SPECTRAL AND ELECTROCHEMICAL-BEHAVIOR OF COPPER(II)-PHENANTHROLINES BOUND TO CALF THYMUS DNA - [(5,6-DIMETHYL-OP)(2)CU](2-DIMETHYL-OP = 5,6-DIMETHYL-1,10-PHENANTHROLINE) INDUCES A CONFORMATIONAL TRANSITION FROM B-DNA TO Z-DNA() (5,6)

The interaction of 1:2 copper(II) complexes of 1,10-phenanthroline (OP ) and variously methyl-substituted phenanthrolines with calf thymus DN A has been investigated by viscometry and spectral and electrochemical techniques. Viscometry and competitive, ethidium bromide (EthBr) emis sion studies reveal that substitutions at 4- and 4,7-positions confer the complex a reduced affinity for DNA via partial intercalative inter action of the middle ring of OP between the base pairs of DNA, while s ubstitutions at 5- and 5,6-positions confer a weak affinity toward DNA . The tetramethyl substitution at 3,4,7,8-positions lead to an interme diate behavior for the complex. Circular dichroism spectral studies of the interaction disclose for the first time that, of all the complexe s, the 5,6-dimethyl-OP complex is a unique and remarkable reagent in t hat 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 conf ormational transition is unexpected of the low GC content of natural D NA. The ratios of the binding constants (K+/K2+) for DNA binding of th e 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-dim ethyl-substituted OP complexes displays enhanced affinity to bind but noncovalently to the minor groove of DNA. Attempts have been made to i llustrate 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.