Reduction of the Syn-Anti Glycosyl Conformational Barrier in 2'-Deoxyadenosine upon Binding to Ethidium Bromide. Evidence from Ultrasonic Relaxation Measurements

The unimolecular relaxation found by ultrasonic relaxation in dilute aqueous solutions of 2'-deoxyadenosine was examined in the absence and presence of ethidium bromide (a model for an intercalating drug) and indole-3-acetic acid at pH 7.0 (a model for tryptophan as a potential binding site on a protein). This relaxation, which had previously been assigned to the syn-anti glycosyl isomerization, changes both in terms of fr and amplitude in the presence of the added reagents. Both ethidium bromide and indole-3-acetic acid shift the relaxation frequency, fr to higher values. Detailed analysis of the data in the presence of varying amounts of ethidium bromide indicates that the apparent activation energy to syn-anti isomerization is decreased when 2'-deoxyadenosine is bound to ethidium bromide. 1H NMR studies were performed to elucidate the mechanism of binding. Assuming a 1:1 2'-deoxyadenosine-ethidium bromide (heterostack) complex, 1H NMR (in 2H20) gives a Xheterostack of ca. 300 M-1 compared to the value derived from the ultrasonic data (in H2O) of ca. 400 M-1.