Crystal structure of octakis(2,3,6-tri-O-methyl)-gamma-cyclodextrin x 4.5 H2O: evidence for conformational flexibility of permethylated cyclodextrins.

Octakis(2,3,6-tri-O-methyl)-gamma-CD (TRIMEG) cocrystallized at 18 degrees C with 4.5 water molecules in the orthorhombic space group P2(1)2(1)2(1), unit cell dimensions a = 10.7879(3), b = 29.0580(9), c = 32.2909(11) A. The TRIMEG macrocycle is in a 'round' form with all glucose units oriented syn, and one O-6-CH3 methoxy group points 'toward' the molecular cavity. The TRIMEG x 4.5 H2O molecules are stacked to form infinite cylinders with the central cavities aligned into channels filled for each TRIMEG by 4.5 water molecules distributed over 15 partially occupied sites. This structure differs from the two known structures of TRIMEG in which two diametrically opposed glucoses are oriented anti to yield an 'elliptical' form, and their O-6-CH3 groups are directed 'toward' the cavity and close it at this side to form a bowl-shaped molecule.

Crystal structure of hexakis(2,6-di-O-methyl)-alpha-cyclodextrin-acetonitrile dihydrate: a channel formed by methyl groups harbors a chain of five partially occupied water sites.

Hexakis(2,6-di-O-methyl)-alpha-cyclodextrin (DIMEA) crystallizes from 1:1 water-acetonitrile as DIMEA-acetonetril-dihydrate in the orthorhombic space group P2(1)2(1)2(1), unit cell dimensions a = 14.2775(5), b = 15.7312(5), c = 31.1494(11) A. Refinement of the structure against 5540 X-ray diffraction data converged at an R factor of 0.083. The macrocycle exhibits a 'round' conformation and is stabilized by intramolecular, interglucose O-3-H(n)...O-2(n + 1) and C-6-H(n)...O-5(n + 1) hydrogen bonds. Acetonitrile is included in the central cavity of DIMEA and held in position by C-5-H...N interactions. The two water molecules in the asymmetric units are distributed over six sites. One is fully occupied due to hydrogen bonding to O-3 groups of two symmetry-related DIMEA molecules, whereas the five remaining sites show occupancies between 0.15 and 0.25. These sites are in hydrogen bonding contact with O...O distances between 2.59 and 3.50 A and are located in infinite, hydrophobic channels parallel to the alpha-axis, which are coated with methyl groups of symmetry-related DIMEA.

N-n-alkyl N,N-dimethylammonioacetic acid bromides: the first complete series of crystal and molecular structure determinations of an amphiphilic compound with alkyl chain lengths n = 1,..., 16

The molecular and crystal structures of 16 N-n-alkyl N,N-dimethylammonioacetic acid bromides with chain lengths between n = 1 and n = 16 have been determined. All compounds from n = 5 to n = 16 form bilayers with interdigitated chains. The even-numbered chains display the chain packing type M2(II). The chain packing of the odd-numbered chain compounds is less regular. The head groups of all compounds are connected via electrostatic N+...Br- interactions, and by OH...Br- hydrogen bonds. The compounds with short chains are packed in different ways. Their molecular conformation depends on the crystal packing.

Chiral J-aggregates formed by achiral cyanine dyes.

The self-assembly of helical supramolecular structures from chiral building units is a basic principle of biological materials. The mesoscopic structure of a chiral molecular aggregate, which formed spontaneously from a nonchiral J-aggregating cyanine dye in aqueous solution, is presented. In single crystals (as shown in the picture) a coexistance of planar molecules with left- and right-handed twisted conformers of the same dye are found; the latter may act as templates to build up the helical superstructures.

Laser-induced predissociative fluorescence: dynamics and polarization and the effect of lower-state rotational energy transfer on quantitative diagnostics.

Laser-induced predissociative fluorescence is often used for diagnostics because its short-lived upper states are minimally disturbed by collisions. We discuss the effects of lower-state collisions with parameters relevant to our atmospheric H(2)-O(2) flame. A pulse of tunable KrF excimer-laser light induces the A ? X, Q(1)(11), 3 ? 0 transition in OH. We measure the intensity and the polarization of the resulting A ? X, Q(1)(11), 3 ? 2 fluorescence as a function of laser brightness. A simple model that uses no adjustable parameters produces a reasonable fit to the data. It predicts that, even at very modest laser energies, the fluorescence intensity is almost directly proportional to the rate constant for rotational energy transfer (RET) within the lower vibrational state. That rate constant can be a strong function of local conditions. Furthermore, under typical operating conditions the excimer will pump an amount of OH out of the lower state that is many times as large as that originally present. This occurs because RET within the X-state continuously replenishes the lower state during the laser pulse. Even when this occurs, the signal may still vary linearly with laser intensity, and the polarization may be nearly that expected for weak pumping. At the higher laser intensities, a significant fraction of the measured OH arises from two-photon photodissociation of the water from the flame reaction.

A "Double-Diamond Superlattice" Built Up of Cd17S4(SCH2CH2OH)26 Clusters.

A simple preparation of Cd(17)S(4)(SCH(2)CH(2)OH)(26) clusters in aqueous solution leads to the formation of colorless blocky crystals. X-ray structure determinations revealed a superlattice framework built up of covalently linked clusters. This superlattice is best described as two enlarged and interlaced diamond or zinc blende lattices. Because both the superlattice and the clusters display the same structural features, the crystal structure resembles the self-similarities known from fractal geometry. The optical spectrum of the cluster solution displays a sharp transition around 290 nanometers with a large absorption coefficient ( approximately 84,000 per molar per centimeter).

Identification of serine-143 as the most likely precursor of dehydroalanine in the active site of histidine ammonia-lyase. A study of the overexpressed enzyme by site-directed mutagenesis.

The gene coding for histidase (histidine ammonia-lyase, HAL, EC 4.3.1.3) was isolated from a lambda-EMBL3 genomic library from Pseudomonas putida nicII and subcloned into the expression vector pT7-7. Transformation of Escherichia coli BL21 (DE3) cells with the recombinant vector led to the expression of catalytically active histidase amounting to 20-30% of the total soluble protein in the crude cell extract. A new rapid and highly efficient isolation procedure is described leading to electrophoretically homogeneous histidase within 1.5 days. Six grams of E. coli BL21 (DE3) cells (wet weight) gives approximately 100 mg of homogeneous histidase with a specific activity of 27 IU/mg. To investigate the possible role of serine as a precursor of dehydroalanine in the active site of histidase, each of the four serines, conserved in all known histidases and phenylalanine ammonia-lyases, was consecutively changed to alanine by site-directed mutagenesis. The resulting mutant genes were subcloned into the expression vector pT7-7 and were assayed for histidase activity. The catalytic activities of the four mutants and of wild-type histidase were compared. The Km and Vmax values of the overexpressed mutants S112A, S393A, and S418A and wild-type histidase did not show any significant differences. Mutant S143A, however, was devoid of catalytic activity (< 0.01%), pointing to the outstanding importance of this serine for the formation of an active enzyme. We conclude that serine-143 is the most probable precursor of the active-site dehydroalanine. The role of serine-143 in the biosynthesis of active histidase is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pregnancy following sterilization and endometrium resection]. / Schwangerschaft nach Sterilisation und Endometriumresektion.

We report on the successful outcome of a pregnancy after bipolar electrocoagulation of Fallopian tubes for sterilisation followed by electroresection of the endometrium for menorrhagia. Reasons for sterilisation failure are discussed with special attention to benefits and risks of endometrial ablation as a new "minimally invasive" therapy for menstrual disorders. We propose guidelines for patients' counselling and preoperative consent.

Evidence that V+ fibronectin, GFAP and S100 beta mRNAs are increased in the hippocampus of aged rats.

In the present study, using RNA gel-blot analysis, we characterized the developmental changes in the prevalence of mRNA coding for fibronectin (FN), glial fibrillary acidic protein (GFAP), neurotrophic protein S100 beta, and beta-actin mRNA in rat hippocampus and forebrain from 1 to 720 days of age. We found that the FN and mRNA containing the V segment (FN-V) was relatively abundant at early postnatal stages, but very few transcripts were detected in adult rats. However, the hybridization signal for the juvenile FN-V mRNA was up to approximately 8-fold increased in some but not all 24-versus 6-month-old rats. Also, GFAP and S100 beta transcripts were faintly expressed at an early developmental stage, then the level of expression steadily increased starting with day 21. The greatest increase averages approximately 1.8-fold for GFAP in 24-month-old rats, and approximately 1.5-fold for S100 beta in 15-month-old versus 6-month-old rats. As all these messages are localized primarily in astrocytes, we conclude that (a) astrocyte might play an active role in aging hippocampus and (b) an increase in S100 beta and GFAP mRNA expression may precede that for FN-V mRNA expression in a hypothetical pathway of molecular events underlying neurodegeneration in the hippocampus of old rats. We also note the considerable variability among the 24-month-old rats, suggesting that aging is an individual process.

[Antiarrhythmic amidinohydrazone substituted benzophenones. 2. Preparation and determination of configuration of (Z)- and (E)-2-amino-5-chlorobenzophenone amidinohydrazone salts]. / Antiarrhythmisch wirksame Amidinohydrazone substituierter Benzophenone. 2. Mitteilung: Darstellung und Konfigurationszuordnung von (Z)- und (E)-2-Amino-5-chlorbenzophenonamidinohydrazonsalzen.

The configurational isomers of the 2-amino-5-chlorbenzophenoneamidinohydrazones could be obtained as TLC pure samples by fractionating crystallization of the product mixture. The determination of their configuration by comparison of the UV spectra with the corresponding oximes could be confirmed by X-ray structure analysis.

[Potential cardiotonics. 16. Molecular and crystal structures of three polymorphic forms and a hydrochloride monohydrate of 3-cyano-2-morpholino-5-(pyridin-4-yl)pyridine (AWD 122-14)]. / Potentielle Kardiotonika. 16. Mitteilung3: Molekül-und Kristallstrukturen dreier polymorpher Formen und eines Hydrochlorid-Monohydrates von 3-Cyan-2-morpholino-5-(pyrid-4-yl) pyridin (AWD 122-14).

The results of an X-ray structure analysis of the alpha-modification were the starting point for the prediction and establishment of further polymorphic and pseudopolymorphic, respectively, forms of AWD 122-14. A complete structure determination of the gamma- and delta-modifikation as well as of a hydrochloride monohydrate could be carried out. Molecular parameters, conformational flexibility, and intermolecular interactions are discussed in this paper.

[Potential cardiotonics. 15. Crystal modifications of 3-cyano-2-morpholino-5-(4-pyridinyl)pyridine (AWD 122-14)]. / Potentielle Kardiotonika. 15. Mitteilung: Kristallmodifikationen von 3-Cyan-2-morpholino-5-(pyrid-4-yl)pyridin (AWD 122-14).

The preparation and X-ray crystallographic characterisation of 10 polymorphic or pseudo-polymorphic forms of the novel cardiotonic AWD 122-14 are described. Thermic transformations of some polymorphic forms into the alpha-form was proved by thermogravimetric analysis and powder diffraction pattern. In dissolution behaviour no significant differences were found between the crystalline modifications but with regard to galenic processing compact alpha-, gamma- and epsilon-forms show advantages.

Dynamics of gene expression for microtubule-associated protein MAP1B, embryonic alpha-tubulin and late neural beta-tubulin mRNAs in the hippocampus of aged rats.

In the present study we characterized the developmental changes in the prevalence of mRNA coding for microtubule-associated protein, MAP1B, embryonic alpha-tubulin and late neural beta-tubulin in rat hippocampus and forebrain from 1 to 720 days of age using RNA gel-blot analysis. We find that (i) the microtubule-associated protein, MAP1B, signal was relatively abundant at early postnatal stages when compared with mature animals. The hybridization signal in the 24-month-old rats was was approximately 1.7 times that observed in 6-month-old rats. (ii) Embryonic alpha-tubulin and late neural beta-tubulin were differentially regulated during rat brain development. This regulation is characterized by a dramatic decrease in the amount of alpha-tubulin after day-1 and a coincident increase in the production of late neural beta-tubulin. Both messages became stabilized at moderate levels during the subsequent developmental stages. However, the averaged signal for beta-tubulin was then approximately 1.8-fold increased in 24- vs. 6-month-old rats. These results are consistent with hypothesis of an age-associated increase in reactive synaptogenesis where the healthy neurons sprout new connections to compensate for neuronal loss occurring in neighboring neurons.

[Potential cardiotonics. 13. Crystal structure, charge distribution and molecular electrostatic potential of 3-cyano-2-(3-diethyl-aminopropylamino)-5-(4-pyridinyl)pyridine (AWD 122-60)]. / Potentielle Kardiotonika. 13. Mitteilung: Kristallstruktur, Ladungsverteilung und molekulares elektrostatisches Potential von 3-Cyan-2-(3-diethylamino-propylamino)-5-(pyrid-4-yl)pyridin (AWD 122-60).

The crystal and molecular structure of the potential cardiotonic agent AWD 122-60 have been determined by X-ray structure analysis. Based on the molecular structure charge distribution and molecular electrostatic potential were evaluated. The results are discussed in comparison with those of other cardiotonic 3,4'-bipyridines.

Neural cell adhesion molecule (NCAM) and N-cadherin mRNA during development and aging: selective reduction in the 7.4-kb and 6.7-kb NCAM mRNA levels in the hippocampus of adult and old rats.

By examining the time course, from E15 to 720 days of age, for changes in the prevalence of mRNAs coding for neural cell adhesion molecule (NCAM), N-cadherin and alpha-tubulin in rat hippocampus and forebrain, it was concluded that (i) the NCAM 7.4-, 6.7-, 5.2-, 4.3- and 2.9-kb mRNAs are differentially regulated during development and aging; (ii) the 7.4- and 6.7-kb mRNA are drastically reduced starting from day 21 onward; (iii) the E15- and day-1-specific mRNA of 4.3 kb is replaced with the 5.2-kb mRNA starting with 21 days, thereafter the 5.2-kb message remained relatively constant over the entire life-span studied. Likewise, the 2.9-kb mRNA, which was very abundantly expressed at E15 and early postnatal stages, remained relatively constant between 180 days and 720 days; (iv) postnatal rat brains showed both qualitative and quantitative changes in N-cadherin 4.3- and 4.0-kb transcripts. The 4.3-kb mRNA was relatively abundant at 1 and 21 days postnatal stages, thereafter the signal remained very low over the entire life-span studied. The 4.0-kb message, which was specific for the E15 stage, was replaced with the 4.3-kb message; (v) as expected, the 1.8-kb mRNA coding for embryonic alpha-tubulin decreased dramatically after 1 day, but became stabilized at moderate levels during the subsequent developmental stages. At least for the NCAM gene, the regulation seems to occur post-transcriptionally, possibly at the level of RNA processing while the N-cadherin mRNA expression seems to be transcriptionally regulated.

Evidence that the V+ fibronectin mRNA is increased in the hippocampus of aged rats.

In this study we investigated the splicing pattern of fibronectin (FN) mRNA during development and aging by using Northern blot hybridization with probes that either recognize all forms of FN mRNA or that are specific for the different spliced forms (FN-EIIIA, FN-EIIIB, and FN-V). We find that (1) the FNmRNA in the hippocampus of some but not all old rats showed a pattern of splicing similar to that found in the forebrain of 21 day old rats and (2) the hybridization signal for the alternatively spliced FN mRNA containing the EIIIA, EIIIB, and V95 segments was relatively abundant at early postnatal stages but very few transcripts were detected in adult and old rats. However, the hybridization signal for the juvenile FN-V mRNA was markedly increased in some but not all two-year-old rats suggesting that aging is an individual process.

Prediction and establishment of a new crystalline piroxicam modification.

The existence of a new crystalline modification of the analgesic and antiinflammatory agent piroxicam was predicted. A model of the structure was derived from the crystal data of the alpha-modification. Lattice constants and molecular packing parameters were refined using X-ray powder diffraction data.

[Potential cardiotonic agents. 4. Synthesis, cardiovascular activity, molecular and crystal structure of 5-phenyl- and 4-(4-pyridinyl)-substituted 2(1H)-pyridinethiones]. / Potentielle Kardiotonika. 4. Mitteilung5: Darstellung, kardiovaskuläre Wirksamkeit, Molekül- und Kristallstruktur von 5-phenyl- und 5-(pyrid-4-yl)-substituierten 1,2-Dihydro-pyrid-2-thionen.

Cyclisation of the vinylogous amidinium salt 1 or the 4-ethoxy- and 4-morpholino-3-butene-2-ones, respectively, 4 and 6 with cyano-thioacetamide yielded the 5-(4-pyridinyl)-, 6-methyl-5-(4-pyridinyl)- and 6-methyl-5-phenyl-, respectively, substituted 3-cyano-2(1H)-pyridinethiones 3, 5 and 7. The 2(1H)-pyridinethiones 3, 5 and 7a as well as the in 3-position unsubstituted or carbamoyl substituted derivatives 8 and 9 were obtained from the corresponding 2-chloro-pyridines and potassium sulfide, too. Especially compound 5 showed remarkable positive inotropic potency and, additionally, vasodilator activity. The molecular and crystal structure of 5 have been determines by X-ray structure analysis. Based on the molecular structure charge distribution and electrostatic potential were evaluated. The results are discussed in comparison with those of milrinone.