Penelope W. Codding

Structural requirements for the binding of dexamethasone to nuclear envelopes and plasma membranes.

The specificity of dexamethasone binding sites on nuclear envelopes (NE) and plasma membranes (PM) was determined in competition studies with natural and synthetic steroids. The binding affinities for nuclear envelopes and plasma membranes were then correlated with the three-dimensional structures of the ligands. Three major factors are implicated in the ability of the steroid to bind to the membrane sites: (1) the separation between the terminal oxygen atoms substituted at atoms C3 and C17, or attached to the substituent at C17, is found to be longer than 10 A for the medium and high affinity steroids; (2) the beta-orientation of the oxygen atom in the C17-substituent to the D-ring is favored over alpha-orientation; and (3) bulky substituents and nontypical configurations are not accepted by the binding sites. A nearly linear correlation between the O3...O (substituted at C17) distance and the binding affinity of the tested steroids is observed; explanations for the lack of linear correlation of some steroids are given. A preliminary model for the interaction of steroids with these membrane sites is proposed which requires two hydrogen bonding regions that interact with the 2 oxygen atoms and some steric restriction sites that prevent the binding of steroids with large substituents. The hydrophobicities of the steroids do not correlate with binding affinities to the dexamethasone binding sites; hydrophobicity seems to play a minor role in these steroid-membrane interactions. Comparisons of the specificity of the dexamethasone binding sites on membranes to the specificity of various steroid receptors are also presented.

Hydrogen-bond patterns in 1,4-dihydro-2,3-quinoxalinediones: ligands for the glycine modulatory site on the NMDA receptor.

The crystal structures of five 1, 4-dihydro-2, 3-quinoxalinediones, antagonists of the NMDA modulatory glycine binding site on the excitary amino acid (EAA) receptor complex, have been determined: (I) 6, 7-dinitro-1, 4-dihydro-2, 3-quinoxalinedione (DNQX); (II) 5, 7-dinitro-1,4-dihydro-2, 3-quinoxalinedione (MNQX); (III) 6-nitro-1,4-dihydro-2, 3-quinoxalinedione hydrate; (IV) 6, 7-dichloro-1, 4-dihydro-2, 3-quinoxalinedione; (V) 5, 7-dichloro-I, 4-dihydro-2, 3-quinoxalinedione dimethylformamide. The crystal structure of the most active compound (II) contains a unique intramolecular N--H...O(NO2) hydrogen bond, which may be important for activity, as semiempirical calculations show that this bond is stable over a wide range of dihedral angles between the planes of the molecule and of the nitro group. In the other compounds the intermolecular hydrogen bonds connect molecules into three-dimensional networks. In compounds (I), (III) and (IV) head-to-tail pi-stacking is found between molecules connected by a center of symmetry. The geometries of the hydrogen-bonded -NH-C = O fragments show evidence of pi-cooperativity or resonance-assisted hydrogen bonding. Graph-set analysis of the hydrogen-bond patterns of quinoxalinedione derivatives shows a tendency to form two types of hydrogen-bonding motifs: a centrosymmetric dimeric ring and an infinite chain. Even though this pattern may be modified by the presence of additional hydrogen-bond acceptors and/or donors, as well as by solvent molecules, general similarities have been found. Comparison of all quinoxalinedione structures suggests that the hydrogen-bonding pattern necessary for the biological activity at the glycine binding site contains one donor and two acceptors.

The alkaloids of nutt.

The structures of alkaloid- and - were established via X-ray crystallography of the former as its HI salt, and its chemical conversion to the latter.Abstract The structures of alkaloid- A and - B were established via X-ray crystallography of the former as its HI salt, and its chemical conversion to the latter.

Tricarbonyl (triquinacene)-molybdenum and-tungsten

Summary Triquinacene reacts with hexacarbonylmolybdenum to give tricarbonyl(triquinacene)molybdenum, and with tris(acetonitrile)tricarbonyltungsten to give tricarbonyl(triquinacene)tungsten, whereas efforts to synthesize the corresponding chromium complex, tricarbonyl(triquinacene)chromium, were unsuccessful. The molybdenum complex was characterized by 1H and 13C NMR spectroscopy, mass spectra, and a single crystal X-ray structure determination. The tungsten complex is thermally less stable and more susceptible to oxidation than its molybdenum analogue and was characterized by the mass spectrum and the 1H NMR spectrum. The crystal structure of the tricarbonyl(triquinacene)molybdenum is compared to that for the free ligand. Besides the expected lengthening of the C=C bonds, the complex shows a deepening of the triquinacene “basket”, presumably to give better overlap of the C=C bonds with molybdenum orbitals.

The structure of delphinifoline, a diterpenoid alkaloid from aconitum delphinifolium

Abstract The structure of delphinifoline, a minor alkaloid of Aconitum delphinifolium DC, was established by spectroscopic methods, and X-ray crystallography.

Methyl 4-(benzylamino)-6-methyl-2-oxo-3-cyclohexene-1-carboxylate, C16H19NO3

The cyclohexene ring adopts an almost ideal sofa conformation. The bond lengths of the C---C--C--O fragment indicate strong conjugation through these bonds. Other planar fragments of the molecule, i.e. the phenyl ring and the ester group, make angles of 60.82 (4) and 75.20 (6) °, respectively, with the plane of the cyclohexene ring. The methyl substituent occupies an equatorial position. In the crystal structure, the intermolecular N--H...O hydrogen bonds form infinite chains of molecules along the [010] direction.

Structure of suriclone, a benzodiazepine receptor agonist.

6-(7-Chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-4-methyl-7- oxo-5H-1,4-dithiino[2,3-c]-pyrrol-5-yl-1-piperazinecarboxylic++ + acid, C20H20C1N5-O3S2, Mr = 477.9, triclinic, P1, a = 8.7066 (3), b = 9.7665 (8), c = 14.2515 (16) A, alpha = 80.986 (9), beta = 75.168 (6), gamma = 65.884 (5) degrees, V = 1067.4 (2) A3, Z = 2, F(000) = 496, room temperature, Dm = 1.482, D chi = 1.487 g cm-3, lambda(Cu K alpha) = 1.54178 A, Ni filter, mu = 36.3 cm-1, R = 0.053, omega R = 0.070 for the 3538 reflections included in the refinement. Comparisons of the structures of the two enantiomers of suriclone and the active conformer of the 1,4-benzodiazepine anxiolytics allow the identification of the active form of suriclone as the R isomer.

Crystal and moleclar structures of 5-allyl-25-methoxy-26,27,28-tribenzoylcalix[4]arene

The crystal and molecular structures of 5-allyl-25-methoxy-26,27,28-tribenzoylcalix[4]arene, an unsymmetrically substituted macrocycle, are reported. The space group is orthorhombic,P212121, witha=13.4181(6),b=16.6652(10) andc=18.9936(14) Å andZ=4. Refinement by least-squares calculations converged with aR=0.060 for 4018 observed reflections. The molecule assumes a 1,3 alternate conformation with 2 benzoate rings and the disordered allyl side chain on one side and the third benzoate ring and the methoxy group on the opposite side of the mean plane of the methylene bridging groups. The four phenyl rings that comprise the macrocycle are approximately parallel in pairs; the members of a pair are 5.6 Å apart. The carbonyl oxygen atoms of the 3 benzoate groups are oriented away from the center of the cavity while the ester oxygen atoms and the methoxy oxygen atom are oriented toward the cavity center.

The crystal structure of triphenylarsine sulphide

Crystals of AsPh3S obtained from acetone solution are monoclinic, space group P21/c, Z= 8, with unit-cell dimensions a= 18.523(8), b= 9.642(4), c= 18.140(8)A, and β= 105.93(4)°. The compound is isomorphous with PPh3S and PPh3Se. The structure has been elucidated on the basis of this isomorphism, from 2 795 observed reflections and refined to R 0.042 2. The AsS bond is essentially a double bond, and in both molecules of the asymmetric unit one phenyl ring lies almost coplanar with the As–S bond, while the other rings have an average torsion angle of 53°. The molecular structure is compared with those of PPh3S and PPh3Se in an attempt to elucidate the reasons for the observed conformations.

Two cyclic dipeptide anticonvulsants: cyclo-glycyl-l-phenylglycine (1) and cyclo-l-alanyl-d-phenylglycine (2)

In the title compounds, C 10 H 10 N 2 O 2 .0.25H 2 O (1) and C 11 H 12 N 2 O 2 (2), the phenyl rings are almost perpendicular to the mean planes of the diketopiperazine rings, which assume flattened twist-boat conformations. The methyl group of the alanyl residue in (2) lies in a quasiaxial position. In both structures, hydrogen bonds connect molecules into infinite layers. In compound (1), there are two molecules per asymmetric unit and each forms an independent layer. Water molecules bind the neighboring layers of only one type into pairs. There is no interaction between symmetrically independent molecules