Study on the molecular structure and thermal stability of pyrimidine nucleoside analogs

Abstract

The thermal decomposition processes for ten pyrimidine nucleoside analogs were measured with thermogravimetry and differential scanning calorimetry. The IR spectra, high-performance liquid chromatography, and liquid chromatography–mass spectrometry of pyrimidine nucleoside analogs and their residues of thermal decomposition at various temperatures were determined. The molecular bond orders of pyrimidines and pyrimidine nucleoside analogs were calculated with an ab initio method from the GAMESS program. We then discuss mechanisms of thermal decomposition in these pyrimidine nucleoside analogs. The results indicate that there are four types of mechanisms. The decomposition mechanism depends on the relative strength of the peptide bond and the amide bond within pyrimidine ring and whether or not accompanied by oxidation reaction. The substituent groups affect the thermal stability and the thermal decomposition mechanism of pyrimidine nucleoside analogs. Increasing the number of electron-donating groups on the pyrimidine ring and furan ring will enhance the peptide bond, and will elevate the temperature of thermal decomposition. There is a positive correlation between the molecular bond orders calculated by quantum chemistry and the thermal decomposition temperature of pyrimidine nucleoside analogs. The stronger the weakest bond order, the higher the decomposition temperature. The molecular bond orders thus can be used as a basis to judge molecular thermal stability for analog compounds with similar molecular structure, size, and energy.