John J. Stezowski

The crystal structure of uncomplexed-hydrated cyclooctaamylose

Abstract Cyclooctaamylose crystallizes from aqueous solution with space-group symmetry P21 and lattice parameters: a = 20.253(8), b = 10.494(5), c = 16.892(6) A and β = 105.32(1)o, Z = 2; the apparent formular per asymmetric unit is C48H80O40·17H2O. The macrocycle is in an open conformation but displays significant deviations from ideal eight fold molecular symmetry. Of the 19 water molecules thus far located, four of which have occupancy factors of one half, 12 may be characterized as being in the torus of the cycloamylose.

Structure, Phase Diagram and Fluorescence Spectra of 2,3-Dimethylnaphthalene (Anthracene) Mixed Crystals

Abstract An X-ray crystal structure determination for 2,3-dimethylnaphthalene (2,3-DMN) at 300 K was carried out. The two noncentrosymmetric molecules in the unit cell, space group P21/a, (a = 7.916(10) A, b = 6.052(8) A, c = 10.017(8) A, β = 105.43(1)°) are statistically dipolarly disordered. Perfect cleavage along (001) is examined in terms of the disordered structure. There are two phase transitions, one of higher order from monoclinic to triclinic, occuring at ∼ 210K, and another one at ∼ 100K. The phase diagram of 2,3-DMN/anthracene exhibits a peritectic at 377.4K (104.2°C) with continuous mixed crystal formation from 0 to ∼ 23% anthracene (confirmed by X-ray Guinier technique). From normal freezing experiments a concentration-dependent distribution coefficient k of anthracene (A) in 2,3-DMN is derived with k(cA → 0) = 2.16. Packing of the mixed crystals is analyzed in terms of lattice geometry and packing coefficients. Liq. He fluorescence and absorption spectra of anthracene in 2,3-DMN display a fa...

Crystal and molecular structure of a 2,6-tetradeca-O-methyl-β-cyclodextrin–adamantanol 1 : 1 inclusion complex

The first crystal structure to be determined for an inclusion complex in which a chemically modified cyclodextrin serves as the host reveals a host molecular parent molecule but provides an extended toroidal region in which larger hydrophobic substrate molecules can be accommodated.

Overcrowded twisted bi-4H-cyclopenta[def]-phenanthren-4-ylidene versus bi-9H-fluorenylidene, syn pyramidalization

A crystal structure determination for bi-4H-cyclopenta[def]-phenanthren-4-ylidene, 1, reveals a molecular conformation rather like that reported earlier for bifluorenylidene,2. However, unexpectedly, the twist angle about the ethylenic linkage is substantially smaller in1 (average values are 30.8 and 40.7°, respectively). Comparison of bonding geometry, combined with the results of molecular mechanics calculations for1, demonstrates that syn pyramidalization can play an important role in determining a stable conformation for overcrowded, twisted aromatic enes. The average out-of-plane bending angles for the ethylenic carbon atoms of1 and2 are 8.6 and 4.4°, respectively.

Diastereoselective synthesis of ribofuranosyl glycines

Abstract The diastereoselective synthesis of β-C-ribofuranosyl glycines by condensation of ribofuranoses and phosphoryl glycinesters1 in a one-pot procedure is described.

Theoretical studies of the benzene oxide—oxepin valence tautomerism

We have calculated the geometry and energy of the valence tautomers benzene oxide and oxepin using the semiempirical AM1 model and the 6–31G and 6–31G* basis sets utilizing full geometry optimization. In the oxide the folding angleα, the angle between the epoxide ring and the adjacent plane containing four carbon atoms, is about 106°. The carbon skeleton is almost planar, the folding angleβ, the angle between the two four-carbon atom planes being about 175°. In contrast, oxepin is found to have a marked boat-shaped structure with the correspondingα andβ angles about 137° and 159°, respectively. The AM1, 6–31G, and 6–31G* calculations give −11.4, −10.8, and −2.9 kcal mol−1 for the energy change that accompanies the valence tautomerism, oxide-oxepin, compared to an experimental value of about +0.3 kcal mol−1. Single point calculations of the energies at the 6–31 G* geometry using Møller-Plesset perturbation theory to second order (MP2/6–31 G*) and third order (MP3/6–31G*) give ΔET=+3.3 and +0.8 kcal mol−1. The values for the energy change in the transfer of epoxide oxygen from ethylene oxide to benzene using AM1, 6–31G, and 6–31G* are in good agreement, viz., +31.1, +34.5, and +33.6 kcal mol−1, respectively. A large positive energy change is to be expected in view of the loss of benzene aromaticity.

The conformation of cyclo[l-pro-l-leu-l-val-(gly)thz-(gly)thz], a dolastatin 3 analog, in the crystalline and solution states

Abstract Cyclo[L-Pro-L-Leu-L-Val-(gly)Thz-(gly)Thz], (1), has been prepared in high yield using pentafluorophenol in the ring closure reaction. This dolastatin 3 analog has been subjected to crystal structure analysis (space-group P65, a = b = 34.897(9), c = 24.611(10)A, asymmetric unit contents:(C26H35N7O5S2)4·(C7H8)7·(CH30H)4, ϱcalc = 1.202gcm-3.) and solution (CDCl3 and DMSO-d6) studies using 1H- and 13C-NMR techniques. The molecule has been found to adopt a clearly preferred conformation both in the crystal and in solution. The conformation contains a cis (gly)Thz-Pro peptide bond and two intramolecular hydrogen bonds, one from Leu-NH to a thiazole endocyclic nitrogen atom and the other from a (gly)Thz-NH to the Leu-C=O. The results of this study not only demonstrate that the conformation of (1) is very similar in the crystal and solution, but also provide conclusive evidence that the conformation proposed by Bernier, et al 4. earlier is incorrect. The crystal packing demonstrates that (1) is a very hydrophobic cyclopeptide with a tendency to self associate. In the crystal (1) associates via systematic hydrogen bonding to form a network of interlocking hydrophobic tubes filled with toluene molecules. The solvent molecules migrate out of the crystals on exposure to air resulting in fragmentation.

Co-ordination-assisted inclusion of neutral molecules by the racemic 9,9′-spirobifluorene-2,2′-dicarboxylic acid host lattice. X-Ray crystal structure of the dimethylformamide clathrate at 170 K

The title compound acts as a clathrate host for dimethylformamide (DMF), ethanol, and propan-2-ol; DMF is held inside a rectangular void of the host lattice via hydrogen bonding and steric interaction.

Molecular distortions in 1-nitro-9-methylacridine and 1-nitro-9-aminoacridine

Abstract The high antitumor activity of certain 1-nitroacridines has been reported, and Ledakrin (1-nitro-9-(3-dimethylaminopropylimino)-acridine) is used clinically in Poland as an antineo-plastic agent. To investigate the role of the 1-nitro group in enhancing antitumor activity, the crystal structures of 1-nitro-9-aminoacridine and 1-nitro-9-methylacridine have been determined. 1-Nitro-9-methylacridine crystallizes in the orthorhombic space group Pbca , with Z = 8 and a = 13.822(4), b = 9.927(3), c = 17.248(6) A , V = 2217(1) A 3 . The final R value, after least-squares refinement, is 0.056, for 2155 observed intensities. The structure of 1-nitro-9-aminoacridine is approximately isomorphous with that of the 9-methyl derivative, with unit cell dimensions a = 13.217(2), b = 10.011(1), c = 16.373(1) A , V = 2166.4(5) A 3 . The final R value, after least-squares refinement, is 0.058, for 1534 observed intensities. The structures were solved independently by direct methods. The steric interference between the 1-nitro and the 9-methyl- or 9-amino-substituents on the acridine ring system causes considerable deviations from planarity in both structures. There are two possible intramolecular hydrogen bonds between the amino group and the disordered nitro group in 1-nitro-9-aminoacridine. Unlike N 9 -alkyl derivatives of 1-nitroacridines that have been previously described, in the 9-amino derivative the exocyclic nitrogen adopts the amino rather than the imino form.

Preparation and Characterization in Solution of Oligonucleotides Alkylated by Activated Carcinogenic Polycyclic Aromatic Hydrocarbons

The effects of aralkylation of selected oligonucleotides by a bulky chemical carcinogen, 7,12-dimethylbenz(a)anthracene (after activation) have been studied. The aralkylation involves the base adenine, designated A* at the modification site, in the center of synthetic heptameric, nonameric and pentadecameric oligonucleotides; complementary strands lacking any modification were also synthesized. The products were studied by UV melting curves and CD spectral techniques. Duplex formation was modified by such aralkylation of a central base in the oligomers. The extent of duplex formation was found to depend on chain length as follows: no evidence was found for duplex formation of the heptamer d(GTCA*GAC) + d(GTCTGAC); the nonamer, d(GTGCA*ATCC) + d(GGATTGCAC), appears to form a duplex at high salt concentrations and reduced temperature; the pentadecamer, d(CCGCT-GCGA*TCCGGC) + d(GCCGGATCGCAGCGG), forms a duplex at low salt concentration and room temperature, but its melting temperature is lower than that of the nonalkylated parent system. CD-spectra for the duplexes formed by the nonamer or pentadecamer are indicative of a right-handed helical conformations. On phosphordiesterase digestion it appears that the aralkylated adenine and the base on its 5-side act as stops for enzymatic digestion from either direction. We suggest, from model building, that this inhibition of phosphodiesterase activity is the result of the steric bulk and disposition of the polycyclic aromatic hydrocarbon. We further suggest that unusual base pairing (mismatching), such as A...A, which would lead to an AT transversion, may be favored by the bulkiness of the aromatic group.