Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents

We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (1) robust targeting of peptide N-termini and lysyl side chains, (2) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (3) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (4) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da, are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition, we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally, we provide exemplar data that extend the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers.

Double Salt Formation in the Cu(HCOO)2–Sr(HCOO)2–H2O System

The solubility in the Cu(HCOO)₂–Sr(HCOO)₂–H₂O system has been studied by the method of physico-chemical analysis at 25 and 50 °C. It has been established that two double salts are formed in the system: CuSr₂(HCOO)₆ · H₂O at 25 °C and CuSr(HCOO)₄ · 4 H₂O at 50 °C. The latter salt has not yet been described in the literature. It has been characterized by X-ray powder diffraction and DT and TG analysis. CuSr(HCOO)₄ · 4 H₂O crystallizes in the triclinic system with lattice parameters a = 12.376(6) Å, b = 13.394(4) Å, c = 11.508(6) Å, α = 93.38(3)°, β = 94.01(3)°, γ = 75.04(3)°. Dehydration proceeds in two stages.     

Characterization of superparamagnetic Mg x Zn1−x Fe2O4 powders

Structural and magnetic properties of Mg _x Zn_1−x Fe₂O₄ powders have been studied with respect to the application for thermal cancer therapy (magnetic hyperthermia). Mg _x Zn_1−x Fe₂O₄ (x=0.1–0.5) powders with particle sizes between 5 and 8 nm were produced by citrate method. The X-ray diffraction patterns of the samples correspond to a spinel phase. The lattice constant and the volume of the elementary cell increase when x changes from 0.1 to 0.5. The FTIR-spectra ascertain the spinel phase formation. The Mossbauer studies reveal the presence of extremely small particles, which undergo superparamagnetic relaxation at room temperature. The core-shell model has been applied to explain quadruple doublets. The quadruple splitting at “shells” is bigger than those at “cores” whereas the isomer shifts remain close. Magnetic studies confirm the presence of extremely small particles that behave as superparamagnetic ones.      

New N-Substituted (±)-Dehydronorglaucine Analogs

The aporphine alkaloid N-carbethoxydehydronorglaucine (1) was found to have promising in vitro antitumor activity, but poor water solubility. We report the synthesis of 1, the efficient hydrolysis of its urethane group and the further transformation into several new dehydronorglaucine analogs.     

Direct Limits and Inverse Limits of SHR Semigroups

In this paper, it is proved that the direct limit (inverse limit) of an SHR direct (respectively, inverse) family of SHR semigroups is an SHR semigroup.AMS Subject Classifications Primary 20N20 Secondary 20M99     

Polarization reflection holographic gratings in azobenzene-containing gelatine films

We have written polarization reflection holograms in an azobenzene-containing material. Two waves with circular polarization were used to record the gratings; the light resulting from their overlap induces chirality in the samples. The holographic reflection of the polarization gratings has the properties of Bragg reflection in cholesteric liquid crystals.     

Langmuir monolayers of bent-core molecules

A systematic study of five different, symmetric bent-core liquid crystals in Langmuir thin films at the air/water interface is presented. Both the end chains (siloxane vs hydrocarbon) and the core (more or less amphiphilic) are varied, to allow an exploration of different possible layer structures at the interface. The characterization includes systematic surface pressure isotherms, Brewster angle microscopy, and surface potential measurements. The properties of these layers are strongly dependent on the individual type of molecule: the molecules with amphiphilic end chains lie quite flat on the surface, while the molecules with hydrophobic end chains construct multilayer structures. In both cases, the three-dimensional collapse structure is reversible.     

Comprehensive comparison of ligand-based virtual screening tools against the DUD data set reveals limitations of current 3D methods

In recent years, many virtual screening (VS) tools have been developed that employ different molecular representations and have different speed and accuracy characteristics. In this paper, we compare ten popular ligand-based VS tools using the publicly available Directory of Useful Decoys (DUD) data set comprising over 100?000 compounds distributed across 40 protein targets. The DUD was developed initially to evaluate docking algorithms, but our results from an operational correlation analysis show that it is also well suited for comparing ligand-based VS tools. Although it is conventional wisdom that 3D molecular shape is an important determinant of biological activity, our results based on permutational significance tests of several commonly used VS metrics show that the 2D fingerprint-based methods generally give better VS performance than the 3D shape-based approaches for surprisingly many of the DUD targets. To help understand this finding, we have analyzed the nature of the scoring functions used and the composition of the DUD data set itself. We propose that to improve the VS performance of current 3D methods, it will be necessary to devise screening queries that can represent multiple possible conformations and which can exploit knowledge of known actives that span multiple scaffold families.     

Kinetic spectrophotometric determination of hydrazine

A kinetic spectrophotometric method for hydrazine determination in the range of 9.36×10⁻⁷ to 4.37×10⁻⁵ mol dm⁻³, based on the inhibitory effect of hydrazine on the oxidation of Victoria Blue 4- R by KBrO₃, was developed and validated. Kinetic parameters are reported for both the indicating and the inhibiting reaction. The detection limit was established as 9.98×10⁻⁸ mol dm⁻³. The selectivity of the proposed method was tested considering the influence of different ions that may be present in real samples. The method was successfully applied for hydrazine determination in various samples (very pure water from the water-steam system of a power plant and Isoniazid tablets, a pharmaceutical product).      

A computational study on the stability–aromaticity correlation of triply N-confused porphyrins: CMMSE-09

The B3LYP density functional theory methodology in conjunction with the 6-31G(d,p) basis set has been used to characterize triply N-confused meso-tetraphenylporphyrins. According to our computations, there is no a direct correlation between stability and aromaticity as already found for non-substituted confused porphyrins. The inclusion of these substituents in the calculations provokes a decrease of the planarity and aromaticity of these macrocycles along with a notable rise of their relative stability with respect to the non-substituted case. Steric repulsions, both among phenyl rings and β atoms in the pyrrolic rings, and among H atoms in the core of the macrocycles, dominate over aromaticity in the establishment of the most stable conformation of each isomer.