2,4-Ditellurouracil and its 5-fluoro derivative: Theoretical investigations of structural, energetics and ADME parameters

Ibrahim A Alswaidan; Kritish Sooknah; Lydia Rhyman; Cemal Parlak; Derek T Ndinteh; Mohamed I Elzagheid; Ponnadurai Ramasami

doi:10.1016/j.compbiolchem.2017.02.002

2,4-Ditellurouracil and its 5-fluoro derivative: Theoretical investigations of structural, energetics and ADME parameters

Comput Biol Chem. 2017 Jun:68:56-63. doi: 10.1016/j.compbiolchem.2017.02.002. Epub 2017 Feb 9.

Authors

Ibrahim A Alswaidan¹, Kritish Sooknah², Lydia Rhyman³, Cemal Parlak⁴, Derek T Ndinteh⁵, Mohamed I Elzagheid⁶, Ponnadurai Ramasami⁷

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
² Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius.
³ Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, Johannesburg 2028, South Africa; Department of Chemistry, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg, 2006, South Africa.
⁴ Department of Physics, Science Faculty, Ege University, Bornova, Izmir, 35100, Turkey.
⁵ Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, Johannesburg 2028, South Africa.
⁶ Department of Chemical and Process Engineering, Jubail Industrial College, Jubail Industrial City 31961, Saudi Arabia.
⁷ Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius; Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, Johannesburg 2028, South Africa; Department of Chemistry, University of Johannesburg, PO Box 524, Auckland Park, Johannesburg, 2006, South Africa. Electronic address: ramchemi@intnet.mu.

PMID: 28236747
DOI: 10.1016/j.compbiolchem.2017.02.002

Abstract

2,4-Ditellurouracil exhibits keto-enol tautomerism via different pathways resulting in seven tautomers. These pathways were studied in the gas phase using density functional theory method. The functionals used were BLYP, B3LYP and BHLYP and the basis sets were 6-311++G(d,p) for all atoms except that LanL2DZ ECP was used for tellurium atom only. The results indicate that the diketo form is more stable as observed for uracil and its sulfur and selenium analogues. The effect of introducing fluorine at position 5 was also investigated and the energy difference between the diketo and dienol forms is reduced. 2,4-Ditellurouracil and its 5-fluoro analogue are expected to exist exclusively as the diketo form due to the high interconversion energy barrier. We extended the investigation to predict ADME parameters of the most stable diketo and dienol tautomers in view of understanding their biological properties. This research enlightens keto-enol tautomerism of 2,4-ditellurouracil and its 5-fluoro derivative with additional insights to biological functions.

Keywords: ADME; COSMO-RS; DFT; Keto-enol tautomerism; Tellurouracil.

MeSH terms

Blood-Brain Barrier / metabolism
Halogenation
Intestinal Absorption
Isomerism
Molecular Structure
Organometallic Compounds / chemistry*
Organometallic Compounds / metabolism
Permeability
Quantum Theory
Tellurium*
Thermodynamics
Uracil / analogs & derivatives*
Uracil / chemistry*
Uracil / metabolism

Substances

Organometallic Compounds
Uracil
Tellurium