Analysis of carbonyl compounds via headspace solid-phase microextraction with on-fiber derivatization and gas chromatographic-ion trap tandem mass spectrometric determination of their O-(2,3,4,5,6-pentafluorobenzyl)oxime derivatives

An improved method for the analysis of carbonyls is described utilizing a headspace solid-phase microextraction (HS-SPME) step and on-fiber derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) hydrochloride. Thermal desorption of the oxime derivatives formed on the fiber is followed by gas chromatographic separation coupled to an ion trap tandem mass spectrometer (GC-ITMS). Selecting specific fragment ions within the electron ionization (EI(+)) mass spectra of these oxime derivatives as precursor ions for MS-MS fragmentation provides a suitable method for the target analysis of individual carbonyl classes, such as alkanals, (E)-2-alkenals, (E,E)-2,4-alkadienals, and others. Retention indices on polar as well as on apolar stationary phases along with EI(+) mass spectra patterns are presented for a large set of oxime derivatives, giving valuable information needed for unambiguous assignment of substances in complex sample matrices. The fast sample preparation and derivatization step via HS-SPME can be automated and is applicable to a variety of biological samples and foodstuffs, allowing rapid and sensitive screening analyses of important aldehydic biomarkers and aroma active compounds.     

Optimization of augmentation functions for correlated calculations of spin-spin coupling constants and related properties

A new hierarchy of augmented basis sets optimized for the calculation of molecular properties such as indirect spin-spin coupling constants is presented. Based on the Dunning hierarchy of cc-pVXZ (X = D, T, Q, and 5) basis sets augmentation functions with tight exponents have been optimized for coupled-cluster calculations of indirect spin-spin coupling constants. The optimal exponents for these tight functions have been obtained by optimizing the sum of the absolute values of all contributions to the coupling constant. On the basis of a series of test cases (CO, HF, N(2), F(2), H(2)O, NH(3), and CH(4)) we propose a set of tight s, p, and d functions to be added to the uncontracted Dunning basis sets, and, subsequently, to recontract. The resulting ccJ-pVXZ (X = D, T, Q, and 5) basis sets demonstrate excellent cost efficiency in benchmark calculations. These new basis sets should generally be applicable for the calculation of spin-spin coupling constants and other properties that have a strong dependence on powers of 1r or even contain a delta distribution for correlated ab initio methods.     

The Munich Compact Light Source: initial performance measures

While large‐scale synchrotron sources provide a highly brilliant monochromatic X‐ray beam, these X‐ray sources are expensive in terms of installation and maintenance, and require large amounts of space due to the size of storage rings for GeV electrons. On the other hand, laboratory X‐ray tube sources can easily be implemented in laboratories or hospitals with comparatively little cost, but their performance features a lower brilliance and a polychromatic spectrum creates problems with beam hardening artifacts for imaging experiments. Over the last decade, compact synchrotron sources based on inverse Compton scattering have evolved as one of the most promising types of laboratory‐scale X‐ray sources: they provide a performance and brilliance that lie in between those of large‐scale synchrotron sources and X‐ray tube sources, with significantly reduced financial and spatial requirements. These sources produce X‐rays through the collision of relativistic electrons with infrared laser photons. In this study, an analysis of the performance, such as X‐ray flux, source size and spectra, of the first commercially sold compact light source, the Munich Compact Light Source, is presented.     

Questions on generalised Baire spaces

We provide a list of open problems in the research area of generalised Baire spaces, compiled with the help of the participants of two workshops held in Amsterdam (2014) and Hamburg (2015).     

Metal‐Assisted One‐Pot Synthesis of Isoporphyrin Complexes

Zinc and cadmium complexes of meso‐arylisoporphyrins carrying a pyrrolyl or dipyrrinyl substituent at the sp³ carbon atom were obtained through a simple one‐pot variation of the Alder–Longo porphyrin synthesis. Key to the formation and stabilization of isoporphyrins is the presence of metal acetates during the oxidative macrocyclization step. The characteristic Q‐bands of isoporphyrins are found in the NIR region between 750 nm and 880 nm. All of the isolated pyrrolyl‐ and dipyrrinyl‐appended isoporphyrins are stable under typical laboratory conditions and allow chemical transformations like BF₂ coordination, transmetalation, and ligand exchange.     

IR-renormalon contributions to the structure functions g 3 and g 5

We calculate the leading 1/N _f perturbative contributions to the polarized nonsinglet structure functions g ₃ and g ₅ to all orders in α_s. The contributions from the first renormalon pole are determined. It is a measure for the ambiguity of the perturbative calculation and is hypothetically assumed to dominate the power corrections. The corrections Δg ₃ and Δg ₅ are given as functions of the Bjorken variable x and turn out to be negligible. The anomalous dimensions of the leading twist operators are obtained in the next-to-leading order. Received: 10 June 1998 / Revised version: 25 September 1998     

Picomolar FKBP inhibitors enabled by a single water-displacing methyl group in bicyclic [4.3.1] aza-amides

Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report the stereospecific effect of a single, solvent-exposed methyl group in bicyclic [4.3.1] aza-amides, robustly leading to a 2 to 10-fold increase in binding affinity for FK506-binding proteins (FKBPs). This resulted in the most potent and efficient FKBP ligands known to date. By a combination of co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory (DFT), and 3D reference interaction site model (3D-RISM) calculations we elucidated the origin of the observed affinity boost, which was purely entropically driven and relied on the displacement of a water molecule at the protein–ligand–bulk solvent interface. The best compounds potently occupied FKBPs in cells and enhanced bone morphogenic protein (BMP) signaling. Our results show how subtle manipulation of the solvent network can be used to design atom-efficient ligands for difficult, solvent-exposed binding pockets.

Enhancement by displacement. A single methyl group displaces a water molecule from the binding site of FKBPs, resulting in the most potent binders known, outperforming the natural products FK506 and rapamycin in biochemical and cellular assays.     

On the distribution of penalized maximum likelihood estimators: The LASSO, SCAD, and thresholding

We study the distributions of the LASSO, SCAD, and thresholding estimators, in finite samples and in the large-sample limit. The asymptotic distributions are derived for both the case where the estimators are tuned to perform consistent model selection and for the case where the estimators are tuned to perform conservative model selection. Our findings complement those of Knight and Fu [K. Knight, W. Fu, Asymptotics for lasso-type estimators, Annals of Statistics 28 (2000) 1356–1378] and Fan and Li [J. Fan, R. Li, Variable selection via non-concave penalized likelihood and its oracle properties, Journal of the American Statistical Association 96 (2001) 1348–1360]. We show that the distributions are typically highly non-normal regardless of how the estimator is tuned, and that this property persists in large samples. The uniform convergence rate of these estimators is also obtained, and is shown to be slower than n^−1/2 in case the estimator is tuned to perform consistent model selection. An impossibility result regarding estimation of the estimators’ distribution function is also provided.