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.
ABSTRACT
Base pairs of 4-amino-3-nitrobenzonitrile (4A-3NBN) molecule with uracil, thymine and cytosine nucleobases were optimized and compared to natural Watson-Crick (WC) pairs. The slightly greater flexibility of the -NO2 group of 4A-3NBN than the N3-H group of the natural nucleobases together with a noticeable higher dipole moment of its pairs can facilitate disruption of the DNA/RNA helix formation. Several new mutagenic modified nucleosides with 4A-3NBN and 3-amino-2-nitrobenzonitrile (3A-2NBN) were proposed as antiviral prodrugs and their base pairs optimized. The special characteristics of these prodrugs appear appropriated for their clinical use. The counterpoise (CP) corrected interaction energies of the base pairs were calculated and compared to the natural ones. The M06-2X DFT method was used for this purpose. The molecular structure of 4A-3NBN was analyzed in detail and the crystal unit cell was simulated by a tetramer form and eight dimer forms. The performance of the B3LYP, X3LYP and M06-2X methods was tested on the vibrational wavenumbers in the monomer, dimer and tetramer forms of 4A-3NBN. The observed IR and Raman bands were assigned according to the optimum dimer II form determined by B3LYP and by the tetramer form calculated by M06-2X, which is the expected unit cell that forms the crystal net. The two best scaling procedures were used.Communicated by Ramaswamy H. Sarma.
