Structural and Electronic Analysis of Tautomerism in 5,6-Difluor-2,4(1H,3H)-Pyrimidindion




Pyrimidindion, DFT, Tautomer, Conformation, Drug design


Density functional theory (DFT) calculations were performed to analyze the structural and electronic features of tautomers of 5,6-difluor-2,4(1H,3H)-pyrimidindion, as a possible compound for pharmaceutical applications. To this aim, possible structures of tautomers were obtained by performing optimization calculations and their electronic features were investigated. The results indicated that the tautomerism process could change the original features of 5,6-difluor-2,4(1H,3H)-pyrimidindion, in which different impacts of such changes could be observed for the list of tautomeric structures. Finally, further pharmaceutical uses of 5,6-difluor-2,4(1H,3H)-pyrimidindion compound should be in accordance with the structural and electronic features of the tautomeric formations.


Harismah K, Fazeli F, Zandi H. Barbituric acid tautomers: DFT computations of keto-enol conversions, frontier molecular orbitals and quadrupole coupling constants. Biointerface Research in Applied Chemistry. 2021;12:244-52.

Dhaked DK, Guasch L, Nicklaus MC. Tautomer database: a comprehensive resource for tautomerism analyses. Journal of Chemical Information and Modeling. 2020;60:1090-100.

Kondrashova SA, Polyancev FM, Latypov SK. Tautomeric preference in lumazines, deazalumazines, isoalloxazines and pyrimidines and its effect on the reactivity of alkyl groups. Bioorganic Chemistry. 2021;109:104725.

Slocombe L, Al-Khalili JS, Sacchi M. Quantum and classical effects in DNA point mutations: Watson–Crick tautomerism in AT and GC base pairs. Physical Chemistry Chemical Physics. 2021;23:4141-50.

Smalley CJ, Logsdail AJ, Hughes CE, Iuga D, Young MT, Harris KD. Solid-state structural properties of alloxazine determined from powder XRD data in conjunction with DFT-D calculations and solid-state NMR spectroscopy: unraveling the tautomeric identity and pathways for tautomeric interconversion. Crystal Growth & Design. 2021;22:524-34.

Ibrahim AA, Ibrahim MA, Sulliman EA, Daood SM, Ismael GQ. Comparison study of HOMO-LUMO energy gaps for tautomerism of triazoles in different solvents using theoretical calculations. NTU Journal of Pure Sciences. 2021;1:38-43.

Li N, Wang C, Georgiev MI, Bajpai VK, Tundis R, Simal-Gandara J, Lu X, Xiao J, Tang X, Qiao X. Advances in dietary polysaccharides as anticancer agents: structure-activity relationship. Trends in Food Science & Technology. 2021;111:360-77.

Barley MH, Turner NJ, Goodacre R. Improved descriptors for the quantitative structure–activity relationship modeling of peptides and proteins. Journal of Chemical Information and Modeling. 2018;58:234-43.

Zhang M, Xu J, Wang X. The theoretical investigation on the properties of fluorine-substituted uracil. Computational and Theoretical Chemistry. 2019;1156:43-51.

Gmeiner WH. Chemistry of fluorinated pyrimidines in the era of personalized medicine. Molecules. 2020;25:3438.

Wang Q, Xue J, Wang Y, Jin S, Zhang Q, Du Y. Investigation into tautomeric polymorphism of 2-thiobarbituric acid using experimental vibrational spectroscopy combined with DFT theoretical simulation. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2018;204:99-104.

Borbulevych OY, Martin RI, Westerhoff LM. The critical role of QM/MM X-ray refinement and accurate tautomer/protomer determination in structure-based drug design. Journal of Computer-Aided Molecular Design. 2021;35:433-51.

Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09 Program. Gaussian Inc., Wallingford, CT. 2009.

Zandi H, Harismah K. Computer-based tools for structural characterizations and activity specifications of natural products: a quick review. Lab-in-Silico. 2021;2:50-4.

Mousanasab B, Mirzaei M. PNA-CNT interacting system: in silico investigation of nanocarbon sensors for PNA detection. Lab-in-Silico. 2021;2:15-9.




How to Cite

Zandi, H. (2022). Structural and Electronic Analysis of Tautomerism in 5,6-Difluor-2,4(1H,3H)-Pyrimidindion. Advanced Journal of Science and Engineering, 3(1), 2–6.



Original Research Article