A Theoretical Study on the Stability, Reactivity and Protonic Affinity of 2-Phenylbenzothiazole Derivatives

Abstract

The 2-phenylbenzothiazole derivatives have antitumor activities. Work has shown that these derivatives have mesomeric forms. The electrophilic centers of these mesomers form adducts with the nucleophilic centers of deoxyribonucleic acid (DNA). These adducts destroy the tumor cells and prevent the proliferation of these. In this sense, the knowledge of electrophilic sites, nucleophiles and the capacity to protonate these derivatives is therefore useful if we want to know their future in the biological environment. Using DFT/B3LYP method associated with the bases 6-31G (d, p) and 6-31+G (d, p), this work aims at determining the preferential protonation site, the electrophilic and nucleophilic centers of six 2-phenylbenzothiazole. This study also analyzes the stability of these derivatives. Calculations are carried out in gas and aqueous phases. Results show that fluorinated derivatives are the most stable. 2-(4-aminophenyl) benzothiazoles are the most reactive. The atoms carbon C4, C5 and C6 of benzothiazole ring are the most electrophilic. Interactions of these derivatives with nucleophilic centers of deoxyribonucleic acid (DNA) will probably be at these atoms. Nitrogen sp2 (N1) of benzothiazole ring remains the most nucleophilic center and the preferential site of protonation in all the molecules studied. These results highlight the influence of the substituents on the basicity of the nitrogen sp2 (N1) and reactivity of the 2-phenylbenzothiazole derivatives studied.