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Readily available from alpha-cyclodextrin in three steps, 2,3-anhydro-alpha-cyclomannin composed of six alpha-(1-->4)-linked 2,3-anhydro-D-mannopyranose residues, crystallizes well when precipitated from aqueous ethanol. An X-ray structure reveals the macrocycle to contain ethanol in its cavity, thus representing the first inclusion complex of a non-glucose cyclooligosaccharide. The wider rim of the torus-shaped macrocycle holds the six epoxide rings whose oxygens point away from the cavity, thereby sculpturing the unique over-all shape of a six-pointed star.

Dissolution of alpha-cyclodextrin (alpha-CD) in 9:1 water-nitromethane smoothly generates the title compound, which crystallizes as the pentahydrate in the orthorhombic space group P2(1)2(1)2(1) with a = 9.452(4), b = 14.299(3), c = 37.380(10) A, and Z = 4. Its crystal structure analysis revealed the alpha-CD macrocycle in an unstrained conformation stabilized through a ring of O-2...O-3' hydrogen bonds between five of the six adjacent glucose residues. The nitromethane is located in the alpha-CD cavity in an orientation parallel to the plane of the macrocycle, and assumes two sites of equal population with the nitro group in excessive thermal motion; the guest is held by van der Waals contacts and C-H...O-type hydrogen bonds to the pyranose H-3 and H-5 protons. The packing of the macrocycles in the crystal lattice is of cage herringbone-type with an extensive intra- and intermolecular hydrogen bonding network. The ready formation of a nitromethane inclusion complex in aqueous nitromethane, and the subtleties of its molecular structure amply demonstrate the ease with which water is expelled from the alpha-CD cavity by a more hydrophobic co-solvent.

A series of trifluoromethyl-containing analogs of captopril as well as analogs and homologs of enalaprilat were synthesized and evaluated for inhibition of angiotensin converting enzyme (ACE). It was found that direct substitution of trifluoromethyl for methyl produced a very potent captopril analog with an IC50 of 3 x 10(-10) M in vitro. Hydrophobicity and conformational effects of trifluoromethyl group are among the reasons accounting for this activity. Structure-activity relationship is studied based on molecular mechanics calculations using a II-SCF-molecular mechanics program (PIMM) as well as SYBYL molecular mechanics program. It was found that simultaneous incorporation of trifluoromethyl and an indoline residue unexpectedly yielded a less potent captopril analog (IC50 = 8 x 10(-8) M). Enalaprilat analogs derived from replacement of the alanine residue with trifluoronorvaline and trifluoronorleucine residues gave moderately potent compounds (IC50 = 2-6 x 10(-8) M). The structure-activity relationship for these fluoroenalaprilat analogs is discussed in comparison with known analogs.

2,6-Dihydropyran-3-ones carrying substituents at C-2 and C-6 in cis-arrangement invariably adopt half-chair conformations in which the ring oxygen and the carbon atom next to the carbonyl group are above and below, respectively, the plane formed by the other four carbon atoms, i.e., the 2Ho or oH2 conformation. In the case of a trans-arrangement of 2,6-substituents, the geometry of the pyranoid ring falls into the Bo,6<-->Eo<-->2Ho or thet inverse o,6B<-->oE<-->oH2 section of the conformational cycle, depending on the absolute configuration of the compound; for two of the dihydropyranones, 4B and 6, a unique skew-boat (SBo,6) conformation, fixed between the Bo,6 and Eo geometries, was ascertained, which previously has only been observed for pyranoid enelactones.

A pi-SCF/Molecular Mechanics method (PIMM) for the calculation of heats of formation, molecular geometries and charge density distributions of organic molecules is described. The method combines a pi-SCF molecular orbital calculation and the sigma-charge evaluation procedure PEOE of Marsilli and Gasteiger with molecular mechanics. The formulas and parameters used are given. A series of results for small molecules is presented and compared with experimental data.

The crystal structure of 5-nitrouridine was determined by X-ray analysis. The pyrimidine ring is slightly non-planar, showing a shallow boat conformation. The nitro group has no influence on the C4 - O4 bond length as compared to uridine. The ribose shows the C3'-endo conformation and the base is in the anti orientation to the sugar with a torsion angle of 25.6 degrees. This conformation is stabilized by a hydrogen bond from the base to the ribosyl moiety (H6 ... 05'). Stacking interactions between neighboring bases are almost negligible in the crystal. A water molecule is involved in a bifurcated donating hydrogen bond to 04 and to 052 of the nitro group of the one base and an accepting bond from the H3 of the other base. Two more hydrogen bonds are formed between the water molecule and the ribose. The structural aspects of 5-nitrouridine are discussed with respect to the special stacking features found for 5-nitro-1-(beta-D-ribosyluronic acid)-uracil monohydrate in the crystal (1).

A system for measuring oxygen consumption from momentary respiratory values of free moving person is described. The main part presented here is a sensor consisting of a flowmeter based on the impeller principle, called 'Wirbelrespirometer', joint with a polarographic electrode sensitive to oxygen, and a very fast reacting thermistor. First comparative studies in computation of respiratory volume and oxygen consumption yielded average deviations against comparison methods of less than +/- 1% for computation of volume, and +/- 4% for computation of oxygen consumption.

In contrast to the drug testing under clinical conditions, many other problems appear in regard to outpatients. These investigations were carried out on 49 outpatients with various degrees of angina pectoris under the conditions of an intraindividual comparison with d,l-oxyfedrine (Myofedrin), l-oxyfedrine (ildamen) or placebo for a period of 16 weeks and a daily dose of 48 mg applied orally altogether. The severity degrees of the angina pectoris were diminished after the chronic application of l- and d,l-oxyfedrine. There are no differences in the activity and side-effects.