Gemcitabine (GTB) is a nucleoside drug used in chemotherapy for various carcinomas. In order to know why does GTB have good thermal stability, and to further understand the relationship between thermal stability and molecular structure. The thermal decomposition of GTB was measured with various thermal analytical techniques, the gaseous products and the residues of thermal decomposition were determined and identified. The molecular bond orders were calculated. The thermal decomposition mechanism of GTB was discussed. The thermal decomposition kinetics and the prospective lifetime of GTB were studied using the ATSM method. The results indicated that two strong electronegative fluorine atoms on furan ring make the strong charge-transfer (CT) structure to be formed, this strong CT structure remarkably enhance the N-glycosidic bond and the weakest bond, and lead to higher thermal stability and distinctive thermal decomposition mechanism. The thermal decomposition of GTB is a three-stage process. The initial step of decomposition is likely due to the loss of a furan ring. Most of GTB decompose and carbonizes directly to form insoluble substance and small molecules and just part of GTB decompose by way of cytosine stage. The initial decomposition temperature in either nitrogen or air is 235 °C. For decomposition in nitrogen, the apparent activation energy E a and pre-exponential factor A for the initial thermal decomposition are 123.4 kJ mol −1 and 3.80 × 10 10 min −1 , respectively. For decomposition in air, the corresponding E a and A are 126.3 kJ mol −1 and 7.94 × 10 10 min −1 , respectively. GTB has very good thermal stability under routine temperature and dry air atmosphere.
The thermal decomposition processes of eight purine nucleoside analogs were measured with thermogravimetry (TG) and differential scanning calorimetry (DSC). The IR spectra and high-performance liquid chromatography (HPLC) of purine nucleoside analogs and their residues from thermal decomposition at various temperatures were determined. The molecular bond orders were calculated with an ab initio method from the GAMESS program. The mechanisms of thermal decomposition for purine nucleoside analogs were discussed. The results indicate that the main decomposition pathway of purine nucleoside analogs is the fracture of the N -glycosidic bond first, and the residues of the initial stage of decomposition are mainly corresponding purines. A part of purine nucleoside analogs decomposes directly to small molecules and insoluble substances at the first stage. When the N -glycosidic bond order is close to that of the weakest bond within purine ring, most of purine nucleoside analogs will decompose directly. The amino group at purine ring is easy to be oxidized, some oxidation products can be found in the residues of some purine nucleoside analogs. There is a positive correlation between the calculated weakest bond orders and the decomposition temperatures of purine nucleoside analogs. The stronger the weakest bond order, the higher the decomposition temperature. The molecular bond orders can serve as the basis to judge molecular thermal stability for analog compounds with similar molecular structure, size, and energy. The substituent group affects the thermal stability of the purine nucleoside analogs. Increasing the number of electron-donating groups on the purine ring and furanose ring will enhance the N -glycosidic bond, will increase the temperature of thermal decomposition, and be likely to change the mechanism of thermal decomposition.
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