NONCOVALENT DNA-BINDING OF BIS(1,10-PHENANTHROLINE)COPPER(I) AND RELATED-COMPOUNDS

The noncovalent DNA binding of the bis(1,10-phenanthroline)copper (I) complex [(Phen)2CuI] was examined under anaerobic conditions by absorption and circular dichroism spectroscopy, and viscometry, as a function of phenanthroline concentration. Analyses according to the McGhee-von Hippel method indicated that binding exhibited both neighbor-exclusion and positive cooperativity effects, with a neighbor-exclusion parameter n almost-equal-to 2 and a cooperativity parameter w almost-equal-to 4. The association constant for (Phen)2CuI binding decreased with increasing concentration of phenanthroline in excess over that required to stoichiometrically generate (Phen)2Cu1, indicating that free phenanthroline was a weak competitive inhibitor of (Phen)2Cu1 binding. The maximal association constant for DNA binding of (Phen)2Cu1 in 0.2 M NaCl and 9.8% ethanol, extrapolated to zero concentration of excess phenanthroline, was 4.7 X 10(4) M(-1) DNA base pairs). The magnitude of the neighbor-exclusion parameter, the changes in spectral properties of (Phen)2Cu1 induced by DNA binding, and the increase in DNA solution viscosity upon (Phen)2Cu1 addition are consistent with a model for DNA binding by (Phen)2Cu1 involving partial intercalation of one phenanthroline ring of the complex between DNA base pairs in the minor groove as suggested previously [Veal & Rill (1989) Biochemistry 28, 3243-3250]. Viscosity measurements indicateds that the moni(phenanthroline)copper(I) complex also binds to DNA by intercalation; however, no spectroscopic or viscometric evidence was found for DNA binding of free phenanthroline or the bis(2,9-dimethyl-1,10-phenanthroline)copper(I) complex. DNA binding of free phenanthroline may be cooperative and induced by prior binding of (Phen)2Cu1.