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First Principles Calculation of pK_a Values for 5-Substituted Uracils

Jang, Yun Hee and Sowers, Lawrence C. and Çağin, Tahir and Goddard, William A., III (2001) First Principles Calculation of pK_a Values for 5-Substituted Uracils. Journal of Physical Chemistry A, 105 (1). pp. 274-280. ISSN 1089-5639. https://resolver.caltech.edu/CaltechAUTHORS:20170720-070311835

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Abstract

Oxidation of uracil (U) and thymine (5-Me-U) are believed to play a role in genetic instability because of the changes these oxidations cause in the ionization constants (pK_a values), which in turn affects the base pairing and hence coding. However, interpretation of the experimental evidence for the changes of pK_a with substitution at U has been complicated by the presence of two sites (N1 and N3) for ionization. We show that a procedure using first principles quantum mechanics (density functional theory with generalized gradient approximation, B3LYP, in combination with the Poisson−Boltzmann continuum-solvation model) predicts such pK_a values for a series of 5-substituted uracil derivatives in excellent correlation with experiment. In particular, this successfully resolves which cases prefer ionization at N1 and N3. Such first principles predictions of ionization constant should be useful for predicting and interpreting pK_a for other systems.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/jp994432bDOIArticle
http://pubs.acs.org/doi/full/10.1021/jp994432bPublisherArticle
ORCID:
AuthorORCID
Çağin, Tahir0000-0002-3665-0932
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2001 American Chemical Society. Received 17 December 1999. Published online 8 December 2000. Published in print 1 January 2001. This work was supported in part by the National Institutes of Health [HD36385 (W.A.G.), GM 41336 (L.C.W.), and CA 33572 (L.C.W.)]. In addition, the facilities of the MSC are also supported by DOE-ASCI, ARO-MURI, ARO-DURIP, National Science Foundation (CHE-95-22179), Exxon Corp., Dow Chemical, 3M, Beckman Institute, Avery-Dennison, Chevron Corp., Seiko Epson, Asahi Chemical, and BP Amoco.
Funders:
Funding AgencyGrant Number
NIHHD36385
NIHGM41336
NIHCA33572
Department of Energy (DOE)UNSPECIFIED
Army Research Office (ARO)UNSPECIFIED
NSFCHE-95-22179
Exxon Corp.UNSPECIFIED
Dow ChemicalUNSPECIFIED
3MUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Avery-DennisonUNSPECIFIED
Chevron Corp.UNSPECIFIED
Seiko-EpsonUNSPECIFIED
Asahi ChemicalUNSPECIFIED
BP AmocoUNSPECIFIED
Issue or Number:1
Record Number:CaltechAUTHORS:20170720-070311835
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170720-070311835
Official Citation:First Principles Calculation of pKa Values for 5-Substituted Uracils Yun Hee Jang, Lawrence C. Sowers, Tahir Çaǧin, and William A. Goddard III The Journal of Physical Chemistry A 2001 105 (1), 274-280 DOI: 10.1021/jp994432b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79226
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:20 Jul 2017 18:44
Last Modified:03 Oct 2019 18:17

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