A New Class of Supramolecular, Mixed-Metal DNA-Binding Agents: The Interaction of RuII,PtII and OsII,PtII Bimetallic Complexes with DNA
- 1 September 1997
- journal article
- research article
- Published by American Chemical Society (ACS) in Inorganic Chemistry
- Vol. 36 (20) , 4534-4538
- https://doi.org/10.1021/ic970054i
Abstract
A new type of mixed-metal, supramolecular complex has been designed that incorporates a platinum center to allow binding to DNA. The interaction of two such platinum heterobimetallic complexes of the general formula [(bpy)2M(dpb)PtCl2]Cl2 (M = RuII, OsII; bpy = 2,2‘-bipyridine; dpb = 2,3-bis(2-pyridyl)benzoquinoxaline) with DNA is reported herein. The modular design of these systems allows for synthetic variation of individual components within this structural motif. In this case, the remote metal is varied from RuII to OsII. DNA binding was analyzed using non-denaturing agarose gel electrophoresis. The interaction of these complexes with DNA was studied relative to the known DNA cross-linkers, cis-[Pt(NH3)Cl2] (cisplatin) and trans-{[PtCl(NH3)2]2(μ-H2N(CH2)6NH2)}2+ (1,1/t,t). Our mixed-metal Ru,Pt and Os,Pt compounds retard the migration of DNA through the gel in both a concentration- and time-dependent manner. Their effect on the migration of DNA is similar to, although much more dramatic than, that observed for either cisplatin or 1,1/t,t. Our evidence suggests a covalent binding of our mixed-metal complexes to DNA through the platinum site. The degree of retardation of DNA migration suggests a large change in DNA conformation is induced by binding of our mixed-metal complexes. This work establishes these inorganic systems as a new class of DNA-binding agents and lays the groundwork for future efforts to enhance binding in an effort to develop novel anticancer drugs through serial design and testing.Keywords
This publication has 35 references indexed in Scilit:
- Spectroscopic and Electrochemical Properties of a Series of Mixed-Metal d6,d8Bimetallic Complexes of the Form [(bpy)2M(BL)PtCl2]2+(bpy = 2,2‘-Bipyridine; BL = dpq (2,3-Bis(2- pyridyl)quinoxaline) or dpb (2,3-Bis(2-pyridyl)- benzoquinoxaline); M = OsIIor RuII)Inorganic Chemistry, 1996
- Carboplatin and ifosfamide and selective consolidation in advanced seminomaEuropean Journal Of Cancer, 1995
- Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatinNature, 1995
- Interactions of Enantiomeric Ruthenium (II) Complexes with Polynucleotides as Studied by Circular Dichroism, Electric Dichroism Measurements, and PhotolysisInorganic Chemistry, 1995
- Sequence Specificity of DNA-DNA Interstrand Cross-Link Formation by Cisplatin and Dinuclear Platinum ComplexesBiochemistry, 1994
- Photophysics of Polyazaaromatic Ruthenium(II) Complexes Interacting with DNAThe Journal of Physical Chemistry, 1994
- New Cisplatin Analogues in DevelopmentDrugs, 1993
- DNA hairpin formation in adducts with platinum anticancer drugs: gel electrophoresis provides new information and a caveatJournal of the American Chemical Society, 1993
- Synthesis, characterization, DNA binding, and cytotoxic studies of some mixed-ligand palladium(II) and platinum(II) complexes of α-diimine and amino acidsJournal of Inorganic Biochemistry, 1991
- A comparison of chemical reactivity, cytotoxicity, interstrand crosslinking and DNA sequence specificity of bis(platinum) complexes containing monodentate or bidentate coordination spheres with their monomeric analogsBiochemistry, 1990