Structural features of DNA interaction with caffeine and theophylline

Caffeine and theophylline are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. However, there has been no information on the interactions of these xanthine derivatives with individual DNA at molecular level. The aim of this study was to examine the stability and structural features of calf-thymus DNA complexes with caffeine and theophylline in aqueous solution, using constant DNA concentration (6.25 mM) and various caffeine or theophylline/DNA(P) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. FTIR, UV–visible spectroscopic methods were used to determine the ligand external binding modes, the binding constant and the stability of caffeine, theophylline–DNA complexes in aqueous solution.Spectroscopic evidence showed that the complexation of caffeine and theophylline with DNA occurred via G-C and A-T and PO2 group with overall binding constants of K(caffeine–DNA) = 9.7 × 103 M−1 and K(theophylline–DNA) = 1.7 × 104 M−1. The affinity of ligand–DNA binding is in the order of theophylline > caffeine. A partial B to A-DNA transition occurs upon caffeine and theophylline complexation.