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dc.contributor.authorKaraman, Rafik
dc.contributor.authorDajani, Khuloud K.
dc.contributor.authorQtait, Alaa
dc.contributor.authorKhamis, Mustafa
dc.date.accessioned2018-09-08T13:48:51Z
dc.date.available2018-09-08T13:48:51Z
dc.date.issued2012-02-12
dc.identifier.issn1747-0285
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/858
dc.description.abstractDensity functional theory calculation results demonstrated that the efficiency of the acid-catalyzed hydrolysis of Kirby’s acid amides 1–15 is strongly dependent on the substitution on the C–C double bond and the nature of the amide N-alkyl group. Further, the results established that while in the gas phase the hydrolysis rate-limiting step is the tetrahedral intermediate formation in polar solvents such as water, the rate-limiting step could be either the formation or the collapse of the tetrahedral intermediate depending on the substitution on the C–C double bond and on the amide nitrogen substituent. Based on a linear correlation between the calculated and experimental effective molarities, the study on the systems reported herein could provide a good basis for designing prodrug systems that are less hydrophilic than their parental drugs and can be used, in different dosage forms, to release the parent drug in a controlled manner. For example, based on the calculated log effective molarities values, the predicted t1/2 (a time needed for 50% of the reactant to be hydrolyzed to products) for acyclovir prodrugs, ProD 1–4, was 29.2 h, 6097 days, 4.6 min, and 8.34 h, respectively. Hence, the rate by which acyclovir prodrug releases acyclovir can be determined according to the structural features of the linker (Kirby’s acid amide moiety).en_US
dc.description.sponsorshipThe Karaman Co. is thanked for support of our computational facilities. Special thanks are also given to Angi Karaman, Donia Karaman, Rowan Karaman, and Nardene Karaman for technical assistance.en_US
dc.language.isoen_USen_US
dc.publisherJohn Wiley & Sonsen_US
dc.subjectacyclovir prodrugsen_US
dc.subjectbioavailability of acycloviren_US
dc.subjectdensity functional theory calculationsen_US
dc.subjectintramolecular amide hydrolysisen_US
dc.subjectmaleamic acid amidesen_US
dc.titleProdrugs of Acyclovir - A Computational Approachen_US
dc.typeArticleen_US


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