NUCLEIC-ACID BINDING DRUGS .2. PROFLAVINE FREE BASE

C13HIIN3.H20 , orthorhombic, Cmc21, a= 14.493 (8), b= 14.675 (8), c= 5.772 (5) A, Din= 1.29 (1), De= 1.298 g cm -3 for Z=4. Equi-inclination Weissenberg intensities, scanned with an automatic densitometer. The structure, solved by direct methods, was refined to R 0.0928 and Rw 0.0910 for 418 reflexions. The ring system is slightly non-planar, and the crystal structure is characterized by a lack of interplanar stacking

NUCLEIC-ACID BINDING-DRUGS .6. THE STRUCTURE OF 3,9-DIAMINO-7-ETHOXYACRIDINE (RIVANOL) AS THE LACTATE MONOHYDRATE SALT

C15H16N3 O+ • C3H50~-. H20, M r = 361.4, triclinic, Pi, with a = 7.912 (2), b = 10.016 (1), c = 12.246 (3)/k, = 107.75 (1),/~ = 103.08 (2), y = 94.47 (2) °, U = 888.9 ,/k 3, Z = 2, D m = 1.35 (2), D c = 1.350 Mg m -3, F(000) = 380, 2(Cu Ka) = 1.5418/~, /t = 0.836 mm -~. 3542 reflections were measured, of which 2149 had significant intensity. The structure refined to an R of 0.063 after having been solved by reciprocal-space search methods. The molecular geometry reflects the 3,9-diamino substitution of the planar acridine ring, in terms of bond distances. The crystal structure is extensively hydrogen-bonded with interactions involving anions, acridine substituents and water molecules

9-CHLOROACRIDINE

C~3HsNC1, orthorhombic, P212~2 ~, a = 6.850 (3), b = 11.662 (5), c = 12.705 (5) A, O m = 1.40 (1), D c = 1.393 g cm -3 for Z = 4. Equi-inclination Weissenberg intensities, scanned with an automatic densitometer. The structure, solved by direct methods, refined to R 0.0577 and R w 0.0649 for 1653 reflexions. The crystal structure is characterized by partial stacking of the chromophores, these are slightly non-planar

STRUCTURE OF BENZ[A]ANTHRACENE-7,12-DIONE

C18H1002, monoclinic, C2/c, a = 10.918 (1), b = 11.369(1), c = 19.850(1)A, /~= 97.224(7) ° , U = 2444.4 A 3, Z = 8, D,n = 1.41 (2), D c = 1.403 Mg m -3, F(000) = 1072, 2(CuKa) = 1.5418/~, ~t = 0.742 mm -1. 2253 reflections were measured, of which 1039 had significant intensities. Refinement converged to a final R of 0.045. The molecule is approximately planar. Ring C is significantly non-delocalized. Bonds C(3)-C(4) and C(5)-C(6) are short, and indicate pronounced olefinic character for these bonds

CRYSTAL-STRUCTURE OF AN ORTHORHOMBIC FORM OF ADENOSINE-5'-MONOPHOSPHATE

Adenosine-Y-phosphate monohydrate was crystallized in the orthorhombic space group P212121, with a=22"997 (2), b=9.406 (1), c=6.599 (1)A,, Z=4. The structure was solved by direct methods and refined to a final Rw of 0.0639 for 1320 significant reflexions measured on an automatic diffractometer. The conformation of the molecule differs significantly from that previously reported for the monoclinic monohydrate [Kraut & Jensen, Acta Cryst. (1963), 16, 79-88]. The sugar conformation, for example, is here C(2)'-endo, and the glycosidic torsion angle has altered by almost 50 °

X-RAY STRUCTURAL STUDIES ON 3 ANALOGS OF THE ALPHA-ANOMER OF THE ANTITUMOR ANTIBIOTIC SHOWDOMYCIN - DIFFERENTIAL RING-PUCKERING EFFECTS OF HYDROXYL SUGAR SUBSTITUENTS IN LYXO AND ARABINO CONFIGURATIONS

The crystal structures of three a-analogues of the anititumour antibiotic showdomycin (1) have been determined at room temperature. They are 2-(a-D-2'- deoxyribofuranosyl)maleimide (2), 2-(a-D-arabinofuranosyl) maleimide (3) and 2-(a-D-lyxofuranosyl)- maleimide (4). The structures were refined to R factors of 0-039, 0-042 and 0-029 for 971, 1025 and 716 observed reflections. The conformational properties of the sugar rings are discussed in detail, in relation to the differing hydroxyl group substitutions. Compounds (2) and (3) have CY-endo, C4"-exo and CY-endo ring puckers, whereas (3) has C2"-endo, C l'-exo puckers. Compound (3) has an intramolecular hydrogen bond between the 05' and 02' hydroxyl groups. This and the sugar pucker difference are in accord with NMR chemical shift data for the O5' and O2' protons. Crystal data: compound (2), C9H11NOs, orthorhombic, P212~21, a = 5-916 (1), b = 8-191 (1), c = 19.691 (3) A, Z = 4; compound (3), C9HIINO6, orthorhombic, P212121, a = 6.785 (1), b = 8.006 (1), c = 17.564 (2) A, Z= 4; compound (4), C9HI1NO6, monoclinic, P2~, a = 8.681 (1), b = 5.135 (1), c= 11-364 (1) A, Z= 2

THE STRUCTURE OF THE RIBODINUCLEOSIDE MONOPHOSPHATE GUANYLYL-3',5'-CYTIDINE AS ITS AMMONIUM OCTAHYDRATE SALT

The crystal and molecular structure of an ammonium octahydrate salt of the ribodinucleoside monophos-phate guanylyl-3',5'-cytidine (CIgH24NsOI2P) has been determined by X-ray methods, and refined to a final R of 0.111 for 1197 observed reflections. The salt crystallizes in space group C2 with cell dimensions a -- 20.987 (6), b = 16.470 (4), c = 9.566 (1) fit and fl = 94.36 (2)°; Z = 4 for a calculated density of 1.50 Mg m -3 and #(Cu Ka) = 1.19 mm -1. The unit-cell dimensions are very similar to those of the sodium salt [Rosenberg, Seeman, Day & Rich (1976). J. Mol. Biol. 104, 145-167]; however, the two structures are non-isomorphous. Conformational features of the ammonium salt are as expected for an RNA-like Watson-Crick base-paired duplex

CRYSTAL AND MOLECULAR-STRUCTURE OF 2',3',5'-TRI-O-ACETYL-6-O-(MESITYLENESULPHONYL)GUANOSINE

The structure of a 6-O-mesitylenesulphonyl derivative of 2',3',5'-tri-O-acetylguanosine, C 24 H 29 N50 10 S, has been determined by X-ray diffraction. Crystals are monoclinic, a = 26.370 (4), b = 8.200 (2), c = 17.991 (3) A, fl = 132.77 (4) o. The solution of the structure in space group C2 was not straightforward and is described in detail. Refinement converged at R = 0.110 for 1102 observed reflections. The guanine base displays some deviations from its usual geometry due to the loss of C(6)-O(6) double-bond character. The ribose sugar is C(2')-endo puckered

Inhibition of the hypoxia-inducible factor pathway by a G-quadruplex binding small molecule.

The hypoxia-inducible transcription factor (HIF) co-ordinates the response of tumours to low oxygen by stimulating genes involved in metabolism and angiogenesis. HIF pathway activation is associated with decreased progression-free survival and increased mortality; compounds that target this pathway are potential agents for the treatment of a range of solid tumour malignancies. Renal cancers are likely to be particularly sensitive to inhibition of the HIF pathway since ~80% show constitutive activation of HIF. We have previously described the di-substituted naphthalene derivative, CL67, which binds to a G-quadruplex higher-order structure in the HIF promoter sequence in vitro. We show here that CL67 blocks HIF expression leading to inhibition of HIF-transactivation and down-regulation of downstream target genes and proteins in renal carcinoma cell lines and in a mouse xenograft model of renal cancer. This inhibition is independent of pathways that control HIF abundance through oxygen-dependant degradation and oxygen dependant HIF sub-unit expression

Diffraction in low-energy electron scattering from DNA: bridging gas phase and solid state theory

Using high-quality gas phase electron scattering calculations and multiple scattering theory, we attempt to gain insights on the radiation damage to DNA induced by secondary low-energy electrons in the condensed phase, and to bridge the existing gap with the gas phase theory and experiments. The origin of different resonant features (arising from single molecules or diffraction) is discussed and the calculations are compared to existing experiments in thin films.Comment: 40 pages preprint, 12 figures, submitted to J. Chem. Phy