Tautomerism in some pyrimidine nucleoside analogues used in the treatment of cancer: an ab initio study

Mejía-Mazariegos, Luis; Robles, Juvencio; García‐Revilla, Marco A.

doi:10.1007/s00214-016-1985-7

Cited by 6 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many theoretical papers have been devoted to the conformational isomerism of DNA and RNA structural components, − but few studies appear on inosine. The prototropic tautomerism and basic molecular principles of hypoxanthine mutagenicity were investigated to understand the elementary molecular mechanisms of mutagenic action of hypoxanthine as a product of adenine deamination in DNA .…”

Section: Introductionmentioning

confidence: 99%

Tautomerism of Inosine in Water: Is It Possible?

Маркова

Enchev

2019

J. Phys. Chem. B

View full text Add to dashboard Cite

Syn- and anti-conformers of four tautomer structures of inosine were studied in the gas phase and in solvent water to investigate the possibility of hydrogen bonding and tautomeric conversion. It was found that in the gas phase and in water solution the most stable is the syn-conformer of the 6-keto tautomer followed by its anti-conformer and syn-conformer of the 6-enol form. In the gas phase, the percent content of syn- and anti-conformers is 83.77 and 12.86%, respectively, whereas syn-enol tautomer is calculated to be 2.54%. However, in water solution the syn-conformer of the keto tautomer is 99.9%. The water-assisted proton transfer process in inosine was investigated using ab initio MP2 and SCS-MP2 quantum chemical approaches. Solute–solvent clusters containing an inosine molecule and five water molecules embedded in the “bulk” solvent treated as polarizable continuum (the CPCM/MP2/6-31+G(d,p) level of theory) were explored. The energy barrier of the water-assisted proton transfer reaction in inosine is found to be 12.9 kcal mol–1 and the rate constant (k = 6.68 × 101 s–1) is sufficiently large to generate the 6-enol tautomer. From the reaction profile of the proton transfer we can conclude that the process is realized through the asynchronous concerted mechanism.

show abstract

Section: Introductionmentioning

confidence: 99%

Tautomerism of Inosine in Water: Is It Possible?

Маркова

Enchev

2019

J. Phys. Chem. B

View full text Add to dashboard Cite

show abstract

“…Theoretical works devoted to the structure of cytidine and deoxycytidine in gas phase and in aqueous solution are even scarcer [88–93]. Molecular Dynamics simulations of the Cyd and dCyd in aqueous solutions have been undertaken to compare their hydration pattern and association abilities [86].…”

Section: Introductionmentioning

confidence: 99%

“…Theoretical works devoted to the structure of cytidine and deoxycytidine in gas phase and in aqueous solution are even scarcer [88][89][90][91][92][93].…”

mentioning

confidence: 99%

Tautomerism of cytosine, cytidine, and deoxycytidine: Proton transfer through water bridges

Stoyanova

Enchev

2022

Int J of Quantum Chemistry

View full text Add to dashboard Cite

Altogether six tautomers of cytosine and three tautomers of cytidine and deoxycytidine are studied theoretically in the gas phase and in a microhydrated environment. Their structures are optimized at MP2/6-31 + G(d,p) level. The relative energies of the isolated and the hydrated tautomers included the correction to higher correlation energy terms evaluated at the SCS-MP2, MP4, and CCSD(T) levels. The free energies at 298 K and higher temperatures are based on the above-mentioned relative energies and temperature-dependent enthalpy terms and entropies evaluated at the MP2/6-31 + G(d,p) level. Theoretical predictions for the coexistence of five species for cytosine in the gas phase (canonical, trans-and cis-enol-amino, transand cis-imino-oxo forms) fully agree with recent experimental results. Five-hydrated cytosine tautomeric forms of are investigated at CPCM/SCS-MP2/6-31 + G(d,p) level to evaluate the interconversion barriers between them and to explain the coexistence, experimentally proven, of two amino-oxo and one imino-oxo tautomers of cytosine in aqueous solution. The presence of coordinated water molecules acting as a catalyst make the tautomerization processes quite easier. It appeared clear from the obtained data that the influence of the hydrogen-bonded water molecules as well as the introduction of solvent effects in reducing the height of the tautomerization barriers for these five-hydrated systems is quite substantial. Similar results are obtained for the tri-hydrated cytidine and the 2-deoxycytidine tautomeric forms. In aqueous solution of cytidine, syn-and syn-clinal-conformers оf the amino-oxo tautomer should coexist with small amounts of syn-and syn-clinal conformers оf iminooxo tautomer. For 2-deoxycytidine an equilibrium has been found to exist between the syn-and anti-conformers of the amino-oxo and the imino-oxo tautomers. The water-assisted proton transfer reactions released through asynchronous concerted mechanism and the conformation of the sugar ring in nucleosides does not change during the tautomerization.

show abstract

“…Despite the vast use of computational chemistry to predict pair species of the G·U and G· X U mismatches in different situations, only four studies are about G· F U. Three studies reported about the interaction between the explicit water molecules and F U. − The comparison of the computational studies of G·U and G· X U with many experimental and computational studies on the relevant single bases shows that the activation energies of the enolization or ionization of single bases are 1 order of magnitude larger than those of the pairs, although when they are considered in pair with water. For example, although calculations on the microsolvated state of Br U show that its enolic form in the microsolvated state, and in conclusion in the real water solvation state, is more stable than its keto form, experimental results verify that the population of its enolic form is only about 0.004% of the keto form in a typical RNA duplex. , Thus, the structural and energetic parameters obtained from single bases are not applicable for base pairing, and three studies that report water– F U species cannot produce reliable data for G· F U. − On the other hand, the base pair formation within the oligonucleotide duplexes under more physiological conditions is governed by the mutual orientation of the bases, as enforced by the sugar–phosphate backbone and its conformation.…”

Section: Introductionmentioning

confidence: 99%

“…For example, although calculations on the microsolvated state of Br U show that its enolic form in the microsolvated state, and in conclusion in the real water solvation state, is more stable than its keto form, experimental results verify that the population of its enolic form is only about 0.004% of the keto form in a typical RNA duplex. , Thus, the structural and energetic parameters obtained from single bases are not applicable for base pairing, and three studies that report water– F U species cannot produce reliable data for G· F U. − On the other hand, the base pair formation within the oligonucleotide duplexes under more physiological conditions is governed by the mutual orientation of the bases, as enforced by the sugar–phosphate backbone and its conformation. The four mentioned computational studies about G· F U using the MP2 method, which uses a little different basis set, report approximately the same interaction energies for each unique orientation of this pair. − One of these studies also reports the Δ G values between wobble G· F U and its tautomeric orientations . These Δ G values may be considered as reliable amounts for this pair as a truncated part of the nucleic acid duplexes because of the observed agreements among all of these studies in the case of interaction energies .…”

Section: Introductionmentioning

confidence: 99%

Relative Populations of Some Tautomeric Forms of 2′-Deoxyguanosine-5-Fluorouridine Mismatch

Amini

2018

J. Phys. Chem. B

View full text Add to dashboard Cite

The importance of the 2'-deoxyguanosine-uridine mispair as the most occurring mismatch in transcriptional studies of RNAs from DNAs is multiplied when 5-halo-substituted uridine species cause a serious increase in the probability of its occurrence. Many studies relate this higher probability to the existence of possible tautomeric and ionic forms of its constituent bases. According to these statements, relative populations of mismatches between 5-fluorouridine and both keto and enol forms of 2'-deoxyguanosine are computed by using a conformational search. In order to have a complete scan of all of the highly probable conformers in a moderate computational time, an extensive conformational search methodology is employed here, which benefits from the advantages of both the molecular dynamics simulations and quantum mechanics calculations. The population of an enolic tautomer of normal wobble orientation is about 0.057% of that of its keto tautomer, whereas the population of an enolic tautomer of reverse wobble orientation is about 0.0054% of that of its keto tautomer. Totally, the reverse wobble orientation is about six times more populated than the normal wobble orientation. Calculated populations are in good agreement with experimental populations of closely related compounds. The reliability of the applied methodology is certified, in part, by a good agreement obtained between some experimental data and corresponding Boltzmann-weighted average data of most probable conformers such as NMR parameters. The validation of this methodology is certified with high accuracy by applying it on the substituted diuridine pairs, where experimental populations are available. Not only are the calculated populations and NMR parameters of this test in very good agreement with the experimental data, but also they are free of the ambiguities mentioned by experimentalists.

show abstract

Tautomerism in some pyrimidine nucleoside analogues used in the treatment of cancer: an ab initio study

Cited by 6 publications

References 46 publications

Tautomerism of Inosine in Water: Is It Possible?

Tautomerism of Inosine in Water: Is It Possible?

Tautomerism of cytosine, cytidine, and deoxycytidine: Proton transfer through water bridges

Relative Populations of Some Tautomeric Forms of 2′-Deoxyguanosine-5-Fluorouridine Mismatch

Contact Info

Product

Resources

About