Base pairs with 5-chloroorotic acid and comparison with the natural nucleobase. Structural and spectroscopic study, and three suggested antiviral modified nucleosides

Abstract

A structural and spectroscopic study of 5-chloroorotic acid (5-ClOA) biomolecule was carried out by IR and FT-Raman and the results obtained were compared to those achieved in 5-fluoroorotic acid and 5-aminoorotic acid compounds. The structures of all possible tautomeric forms were determined using DFT and MP2 methods. To know the tautomer form present in the solid state, the crystal unit cell was optimized through dimer and tetramer forms in several tautomeric forms. The keto form was confirmed through an accurate assignment of all the bands. For this purpose, an additional improvement in the theoretical spectra was carried out using linear scaling equations (LSE) and polynomic equations (PSE) deduced from uracil molecule. Base pairs with uracil, thymine and cytosine nucleobases were optimized and compared to the natural Watson-Crick (WC) pairs. The counterpoise (CP) corrected interaction energies of the base pairs were also calculated. Three nucleosides were optimized based on 5-ClOA as nucleobase, and their corresponding WC pairs with adenosine. These modified nucleosides were inserted in DNA:DNA and RNA:RNA microhelices, which were optimized. The position of the -COOH group in the uracil ring of these microhelices interrupts the DNA/RNA helix formation. Because of the special characteristic of these molecules they can be used as antiviral drugs.

Communicated by Ramaswamy H. Sarma

Keywords:

• WC pair
• 5-chloroorotic acid
• antiviral drugs
• base pairs
• raman spectroscopy
• DFT methods

Acknowledgements

One of the authors (VKR) is grateful to Prof Sebastian Schulecker, University of Duisburg-Essen Universitaetsstr. 5,D-45141 Essen,Germany, for providing the compound 5-chloroorotic acid and to Prof J Popp, Institute for Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743, Jena, Germany, for providing IR and Raman Spectra of the compound. The authors are also grateful to Prof W Kiefer, University of Wuerzberg, Germany for motivation and encouragement during the course of this work. The administrative support received by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0004-C01 is greatly acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Recently, we have received support by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0004-C01.