H-1-NMR DETERMINATION OF THE THERMODYNAMICS OF DRUG COMPLEXATION WITHSINGLE-STRANDED AND DOUBLE-STRANDED OLIGONUCLEOTIDES IN SOLUTION - ETHIDIUM-BROMIDE COMPLEXATION WITH THE DEOXYTETRANUCLEOTIDES 5'-D(APCPGPT), 5'-D(APGPCPT), AND 5'-D(TPGPCPA)

The thermodynamical parameters (free energy, enthalpy, and entropy) of complex formation between ethidium bromide and single-stranded and do uble-stranded tetranucleotides of different base sequence [5'-d(TpGpCp A), 5'-d(ApCpGpT), and 5'-d(ApGpCpT)] have been determined from the te mperature dependencies of 500 MHz proton nmr chemical shifts. The anal ysis enables the contributions to be differentiated for the formation of different types of complexes (1:1, 2:1, 1:2, and 2:2) in aqueous so lution. The results have been interpreted in terms of the main types o f intermolecular interactions responsible for formation of the differe nt complexes; van der Waals and electrostatic interactions are importa nt for formation of complexes of ethidium bromide with single-stranded tetranucleotides, whereas van der Waals and hydrophobic interactions play a significant role in the binding of the dye to the tetramer dupl exes. (C) 1997 John Wiley & Sons, Inc.