Uracil dimers

Uracil dimers were studied at the MP2 level using the 6-3IG basis with modified polarization functions. Eleven low-energy minima were located Seven of them are H-bonded, one is T-shaped, and three correspond to various stacked arrangements. The most stable structure was found to be the H-bonded dimer with two Ni-H O2-H bonds (Scheme 85) [98JPC(A)6921]. 

An ab initio study on the structure and splitting of the uracil dimer anion-radical (see Scheme 3.72, R = H) gives preference to the one-step mechanism (Voityuk and Roesch 1997). Anion-radical anions of the pyrimidine dimers cleave with rate constants in excess of 10 s ... 

The dimer has been shown by Blackburn and Davies40 to have a geometrical structure similar to that of thymine dimer (10). The proof consisted in observation of the 13C—H satellite NMR spectrum of 5,5 -dideutero-,3,3 -dimethyl uracil dimer (prepared by methylation of the dimer from photolysis of uracil-5-rf). The magnitude of the H6H6 coupling constant showed that these hydrogens were vicinal, and was... 

The stability of the uracil dimer is the subject of conflicting reports. Ishihara reports33 that it is destroyed by IN NaOH at 100°C, and Wacker states that it is unstable in acid, alkali, or even in boiling water. Setlow et al.46 report that 50% of the uracil dimer is destroyed by formic acid hydrolysis (presumably at 175°C). But Smith32 found it to be stable to boiling water, IN NH4OH, IN HC1, and trifluoracetic acid both at room temperature and at 155°C. 

Photolysis of a frozen mixture of 5 x 10 4M thymine-2-14C and 5 x 10" M uracil-2-14C gave a thymine dimer, a uracil dimer, and a mixed dimer of thymine and uracil,10,32 47 with the identities established as usual by the stability to heat and by photoreversion to monomers in solution. Wacker reports that the uracil dimer obtained in that investigation showed some instability to heat. These collected bits of evidence taken together with the reported441 thermal instability and chromatographic similarity of a synthetic tram dimer suggests that the dimer ordinarily obtained from uracil may be a mixture.46... 

Despite the frequent use of photoreversal as a measure of dimer formation in many biological materials, few detailed studies of this phenomenon have been made. The action spectrum for photoreversal of uracil dimer (and thymine dimer) has been reported by Swenson and Setlow,48 and is shown in Figure 1. Purified, crystalline dimer was used in these studies. The quantum yield for dimer breaking was found to be 0.45, one-half of that for monomerization of thymine dimers.49... 

Fig. 1. The action spectrum for uracil dimer splitting. The corresponding curve for thymine dimer splitting is included for comparison (Swenson and Setlow48).

Smith32 reported that the absorbance of frozen cytosine solutions (0.5 mg/ml) decreased only 3-5% when irradiated with light from a mercury resonance lamp, but that the rate of loss of cytosine doubled when the frozen solution contained both cytosine and uracil. In solutions containing cytosine and thymine, a mixed dimer was apparently formed. Dried films of cytosine were apparently stable to the resonance radiation under conditions where there was 9% conversion of uracil and 17% conversion of thymine. There is a report that uracil dimer was formed in low yield in the photolysis of frozen cytosine solutions.32,81... 

Fig. 5. The rates of formation of dimethyluracil hydrate, uracil hydrate, and uracil dimer in mixtures of acetonitrile and water. Temperature about 24°C (Burr and Park64).

Fig. 28. The fraction of uracil dimers in irradiated poly U as a function of the dose of 265 nm light (Swenson and Setlow48).

The existence of photoreversible, but not of heat-reversible, absorbance change in irradiated poly dI dC was taken to prove that the photoproducts are entirely dimers (in contrast to those in poly C irradiations where the product is almost entirely the hydrate82a). It was possible to detect dimers of uracil as well as those of cytosine, by means of the much slower photoreversal of uracil dimers. In the acid hydrolysates of irradiated dl-dC, both uracil dimers and uracil could be identified. Enzymatic hydrolysis (snake venom phosphodiesterase) does not split pyrimidine dimers, and the products of such hydrolysis of irradiated tritium-labeled poly dl dC contained trinucleotides shown by radioactivity to contain cytosine dimers. Thymine dimers were formed in the photolysis of the poly dA dT, and were detected and assayed by the same methods. The yield of thymine dimers in irradiated poly... 

The techniques of Nirenberg and Leder (see Glossary) have been used to measure the coding activity of uracil dimers and hydrates contained in known positions in tri- and tetranucleotides.148 Mixtures of... 

The quenching of thymine fluorescence in frozen aqueous solution has led Eisinger and Shulman168 to conclude that the precursor of thymine ice dimer is the singlet excited state of thymine Weinblum165 has shown that the ice thymine dimer and the mixed thymine-uracil dimer formed in frozen solutions are the same stereoisomers as those formed by photolysis of DNA, using infrared spectral evidence. 

Quinolone undergoes photochemical addition of tetramethylethylene to give (434) (70AHC(ii)50), l,3-oxazin-4-ones photocycloadd ketene acetals to give (435), and irradiation of 2,6-dimethylpyran-4-one yields the cage dimer (436). 2-Pyranones form [2 + 2] photodimers whose structure is similar to that of uracil dimers (432 or 433). 

An ab initio study on the structure and splitting of the uracil dimer anion radical (see Scheme 3-66 and keep R = H) gives preference to the one-step mechanism (Voityuk Roesch 1997). Anion radical anions of the pyrimidine dimers cleave with rate constants in excess of 106 sec 1 (Yeh Falvey 1991). However, the cyclobutyl dimer of a quinone, dithymoquinone, also cleaves upon single-electron reduction but much more slowly than the pyrimidine dimers (Robbins Falvey 1993). It is truly an unresolved issue as to why the anion radical cleavage depicted in Scheme 3-66 is so facile. Water participation can probably decrease the barrier of the cycloreversion on physiological conditions (Saettel Wiest 2001). 

Z. Czyznikowska, R. Zalesny, M. Ziolkowski, R.W. Gora, P. Cysewski, The nature of interactions in uracil dimer An ab initio study. Chem. Phys. Lett. 450, 132-137 (2007)... 

The lifetime of Pyr +oPyr seemed to depend on the structure of the parent dimer. It was observed that the presence of a trimethylene bridge linking both pyrimidine units at N(l) and N(l ), as in the mixed thymine-uracil dimer 4 and in the thymine dimer 5, leads to significant stabilization of the corresponding dimer radical cation, whereas in unbridged dimers a maximum lifetime of 10-1°-10-9 s was proposed for their dimer radical cations [6]. It was further shown that in bridged pyrimidines dimers of types 4 and 5 the interconversion of dimer and... 

Morgado, C. A. Jurecka, R Svozil, D. Hobza, R Sponer, J. 1. Balance of attraction and repulsion in nucleic-acid base stacking CCSD(T)/complete-basis-set-limit calculations on uracil dimer and a comparison with the force-field description, J. Chem. Theor. Comput. 2009, 5, 1524-1544. 

Table 7. Interaction energies (AE in kcal/mol), changes of Gibbs energies (AG° in kcal/mol) calculated within RR-HO-IG approximation using AMBER 4.1 and ab initio constants, and relative populations from NVE analysis for various structures of uracil dimer...

Among 11 minima found on the PES of uracil dimer, the H-bonded structure 4 was clearly dominant energy difference between this and other H-bonded and stacked structures was rather large. Methylation at the Nj position will prevent formation of this structure and it is possible to expect that all structures of the Nj-methyluracil dimer will be closer in energy. 

A wide assortment of different possible geometries for the uracil dimer were examined [127] in 1998. The most stable of all these contained a pair of NH- -O bonds, but another was identified, only slightly less stable than the others, in which one of these conventional H-bonds was replaced by CH- -O = C. There was no way of estimating the energetic contribution of this particular interaction, as it was secondary to the stronger NH- -O bond. A study of the adenine thymine pair [128] noted a blue shift of the C-H stretching frequency, an indication of a H-bond, but the authors did not attempt to extract an interaction energy. 

Kratochvil, M., Engkvist, O., Sponer, J., Jungwirth, P., and Hobza, P. (1998) Uracil dimer potential energy and free energy surfaces. Ab initio beyond Hartree-Fock and empirical potential surfaces, J. Phys. Chem. A 102, 6921-6926. 

Speedups for MP2 algorithms PI and P2 (dynamic version) measured relative to timings for one process (Pli and P2i) and sixteen processes (Plie and P2i6). Computations tvere performed on a Linux cluster for the uracil dimer molecule using the cc-pVDZ basis set (cf. Figure 9.8). Inflated speedup curves are obtained by measuring speedups relative to a number of processes greater than one. 

Superlinear speedups for Fock matrix formation in the iterative part of the Harlree-Fock procedure as a consequence of storing a larger fraction of the integrals on each process as the number of processes increases. Speedups for the entire Hartree-Fock procedure are shown as well. Computations were performed on a Linux cluster for the uracil dimer using the aug-cc-pVTZ basis set (cf. Figure 8.3). A static task distribution of atom quartets was employed (see section 8.3 for details of the algorithm). 

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