Targeting DNA sites with chiral metal complexes
Complexes derived from tris(phenanthro1ine) metal cations possess several features in common which are critical to their application as site-specific DNA binding molecules. Transition metal complexes have been designed which recognize and react at specific conformations along the DNA strand. The complexes, derivatives of tris(phenanthro1ine) metal cations, possess several features in common which are critical to their application as site-specific DNA binding molecules. The complexes all are rigid, chiral, and contain a coordinatively saturated metal ion at their core. The complexes bind to DNA in a non-covalent fashion. Spectroscopic studies have been useful in characterizing both intercalative and groove-bound interactions of the complexes with the DNA helix (ref 1). Because the complexes are rigid, once aspects of the binding interaction with DNA are determined, the orientation of the molecule as a whole with respect to the DNA helix can be considered. The chirality of the complexes is furthermore useful in specifying conformation-selective recognition along the strand (ref 2). The two binding modes to DNA show differing enantiomeric selectivity. In addition, simply, the diastereomeric interaction of the transition metal complexes with the dissymmetric DNA helical structure in itself provides a level of specificity that is usefully exploited. Lastly, the importance of the central metal ion at the core of the structure of the DNA binding molecule is noteworthy. Besides serving as a spectroscopic and photoreactive handle to monitor sensitively the binding of the complex to DNA, the central metal ion provides the core to hold together the ligand scaffolding around it. The metal, though not directly coordinating to the DNA helix, instead defines the shape of the rigid asymmetric structure which may be matched to that of the DNA. Some of the complexes which recognize and react at sites along the DNA are shown below: