Thermodynamic and spectroscopic characterization of the berenil and pentamidine complexes with the dodecanucleotide d(CGCGATATCGCG)2.

The dodecanucleotide d(CGCGATATCGCG)2 was characterized by thermodynamic and UV-spectrophotometric measurements. A van't Hoff enthalpy of delta H(uv)v.H. approximately -190 kJ/mol was determined for the thermal transition using UV spectroscopy. This value was confirmed by differential scanning calorimetry (DSC). In addition we obtained the thermodynamic data delta HDSC = -405.1 kJ/mol, delta SDSC = -1290 J/mol.K and delta GDSC = -53.2 kJ/mol for the helix to coil transition of the dodecanucleotide. The association of berenil and the oligonucleotide was accompanied with a stabilization of the host duplex (increase in Tm) and an increase in the van't Hoff enthalpy. The berenil binding parameters (delta delta HDSC = -32.6 kJ/mol, delta delta SDSC = -72 J/mol.K and delta delta GDSC = -11.1 kJ/mol) revealed significant differences compared to those of the pentamidine aggregation (delta delta HDSC = -23.7 kJ/mol, delta delta SDSC = -53 J/mol.K and delta delta GDSC = -7.8 kJ/mol). The transition of the pure oligonucleotide was characterized by a substantial amount of intermediate states (sigma DSC = 0.43) which decreased significantly upon binding of the drugs (sigma DSC approximately 0.80). The structural features of the complexes were analyzed by FT-IR spectroscopy. From these experiments we conclude that the configurations in the berenil and pentamidine complexes are different.