Synthesis of novel types of copper-bipyridyl porphyrins and characterization of their interactions and reactivity with DNA.
The inherent ability to interact with DNA makes cationic metallo-porphyrins attractive targets as antitumor drugs. Many studies describe their interaction with DNA and the mechanism by which they induce DNA cleavage. Since porphyrins can be used as anchors for chemically reactive groups, it is possible to modify them to generate a family of compounds with specific functions. In the present work, we used chemical groups such as copper-bipyridinium (Cu-bpy), which hydrolyze phosphodiester bonds, and a porphyrin core to synthesize two novel Cu(2)-bpy-porphyrins. Their interactions with DNA have been characterized using classic spectroscopic methods, and their oxidative and hydrolytic reactivity toward supercoiled plasmid DNA has been studied in vitro. Our results show that Cu(2)-bpy-porphyrins interact with DNA via external association and intercalation and that their ability to cleave DNA and the mechanisms depends on the experimental conditions.
Lainé
M
M
Laboratoire de Chimie Bioorganique et Bioinorganique, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Université Paris XI Orsay, 91405 Orsay cedex, France. mlaine@members.nyas.org
Richard
F
F
Tarnaud
E
E
Bied-Charreton
C
C
Verchère-Béaur
C
C
D015082:2,2'-Dipyridyl / Q000737:chemistry* / Q000378:metabolism; D000693:Anaerobiosis; D002412:Cations; D002563:Cerium / Q000737:chemistry; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers; D006868:Hydrolysis; D007364:Intercalating Agents / Q000737:chemistry; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000138:chemical synthesis* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D002412:Cations; D016166:Free Radical Scavengers; D007364:Intercalating Agents; D011166:Porphyrins; D002563:Cerium; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA