Determination of thermodynamic pKa values of benzimidazole and benzimidazole derivatives by capillary electrophoresis

Thermodynamic pK_a values for benzimidazole and several substituted benzimidazoles were determined by CE. Electrophoretic mobilities of benzimidazoles were determined by CE at different pH levels and ionic strengths. The dependence of electrophoretic mobilities on pH was used to obtain pK_a values at different ionic strengths. Extrapolations to zero ionic strength were used to determine the thermodynamic pK_a values. Using this method the thermodynamic pK_a values of 15 benzimidazoles were determined and found to range from 4.48 to 7.38. Results from the CE measurements were compared with spectrophotometric measurements which were evaluated at wavelengths where the highest absorbance difference for varying pH was recorded. The two analytical techniques were in good agreement.     

Direct imaging of repulsive and attractive colloidal glasses

Coherent anti-Stokes Raman scattering microscopy is performed on glassy systems of poly(methylmethacrylate) colloidal particles in density- and refractive-index-matched solvents. Samples are prepared with varying amounts of linear polystyrene, which induces a depletion driven attraction between the nearly hard-sphere particles. Images collected over several hours confirm the existence of a reentrant glass transition. The images also reveal that the dynamics of repulsive and attractive glasses are qualitatively different. Colloidal particles in repulsive glasses exhibit cage rattling and escape, while those in attractive glasses are nearly static while caged but exhibit large displacements upon (infrequent) cage escape.     

PLS and first derivative of ratio spectra methods for determination of hydrochlorothiazide and propranolol hydrochloride in tablets

Two new analytical methods have been developed as convenient and useful alternatives for simultaneous determination of hydrochlorothiazide (HCT) and propranolol hydrochloride (PRO) in pharmaceutical formulations. The methods are based on the first derivative of ratio spectra (DRS) and on partial least squares (PLS) analysis of the ultraviolet absorption spectra of the samples in the 250–350-nm region. The methods were calibrated between 8.7 and 16.0 mg L⁻¹ for HCT and between 14.0 and 51.5 mg L⁻¹ for PRO. An asymmetric full-factorial design and wavelength selection (277–294 nm for HCT and 297–319 for PRO) were used for the PLS method and signal intensities at 276 and 322 nm were used in the DRS method for HCT and PRO, respectively. Performance characteristics of the analytical methods were evaluated by use of validation samples and both methods showed to be accurate and precise, furnishing near quantitative analyte recoveries (100.4 and 99.3% for HCT and PRO by use of PLS) and relative standard deviations below 2%. For PLS the lower limits of quantification were 0.37 and 0.66 mg L⁻¹ for HCT and PRO, respectively, whereas for DRS they were 1.15 and 3.05 mg L⁻¹ for HCT and PRO, respectively. The methods were used for quantification of HCT and PRO in synthetic mixtures and in two commercial tablet preparations containing different proportions of the analytes. The results of the drug content assay and the tablet dissolution test were in statistical agreement (p < 0.05) with those furnished by the official procedures of the USP 29. Preparation of dissolution profiles of the combined tablet formulations was also performed with the aid of the proposed methods. The methods are easy to apply, use relatively simple equipment, require minimum sample pre-treatment, enable high sample throughput, and generate less solvent waste than other procedures. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Parity-violating electron scattering from 4He and the strange electric form factor of the nucleon

We have measured the parity-violating electroweak asymmetry in the elastic scattering of polarized electrons from 4He at an average scattering angle = 5.7 degrees and a four-momentum transfer Q2 = 0.091 GeV2 . From these data, for the first time, the strange electric form factor of the nucleon G(E)s can be isolated. The measured asymmetry of A(PV) = (6.72 +/- 0.84(stat) +/- 0.21(syst) x 10(-6) yields a value of G(E)s = -0.038 +/- 0.042(stat) +/- 0.010(syst), consistent with zero.     

On expansion and topological overlap

We give a detailed and easily accessible proof of Gromov’s Topological Overlap Theorem. Let X be a finite simplicial complex or, more generally, a finite polyhedral cell complex of dimension d. Informally, the theorem states that if X has sufficiently strong higher-dimensional expansion properties (which generalize edge expansion of graphs and are defined in terms of cellular cochains of X) then X has the following topological overlap property: for every continuous map \(X\rightarrow \mathbb {R}^d\) there exists a point \(p\in \mathbb {R}^d\) that is contained in the images of a positive fraction \(\mu >0\) of the d-cells of X. More generally, the conclusion holds if \(\mathbb {R}^d\) is replaced by any d-dimensional piecewise-linear manifold M, with a constant \(\mu \) that depends only on d and on the expansion properties of X, but not on M.     

Method for determination of silicon in plant materials by neutron activation analysis

Silicon has been found to be an essential element for the growth and development of many ecomomically important plants such as sugarcane, rice, oats, and wheat. A method is described for the quantitative determination of silicon in plant samples. Measurements were made with two Ge(Li) detectors matched with a multiplexing unit to provide a single amplified signal to a computerized analyzer system. For those materials containing greater than 0.5 weight percent silicon, the reaction²⁹Si(n, p)²⁹Al (1273 keV) provides a direct measurement of the quantity of silicon provided the irradiation is done in a special boron nitride capsule to reduce interferences from thermal neutron reactions and a correction is made for the single escape line from²⁸Al (1268 keV). For lesser quantities of silicon, a technique which utilizes the fast neutron reaction²⁸Si(n, p)²⁸Al is preferred. Corrections for the interference produced by the presence of phosphorus³¹P(n, α)²⁸Al are made by determining the phosphorus content following the instrumental analysis using a unique application of neutron activation analysis, i. e., measurement of tungsten in tungstomolybdophosphoric acid produced when molybdate and tungstate ions are added to dissolved samples of the plant material containing phosphorus. Aluminum, which may also produce an interference by thermal neutron reaction²⁷Al(n, γ)²⁸Al, is determined directly from the original activation data after subtracting out the effect of the phosphorus. Thus, three irradiations in the pneumatic sample irradiator are necessary; one short irradiation (1 min) without thermal neutron shielding, a longer irradiation (6 min) in the boron capsule, and a final irradiation of the tungstomolybdophosphoric acid provide all data required to accurately determine silicon in plant materials. A computer program has been developed that provides rapid reduction of the data in final report format. Elements such as sodium, chlorine, calcium, manganese, potassium, and magnesium extrinsic to the analysis for silicon are also determined by this method. The method has been tested on a large number of samples and reliable results are obtained with less than 0.2 g of sample. This work was supported by Grant 533 from the Michigan Memorial—Phoenix Project.     

Kinetics of the reaction of OH with HCl

The rate constant of the reaction OH + HCl → H₂O + Cl was measured in a flow tube over the temperature range 224 to 460°K using resonance fluorescence detection of OH. An Arrhenius expression k₁ = (2.0 ± 0.1) × 10^?12 exp [?(620 ± 20 cal/mole)/RT] was obtained. Stratospheric and reaction kinetic implications are discussed briefly.     

Micelle-induced curvature in a water-insoluble HIV-1 Env peptide revealed by NMR dipolar coupling measurement in stretched polyacrylamide gel

The structure of a water-insoluble fragment encompassing residues 282-304 of the HIV envelope protein gp41 is studied when solubilized by dihexanoyl phosphatidylcholine (DHPC) and by small bicelles, consisting of a 4:1 molar ratio of DHPC and dimyristoyl phosphatidylcholine (DMPC). Weak alignment with the magnetic field was accomplished in a stretched polyacrylamide gel, permitting measurement of one-bond (1)H-(15)N, (13)Ca-(13)C', and (13)C'-(15)N dipolar couplings, which formed the basis for determining the peptide structure. In both detergent systems, the peptide adopts an alpha-helical conformation from residue 4 through 18. In the presence of the DHPC micelles the helix is strongly curved towards the hydrophobic surface, whereas in the presence of bicelles a much weaker curvature in the opposite direction is observed.     

1-substituted beta-carbolines by a Pictet-Spengler cyclization with thioortho esters and carbon-carbon bond formation via N-sulfonyl iminium ions generated from N,S-sulfonyl acetals

The reaction of N-tosyltryptamines with thioortho esters, leading to 1-thiosubstituted tetrahydro-beta-carbolines under modified Pictet-Spengler conditions, is described. The 1-heterosubstituted beta-carbolines furnished 1-substituted beta-carbolines upon reaction with Grignard reagents and silyl derivatives under Lewis acid promotion. [reaction: see text]     

Ab-initio and approximately rigorous calculations on small,medium, and large systems

We have explored two areas of approximately rigorous calculations for computing nonempirical wave functions for heavy and/or large molecules orders of magnitude faster than with conventional ab-initio methods but with the same chemical accuracy. First, we have developed and used a series of programs (starting from our new fast sets of ab-initio Gaussian SCF and SCF -CI programs) incorporating ab-initio effective core model potentials (MOD -POT ) which allow one to treat only the valence electrons explicitly, plus a charge conserving integral prescreening, which cuts down significantly on the number of integrals that have to be calculated, stored, or processed for a large molecule. We have named this latter procedure VRDDO (variable retention of diatomic differential overlap). With these MODPOT and MODPOT /VRDDO methods we have explored a variety of small, medium, and large systems ranging from electron affinities of atoms through to molecules of biological interest and large boron hydrides. The results compared to ab-initio SCF or SCF /CI calcuations are very good, usually within 0.001 to 0.002 a.u. for orbital energies and gross atomic populations (GAPS ) and even better along potential energy curves. Secondly, we have explored the use of the MS -Xα method for less conventional molecules and properties than those for which it is customarily employed.