Collision-induced dissociation of uracil and its derivatives

The collision-induced dissociation of protonated uracil has been studied by tandem mass spectrometry using models extensively labeled with stable isotopes, and derivatives of the kinds found in nucleic acids. Following collisional activation at 30 eV translational energy, protonated uracil dissociates through two principal pathways which do not occur in electron ionization mass spectra: (1) elimination of NH3 almost entirely from N-3, followed by loss of CO from C-4, 0⁴; (2) loss of H2O, equally from 0² and 0⁴. Elimination of HNCO, also the principal dissociation process from odd-electron molecular ions, proceeds primarily by loss of N-3, C-Z, O² and 10% from N-l, C-Z, 0². Several secondary dissociation products are formed with quantitative site specificity of skeletal atoms: C,HO+ (4-C0, C-5, C-6); H2CN+ (N-l, C-6); C2H2+ (N-l, C-5, C-6). First-step dissociation reactions are interpreted in terms of pyrimidine ring opening at likely sites of protonation after collisional activation of MH+. Collision-induced dissociation mass spectra of uracils with structural themes common to nucleic acids (methylation, replacement of 0 by S, C-5 substitution) follow analogous reaction paths which permit assignment of sites of substitution, and exhibit ion abundance changes attributed to differences in substituent basicity and electron density.     

Preparation and reactivity of polyfunctional phenazine derivatives

Treatment of 2,3,6,7-tetramethylphenazine with N-bromosuccinimide under light irradiation afforded in good yield the tetrakis(bromomethyl) derivative. Weakly basic nucleophilic reagents such as thiols, phenols, amines and the azide anion allow the preparation of a variety of functionalized derivatives. Some 2,7-disubstituted phenazines have also been obtained.     

Interactions of xanthine and its derivatives with cyclodextrins in aqueous solutions

Using calorimetry, ¹H NMR, UV spectroscopy, and solubility methods, the interactions of natural and hydroxypropylated 6h-, β-, and γ-cyclodextrins with xanthine and its methylated derivatives (theophylline, theobromine, and caffeine) were studied in aqueous solutions at 298.15 K. Cyclodextrins revealed low complexation ability toward xanthine and its methylated derivatives. Hydroxypropyl-γ-cyclodextrin with the largest internal cavity is the most effective solubilizing agent for this type of compounds. The calculated thermodynamic parameters are discussed in terms of structural effects of cyclodextrins and purine alkaloids on the character of their intermolecular interactions in aqueous medium.     

Interaction of Ca2+ with uracil and its thio derivatives in the gas phase

The structures and relative stabilities of the complexes formed by uracil and its sulfur derivatives, namely, 2-thio-, 4-thio, and 2,4-dithio-uracil when interacting with Ca(2+) in the gas phase have been analyzed by means of density functional theory (DFT) calculations carried out at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) level. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Ca(2+) attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl or a thiocarbonyl group, are present, Ca(2+)-oxygen association is favored. The most stable complexes correspond to structures with Ca(2+) bridging between the heteroatom at position 2 of the 4-enol (or the 4-enethiol) tautomer and the dehydrogenated ring nitrogen, N3. The enhanced stability of these enolic forms is two-fold, on the one hand Ca(2+) interacts with two basic sites and on the other triggers a significant aromatization of the ring. Besides, Ca(2+) association has a clear catalytic effect on the tautomerization processes which connect the oxo-thione forms with the enol-enethiol tautomers. Hence, although the enol-enethiol tautomers of uracil and its thio derivatives should not be observed in the gas phase, the corresponding Ca(2+) complexes are the most stable species and should be accessible, because the tautomerization barriers are smaller than the Ca(2+) binding energies.     

Antioxidant activity of uracil derivatives

The antiradical properties of a number of uracil derivatives are studied in initiated 1,4-dioxane oxidation as a model reaction. The antioxidant activity of the uracil derivatives as inhibitors is estimated. The antiradical activity of the compounds is quantitatively characterized in terms of the effective rate constant of inhibition, fk _In.     

Polarographic study of uracil derivatives

Eighteen uracil derivatives were studied by d.c. polarography, differential-pulse (d.p.)polarography and d.p. cathodic stripping voltammetry. In a borax buffer at ca. pH 7.6, uracil, thymine and derivatives such as 5-halouracils, 5-trifluoromethyl-,5-aza-,5-acetyl-, 5-formyl- and 5-vinyl-uracil produced well-defined peaks at potentials between 0 V and ca. 160 mV vs. silver/ silver chloride (satd. KCl). The peaks are ascribed to the formation of sparingly soluble mercury salts. For the other derivatives tested (e.g., 5-nitro- and 5-ethynyl-uracil and 6-substituted uracils), the peaks were less well-defined and in some cases the polarographic curves were very complex. 2-Thiouracil produced a single peak at ca. ?400 mV, but only at pH 12.2. The shapes, heights and potentials of the peaks depended on the kind and position of the substituent on the pyrimidine ring. Rectilinear relationships of peak current vs. concentrations were found for most compounds (10^?5-10^?4 M) by d.p. polarography; d.c.polarography was not tested quantitatively. For 5-fluorouracil and 5-vinyluracil, linear calibrations were found for concentrations of 0.5–5 × 10^?7 M by d.p. cathodic stripping voltametry. Interference studies showed that small amounts of chloride and phosphate did not interfere but 5-fluorodeoxyuridine, which did not itself produce a peak, and proteins interfered seriously.     

New synthesis of uracil derivatives

When N,N-dialkylamide dimethylsulfate adducts are reacted with cyanoacetyl urea or carbethoxy acetyl urea, the corresponding dialkylamino alkylidene derivatives are formed which cyclize to substituted uracils in the presence of a strong base. When the adducts of cyclic amides are used, the lactam ring is opened simultaneously on cyclisation.     

Desulfurizative stannylation of uracil derivatives

Phenylthio group in the C-6 or C-5 position of uracil moiety can be removed by radical mediated stannylation with tributyltin hydride followed by protonolysis, providing a new route to 5-substituted uridines.     

Reactivity of nucleophilic uracil derivatives

The reactivity of uracil derivatives bearing acidic methylene groups at N1 was investigated. On treatment with strong base, compounds with nitrile as the activating group underwent extensive dimerisation to give new tricyclic systems. Ester-activated compounds also produced dimers in the absence of an external electrophile, but their monomeric carbanions could be trapped by prompt addition of benzyl bromide to give normally alkylated products.     

Structural and polymer-analogous transformations in cellulose on esterification with polyfunctional acids

Structural transformations of cellulose in ethylenediamine and in liquid ammonia and on subsequent esterification with polyfunctional organic and inorganic acids have been studied.The authors thank Prof. G. A. Petropavlovskii for valuable advice and consultation.Tashkent Institute of Chemical Technology, Tashkent, 700029, ul. T. Shevchenko, 1. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 160–164, January-February, 1995. Original article submitted October 11, 1994.     

Association of Cu2+ with uracil and its thio derivatives: a theoretical study.

The structures and relative stabilities of the complexes between Cu2+ and uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil were investigated by B3LYP/6-311+G(2df,2p)//B3LYP/6-31G* DFT calculations. In those systems in which both types of basic centers, that is, a carbonyl and a thiocarbonyl group, are present, association of Cu2+ with the oxygen atom is systematically favored, in contrast to what was found for the corresponding Cu+ complexes. This can be understood by considering that association of Cu2+ is immediately followed by oxidation of the base, which accumulates the negative charge at the oxygen atoms. Similarly, for 2,4-dithiouracil the most basic site for Cu+ attachment is the sulfur atom at the 4-position, while for association of Cu2+ it is sulfur at the 2-position. In contrast, differences between uracil-Cu+ and uracil-Cu2+ complexes are very small, and in both cases the oxygen atom at the 4-position is the most basic. Cu2+ binding energies are about 4 and 1.2 times larger than Cu+ binding energies and proton affinities, respectively. Uracil- and thiouracil-Cu2+ complexes are thermodynamically unstable but kinetically stable with respect to their dissociation into uracil*+ + Cu+ or thiouracil*+ + Cu+. The Cu2+ binding energies vary with the difference between the second ionization potential of the metal and the first ionization potential of the base. regardless of the reference acid (H+, Cu+, Cu2+) the basicity trend is 2,4-dithiouracil > 4-thiouracil > 2-thiouracil > uracil.     

Electrophilic ipso-substitution in uracil derivatives

Treatment of 5-iodo-1,3,6-trimethyluracil with 50% H₂SO₄ gives 1,3,6-trimethyluracil; with 5-bromo-1,3,6-trimethyluracil, a mixture of 1,3,6-trimethyluracil and 6-bromomethyl-1,3-dimethyluracil is obtained. 5-Chloro-1,3,6-trimethyluracil remains inert under these conditions. According to the DFT modeling of the reactions of 5-halo-1,3,6-trimethyluracils, a nucleophilic agent can abstract either Hal⁺ or the methyl proton from the carbocation formed by protonation of the starting halouracil at position 5, which accounts for the formation of two products from the 5-bromo derivative. Under similar conditions, 6-methyluracil dibromohydrin yields N-bromo-5-bromo-6-hydroxymethyluracil. Bromination or chlorination of 5-hydroxymethyl- or 5-formyl-6-methyluracils follows the ipso-substitution scheme leading to 6-methyluracil 5-halo- and 5,5-dihalohydrins.     

Pro- and antioxidant properties of uracil derivatives

Russian Chemical Bulletin - The review summarizes data on pro- and antioxidant properties of uracil derivatives comprising an important group of pharmacologically active compounds. The presence of...     

Synthesis of uracil derivatives by oxidation of Fischer tungsten-carbene uracil complexes

A study on the oxidation of Fischer tungsten-carbene uracil complexes has been carried out. Several commonly used oxidants gave results strongly influenced by the presence of substituent on nitrogen atoms. In particular, usual oxidants failed in the oxidation of 3-alkyl uracil carbene complexes. Finally, we showed that t-butyl hydroperoxide is able to oxidize successfully also 3-alkyl uracil carbene complexes and can be used as a good alternative to the other methods.     

Relationships observed in the structure and spectra of uracil and its 5-substituted derivatives

The effects on the geometry structure, atomic charges and vibrational wavenumbers of the main different substituents in the 5th position of the uracil ring were analysed, and relationships were established. The 5-monosubstituted derivatives studied were 5-XU (X = F, Cl, Br, I, CH₃, NH₂, NO₂). The geometry and vibrational wavenumbers were determined in these molecules. The FT-IR and Raman spectra were studied with the support of B3LYP calculations using several basis sets. Several general conclusions were underlined.