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First Principles Calculations of the pK_a Values and Tautomers of Isoguanine and Xanthine

Noyes Rogstad, Katherine and Jang, Yun Hee and Sowers, Lawrence C. and Goddard, William A., III (2003) First Principles Calculations of the pK_a Values and Tautomers of Isoguanine and Xanthine. Chemical Research in Toxicology, 16 (11). pp. 1455-1462. ISSN 0893-228X. doi:10.1021/tx034068e.

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The accurate replication of DNA requires the formation of complementary hydrogen bonds between a template base and the base moiety of an incoming deoxynucleotide-5‘-triphosphate. Recent structural studies suggest that some DNA polymerases contribute additional constraints by interrogating the minor groove face of the incoming and template bases. Therefore, the hydrogen bond-donating or -accepting properties of the base pairing as well as minor groove faces of the bases could be important determinants of correct base selection. In this paper, we investigate two purines that could arise by endogenous damage of the normal DNA bases:  isoguanine (which can be generated by the oxidation of adenine) and xanthine (which can be generated by the deamination of guanine). In both cases, the potential exists for the placement of a proton in the N3 position, converting the N3 position from a hydrogen bond acceptor to a donor. In this paper, we use first principles quantum mechanical methods (density functional theory using the B3LYP functional and the 6-31G++G**basis set) to predict the ionization and tautomeric equilibria of both isoguanine and xanthine in the gas phase and aqueous solution. For isoguanine, we find that the N1H and N3H neutral tautomeric forms are about equally populated in aqueous solution, while the enol tauotomers are predominant in the gas phase. In contrast, we find that xanthine displays essentially no tautomeric shifts in aqueous solution but is nearly equally populated by both an anionic and a neutral form at physiological pH. To obtain these results, we carried out an extensive examination of the tautomeric and ionic configurations for both xanthine and isoguanine in solution and in the gas phase. The potential hydrogen-bonding characteristics of these damaged purines may be used to test predictions of the important components of base selection by different DNA polymerases during DNA replication.

Item Type:Article
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URLURL TypeDescription Information
Jang, Yun Hee0000-0002-6604-5813
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2003 American Chemical Society. Received April 3, 2003. Publication Date (Web): October 25, 2003. This work was supported in part by the National Institutes of Health GM41336 (L.C.S.) and CA85779 (L.C.S. and W.A.G.) as well as the BK21 program of Korea (Y.H.J.). In addition, the facilities of the MSC used for this project were supported by ARO-DURIP, ONR-DURIP, NSF-MRI, and IBM (SUR grant).
Funding AgencyGrant Number
BK21 Program of KoreaUNSPECIFIED
Army Research Office (ARO)UNSPECIFIED
Office of Naval Research (ONR)UNSPECIFIED
Issue or Number:11
Record Number:CaltechAUTHORS:20170808-100937143
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Official Citation:First Principles Calculations of the pKa Values and Tautomers of Isoguanine and Xanthine Katherine Noyes Rogstad, Yun Hee Jang, Lawrence C. Sowers, and William A. Goddard, III Chemical Research in Toxicology 2003 16 (11), 1455-1462 DOI: 10.1021/tx034068e
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79926
Deposited By: Tony Diaz
Deposited On:09 Aug 2017 19:27
Last Modified:15 Nov 2021 17:51

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