Reproducability and transferability of topological properties; experimental charge density of the hexapeptide cyclo-(D,L-Pro)2-(L-Ala)4 monohydrate.

The charge density of a hexapeptide was determined from high-resolution CCD area-detector experiments at 100 K. Two datasets, one from a rotating anode and a second one from synchrotron radiation, were measured and the results are compared. The data are interpreted in terms of the 'rigid pseudoatom' model. The topology of the experimental density is analyzed and compared with the topology of the constituting amino acids, and shows good agreement. All critical points of the electron density at the covalent and hydrogen bonds, as well as those of the Laplacian, were located. With respect to the transferability of electronic and bond topological properties the six peptide bonds were compared with values given in the literature.

Electron-density distribution in stishovite, SiO2: a new high-energy synchrotron-radiation study.

The electron-density distribution of the high-pressure polymorph of SiO2, stishovite [a = 4.177 (1), c = 2.6655 (5) A, space group P4(2)/mnm, Z = 2], has been redetermined by single-crystal diffractometry using synchrotron radiation of 100.42 and 30.99 keV, respectively, in order to obtain essentially absorption- and extinction-free data. Room-temperature diffraction experiments on two samples of irregular shape were carried out on two different diffractometers installed at HASYLAB/DESY, Hamburg, Germany. The structure refinement on the high-energy data converged at R(F) = 0.0047, wR(F) = 0.0038, GoF = 0.78, for a multipole model with neutral atoms and multipole expansions up to seventh order. For each atom, the radial expansion coefficients of the multipole orders (l > 0) were constrained to a common value. The absence of extinction was indicated by a refined correction parameter equalling zero within error limit. The excellent quality of the data is also illustrated by a high-order (HO) refinement (s > 0.7 A(-1)) yielding R(F) = 0.0060, wR(F) = 0.0048, GoF = 0.85. Both static deformation electron-density distribution and structure amplitudes compare well with corresponding results obtained from band-structure calculations using the linearized-augmented-plane-wave (LAPW) method. Ensuing topological analysis of the total model electron density distribution revealed bond critical point properties for the two unique Si--O bonds, indicating a predominantly closed-shell interaction mixed with a significant shared interaction contribution that decreases with increasing interatomic distance. Calculation of atomic basins yielded charges of +3.39 e and -1.69 e for Si and O, respectively, in good agreement with the theoretically calculated values of +3.30 e and -1.65 e. The volumina of the Si and O basins are 2.32 and 10.48 A3, corresponding to spheres with radii of 0.82 and 1.36 A, respectively. The results also conform well with correlations between bond length and bond critical point properties reported in the literature for geometry-optimized hydroxyacid molecules. Estimates of the Si cation electronegativity indicate that the change of Si coordination by oxygen from 4 to 6 is accompanied by an increase of the ionicity of the Si--O bond of about 7%.

Synthesis and antibacterial study of unsaturated Mannich ketones.

Several Mannich ketones of 2-arylmethylenecycloalkanones were synthesised using the classical acid-catalysed Mannich reaction. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cell line cytotoxicity of our new compounds was evaluated against HeLa cell lines. Some compounds showed low cytotoxicity (41.52 nM mL(-1) for 14 and 46.60 nM mL(-1) for 18) and proved to be efficient antibacterial agents against the Gram-positive strains. Minimum inhibitory concentrations varied from 1.56 to 100 microg mL(-1). The mechanism of action was examined, too.

Topological properties of the peptide bond in glycyl-L-threonine dihydrate based on a fast synchrotron/CCD-diffraction experiment at 100 K.

The charge density of glycyl-L-threonine dihydrate is extracted from a synchrotron data set of 98405 reflections collected at 100 K with a Bruker CCD area detector up to a resolution of d=0.38 A (sintheta/lambda = 1.32 A 1). The data are interpreted in terms of the "rigid pseudoatom" model. The topology of the experimental density is analyzed and compared with the topology obtained experimentally for the constituting amino acids and to that derived from Hartree-Fock calculations for the isolated molecule. All critical points of the electron density at the covalent and hydrogen bonds, as well as those of the Laplacian, were located, thereby deriving quantitative topological data for the peptide and side chain bonds. Bond topological indices in the dipeptide compare well with those of the corresponding bonds in the building amino acids, thus suggesting transferability of electronic properties of atoms and functional groups when these are derived by Bader's partitioning. Discrepancies between theoretical and experimental results could be attributed to crystal field effects.

Accurate experimental electronic properties of dl-proline monohydrate obtained within 1 Day

A 1-day x-ray diffraction experiment on dl-proline monohydrate was performed at 100 kelvin with synchrotron radiation and a charge-coupled device area detection technique. The accuracy of the charge density distribution and of the related electronic properties extracted from these data is comparable or even superior to the accuracy obtained from a 6-week experiment on dl-aspartic acid with conventional x-ray diffraction methods. A data acquisition time of 1 day is comparable to the time needed for an ab initio calculation on the isolated molecules. This technique renders larger molecular systems of biological importance accessible to charge density experiments.

A Mirror Furnace for Synchrotron Diffraction Experiments up to 1600K.

An X-ray mirror fumace is described that has been developed for in situ diffraction experiments at a synchrotron source for temperatures up to 1600 K. It can be used in a reducing as well as in an oxidizing atmosphere. In this kind of furnace, the sample is located at one focus of a rotational ellipsoid and heated by the radiation of a halogen lamp located at the other focus. The furnace has been designed to work on a four-circle diffractometer with minimum restriction of the setting angles.

Influence of glucose, insulin and sera from diabetic patients on the prostacyclin synthesis in vitro in cultured human endothelial cells.

The effects of glucose, insulin and sera from Type 1 (insulin-dependent) diabetic patients on the synthesis of prostacyclin in vitro were studied in confluent primary cultures of human endothelial cells. The stable metabolite, 6-keto-prostaglandin F1 alpha, was measured in growth medium after 24 h of incubation with endothelial cells in a buffer incubated with the cells for 10 min on a rocker platform, and in a buffer solution of ruptured cells. Glucose (11, 15, 20 or 25 mmol/l) and glucose (11 mmol/l) plus insulin (10(3), 10(4) or 10(6) mU/l) in growth medium did not have any effects on the prostacyclin synthesis. The prostacyclin synthesis was significantly reduced in cell cultures incubated with medium supplemented with 10% serum from patients with Type 1 diabetes (p less than 0.01) compared with cultures incubated with pooled serum from healthy blood donors. These data suggest that diabetic sera inhibit the prostacyclin synthesis in cultured endothelial cells unrelated to the glucose and insulin levels.

The effect of albumin bound polyunsaturated fatty acids on human platelets.

Platelet rich plasma (PRP) was incubated at 22-24 degrees C for 24 hr with various polyunsaturated fatty acids (PUFA), bound to albumin, to determine whether changes in the FA composition of the platelet phospholipids might induce changes in platelet behavior and in platelet structural integrity. The PUFA tested were linoleic (18:2 w6), linoleic (18:3 w3), dihomo-gamma linolenic (20:3 w6), arachidonic (20:4 w6) and eicosapentaenoic acids (20:5 w3). Only PRP incubated with 20:3 w6 and 20:5 w3 incorporated significant amounts of these FA into the platelet phospholipids and showed inhibition of aggregation and TxB2 production with collagen. However, the inhibition was not due to the incorporation of these FA's into the phospholipids as observed by washing and resuspension of the FA incorporated platelets in control plasma, or to any change in structural integrity. It is suggested that the effect of 20:3 w6 and 20:5 w3 on aggregation is due to metabolites of these FA's released from the platelets.