Isoorotic Acid Research Articles

Extended Peptide Nucleic Acid Nucleobases Based on Isoorotic Acid for the Recognition of A-U Base Pairs in Double-Stranded RNA.

Peptide nucleic acids (PNA) with extended isoorotamide containing nucleobases (Io ) were designed for binding A-U base pairs in double-stranded RNA. Isothermal titration calorimetry and UV thermal melting experiments revealed improved affinity for A-U using the Io scaffold in PNA. PNAs having four sequential Io extended nucleobases maintained high binding affinity.

Correction: 1D chains, 2D networks and 3D interdigitated frameworks of isoorotic acid or 4,4′-bipyridyl and isoorotic acid: syntheses, structures, and sorption properties

Correction for ‘1D chains, 2D networks and 3D interdigitated frameworks of isoorotic acid or 4,4′-bipyridyl and isoorotic acid: syntheses, structures, and sorption properties’ by Ritesh Haldar et al., Inorg. Chem. Front., 2015, 2, 278–289.

Stable and Controllable Polymer/Fullerene Composite Nanofibers through Cooperative Noncovalent Interactions for Organic Photovoltaics

A novel methodology of precisely constructing stable and controllable conjugated polymer (CP)/fullerene nanostructures is presented. By building in noncovalent interactions between CP nanofibers (NFs) and fullerene derivatives, supramolecular polymer/fullerene composite NFs are obtained in solution for the first time. Specifically, a conjugated block copolymer having poly(3-hexylthiophene) (P3HT) backbone selectively functionalized with polar isoorotic acid (IOA) moieties, P1, is used as the building block. Self-assembly of P1 in mixed solvents leads to well-defined NFs decorated with IOA groups on the periphery, onto which phenyl-C61-butyric acid methyl ester (PCBM) molecules are subsequently attached noncovalently. Formation of such complex structures are studied in detail and confirmed by UV–vis absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray scattering measurements. Application of these composite NFs in organic photovoltaic (OPV) devices not on...

Synthesis, Crystal Structure, Thermal and Luminescent Characterization of Two New 3D Cadmium–Carboxylate Frameworks

Two new cadmium coordination polymers have been synthesized with composition {[Cd2(tma)(atz)(H2O)]·(H2O)} n (1) (tmaH3 = benzene-1,3,5-tricarboxylicacid, atzH = 5-aminotetrazole) and [Cd(isoor)2(H2O)2] (2) (isoorH = isoorotic acid). X-ray single crystal structure analysis reveals that complex 1 is 3D coordination polymer. However 2 is mononuclear and turned 3D via hydrogen bonding. Thermogravimetric and luminescence characterization of the complexes were done. Two new 3D coordination polymers of cadmium have been synthesized by using benzene-1,3,5-tricarboxylicacid, 5-aminotetrazole and isoorotic acid. Both the complexes are characterized by X-ray single crystal structure, thermal and photoluminescence study.

New Uracil Dimers Showing Erythroid Differentiation Inducing Activities

The synthesis of C5 linked uracil dimers was carried out according to a model developed in order to bind adenine in DNA. N1-Alkylated uracil derivatives were synthesized from isoorotic acid (uracil-5-carboxylic acid) or thymine. The carboxylic acid derivatives were condensed with diamines in order to produce dimeric compounds or with monoamines in order to obtain reference monomeric compounds. Some of the derivatives, in particular the uracil dimers, showed antiproliferative and erythroid differentiation induction properties towards human chronic myelogenous leukemia K562 cells, thus indicating that these compounds could represent a new class of drugs useful for the development of antitumor therapy based on the ability to induce terminal differentiation.

Solid-Phase Molecular Recognition of Cytosine Based on Proton-Transfer Reaction

The proton-transfer molecular adducts cytosine/isoorotic acid (1:1) dihydrate (CytIsor) and cytosine/maleic hydrazide (2:2) dihydrate (CytMal) have been studied by X-ray diffraction methods. CytIsor crystallizes in the orthorhombic system, space group Pbnb, a = 7.4859 (4), b = 12.7977 (9), c = 26.4573 (16) A, V = 2534.7 (3) A3. CytMal crystallizes in the triclinic system, space group P − 1, a = 6.7767 (9), b = 12.063 (2), c = 12.937 (3) A, α = 78.58 (2), β = 75.87 (2), γ = 75.63 (1)°, V = 982.8 (3) A3. In both compounds protonation occurs at the N3 atom of the cytosine aminooxo tautomer as a result of the proton-transfer process from the acidic hydroxy groups of the counterions. In the crystal structure, both cocrystals are stabilized by a plethora of N–H···O, N–H···N and O–H···O hydrogen bonds. It is shown the ability of cytosine to form large organic assemblies, with the appropriate guest, due to solid-state recognition involving synthons based on hydrogen bonding between functional groups as sites of proton-transfer reactions. The proton-transfer molecular adducts of cytosine with isoorotic acid and with maleic hydrazide have been synthesized in the solid state and their hydrogen-bonding patterns have been studied by X-ray diffraction methods.

Theoretical investigation of the tautomerism of isoorotic acid in gaseous and aqueous phases

AbstractIn the present investigation, the tautomeric and conformational equilibrium of isoorotic acid have been studied using Møller–Plesset second‐order (MP2) and density functional theory (DFT) methods in the gas phase and aqueous solution (ε = 78.5) using the IPCM model. The relative energies of these tautomers have been calculated at the two levels of theory using 6‐311++G** basis set. Energetics and relative stabilities of the tautomers were compared and analyzed in both the gaseous and aqueous phases. The results indicate that the diketo tautomer (iso) is the most stable form in the gas phase and water. The carboxylic substitution in the uracil ring does not alter its relative stability order of the tautomers. The proton affinity of the oxygen atoms and the deprotonation enthalpy of the NH bonds of isoorotic acid have been compared with recent data of uracil. The relative stability of both syn‐ and anti‐conformations was investigated and the syn form was found to be more stable by 17.65 kcal/mol. It was determined in ab initio calculations that an electron can attach to isoorotic acid, forming a stable anion better than uracil. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

Three-dimensional porous frameworks constructed by transition metal ions and isoorotic acid

Four new coordination polymers, [M(Hiso)(H 2O) 3] n (M = Co ( 1); M = Ni ( 2)) and {[M 2(Hiso) 2(bipy) 2(H 2O) 4] · 2(bipy)} n (M = Co ( 3); M = Ni ( 4)) (H 2iso = isoorotic acid, bipy = 4,4′-bipyridine), were synthesized by hydrothermal reactions and characterized by single-crystal X-ray diffraction. The four complexes all comprise 1D chains that are further interlinked via hydrogen bonds, resulting in the formation of 3D frameworks. There are small channels in 1 and 2 and two kinds of larger channels in 3 and 4, in which free bipy molecules residue. In 1 and 2, the Hiso 2− anions act as tridentate ligands to link metal ions; in 3 and 4, the Hiso 2− anions act as bidentate ligands and the metal ions are bridged by bipy.

Vibrational spectra of alkali metal isoorotates

The FTIR and FTRaman spectra were taken for polycrystalline samples of isoorotic acid and its alkali metal salts. For the isoorotic acid the low temperature Ar-matrix IR spectrum was also registered and analysed. Assignment of the selected experimental vibrational bands was supported by the MP2/3-21G ∗∗ calculated vibrational spectra and the potential energy distribution analysis. Influence of type of the alkali metal on the spectra is also discussed.

Rate constants of ozone reactions with DNA, its constituents and related compounds

The rate constants of the reaction of ozone with DNA, its constituents and related compounds have been determined as a function of pH by competition with nitrite and/or buten-3-ol and, when the rate constant was ≤103 dm3 mol−1 s−1, by the indigo method. Depending on the degree of protonation, the rate constant (in units of dm3 mol−1 s−1) varies substantially, e.g. in the case of cytosine, k = 18 (protonated), k = 1.4 × 103 (neutral) and k = 1.5 × 106 (deprotonated). A similar variation has been found with the other nucleobases. Upon deprotonation the mechanism of the ozone reaction may also change; e.g. no singlet dioxygen (O21Δg) is formed in its reaction with 5-chlorouracil, but when the 5-chlorouracilate ion predominates it becomes a major product (∼42%). Rate constants for the neutral compounds are: thymine (4.2 × 104), thymidine (3.0 × 104), 1,3-dimethyluracil (2.8 × 103), uracil (650), 6-methyluracil (140), 5-chlorouracil (4.3 × 103), orotic acid (5.9 × 103), isoorotic acid (3.7 × 103), 2′-deoxycytidine (3.5 × 103), cytidine (3.5 × 103), adenine (12), 2′-deoxyadenosine (14), adenosine (16), guanosine (1.6 × 104), 2′-deoxyguanosine (1.9 × 104) and DNA (410). In the case of adenine and its derivatives, and thus also in the case of DNA, ˙OH is produced (via O2˙− as an intermediate). For the determination of their intrinsic ozone rate constants, tert-butyl alcohol was added as the ˙OH scavenger.

A new potentially useful complex for lithium therapies: dimeric monoaqua lithium isoorotate

The synthesis and X-ray crystal and molecular structures of a new Li(I) complex of stoichiometry [Li(isoor)H 2O] 2, where isoor is the monoanion of 5-carboxyuracil (isoorotic acid), are reported. It crystallizes in the monoclinic P2 1/ n space group with Z=2, and a five-fold bipyramidal coordination around the Li(I) was observed for the first time. The electronic, infrared and Raman spectra of the complex are briefly discussed. Its thermal behavior was investigated by means of thermal gravimetry (TG) and differential thermal analysis (DTA). Dissolution studies were also performed in order to test the pharmacological characteristics of the complex.

Characterization of bis(isoorotato)diaquamagnesium(II) dihydrate: a potentially useful complex for magnesium supplementation

The synthesis and crystal structure of a new Mg(II) complex of stoichiometry [Mg(isoor) 2(H 2O) 2] ·2H 2O, where isoor is the monoanion of 5-carboxyuracil (isoorotic acid), are reported. The structure, solved by single-crystal X-ray diffractometry, shows that it crystallizes in the triclinic space group P(−1) with Z=1. The electronic, IR and Raman spectra of the complex are briefly discussed. Its thermal behavior was also investigated by means of thermal gravimetry (TG) and differential thermal analysis (DTA) measurements in an oxygen atmosphere. Dissolution studies support the usefulness of the compound for magnesium supplementation.

Coordinating properties of isoorotic acid

The complexes [M(H 2isor) 2(H 2O) 2]·H 2O (M = Mn, Co, Ni, Cu, Zn), [M(H 2isor) 2(H 2O) 2] (M = Fe, Cd), and [M(Hisor)(H 2O) 2] (M = Hg,Pd), where H 3isor = isoorotic acid, have been isolated. The complexes were characterized by elemental analyses, conductivity measurements, x-ray powder patterns, thermal methods, magnetic susceptibilities, and spectral (IR and far-IR, Raman, ligand field) studies. Pseudo-octahedral monomeric stereochemistries are assigned for the Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes in the solid state, while [Pd(Hisor)(H 2O) 2] has a square planar structure. The H 2isor − ion behaves as a bidentate chelated O carboxylato, O(4) ligand; the uncoordinated amide group of H 2isor − is present in the lactim (enolic) tautomeric form in the Cu(II) and Cd(II) complexes. Only Pd(II) and Hg(II) promote deprotonation of the monolactim form on coordination and yield 1:1 neutral complexes of the doubly deprotonated ligand; the Hisor 2− ion behaves as a bidentate chelated O carboxylato, O(4) deprotonated enolic ligand.

ChemInform Abstract: PHOTOPHYSICAL PROPERTIES OF THE PYRIMIDINE BASES OROTIC AND ISOOROTIC ACID

Chemischer InformationsdienstVolume 14, Issue 20 Physical Organic Chemistry ChemInform Abstract: PHOTOPHYSICAL PROPERTIES OF THE PYRIMIDINE BASES OROTIC AND ISOOROTIC ACID D. MURRAY, D. MURRAYSearch for more papers by this authorR. S. BECKER, R. S. BECKERSearch for more papers by this author D. MURRAY, D. MURRAYSearch for more papers by this authorR. S. BECKER, R. S. BECKERSearch for more papers by this author First published: May 17, 1983 https://doi.org/10.1002/chin.198320049AboutPDF 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 No abstract is available for this article. Volume14, Issue20May 17, 1983 RelatedInformation

Photochemistry of pyrimidine bases as studied by e.s.r. and spin-trapping.

The direct photoexcitation of pyrimidine bases in D2O solutions yields free radicals which could be conveniently identified by spin-trapping with 2-methyl-2-nitrosopropane. Most of the radicals formed were attributed to D-addition to one end of the 5,6 double bond. However, orotic acid and iso-orotic acid yielded N(3) centred free radicals, formed by homolytic cleavage of the N-H bond. No indication could be found for a free radical involvement in the photocleavage of cyclobutane-type pyrimidine dimers.

Radiation-Chemical Studies of the Reaction of S . O   4 - with Uracil and Its Derivatives

Several radiation-chemical methods have been used to study the reaction of SO/sub 4//sup -/ with uracil, isoorotic acid, and thymine. Pulse radiolysis with spectrophotometric detection has shown that the products in neutral solution absorb well beyond 500 nm and in each case are different from those produced by OH reaction. The spectrum of the radical from uracil has peaks at 410 and 560 nm with calculated extinction coefficients of 1000 and 750 M/sup -1/ cm/sup -1/ respectively. The spectrum obtained with thymine is similar while that obtained with isoorotic acid shows a single peak at 470 nm with an extinction coefficient of 2200 M/sup -1/ cm/sup -1/. Conductometric experiments show that release of a proton accompanies radical formation. The ESR spectra obtained in steady-state radiolysis experiments with uracil and isoorotic acid are characterized by g factors of about 2.0044. These radicals represent the acidic forms of radicals previously observed to be formed by OH in basic solution. The ESR parameters match those found in single crystal experiments for radicals believed to be formed by the net loss of a hydrogen atom from N1. Possible reaction mechanisms are discussed. The reaction of Cl/sub 2//sup -/ with uracil gave the same productmore » as did SO/sub 4//sup -/. Conductometric experiments were also carried out which show that the electron adduct to uracil reacts with S/sub 2/O/sub 8//sup 2 -/ with k = 2.2 x 10/sup 8/ M/sup -1/ sec/sup -1/.« less

2,4-Dioxohexahydropyrimidine derivatives V. 5-Bromo-6-alkoxydihydroorotic acids, amides, and esters

The corresponding 5-bromo-6-alkoxydihydroorotic acid derivatives were obtained by reaction of orotic acid, its methyl ester, and amide with bromine in methanol and ethanol. The reaction of methyl and butyl orotates with methyl and ethyl hypobromites gives 5,5-dibromo-6-alkoxydihydroorotic acid esters. Isoorotic acid reacts with methyl hypobromite to give 5,5-dibromo-6-methoxydihydrouracil.

Electron Spin Resonance Study of Radicals Produced in Irradiated Aqueous Solutions of Uracil and Related Pyrimidines

Radicals produced in irradiated aqueous solutions of uracil, orotic and isoorotic acid, barbituric acid, thymine, and 6-methyluracil have been studied using the in situ radiolysis steady-state ESR method. For each compound different spectra were observed at the different pH values examined. The reaction of OH radicals with the pyrimidine bases was found to take place through addition of the OH to either position 5 or 6 and in most compounds studied both possibilities were observed. Radicals formed by addition of OH to position 5 were found to undergo enolization between C5 and C4 followed by dissociation. Radicals formed by addition of OH to position 6 were found in most cases to undergo rapid ring opening between C6 and N1. The spectra of all the radicals observed changed considerably with pH because of acid-base dissociations. In the case of thymine and 6-methyluracil it was found that at high pH ${\rm O}^{-}$ can abstract hydrogen from the methyl group to form an allyl-type radical. Radicals produced b...

Linear free energy relationships for proton dissociation and metal complexation of pyrimidine acids

Linear free energy relationships for proton dissociation and metal complexation have been investigated for the pyrimidine acid system. Linear correlations are obtained when p K a2 0′ − p K a2′ values for 5-substituted uracil carboxylic acids are plotted against Hammett's substituent constants, σ m. The large calculated ϱ value of 5·78 indicates that the second proton dissociation for this acid series is very sensitive to substituent effects. Calculated “effective” substituent constants ( σ m) for these pyrimidine acids are in reasonable agreement with Hammett's σ m values. With the exception of 5-nitro-orotic acid, a fair linear correlation is obtained in plotting σ m or p K a2′ vs. log K MA for 5-substituted uracil-6-carboxylic (orotic) acid complexes of Ni(II), Co(II), Zn(II) and Cd(II). Abnormally high log K MA values for 5-nitro-orotic acid, as compared with ligand basicity, have been partly attributed to π-electron back-donation by the metal ion to the ligand. In plots of log K ZnA vs. log K M′A, where M′ is Co(II), Ni(II) or Cd(II) and “A” is a 5-substituted orotic acid, linear correlations have been observed with unit slopes. That linear correlations are best observed by comparing structurally similar ligands with identical reaction sites, has been illustrated by plotting log K MA for iso-orotic acid vs. log K MA for 2-ethylthio-iso-orotic acid, or orotic acid. A good linear correlation was observed between iso-orotic acid and 2-ethylthio-iso-orotic acid complexes, but no linear correlation was observed between iso-orotic acid and orotic acid complexes.

Metal complexation with pyrimidine derivatives—II Spectrophotometric studies

Ultra-violet light absorption studies were made on a number of pyrimidine derivatives in water or deuterium oxide both as a function of pH and in the absence or presence of metal ions. The pyrimidine compounds studied included: uracil-5-carboxylic acid (iso-orotic acid), 2-ethylthio-iso-orotic acid, uracil-6-carboxylic acid (orotic acid), 5-nitro-orotic acid and their corresponding esters. Iso-orotic acid was found to be very pH sensitive in water and deuterium oxide. Identical spectral curves were obtained in both solvent systems. A lowering of the extinction coefficient at pH 6, as compared with pH 1, could indicate an ionization effect rather than enolization since no appreciable wavelength shift was observed. However, enolization is predominant in the region of pH 12. A confirmation that p K 2 in iso-orotic acid refers to proton dissociation from an enolic species was obtained by determining the p K 2 of iso-orotic acid in water and in deuterium oxide. In the presence of Cu(II) ions at pH 3, there was noted a slight shift towards the visible in the region of the uracil absorption band of iso-orotic acid. This slight shift is attributed to complexing through the ketonic oxygen and carboxyl group. Very little shift in the uracil lactam band occurred in going from the acidic to neutral region for orotic acid and a slight shift to longer wavelengths resulted when approaching the region of pH 12. Ultra-violet absorption spectra obtained in deuterium oxide indicated that even up to pH 12, orotic acid was still predominantly mono or diketonic. Deuterium iostope studies indicate at least one monoketonic form at pH 10. Spectral curves show that in the presence of Zn(II), Co(II) and Mn(II), orotic acid forms weak complexes. However, in the presence of Cu(II) and Ni(II) ions strong complexing is observed. A deuterium isotope effect was noted with orotic acid and Ni(II) ions in deuterium oxide resulting from the cleavage of the DN 1 bond and verifying complexation through the carboxyl group and nitrogen in the 1-position. The nitro group in 5-nitro-orotic acid appears to considerably modify the lactam-lactim equilibria in the pyrimidine nucleus, favouring enolization in the neutral and high pH regions. It was found that 5-nitro-orotic acid complexes strongly with Cu(II) at pH 6, but is almost independent of Ni(II) ions. The ethylthio group in 2-ethylthio-iso-orotic acid appears to cause enhanced enolization of the carbonyl group in the 4-position. Complexing with Cu(II) ions is quite similar to iso-orotic acid in magnitude.