Radical formation in salts of pyrimidines III. Cytosine . H2O cyrstals.

The radicals produced by X-irradiation at 77 K and at 300 K in cytosine monohydrate crystals have been analysed by electron-spin-resonance (e.s.r.) spectroscopy. Three radicals have been identified at 77 K: the anion radical and the cation radical of the cytosine molecule, together with the radical resutling from H-abstraction from the nitrogen N1. Irradiation at 300 K produces radicals resulting from H-adition at three different positions of the cytosine molecule. These are the C5-addition radical, the C6-addition radical, and the O2-addition radical. The results are compared with those found previously by other authors.     

Radical formation in salts of pyrimidines. I. 1-methyluracil. HBr crystals.

Radicals produced by X-irradiation at 77 K of 1-methyluracil. HBr crystals have been analysed by electron spin resonance spectroscopy. The results are compared with those obtained on 1-methyluracil crystals. Four radicals have been identified, two of which are present only in 1-methyluracil. HBr crystals: the C6-addition radical and the pyrimidine--anion radical. Warming-up experiments have been performed in order to study the secondary radical reactions. The different mechanisms proposed for the radiolysis of DNA constituents in the solid state are discussed in connection with these findings.     

Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine, and the disodium salt of 5'-inosine-monophosphate.

Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine and Na2-5'-IMP.(7.5 H2O) by X-irradiation has been studied using electron-spin-resonance spectroscopy at 9.5 and 35 GHz. In all crystals both H-addition radicals at position C2 and C8 of the purine ring are found. The coupling constants of these two radicals are different and depend strongly on the protonation state of the base. INDO-calculations indicate that the C8-radical is protonated at O6. In Na2-5'-IMP OH-addition radicals at position C2 of the purine ring are formed. Electron adduct radicals are found in the neutral and the N7-protonated base after X-irradiation at 77 K. In Na2-5'-IMP no electron adduct is formed but a radical which probably is the cation. In hypoxanthine.HCl.H2O a radical could be observed after X-irradiation at 77 K, which results from addition of a Cl- to the nitrogen N1.     

Radical formation in salts of pyrimidines. II. Cytosine. HCl crystals.

Radicals produced by X-irradiation at 77 K and at 300 K of cytosine. HCl crystals have been analysed by electron spin resonance spectroscopy. Four radicals have been identified: the anion radical of the cytosine molecule, the radical resulting from H-addition at position C6, the radical resulting from H-addition at position O2, and finally a radical resulting from addition of a Cl- to nitrogen N3. Hückel molecular orbital calculations are presented, which support the hypothesis according to which in unsaturated pyrimidines the site of hydrogenation or protonation depends on the state of the molecule.     

A C5'-centred deoxyribose radical in single crystals of 5-chloro-and 5-bromodeoxyuridine X-irradiated at low temperatures.

X-irradiation at 77 K and subsequent warming to 150 K of single crystals of 5-chloro-and 5-bromodeoxyuridine produces a radical located at position C5' of the deoxyribose moiety. The radical exhibits identical spectral properties in both crystal systems. It is characterized by interaction of the unpaired electron with an alpha-proton(-17-0, -8-7, -33-7G), a beta-proton (18-6, 21-3, 17-5 G) as well as an OH-proton (4-8, 7-9, 12-8 G). The principal values of the g-tensor are 2-0034, 2-0049 and 2-0042. The spectral parameters are discussed in relation to those of the same or similar radicals in other nucleosides (-tides).     

5-Nitrouridine-monohydrate: crystal structure and conformation.

The crystal structure of 5-nitrouridine was determined by X-ray analysis. The pyrimidine ring is slightly non-planar, showing a shallow boat conformation. The nitro group has no influence on the C4 - O4 bond length as compared to uridine. The ribose shows the C3'-endo conformation and the base is in the anti orientation to the sugar with a torsion angle of 25.6 degrees. This conformation is stabilized by a hydrogen bond from the base to the ribosyl moiety (H6 ... 05'). Stacking interactions between neighboring bases are almost negligible in the crystal. A water molecule is involved in a bifurcated donating hydrogen bond to 04 and to 052 of the nitro group of the one base and an accepting bond from the H3 of the other base. Two more hydrogen bonds are formed between the water molecule and the ribose. The structural aspects of 5-nitrouridine are discussed with respect to the special stacking features found for 5-nitro-1-(beta-D-ribosyluronic acid)-uracil monohydrate in the crystal (1).     

Study on temperature-dependent changes in hydrogen bonds in cellulose Ibeta by infrared spectroscopy with perturbation-correlation moving-window two-dimensional correlation spectroscopy

Infrared (IR) spectra were measured for cellulose Ibeta prepared from the mantle of Halocynthia roretzi over a temperature range of 30-260 degrees C to explore the temperature-dependent changes in hydrogen bonds (H-bonds) in the crystal. Structural changes at the phase transition temperature of 220 degrees C are elucidated at the functional group level by perturbation-correlation moving-window two-dimensional (PCMW2D) correlation spectroscopy. The PCMW2D correlation spectra show that the intensities of bands arising from O3-H3...O5 and O2-H2...O6 intrachain H-bonds dramatically decrease at 220 degrees C, whereas the intensity changes of bands due to interchain H-bonds are not observed adequately. These results suggest that the phase transition is induced by the dissociation of the O3-H3...O5 and O2-H2...O6 intrachain H-bonds. However, the interchain H-bonds are not so much responsible for the transition directly.     

O6-ethylguanine carcinogenic lesions in DNA: an NMR study of O6etG.C pairing in dodecanucleotide duplexes

The pairing of O6etG with C located four base pairs in from either end of the self-complementary d(C1-G2-C3-O6etG4-A5-G6-C7-T8-C9-G10-C11-G12) duplex (designated O6etG.C 12-mer) has been investigated from an analysis of proton and phosphorus two-dimensional NMR experiments. The structural consequences of increasing the alkyl group size were elucidated from a comparative study of the pairing of O6meG4 with C9 in a related sequence (designated O6meG.C 12-mer). The NMR parameters for both O6alkG-containing dodecanucleotides are also compared with those of the control sequence containing G4.C9 base pairs (designated G.C 12-mer). The NOE cross-peaks detected in the two-dimensional NOESY spectra of the O6alkG.C 12-mer duplexes in H2O solution establish that the O6etG4/O6meG4 and C9 bases at the lesion site stack into the helix between the flanking C3.G10 and A5.T8 Watson-Crick base pairs. The amino protons of C9 at the O6alkG4-C9 lesion site resonate as an average resonance at 7.78 and 7.63 ppm in the O6etG.C 12-mer and O6meG.C 12-mer duplexes, respectively. The observed NOEs between the amino protons of C9 and the CH3 protons of O6alkG4 establish a syn orientation of the O6-alkyl group with respect to the N1 of alkylated guanine. A wobble alignment of the O6alkG4.C9 base pair stablized by two hydrogen bonds, one between the amino group of C9 and N1 of O6alkG and the other between the amino group of O6alkG and N3 of C9, is tentatively proposed on the basis of the NOEs between the amino protons of C9 at the lesion site and the imino protons of flanking Watson-Crick base pairs. The proton and phosphorus chemical shift differences between the O6etG.C 12-mer and O6meG.C 12-mer duplexes are small compared to the differences between these O6alkG-containing duplexes and the control G.C 12-mer duplex.     

Radiation damage in solid 5-halouracils: free radicals in single crystals of 5-fluorouracil

X-irradiation at 300 K of single crystals of 5-fluorouracil results in the formation of two different radical species observable by e.s.r. and ENDOR-spectroscopy. One is an alpha-fluoro radical RCF(CH2)R' formed by saturation of the 5,6-double bond of the pyrimidine ring. The principal values of its alpha-fluorine interaction are 170, -9 and -18 G; the isotropic part of the methylene beta-proton couplings are 46.3 and 28 G, respectively; the g-tensor has principal values of 2.0029, 2.0066, and 2.0052. The other radical species is formed by enolization of the C4-carbonyl function. The resulting spin-density distribution gives rise to three observable interactions, an alpha-proton (-5.2, -14.9, -11.2 G) at C6, an OH-proton from the C4--OH group (-1.7, -5.0, -4.1 G) and a residual alpha-fluorine interaction (0,0,11.2G). Irradiation at 77 K yields an e.s.r.-pattern which is tentatively assigned to the molecular anion radical. These findings are related to the radiation chemistry of solid 5-halouracils.     

E.s.r. of free radicals in irradiated uracil-beta-D-arabinofuranoside.

Electron-spin-resonance measurements have been made on single crystals of uracil-beta-D-arabinofuranoside, which were irradiated by 4-0 MeV electrons at 77 K. At low temperatures, two radicals have been identified, one attributed to a hydrogen abstraction from 05' in the sugar moiety and the other to a radical anion located on the pyrimidine ring. The former is very unstable and seems to act as a precursor to other unidentified radical species stable at 77K. At room temperature, the main resonance is due to hydrogen addition to C5 and is probably produced by protonation of the anion. This same radical is also produced by X-irradiation at room temperature.     

Molecular structure of cyclo[-(D-Val-L-Hyi-L-Val-D-Hyi)2-] revealed by x-ray analysis.

The crystal structure of a synthetic analogue of valinomycin, cyclo[-(D-Val-L-Hyi-L-Val-D-Hyi)2-] (octa-meso-valinomycin) (I) (C40H68N4O12.1.5.C4H8O2, M(r) = 937.01 + 88.10), has been determined. Crystals grown from dioxane are monoclinic, space group P2(1)/a, with cell parameters a = 21.487 (8), b = 16.836 (5), c = 16.089 (4) A, beta = 111.70 (4), and Z = 4. The atomic coordinates for nonhydrogen atoms were refined in the anisotropic thermal motion approximation. H atom positions were included in the structure factor calculations at their geometrically expected positions. Values of the standard and weighted R factors after refinement are 0.11 and 0.13, respectively. The conformation of the depsipeptide crystallized from dioxane is different from that crystallized from chloroform (II). The molecule adopts a rectangular shape with two type IV beta-turns containing a hydrogen bond and possesses pseudorotational symmetry. The side chains are located on the molecular periphery. The orientation of the carbonyl groups of the molecule is not conducive for efficient metal-ion coordination and in the observed conformation cannot behave as an ionophore. In the crystal the molecules form infinite chains parallel to the c axis, and are stabilized by two intermolecular hydrogen bonds that are shorter and have better geometry than the intramolecular hydrogen bonds. A phi/psi plot for dodecadepsipeptides with a (DLLD)3 sequence has well-defined areas for Val and Hyi residues only in cases when the crystals have been grown from nonpolar or medium-polar solvents. The phi/psi plot for octadepsipeptides crystallized from chloroform (II) shows this behavior also.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new crystal form of beta-cyclodextrin-ethanol inclusion complex: channel-type structure without long guest molecules

A new crystal form of beta-cyclodextrin (beta-CD)[bond]ethanol[bond]dodecahydrate inclusion complex [(C(6)H(10)O(5))(7).0.3C(2)H(5)OH.12H(2)O] belongs to monoclinic space group C2 (form II) with unit cell constants a=19.292(1), b=24.691(1), c=15.884(1) A, beta=109.35(1) degrees. The beta-CD macrocycle is more circular than that of the complex in space group P2(1) [form I: J. Am. Chem. Soc. 113 (1991) 5676]. In form II, a disordered ethanol molecule (occupancy 0.3) is placed in the upper part of beta-CD cavity (above the O-4 plane) and is sustained by hydrogen bonding to water site W-2. In form I, an ethanol molecule located below the O-4-plane is well ordered because it hydrogen bonds to surrounding O-3[bond]H, O-6[bond]H groups of the symmetry-related beta-CD molecules. In the crystal lattice of form I, beta-CD macrocycles are stacked in a typical herringbone cage structure. By contrast, the packing structure of form II is a head-to-head channel that is stabilized at both O-2/O-3 and O-6 sides of each beta-CD by direct O(CD)...O(CD) and indirect O(CD)...O(W)...(O(W))...O(CD) hydrogen bonds. The 12 water molecules are disordered in 18 positions both inside the channel-like cavity of beta-CD dimer (W-1[bond]W-6) and in the interstices between the beta-CD macrocycles (W-7[bond]W-18). The latter forms a cluster that is hydrogen bonded together and to the neighboring beta-CD O[bond]H groups.     

Radiation-induced free radicals in solid 5-halouracil derivatives: single crystals of 5-iododeoxyuridine

X-irradiation of single crystals of 5-iododeoxyuridine (IUdR) in the temperature range 8-300 K produces mainly four different radicals which have been studied by electron spin resonance (e.s.r.) and electron nuclear double resonance (ENDOR)-spectroscopy. At low temperatures, a pi-anion is formed which shows predominantly an interaction of the unpaired electron with a proton at carbon C6 of the base (-11.8 G, -23.9 G, -4.6 G). Above 10-20 K, the anion protonates at C6 to yield a RC-I(CH2)-R' radical comprising alpha-iodo and beta-methylene proton hyperfine interactions. The primary oxidation product is an O5'-situated alkoxy radical RCH2O which shows inequivalent beta-proton couplings of about 100 G and 35 G together with a highly anisotropic g-tensor. Upon warming to 265 K, a C2'-located radical on the deoxyribose is formed which is stable at room temperature. A detailed account of its spectral features as obtained by ENDOR exhibits three different alpha-type couplings, two small beta-protons and a dipolar interaction. Other radicals, not reproducibly observed, involve a C5'-hydroxyalkyl radical and a species related to the base cation at low temperatures.     

Absolute configuration of Rp-uridine 3'',5''-cyclic phosphorothioate.

Triethylammonium uridine-3',5'-cyclic phosphorothioate crystallizes in space group P2(1)2(1)2(1), a = 7.177(1), b = 13.155(6), c = 21.114(7) A, C15H26N3O7PS, MW 423.4, Z = 4, dx = 1.41g/cm3. The crystal structure was solved by direct methods on the basis of 1493 counter X-ray diffraction data (CuK alpha) and refined to R = 5.1%. The configuration of the thiophosphate group is Rp; conformational parameters are: glycosyl torsion angle anti, -151.9(5) degrees, sugar pucker C(3')-endo with P = 27.3 degrees, vmax = 45.5 degrees, six-membered cycle in chair form. The bond distances in the non-esterified P-S and P-O suggest that the negative charge is distributed between the groups. As illustrated in this and other studies, P-O has a much higher affinity for hydrogen bonds than P-S, indicated here by interactions with triethyl-ammonium N-H and O(2')-H as donors. One additional hydrogen bond N(3)-H---0(4) ties the bases which form a ribbon-like structure. 0(2) and S are not engaged in hydrogen bonds. The triethylammonium ion is two-fold disordered.     

The structure and antiviral activity of ribavirin analogs. I. Molecular and crystal structure of 1-(2-hydroxyethoxymethyl)-1,2,4-triazole-5-carboxamide

The crystal and molecular structures of the antiviral compound 1-(2-hydroxyethoxymethyl)-1,2,4-triazole-5-carboxamide has been determined by the X-ray diffraction method. The space group is P2i/c, unit cell parameters a = 4,381, b = 18,679, c = 10,776 A, beta = 107,40 degrees, Z = 4. The structure was solved by the direct method and refined by a full-matrix least-squares procedure to R = 4.9%. Two planar groups of atoms can be distinguished in the molecule. The first group involves the atoms of triazole ring, C6, and C1', the second one contains C5, C6, O6 and N6 atoms. The angle between these planes is 5.6 degrees. The carboxyamide group is rotated by 180 degrees in comparison with this group in ribavirin. That is why the intramolecular hydrogen bond C1'-H1'. 1...O6 can form. Torsion angle O5'-C5'-C4'-O4' is 73.9 degrees and it corresponds to gauche-rotamer. The conformation about O4'-C4' bond is trans. The C1'-C4' bond is approximately perpendicular to the aglycone.     

Conformation and hydrogen bonding of N-formylpeptides: crystal and molecular structure of N-formyl-L-alanyl-L-aspartic acid.

Crystals of N-formyl-L-alanyl-L-aspartic acid (C8H11N2O6) grown from aqueous methanol solution are orthorhombic, space group, P2(1)2(1)2(1) with cell parameters at 294K of a = 13.619(2), b = 8.567(2), c = 9.583(3)A, V = 1118.1A3, M.W. = 232.2, Z = 4, Dm = 1.38 g/cm3 and Dx = 1.378 g/cm3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.075 for 1244 reflections with I greater than or equal to 3 sigma collected on a CAD-4 diffractometer. The structure contains two short intermolecular hydrogen bonds: (i) between the C-terminal carboxyl OH and the N-acyl oxygen (2.624(3)A), a characteristic feature found in many N-acyl peptides and (ii) between the aspartic carboxyl OH. and the peptide oxygen OP1 (2.623(3)A). The peptide is nonplanar (omega = 165.5(6) degrees). The molecule takes up a folded conformation in contrast to N-formyl peptides which form extended beta-sheets; the values of phi 1, psi 1, phi 2, psi 2(1), and psi 2(2) are, respectively -65.7(6), 152.0(5), -107.2(5), 30.9(5), and -150.3(6). The aspartic acid side chain conformation is g- with chi 1 = 73.1(5). The formyl group, as expected, is transplanar [OF-CF-N1-CA1 = -4.0(8) degrees]. The presence of the short O-H ... O hydrogen bond emerges as a structural feature common to this peptide and several other N-formyl peptides. There are no C-H ... O hydrogen bonds in this structure.     

Crystal structure of beta-D-psicopyranose

Here, we report the crystal structure of d-psicose, C(6)H(12)O(6), one of the rare sugars. The compound crystallizes as the beta-anomer with rarely observed in pyranose carbohydrate structures trans-gauche orientation of the hydroxymethyl group relative to the pyranosyl ring. The crystal system is orthorhombic, space group P2(1)2(1)2(1), Z=4, with cell dimensions a=7.727(2), b=8.672(2), c=11.123(3)A, V=745.3(3)A(3). The pyranosyl ring adopts chair (2)C(5) conformation. The crystal structure at 100(2)K is stabilized by three-dimensional network of O-Hcdots, three dots, centeredO and C-Hcdots, three dots, centeredO intermolecular hydrogen bonds.     

Crystal structure of cholesteryl decanoate.

Cholesteryl decanoate (C37H64O2) is monoclinic, space group P2I, with cell dimensions a = 12.931 (6), b = 9.066 (2), c = 30.22 (1) A, beta = 91.14 (4) degrees, and Z = 4. The atomic coordinates from cholesteryl laurate were used in an initial trial structure which was refined by block diagonal least-squares methods with 1846 observed X-ray reflections (R = 0.129). Molecules A and B have almost fully extended conformations, except at the ester bonds and towards the end of the decanoate B chain. The molecules are arranged in antiparallel array forming monolayers of thickness d001 = 30.22 A, with the molecular long axis making an angle of about 67 degrees with the layer interface. The crystal structure is very similar to that of cholesteryl nonanoate and cholesteryl laurate.     

Structural studies of O6-methyldeoxyguanosine and related compounds: a promutagenic DNA lesion by methylating carcinogens.

O6-Methylation of guanine residues in DNA can induce mutations by formation of base mispairing due to the deprotonation of N(1). The electronic, geometric and conformational properties of three N(9)-Substituted O6-methylguanine derivatives, O6-methyldeoxyguanosine (O6mdGuo), O6-methylguanosine (O6mGuo) and O6, 9-dimethylguanine (O6mdGua), were investigated by X-ray and/or NMR studies. O6mdGuo crystallizes in the monoclinic space group P2(1) with cell parameters a = 5.267(1), b = 19.109(2), c = 12.330(2) A, beta = 92.45(1) degrees, V = 1239.8(3) A3, z = 4 (two nucleosides per asymmetric unit), and O6mGua in the monoclinic space group P2(1)/n with cell parameters a = 10.729(2), b = 7.640(1) c = 10.216(1) A, beta = 92.17(2) degrees, V = 836.7(2) A3, z = 4. The geometry and conformation of O6-methylguanine moieties observed in both crystals and are very similar. Furthermore, the molecular dimensions of the O6methylguanine residue resemble more closely those of adenine than those of guanine. The methoxy group is coplanar with the purine ring, the methyl group being cis to N(1). The conformation of O6-methylguanine nucleosides is variable. The glycosidic conformation of O6mdGuo is anti for molecule (a) and high-anti for molecule (b) in the crystal, while that of O6mGuo is syn [Parthasarathy, R & Fridey, S. M. (1986) Carcinogenesis 7, 221-227]. The sugar ring pucker of O6mdGuo is C(2')-endo for molecule (a) and C(1')-exo for molecule (b). The C(4')-C(5') exocyclic bond conformation in O6mdGuo is gauche- for molecule (a) but trans for molecule (b), in contrast with gauche+ for O6mGuo. The hydrogen bonds exhibited by O6-methylguanine derivatives differ from those in guanine derivatives; the amino N(2) and ring N(3) and N(7) atoms of O6-methylguanine residues are involved in hydrogen bonding. 1H-NMR data for O6mdGuo and O6mdGuo reveal the predominance of a C(2')-endo type sugar puckering. In O6mdGuo, however, a contribution of a C(1')-exo sugar puckering is significant. The NOE data also indicate that O6mdGuo molecules exist with nearly equal population for anti (including high anti) and syn glycosidic conformations. These observations and their biological implications are discussed.