Ammonium carbamate type self-derivative salts of (R-)- and racemic α-methylbenzylamine

Two different compounds have formed from liquid enantiomeric (R-) and racemic α-methylbenzylamine (α-MBA, named also as 1-phenylethylamine, 1-FEA) with supercritical fluid CO₂. The crystalline solids have been characterized by elemental CHN analysis, X-ray diffraction (XRD), FTIR, ¹H, and ¹³C NMR spectroscopy, and found to be α-methylbenzylammonium α-methylbenzylcarbamate self-derivative ionic salts 1 (R/R) and 2 (rac RS), respectively, of the corresponding amines. Compound 2 (rac RS) has shown different XRD pattern from that of enantiomerically pure 1 (R/R), indicating a preferential formation of a 1:1 mixture of (R/S-) and (S/R-) or rather a racemate compound of (RS/SR-) ammonium carbamate salt (2 (rac RS)) from racemate. For thermal stability, the compounds have been checked by differential scanning calorimetry (DSC), simultaneous thermogravimetry and differential thermal analysis (TG/DTA), and in situ coupled evolved gas analysis by mass spectroscopy (TG/DTA?EGA?MS) and FTIR-gas cell (TG?FTIR). No melting point is observed because of the low thermal stability of the compounds. Decomposition stages are tried to be separated with using semi-closed (sealed with a pinhole on the top) crucibles, thus different evolution courses of CO₂ and organic vapors could be followed by MS and FTIR spectroscopy. The α-MBA vapors themselves, evolved from open crucibles could be identified by FTIR-gas cell, while vapors up to m/z = 164 have been detected by MS from semi-closed Al crucible.     

Fractionation of the human plasma proteome for monoclonal antibody proteomics-based biomarker discovery

mAb proteomics, a reversed biomarker discovery approach, is a novel methodology to recognize the proteins of biomarker potential, but requires subsequent antigen identification steps. While in case of high-abundant proteins, it generally does not represent a problem, for medium or lower abundant proteins, the identification step requires a large amount of sample to assure the proper amount of antigen for the ID process. In this article, we report on the use of combined chromatographic and precipitation techniques to generate a large set of fractions representing the human plasma proteome, referred to as the Analyte Library, with the goal to use the relevant library fractions for antigen identification in conjunction with mAb proteomics. Starting from 500?mL normal pooled human plasma, this process resulted in 783 fractions with the average protein concentration of 1?mg/mL. First, the serum albumin and immunoglobulins were depleted followed by prefractionation by ammonium sulfate precipitation steps. Each precipitate was then separated by size exclusion chromatography, followed by cation and anion exchange chromatography. The 20 most concentrated ion exchange chromatography fractions were further separated by hydrophobic interaction chromatography. All chromatography and precipitation steps were carefully designed aiming to maintain the native forms of the intact proteins throughout the fractionation process. The separation route of vitamin D-binding protein (an antibody proteomics lead) was followed in all major fractionation levels by dot blot assay in order to identify the library fraction it accumulated in and the identity of the antigen was verified by Western blot.     

Trans titanium(IV) complexes of salen ligands exhibit high antitumor activity

Salen-titanium(IV) complexes are introduced as a new family of highly efficient antitumor complexes, being the first cytotoxic titanium(IV) complexes of trans labile ligands, as characterized crystallographically. Four complexes with different aromatic substitutions were analyzed, reveling a meaningful effect of the ligand structure on the complex performance. All complexes exhibit high hydrolytic stability, where the labile OAr ligands hydrolyze in a 10% D(2)O solution with t(1/2) ranging from 2 to 11 h. The IC(50) values obtained for three of the salen complexes studied on HT-29 colon and OVCAR-1 ovarian cells demonstrate activity that exceeds those of the known tianium(IV) complexes Cp(2)TiCl(2) and (bzac)(2)Ti(OiPr)(2) and that of cisplatin, where the most active para-chlorinated complex exhibits activity enhancement relative to cisplatin by 10-fold.     

New insights on the active species and mechanism of cytotoxicity of salan-Ti(IV) complexes: a stereochemical study

Following the discovery of cisplatin, much effort has been devoted to the exploration of transition metal complexes as cytotoxic agents. We have recently introduced the highly efficient C(2)-symmetrical salan-Ti(IV) family of complexes, demonstrating high cytotoxicity toward colon and ovarian cells and enhanced hydrolytic stability in mixed organic/water solutions. The effect of stereochemistry is hereby reported, by comparing the cytotoxic activity and hydrolysis of pure enantiomers and their racemic mixture for four complexes of this family with different aromatic substitutions: para-Me, para-Cl, ortho-Cl, and ortho-OMe. These complexes include the trans-diaminocyclohexyl bridge, which enables ligand-to-metal chiral induction to give solely the Δ isomer when starting from the R,R ligand and vice versa. Different activity is obtained for the different stereochemical forms (Δ, Λ, and rac) in two of the four complexes, where for the other two either all forms are inactive or all are highly active. Additionally, where not all are of similar activity, the racemic mixture is the least active of the three. We therefore conclude that the salan ligand is essential for the fruitful biological interaction, which probably involves a chiral cellular target. The activity of the racemate differing from that expected from a simple mixture of enantiomers operating separately may be explained by the involvement of a polynuclear active species, where different metal centers might be of different configurations. This is particularly supported by the different polynuclear products of hydrolysis obtained from an optically pure complex and from the racemic one, as analyzed crystallographically. The former is an all-R,R chiral C(1)-symmetrical homodimer, while the latter is an achiral R,R-S,SC(i)-symmetrical heterodimer obtained through chiral recognition.     

Effect of salt on the equilibrium and nonequilibrium features of polyelectrolyte/surfactant association

The impact of an electrolyte on aqueous mixtures of oppositely charged macromolecules and surfactants is usually explained by assuming an equilibrium association between the components. In this work, it is shown that the nonequilibrium character of polyelectrolyte/surfactant systems plays a crucial role in the interpretation of the effect of salt. Experimental investigations of mixtures of sodium poly(styrenesulfonate) (PSS) and hexadecyltrimethylammonium bromide (CTAB) reveal two distinct effects of added sodium chloride (NaCl). At small and moderate NaCl concentrations, the major impact of the electrolyte is manifested in the reduction of the kinetically stable composition range in which the PSS/CTAB mixtures are trapped in the nonequilibrium colloidal dispersion state. The application of high salt concentrations, however, primarily affects the equilibrium phase properties through considerably decreasing the amount of surfactant bound to the polyelectrolyte.     

The Mechanism of Adsorption of Rh(III) Bromide Complex Ions on Activated Carbon

In the paper, the mechanism of the process of the Rh(III) ions adsorption on activated carbon ORGANOSORB 10—AA was investigated. It was shown, that the process is reversible, i.e., stripping of Rh(III) ions from activated carbon to the solution is also possible. This opens the possibility of industrial recovery of Rh (III) ions from highly dilute aqueous solutions. The activation energies for the forward and backward reaction were determined These are equal to c.a. 7 and 0 kJ/mol. respectively. Unfortunately, the efficiency of this process was low. Obtained maximum load of Rh(III) was equal to 1.13 mg per 1 g of activated carbon.     

Analysis of chloroquine and metabolites directly from whole‐body animal tissue sections by liquid extraction surface analysis (LESA) and tandem mass spectrometry

The rapid and direct analysis of the amount and spatial distribution of exogenous chloroquine (CHQ) and CHQ metabolites from tissue sections by liquid extraction surface sampling analysis coupled with tandem mass spectrometry (LESA‐MS/MS) was demonstrated. LESA‐MS/MS results compared well with previously published CHQ quantification data collected by organ excision, extraction and fluorescent detection. The ability to directly sample and analyze spatially resolved exogenous molecules from tissue sections with minimal sample preparation and analytical method development has the potential to facilitate the assessment of target tissue penetration of pharmaceutical compounds, to establish pharmacokinetic/pharmacodynamic relationships, and to complement established pharmacokinetic methods used in the drug discovery process during tissue distribution assessment. Copyright © 2012 John Wiley & Sons, Ltd.     

PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium-68 Complexes at Physiological pH

Two structurally constrained chelators based on a fused bicyclic scaffold, 4-amino-4-methylperhydro-pyrido[1,2-a][1,4]diazepin-N,N′,N′-triacetic acids [(4R*,10aS*)-PIDAZTA ( L1 ) and (4R*,10aR*)-PIDAZTA ( L2 )], were designed for the preparation of Ga^III-based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga( L2 )OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of Ga^III into the cavity of L2 . Fast and efficient formation of the Ga^III chelates at room temperature was observed at pH values between 7 and 8, which enables ⁶⁸Ga radiolabeling under truly physiological conditions (pH 7.4).