Molecular structure,p<Emphasis Type="Italic">K</Emphasis>a,lipophilicity, solubility,absorption, polar surface area,and blood brain barrier penetration of some antiangiogenic agents

The methods of theoretical chemistry have been used to elucidate molecular properties of selected and novel antiangiogenic agents (semaxanib, sunitinib, N-methylsunitinib, sorafenib, motesanib, ABT-869, vatalanib, vandetanib, AEE 788, CP-547632, A-1, A-2, A-3, and A-4). The geometries and energies of these drugs have been computed using HF/6-31G(d), Becke3LYP/6-31G(d) and Becke3LYP/6-31++G(d,p) model chemistries. Wherever possible the most stable conformations of inhibitors studied are stabilized by means of intramolecular hydrogen bonds. Water has a remarkable effect on the geometry of the antiangiogenic agents studied. Computed partition coefficients (ALOGPS method) varied between 2.3 and 5. Compounds studied are described as lipophilic inhibitors. Semaxanib is inhibitor with lowest lipophilicity. The antiangiogenic agents studied are only slightly soluble in water; their computed solubility (log S) from interval between −3.4 and −5.4 is sufficient for fast absorption. Selection criteria for drug-like properties of VEGFR2 inhibitors investigated were designed. Based on these criteria, three compounds (A-2, A-3, and A-4) were selected for synthesis and biological testing for antianiogenic activity on VEGFR2 receptor.     

Abkühlungskurven von Natriumstearatlösungen in Gegenwart von Elektrolyten

Ohne Zusammenfassung Ins Deutsche übersetzt von E. Lottermoser (Leipzig).     

Relaxation of piezobirefringence in triglycine sulfate crystals

The effect of photoelastic relaxation is investigated using triglycine sulfate ferroelectric crystals as an example. The optical and deformation contributions to the photoelastic relaxation are described, and their percentage in the combined effect is determined. Consideration is given to the temperature dependences of the relaxation amplitudes of the path difference and birefringence, which are induced by mechanical stress.     

Calibration relations for nonpolynomial splines

Nonpolynomial (X, A, ϕ)-splines of the third order and the special case of B _ϕ-splines of class C² are studied. For such splines calibration relations are obtained, owing to which the coordinate splines on the original grid is represented in terms of the coordinate splines on a refined grid. A nonlinear mapping (ℝ⁴)⁹ ↦ ℝ⁴ and locally orthogonal chains of vectors are used for this purpose. Bibliography: 22 titles. __________ Translated from Problemy Matematicheskogo Analiza, No. 34, 2006, pp. 39–54.     

ToF-SIMS characterisation of diterpenoic acids after chromatographic separation

Microcolumn liquid chromatography (μHPLC) coupled on-line with time of flight secondary ion mass spectrometry (ToF-SIMS) was applied for mixture of diterpenoic acids (abietic, gibberellic and kaurenoic) analysis. Chromatographic effluent, with analytes separated, was carried out directly onto different, ToF-SIMS compatible surface substrates, for further ToF-SIMS analysis. Silica gel Si₆₀, aluminium backplate modified Si₆₀, monolithic silica gel and Raman spectroscopy chromatographic thin layers were used as the deposition substrates in this experiment. By ToF-SIMS surface imaging the deposition trace picture has been obtained. Effluent deposition surface area was scanned for diterpenoic acid fragment mass values based on mass spectrometric library. Measured ToF-SIMS dataset of fragment abundance and intensities were used for preliminary fragmentation schemes construction. The lowest substrate background activity has been established for monolithic silica gel thin layer and aluminium backplate modified Si₆₀ thin layer. In the case of Raman spectroscopy pre-treated thin layer or conventional chromatographic thin layer Si₆₀, the both, high background signal intensity and impossibility to construct negative ions surface image, were observed. Diterpenoic acids studied serve the similar mass spectrum but ToF-SIMS coupled with liquid chromatographic separation brings new impact to the positive identification of analytes studied.     

Gravitational Stability of the Interface in Water Over Steam Geothermal Reservoirs

Stability of a geothermal system is considered in a case when the water layer lies over the layer of superheated vapor in a stratum having relatively low permeability. This stratum locates between two parallel high permeable layers. Under the assumption of smallness of advective energy transfer as compared with the conductive one, the stationary distribution of the characteristics in the stratum with an interface of phase transition is obtained. The interface separates the domains occupied by water and vapor. Investigation of normal stability of the interface shows, that stable configurations in the geothermal system under consideration exist within the range of permeability values bounded by k 0.6 × 10^–15 m² from above. The most unstable configurations occur to be the quiescent states when the permeability exceeds a certain threshold. A sufficiently high value of permeability, satisfying the criterion of smallness of the advective energy transfer as compared with the conductive one makes it possible to explain the existence of a wide class of stable natural geothermal reservoirs, where the vapor layer underlies the water one.