Complexes of Click‐Derived Bistriazolylpyridines: Remarkable Electronic Influence of Remote Substituents on Thermodynamic Stability as well as Electronic and Magnetic Properties

2,6‐Bis(1,2,3‐triazol‐4‐yl)pyridine (btp) ligands with substitution patterns ranging from strongly electron‐donating to strongly electron‐accepting groups, readily prepared by means of Cu‐catalyzed 1,3‐dipolar cycloaddition (the “click” reaction), were investigated with regard to their complexation behavior, and the properties of the resulting transition‐metal compounds were compared. Metal–btp complexes of 1:1 stoichiometry, that is, [Ru(btp)Cl₂(dmso)] and [Zn(btp)Br₂], could be isolated and were crystallographically characterized: they display octahedral and trigonal‐bipyramidal coordination geometries, respectively, and exhibit high aggregation tendencies due to efficient π–π stacking leading to low solubilities. Metal–btp complexes of 1:2 stoichiometry, that is, [Fe(btp)₂]²⁺ and [Ru(btp)₂]²⁺, could also be synthesized and their metal centers show the expected octahedral coordination spheres. The iron compounds exhibit quite a complex magnetic behavior in the solid state including spin crossover near room temperature, and hysteresis and locking into high‐spin states on tempering at 400 K, depending on the substituents on the btp ligands. Cyclic voltammetry studies of [Ru(btp)₂]²⁺ reveal strong modulation of the oxidation potentials by more than 0.6 V and a clear linear correlation to the Hammett constant (σ_para) of the substituent at the pyridine core. Isothermal titration calorimetry was used to measure the thermodynamics of the Fe^II–btp complexation process and enabled accurate determination of the complexation enthalpies, which display a linear relationship with the σ_para values for the terminal phenyl substituents. Detailed NMR spectroscopic studies finally revealed that in the case of Fe^II complexation, dynamics are rapid for all investigated btp derivatives in acetonitrile, while replacing Fe^II by Ru^II or changing the solvent to dichloromethane effectively slows down ligand exchange. The results nicely demonstrate the utility of substituent parameters, originally developed for linear free‐energy relationships to explain reactivity in organic reactions, in coordination chemistry, and to illustrate the potential to custom‐design btp ligands and complexes thereof with predictable properties. The fast equilibration of the [Fe(btp)₂]²⁺ complexes together with their tunable stability and interesting magnetic properties should enable the design of dynamic metallosupramolecular materials with advantageous properties.     

Ultrathin Carbon Film Electrodes from Vacuum‐Carbonised Cellulose Nanofibril Composite

A novel way to produce ultrathin transparent carbon layers on tin‐doped indium oxide (ITO) substrates is developed. The ITO surface is coated with cellulose nanofibrils (from sisal) via layer‐by‐layer electrostatic binding with poly(diallyldimethylammonium chloride) or PDDAC acting as the binder. The cellulose nanofibril‐PDDAC composite film is then vacuum‐carbonised at 500 °C. The resulting carbon films are characterised by atomic force microscopy (AFM), small angle X‐ray scattering (SAXS), wide‐angle X‐ray scattering (WAXS), and Raman methods. Smooth carbon films with good adhesion to the ITO substrate are formed. The electrochemical characterisation of the carbon films is based on the oxidation of hydroquinone and the reduction of benzoquinone in aqueous phosphate buffer media. A modest effect of the cellulose nanofibril‐PDDAC film on the rate of electron transfer is observed. The effect of the film on the rate of electron transfer after carbonisation is more dramatic. For a 40‐layer cellulose nanofibril‐PDDAC film after carbonisation a two‐order of magnitude change in the rate of electron transfer occurs presumably due to a better interaction of the hydroquinone/benzoquinone system with the electrode surface.     

A rapid and specific derivatization procedure to identify acyl‐glucuronides by mass spectrometry

A simple procedure is described to identify acyl‐glucuronides by coupled liquid chromatography/mass spectrometry after derivatization to a hydroxamic acid with hydroxylamine. The reaction specificity obviates the need for isolation of the acyl‐glucuronide from an extract. Glucuronides derived from carbamic acids, and alkyl‐ and aromatic amines, are inert to the derivatization reaction conditions, making the hydroxamic acid derivative a fingerprint for acyl‐glucuronides. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of mobile phase pH, aqueous-organic ratio, and buffer concentration on electrospray ionization tandem mass spectrometric fragmentation patterns: implications in liquid chromatography/tandem mass spectrometric bioanalysis

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) based on selected reaction monitoring (SRM) is the standard methodology in quantitative analysis of administered xenobiotics in biological samples. Utilizing two SRM channels during positive electrospray ionization (ESI) LC/MS/MS method development for a drug compound containing two basic functional groups, we found that the response ratio (SRM1/SRM2) obtained using an acidic mobile phase was dramatically different from that obtained using a basic mobile phase. This observation is different from the well-established phenomenon of mobile phase affecting the [M+H](+) response, which is directly related to the amount of the [M+H](+) ions produced during the ionization. Results from follow-up work reported herein revealed that the MS/MS fragmentation patterns of four drug or drug-like compounds are affected not only by the pH, but also by the aqueous-organic ratio of the mobile phase and the buffer concentration at a given apparent pH. The observed phenomenon can be explained by invoking that a mixture of [M+H](+) ions of the same m/z value for the analyte is produced that is composed of two or more species which differ only in the site of the proton attachment, which in turn affects their MS/MS fragmentation pattern. The ratio of the different protonated species changes depending on the pH, aqueous-organic ratio, or ionic strength of the mobile phase used. The awareness of the mobile phase dependency of the MS/MS fragmentation pattern of precursor ions of identical m/z value will influence LC/MS/MS-based bioanalytical method development strategies. Specifically, we are recommending that multiple SRM transitions be monitored during mobile phase screening, with the MS/MS parameters used for each SRM optimized for the composition of the mobile phase (pH, organic percentage, and ionic strength) in which the analyte elutes.     

Covalent selection of the thiol proteome on activated thiol sepharose: A robust tool for redox proteomics

Protein thiols contribute significantly to antioxidant defence and selective oxidation of cysteines is important in signal transduction even in sub-stress scenarios. However, cysteine is the second rarest residue in proteins and it can be difficult to target low-abundance thiol (-SH)-containing proteins in proteomic separations. Activated thiol sepharose (ATS) allows covalent selection of -SH-containing proteins which can then be recovered by reduction with mercaptoethanol or dithiothreitol. This is a robust method for enriching -SH-containing proteins. We have used ATS to estimate the percentage (by weight) of thiol-containing proteins in cell extracts from a range of biological sources: a bacterium, Escherichia coli; a fungus, Trichoderma harzianum; and a bivalve mollusc Mytilus edulis. -SH-containing proteins account for 2.52% (E. coli), 1.4% (T. harzianum) and 1.4% (M. edulis) of total protein. Exposure to pro-oxidants did not materially alter these values. On removal of low M_r thiols such as glutathione, the values for M. edulis did not significantly change but those for T. harzianum increased threefold. The two-dimensional electrophoresis profiles of ATS-selected proteins for each organism were compared in control and pro-oxidant-exposed preparations. This revealed that some proteins present in controls were absent in pro-oxidant-treated extracts which we attribute to thiol oxidation. ATS has significant potential in enrichment for -SH-containing proteins in redox proteomics.     

Evaluation of Morphology and Deformation Micromechanisms in Multilayered PP/PS Films: An Electron Microscopy Study

Nanostructured polymers and ultra-thin polymer layers are used more and more in technical applications like nanotechnology and microelectronics. Therefore, it is really important to understand the size-scale dependent properties as bulk polymers become thinner and more two-dimensional. Here the morphology as well as the macroscopic and the microscopic deformation behaviour of multilayered films of polypropylene (PP) and polystyrene (PS) have been investigated. For investigation different microscopic techniques and tensile testing were used. The films were prepared by multilayer coextrusion, whereas the composition of PP and PS and the film thickness – and therefore the thickness of each layer – varied. The thinnest calculated thickness of a single layer was about 5 nm. It is shown that the PP/PS films consist usually of homogeneous layers with only few defects. As the composition of PP/PS deviates strongly from 50/50 or the films get thinner the number of defects increases and the layered system turns to irregular lamellar system. In macroscopic tensile tests the small PS layers affect the elongation at break enormously: Most of the samples are brittle. For the films with a composition of PP/PS 90/10 and the film PP/PS 70/30 with a film thickness of 25 µm an elongation at break of 66% and higher could be reached. Transmission electron microscopy on these samples shows that the layers are characterized by plastic yielding in local deformation zones.     

Epoxy-functionalized large-pore SBA-15 and KIT-6 as affinity chromatography supports

Mesoporous silica supports are proposed as an alternative to polymeric stationary phases for fast affinity chromatography due to their better mechanical strength compared to polymers. Ideal supports should combine high surface area and large pore size to allow a high loading capacity of large molecules, such as proteins, and favor their accessibility. Increasing the pore size of large-surface area micelle-templated silicas (SBA-15, KIT-6) has been achieved by swelling the micelles by the addition of organic molecules and increasing synthesis time and temperature. The pore size of hexagonal silica mesostructured SBA-15 has been increased up to 35 nm. These materials could find therefore application as affinity chromatography for immunoextraction.     

Characterization of tetra,dodeca and tetradeca MoV polyoxometalate wheels structured by etidronate ligands

The reactivity of the [Mo^V₂O₄]²⁺ dinuclear unit with the [O₃P(C(CH₃)(OH))PO₃]^4? etidronate ligand has been investigated. Three complexes have been isolated and characterized by IR spectroscopy, elemental analysis and single crystal X-Ray diffraction studies. Structural determination of the tetranuclear compound (CN₃H₆)₆[(Mo^V₂O₄)₂(O₃P(C(CH₃)O)PO₃)₂]·12H₂O (1) revealed that the hydroxo group of the etidronate ligand can be deprotonated in presence of Mo^V even in acidic media. It follows that its coordination mode thus differs from that of the methylenediphosphonate ligand [O₃P(CH₂)PO3]4?, which reactivity with Mo^V has been previously widely studied. In contrast, no such deprotonation of the hydroxo group is observed in the (NH₄)₁₈[(Mo^V₂O₄)₆(OH)₆(O₃P(C(CH₃)(OH))PO₃)₆]·35H₂O complex 2. This species contains a dodecanuclear core analogous to the one previously found in the [(Mo^V₂O₄)₆(OH)₆(O₃PCH₂PO₃)₆]^18? methylenediphosphonato polyanion. In 2, six interconnected {(Mo^V₂O₄)(O₃P(C(CH₃)(OH))PO₃)} units form a cyclohexane-like ring in a chair conformation. In the (CN₃H₆)₁₈Na₃[(Mo^V₂O₄)₇(O₃P(C(CH₃)(OH))PO₃)₇(CH₃COO)₇]·5CH₃COONa 52H₂O compound 3, seven {(Mo^V₂O₄)(O₃P(C(CH₃)(OH))PO₃)(CH₃COO)} units are connected, forming an almost planar tetradecanuclear wheel. This compound represents the largest homometallic Mo^V polyoxometalate cyclic system reported to date. Finally, ³¹P NMR studies revealed that only complex 1 is stable in aqueous solution.     

Presenegenin Glycosides from Securidaca welwitschii

The five new presenegenin glycosides 1 – 5 were isolated from Securidaca welwitschii, together with one known sucrose diester. Compounds 1 – 4 were obtained as pairs of inseparable (E)/(Z)‐isomers of a 3,4‐dimethoxycinnamoyl derivative, i.e., 1 / 2 and 3 / 4 . Their structures were elucidated mainly by 2D‐NMR techniques and mass spectrometry as 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐{O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[β‐D ‐glucopyranosyl‐(1→3)]‐4‐O‐[(E)‐3,4‐dimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 1 ) and its (Z)‐isomer 2 , 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐{O‐β‐D ‐galactopyranosyl‐(1→4)‐O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐3‐O‐acetyl‐α‐L ‐rhamnopyranosyl‐(1→2)‐O‐[β‐D ‐glucopyranosyl‐(1→3)]‐4‐O‐[(E)‐3,4‐dimethoxycinnamoyl]‐β‐D ‐fucopyranosyl} ester ( 3 ) and its (Z)‐isomer 4 , and 3‐O‐(β‐D ‐glucopyranosyl)presenegenin 28‐[O‐β‐D ‐galactopyranosyl‐(1→3)‐O‐β‐D ‐xylopyranosyl‐(1→4)‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐β‐D ‐fucopyranosyl] ester ( 5 ) (presenegenin=(2β,3β,4α)‐2,3,27‐trihydroxyolean‐12‐ene‐23,28‐dioic acid).