Two rhodamine derivatives: 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis-(ethylamino)-2,7-dimethylxanthylium chloride monohydrate and 3,6-diamino-9-[2-(methoxycarbonyl)-phenyl]xanthylium chloride trihydrate.

The title compounds, C28H31N2O3(+)-Cl(-)-H2O (common name rhodamine-6g), (I), and C21H17N2O3(+)-Cl(-)-3H2O (common name rhodamine-123), (II), both have planar xanthene skeletons with a formal +1 charge on the amino N atoms delocalized through the pi-electron system so that the N-Csp(2) bond distances indicate significant double-bond character. The substituted planar phenyl groups make angles of 63.29 (8) and 87.96 (11) degrees with the xanthene planes in (I) and (II), respectively. In both molecules, the carbonyl bond vectors point toward the xanthene rings. The ethylamine groups in (I) are oriented similarly with their CH2-CH3 bond vectors pointing nearly perpendicular to the xanthene plane. The chloride ions and water molecules are disordered in both structures. In (I), the chloride ion and water molecule are disordered between two sites. One water and chloride alternately occupy the same site with occupancy factors of 0.5. The other 0.5-chloride and 0.5-water occupy two distinct positions separated by 0.747 (8) A. In (II), the chloride ion is disordered between three sites and one of the waters is disordered about two other sites. Both crystal structures are stabilized by hydrogen bonds involving the chloride ions, amino groups and water molecules, as well as by pi-pi stacking between xanthene planes.

Crystal structure of the hydrated strontium salt of methotrexate: two independent molecules with different conformations.

The crystal and molecular structure of methotrexate has been determined by X-ray diffraction from a highly hydrated triclinic crystal form in which the asymmetric unit contains two independent methotrexate molecules with their glutamate carboxyl groups coordinated to two strontium ions. The two methotrexates exhibit differing conformations: They are almost related to one another by a pseudocenter of symmetry. This places the C(9)-N(10) bond vectors on opposite sides of the planes of the pteridine rings. The 2,4-diaminopteridines form 2-fold symmetry-related hydrogen-bonded dimers as well as hydrogen bonds to benzoyl carbonyl oxygens and lattice water molecules. This structure provides experimental proof of the existence of pteridine conformers through rotation about the C(6)-C(9) bond. Comparison of these conformers with other free and enzyme-bound methotrexate conformations shows them all to be different and illustrates the ability of the molecule to adapt to its chemical environment. The results from this crystal structure determination are experimental proof that methotrexate has not one preferred molecular conformation but may freely rotate about several bonds. They also suggest that the dihydrofolate reductase-bound methotrexate conformation is greatly influenced by the specific binding site environment of the enzyme.

The antifolate trimetrexate: observation of the enzyme-binding conformation.

The crystal structure of the title compound contains four 2, 4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline molecules, two dimethyl sulfoxide molecules and three water molecules in the asymmetric unit, i.e. 4C(19)H(23)N(5)O(3).-2C(2)H(6)OS.3H(2)O. All four quinazoline molecules adopt trans,-gauche conformations. An extensive hydrogen-bond network involving N. N base-pairing interactions, as well as the dimethyl sulfoxide and water molecules, stabilizes the crystal structure.

Ranitidine hydrochloride, a polymorphic crystal form.

In the title compound, dimethyl(¿5-[2-(1-methylamino-2-nitroethenylamino)ethylthiometh yl]-2- furyl¿methyl)ammonium chloride, C(13)H(23)N(4)O(3)S(+).Cl(-), protonation occurs at the dimethylamino N atom. The ranitidine molecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N'-dimethyl-2-nitro-1, 1-ethenediamine system of the molecule. The nitro and methylamino groups are trans across the side chain C=C double bond, while the ethylamino and nitro groups are cis. The Cl(-) ions link molecules through hydrogen bonds.

Bis(2,2-dimethylaziridinyl)phosphinic amide.

The asymmetric unit of the title compound, C8H18N3OP, contains one bis(2,2-dimethylaziridinyl)phosphinic amide molecule. The crystal structure is characterized by hydrogen bonds from the amide-N atom, which involve both H atoms of the amino group, to the phosphinic-O atom in two different molecules, thus forming infinite double-stranded chains along the base vector [100], and by hydrophobic contacts between these chains.

FF-beta-D-arabinofuranosyluracil.

In the title compound, 1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl)-5-fluoropyrimidine-2, 4(1H,3H)-dione, C9H10-F2N2O5, the furanosyl ring adopts the twisted conformation (T) with O1' endo and C1' exo. The crystal structure is characterized by a three-dimensional hydrogen-bond network involving the three H atoms bonded to heteroatoms.

A Schiff base formed from sulfanilic acid and dimethylformamide.

The crystal structure the Schiff base contains one 4-dimethylaminomethyleneaminobenzenesulfonic acid molecule in zwitterionic form [4-(dimethylaminomethyleneammonio)benzenesulfonate], and one water molecule in the asymmetric unit (C9H12N2O3S.H2O). Protonation occurs at nitrogen atom N1, but the charge is delocalized.

Crystal and molecular structure of paclitaxel (taxol).

Paclitaxel (formerly called taxol), an important anticancer drug, inhibits cell replication by binding to and stabilizing microtubule polymers. As drug-receptor interactions are governed by the three-dimensional stereochemistries of both participants, we have determined the crystal structure of paclitaxel to identify its conformational preferences that may be related to biological activity. The monoclinic crystals contain two independent paclitaxel molecules in the asymmetric unit plus several water and dioxane solvent molecules. Taxane ring conformation is very similar in both paclitaxel molecules and is similar to the taxane ring conformation found in the crystal structure of the paclitaxel analogue docetaxel (formerly called taxotere). The two paclitaxel molecules have carbon-13 side-chain conformations that differ from each other and from that of the corresponding side chain in the docetaxel crystal structure. The carbon-13 side-chain conformation of one paclitaxel molecule is similar to what was proposed from NMR studies done in polar solvents, while that of the other paclitaxel molecule is different and hitherto unobserved. The paclitaxel molecules interact with each other and with solvent atoms through an extensive network of hydrogen bonds. Analysis of the hydrogen-bonding network together with structure-activity studies may suggest which atoms of paclitaxel are important for binding to microtubule receptors.

Glucosidase inhibitors: structures of deoxynojirimycin and castanospermine.

High-resolution structures of the glucosidase inhibitors deoxynojirimycin (dNM) and castanospermine (CAST) have been determined by X-ray diffraction. The crystal parameters are a = 10.751(3) and 8.788(3) A, b = 9.263(3) and 8.172(3) A, c = 7.719(2) and 6.507(2) A, and space group P2(1)2(1)2(1) and P2(1) for dNM and CAST, respectively. (beta = 105.44(8) degrees for CAST.) The absolute configuration of CAST has also been established. Stereochemical comparisons with natural glucosidase substrates such as maltose and methyl glucoside show great similarities in the positioning of functional groups, and indicate the basis for enzyme inhibition. Conformational comparison between dNM and CAST suggests the greater activity of CAST may be due to the fixed axial positioning of the O6 atom; the results have implications for the design of analogues for potential anti-HIV and other antiviral therapies.

Structure of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine and electronic charge calculations for 3'-deoxythymidines.

The crystal and molecular structures of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine have been determined by x-ray diffraction and stereochemical comparisons with thymidine have been made. Atomic charge distributions have been calculated by the complete neglect of differential overlap method for thymidine and antiretrovirally active and inactive C3'-substituted analogues. The structural and electronic results suggest that antiviral activity in these analogues may be correlated with the presence of an electronegative atom attached to C3'.

Azidothymidine: crystal structure and possible functional role of the azido group.

The crystal and molecular structures of the anti-acquired immunodeficiency syndrome agent 3'-azido-3'-deoxythymidine (AZT) have been determined by x-ray diffraction. There are two crystallographically independent AZT molecules in the crystal asymmetric unit; they have similar conformations and differ primarily in the glycosyl torsion angle. Comparisons with a hydrated thymidylate structure indicate that the azido group does not significantly affect the gross conformational preference of the molecule. The comparisons also suggest possible functional roles for the azido group in enzyme binding.

Crystal structure of an extended-conformation leucine-enkephalin dimer monohydrate.

The structure of a new crystal form of leucine-enkephalin has been determined by X-ray diffraction. There are two independent molecules in the asymmetric unit and both have extended peptide backbone conformations with side-chains arranged alternately above and below the backbone planes. The two pentapeptides are hydrogen-bonded to each other and to other molecules forming an extended antiparallel beta-pleated sheet. The structure differs from that in similar crystals of methionine enkephalin primarily in side-chain orientations and inter-sheet interactions.

Crystal structure of quinespar, a quinazoline analogue of methotrexate.

The molecular structure of quinespar, a quinazoline analogue of methotrexate and aminopterin, has been determined by X-ray crystallography. The molecule displays an extended conformation with the p-aminobenzoyl plane rotated 66 degrees from the plane of the quinazoline. The orientation of the quinazoline ring relative to the rest of the molecule is intermediate between the orientations of the comparable pteridine rings in folic acid and in DHFR-bound methotrexate. Evidence is presented to suggest that 2,4-diaminoquinazolines bind to DHFR in the same manner as do 2,4-diaminopteridines.

Crystal structure of methionine-enkephalin.

The crystal structure of methionine-enkephalin has been determined by X-ray crystallography. There are two independent pentapeptides in the asymmetric unit and both display extended backbone conformations with their side chains arranged alternately below and above the backbone plane. The two molecules form a hydrogen-bonded head-to-tail dimer similar in conformation to one dimeric pair of leucine-enkephalin molecules in a previously reported crystal structure.

Crystal structure of leucine-enkephalin.

The crystal structure of leucine-enkephalin has been determined in a crystal form that has four independent enkephalin molecules and much water and dimethylformamide solvent in the asymmetric unit. All four enkephalins have extended peptide backbones with the Tyr, Phe and Leu side chains above and below the plane of the backbone. There is evidence that this extended conformation may provide an acceptable model for enkephalin binding to opiate mu-receptors.

Hydrogen bonding interaction of diphenylhydantoin and 9-ethyladenine.

A hydrogen-bonded complex of diphenylhydantoin (DPH) and 9-ethyladenine (EtAd) crystallizes from 2,4-pentanedione with the asymmetrical unit consisting of two DPH molecules, one EtAd molecule, and one solvent molecule. The crystal structure was solved by direct methods and refined to a residual of R = 0.054. Structure determination reveals that one DPH hydrogen-bonds to EtAd in a Watson-Crick scheme while the second DPH N(3)--H bonds to EtAd N(3) to form a 2:1 DPH-EtAd complex. Comparisons are made with barbiturate-adenine complexes and with an earlier postulation of a 1:1 DPH-EtAd complex derived from NMR and IR data. The 2,4-pentanedione molecule adopts the keto-enol configuration with an asymmetrical intramolecular hydrogen bond.

Folic acid: crystal structure and implications for enzyme binding.

The crystal and molecular structure of folic acid dihydrate has been determined by x-ray diffraction. Folic acid is in an extended conformation with the pteridine ring in the keto form. The C(4) oxygen and N(10) atoms are on the same side of the molecule, hydrogen-bonded to the same water. This conformation has the pteridine rotated approximately 180 degrees away from the orientation of the pteridine ring of methotrexate bound to dihydrofolate reductase. The folic acid pteridine and phenyl rings interact in a stacking manner which is suggestive of the type of associations these groups could form in a complex of folate, dihydrofolate reductase, and reduced nicotinamide adenine dinucleotide phosphate.