Hexicon 2: Automated Processing of Hydrogen-Deuterium Exchange Mass Spectrometry Data with Improved Deuteration Distribution Estimation

Hydrogen–deuterium exchange (HDX) experiments analyzed by mass spectrometry (MS) provide information about the dynamics and the solvent accessibility of protein backbone amide hydrogen atoms. Continuous improvement of MS instrumentation has contributed to the increasing popularity of this method; however, comprehensive automated data analysis is only beginning to mature. We present Hexicon 2, an automated pipeline for data analysis and visualization based on the previously published program Hexicon (Lou et al. 2010). Hexicon 2 employs the sensitive NITPICK peak detection algorithm of its predecessor in a divide-and-conquer strategy and adds new features, such as chromatogram alignment and improved peptide sequence assignment. The unique feature of deuteration distribution estimation was retained in Hexicon 2 and improved using an iterative deconvolution algorithm that is robust even to noisy data. In addition, Hexicon 2 provides a data browser that facilitates quality control and provides convenient access to common data visualization tasks. Analysis of a benchmark dataset demonstrates superior performance of Hexicon 2 compared with its predecessor in terms of deuteration centroid recovery and deuteration distribution estimation. Hexicon 2 greatly reduces data analysis time compared with manual analysis, whereas the increased number of peptides provides redundant coverage of the entire protein sequence. Hexicon 2 is a standalone application available free of charge under http://hx2.mpimf-heidelberg.mpg.de.

Unprecedented Strong Lewis Bases—Synthesis and Methyl Cation Affinities of Dimethylamino‐Substituted Terpyridines

A versatile method for the synthesis of functionalized 2,2′:6′,2′′‐terpyridines by assembly of the terminal pyridine rings is presented. The cyclization precursors—bis‐β‐ketoenamides—are prepared from 4‐substituted 2,6‐pyridinedicarboxylic acids and acetylacetone or its corresponding enamino ketone. Treatment with trimethylsilyl trifluoromethanesulfonate induces a twofold intramolecular condensation providing an efficient access to 4,4′′‐di‐ and 4,4′,4′′‐trifunctionalized 6,6′′‐dimethyl‐2,2′:6′,2′′‐terpyridines. Using this method, hitherto unknown 4,4′′‐bis(dimethylamino)‐ and 4,4′,4′′‐tris(dimethylamino)terpyridines have been prepared that show remarkably high calculated Lewis basicities.     

Evaluation,Pitfalls and Recommendations for the “Water Layer Test” for Solid Contact Ion‐selective Electrodes

The “water layer test” is a crucial validation step of solid‐contact ion‐selective electrodes. It can confirm or contest the claim that the tested electrode is indeed a genuine solid contact electrode without an aqueous film between the ion‐selective membrane and its solid contact. Information about the presence of a water layer is essential for the interpretation of drifts in the electrode potentials commonly experienced with solid contact electrodes. Since its publication, the water layer test has been ubiquitously used, but without a standardized protocol the interpretation (or misinterpretation) of the test results led to uncertainties in the conclusions. Through both experiments and simulations based on theoretical models we have investigated the experimental parameters that can influence the results of the water layer test. We propose guidelines to minimize the possibility of misinterpretation of the results of the water layer test by considering the key factors that affect the shape of transients recorded during the water layer test. Most importantly, we emphasize the importance of allowing sufficient time for conditioning the tested electrode before the water layer test and providing adequate time for equilibration during the experiment. Using a thin ion‐selective membrane and thin solid‐contact layer for the tests is also recommended.     

Enhancement of inhomogeneities in gels upon swelling and stretching

In this paper, it is shown how a percolation process can be used to describe the inhomogeneities of polymer concentration, appearing in gels prepared by random crosslinking of a semi-dilute solution, and how they are modified by swelling or stretching of the network. Neutron scattering experimental data are compared to the predictions of this model in the isotropic and anisotropic cases. A good agreement is found. In particular, “abnormal” butterfly patterns in the iso-intensity curves have been detected, as expected from the model.     

General survey and microanalytical aspects of ion-selective electrodes

Summary A survey is presented of recent developments in the field of ion-selective electrodes. Special emphasis is placed on problems of electrode miniaturization and ISFET production. Different electrode types in present use are described and theories for the interpretation of electrode mechanisms are outlined. It is pointed out that the electrode potentials are due to the formation of a space charge. Different applications of ion-selective electrodes are dealt with and the problems connected with the determination of small concentrations are discussed. Attention is given to the selection of conditions under which a reliable measurement of extremely small amounts or extremely small concentrations can be ensured.     

Synthesis and characterization of water-soluble palladium(II)-functionalized diphosphine complexes

Water-soluble functionalized bis(phosphine) ligands L (a–h) of the general formula CH₂(CH₂PR₂)₂, where for a: R = (CH₂)₆OH; b–g: R = (CH₂)_nP(O)(OEt)₂, n = 2–6 and n = 8; h: R = (CH₂)₃NH₂ ( Scheme 1), have been prepared photochemically by hydrophosphination of the corresponding 1-alkenes with H₂P(CH₂)₃PH₂. Water-soluble palladium complexes cis-[Pd(L)(OAc)₂] (1–8) were obtained by the reaction of Pd(OAc)₂ with the ligands a–h in a 1:1 mixture of dichloromethane:acetonitrile. The water-soluble phosphine ligands and their palladium complexes were characterized by IR, ¹H and ³¹P NMR. A crystallographic study of complex 1 shows that the Pd(II) ion has a square planar coordination sphere in which the acetate ligands and the diphosphine ligand deviate by less than 0.12 Å from ideal planar.     

Large N‐Heteroacenes: New Tricks for Very Old Dogs?

Azaacenes have been known for a very long time, either as N,N′‐dihydro compounds or in their oxidized form as 4 n+2π systems, but only recently have processable and charcterizable derivatives been sought. In the last three years synthetic routes to large N‐heteroacenes have been developed. In particular, the Pd‐catalyzed coupling of aromatic diamines with activated aromatic dihalogenides has enabled simple access to numerous new azaacenes. Since 2010, azapentacene and stabile oligoazahexacene have been synthesized, as well as a symmetrical tetraazapentacene, which acts as an excellent electron‐transport material for thin‐film transistors.     

Ice structuring proteins - a new name for antifreeze proteins

Antifreeze proteins (AFPs) have been reported in the academic literature for many years, and are increasingly arousing interest in the technical and popular media, particularly because of their potential applications. However, the term "antifreeze" does not always accurately describe their natural function, or their application in frozen systems, where they do not prevent freezing, but control the size, shape and aggregation of ice crystals. We survey the properties and applications of AFPs and propose a more generally applicable name based on the fact that all AFPs bind to ice and consequently influence crystal growth and interactions: "Ice Structuring Proteins".