| Abstract
| - A new class of ternary copper(II) complexes of formulation [Cu(Ln)B](ClO4) (1−4), where HLn isa NSO-donor Schiff base (HL1, HL2) and B is a NN-donor heterocyclic base viz. 1,10-phenanthroline (phen)and 2,9-dimethyl-1,10-phenanthroline (dmp), are prepared, structurally characterized, and their DNA bindingand photocleavage activities studied in the presence of red light. Ternary complex [Cu(L3)(phen)](ClO4) (5)containing an ONO-donor Schiff base and a binary complex [Cu(L2)2] (6) are also prepared and structurallycharacterized for mechanistic investigations of the DNA cleavage reactions. While 1−4 have a squarepyramidal (4 + 1) CuN3OS coordination geometry with the Schiff base bonded at the equatorial sites, 5has a square pyramidal (4 + 1) geometry with CuN3O2 coordination with the alcoholic oxygen at the axialsite, and 6 has a square planar trans-CuN2O2 geometry. Binding of the complexes 1−4 to calf thymusDNA shows the relative order: phen ≫ dmp. Mechanistic investigations using distamycin reveal minorgroove binding for the complexes. The phen complexes containing the Schiff base with a thiomethyl orthiophenyl moiety show red light induced photocleavage. The dmp complexes are essentially photonucleaseinactive. Complexes 5 and 6 are cleavage inactive under similar photolytic conditions. A 10 μM solution of1 displays a 72% cleavage of SC DNA (0.5 μg) on an exposure of 30 min using a 603 nm Nd:YAG pulsedlaser (60 mJ/P) in Tris-HCl buffer (pH 7.2). Significant cleavage of 1 is also observed at 694 nm using aRuby laser. Complex 1 is cleavage inactive under argon or nitrogen atmosphere. It shows a more enhancedcleavage in pure oxygen than in air. Enhancement of cleavage in D2O and inhibition with sodium azideaddition indicate the possibility of the formation of singlet oxygen as a reactive intermediate leading toDNA cleavage. The d−d band excitation with red light shows significant enhancement of cleavage yield.The results indicate that the phen ligand is necessary for DNA binding of the complex. Both the sulfur-to-copper charge transfer band and copper d−d band excitations helped the DNA cleavage. While theabsorption of a red photon induces a metal d−d transition, excitation at shorter visible wavelengths leadsto the sulfur-to-copper charge transfer band excitation at the initial step of photocleavage. The excitationenergy is subsequently transferred to ground state oxygen molecules to produce singlet oxygen that cleavesthe DNA.
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