Influence on elemental status by hip-endoprostheses

For many clinical purposes various artificial devices are applied, which contact human tissue and can thus cause adverse reactions between prosthetic surfaces and body components. Of the many materials applied for orthopaedic joint replacements the most common are cobalt-chromium-molybdenum alloys. In these cases considerable amounts of cobalt-chromium-molybdenum wear particles are released from the prostheses which have to be regarded as a cause of long-time problems for the patient.Since these particles are dissolved in body fluids of the surrounding area they are distributed in the whole body via blood. Elevated metal concentrations have been found in blood and urine of persons with endoprostheses. Partly the metals are excreted via urine, but to some extend they accumulate in different organs.Therefore this study dealt with the development of an analytical method for the determination of seven relevant trace elements, namely Al, Co, Cr, Mo, Nb, Ni, and Ti in nine kinds of human tissue (brain, heart, kidney, liver, lung, muscle, lymphatic nodes, spleen, body fat) starting with drawing of the sample, sample work up and finally analysis by means of atomic spectrometry. The optimized method was then applied to determine the metal contents in organs of persons (post mortem) with total hip replacements with metal on metal bearing surfaces. Comparison of the data obtained with those of persons without hip-endoprostheses shows that brain and lung are the main targets for elemental accumulation in persons with hip-endoprostheses. Mo and Nb represent the elements with the highest tendency to be accumulated.     

Isolation and Total Synthesis of Kirkamide,an Aminocyclitol from an Obligate Leaf Nodule Symbiont

The new C₇N aminocyclitol kirkamide ( 1 ) was isolated from leaf nodules of the plant Psychotria kirkii by using a genome‐driven ¹H NMR‐guided fractionation approach. The structure and absolute configuration were elucidated by HRMS, NMR, and single‐crystal X‐ray crystallography. An enantioselective total synthesis was developed, which delivered kirkamide ( 1 ) on a gram scale in 11 steps and features a Ferrier carbocyclization and a Pd‐mediated hydroxymethylation. We propose that kirkamide is synthesized by Candidatus Burkholderia kirkii, the obligate leaf symbiont of Psychotria kirkii. Kirkamide ( 1 ) was shown to be toxic to aquatic arthropods and insects, thus suggesting that bacterial secondary metabolites play a protective role in the Psychotria/Burkholderia leaf nodule symbiosis.     

Rh-catalyzed reagent-free ring expansion of cyclobutenones and benzocyclobutenones

Here we report a reagent-free rhodium-catalyzed ring-expansion reaction via C–C cleavage of cyclobutenones. A variety of poly-substituted cyclopentenones and 1-indanones can be synthesized from simple cyclobutenones and benzocyclobutenones. The reaction condition is near pH neutral without additional oxidants or reductants. The potential for developing a dynamic kinetic asymmetric transformation of this reaction has also been demonstrated. Further study supports the proposed pathway involving Rh-insertion into the cyclobutenone C–C bond, followed by β-hydrogen elimination, olefin insertion and reductive elimination.     

Late‐Stage Peptide Diversification by Bioorthogonal Catalytic CH Arylation at 23 °C in H2O

The step‐economical late‐stage diversification of tryptophan‐containing peptides was accomplished through chemo‐ and site‐selective palladium‐catalyzed C?H arylation under exceedingly mild reaction conditions. Thus, the C?H functionalization occurred efficiently at 23 °C with a catalyst loading as low as 0.5 mol %, and/or in H₂O.     

An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.     

The development of an approach toward sterically-hindered chiral 2′-aryl-1,1′-binaphthalenes functionalized at position 2

Several approaches were examined for the preparation of 1,1′-binaphthalene derivatives bearing sterically demanding ortho-substituted aryl at position 2′ which are suitable for further functionalization at position 2. Steric hindrance of ortho-substituted aryl groups was critical for the approach through BINOL monotriflate. Among variations of cross-coupling reactions of 2,2′-dihalo-1,1′-binaphthalenes, Negishi arylation of an enantiopure 2,2′-dibromide was found to be the method of choice for regioselective and stereoconservative preparation of the target 2′-monoarylated precursor. Functionalization of the latter at position 2 was demonstrated by bromine substitution via lithiation followed by the reaction with several electrophiles.     

Comparison of sample preparation methods for the ICP-AES determination of minor and major elements in clarified apple juices

Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used for the determination of minor and major elements present in apple juices. Prior to ICP-AES measurement, samples were diluted with nitric acid or digested in a microwave assisted digestion system. The differences in the measured element concentrations after application of different types of sample preparation procedures are discussed. The direct measurement compared to closed microwave dissolution was found to be the best sample preparation procedure. Prior to the measurements the ICP-AES method was validated and optimized for the determination of elements in apple juices. For diluted apple juice samples the lowest limits of detection (LOD) were obtained for Ba and Cd (< 20 μg L^{− 1}), moderate ones for Cu, Mn, Ni, Fe, Ag, Ca, Cr, Zn, Mg, and Sr (20–100 μg L^{− 1}), and the highest LODs for K, Pb, Na, and Al (> 110 μg L^{− 1}). The results obtained for the repeatability (< 0.9%), the intermediate precision (< 4.5%), the day-to-day reproducibility (< 5.2%), and the overall uncertainty of measurement (approx. 4–7%) for all elements analyzed demonstrated the good applicability of the proposed method. Differences in major element content in fresh and commercial apple juice are discussed.     

Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of "clicked" multivalent glycoclusters

The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called "glycoside cluster effect", the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity. The synthesis was achieved through copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) under microwave activation between propargylated multivalent scaffolds and an azido-functionalised carbohydrate derivative. The interactions of two galactose-binding lectins from Pseudomonas aeruginosa (PA-IL) and Erythrina cristagalli (ECA) with the synthesized glycoclusters were studied by hemagglutination inhibition assays (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). The results obtained illustrate the influence of the scaffold's geometry on the affinity towards the lectin and also on the relative potency in comparison with a monovalent galactoside reference probe.