Reaction Of Thymine Research Articles

Synthesis, crystal structure, Hirshfeld surface and interaction energies analysis of 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione

The title compound 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione was obtained by reaction of thymine with 3-nitrobenzylbromide in the presence of cesium carbonate. Characterization of the product was achieved by NMR spectroscopy and its stability was probed in basic condition using UV-Visible analysis. Furthermore, the molecular structure was confirmed by X-ray diffraction analysis. The compound crystallizes in orthorhombic Pna21 space group with unit cell parameters a = 14.9594 (15) Å, b = 25.711 (3) Å, c = 4.5004 (4) Å, V = 1731.0 (3) Å3 and Z = 4. The crystal packing of the title compound is stabilized by intermolecular hydrogen bond, π···π and C−H···π stacking interactions. The intermolecular interactions were furthermore analyzed through the mapping of different Hirshfeld surfaces. The two-dimensional fingerprint revealed that the most important contributions to these surfaces come from O···H (37.1%), H···H (24%) and H···C/C···H (22.6%) interactions. The interaction energies stabilizing the crystal packing were calculated and were presented graphically as framework energy diagrams. Finally, the energy-framework analysis reveals that π···π and C−H···π interactions energies are mainly dispersive and are the most important forces in the crystal.

Theoretical kinetics study of thymine tautomerism and interaction of Na+ with its tautomers

ABSTRACTThe current work is a theoretical study of the tautomerism of thymine in the gas phase. Eighteen structures were found in the isomerisation reaction of thymine, some of which are reported for the first time. Thirty hydrogen transfer reactions were carried out. In 24 of the reactions, the hydrogen abstractions N―H→O, N―H→C and C―H→O were considered. The potential energy surface for all trajectories was determined for 18 tautomers and 40 transition states. The RRKM-TST model was used to calculate the rate constants of the reactions to examine their kinetics. Nonlinear least-squares fitting was used to calculate the rate constants expressions. The interaction of sodium ion and tautomers in the gas phase was also investigated. Three types of interaction of metal cations with thymine were found. In the first, metal cations interact with a lone pair of nitrogen or oxygen tautomers. The second type is the interaction of metal cations with two nitrogen and oxygen of tautomers. The last type is the interaction of metal cations and the electron density of the π-system of thymine in which the metal ion is perpendicular to the ring of tautomers. The stability ranking of the thymine tautomers and their complexes was also determined.

Inside Cover, Volume 114, Issue 6

International Journal of Quantum ChemistryVolume 114, Issue 6 p. iii-iv Cover ImageFree Access Inside Cover, Volume 114, Issue 6 First published: 05 February 2014 https://doi.org/10.1002/qua.24615AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract B3LYP and MP2 methods are used to study the hydroxylation and dehydrogenation of thymine at different sites in the presence of hydroxyl radicals (·OH). The MP2 method captures a feature in the reaction of thymine with hydroxyl radicals that the B3LYP method misses. A transition state exists in the hydroxylation of thymine at its C6 site, according to the MP2 calculations by Rongri Tan, Dongqi Wang, Lin Hu, and Feng-Shou Zhang on page 367. This is consistent with the experimental observation that there is a larger population for the C5-hydroxylated product than for the C6-hydroxylated product. Volume114, Issue615 March 2014Pages iii-iv RelatedInformation

Ring‐Opening Photoreactions of 5‐Methylcytosine with 3‐Mercaptopropionic Acid and Other Thiols

The photoproducts from reaction of thymine with cysteine, an amino acid containing a sulfhydryl group, have been studied in detail, whereas results of less extensive studies have been reported for the uracil-cysteine system. However, products arising from corresponding reactions of cytosine and related compounds with compounds containing a sulfhydryl group have not been similarly studied. We report here the results of our study of the photoreaction of 5-methylcytosine (5MeCyt), a minor base occurring in mammalian DNA, with 3-mercaptopropionic acid (3MP), a model compound for cysteine. We found that this reaction proceeds at pH 7 to yield N-(N'-(2'-carboxyethyl)thiocarbamoyl)-3-amino-2-methylacrylamidine (Ia) as a primary photoproduct. A secondary thermal product, identified as 3-(2'-carboxyethylthio)-2-methylacrylamidine (IIa), appears if photoreacted solution is allowed to stand for appreciable times prior to workup; this latter compound is formed via an intermediate product. Heating of purified Ia at 100°C or standing at lower temperatures produces 3-amino-2-methylacrylamidine (IId); similarly, irradiation of Ia with UVB light in aqueous solution converts it into IId. Results from exploratory studies suggest that 5MeCyt similarly reacts with other thiols (2-mercaptoethanol, 2-mercaptoacetic acid) to form analogs of Ia and IIa. Other preliminary results suggest that 5-methyl-2'-deoxycytidine and 1,5-dimethylcytosine photoreact with 3MP to form compounds similar to Ia.

Theoretical studies on the reactions of thymine with six methylating agents

The reaction mechanisms of the three carcinogenic methylating agents, dimethyl sulfate (DMS), methyl methanesulfonate (MMS), and iodomethane (MeI), with keto and enol tautomers of thymine (K-thymine and E-thymine) were studied by using the B3LYP method in the 6-311+G (d, p) basic set. Using the same method, reactions of K- and E-thymine were explored with the three common methylating agents, dimethyl carbonate (DMC), methyl fluorosulfonate (MFS), and methyl trifluorosulfonate (MTFS). The solvent effects were examined using the polarizable continuum model (PCM) in water, acetone, and carbon tetrachloride. Our calculations found that K-thymine is appreciably more stable than the enol form in the gas phase and the three solvents. The calculated results show that the reactions of K-thymine with MeI, MFS, and MTFS are a two-step mechanism, while those of K-thymine with DMS, MMS and DMC are a one-step mechanism. Moreover, all reactions of E-thymine with the six methylating agents are a one-step mechanism. The reaction barriers of K-thymine with three carcinogenic methylating agents range from 211.2 to 267.6 kJ/mol. For K-thymine with DMC, MFS and MTFS, the reaction barriers range from 191.1 to 287.6 kJ/mol. These results indicate that all reactions mentioned above could not efficiently occured in biological organism in the absence of the catalyst. Our conclusion is in agreement with the previous study on the reactions of guanine with methyl chloride and methyl bromide.

Interconversion of the cis-5R,6S- and trans-5R,6R-Thymine Glycol Lesions in Duplex DNA

Thymine glycol (Tg), 5,6-dihydroxy-5,6-dihydrothymine, is formed in DNA by the reaction of thymine with reactive oxygen species. The 5R Tg lesion was incorporated site-specifically into 5′-d(G1T2G3C4G5Tg6G7T8T9T10G11T12)-3′; Tg = 5R Tg. The Tg-modified oligodeoxynucleotide was annealed with either 5′-d(A13C14A15A16A17C18A19C20G21C22A23C24)-3′, forming the Tg6•A19 base pair, corresponding to the oxidative damage of thymine in DNA, or 5′-d(A13C14A15A16A17C18G19C20G21C22A23C24)-3′, forming the mismatched Tg6•G19 base pair, corresponding to the formation of Tg following oxidative damage and deamination of 5-methylcytosine in DNA. At 30 °C, the equilibrium ratio of cis-5R,6S:trans-5R,6R epimers was 7:3 for the duplex containing the Tg6•A19 base pair. In contrast, for the duplex containing the Tg6•G19 base pair, the cis-5R,6S:trans-5R,6R equilibrium favored the cis-5R,6S epimer; the level of the trans-5R,6R epimer remained below the level of detection by NMR. The data suggested that Tg disrupted hydrogen bonding interactions, either when placed opposite to A19 or G19. Thermodynamic measurements indicated a 13 °C reduction of Tm regardless of whether Tg was placed opposite dG or dA in the complementary strand. Although both pairings increased the free energy of melting by 3 kcal/mol, the melting of the Tg•G pair was more enthalpically favored than was the melting of the Tg•A pair. The observation that the position of the equilibrium between the cis-5R,6S and trans-5R,6R thymine glycol epimers in duplex DNA was affected by the identity of the complementary base extends upon observations that this equilibrium modulates the base excision repair of Tg [Ocampo-HafallaM. T.; AltamiranoA.; BasuA. K.; ChanM. K.; OcampoJ. E.; CummingsA.Jr.; BoorsteinR. J.; CunninghamR. P.; TeeborG. W.DNA Repair (Amst)2006, 5, 444−454].

The reactions of thymine and thymidine with ozone

The ozonolysis of thymine and thymidine has been investigated by a product study complemented by kinetic studies using spectrophotometry, conductometry and stopped-flow with optical and conductometric detection. Material balance has been obtained. Ozonolysis of thymine (k = 3.4 × 104 dm3 mol−1 s−1) leads to the formation of the acidic (pKa = 4) hydroperoxide 1-hydroperoxymethylene-3-(2-oxopropanoyl)urea 5 (∼34%), neutral hydroperoxides (possibly mainly 1-hydroperoxyhydroxymethyl-3-(2-oxopropanoyl)urea 6, total ∼41%) and H2O2 (25%, with corresponding formation of 1-formyl-5-hydroxy-5-methylhydantoin 11). The organic hydroperoxides decay (∼1.1 × 10−3 s−1 at 20 °C, 1.3 × 10−4 s−1 at 3 °C) releasing formic acid (formation of 5-hydroperoxy-5-methylhydantoin 18) and also to some extent H2O2 (and 11). After 100 min, the formic acid yield is 75%. Upon treatment at high pH, it increases to 100%. Reduction of the organic hydroperoxides with bis(2-hydroxyethyl) sulfide (k = 50 dm3 mol−1 s−1) leads to 11 whose subsequent treatment with base yields 5-hydroxy-5-methylhydantoin 13 in 100% yield. It is suggested that the Criegee ozonide formed upon reaction with ozone at the C(5)–C(6) double bond opens heterolytically in two directions with subsequent opening of the C(5)–C(6) bond. In the preferred route (75%), the positive charge resides at C(6). Deprotonation at N(1) gives rise to 5, while its reaction with water yields 6. Loss of formic acid yields 5-hydroperoxy-5-methylhydantoin 18. Reduction of 5 and 6 with the sulfide yields 11. In the minor route (25%), the positive charge remains at C(5) followed by a reaction with water. The resulting α-hydroxy hydroperoxide rapidly loses H2O2 (formation of 11). In basic solution, singlet dioxygen is formed (8%). The concomitant product, 5,6-dihydroxy-5,6-dihydrothymine has been detected. In the ozonolysis of thymidine, the rapid formation of conductance (k = 0.55 s−1) is due to the release of acetic acid (18%). In this reaction a short-lived hydroperoxide is destroyed. As a consequence of this, 25 s after ozonolysis the total hydroperoxide yield is only ∼78% (including 8% H2O2). The products corresponding to acetic acid are suggested to be CO2 and N-(2-deoxy-β-D-erythropentofuranosyl)formylurea 22. A number of organic hydroperoxides have been detected by HPLC by post-column derivatisation with iodide. An acidic hydroperoxide such as 5 in the case of thymine is not among the products. Upon sulfide reduction, the organic hydroperoxides yield mainly (43–50%) N1-(2-deoxy-β-D-erythropentofuranosyl)-5-hydroxy-5-methylhydantoin 23. The reasons for some striking differences in the ozonolyses of thymine and thymidine are discussed.

Oxidation of Nucleic Acid Related Compounds by the Peroxodisulfate Ion

Abstract The treatment of nucleic acid bases, nucleosides, and nucleotides with peroxodisulfate ion in a phosphate buffer solution at pH 7.0 or water at 70—75 °C was investigated. The reaction of thymine and 5-methylcytosine nucleosides and nucleotides resulted in the oxidation of the 5-methyl groups. The oxidation products from 1,3-dimethyluracils and the time-course of the reaction of uracils led to two plausible reaction mechanisms for the oxidation of uracils.

Formation of 5-hydroxymethyl-2′-deoxyuridine in hepatic DNA of rats treated with γ-irradiation, diethylnitrosamine, 2-acetylaminofluorene or the peroxisome proliferator ciprofibrate

The peroxisome proliferator ciprofibrate was tested for its ability to induce DNA damage in the form of 5-hydroxymethyl-2'-deoxyuridine (HMdU), an adduct that results from the reaction of thymine in DNA with hydroxyl radicals. In order to quantify HMdU, DNA containing [3H]thymidine of high specific activity had to be obtained. Since hepatocytes normally have a very low rate of DNA synthesis, rats were subjected to partial hepatectomy to stimulate DNA synthesis and then were administered [methyl-3H]thymidine by three p.o., i.p. or i.v. injections 20, 22 and 24 h after partial hepatectomy; or by slow infusion through the portal vein, starting 20 h after partial hepatectomy for 4 h. The specific activity of DNA in rats receiving [3H]thymidine through the portal vein was considerably higher than in rats receiving p.o., i.p. or i.v. injections. Rats were then exposed to various doses of gamma-irradiation after partial hepatectomy and infusion of [6-3H]thymidine through the portal vein. DNA from the liver was extracted, enzymatically hydrolyzed and analyzed by HPLC. The percentage of HMdU in DNA increased in a dose-dependent manner. Rats were then treated with the carcinogens 2-acetylaminofluorene (AAF) or diethylnitrosamine (DEN) in conjunction with partial hepatectomy and infusion of [methyl-3H]thymidine. There was an increase in HMdU formation after a single administration of DEN or AAF. Another group of rats was fed a diet containing the peroxisome proliferator ciprofibrate for 3 weeks. After partial hepatectomy and infusion of [6-3H]thymidine, these rats were fed the same ciprofibrate-containing diet for 2-4 more weeks. HMdU was detected in DNA at 2-4 weeks after [6-3H]thymidine infusion, but the level at 4 weeks was nearly 50% less than at 2 weeks. This study shows that oxidative DNA damage in the form of HMdU is induced in the liver by gamma-irradiation, DEN, AAF and peroxisome proliferation.

Far ultraviolet induced decomposition of thymine in deaerated and aerated aqueous solutions

Thymine in aqueous solution was decomposed with quantum yields of 0.3 and 0.4 under N2-saturated and aerated conditions by far-ultraviolet light (> 180 nm, far-uv), and quantum yields of 2 × 10−4 and 3 × 10−4 by near-ultraviolet light (> 220 nm, near-uv), respectively. The main photolytic products by far-uv were 5,6-dihydrothymine (DHT) (selectivity: S (DHT) = 0.2) and 5-hydroxymethyluracil (HMU) (S(HMU) = 0.1) under N2-saturated conditions, cis- and trans-5,6-Dihydroxy-5,6-dihydrothymine (TG), 6(5)-hydroperoxy-5(6)-hydroxy-5,6-dihydrothymine (HTP) (S(TG) + S (HTP) = 0.2), and N1 -formyl-N2-pyruvylurea (FPU) (S(FPU) = 0.4) were obtained under aerated conditions. These products were attributed to the reactions of thymine with the H and OH produced by photolysis of water.

The Photoreactions of Thymine with Hypoxanthine and Imidazole

Photochemical reactions of thymine linked to hypoxanthine or imidazole by a trimethylene chain were studied in aqueous solution. Irradiation (λ = 254 nm) of thymine-hypoxanthine pair yielded two internal cycloadducts with azetidine and cyclobutane part structures. Sensitization and quenching experiments suggested that the excited singlet was the reactive state in the photo-cycloaddition reactions. Only cyclobutanes were isolated from irradiated (λ = 290 nm) solutions of thymine-imidazole pairs. Photocycloadditions were reversible upon irradiation at λ = 254 nm

Matrix isolation of thymine radicals in ?-irradiated alkaline ice matrices

E.s.r. techniques have been used to study the reactions of thymine, thymidine and dihydrothymine with electrons and O– radical ions which are produced in the γ-irradiation of frozen aqueous solutions of sodium hydroxide. Electrons can attack thymine at the 5,6 double bond when after proton transfer the thymine radical is produced and an eight-line e.s.r. spectrum is observed. After annealing at temperatures above 77 K the O– radical ion can react with the methyl group at the 5 position. In thymidine the eight-line e.s.r. spectrum is observed already at 77 K and this increases further in intensity on annealing. The O– presumably reacts with the methyl group of dihydrothymine.

On the Radiation Chemistry of Thymine in Aqueous Solution

The reactions of thymine in aqueous solution with radiation-induced radicals OH, H, and e-aq were studied under various conditions. Competition studies using scavengers of OH radicals (methanol, ethanol, iodide) or of e-aq and/or H atoms (N2O, H+, O2) led to the conclusion that OH and H radicals destroy the chromophoric group of thymine, but e-aq does not. A trace of O2 proved to be necessary to obtain maximal destruction. Removal of the last traces of O2 resulted in a decrease of the destruction yield, possibly through restitution reactions. It was found that (1) alcohol radicals destroy thymine, even in the presence of O2; (2) the rate constant, k(OH + thymine) = 4.3 X 10(9) M(-1) sec(-1) (from competition with iodide); and (3) k(H + thymine) = 8 X 10(8) M(-1) sec(-1) (from competition with O2 in acid solution).

Reaction of thymine and 5-fluorouracil with acrylonitrile

It is known [1] that acrylonitrile reacts smoothly with uracil in liquid ammonia at −50° C, giving only β-(uracil-N3) propionitrile. Reaction with thiouracil proceeds in exactly the same way [2].