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dc.contributor.authorKaraman, Rafik
dc.contributor.authorDokmak, Ghadeer
dc.contributor.authorBader, Maryam
dc.contributor.authorHallak, Hussein
dc.contributor.authorKhamis, Mustafa
dc.date.accessioned2018-09-04T09:51:08Z
dc.date.available2018-09-04T09:51:08Z
dc.date.issued2012-09-02
dc.identifier.issn0948-5023
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/830
dc.description.abstractDensity functional theory (DFT) calculations at B3LYP/6-31 G (d,p) and B3LYP/6-311+G(d,p) levels for the substituted pyridine-catalyzed isomerization of monomethyl maleate revealed that isomerization proceeds via four steps, with the rate-limiting step being proton transfer from the substituted pyridinium ion to the C0C double bond in INT1. In addition, it was found that the isomerization rate (maleate to fumarate) is solvent dependent. Polar solvents, such as water, tend to accelerate the isomerization rate, whereas apolar solvents, such as chloroform, act to slow down the reaction. A linear correlation was obtained between the isomerization activation energy and the dielectric constant of the solvent. Furthermore, linearity was achieved when the activation energy was plotted against the pKa value of the catalyst. Substitutedpyridine derivatives with high pKa values were able to catalyze isomerization more efficiently than those with low pKa values. The calculated relative rates for prodrugs 1–6 were: 1 (406.7), 2 (7.6×106), 3 (1.0), 4 (20.7), 5 (13.5) and 6 (2.2×103). This result indicates that isomerizations of prodrugs 1 and 3–5 are expected to be slow and that of prodrugs 2 and 6 are expected to be relatively fast. Hence, prodrugs 2 and 3–5 have the potential to be utilized as prodrugs for the slow release of monomethylfumarate in the treatment of psoriasis and multiple sclerosis.en_US
dc.language.isoen_USen_US
dc.publisherSpringer-Verlag 2012en_US
dc.subjectProdrugen_US
dc.subjectPsoriasisen_US
dc.subjectMultiple sclerosisen_US
dc.subjectMonomethylmaleateen_US
dc.subjectIsomerization ofmonomethylmaleateen_US
dc.subjectDFTcalculationen_US
dc.subjectPyridine-catalyzed cis-trans isomerizationen_US
dc.titleProdrugs of fumarate esters for the treatment of psoriasis and multiple sclerosis—a computational approachen_US
dc.typeArticleen_US


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