A 3D QSAR study on a set of dopamine D4 receptor antagonists

The molecular alignments obtained from a previously reported pharmacophore model have been employed in a three-dimensional quantitative structure-activity relationship (3D QSAR) study, to obtain a more detailed insight into the structure-activity relationships for D(2) and D(4) receptor antagonists. The frequently applied CoMFA method and the related CoMSIA method were used. Statistically significant models have been derived with these two methods, based on a set of 32 structurally diverse D(2) and D(4) receptor antagonists. The CoMSIA and the CoMFA methods produced equally good models expressed in terms of q(2) values. The predictive power of the derived models were demonstrated to be high. Graphical interpretation of the results, provided by the CoMSIA method, brings to light important structural features of the compounds related to either low- or high-affinity D(2) or D(4) antagonism. The results of the 3D QSAR studies indicate that bulky N-substituents decrease D(2) binding, whereas D(4) binding is enhanced. Electrostatically favorable and unfavorable regions exclusive to D(2) receptor binding were identified. Likewise, certain hydrogen-bond acceptors can be used to lower D(2) affinity. These observations may be exploited for the design of novel dopamine D(4) selective antagonists.     

Diphosphacarbollide analogues of the C5H5- anion: isolation of the nido-di- and triphosphacarboranes 7,8,9-P2CB8H10, [7,8,9-P2CB8H9]-, [7,8,10-P2CB8H9]-, and 7,8,9,10-P3CB7H8

Treatment of a solution of excess PCl(3) and PS (PS = "proton sponge" = 1,8-dimethylamino naphthalene) with arachno-4-CB(8)H(14) (1) in CH(2)Cl(2), followed by hydrolysis of the reaction mixture, resulted in the isolation of the eleven-vertex diphosphacarbaborane nido-7,8,9-P(2)CB(8)H(10) (2) (yield 34%) as the main product. Other products isolated from this reaction were the phosphacarboranes nido-7,8,9,10-P(3)CB(7)H(8) (3) (yield 5%) and closo-2,1-PCB(8)H(9) (4) (yield 15%). Compound 2 can be deprotonated by PS in CH(2)Cl(2) or NaH in diethyl ether to give the [nido-7,8,9-P(2)CB(8)H(9)](-) (2(-)()) anion, which gives back the original compound, 2, upon re-protonation. Thermal rearrangement of anion 2(-) (Na(+) salt) at 350 degrees C for 2 h produced the isomeric [nido-7,8,10-P(2)CB(8)H(9)](-) (5(-)()) anion, which was isolated as a PPh(4)(+) salt (yield 86%). Multinuclear ((1)H, (11)B, (31)P, and (13)C), two-dimensional [(11)B-(11)B] COSY, (1)H{(11)B(selective)}, (1)H{(31)P(selective)}, and gradient-enhanced ([(1)H-(13)C] HSQC) magnetic resonance measurements led to complete assignments of all resonances which are in excellent agreement with the structures proposed. Coupling constants, (1)J((31)P,(13)C), (2)J((31)P,C,(1)H), and (1)J((31)P,(31)P), were calculated using the DFT method B3LYP/6-311+G(d,p). The molecular geometries of all compounds were optimized ab initio at a correlated level of theory (RMP2(fc)) using the 6-31G basis set, and their correctness was assessed by comparison of the experimental (11)B and (13)C chemical shifts with those calculated by the GIAO-SCF/II//RMP2(fc)/6-31G method. The computations also include the structures and chemical shieldings of the still unknown isomers [nido-7,10,8-P(2)CB(8)H(9)](-) (6(-)) and [nido-7,9,8-P(2)CB(8)H(9)](-) (7(-)).     

Determination of the enantiomeric composition of chiral carboxylic acids using chiral derivatization and HPLC

Summary The enantiomers of chiral carboxylic acids were separated as their diastereomeric amides with (1R,2R)-(−)-1-(4-nitrophenyl)-2-amino-1,3-propanediol (“levobase”) and with “dextrobase” (the enantiomer of levobase) by high-performance liquid chromatography using a conventional C-18 column and various solvent systems containing acetonitrile, methanol, water, and phosphoric acid.     

Analysis of cyanobacterial toxins (anatoxin-a, cylindrospermopsin, microcystin-LR) by capillary electrophoresis

Capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) were applied to the simultaneous separation of cyanobacterial toxins (anatoxin-a, microcystin-LR, cylindrospermopsin). The analytical performance data of both methods, optimized for the three toxins, were similar with a precision of migration times smaller than 0.8 RSD% and a detection limit in the range of 1-4 microg/mL, using spectrophotometric detection at 230 nm. Both methods were applied to an analysis of cyanotoxins in water bloom samples and crude cyanobacterial extracts. The results obtained indicate that, for complex matrices, the sequential application of CZE and MEKC is necessary. It is recommended to use both CE techniques for the analysis of the same sample in order to confirm the results by an orthogonal approach.     

Charged particle evaporation from compound nuclei formed by bombardment of58Ni with 70 MeV16O ions II

The experimental data have been compared with the result of extensive compound nucleus calculations based on the statistical theory. The shapes and the absolute cross sections for the high energy parts of the proton- and -spectra are reproduced with a level density parametera 0·11 A MeV^–1 and a moment of inertiaJ1·3J _rig. The same parameters fairly well reproduce the angular distributions corresponding to the high energy parts of the spectra whereas deviations between theory and experiment are observed for the lower energies where particles emitted by higher order processes contribute. The observed total cross section for emission of an -particle is 500 mb or 1·7 times calculated value. For protons the corresponding numbers are 2313 mb and 3·0. The increase in cross section is ascribed to the process in which several particles are evaporated. Various methods are discussed for determination of the average orbital angular momentum of the emitted particle or the average spin of the daughter nucleus.On leave fromFaculty of Matematics and Physics, Charles University, Prague, Czechoslovakia.     

Applications of the MBPT in the localized representation

Diagrammatic formulation of the MBPT is applied when the occupied and the virtual canonical orbitals are separately localized by unitary transformations. In this localized representation, due to the off-diagonal Fock matrix elements, the perturbation operator contains extra terms generating the so-called localization corrections. These corrections enter the perturbation energy in third and higher orders. Their magnitude depends on the type of localization, but they represent only a small fraction of the canonical corrections. The calculation of the localization corrections, however, does not need a significant amount of extra computer time. It is shown that by introducing an “order of neighborhood” local and nonlocal effects of the electron correlation can be separated and the contribution of the nonlocal effects can be neglected to a good approximation. Ab initio calculations have been carried out for the normal saturated hydrocarbons: C_2n+1H_4n+4 and for the all-trans conjugated polyenes C_2n+2H_2n+4. As to the ratio of the local and nonlocal corrections, it is shown that there is only a quantitative difference for these two kinds of systems (strongly or weakly localizable). Neglecting nonlocal effects, considerable amount of computer time can be saved.     

First order magnetic transition,magnetic structure,and vacancy distribution in Fe2P

The para- to ferromagnetic transition in Fe₂P has been studied using Mössbauer spectroscopy. The magnetic hyperfine fields drop abruptly from about half of their saturation values to zero at 214.5 K indicating a first order transition. The isomer shifts show a discontinuous change at the transition point. For some samples the transition takes place over a wide temperature range, probably due to impurities and other imperfections in the samples. From the magnetic hyperfine fields at 15 K the magnetic moments can be deduced to be 1.14 μ_B and 1.78 μ_B for Fe(1) and Fe(2), respectively. An assignment of the components in the Mössbauer spectra to the two crystallographically nonequivalent iron positions has been made from the temperature variation of the spectra.The ordering of metal vacancies has been investigated by a Mössbauer study of a nonstoichiometric Fe₂P sample and by an X-ray diffraction study of a nonstoichiometric Mn₂P crystal.     

A New Gamma-Ray Spectrum Catalog for PGAA

A major obstacle to the use of the prompt gamma activation analysis (PGAA) method has so far been the lack of a suitable library. Therefore, new measurements have been performed at the PGAA facility at Budapest Research Reactor (BRR) in order to create a prompt -ray catalog for qualitative and quantitative analysis. Prompt -ray energies and associated k ₀-factors have been determined by internal standardization. The resulting catalog contains prompt -ray data from neutron capture and other reactions such as (n,), and decay -ray data from short-lived reaction products. Data have been measured for nearly all stable elements, from hydrogen to uranium. Generally, data for several isotopes are given, to enable isotopic analysis as well.     

A new synthesis of pyrazolo[1,5-d][1,2,4]triazines from pyrazolecarboxylic acid hydrazides and carbonyl compounds. I

Pyrazolo[1,5-d][1,2,4]triazines were synthesized from pyrazolecarboxylic acid hydrazides and carbonyl compounds. Pyrazolecarboxylic acid N-phenylhydrazide (1c) and formaldehyde gave not only the expected 4hn but 5 , respectively. The methyl substituted hydrazides with acetone afforded hydrazones, pyrazolotriazines or 13 depending on the position of the substituents. The reduction of both products yielded pyrazolecarboxylic acid hydrazides.     

Synthesis of N-(4′-Benzo[15-crown-5])biphenylaminoglyoxime and Its Complexes with Some Transition Metals

N-(4-Benzo[15-crown-5])biphenylaminoglyoxime (H₂L) and sodium chloride salt of N-(4-benzo[15-crown-5])biphenylaminoglyoxime (H₂L · NaCl) have been prepared from 4-biphenylchloroglyoxime, 4-aminobenzo[15-crown-5], and sodium bicarbonate and sodium chloride. Nickel(II), cobalt(II), and copper(II) complexes with H₂L and H₂L · NaCl have a metal–ligand ratio of 1 : 2 and the ligand coordinates through the two N atoms, as do most of the vic-dioximes. Their IR spectra and elemental analyses are given, together with ¹H NMR spectra of the ligands.