Real-time detection of DNA cleavage induced by [M(2,2′-dipyridylamine) 2(NO 3) n] x+ (M = Cd, Cu, Ni, Zn, n = 1,2, x = 0,1): Effect of central metal ions

Abstract

[M(Hdpa) 2(NO 3) n ] x+ (M = Zn II, Cd II, Cu II and Ni II, n = 1,2, and x = 0, 1) complexes were synthesized, and their activity as catalysts for DNA cleavage reactions were investigated using electrophoresis and linear dichroism technique (LD). All four metal complexes effectively cleaved pBR322 super-coiled DNA. The electrophoresis analysis showed that the [Zn(Hdpa) 2(NO 3)] + and [Cd(Hdpa) 2(NO 3) 2] complexes most effectively cleaved the super-coiled DNA, whereas the [Ni(Hdpa) 2(NO 3)] + complex was least effective. The magnitude of LD in the DNA absorption region reflects the flexibility and length of DNA when the conditions for measurement are properly adjusted. The double stranded DNA cleavage increases the flexibility of DNA and reduces the length, reducing the magnitude of LD in DNA absorption region. Utilizing this LD property, the cleavage was detected in real-time by measuring the LD magnitude with respect to time. The decrease in the LD magnitude was described as the sum of two exponentials. The fast component was tentatively assigned to the cleavage of the single strand, reflecting the increase in the flexibility of DNA, and the slow component was assigned to the cut of the double strand which reduced the length of DNA. The average reaction time was the fastest for the Zn II complex and the slowest for the Ni II complex. The reaction time of the Cd II complex was as fast as that of the Zn II complex. Both the Zn II and Cd II belong to group 12, suggesting that [M(Hdpa) 2(NO 3) n ] x+ with central metal ions from group 12 most efficiently cleaved double stranded DNA.