Thermodynamic study of the discrimination between uridine and thymidine derivatives by hydrophobic, stacking, and intercalating interactions

Thermodynamic parameters for the complexation reactions of uridine/thymidine nucleobases and related compounds, with hosts of differing binding modes and properties (natural cyclodextrins, 5,10,15,20-tetrakis (1-methlpyridinium-4-yl) porphyrin tetrachloride and bis-intercaland macrocycle) have been determined by titration microcalorimetry and/or fluorometry, in an aqueous buffer. For each of these hosts the effect of the 5-methyl group on the binding affinities was investigated. Although the affinities of uridine and thymidine towards cyclodextrins and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetrachloride are very similar, the intercalation of these compounds into the bis-intercaland macrocycle has been shown to result in a high degree of discrimination of approximately 10 times. On the basis of thermodynamic data, the obtained contribution made by the 5-methyl group of thymidine to the structural characteristics of DNA and RNA is discussed.