Crystal and electronic structure of a fluorescent columnar liquid crystalline electron transport material.

A very favorable LUMO energy for cathodic electron injection is found in the crystalline state of the mesogenic red fluorescent perylene derivative 1. It is one of the rare cases where the columnar crystal structure of such a compound could be established directly by X-ray investigation.

Release of the cyano moiety in the crystal structure of N-cyanomethyl-N-(2-methoxyethyl)-daunomycin complexed with d(CGATCG).

Doxorubicin is among the most widely used anthracycline in cancer chemotherapy. In an attempt to avoid the cardiotoxicity and drug resistance of doxorubicin therapy, several analogues were synthesized. The cyanomorpholinyl derivative is the most cytotoxic. They differ greatly from their parent compound in their biological and pharmacological properties, inducing cross-links in drug DNA complexes. The present study concerns N-cyanomethyl-N-(2-methoxyethyl)-daunomycin (CMDa), a synthetic analogue of cyanomorpholino-daunomycin. Compared to doxorubicin, CMDa displays a cytotoxic activity on L1210 leukemia cells at higher concentration but is effective on doxorubicin resistant cells. The results of fluorescence quenching experiments as well as the melting temperature (DeltaTm = 7.5 degrees C) studies are consistent with a drug molecule which intercalates between the DNA base pairs and stabilizes the DNA double helix. The crystal structure of CMDa complexed to the hexanucleotide d(CGATCG) has been determined at 1.5 A resolution. The complex crystallizes in the space group P41212 and is similar to other anthracycline-hexanucleotide complexes. In the crystal state, the observed densities indicate the formation of N-hydroxymethyl-N-(2-methoxyethyl)-daunomycin (HMDa) with the release of the cyano moiety without DNA alkylation. The formation of this degradation compound is discussed in relation with other drug modifications when binding to DNA. Comparison with two other drug-DNA crystal structures suggests a correlation between a slight change in DNA conformation and the nature of the amino sugar substituents at the N3' position located in the minor groove.

A crystallographic study of haem binding to ferritin.

Ferritin, the iron-storage protein, binds porphyrins, metalloporphyrins and the fluorescent dyes ANS (8-anilino-1-naphthalenesulfonic acid) and TNS (2-p-toluidinyl-6-naphthalenesulfonic acid), similarly to apo-myoglobin. Octahedral crystals of horse-spleen apo-ferritin (HSF; 174 amino acids) complexes prepared by the addition of haem, hematoporphyrin or Sn-protoporphyrin IX to a solution of apo-ferritin crystallize in space group F432 with cell parameter a = 184.0 A. X-ray crystallographic analysis of single crystals prepared from a mixture containing haem or Sn-protoporphyrin IX shows that the haem-binding sites in these crystals are occupied by protoporphyrin IX, which is free of metal, rather than by the original metalloporphyrin. The present paper describes the structure of horse-spleen apo-ferritin cocrystallized with Sn-protoporphyrin IX. The 6797 reflections up to 2.6 A resolution used in the refinement were obtained from a data set recorded on a Nicolet/Xentronics area detector with Cu Kalpha radiation from a Rigaku RU 200 rotating anode. The final structure comprises 1613 non-H atoms, two Cd atoms and 170 solvent molecules. Four residues are described as disordered. The root-mean-square deviations from ideal bond lengths and angles are 0.013 A and 2.88 degrees, respectively. Protoporphyrins are observed in special positions on the twofold axes of the ferritin molecule with a stoichiometry of 0.4 per subunit.

Orthorhombic crystal structure of the A-DNA octamer d(GTACGTAC). Comparison with the tetragonal structure.

The X-ray crystal structure of the double-helical A-DNA octanucleotide d(GTACGTAC) has been solved by molecular replacement and refined to a resolution of 0.219 nm. The final R-factor is equal to 16.1% for 1516 observed reflections with F > 4 sigma(F). The sequence crystallizes as an A-DNA-type double helix in the orthorhombic space group P2(1)2(1)2, with one duplex molecule solvated by 66 water molecules in the asymmetric unit. Cell parameters are a = 3.860 nm, b = 5.082 nm, c = 2.174 nm. It is the first time that such a crystal form has been observed. This orthorhombic structure has been compared with the tetragonal structure of the same oligonucleotide. It adopts a bent structure with an unusual packing between symmetry-related molecules.

Monoclinic uncomplexed double-stranded, antiparallel, left-handed beta 5.6-helix (increases decreases beta 5.6) structure of gramicidin A: alternate patterns of helical association and deformation.

A comparison of the monoclinic and orthorhombic crystal structures of the uncomplexed double-stranded, antiparallel, left-handed beta-helix (5.6 amino acid residues per turn) (increases decreases beta 5.6) conformers of gramicidin A reveals marked differences in the tryptophan side-chain orientations and the degree of helical uniformity of the dimer and in the manner in which these helical dimers associate with one another in the crystal. The helix of the orthorhombic dimer exhibits a regular pattern of bulges and constrictions that appears to be induced by crystal packing forces affecting tryptophan side chains that are aligned parallel to the helix axis. The monoclinic dimer is more uniform than the orthorhombic dimer as a consequence of pi stacking interactions between dimers in which orientation of tryptophan side chains is normal to the helix axis to relieve the lateral crystal packing forces that may locally twist and deform the helix. It may be inferred from these observations that lipid interactions may be expected to destabilize the increases decreases beta 5.6 helix when it is inserted into a membrane bilayer.

Structure of an antitumour drug: 9-hydroxy-2,5,11-trimethyl-6H-pyridol[4,3-b]-carbazolium acetate (9-hydroxy-2-methylellipticinium acetate; Celiptium) dihydrate.

C18H17N2O. C2H3O2. 2H3O, Mr = 336.2, monoclinic, C2/c, alpha = 21.789 (2), b = 12.853 (1), c = 14.004 (2) A, beta = 114.80 (1) degree, V = 3560.2 A3, Z = 8, Dm = 1.24, Dx = 1.255 Mg m3, lambda (Cu K alpha) = 1.54178 A, mu = 0.754 mm-1, F(000) = 1584, T = 298 K, R = 0.052 for 2236 observed reflections. Antitumor drug. The crystal structure involves the packing of resonant rings held together by a network of hydrogen bonds involving hydroxyl groups, acetate ions and water molecules. The main feature is the two stacking patterns found together in the crystal structure; this feature appears to differ from other derivatives.

Nucleic acid intercalating drug. The structure of 9-hydroxy-2,5,11- tetramethylpyrido[4,3-b]carbazolium (9-hydroxy-2,6- dimethylellipticinium) chloride monohydrate.

C19H19N2O.Cl. H2O, Mr = 344.6, triclinic, P1, alpha = 12.980 (1), b = 9.454 (2), c = 7.148 (1) A, alpha = 75.23 (2), beta = 99.73 (3), gamma = 91.83 (2) degree, V = 835.9 A3, Z = 2, Dm = 1.35 (2), Dx = 1.369 Mg m-3, lambda (Cu Ka) = 1.54178 A, mu = 2.11 mm-1, F(000) = 364, T 298 k, R 0.059 for 2767 observed reflections. Antitumour drug that displays one of the highest DNA affinities (4 x 10(6) M 1) among ellipticine derivatives. The structure analysis confirms the intercalation hypothesis. There is stacking of centrosymmetrically related parallel molecules along c, alternately spaced by 3.43 and 3.48 A. The crystal structure confirms the desolvation effect of the sixth nitrogen position.

A DNA-intercalating compound derived from 7H-pyridocarbazole: the structure of 10-methoxy-2-methyl-7H-pyrido[4,3-c]carbazolium iodide.

C17H15N2O+.I-, Mr = 390.22, monoclinic, P21/c, a = 10.017 (2), b = 8.123 (5), c = 19.074 (4) A, beta = 95.86 (2) degrees, V = 1544 (2) A3, Z = 4, D chi = 1.67 g cm-3, mu = 2.10 cm-1, lambda (Mo K alpha) = 0.7107 A, F(000) = 768, R = 0.04 for 1236 unique reflections measured at 295 K. Dimensions of the ring system are similar to those found in 6H-pyridocarbazole analogues (ellipticine derivatives). The iodine ion and pyridocarbazolium system are linked by a hydrogen bond. The planar 7H-pyridocarbazole cations form stacks approximately parallel to b. Interactions between stacks occur by weak van der Waals forces.

[Structure of a psoralen-thymine photoproduct: model for the interaction with DNA on the pyrone ring of psoralen]. / Structure d'un photoproduit psoralène-thymine: modèle pour l'interactio avec l'ADN sur le cycle pyrone du psoraléne.

Photoadduct 4-ethoxypsoralen-thymine (4a-methyl-11,1-epoxyethanofuro [3'',2'',:6',7']chromeno-[2',3':1,2]cyclobutal[4,3-d]pyrimid in e-2,4, 5-trione), C18-H14N2O6, Mr = 354.1, monoclinic, P21/c, a = 9.021 (3), b = 11.504 (1), c = 16.397 (3) A, beta = 110.45 (1) degrees, V = 1594.4 A 3, Z = 4, Dm = 1.46, D chi = 1.475 Mg m-3, lambda (Mo K alpha) = 0.71069 A, mu = 0.072 mm-1, F(000) = 736, T = 298 K, R = 0.032 for 1442 observed reflections. This original structure of an intramolecular photoproduct obtained photochemically gives structural information about the cycloaddition of the thymine base on the pyrone ring of the psoralen. The crystal structure displays deformations of the planes of the two rings which form a dihedral angle of 40.5 degrees and a cis-anti conformation relative to the cyclobutane bridging component.