Thymine derivatives

Fig. 21. (a) Diagrammatical representation of an allosteric receptor mechanism (b) allosteric binding of a thymine derivative promoted on uptake (34). 

Gustavsson T, Sarkar N, Lazzarotto E, Markovitsi D, Improta R (2006) Singlet excited-state dynamics of uracil and thymine derivatives a femtosecond fluorescence upconversion study in acetonitrile. Chem Phys Lett 429 551-557... 

Figure 2 Double-stranded oligonucleotide photoprobes that simulate modified DNA and intended to cross-link to DNA-binding proteins. (A) Probe modeling interstrand cross-linking by cisplatin Source From Ref. [63], with permission from the American Chemical Society via the Rightslink service (license number 2458870278307 granted June 30, 2010). The benzophenone probe prior to reaction with DNA is shown in the lower part of the panel. (B) Photoaffinity probe for bacterial DNA repair proteins. TT is a simulated thymine dimer intended to be recognized as a site of damage in DNA, and T (two instances) is the diazirine thymine derivative T Source From Ref. [64], with permission from Wiley.

Platination of the N3 position in 1-substituted uracil and thymine derivatives requires proton abstraction and usually occurs only at high pH, but the Pt-N3 bond, once formed, is thermodynamically stable (log K 9.6) [7]. Platinum binding to N3 increases the basicity of 04, which becomes an additional binding site leading to di- and trinuclear complexes. A list of X-ray structurally characterized species is given by Lippert [7]. Pt complexes of uracil and thymine can form intensely colored adducts (e.g. platinum pyrimidine blues), which show anticar-cinogenic activity analogously to the monomeric species [7]. 

The double-helical rope formation in T-10-T was unexpected, since neither T-10-T nor its precursor thymine is chiral, as verified by CD spectroscopy. The authors speculate that photodimerization of two thymine derivatives leads... 

Thymine derivatives - 5-[7V-(2-Amino-4-hydroxy-6-methyl-5-pyrimidinyl-propyl)-p-carboxyanilinomethyl] uracil (XXXIII) was synthesized for study as a possible intermediate in the enzymatic synthesis of thymidylate. It is active as an enzyme inhibitor against thymidylate synthetase isolated from E. coli [298]. Certain thymine derivatives containing a 2-thioimidazole moiety (XXXIV, R = alkyl) inhibit growth of Ehrlich ascites carcinoma (fluid form) in mice [299]. 

In attempts to isolate the aforementioned irradiated products of thymine derivatives at lower temperature, the photochemical reactions were carried out in frozen aqueous solutions containing either thymine or 1,3-dimethylthymine. The resulting products were not hydrates, but had elementary analyses corresponding to the starting material. Molecular weight determination indicated that the products were dimers, and infrared and ultraviolet spectral data suggested cyclo addition across the 5,6-double bond to form a cyclobutane system... 

Alkyl halides can also be used to generate the radical center, and N -substituted uracil and thymine derivatives have been used to prepare octahydropyrrolo[l,2-f]pyrimidinedione derivatives <2001TL6637, 2006CC844> as demonstrated by diasteroeoselective synthesis of the azabicycle 447 <2006CG844>. 

The thymine anion is only a weak base = 6.9) [22]. This means that protonation of the anion may depend on the specific environment. The primary reduction product observed in the solid state in thymine derivatives is the C4-OH protonated anion [17]. This species exhibits significant spin density at C6 and 04. Here one must distinguish between two different situations. In single crystals of thymidine, the C4-OHp proton is out of the molecular plane which gives rise to an additional 33.1-MHz isotropic hyperfine coupling [31]. A similar situation is observed in single crystals of anhydrous thymine [32]. In 1-meThy, however, the C4—OHp proton is in the molecular plane. Consequently, the proton coupling is very small. 

In all thymine derivatives studied so far in the solid state, there is always a significant concentration of a radical formed by net H abstraction from the >C5-CH3 group, Thy(Me—H) [17]. This allyl-like radical is present at helium temperatures. From studies of frozen thymine solutions and poly(T), it can be shown that the precursor of the allyl-like radical is the thymine cation [33,34]. 

Figure 12. Concentration dependence of the responses to 5 -GMP and 5 -AMP of the oriented membranes based on (a) cytosine derivative 10b, (b) thymine derivative 11b, and (c) cytosine derivative 22. The response factor, R(sample), is expressed by the decrease in the oxidation peak current (/e) upon analyte addition [/ (sample) = [/p(blank) - /p(sample)]//p(blank)l. Measured at 20 °C with a 0.1 M phosphate buffer solution (pH 6.0, 20 °C) containing 1.00 mM [FeICNIel .

Adenine derivative Thymine derivative Sodium dodecyl sulfate... 

To test the hypothesis, aliquots of 5.0 mM adenine derivative were mixed with aliquots of 5.0 mM thymine derivative in proportions shown in the table. Each solution also contained 20 mM sodium dodecyl sulfate. The concentration of product measured by nuclear magnetic resonance also is shown in the table. Are the results consistent with formation of a 1 1 complex Explain your answer. 

In 2005, the Kinugasa reaction performed on /V-propargyl nucleobases, such as adenine, uracil, and thymine derivatives, with diphenyl nitrone has been reported to produce cis- and trans-(3-lactam nucleosides (Scheme 63), [157]. 

Deeble DJ, von Sonntag C (1985) TheUV absorption spectra of theC(5) and C(6) OH adduct radicals of uracil and thymine derivatives. A pulse radiolysis study. Z Naturforsch 40c 925-928 Deeble DJ, von Sonntag C (1987) Radioprotection of pyrimidines by oxygen and sensitization by phosphate a feature of their electron adducts. Int J Radiat Biol 51 791-796 Deeble DJ, Das S, von Sonntag C (1985) Uracil derivatives sites and kinetics of protonation of the radical anions and the UV spectra of theC(5) and C(6) H-atom adducts. J Phys Chem 89 5784-5788... 

Deeble DJ, Schuchmann MN, Steenken S, von Sonntag C (1990) Direct evidence for the formation of thymine radical cations from the reaction of SO/" with thymine derivatives a pulse radiolysis study with optical and conductance detection. J Phys Chem 94 8186-8192 DeFelippis MR, Murthy CP, Faraggi M, Klapper MH (1989) Pulse radiolytic measurement of redox potentials the tyrosine and tryptophan radicals. Biochemistry 28 4847-4853 Delatour T, Douki T, D Ham C, Cadet J (1998) Photosensitization of thymine nucleobase by benzo-phenone through energy transfer, hydrogen abstraction and one-electron oxidation. J Photo-chem Photobiol 44 191-198... 

Ito T, Shinohara H, Hatta H, Nishimoto S-l (1999) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers product and laser flash photolysis studies on the oxidative splitting mechanism. J Phys Chem A 103 8413-8420 ItoT, Shinohara H, Hatta H, Fujita S-l, Nishimoto S-l (2000) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers. 2. Conformational effects on the reductive splitting mechanism. J Phys Chem A 104 2886-2893 ItoT, Shinohara H, Hatta H, Nishimoto S-l (2002) Stereoisomeric C5-C5 -linked dehydrothymine dimers produced by radiolytic one-electron reduction of thymine derivatives in anoxic solution structural characteristics in reference to cyclobutane photodimers. J Org Chem 64 5100-5108 Jagannadham V, Steenken S (1984) One-electron reduction of nitrobenzenes by a-hydroxyalkyl radicals via addition/elimination. An example of an organic inner-sphere electron-transfer reaction. J Am Chem Soc 106 6542-6551... 

Nishimoto S, Ide H, Otsuki N, Nakamichi K, Kagiya T (1985) Radiation-induced reduction of thymine derivatives in aqueous solution. Part 4. Promoted transformation of thymine glycol into thymine by aromatic amines and low-valent transition metal salts. J Chem Soc Perkin Trans 2 1127-1134... 

The same methodology has been used by Monneret and co-workers in the allylations of 181 to yield 185 and 186, as well as in the allylations of thymine derivative 187 which afford 188 and 189 (94TL4351), as shown in Scheme 42). It can be concluded from both papers that the difference in reactivity between N-l and N-3 is not high. 

Photo-CIDNP experiments using anthraquinones as photosensitizers for oxidation of a variety of uracil- and thymine-derived cyclobutane dimers, e.g. c,s-l, t,s-l, c,a-1, t,a-l, and c,s-2, 4, and 5, demonstrated the existence of both Pyr +oPyr and its dissociation product, the monomer radical cation Pyr + [6, 7]. 

An analogous stereoelectronic influence on the rate of the reductive repair process was also observed by Carell et al. [28]. The ring opening of the dimer radical anion also proceeds stepwise, but with the C(5)-C(5 ) bond being broken first. The C(5) and C(5 )-methyl groups of thymine-derived dimers, which were found to be repaired more slowly than the uracil-derived dimers, lead to distortion of the geometry, which results in deceased overlap of the n C(4)-0(4) orbital with the a C(5)-C(5 ) orbital. 

In all thymine derivatives studied so far in the solid-state there is always a significant concentration of a radical formed by net H abstraction from the >C5-CH3... 

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