2.50
Hdl Handle:
http://hdl.handle.net/10547/302098
Title:
Diketoacid HIV-1 integrase inhibitors:  an ab initio study
Authors:
Huang, Meilan; Richards, W. Graham; Grant, Guy H.
Abstract:
The stable tautomeric forms of two representative arene-substituted diketoacid HIV-1 integrase inhibitors, 5-ClTEP and L-731,988, were investigated by B3LYP with 6-31G*, 6-31G(d,p), and 6-31+G(d,p) basis sets. Optimization with MP2/6-31G* was also performed for 5-ClTEP. The solvation effect was considered using a conductor-like screening model. With the density functional theory method, the trans diketo conformations are more stable than the cis conformers. The difference is 14 kJ mol-1 for 5-ClTEP and 33 kJ mol-1 for L-731,988. Two trans diketo structures were obtained. The difference between these two trans diketo structures is less than 4 kJ mol-1 calculated at the B3LYP/6-311+G(3df,2p) level. Two enol forms prevail over the diketo tautomers and are calculated to have the same free energy. Because there is no barrier observed between these two enol forms, they can interchange easily such that a delocalized transition state is suggested to be the observed form. Contradictory to the results of the MP2 method that predicts a preference for the trans diketo forms, the B3LYP method predicts a preference for the enol tautomers, which is in agreement with the experimental results.
Affiliation:
University of Oxford
Citation:
Huang, M., Grant, G.H. and Richards, W.G. (2005) 'Diketoacid HIV-1 Integrase Inhibitors:  An Ab Initio Study', The Journal of Physical Chemistry A, 109(23),pp.5198-5202
Publisher:
American Chemical Society
Journal:
The Journal of Physical Chemistry A
Issue Date:
2005
URI:
http://hdl.handle.net/10547/302098
DOI:
10.1021/jp045247n
Additional Links:
http://pubs.acs.org/doi/abs/10.1021/jp045247n
Type:
Article
Language:
en
ISSN:
1089-5639; 1520-5215
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorHuang, Meilanen_GB
dc.contributor.authorRichards, W. Grahamen_GB
dc.contributor.authorGrant, Guy H.en_GB
dc.date.accessioned2013-09-23T12:20:07Z-
dc.date.available2013-09-23T12:20:07Z-
dc.date.issued2005-
dc.identifier.citationHuang, M., Grant, G.H. and Richards, W.G. (2005) 'Diketoacid HIV-1 Integrase Inhibitors:  An Ab Initio Study', The Journal of Physical Chemistry A, 109(23),pp.5198-5202en_GB
dc.identifier.issn1089-5639-
dc.identifier.issn1520-5215-
dc.identifier.doi10.1021/jp045247n-
dc.identifier.urihttp://hdl.handle.net/10547/302098-
dc.description.abstractThe stable tautomeric forms of two representative arene-substituted diketoacid HIV-1 integrase inhibitors, 5-ClTEP and L-731,988, were investigated by B3LYP with 6-31G*, 6-31G(d,p), and 6-31+G(d,p) basis sets. Optimization with MP2/6-31G* was also performed for 5-ClTEP. The solvation effect was considered using a conductor-like screening model. With the density functional theory method, the trans diketo conformations are more stable than the cis conformers. The difference is 14 kJ mol-1 for 5-ClTEP and 33 kJ mol-1 for L-731,988. Two trans diketo structures were obtained. The difference between these two trans diketo structures is less than 4 kJ mol-1 calculated at the B3LYP/6-311+G(3df,2p) level. Two enol forms prevail over the diketo tautomers and are calculated to have the same free energy. Because there is no barrier observed between these two enol forms, they can interchange easily such that a delocalized transition state is suggested to be the observed form. Contradictory to the results of the MP2 method that predicts a preference for the trans diketo forms, the B3LYP method predicts a preference for the enol tautomers, which is in agreement with the experimental results.en_GB
dc.language.isoenen
dc.publisherAmerican Chemical Societyen_GB
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/jp045247nen_GB
dc.rightsArchived with thanks to The Journal of Physical Chemistry Aen_GB
dc.titleDiketoacid HIV-1 integrase inhibitors:  an ab initio studyen
dc.typeArticleen
dc.contributor.departmentUniversity of Oxforden_GB
dc.identifier.journalThe Journal of Physical Chemistry Aen_GB
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