Abstract: Described herein is the development of synthetic routes to produce a wide variety of substituted phenanthridines, specifically, multidentate phenanthridine-containing ligand frameworks capable of anchoring to Pt via more than one binding site and with the phenanthridinyl moiety co-planar to the coordination plane of Pt. The multidentate chelation is designed to attenuate the reactivity of the platinum complex in vivo, and ultimately help mitigate side effects. In addition, the geometry of phenanthridine binding to the metal centre is altered compared to in phenanthriplatin, thanks to the constraints of the ligand geometry. By enforcing coplanar binding with the metal's square planar coordination plane, these compounds exhibit altered modes of activity, and should hence enhance/change the spectrum of activity of our prodrug candidates compared with phenanthriplatin.

Abstract: Described herein is the development of synthetic routes to produce a wide variety of substituted phenanthridines, specifically, multidentate phenanthridine-containing ligand frameworks capable of anchoring to Pt via more than one binding site and with the phenanthridinyl moiety co-planar to the coordination plane of Pt. The multidentate chelation is designed to attenuate the reactivity of the platinum complex in vivo, and ultimately help mitigate side effects. In addition, the geometry of phenanthridine binding to the metal centre is altered compared to in phenanthriplatin, thanks to the constraints of the ligand geometry. By enforcing coplanar binding with the metal's square planar coordination plane, these compounds exhibit altered modes of activity, and should hence enhance/change the spectrum of activity of our prodrug candidates compared with phenanthriplatin.