Quantum-Mechanical Prediction of Tautomeric Equilibria

Kwiatkowski, Józef S.; Zielinski, Theresa Julia; Rein, Robert

doi:10.1016/s0065-3276(08)60048-9

Cited by 152 publications

(69 citation statements)

References 103 publications

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“…In fact, our results show that the frequency of the minor tautomer of the anionic form of HO 5 dCyt, which has substantial presence at physiological pH, is at least 100-fold higher than that of dCyt. Then, at pH 10.5, its UVRR temperature-difference spectrum contains a distinguishing marker band at 1658 cm Ϫ1 that is diagnostic of the carbonyl bond of the imino tautomer.…”

mentioning

confidence: 66%

“…The major mutagenic modification of these C residues is HO 5 dCyt, an oxidation product. HO 5 dCTP is incorporated efficiently into DNA by a DNA polymerase in vitro (10).…”

mentioning

confidence: 99%

“…The major mutagenic modification of these C residues is HO 5 dCyt, an oxidation product. HO 5 dCTP is incorporated efficiently into DNA by a DNA polymerase in vitro (10). On transfection of this DNA into Escherichia coli, it causes C 3 T transitions at a frequency of Ϸ2.5%, very much higher than that observed for any previously identified base analog-induced DNA lesion.…”

mentioning

confidence: 99%

“…On transfection of this DNA into Escherichia coli, it causes C 3 T transitions at a frequency of Ϸ2.5%, very much higher than that observed for any previously identified base analog-induced DNA lesion. A possible mechanism for these transitions involves a much greater frequency of the imino tautomer of HO 5 dCyt, which would increase the tendency to pair with A (2).…”

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confidence: 99%

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Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2′-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2′-deoxycytidine

Suen

Spiro

Sowers

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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UV resonance Raman spectroscopy was used to detect and estimate the frequency of the unfavored imino tautomer of the transition mutagen 5-hydroxy-2-deoxycytidine (HO 5 dCyt) in its anionic form. In DNA, this 2-deoxycytidine analog arises from the oxidation of 2-deoxycytidine and induces C 3 T transitions with 10 2 greater frequency than such spontaneous transitions. An imino tautomer marker carbonyl band (Ϸ1650 cm ؊1 ) is enhanced at Ϸ65°C against an otherwise stable spectrum of bands associated with the favored amino tautomer. This band is similarly present in the UV resonance Raman spectra of the imino cytidine analogs N 3 -methylcytidine at high pH and N 4 -methoxy-2-deoxycytidine at pH 7 and displays features attributable to the imino form of C residues and their derivatives. The fact that the imino tautomer of HO 5 dCyt occurs at a frequency consistent with its high mutagenic enhancement lends strong support to the hypothesis that unfavored base tautomers play important roles in the mispair intermediates of replication leading to substitution mutations.The tautomerism of nucleic acid bases is of great interest because of the putative role of their unfavored tautomers in substitution mutagenesis (1, 2). Thus, whereas the dominant amino and keto forms of the base residues enable correct gene replication by complementary base pairing between A and T and between G and C, the minor tautomeric imino and enol species allow for mispairing of A with C, G with T, and also are involved in mispairing of A with A, G with G, A with G, and G with A, resulting in transition and transversion mutations, respectively.Experimental and theoretical investigations involving pK measurement of various tautomer analogs (3), relaxation methods (4), and quantum mechanical calculations (5) have afforded estimates of the frequency of these rare tautomers. However, because of the very low level of minor tautomeric species in solution (Ϸ10 Ϫ4 -10 Ϫ5 ; refs. 6-8), it has not been possible to observe them directly by spectroscopy. Here, we report evidence obtained by UV resonance Raman spectroscopy (UVRR) for the minor tautomer of a highly mutagenic analog of the 2Ј-deoxycytidine (dCyt) residue, 5-hydroxy-2Ј-deoxycytidine (HO 5 dCyt).Earlier, it was found that C 3 T mutations resulting from transition metal-mediated damage to DNA by reactive oxygen species most frequently occur opposite C residues (9). The major mutagenic modification of these C residues is HO 5 dCyt, an oxidation product. HO 5 dCTP is incorporated efficiently into DNA by a DNA polymerase in vitro (10). On transfection of this DNA into Escherichia coli, it causes C 3 T transitions at a frequency of Ϸ2.5%, very much higher than that observed for any previously identified base analog-induced DNA lesion. A possible mechanism for these transitions involves a much greater frequency of the imino tautomer of HO 5 dCyt, which would increase the tendency to pair with A (2).In fact, our results show that the frequency of the minor tautomer of the anionic form of HO 5 dCyt, wh...

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mentioning

confidence: 66%

“…The major mutagenic modification of these C residues is HO 5 dCyt, an oxidation product. HO 5 dCTP is incorporated efficiently into DNA by a DNA polymerase in vitro (10).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2′-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2′-deoxycytidine

Suen

Spiro

Sowers

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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“…Molecular orbital calculations have proved useful in studies of tautomeric phenomena (34)(35)(36). The systems investigated were relatively large; therefore we chose the semiempirical AM1 method, which has recently been used very successfully when examining structure, energetics, and properties of various tautomeric forms (36)(37)(38)(39).…”

Section: Introductionmentioning

confidence: 99%

Studies on nitracrine and its nitro isomers devoted to tautomeric phenomena, structural and physicochemical features, as well as surrounding electrostatic potential

Rak¹,

Byażejowski²,

Zauhar³

1993

Can. J. Chem.

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Relative stabilities and features of tautomers of N, N-dimethyl-N'-(l-nitro-9-acridinyl)-1,3-propanediamine (known as nitracrine by the World Health Organization (WHO) or as Ledakrin in Poland), which exhibits antitumour activity, and its three nitro isomers were examined by AM1 and, in some cases, by PM3 and ab initio (STO-3G) methods. The lowest energy form of three compounds was always an imino tautomer, while the energy of the amino tautomers was a few kcal mol-' higher and that of the aci forms (in the case of the 2-and 4-nitro isomers) was more than 25 kcal mol-' higher. Each tautomer can further exist in several structural forms (conformers or stereoisomers). In some of them internal hydrogen bonding interactions are feasible. The barriers to rotation of the -NHR group, as well as to inversion of the -NHR group (in amino tautomers of nitracrine and its 2-nitro isomer) and of the whole molecule (in the case of nonplanar imino structures), were also evaluated, as were enthalpies of formation (total energies), entropies, free energies, dipole moments, and energies of HOMO and LUMO orbitals. Molecular electrostatic potential maps reveal that only in nitracrine are both -NO2 and -NHR groups surrounded by a negative electrostatic potential, whereas in other isomers the -NHR fragment is surrounded by a positive electrostatic potential while the -NOz group remains in the region of a negative electrostatic potential. The possible influence of physicochemical features on the biological activity of the molecules is also considered. [Traduit par la rCdaction]

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Generalized conductor-like screening model (GCOSMO) for solvation: An assessment of its accuracy and applicability

Truong

Nguyen

Stefanovich

1996

Int. J. Quantum Chem.

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Quantum-Mechanical Prediction of Tautomeric Equilibria

Cited by 152 publications

References 103 publications

Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2′-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2′-deoxycytidine

Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2′-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2′-deoxycytidine

Studies on nitracrine and its nitro isomers devoted to tautomeric phenomena, structural and physicochemical features, as well as surrounding electrostatic potential

Generalized conductor-like screening model (GCOSMO) for solvation: An assessment of its accuracy and applicability

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