Spectral and Electrochemical Behavior of Copper(II)-Phenanthrolines Bound to Calf Thymus DNA. [(5,6-dimethyl-OP)(2)Cu](2+) (5,6-dimethyl-OP = 5,6-Dimethyl-1,10-phenanthroline) Induces a Conformational Transition from B to Z DNA.

Abstract

The interaction of 1:2 copper(II) complexes of 1,10-phenanthroline (OP) and variously methyl-substituted phenanthrolines with calf thymus DNA has been investigated by viscometry and spectral and electrochemical techniques. Viscometry and competitive ethidium bromide (EthBr) emission studies reveal that substitutions at 4- and 4,7-positions confer the complex a reduced affinity for DNA via partial intercalative interaction of the middle ring of OP between the base pairs of DNA, while substitutions at 5- and 5,6-positions confer a weak affinity toward DNA. The tetramethyl substitution at 3,4,7,8-positions lead to an intermediate behavior for the complex. Circular dichroism spectral studies of the interaction disclose for the first time that, of all the complexes, the 5,6-dimethyl-OP complex is a unique and remarkable reagent in that it reversibly binds to DNA and effects the important conversion of right-handed B DNA to left-handed Z DNA even in the presence of EthBr, an allosteric effector of the B conformation of DNA. This novel conformational transition is unexpected of the low GC content of natural DNA. The ratios of the binding constants (K(+)/K(2+)) for DNA binding of the Cu(I) and Cu(II) forms of the redox active OP complexes rather than the Cu(II)/Cu(I) redox potentials (0.023 to -0.098 V vs SCE) are good measures of the substituent dependent DNA cleavage efficiency and rate. They also reveal that the Cu(I) form of OP and 4-methyl- and 5,6-dimethyl-substituted OP complexes displays enhanced affinity to bind but noncovalently to the minor groove of DNA. Attempts have been made to illustrate the cleavage rate and efficiency of nucleolytic reactions in the light of the relative binding constants of Cu(I) and Cu(II) forms of the OP complexes.