A density functional theory study on the intramolecular proton transfer in 6-thioguanine and alkali metal cations substituted derivatives (M-TG, M=Li+, Na+, K+)

• Published in: Computational and theoretical chemistry Vol. 1002; pp. 37 - 42
• Main Authors: Zhang, Jiao-Qiang, Shi, Chang-Ming, Wan, Wen, Ji, Tie-Zheng, Yi, Na
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.12.2012
• Subjects: 6-Thioguanine; Density functional theory; Intramolecular proton transfer; Tautomerization; Transition state; 6-Thioguanine; Density functional theory; Intramolecular proton transfer; Tautomerization; Transition state
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2012.09.028

The cationization of the alkali metal cations in the proton transfer process greatly increases the energy barrier. The alkali metal cations increase the energy barriers from the thione form to the transition state, but decrease the energy barriers from the transition state to the thoil form. And the corresponding activation energy of the intramolecular proton transfer decreases successively according to the order of Li+, Na+ and K+. [Display omitted] ► Metal cations play a crucial role in many different biochemical and physiological pathways. ► 6-Thioguanine is used widely for its cytotoxic and immunosuppressive properties. ► The influence of metal cations on the tautomerization of 6-thioguanine was studied. ► The study can help to further explore the pharmacological properties of 6-thioguanine. The intramolecular proton transfer in cationized thione form and thiol form of 6-thioguanine substituted derivatives with M=Li+, Na+ and K+ has been studied with the level of B3LYP/6-31+G (d) density functional theory. Which can help us to further explore the pharmacological properties of 6-thioguanine. Vibrational analysis has been performed on these two configurations to obtain the vibrational frequencies, by means of which the entropy of the proton transfer of 6-thioguanine has been evaluated. It is found that the coordination of the alkali metal ions to the nitrogen of 6-thioguanine stabilized the thione form. For all cases the intramolecular proton transfer occurs readily with small energy barriers. The necessary energy barriers of the intramolecular proton transfer are within 105.938–173.141kJ/mol. The energy barriers become higher when 6-thioguanine complexes with the alkali metal cations than that without the alkali metal cations. For the alkali metal cations Li+, Na+ and K+ systems, the thione form becomes very stable. The intramolecular proton transfer reaction takes more easily according to the order: Li+, Na+, K+.