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Synthesis and Biological Activity of a Platinum( II ) 6‐Phenyl‐2,2′‐bipyridine Complex and Its Dimeric Analogue
Author(s) -
Chan HingLeung,
Ma DikLung,
Yang Mengsu,
Che ChiMing
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200390015
Subject(s) - chemistry , dimer , titration , platinum , cytotoxicity , hexafluorophosphate , binding constant , stereochemistry , bipyridine , dna , fluorescence , 2,2' bipyridine , medicinal chemistry , binding site , crystallography , in vitro , organic chemistry , biochemistry , ionic liquid , physics , quantum mechanics , crystal structure , catalysis
We have synthesized (pyridyl)‐(6‐phenyl‐2,2′‐bipyridine)platinum( II ) hexafluorophosphate ( 1 ) and its corresponding dimer , μ‐N,N ′‐bis(isonicotinyl)‐1,6‐hexanediamino bis‐[6‐phenyl‐2,2′‐bipyridine‐platinum( II )] dichloride ( 2 ). The DNA binding constants of 1 and 2 at 20 °C were determined by absorption titration to be 2.25×10 4 M −1 and 3.07×10 6 M −1 , respectively. Compound 1 showed an AT preference, while 2 had no base preference. The binding site sizes of 2 for [poly(dA‐dT)] 2 , calf thymus DNA (ctDNA), and [poly(dG‐dC)] 2 , as determined by fluorescence titration, were 6.6, 4.0, and 2.8 bp, respectively. Compound 2 probably bound to [poly(dA‐dT)] 2 through bisintercalation, and to [poly(dG‐dC)] 2 by monointercalation. Binding of DNA by both complexes is favorable, since the binding free energies of 1 and 2 were estimated to be −5.8 and −8.7 kcal mol −1 , respectively. The results of viscosity measurements and gel mobility shift assay demonstrated that binding of 1 and 2 caused DNA lengthening. The cytotoxicities of the complexes in various human cancer cell lines were determined by MTT assay. Complex 2 exhibited cytotoxicity comparable to that of cisplatin, and was more toxic than 1 by an order of magnitude.