Infrared spectra and tautomerism of 5-fluorocytosine, 5-bromocytosine and 5-iodocytosine. Matrix isolation and theoretical AB initio studies

Jaworski, Adam; Szczȩśniak, M.; Szczepaniak, Krystyna; Bulat, Ku Halim Ku; Person, Willis B.

doi:10.1016/0022-2860(90)80461-r

Cited by 42 publications

(39 citation statements)

References 28 publications

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“…[33,53]). Even though the precise concentrations of rare forms have not been experimentally determined, these results are qualitatively in agreement with available spectroscopic data [17][18][19] (note that we do not consider the aminohydroxo form of cytosine, which was shown to be the most stable in gas phase, because it cannot be present in DNA due to the substitution of the hydrogen atom at N1 position by a sugar moiety). Even though it was shown experimentally that the canonic forms of both cytosine and guanine are the only tautomers present in water solution [16,[25][26][27][28][29][30][31], it is reasonable to consider the complexes with limited number of water molecules.…”

Section: Resultssupporting

confidence: 85%

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Ab Initio Study of the Prototropic Tautomerism of Cytosine and Guanine and Their Contribution to Spontaneous Point Mutations

Podolyan

Gorb

Leszczyński

2003

IJMS

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High-level quantum-chemical and quantum-dynamics calculations are reported on the tautomerization equilibria and rate constants of isolated and monohydrated cytosine and guanine molecules. The results are used to estimate the fraction of the bases present in the cell during DNA synthesis as the unwanted tautomers that forms irregular base pairs, thus giving rise to a spontaneous GC → AT point mutation. A comparison of the estimated mutation frequencies with the observed frequency in E. coli is used to analyze two proposed mechanisms, differing in the degree of equilibration reached in the tautomerization reaction.It was found that the fraction of the rare tautomer in monohydrated complex of cytosine as well as guanine significantly exceed the amount responsible for the observed values of the GC → AT mutations. In the absence of water the equilibrium concentration of tautomeric forms is relatively large, but the barrier to their formation is high. It is possible that the mechanism in which a high tautomerization barrier keeps the tautomeric transformation far from a state of equilibrium is more likely than a mechanism in which water and/or polymerases produce a low equilibrium concentration of the tautomeric forms.

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Section: Resultssupporting

confidence: 85%

“…Experimental [17][18][19] and theoretical [21][22][23] studies have shown that cytosine (C) exists primarily in the two most stable tautomeric forms, i.e. the aminooxo (canonic) and aminohydroxo forms (see Fig.…”

Section: Introductionmentioning

confidence: 99%

Ab Initio Study of the Prototropic Tautomerism of Cytosine and Guanine and Their Contribution to Spontaneous Point Mutations

Podolyan

Gorb

Leszczyński

2003

IJMS

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“…These conditions, however, require the use of nonaqueous aprotic solvents, such as dimethylformamide, ethylacetate, or acetone, that remain liquid up to −61°C, −83°C, and −95°C, respectively. An additional caveat of nonaqueous solvents with low dielectric constants is that they often stabilize minor tautomeric forms even for naturally occurring nucleic acid bases (Jaworski 1990;Mons et al 2002;Bakker et al 2004); in contrast, under aqueous conditions, canonical nucleobases exist predominantly in their keto-and amino major tautomeric forms (Peng et al 2011).…”

Section: Methods For Studying Tautomerism In Nucleic Acidsmentioning

confidence: 99%

Role of tautomerism in RNA biochemistry

Singh

Fedeles

Essigmann

2014

RNA

122

116

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Heterocyclic nucleic acid bases and their analogs can adopt multiple tautomeric forms due to the presence of multiple solventexchangeable protons. In DNA, spontaneous formation of minor tautomers has been speculated to contribute to mutagenic mispairings during DNA replication, whereas in RNA, minor tautomeric forms have been proposed to enhance the structural and functional diversity of RNA enzymes and aptamers. This review summarizes the role of tautomerism in RNA biochemistry, specifically focusing on the role of tautomerism in catalysis of small self-cleaving ribozymes and recognition of ligand analogs by riboswitches. Considering that the presence of multiple tautomers of nucleic acid bases is a rare occurrence, and that tautomers typically interconvert on a fast time scale, methods for studying rapid tautomerism in the context of nucleic acids under biologically relevant aqueous conditions are also discussed.

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“…(27) Vibrational spectroscopy, such as FTIR and Raman, have been used for studying tautomerism under non-physiological gas phase conditions; however, these conditions do not replicate tautomeric distribution present under biologically relevant aqueous conditions. (28–30) In the gas phase, tautomer distribution often favors minor tautomers, even for canonical nucleic acid base pairs. (28, 30) Systematic studies of tautomerism are not only lacking in the context of nucleic acid or nucleic acid-ligand complexes, but there is also little direct evidence to demonstrate that such isomerizations occur within the context of these complex systems.…”

mentioning

confidence: 99%

“…(28–30) In the gas phase, tautomer distribution often favors minor tautomers, even for canonical nucleic acid base pairs. (28, 30) Systematic studies of tautomerism are not only lacking in the context of nucleic acid or nucleic acid-ligand complexes, but there is also little direct evidence to demonstrate that such isomerizations occur within the context of these complex systems. Although, the chemical features such as ionized states or altered p K a of nucleic acid bases in ribozymes have been extensively studied,(17–19, 31–34) a survey of the literature suggests that progress in studying tautomerism is limited by the lack of suitable methods to detect tautomeric species under aqueous conditions.…”

mentioning

confidence: 99%

Direct Observation of Multiple Tautomers of Oxythiamine and their Recognition by the Thiamine Pyrophosphate Riboswitch

Singh

Peng

et al. 2013

ACS Chem. Biol.

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Structural diversification of canonical nucleic acid bases and nucleotide analogues by tautomerism has been proposed to be a powerful on/off switching mechanism allowing regulation of many biological processes mediated by RNA enzymes and aptamers. Despite the suspected biological importance of tautomerism, attempts to observe minor tautomeric forms in nucleic acid or hybrid nucleic acid-ligand complexes have met with challenges due to the lack of sensitive methods. Here, a combination of spectroscopic, biochemical and computational tools probed tautomerism in the context of an RNA aptamer-ligand complex; studies involved a model ligand, oxythiamine pyrophosphate (OxyTPP), bound to the thiamine pyrophosphate (TPP) riboswitch (an RNA aptamer) as well as its unbound non-phosphorylated form, oxythiamine (OxyT). OxyTPP, like canonical heteroaromatic nucleic acid bases, has a pyrimidine ring that forms hydrogen bonding interactions with the riboswitch. Tautomerism was established using two-dimensional infrared (2D IR) spectroscopy, variable temperature FTIR and NMR spectroscopies, binding isotope effects (BIEs) and computational methods. All three possible tautomers of OxyT, including the minor enol tautomer, were directly identified and their distributions were quantitated. In the bound form, BIE data suggested that OxyTPP existed as a 4'-keto tautomer that was likely protonated at the N1'-position. These results also provide a mechanistic framework for understanding the activation of riboswitch in response to deamination of the active form of vitamin B1 (or TPP). The combination of methods reported here revealing the fine details of tautomerism can be applied to other systems where the importance of tautomerism is suspected.

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Infrared spectra and tautomerism of 5-fluorocytosine, 5-bromocytosine and 5-iodocytosine. Matrix isolation and theoretical AB initio studies

Cited by 42 publications

References 28 publications

Ab Initio Study of the Prototropic Tautomerism of Cytosine and Guanine and Their Contribution to Spontaneous Point Mutations

Ab Initio Study of the Prototropic Tautomerism of Cytosine and Guanine and Their Contribution to Spontaneous Point Mutations

Role of tautomerism in RNA biochemistry

Direct Observation of Multiple Tautomers of Oxythiamine and their Recognition by the Thiamine Pyrophosphate Riboswitch

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