A Germylene Stabilized by Homoconjugation

The synthesis of a bicyclic germylene from the reaction of a germole dianion with hafnocene dichloride is reported. This germylene is stabilized by a homoconjugative interaction of the dicoordinated germanium atom with a remote C=C double bond. First reactivity studies revealed its nucleophilic character and resulted in the synthesis of bimetallic hafnium/iron and hafnium/tungsten complexes with a germylene group linker.     

Normal phase HPLC-based activity profiling of non-polar crude plant extracts – acetylcholinesterase inhibiting guttiferones from Montrouziera cauliflora as a case study

The study describes bioactive compounds as inhibitors of acetylcholinesterase (AChE), from the stem bark extract of Montrouziera cauliflora, selected among 19 dichloromethane extracts from Clusiaceae species. Our work focused on the development of an original normal phase HPLC microfractionation strategy to rapidly assess highly active zones from this crude active non-polar plant extract. Two different microfraction collection methods were evaluated for the assessment of the AChE inhibition. Two guttiferones and a tocotrienol were directly isolated among five compounds identified off-line by NMR after upscaling the fractionation and their AChE inhibition was evaluated. The strengths and weaknesses of the two microfractionation collection methods for HPLC-AChE activity-based profiling are discussed.     

Sard theorems for Lipschitz functions and applications in optimization

We establish a “preparatory Sard theorem” for smooth functions with a partially affine structure. By means of this result, we improve a previous result of Rifford [17, 19] concerning the generalized (Clarke) critical values of Lipschitz functions defined as minima of smooth functions. We also establish a nonsmooth Sard theorem for the class of Lipschitz functions from R^d to R^p that can be expressed as finite selections of C^k functions (more generally, continuous selections over a compact countable set). This recovers readily the classical Sard theorem and extends a previous result of Barbet–Daniilidis–Dambrine [1] to the case p > 1. Applications in semi-infinite and Pareto optimization are given.     

Chemiluminescent probe for the in vitro detection of protease activity

A strategy involving the use of a self-immolative linker has been investigated for the chemiluminescent sensing of proteases. The reactive linker enabled the release of a 1,2-dioxetane light precursor. As a proof of principle, caspase-3, a key peptidase involved in apoptosis has been targeted. An in vitro assay has been carried out and proved the decomposition of the linker and the selectivity for caspase-3.     

Alternative to consensus scoring--a new approach toward the qualitative combination of docking algorithms

Since the development of the first docking algorithm in the early 1980s a variety of different docking approaches and tools has been created in order to solve the docking problem. Subsequent studies have shown that the docking performance of most tools strongly depends on the considered target. Thus it is hard to choose the best algorithm in the situation at hand. The docking tools FlexX and AutoDock are among the most popular programs for docking flexible ligands into target proteins. Their analysis, comparison, and combination are the topics of this study. In contrast to standard consensus scoring techniques which integrate different scoring algorithms usually only by their rank, we focus on a more general approach. Our new combined docking workflow-AutoxX-unifies the interaction models of AutoDock and FlexX rather than combining the scores afterward which allows interpretability of the results. The performance of FlexX, AutoDock, and the combined algorithm AutoxX was evaluated on the basis of a test set of 204 structures from the Protein Data Bank (PDB). AutoDock and FlexX show a highly diverse redocking accuracy at the different complexes which assures again the usefulness of taking several docking algorithms into account. With the combined docking the number of complexes reproduced below an rmsd of 2.5 A could be raised by 10. AutoxX had a strong positive effect on several targets. The highest performance increase could be found when redocking 20 protein-ligand complexes of alpha-thrombin, plasmepsin, neuraminidase, and d-xylose isomerase. A decrease was found for gamma-chymotrypsin. The results show that--applied to the right target-AutoxX can improve the docking performance compared to AutoDock and FlexX alone.     

A food freshness sensor using the multistate response from analyte-induced aggregation of a cross-reactive poly(thiophene)

A single cross-reactive conjugated polymer generates a multidimensional response capable of identifying and differentiating between 22 structurally similar and biologically relevant amines with 97% accuracy in a highly competitive aqueous environment. Statistical analysis on an array of wavelengths was used to assess the viability of this approach. In a separate investigation, the multidimensional response from a single cross-responsive poly(thiophene) has been analyzed using a different ratiometric method to quantify the amount of biogenic amine present in a fish matrix, thereby evaluating the quality of the food.