New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 11; pp. 20642 - 20658
• Main Authors: Barakat, Assem, Al-Majid, Abdullah, Soliman, Saied, Lotfy, Gehad, Ghabbour, Hazem, Fun, Hoong-Kun, Wadood, Abdul, Warad, Ismail, Sloop, Joseph
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.11.2015; MDPI
• Subjects: Acids; Ammonium Compounds - chemical synthesis; Ammonium Compounds - chemistry; barbituric acid; Chemistry Techniques, Synthetic; Convulsions & seizures; Crystallography; Crystallography, X-Ray; DFT; fluorine compound; Hydrogen Bonding; Models, Molecular; Molecular Docking Simulation; molecular docking simulations; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmaceuticals; Pharmacy; Salts - chemical synthesis; Salts - chemistry; Science; Simulation; Thiobarbiturates - chemistry; Saudi Arabia; Riyadh Saudi Arabia; Egypt; DFT; molecular docking simulations; barbituric acid; fluorine compound
• DOI: 10.3390/molecules201119710
• ISSN: 1420-3049

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229.