Formation of γ-oxoacids and 1H-pyrrol-2(5H)-ones from α,β-unsaturated ketones and ethyl nitroacetate

Michael addition of ethyl nitroacetate on α,β-unsaturated ketones followed by Nef oxidation under hydrolytic conditions yields γ-oxoacids instead of the corresponding α,δ-dioxoesters. A concerted decarboxylation step is proposed on the basis of computational results. Finally, conversion of the γ-ketoacids thus prepared into 1H-pyrrol-2(5H)-ones by reaction with primary amines under Paal-Knorr conditions is also reported.     

A new polymorph of Ba(AsO3OH): Synthesis, crystal structure and vibrational spectra

A new monoclinic polymorph of Ba(AsO₃OH) was synthesized under hydrothermal conditions. It represents a previously unknown structure type. Its crystal structure was determined from a racemic twin using single-crystal X-ray diffraction data collected at 120 and 293 K [space group P2₁, a=7.2149(14)/7.2370(2), b=7.7028(15)/7.7133(2), c=21.7385(43)/21.8079(5) Å, β=95.95(3)/96.073(1)°, V=1201.6(4)/1210.51(5) Å³, Z=12]. The crystal structure of P2₁-Ba(AsO₃OH) has a layered character and is built up of four types of regularly alternating layers parallel to (0 0 1). Every AsO₃OH tetrahedron is chelating to two Ba atoms and bridged by another two Ba atoms. Each OH group acts as hydrogen bond donor toward the oxygen atoms positioned in the same or adjacent layers. Although the H atoms could not be located, no ambiguities are present in the hydrogen-bonding scheme. Single-crystal vibrational spectroscopy (FTIR and Raman) was used to describe the vibrational behavior of the hydrogen bond system; particularly the spectroscopic manifestation of the very short and short hydrogen bonds (2.462(7)-2.575(7) Å). In order to complement spectroscopic data on protonated orthoarsenates, infrared spectra of triclinic F1¯-Sr(AsO₃OH) and the orthorhombic variety of Pbca-Ba(AsO₃OH) were recorded and discussed. Furthermore, structural features of other alkaline earth hydrogen arsenates are discussed.     

A novel approach to tag and identify geranylgeranylated proteins

A recently developed proteomic strategy, the “GG‐azide”‐labeling approach, is described for the detection and proteomic analysis of geranylgeranylated proteins. This approach involves metabolic incorporation of a synthetic azido‐geranylgeranyl analog and chemoselective derivatization of azido‐geranylgeranyl‐modified proteins by the “click” chemistry, using a tetramethylrhodamine‐alkyne. The resulting conjugated proteins can be separated by 1‐D or 2‐D and pH fractionation, and detected by fluorescence imaging. This method is compatible with downstream LC‐MS/MS analysis. Proteomic analysis of conjugated proteins by this approach identified several known geranylgeranylated proteins as well as Rap2c, a novel member of the Ras family. Furthermore, prenylation of progerin in mouse embryonic fibroblast cells was examined using this approach, demonstrating that this strategy can be used to study prenylation of specific proteins. The “GG‐azide”‐labeling approach provides a new tool for the detection and proteomic analysis of geranylgeranylated proteins, and it can readily be extended to other post‐translational modifications.     

Ramsey’s theorem for trees: the polarized tree theorem and notions of stability

We formulate a polarized version of Ramsey’s theorem for trees. For those exponents greater than 2, both the reverse mathematics and the computability theory associated with this theorem parallel that of its linear analog. For pairs, the situation is more complex. In particular, there are many reasonable notions of stability in the tree setting, complicating the analysis of the related results.     

Volatile Phthalocyanines: Vapor Pressure and Thermodynamics

The current review summarizes the data of saturated vapor pressure and thermodynamic parameters of the sublimation process of different phthalocyanines as reported in the literature as well as in our work. The volatility of phthalocyanines is analyzed from the standpoint of their molecular and crystal structure. The differences in the saturated vapor pressure value of the investigated phthalocyanines may reach some orders of magnitude and are determined by the Van der Waals and electrostatic interaction of the peripheral atoms of adjacent molecules, as well as to a specific interaction, the type and number of which depend on the type of molecules packing in the crystal.     

Selectivity over coverage in de novo sequencing of IgGs

Although incredibly diverse in specificity, millions of unique Immunoglobulin G (IgG) molecules in the human antibody repertoire share most of their amino acid sequence. These constant parts of IgG do not yield any useful information in attempts to sequence antibodies de novo. Therefore, methods focusing solely on the variable regions and providing unambiguous sequence reads are strongly advantageous. We report a mass spectrometry-based method that uses electron capture dissociation (ECD) to provide straightforward-to-read sequence ladders for the variable parts of both the light and heavy chains, with a preference for the functionally important CDR3. We optimized this method on the therapeutic antibody Trastuzumab and demonstrate its applicability on two monoclonal quartets of the four IgG subclasses, IgG1, IgG2, IgG3 and IgG4. The method is based on proteolytically separating the variable F(ab′)₂ part from the conserved Fc part, whereafter the F(ab′)₂ portions are mass-analyzed and fragmented by ECD. Pure ECD, without additional collisional activation, leads to straightforward-to-read sequence tags covering the CDR3 of both the light and heavy chains. Using molecular modelling and structural analysis, we discuss and explain this selective fragmentation behavior and describe how structural features of the different IgG subclasses lead to distinct fragmentation patterns. Overall, we foresee that pure ECD on F(ab′)₂ or Fab molecules can become a valuable tool for the de novo sequencing of serum antibodies.