3(Suppl)
DOI: 10.4172/2329-6798-C1-006
Kinetics and mechanism of Pt(II)-sulfur adduct formation with bio-relevant molecules
in vitro
aqueous medium: Their anticancer activity, DNA binding, drug reservoir property and a theoretical
approach
Sankar Ch Moi, I Mitra, S Mukherjee
and
V P Reddy B
National Institute of Technology Durgapur, India
S
ynthesis and cytotoxic property of Pt(II)-sulfur adducts are significant in biological aspect. In order to investigate
their relevance, two Pt(II) model complexes were considered for detailed study.
In-vitro
kinetics and their mechanism,
drug reservoir property of the complexes [Pt(ambim)(H2O)2]X2 1A, [Pt(MAMP)(H2O)2]X2 2A (where, AMBIM=
2-aminomethylbenzimidazole, MAMP = 2-[(N-methylamino)methyl]pyridine and X= NO3- or ClO4-) with sulfur containing
bio-molecules DL-methionine (DL-meth), DL-penicillamine (DL-pen) and Glutathione (GSH) were studied to explore the
'drug reservoir' mechanism. The complexes [Pt(ambim)(DL-pen)] 1B, [Pt(ambim)(GSH)] 1C, [Pt(MAMP)(DL-meth)] 2B and
[Pt(MAMP)(DL-pen)] 2C were synthesized from complexes 1A and 2A, which was obtained from the hydrolysis of complexes
[Pt(ambim)Cl2] and [Pt(MAMP)Cl2] and characterized by spectroscopic methods. Interactionmechanismbetween the diaqua
complexes with S-containing ligands have been established by kinetic study. Two step consecutive reaction rate constants
(k1 and k2) and corresponding activation parameters (ΔHǂ and ΔSǂ) for both the steps were calculated and an associative
mechanism was proposed. Theoretical investigations like structural optimization, HOMO-LUMO energy calculations, NBO
analysis were performed to get an insight into their electronic structure. The coordination mode of the biomolecules via (S,
O) were established by spectroscopic methods and confirmed by NBO analysis. DNA binding property of the complexes 2-4
were investigated by UV-Vis spectra, competitive binding experiment, gel electrophoresis and their corresponding binding
constants (kb and ksv) were calculated. The computational molecular docking study was carried out for the complexes with
B-DNA to confirm their DNA binding mode. Cytotoxic property of the proposed complexes were investigated on HeLa,
HepG2 and A549 cell lines. Their corresponding IC50 values were calculated and compared with the well known anticancer
drug cisplatin.
sankarmoi67@yahoo.com