Molecular Modeling Studies of Some Uracil and New Deoxyuridine Derivatives

Abstract

Molecular modeling results reported in this paper are crucial in highlighting the quantitative relationship between the optimized structure and computed molecular properties related to four newly synthesized uracil derivatives with promising biological potential as anticancer bioactive agents. Moreover, 5-fluorouracil (5-FU) and its tautomers and thiouracils molecular properties are studied and correlated with their biological activities. The great medical importance of these and similar molecular systems requires research on their quantitative structure-activity relationships (QSAR) in order to further improve our knowledge about how receptor binding, selectivity, and pharmacological effects are achieved. Modeling is performed in the ground and the first singlet excited states using density functional theory (DFT) and its time-dependent extension (TD-DFT), respectively.

Modeling the Structures and Electronic Properties of Uracil and Thymine in Gas Phase and Water

“…The Hydrogen-Nitrogen bond has the smallest bond length and the C-C bonds have the highest values. This agrees with results obtained by Faal et al, 2016 andYousra &Abdel-Mottaleb, 2016. This shows that N-H bonds are the strongest and C-C bonds are the weakest.…”

“…However, all bond angles are slightly altered in solution. The values at B3LYP level of theory agree with experimental values (Faal et al, 2016) and those obtained using other basis sets (Yousra &Abdel-Mottaleb, 2016). The N11-C1-N12 and C1-N11-C2 bond angles are the smallest and largest respectively.…”

“…This indicates that the non-inclusion of electron correlation in the RHF method affects the LUMO and HOMO energies and consequently all other electronic properties. The HOMO, LUMO and energy band gap values agree with those obtained using Spartan 14 software at B3LYP/6-31+G(d) level of theory (Yousra & Abdel-Mottaleb, 2016). At B3LYP/6-31G(d,p) level of theory, the chemical potential and electrophilicity of both molecules increase in solution.…”

“…Also, Uracil is considered as an essential structure in drug discovery with vast topics of biological activities and synthetic accessibility. Systematic experimental and theoretical studies of nucleic acid bases and their derivatives are of considerable importance from the biological point of view (Yousra & Abdel-Mottaleb, 2016). Uracil and its derivatives are essential ingredients of soluble ribonucleic acid and are used in anti-carcinogenic drug synthesis against cancer and anti-HIV viruses (Singh, 2014).…”

Driving Forces for Covalent Assembly of Porphyrins by Selective C–H Bond Activation and Intermolecular Coupling on a Copper Surface

“…For many applications, robust networks stabilized by covalent bonds between constituent molecules [1,2,[7][8][9][10][11][12] are technologically more promising, compared to supramolecular networks stabilized by other types of inter-molecular interactions such as H-bonding or van der Waals [13][14][15][16][17][18][19]. One broadly applicable approach [2] for the on-surface synthesis of complex and diverse covalent structures is to exploit the prevalence of C-H bonds in organic entities and activate them at a surface to drive intermolecular coupling via C-C or C-Metal-C bond formation [2,12,20,21].…”