A comparative study of calf thymus DNA binding to Cr(III) and Cr(VI) ions - Evidence for the guanine N-7-chromium-phosphate chelate formation

Chromium(VI) salts are well known to be mutagens and carcinogens and to eas ily cross the cell membranes. Because they are powerful oxidizing agents, C r(VD reacts with intracellular materials to reduce to trivalent form, which binds DNA. This study was designed to investigate the interaction of calf thymus DNA with Cr(VI) and Cr(IPI) in aqueous solution at pH 6.5-7.5, using Cr(VI)/DNA(P) molar ratios (r) of 1:20 to 2:1 and Cr(III)/DNA(P) molar rat ios (r) of 1:80 to 1:2, W-visible and Fourier transform infrared (FTIR) dif ference spectroscopic methods were used to determine the metal ion-binding sites, binding constants, and the effect of cation complexation on DNA seco ndary structure. Spectroscopic results showed no interaction of Cr(VI) with DNA at low anion concentrations (r = 1:20 to 1:1), whereas some perturbati ons of DNA bases and backbone phosphate were observed at very high Cr(VI) c ontents (r > 1) with overall binding constant of K = 508 M-1. Cr(III) chela tes DNA via guanine N-7 and the nearest PO2 group with overall binding cons tant of K = 3.15 x 10(3) m(-1) Evidence for cation chelate formation comes from major shiftings and intensity variations of the guanine band at 1717 a nd the phosphate asymmetric stretching vibration at 1222 cm(-1), At low Cr( III) concentration (r = 1:40), the number of Cr(III) ions bound to DNA were 6-7 cations/500 base pairs, and this increased to 30-35 cations/500 base p airs at high metal ion content (r = 1:4), DNA condensation occurred at high cation concentration (r = 1:10). No major alteration of DNA conformation w as observed, and the biopolymer remained in the B family structure upon chr omium complexation.