Polymorphism in Dethoxyprone,a steroidal anesthetic. II. Crystal and molecular structure of 11α-dimethylamino-2β-ethoxy-3α-hydroxy-5α-pregnan-20-one (Dethoxyprone,form II)

The crystal and molecular structure of 11-dimethylamino-2-ethoxy-3-hydroxy-5-pregnan-20-one (Dethoxyprone, formII) (C₂₅H₄₃NO₃) has been determined by direct methods, and refined to a finalR of 0.067 for 4508 observed reflections. The compound crystallizes in space groupP2₁2₁2₁ with cell dimensionsa=10.830 (2),b=12.703 (2),c=17.490 (1) Å;Z=4,D _x =1.12 g cm^–3, (CuK )=5.28 cm^–1. The rings of the steroid skeleton are trans connected. Rings A, B, and C have chair conformations, while ring D has a half-chair conformation. The molecules are hydrogen bonded in a head to tail fashion through the hydroxy and keto groups.     

Quantitative ultraviolet measurements on wetted thin-layer chromatography plates using a charge-coupled device camera

This paper presents the first study of the UV imaging of spots on thin-layer chromatographic plates whilst still wet with solvent. Imaging of spots of benzophenone during and after development was carried out using a charge-coupled device camera. Limits of detection were found to be 5ng on a wetted plate and 3ng for a dry plate and the relationship between peak area and sample loading was found to be linear in the low nanogram range over an order of magnitude for both wet and dry modes with r(2) values>0.99. It was found that UV measurements on wet glass-backed plates suffer from low sensitivity; however, the use of aluminium-backed plates gave increased sensitivity. The apparent absorption coefficient epsilon(app) of 10AUm(2)g(-1) at 254nm is consistent with reflection of the light from the aluminium surface with a double pass through the sorbent layer, and suggests that use of aluminium-backed plates should enable monitoring of separations by UV absorbance during TLC development.     

An interlaboratory capillary zone electrophoresis-UV study of various monoclonal antibodies,instruments, and ε-aminocaproic acid lots

Capillary zone electrophoresis ultraviolet (CZE-UV) has become increasingly popular for the charge heterogeneity determination of mAbs and vaccines. The ε-aminocaproic acid (eACA) CZE-UV method has been used as a rapid platform method. However, in the last years, several issues have been observed, for example, loss in electrophoretic resolution or baseline drifts. Evaluating the role of eACA on the reported issues, various laboratories were requested to provide their routinely used eACA CZE-UV methods, and background electrolyte compositions. Although every laboratory claimed to use the He et al. eACA CZE-UV method, most methods actually deviate from He's. Subsequently, a detailed interlaboratory study was designed wherein two commercially available mAbs (Waters’ Mass Check Standard mAb [pI 7] and NISTmAb [pI 9]) were provided to each laboratory, along with two detailed eACA CZE-UV protocols for a short-end, high-speed, and a long-end, high-resolution method. Ten laboratories participated each using their own instruments, and commodities, showing excellence method performance (relative standard deviations [RSDs] of percent time-corrected main peak areas from 0.2% to 1.9%, and RSDs of migration times from 0.7% to 1.8% [n = 50 per laboratory], analysis times in some cases as short as 2.5 min). This study clarified that eACA is not the main reason for the abovementioned variations.     

Bis[bis-(4-alkoxyphenyl)amino] derivatives of dithienylethene, bithiophene, dithienothiophene and dithienopyrrole: palladium-catalysed synthesis and highly delocalised radical cations

Five diamines with thiophene-based bridges--(E)-1,2-bis{5-[bis(4-butoxyphenyl)amino]-2-thienyl}ethylene (1), 5,5'-bis[bis(4-methoxyphenyl)amino]-2,2'-bithiophene (2), 2,6-bis[bis(4-butoxyphenyl)amino]dithieno[3,2-b:2',3'-d]thiophene (3), N-(4-tert-butylphenyl)-2,6-bis[bis(4-methoxyphenyl)amino]dithieno[3,2-b:2',3'-d]pyrrole (4 a) and N-tert-butyl-2,6-bis[bis(4-methoxyphenyl)amino]dithieno[3,2-b:2',3'-d]pyrrole (4 b)--have been synthesised. The syntheses make use of the palladium(0)-catalysed coupling of brominated thiophene species with diarylamines, in some cases accelerated by microwave irradiation. The molecules all undergo facile oxidation, 4 b being the most readily oxidised at about -0.4 V versus ferrocenium/ferrocene, and solutions of the corresponding radical cations were generated by addition of tris(4-bromophenyl)aminium hexachloroantimonate to the neutral species. The near-IR spectra of the radical cations show absorptions characteristic of symmetrical delocalised species (that is, class III mixed-valence species); analysis of these absorptions in the framework of Hush theory indicates strong coupling between the two amine redox centres, stronger than that observed in species with phenylene-based bridging groups of comparable length. The strong coupling can be attributed to high-lying orbitals of the thiophene-based bridging units. ESR spectroscopy indicates that the coupling constant to the amino nitrogen atoms is somewhat reduced relative to that in a stilbene-bridged analogue. The neutral species and the corresponding radical cations have been studied with the aid of density functional theory and time-dependent density functional theory. The DFT-calculated ESR parameters are in good agreement with experiment, while calculated spin densities suggest increased bridge character to the oxidation in these species relative to that in comparable species with phenylene-based bridges.     

On the perturbation of analytic matrix functions

In this paper behaviour of the spectrum of matrix-valued functions depending analytically on two parameters is studied. Generalizations of the Rellich theorem on analytic dependence of the spectrum and complete regular splitting of multiple eigenvalues are established.This work is partially supported by Natural Sciences and Engineering Research Council of Canada. R. H. also acknowledges appointment as a Post Doctoral Fellow of the Pacific Institute for Mathematical Sciences.     

Energy barriers of proton transfer reactions between amino acid side chain analogs and water from ab initio calculations

Proton transfer reactions were studied in all titratable pairs of amino acid side chains where, under physiologically reasonable conditions, one amino acid may function as a donor and the other one as an acceptor. Energy barriers for shifting the proton from donor to acceptor atom were calculated by electronic structure methods at the MP2/6-31++G(d,p) level, and the well-known double-well potentials were characterized. The energy difference between both minima can be expressed by a parabola using as argument the donor-acceptor distance R(DA). In this work, the fit parameters of the quadratic expression are determined for each donor-acceptor pair. Moreover, it was found previously that the energy barriers of the reactions can be expressed by an analytical expression depending on the distance between donor and acceptor and the energy difference between donor and acceptor bound states. The validity of this approach is supported by the extensive new data set. This new parameterization of proton transfer barriers between titratable amino acid side chains allows us to very efficiently estimate proton transfer probabilities in molecular modelling studies or during classical molecular dynamics simulation of biomolecular systems.     

Measurement and simulations of hollow atom X-ray spectra of solid-density relativistic plasma created by high-contrast PW optical laser pulses

K-shell spectra of solid Al excited by petawatt picosecond laser pulses have been investigated at the Vulcan PW facility. Laser pulses of ultrahigh contrast with an energy of 160 J on the target allow studies of interactions between the laser field and solid state matter at 10²⁰ W/cm². Intense X-ray emission of KK hollow atoms (atoms without n = 1 electrons) from thin aluminum foils is observed from optical laser plasma for the first time. Specifically for 1.5 μm thin foil targets the hollow atom yield dominates the resonance line emission. It is suggested that the hollow atoms are predominantly excited by the impact of X-ray photons generated by radiation friction to fast electron currents in solid-density plasma due to Thomson scattering and bremsstrahlung in the transverse plasma fields. Numerical simulations of Al hollow atom spectra using the ATOMIC code confirm that the impact of keV photons dominates the atom ionization. Our estimates demonstrate that solid-density plasma generated by relativistic optical laser pulses provide the source of a polychromatic keV range X-ray field of 10¹⁸ W/cm² intensity, and allows the study of excited matter in the radiation-dominated regime. High-resolution X-ray spectroscopy of hollow atom radiation is found to be a powerful tool to study the properties of high-energy density plasma created by intense X-ray radiation.     

Methylsulfonyl benzothiazole (MSBT): a selective protein thiol blocking reagent

A new thiol blocking reagent, methylsulfonyl benzothiazole, was discovered. This reagent showed good selectivity and high reactivity for protein thiols.     

Spin waves and revised crystal structure of honeycomb iridate Na2IrO3

We report inelastic neutron scattering measurements on Na2IrO3, a candidate for the Kitaev spin model on the honeycomb lattice. We observe spin-wave excitations below 5 meV with a dispersion that can be accounted for by including substantial further-neighbor exchanges that stabilize zigzag magnetic order. The onset of long-range magnetic order below T(N)=15.3 K is confirmed via the observation of oscillations in zero-field muon-spin rotation experiments. Combining single-crystal diffraction and density functional calculations we propose a revised crystal structure model with significant departures from the ideal 90° Ir-O-Ir bonds required for dominant Kitaev exchange.