Preliminary crystallographic study of an L-asparaginase from Vibrio succinogenes.

Crystals of an L-asparaginase from Vibrio succinogenes were obtained with the hanging drop method from ammonium sulphate-containing solutions. The crystals belong to the orthorhombic space group P22(1)2(1) with unit cell dimensions of a = 71.3 A, b = 85.8 A, c = 114.0 A, and contain two tetrameric enzyme molecules per unit cell. There are two subunits in the asymmetric unit; a molecular dyad is coincident with the crystallographic dyad. The crystal lattice is similar to that reported for an Escherichia coli asparaginase. Rotation function calculations have revealed that the V. succinogenes enzyme has 222 point group symmetry in the crystal. The second and third molecular dyads differ, however, from the corresponding E. coli asparaginase dyads by approximately 40 degrees. The crystals diffract to at least 2.2 A resolution and are suitable for X-ray crystallographic structure determination.

Crystallization and a preliminary X-ray diffraction study of isozyme 3-3 of glutathione S-transferase from rat liver.

Crystals of the homodimeric isozyme 3-3 of glutathione S-transferase from rat liver have been obtained with the hanging drop method of vapor diffusion from ammonium sulfate solutions. The successful crystallization of the enzyme required the presence of both the enzyme inhibitor (9R, 10R)-9, 10-dihydro-9-(S-glutathionyl)-10-hydroxyphenanthrene and the detergent beta-octylglucopyranoside. The crystals belong to the monoclinic space group C2, with cell dimensions of a = 88.24(8) A, b = 69.44(4) A, c = 81.28(5) A, beta = 106.01(6) degrees, and contain four dimeric enzyme molecules per unit cell. The crystals diffract to at least 2.2 A and are suitable for X-ray crystallographic structure determination at high resolution.

Preliminary crystallographic study of glucose-6-phosphate dehydrogenase from rat liver.

Crystals of D-glucose-6-phosphate: NADP+ oxidoreductase were obtained with the hanging drop, vapor diffusion and batch methods from ammonium sulfate-containing solutions. X-ray diffraction photographs indicate that the crystals belong to the orthorhombic space groups I222 or I2(1)2(1)2(1) with unit cell dimensions of a = 66.0 A, b = 140.8 A and c = 177.8 A. These data, together with results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and crystal density experiments, indicate that there is one 116,000 Mr dimer per asymmetric unit. The crystals diffract to at least 2.2 A and are suitable for X-ray crystallographic structure determination.

Role of the (acyloxy)methyl moiety in eliciting the adrenergic beta-blocking activity of 3-(acyloxy)propanolamines.

Some totally aliphatic 3-(acyloxy)propanolamines were synthesized with the aim of testing whether beta-blocking activity could be obtained from this class of drugs, even in the absence of an aromatic group. The significant and, in most cases, competitive beta-blocking activity shown by the compounds under examination, together with the results of a theoretical study in which their reactivity was compared with that of other adrenergic beta-blocking drugs, seems to confirm a hypothesis previously advanced on the basis of knowledge about the action mechanism of adrenergic beta-blocking drugs and of the results of structural studies. It was also possible to suggest some considerations about the role played by the (acyloxy)methyl portion of 3-(acyloxy)propanolamines in eliciting their adrenergic beta-blocking activity.

2,3,4-Tri-O-acetyl-1,6-anhydro-beta-D-mannopyranose, an artifact produced during carbohydrate analysis. A total synthesis of 2,3,5-tri-O-acetyl-1,6-anhydro-beta-D-mannofuranose.

This study confirms that 2,3,4-tri-O-acetyl-1,6-anhydro-beta-D-mannopyranose is an artifact produced during carbohydrate analysis. A new synthesis of 2,3,5-tri-O-acetyl-1,6-anhydro-beta-D-mannofuranose is also described, and a novel dimer, 1,6':6,1'-dianhydro-2,3:2',3'-di-O-isopropylidene-5,5'-di-O-(1-methox yethyl)-di - alpha-D-mannofuranose, has been isolated. The structure of the dimer is confirmed by X-ray analysis of a derivative, 1,6':6,1'-dianhydro-2,3:2',3'-di-O-isopropylidene-di-alpha-D-mannofur anose.

A third blind test of crystal structure prediction.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

Structure of 1,3-dinitronaphthalene.

C10H6N2O4, Mr = 218.2, triclinic, P1, a = 7.5552 (8), b = 7.763 (1), c = 9.073 (1) A, alpha = 110.742 (9), beta = 99.570 (9), gamma = 100.309 (9) degrees, V = 474.1 (2) A3, D chi = 1.528 g cm-3, Z = 2, Cu K alpha (lambda = 1.54178 A, graphite monochromator) mu = 10.5 cm-1, F(000) = 224, T = 293 K, final R = 0.064, wR = 0.092 for 1213 reflections with I greater than 3 sigma (I). The naphthalene ring is planar with an average deviation of 0.004 A from the ten-atom least-squares plane. The C-C distances show the typical naphthalene alternation: C1-C2, C3-C4, C5-C6 and C7-C8 average 1.359 A; C2-C3 and C6-C7 average 1.391 A. The C1 nitro group is twisted out of the ring plane by approximately 37 degrees to relieve non-bonded interactions between an oxygen and the C8-H8 region.

Structure of a 2-arylquinoline dimer, a compound with a new ring system.

The title compound, 6,15-dimethyltribenzo-[c,f,j]naphtho[1,2,3,4-lmn][2,7]phe nanthroline was obtained in low yield from the reaction of 2-(4-methylphenyl)quinoline and various aryllithiums. The compound is a 'dimer' in which two phenylquinoline units are joined by three bonds; the dimer has exact twofold symmetry. Non-bonded interactions produce substantial out-of-plane distortions. Bond lengths between the two phenylquinoline halves suggest that the two phenylquinoline pi-electron systems are more-or-less undisturbed and linked by single bonds. Molecular-mechanics optimizations of models with inversion (1) and twofold symmetry suggest that the latter conformation is the more stable of the two to a slight extent.

Structure of 2-methoxycarbonyl-1,4-dinitrocubane.

The title compound, methyl 2,7-dinitropentacyclo-[4.2.0.0(2,5).0(3,8).0(4,7)]octane-1-carboxy late, is one of the few examples of cubanes with substituents on adjacent C atoms. There are two enantiomeric molecules per asymmetric unit in a structure with a noncentrosymmetric space group, P2(1)2(1)2. The molecules differ primarily in the conformations of the C-NO2 groups adjacent to the methoxycarbonyl sustituents. The 1,2-disubstituted cubane C-C bonds average 1.564 A, a typical value for an unsubstituted cubane bond.

Structure of a photoresponsive crown ether, 21-(4'-methoxyphenylazo)-1,4,7,14,23-pentaoxa[7.2.2] orthometaorthobenzenophane.

3,10,13,16,23-Pentaoxatetracyclo-[23.3.1.0.(4,9)0(17,22)]nonaco sa-1(29), 4,6,8,17,19,21,25,27-nonaene-29-azo-(4'-methoxybenzene), C31H30N2O6, Mr = 526, monoclinic, P2(1)/n, a = 14.564 (3), b = 19.177 (2), c = 10.025 (2) A, beta = 100.42 (1) degrees, V = 2754 (1) A3, Z = 4, Dx = 1.269 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 0.95 cm-1, F(000) = 1112, T = 293 K, final R = 0.050 for 2577 reflections with I greater than 3 sigma(I). The molecule resembles a butterfly with benzene rings for the wings and head. The transazobenzene moiety, which overlays one face of the crown oxygen ring, is in an orientation that creates a partial steric block to cation...crown complex formation.

Structure of 9-nitro-[4]peristylane-1,5-dione.

Decahydro-1,6:3,4-dimethano-3a-nitrocyclobuta [1,2:3,4]dicyclopentene-2,5-dione (II), C12-H11NO4, Mr = 233.2, monoclinic, P2(1)/n, a = 13.378 (7), b = 6.614 (1), c = 23.040 (15) A, beta = 92.53 (5) degrees, V = 2036.6 (4) A3, Z = 8, D chi = 1.521 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 9.3 cm-1, F(000) = 1312, T = 293 K, final R = 0.047, wR = 0.075 for 3075 reflections with I greater than 3 sigma(I). There are no unusually short intermolecular distances. A comparison of the molecular densities and packing coefficients of (I) [4]peristylane-1,5-dione with (II), indicates that the change in crystal density from (I) (1.415 g cm-3) to (II) (1.521 g cm-3) is the sole result of an increase in molecular density with NO2 substitution. The packing coefficients for (I) and (II) are identical.

Structure of 1,5,9-trinitrobishomopentaprismane.

2,3,8-Trinitrohexacyclo[5.4.1.0(2,6).0(3,10).-0(4,8).0(9,12)]do dec ane (IV), C12H11N3O6, Mr = 293.2, orthorhombic, Pna2(1), a = 11.467 (1), b = 8.756 (1), c = 11.9339 (8) A, V = 1198.2 (4) A3, Dx = 1.625 g cm-3, Z = 4, Cu K alpha, lambda = 1.54178 A, mu = 11.6 cm-1, F(000) = 608, T = 293 K, final R = 0.061, wR = 0.091 for 1082 reflections with I greater than 3 sigma(I). There are no unusual intermolecular distances and the crystal packing is normal. The crystal density of (IV) is only 2.3% larger than that of 1,5-dinitrobishomopentaprismane (III) at 1.589 g cm-3 despite a 6.7% higher molecular density of (IV) over (III). An analysis of crystal packing and the calculated crystal packing coefficients indicates that the small crystal-density change is the result of more efficient molecular packing in (III) over (IV), which compensates for the lower molecular density of (III). The molecular shape and polarity of (III) lead to efficient crystal packing.

Structures of secocubane and nortwistbrendane derivatives.

(I): 4,7-Dichloro-1-cyano-N-isopropyltetracyclo-[4.2.0.0(2,5).0(3,8)] octane-4-carboxamide, C13H14Cl2N2O, M(r) = 285.17, orthorhombic, Fdd2, a = 34.012 (1), b = 15.791 (2), c = 10.899(1)A, Z = 16, D chi = 1.29 g cm-3, Cu K alpha (lambda = 1.5418 A), mu = 39.2 cm-1, F(000) = 2368, T = 293 K, 1504 reflections with I > 3 sigma(I), R = 0.042. (II): 4,7-Dichloro-N-isopropyl-10-oxo-9-oxatetracyclo [4.4.0.0(2,5).0(3,8)]decane-4-carboxamide, C13H15Cl2NO3, M(r) = 304.17, monoclinic, P2(1)/a, a = 9.902(2), b = 9.381(2), c = 15.174(2) A, beta = 103.25(1) degrees, Z = 4, D chi = 1.47 g cm-3, Cu K alpha (lambda = 1.5418 A), mu = 43.1 cm-1, F(000) = 632, 2107 reflections with I > 3 sigma(I), R = 0.036. (I) represents the first crystallographic example of a secocubane. The nonbonded distances (C4...C7) are 2.742 (5) and 2.717(3) A in (I) and (II). C--C distances in the cage portions of the molecules are typical of cubanes.

Structure of N,N,N',N'-tetrakis(2-fluoro-2,2-dinitroethyl)oxamide by the consistent electron density approach.

C10H8F4N10O18, Mr = 632.22, monoclinic, Pc, a = 7.8885 (6), b = 6.7787 (4), c = 21.595 (2) A, beta = 108.21 (1) degree, V = 1096 (1) A3, Z = 2, Dx = 1.914 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 18.7 cm-1, F(000) = 636, T = 293 K, 1791 unique data, 1733 with I greater than 3 sigma (I), R = 0.047. The structure was solved by the consistent electron density approach (CEDA), in which a small starting set of random phases was refined and expanded by the application of restraints to the electron density. A refinable preliminary structure was obtained by fitting a model to a 3 A map, calculated with 27 reflections (all data with d greater than 3 A, and magnitude of Fo greater than 170) whose phases had been determined by the CEDA. The molecule has an extended, open conformation; the two pairs of fluorodinitroethyl substituents located across the molecular center from each other show i and C2 pseudo-symmetry respectively.

Structure of (+-)-threo-9,10,16-trihydroxypalmitic acid.

9,10,16-Trihydroxyhexadecanoic acid, C16H32O5, Mr = 304.4, triclinic, P1, a = 4.871 (1), b = 8.801 (1), c = 21.121 (2) alpha = 89.54 (1), beta = 84.88 (2), gamma = 76.35 (2) degrees, V = 876.14 (4) A3, Z = 2, Dx = 1.154 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 0.26 cm-1, F(000) = 336, T = 295 K. Final R = 0.055 for 1556 reflections with I greater than or equal to 3 sigma(I). The 16 C atoms form an all-trans zigzag chain. Each molecule is linked to seven neighboring molecules via eight possible hydrogen bonds with O...O distances varying from 2.591 (6) to 2.673 (3) A. Each carboxyl group is potentially hydrogen-bonded to the carboxyl and C16-OH groups of other molecules with O...O distances of 2.591 (6) and 2.644 (4) A. The conformation around the C9-C10 bond is gauche with an O3-C9-C10-O4 torsion angle of 66.4 (5) degrees.

Structure of a lactone, 2,4,6-trideoxy-4,6-dimethyl-2-(2-oxopropyl)-7-O- (phenylmethyl)-L-glycero-D-manno-heptono-1,5-lactone 3-(3,5-dinitrobenzoate).

C26H28N2O10, Mr = 528.5, triclinic, P1, a = 9.524 (1), b = 11.8187 (8), c = 12.615 (1) A, alpha = 66.512 (7), beta = 83.321 (9), gamma = 88.758 (8) degrees, V = 1293.0 (4) A3, Dx = 1.357 g cm-3, Z = 2, lambda(Cu K alpha) = 1.54178 A, mu = 8.99 cm-1, F(000) = 556, T = 293 K, final R = 0.039, wR = 0.048 for 2425 reflections with I greater than 3 sigma(I). The tetra-substituted valerolactone ring has a boat conformation and the relative stereochemistries of the three pairs of adjacent substituents are cis-trans-trans.

Structure of thialysine hydrochloride.

2-Ammonio-3-[(2-ammonioethyl)thio]propionate chloride, C5H13N2O2S+.Cl-, Mr = 200.7, monoclinic, P2(1), a = 5.1275 (4), b = 7.897 (1), c = 11.208 (1) A, beta = 104.129 (8) degrees, V = 440.1 A3, Z = 2, Dx = 1.519 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 6.12 cm-1, F(000) = 212, T = 295 K, final R = 0.021, wR = 0.027 for 784 reflections with I greater than 3 sigma (I). The two ammonium cations form seven hydrogen bonds: alpha-NH3+ acts as a donor for three carboxylate O atoms and one Cl- ion whereas epsilon-NH3+ is linked to three Cl- ions.

Structure of a lactone, (3 alpha,4 alpha,6 alpha)-4-(tert- butyldimethylsiloxy)-3,4,5,6-tetrahydro-6-methyl-3-(2-oxopropyl)- 2H- pyran-2-one.

C15H28O4Si, Mr = 300.5, monoclinic, P2(1)/a, a = 11.194 (4), b = 10.944 (3), c = 14.815 (5) A, beta = 95.01 (3) degrees, V = 1808 (2) A3, Dx = 1.104 g cm-3, Z = 4, lambda(Mo K alpha) = 0.71069 A, mu = 1.43 cm-1, F(000) = 656, T = 293 K, final R = 0.052, wR = 0.058 for 1630 reflections with I greater than 3 sigma(I). The valerolactone ring is in a boat conformation and the three ring substituents are cis.

Structure of (2'R*,5S*)-(+/-)-5-(tetrahydro-2'H-pyran-2'-yl)-2(5H)-furanone.

C9H12O3, Mr = 168.2, triclinic, P1, a = 5.5385 (6), b = 8.543 (1), c = 10.373 (1) A, alpha = 113.329 (9), beta = 100.78 (1), gamma = 99.82 (1) degree, V = 426.2 (2) A3, Dx = 1.31 g cm-3, Z = 2, Cu K alpha (lambda = 1.54178 A, graphite monochromator), mu = 8.2 cm-1, F(000) = 180, T = 293 K. Final R = 0.036, wR = 0.081 for 1559 reflections with I greater than 3 sigma(I). The relative configurations at the two chiral centers are (S,R). The dihedral angle between the five- and six-membered rings (O1--C4--C5--O3) is 69.9 (1) degree. The tetrahydropyran is in a chair conformation with the furanone ring equatorial.