Pyrimidine Nucleic Acid Bases Research Articles

Synthesis of Nucleic Acid Bases by Metal Ferrite Nanoparticles from a Single Carbon Atom Precursor Molecule: Formamide.

The synthesis of prebiotic molecules from simple precursors is believed to be a crucial scheme in order to study the origin of life processes. The present study describes the one-pot synthesis of purine and pyrimidine nucleic acid bases in the presence of pre-biologically significant binary metal oxide nanoparticles, metal ferrites, namely NiFe2O4, CoFe2O4, CuFe2O4, ZnFe2O4 and MnFe2O4. The products identified are cytosine, isocytosine, 4(3H)-pyrimidinone, adenine, hypoxanthine and purine. The ability of isocytosine (a constitutional isomer of cytosine) to recognize cytosine and guanine through normal and reversed Watson-Crick pairing respectively, demonstrates an important storyline for the genesis of ancient nucleic acids. The relevance of other synthesized nucleic acid bases with respect to the origin of life is also discussed. The divalent metal ions in iron oxide make it an appropriate catalytic system because it demonstrates excellent catalytic performance for the nucleic acid bases synthesis with significantly high yield, as compared to pure iron oxide and some other minerals like silica, alumina, manganese oxides and double metal cyanide complexes.

TD-DFT investigation of the magnetic circular dichroism spectra of some purine and pyrimidine bases of nucleic acids.

We present a computational study of the magnetic circular dichroism (MCD) spectra in the 200-300 nm wavelength region of purine and its derivative hypoxanthine, as well as of the pyrimidine bases of nucleic acids uracil, thymine, and cytosine, using the B3LYP and CAM-B3LYP functionals. Solvent effects are investigated within the polarizable continuum model and by inclusion of explicit water molecules. In general, the computed spectra are found to be in good agreement with the experimental ones, apart from some overall blue shifts. Both the pseudo-A term shape of the MCD spectra of the purines and the B term shape of the spectra of pyrimidine bases are reproduced. Our calculations also correctly reproduce the reversed phase of the MCD bands in purine compared to that of its derivatives present in nucleic acids. Solvent effects are sizable and system specific, but they do not in general alter the qualitative shape of the spectra. The bands are dominated by the bright π → π* transitions, and our calculations in solution nicely reproduce their energy differences, improving the estimates obtained in the gas phase. Shoulders are predicted for purine and uracil due to n → π* excitations, but they are too weak to be observed in the experiment.

Calculation and interpretation of vibronic absorption and fluorescence spectra of the first electronic nπ* transitions of pyridine and pyrimidine

We have calculated vibronic spectra of the first electronic nπ* transitions of pyridine and pyrimidine in the isolated state using the DFT method in the Franck-Condon approximation. Vibrational spectra for the ground and excited states have been calculated in the anharmonic approximation, which allowed us to refine the assignment of normal vibrations of pyridine and pyrimidine. We have done a complete interpretation of the vibrational structure of the absorption and fluorescence spectra of pyridine and pyrimidine. It has been shown that Fermi resonances between fundamental and combination vibrations and overtones 12 and 16b + 4, 6a and 2 × 16b affect the formation of the vibrational structure of electronic spectra of pyrimidine. Good agreement between calculated and experimental spectra confirms the correctness of the models of the two molecules in their ground and excited states, which makes it possible to use the models in further investigations of various properties of these molecules in electronically excited states, e.g., tautomerism of pyrimidine bases of nucleic acids.

Inheritance and correlation of nucleic acid pyrimidine bases

Valence electronic structures of pyrimidine (P, C4N2H4) and nucleic acid (NA) pyrimidine bases, including cytosine (C, C4N3OH5), thymine (T, C5N2O2H6), and uracil (U, C4N2O2H4), are studied using B3LYP/aug-cc-pVTZ, B3LYP/TZVP, SAOP/et-pVQZ, and OVGF/TZVP. The highest occupied molecular orbital (HOMO) and the next HOMO (NHOMO) of pyrimidine are conclusively assigned as 7b2 and 2b1, respectively. The ionization energy spectra and valence orbital momentum distributions studies reveal that the NA bases, that is, cytosine, thymine, and uracil, exhibit a larger degree of similarity to each other than to pyrimidine, although they do inherit certain properties from pyrimidine. © 2013 Wiley Periodicals, Inc.

Inheritance and correlation of nucleic acid pyrimidine bases

Inheritance and correlation of nucleic acid pyrimidine bases

CH/π Interactions in DNA and Proteins. A Theoretical Study

A systematic study of the CH/pi interactions of methane with the purine and pyrimidine bases of nucleic acids and with the lateral chains of the four natural aromatic amino acids has been carried out for the first time. The MPWB1K/6-31+G(d,p) method has shown to be adequate for the study of these weak interactions in which dispersion forces play a main role. It has been shown that two different kinds of clusters exist, depending on whether one or two CH bonds point to the aromatic system. The latter one, which we have called bifurcated, is usually more stable. With regard to aromatic amino acids, our calculations agree with experimental data in the fact that tryptophan leads to the strongest interaction, while hystidine leads to the weakest one. In the case of nucleic acid bases, the differences in binding energies are not large. This is specially true for thymine and uracil, showing that these two bases have a similar acceptor character in CH/pi interactions.

Complex retention behavior of pyrimidines on biomembrane-mimic immobilized-artificial-membrane phase

The influence of the chemical substitutions on the interfacial interactions of pyrimidines with the phospholipid-mimic immobilized-artificial-membrane (IAM) chromatographic stationary phase was evaluated. Monocyclic pyrimidine nucleic acid bases (nucleobases) were revealed behaving differently from their bicyclic purine counterparts substantially. The computed electrostatic potential surfaces for both the IAM phase and the interacting nucleobases are intuitive in deconvoluting the retention patterns of pyrimidines molecularly. A structure-retention model has also been derived using quantitative 3D-QSAR methodology pertinent to the IAM-retention of pyrimidines for the potential use in molecular design. IAM phase is found particularly suitable in assessing the retention of pyrimidines with bulky or elongated exocyclic substituents in the biological context than the alkyl-based chromatographic counterparts.

The Acidity Constants of Some Pyrimidine Bases in Various Water Organic Solvent Media

The acid ionization constants of some pyrimidine bases of nucleic acids were determined pH-metrically at 25 degrees C and at the constant ionic strength I = 0.10 mol l(-1) (KNO3) in pure water as well as in aqueous media containing variable mole percentages (5-30%) of organic solvents. The organic solvents used were methanol, ethanol, N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile, acetone and dioxane. The results obtained indicated that the acidity constants are generally decreased as the content of an organic solvent in the medium is increased. It was deduced that the hydrogen bonding interactions and the solvent basicity in addition to the electrostatic effect are the major effects influencing significantly the acid ionization process of pyrimidine bases in the different water-organic solvent media. Some thermodynamic parameters (deltaH, deltaG degrees, deltaS degrees) of the ionization process over the temperature range 5-45 degrees C in pure water were also determined and discussed.

5- N-Substituted-2-(substituted benzenesulphonyl) glutamines as antitumor agents. Part II: Synthesis, biological activity and QSAR study

Cancer is a major killer disease throughout human history. Thus, cancer becomes a major point of interest in life science. It was proved that cancer is a nitrogen trap and tumor cells are avid glutamine consumers. The non-essential amino acid glutamine, which is a glutamic acid derivative, supplies its amide nitrogen to tumor cells in the biosynthesis of purine and pyrimidine bases of nucleic acids as well as takes part in protein synthesis. Based on these and in continuation of our composite programme of development of new potential anticancer agents through rational drug design, 17 new 5- N-Substituted-2-(substituted benzenesulphonyl) glutamines were selected for synthesis. These compounds as well as 36 earlier synthesized glutamine analogues were screened for antitumor activity using percentage inhibition of tumor cell count as the activity parameter. QSAR study was performed with 53 compounds in order to design leads with increased effectiveness for antitumor activity using both physicochemical and topological parameters. QSAR study showed that steric effect on the aromatic ring is conducive to the activity. n-butyl substitution on aliphatic side chain and atom no 12 is important for antitumor activity of glutamine analogues.

Conformational Analysis of Canonical 2-Deoxyribonucleotides. 1. Pyrimidine Nucleotides

The molecular structure and relative stability of north and south conformers of 2′-deoxyribonucleotides containing pyrimidine nucleic acid bases (2′-deoxythymidilic (pdT), 2′- deoxycytidilic (pdC) acids and their mono- and dianions) have been obtained and analyzed at the DFT/B3LYP level using the standard 6–31G(d) basis set. We have revealed that, when the nucleobase moiety is incorporated into the nucleotides, it maintains a nonplanar and nonrigid conformation due to out-of-plane deformation of the amino group and pyrimidine ring. It has been demonstrated that an increase of negative charge of the phosphate group results in increase of amino group pyramidalization, discrimination between conformers with syn and anti orientation of base with respect to sugar, strengthening of intramolecular C-H…O hydrogen bonds leading to deformation and fixation of geometry of nucleotides, and weakening of phosphodiester bond. These results allow to make suggestions about sources of twist and buckle deformations of base pairs, mechanisms of repaire of DNA via change of base orientation, and conditions for breakage of the P-O bonds during hydrolysis.

Theoretical analysis of intensity distribution in Raman and resonance Raman spectra of biological molecules

Molecules of biological interest, such as purene and pyrimidine bases of nucleic acids, are studied now from experimental and theoretical points of view. In this work classical approach was used to get the relative line intensities in the Raman spectra of adenine and its deuterated-substituted analogues. To describe the intensity of distribution in the resonance Raman spectrum (RRS) of adenine, in contrast, the quantum-mechanical method was used. Satisfactory agreement between theoretical and experimental data was achieved in both cases and the comparable analysis of vibration mode activity was made.

ChemInform Abstract: Synthesis, Transformations and Biological Activity of Chloro Enamines and Ynamines Derived from Chloroalkenyl‐ and Alkynyl‐N‐substituted Purine and Pyrimidine Bases of Nucleic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis, transformations and biological activity of chloro enamines and ynamines derived from chloroalkenyl- and alkynyl-N-substituted purine and pyrimidine bases of nucleic acids

Reactions of nucleic acid bases and related heterocycles 1–5, 18 and 22 with tetra-, tri- and dichloroethylenes 6–9 in hexamethylphosphoric triamide gave the corresponding N-trichloro-, -dichloro- and -chloro- enamines 11–17, 19, 20, 23 and 24 in high regioselectivity (N9 for purines and N1 for pyrimidines). Bases 1, 5, 18, 22 and trichloroethylene 7 gave the respective E-dichloro enamines 15, 16, 20 and 24. Compounds 16 and 20 were identical with the products obtained by addition of bases 1 and 18 to dichloroacetylene. Thymine 18 and compound 7 gave N1,N3-bisdichloro enamine 21 as the major product. The latter exists at room temperature as a mixture of rotamers 28 and 29(ΔG‡≅ 18 kcal mol–1). The reaction of adenine 1 with (Z)-1,2- or 1,1-dichloroethylene 8 or 9 furnished Z-chloro enamine 17 whereas thymine 18 and tetrachloroethylene 6 in dimethyl sulfoxide afforded a reduction product 20. Benzoylation of N9-(trichlorovinyl)adenine 11 gave N6,N6-dibenzoyl derivative 26. The reaction of N1-(dichlorovinyl)cytosine 24 with N,N-dimethylformamide dimethyl acetal afforded amidine 25. Interaction of (E)-N9-(dichlorovinyl)adenine 16 with sodium methoxide gave exclusively E-enamine 27. Trichloro enamines 11–14, 19, 23 and 26 were transformed to ynamines 30–35. Hydrogenation of compounds 30 and 35 furnished N9-ethyladenine 36 and N1-ethylthymine 37. Alkylation of ynamine 30 with acetone 38 gave only carbinol 41 whereas cyclohexanone 39 gave both compound 42 and cyclic ketal 43. The reaction of ynamines 30 and 35 with ketone 40 afforded only ketals 44 and 45. The reaction of compound 30 with N,N-dimethylformamide dimethyl acetal led to N-dimethylaminomethylene derivative 46. Ynamine 30 is a substrate for adenosine deaminase.

Quantum chemical study of relative stability, electric field gradients at nitrogen atoms, rotational constants and electric dipole moments of all uracil, thymine and cytosine isomers

Abstract For four uracil and five cytosine isomeric forms, fully optimized quantum chemical structural data computed at the HF/6-31** level of approximation are reported. Effects of electron correlation (based on pointwise MP2/HF/6-31G** calculations) on the relative energies of all 13 isomers of uracil and thymine and all 14 isomers of cytosine are investigated. Principal values of electric field gradients at N atoms in the 1 and 3 positions of the ring and of the amino/imino substituent in the 6 position of cytosine, rotational constants and electric dipole moments were determined for all isomers at the same level of theory. An attempt to characterize attractive interactions between hydroxy (imino) substituents and lone pair electrons centered at adjacent N atoms (a hitherto unrecognized “intramolecular H-bond”) by means of electron density, difference electron density, field lines of the gradient and a contour map of the Laplacian of the electron density is presented. Electric field gradient tensors and their asymmetry parameters are shown to be correlated in a characteristic manner with repulsive and attractive interaction. These interactions were recently found to be connected in a simple manner with conversion energies of geometric isomers of tautomeric forms of the three pyrimidine nucleic acid bases.

Amidoalkylation of pyrimidine bases of nucleic acids

The reaction of uracil, thymine, and cytosine with acid N-α-chloroalkylamides gave N-substituted derivatives of these compounds. Conditions for the selective amidoalkylation of pyrimidine bases in the 1 position were found.

ChemInform Abstract: Reactions with Dimethyl Carbonate. Part 5. Methylation of the Pyrimidine Bases of Nucleic Acids.

AbstractThe methylation efficiency of dimethyl carbonate (IV) is examined because it is often used as a substitute of the highly dangerous dimethyl sulfate but nothing is known about the risks of (IV) itself.

Notizen: Reaktionen mit Dimethylcarbonat, 5 Methylierung der Pyrimidin-Basen der Nucleinsäuren / Reactions with Dimethyl Carbonate, 5 Methylation of the Pyrimidine Bases of Nucleic Acids

The methylation of the pyrimidine bases of nucleic acids by dimethyl carbonate is described compared to dimethyl sulphate. The reaction needs higher temperature, a base and the help of 18-crown-6 and DMF as cosolvent.

Delivery of photoreactive psoralen derivatives to specific biological targets

Psoralens are bifunctional molecules which photoreact with the pyrimidine bases of nucleic acids to form monoadducts and diadducts, or interstrand cross-links. We have prepared psoralen derivatives with additional functional groups which can be specifically directed to chosen biological targets. A sulfhydryl-containing psoralen which can form site-specific cross-links in plasmid DNA has been used to study psoralen repair and mutagenesis. Cloned DNA containing psoralen monoadducts has been cross-linked to specific regions of viral RNA and used to probe virus assembly. A biotinylated psoralen derivative which binds specifically to avidin has been used to detect small amounts of DNA. Finally, a psoralen derivative of insulin has been used to deliver psoralen specifically to activated lymphocytes.

Photoinduced reactions of anthraquinone antitumor agents with peptides and nucleic acid bases: An electron spin resonance and spin trapping study

The photoexcitation (λ = 313 ± 10 nm) of adriamycin, daunomycin, and mitoxantrone in the presence of peptides or pyrimidine nucleic acid bases was investigated. In airsaturated and air-free solutions, peptides are decarboxylated by the photoexcited drug molecules. The decarboxylation reactions were shown to occur specifically at the C-terminal amino acid of the peptide. The decarboxylated peptide radicals were spintrapped using 2-methyl-2-nitrosopropane (MNP) and identified by electron spin resonance (ESR). In air-free solutions, nucleic acid bases are oxidized by the photoexcited drug molecules predominantly generating C(5)-carbon-centered radicals in the pyrimidine rings of uracil, cytosine, and thymine. However, spin adducts of MNP and thymine were also obtained at the N(1) or N(3) positions of the pyrimidine ring. In air-saturated adriamycin and daunomycin solutions, the spin adducts of MNP with uracil or thymine are similar to those obtained following hydroxyl radical reactions with these pyrimidines. This suggests that in the presence of oxygen, the photoexcited adriamycin and daunomycin transfer an electron to oxygen generating the superoxide anion radicals ( O⨪2), which are precursors of hydroxyl radicals. O⨪2 was also formed when O 2-saturated DNA solutions were photoirradiated (λ = 313 ± 10 and 438 ± 10 nm) in the presence of adriamycin and daunomycin, indicating that the photodegradation of DNA in the presence of these drugs caused by hydroxyl radicals is mediated by dissolved Oxygen.

Raman Excitation Profiles of Purine and Pyrimidine Nucleic Acid Bases

Raman excitation profiles for the monophosphates of guanosine, cytidine, and thymidine have been obtained experimentally using tunable ultraviolet radiation. These data were then fit to a single state, preresonance enhancement equation in order to determine the effective absorption wavelength. In all cases these band origins agreed quite well with the electronic spectral maxima. For two of the bases these studies were performed at drastically varying pH's. A neutral-to-alkaline change produced only minor differences in the spectral data for guanosine, whereas a neutral-to-acidic change had a marked effect on both the spectrum and band origin for cytidine.