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.     

Four cocrystals of thymine with phenolic coformers: influence of the coformer on hydrogen bonding

Cocrystals are molecular solids composed of at least two types of neutral chemical species held together by noncovalent forces. Crystallization of thymine [systematic name: 5‐methylpyrimidine‐2,4(1H,3H)‐dione] with four phenolic coformers resulted in cocrystal formation, viz. catechol (benzene‐1,2‐diol) giving thymine–catechol (1/1), C₅H₆N₂O₂·C₆H₆O₂, (I), resorcinol (benzene‐1,3‐diol) giving thymine–resorcinol (2/1), 2C₅H₆N₂O₂·C₆H₆O₂, (II), hydroquinone (benzene‐1,4‐diol) giving thymine–hydroquinone (2/1), 2C₅H₆N₂O₂·C₆H₆O₂, (III), and pyrogallol (benzene‐1,2,3‐triol) giving thymine–pyrogallol (1/2), C₅H₆N₂O₂·2C₆H₆O₃, (IV). The resorcinol molecule in (II) occupies a twofold axis, while the hydroquinone molecule in (III) is situated on a centre of inversion. Thymine–thymine base pairing is common across all four structures, albeit with different patterns. In (I)–(III), the base pair is propagated into an infinite one‐dimensional ribbon, whereas it exists as a discrete dimeric unit in (IV). In (I)–(III), the two donor N atoms and one carbonyl acceptor O atom of thymine are involved in thymine–thymine base pairing and the remaining carbonyl O atom is hydrogen bonded to the coformer. In contrast, in (IV), just one donor N atom and one acceptor O atom are involved in base pairing, and the remaining donor N atom and acceptor O atom of thymine form hydrogen bonds to the coformer molecules. Thus, the utilization of the donor and acceptor atoms of thymine in the hydrogen bonding is influenced by the coformers.     

Supra­molecular motifs in 1‐(2‐cyano­ethyl)thymine and 1‐(3‐cyano­propyl)­thymine

In both 1‐(2‐cyano­ethyl)thymine [systematic name: 3‐(5‐methyl‐2,4‐dioxo‐1,2,3,4‐tetra­hydro­pyrimidin‐1‐yl)propane­nitrile], C₈H₉N₃O₂, (I), and 1‐(3‐cyano­propyl)thymine [systematic name: 4‐(5‐methyl‐2,4‐dioxo‐1,2,3,4‐tetra­hydro­pyrimidin‐1‐yl)butane­nitrile], C₉H₁₁N₃O₂, (II), the core of the supra­molecular structure is formed by centrosymmetric dimers generated by N—H⋯O hydrogen bonds. Further weak hydrogen bonds of C—H⋯O and C—H⋯N types generate mol­ecular tapes and sheets that resemble those in uracil and its methyl derivatives. The steric hindrance that arises from the cyano­alkyl substituents perturbs the conformations of the tapes and sheets.     

Dissociation Pathway Analysis of Thymine under Low Energy VUV Photon Excitation

Photon-induced dissociation pathways of thymine are investigated with vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. The photoionization mass spectra of thymine at different photon energy are measured and presented. By selecting suitable photon energy, exclusively molecular ion m/z=126 is obtained. At photon energy of 12.0 eV, the major ionic fragments at m/z=98, 97, 84, 83, 70, and 55 are obtained, which are assigned to C₄H₆N₂₄O⁺、C₄H₅N₂O⁺、C₃H₄N₂O⁺(or C₄H₆NO⁺)、C₄H₅NO⁺、C₂NO₂⁺ and C₃H₅N⁺, respectively. With help of theoretical calculations, the detailed dissociation pathways of thymine at low energy are well established.     

Eight new crystal structures of 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil: insights into the hydrogen‐bonded networks and the predominant conformations of the C5‐bound residues

In order to examine the preferred hydrogen‐bonding pattern of various uracil derivatives, namely 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil, and for a conformational study, crystallization experiments yielded eight different structures: 5‐(hydroxymethyl)uracil, C₅H₆N₂O₃, (I), 5‐carboxyuracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₄·C₃H₇NO, (II), 5‐carboxyuracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₄·C₂H₆OS, (III), 5‐carboxyuracil–N,N‐dimethylacetamide (1/1), C₅H₄N₂O₄·C₄H₉NO, (IV), 5‐carboxy‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₃S·C₃H₇NO, (V), 5‐carboxy‐2‐thiouracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₃S·C₂H₆OS, (VI), 5‐carboxy‐2‐thiouracil–1,4‐dioxane (2/3), 2C₅H₄N₂O₃S·3C₆H₁₂O₃, (VII), and 5‐carboxy‐2‐thiouracil, C₁₀H₈N₄O₆S₂, (VIII). While the six solvated structures, i.e. (II)–(VII), contain intramolecular S(6) O—H…O hydrogen‐bond motifs between the carboxy and carbonyl groups, the usually favoured R₂²(8) pattern between two carboxy groups is formed in the solvent‐free structure, i.e. (VIII). Further R₂²(8) hydrogen‐bond motifs involving either two N—H…O or two N—H…S hydrogen bonds were observed in three crystal structures, namely (I), (IV) and (VIII). In all eight structures, the residue at the ring 5‐position shows a coplanar arrangement with respect to the pyrimidine ring which is in agreement with a search of the Cambridge Structural Database for six‐membered cyclic compounds containing a carboxy group. The search confirmed that coplanarity between the carboxy group and the cyclic residue is strongly favoured.     

4‐Vinyl­benzyl analogs of adenine and uracil: reactive monomers for nucleobase polymeric resins

The crystal structures of 9‐(4‐vinyl­benzyl)­adenine, C₁₄H₁₃N₅, and 1‐(4‐vinyl­benzyl)­uracil, C₁₃H₁₂N₂O₂, are composed of zigzag ribbon‐like structures that are stabilized by conventional (N—H?N‐type) hydrogen bonds for the former and conventional (N—H?O‐type) and non‐conventional (C—H?O‐type) hydrogen bonds for the latter; the hydrogen‐bonding patterns are represented by graph‐sets R(9) and R(8), respectively. The adenine and uracil moieties in these alkyl­ated derivatives are planar and are inclined at angles of 84.44 (4) and 79.07 (7)°, respectively, with respect to the phenyl rings.     

Insight into the Mechanism of the Initial Reaction of an OH Radical with DNA/RNA Nucleobases: A Computational Investigation of Radiation Damage

Earlier theoretical investigations of the mechanism of radiation damage to DNA/RNA nucleobases have claimed OH radical addition as the dominating pathway based solely on energetics. In this study we supplement calculations of energies with the kinetics of all possible reactions with the OH radical through hydrogen abstraction and OH radical addition onto carbon sites, using DFT at the ωB97X‐D/6‐311++G(2df,2pd) level with the Eckart tunneling correction. The overall rate constants for the reaction with adenine, guanine, thymine, and uracil are found to be 2.17×10^?12, 5.64×10^?11, 2.01×10^?11, and 5.03×10^?12 cm³ molecules^?1 s^?1, respectively, which agree exceptionally well with experimental values. We conclude that abstraction of the amine group hydrogen atoms competes with addition onto C₈ as the most important reaction pathway for the purine nucleobases, while for the pyrimidine nucleobases addition onto C₅ and C₆ competes with the abstraction of H₁. Thymine shows favourability against abstraction of methyl hydrogens as the dominating pathway based on rate constants. These mechanistic conclusions are partly explained by an analysis of the electrostatic potential together with HOMO and LUMO orbitals of the nucleobases.     

Synthesis and structures of substituted triphenyl(phenylimino)phosphoranes

Three substituted triphenyl(phenylimino)phosphoranes, namely (4‐cyanophenylimino)triphenylphosphorane, C₂₅H₁₉N₂P, (I), (4‐nitrophenylimino)triphenylphosphorane, C₂₄H₁₉N₂O₂P, (II), and (3‐nitrophenylimino)triphenylphosphorane, C₂₄H₁₉N₂O₂P, (III), were synthesized as precursors for the preparation of substituted diphenylcarbodiimides. All three compounds display a supramolecular arrangement in which the substituted benzene rings are organized in an antiparallel fashion. The nitro group on the ring participates in C—H...O and O...π interactions, forming intermolecular dimers. Compound (III) shows disorder which involves the rotation of one of the phenyl rings of the triphenylphosphine group.     

Covalent‐assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4‐tert‐butylbenzoic acid with isoniazid and its derivatized forms

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4‐tert‐butylbenzoic acid via a one‐pot covalent and supramolecular synthesis, namely 4‐tert‐butylbenzoic acid–isoniazid, C₆H₇N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(propan‐2‐ylidene)isonicotinohydrazide, C₉H₁₁N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(butan‐2‐ylidene)isonicotinohydrazide, C₁₀H₁₃N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(diphenylmethylidene)isonicotinohydrazide, C₁₉H₁₅N₃O·C₁₁H₁₄O₂, and 4‐tert‐butylbenzoic acid–N′‐(4‐hydroxy‐4‐methylpentan‐2‐ylidene)isonicotinohydrazide, C₁₂H₁₇N₃O₂·C₁₁H₁₄O₂. The co‐former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan‐2‐one, butan‐2‐one, benzophenone and 3‐hydroxy‐3‐methylbutan‐2‐one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen‐bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.     

Red,orange and yellow crystals of 4,5‐­bis(4‐methoxy­phenyl)‐2‐(3‐nitro­phenyl)‐1H‐imidazole

Red non‐solvate crystals of the title compound from ethanol, C₂₃H₁₉N₃O₄, orange solvate crystals from tert‐butanol, C₂₃H₁₉N₃O₄·C₄H₁₀O, yellow solvate crystals from dioxane–water, C₂₃H₁₉N₃O₄·0.5C₄H₈O₂, and intense yellow solvate crystals from benzene–N,N′‐dimethylformamide, C₂₃H₁₉N₃O₄·C₆H₆, differ from each other in their molecular conformation and hydrogen‐bonding scheme. The bathochromic shifts of the crystal color are explained by the molecular planarity and charge‐transfer effect among the imidazole mol­ecules.     

Synthesis and biological evaluation of novel indoleamide derivatives as antioxidative and antitumor agents

Novel indole amide derivatives C1-C10 were successfully synthesized and characterized by ¹H NMR, ¹³C NMR, IR, MS, and elemental analysis, and their molecular formulas were C₁₄H₁₀N₆O, C₁₃H₁₀N₄O, C₁₆H₁₃N₃O₂, C₁₉H₁₄N₂O₂, C₁₆H₁₁N₃OS, C₁₅H₁₃N₃O, C₁₂H₉N₅O, C₁₆H₁₀ClN₃OS, C₁₅H₁₇N₃O₂, and C₁₃H₁₄N₂O₃, respectively. The primary biological activities of these compounds were evaluated in vitro by the DPPH assay, H₂O₂-induced oxidative stress injury assay, and cytotoxicity assay. The results indicated that compounds C1, C2, C4, C7, and C9 exhibited DPPH·scavenging ability, while C3, C4, C5, and C8 showed potent growth-inhibitory activities against various human tumor cells, including MDA-MB-231, Hela, A549, and HT29. Interestingly, compound C4 showed potent scavenging effects on the DPPH radical and possessed protective effect on H₂O₂-induced oxidative stress injury in human neuroblastoma SH-SY5Y cells at low concentrations; however, C4 exhibited significant toxicity against four human tumor cells at a higher concentration in all treatments, and the range of IC₅₀ value was 7.91 to 13.35 μM.     

Synthon preference in a hydrated β‐resorcylic acid structure and its cocrystal with thymine

Multicomponent crystals or cocrystals play a significant role in crystal engineering, the main objective of which is to understand the role of intermolecular interactions and to utilize such understanding in the design of novel crystal structures. Molecules possessing carboxylic acid and amide functional groups are good candidates for forming cocrystals. β‐Resorcylic acid monohydrate, C₇H₆O₄·H₂O, (I), crystallizes in the triclinic space group P with one β‐resorcylic acid molecule and one water molecule in the asymmetric unit. The cocrystal thymine–β‐resorcylic acid–water (1/1/1), C₅H₆N₂O₂·C₇H₆O₄·H₂O, (II), crystallizes in the orthorhombic space group Pca2₁, with one molecule each of thymine, β‐resorcylic acid and water in the asymmetric unit. All available donor and acceptor atoms in (I) and (II) are utilized for hydrogen bonding. The acid and amide functional groups are well known for the formation of self‐complementary acid–acid and amide–amide homosynthons. In (I), an acid–acid homosynthon is observed, while in (II), an amide–acid heterosynthon is present. In (I), the β‐resorcylic acid molecule exhibits the expected intramolecular S(6) motif between the hydroxy and carbonyl O atoms, and an intermolecular R₂²(8) dimer motif between the carboxylic acid groups; only the former motif is observed in (II). The water solvent molecule in (I) propagates the discrete dimers into two‐dimensional hydrogen‐bonded sheets. In (II), thymine and β‐resorcylic acid molecules do not form self‐complementary amide–amide and acid–acid homosynthons; instead, a thymine–β‐resorcylic acid heterosynthon is observed. With the help of the water molecule, this heterosynthon is aggregated into a three‐dimensional hydrogen‐bonded network. The absence of thymine base pairing in (II) might be linked to the availability of additional functional groups and the preference of the donor and acceptor hydrogen‐bond combinations.     

{2,6‐Bis­[(di­methyl­amino)­methyl]pyridine‐κ3N}(2,2‐methyl­enediphenolato‐κ2O,O′)­dioxouranium(VI) acetone solvate

In the title compound, [UO₂(C₁₃H₁₀O₂)(C₁₁H₁₉N₃)]·C₃H₆O, the U atom is in a pentagonal–bipyramidal environment, with the three N atoms of the 2,6‐bis­[(di­methyl­amino)­methyl]­pyridine ligand and the two O atoms of the dianionic 2,2′‐methyl­ene­diphenolate ligand in the equatorial plane. The geometry is compared with that of previously reported 1:2 uranyl–diphenoxide complexes.     

The crystal and molecular structure of 6-oxadihydrouracil

The crystal and molecular structure of 6-oxadihydrouracil (C₃H₄N₂O₃) has been determined by single crystal x-ray diffraction techniques. The compound crystallizes in the space group P2₁ 2₁ 2₁ with four molecules in a unit cell of dimensions: a = 5.106(1)Å, b = 12.461(2)Å and c = 7.112(1)Å. The structure was solved by direct methods and refined to a final value of R = 0.052. The oxauracil ring is non-planar with the C5 atom assuming tetrahedral geometry and the ring oxygen having oxazinal distances and angle (C-O = 1.43₂Å, N-O = 1.40₈Å, and CON angle of 109.0°). The usual hydrogen bonding patterns associated with the uracil ring are absent in this compound.     

Self‐Assembly and Structure of Cobalt(II) Complexes Using Diaminodiamide Ligands

The self‐assembly of Co(II) with two diaminodiamide ligands, 4,7‐diazadecanediamide and 4,8‐diazaundecanediamide, gave two different crystals, [(C₈H₁₈N₄O₂)Co(OH)₂Co(C₈H₁₈N₄O₂)]Cl₂ ( 1 ) [Co(C₉H₂₀N₄O₂)(Cl)(H₂O)]·Cl·2H₂O ( 2 ). Structures of 1 and 2 were characterized by single‐crystal X‐ray diffraction analysis. Structural data for 1 shows a novel type of binuclear complex with distorted octahederal coordination geometry around the Co atoms through the hydroxo bridges. By using inter‐connector N‐H···N hydrogen bonding interactions as building forces, each cationic moiety [(C₈H₁₈N₄O₂)Co(OH)₂Co(C₈H₁₈N₄O₂)]²⁺ is linked to neighboring ones, producing a charged hydrogen‐bonded 1D chain‐like structure. The chains are further connected into a 2D layer in a (4,4)‐topology via N‐H···Cl_free hydrogen‐bonding interactions. Structural data for 2 indicate that the cobalt atom adopts a six‐coordinated N₂O₄ environment, giving a distorted octahedral geometry, where two N‐ and two O‐donor sets of ligand located at equatorial positions and one water and one chloride occupied at axial positions. Through NH···Cl‐Co and OH···Cl‐Co contacts, each cationic moiety [Co(C₉H₂₀N₄O₂)(Cl)(H₂O)]⁺ in 2 is linked to neighboring ones, producing a charged hydrogen‐bonded 1D chainlike structure. Thus, the crystal‐engineering approach has proved successful in the solid‐state packing due to steric strain effect of the diaminodiamide ligand.     

Ethylenediammonium bis{bis[N‐(2‐aminoethyl)glycinato‐κ3N,N′,O]chromium(III)} tetrachloride dihydrate at 293 and 100 K

The crystal structure of the title compound, (C₂H₁₀N₂)[Cr(C₄H₉N₂O₂)₂]₂Cl₄·2H₂O, has been determined by single‐crystal X‐ray diffraction studies at 293 and 100 K. The analyses demonstrated that the crystal consists of ethyl­enedi­ammonium dications (which lie about inversion centres), bis­[N‐(2‐amino­ethyl)­glycin­ato]­chromium(III) monocations, Cl^? anions and hydrate water mol­ecules, in a molecular ratio of 1:2:4:2. The complex cation unit has a slightly distorted octahedrally coordinated Cr atom, with two Cr—O and four Cr—N bonds in the ranges 1.951 (1)–1.953 (1) and 2.054 (1)–2.089 (2) Å, respectively, at 293 K. The geometry of the bis­[N‐(2‐amino­ethyl)­glycinato]­chromium(III) moiety was found to be trans,cis,cis with respect to the carboxyl­ate O atom and the primary and secondary amine N atoms. The two analyses, at 293 and 100 K, exhibited no remarkable structural differences, although the colour of the crystals did differ, being red at 293 K and orange at 100 K.     

Molecular orbital theory of the hydrogen bond. 25. Water–uracil complexes in excited n → π states

Hydrogen bonding of uracil with water in excited n → π* states has been investigated by means of ab initio SCF -CI calculations on uracil and water–uracil complexes. Two low-energy excited states arise from n → π* transitions in uracil. The first is due to excitation of the C₄? O group, while the second is associated with excitation of the C₂? O group. In the first n → π* state, hydrogen bonds at O₄ are broken, so that the open water–uracil dimer at O₄ dissociates. The “wobble” dimer, in which a water molecule is essentially free to move between its position in an open structure at N₃? H and a cyclic structure at N₃? H and O₄ in the ground state, collapses to a different “wobble” dimer at N₃? H and O₂ in the excited state. The third dimer, a “wobble” dimer at N₁? H and O₂, remains intact, but is destabilized relative to the ground state. Although hydrogen bonds at O₂ are broken in the second n → π* state, the three water–uracil dimers remain bound. The “wobble” dimer at N₁? H and O₂ changes to an excited open dimer at N₁? H. The “wobble” dimer at N₃? H and O₄ remains intact, and the open dimer at O₄ is further stabilized upon excitation. Dimer blue shifts of n → π* bands are nearly additive in 2:1 and 3:1 water:uracil structures. The fates of the three 2:1 water:uracil trimers and the 3:1 water:uracil tetramer in the first and second n → π* states are determined by the fates of the corresponding excited dimers in these states.     

The pentacoordinated [Cr(CO)5]2− dianion in [2,2,2‐crypt‐K]2[Cr(CO)5] ethylenediamine monosolvate

Bis[(4,7,13,16,21,24‐hexaoxa‐1,10‐diazabicyclo[8.8.8]hexacosane)potassium(+)] pentacarbonylchromate(2−) ethylenediamine monosolvate, [K(C₁₈H₃₆N₂O₆)]₂[Cr(CO)₅]·C₂H₈N₂, was obtained from the reaction between K₃Cd₂Sb₂ and Cr(CO)₆ in ethylenediamine in the presence of the macrocyclic 2,2,2‐crypt ligand. The structure provides the first crystallographic characterization of the pentacoordinated [Cr(CO)₅]²⁻ dianion. The central Cr^III atom is coordinated by five carbonyl ligands in a distorted trigonal–bipyramidal geometry. The distribution of the Cr—C bond lengths indicates a greater degree of back bonding from Cr^III to the equatorial carbonyl ligands compared with the axial carbonyl ligands.     

Synthesis and molecular structure of Cr(salen)(μ‐N)RhCl(COD): the first example of a heterobimetallic nitride‐bridged complex containing chromium

Five‐coordinate Cr(N)(salen) {salen is 2,2′‐[ethane‐1,2‐diylbis(nitrilomethylidyne)]diphenolate} reacts with [RhCl(COD)]₂ (COD is 1,5‐cyclooctadiene) to yield the heterobimetallic nitride‐bridged title compound, namely chlorido‐2κCl‐[2(η⁴)‐1,5‐cyclooctadiene]{2,2′‐[ethane‐1,2‐diylbis(nitrilomethylidyne)]diphenolato‐1κ⁴O,N,N′,O′}‐μ‐nitrido‐1:2κ²N:N‐chromium(V)rhodium(I), [CrRh(C₁₆H₁₄N₂O₂)ClN(C₈H₁₂)]. The Cr—N bond of 1.5936 (14) Å is elongated by only 0.035 Å compared to the terminal Cr—N bond in the precursor. The nitride bridge is close to being linear [173.03 (9)°] and the Rh—N bond of 1.9594 (14) Å is very short for a monodentate nitrogen‐donor ligand, indicating significant π‐acceptor character of the Cr[triple‐bond]N group.     

Solid‐state transformation of 4,2′‐an­hydro‐5‐(β‐d‐arabino­furan­osyl)­uracil dihydrate to 4,2′‐an­hydro‐5‐(β‐d‐arabino­furan­osyl)­uracil mono­hydrate

Crystals of 4,2′‐an­hydro‐5‐(β‐d ‐arabino­furan­osyl)­uracil, (I), obtained from an aqueous solution, were characterized as the dihydrate, C₉H₁₀N₂O₅·2H₂O, (Ia). In air, these crystals slowly transform to the mono­hydrate, C₉H₁₀N₂O₅·H₂O, (Ib), but remain crystalline. The solid‐state transformation proceeds with the loss of one water mol­ecule and a rearrangement of hydrogen‐bonded layers of mol­ecules. The furan­ose ring in (I) has an approximate C4′‐exo,O4′‐endo twist conformation. The central five‐membered ring is slightly puckered. The uracil group is planar within experimental uncertainty.