On-line coupling between chromatography and inductively coupled plasma mass spectrometry — a current assessment

The current state of on-line coupling between liquid chromatography and inductively coupled plasma mass spectrometry is reviewed. The applications can be divided into three subgroups by changing the importance of the coupling partners. An overview is given of applications in these subgroups, of its use as preconcentration and matrix elimination techniques, for the elimination of spectral interferences and as a tool for speciation analysis. A discussion of current and future development areas in on-line HPLC-ICP-MS is also included.     

TEAD–YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics

DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or “hot spot”, regions of protein–protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide “hexT”, encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.     

Arene C−H Activation at Aluminium(I): meta Selectivity Driven by the Electronics of SNAr Chemistry

The reactivity of the electron-rich anionic Al^I aluminyl compound K₂[(NON)Al]₂ (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) towards mono- and disubstituted arenes is reported. C−H activation chemistry with n-butylbenzene gives exclusively the product of activation at the arene meta position. Mechanistically, this transformation proceeds in a single step via a concerted Meisenheimer-type transition state. Selectivity is therefore based on similar electronic factors to classical S_NAr chemistry, which implies the destabilisation of transition states featuring electron-donating groups in either ortho or para positions. In the cases of toluene and the three isomers of xylene, benzylic C−H activation is also possible, with the product(s) formed reflecting the feasibility (or otherwise) of competing arene C−H activation at a site which is neither ortho nor para to a methyl substituent.     

Detection of traces of oxidized and reduced sulfur compounds in small samples by combination of different high-performance liquid chromatography methods

Depending on the sulfur species, picomoles of different inorganic sulfur compounds can be detected and separated by HPLC in one arrangement in a sample volume less than 50 μl. The combination of fluorescence labelling of reduced inorganic sulfur compounds such as sulfide (S²⁻), sulfite(SO₃²⁻ and thiosulfate (S₂O₃²⁻) with monobromobimane followed by an extraction of elemental sulfur (S°) by chloroform treatment enables the detection of all mentioned sulfur compounds as well as sulfate (remaining aqueous phase) in the same sample. While the derivatized sulfur compounds could be detected by their fluorescence emission at 480 nm, elemental sulfur is identified by its UV absorption at 263 nm. Sulfate in the remaining aqueous phase is detected by HPLC with indirect UV detection at 254 nm. Detection ranges for the different sulfur compounds examined are as follows: sulfide (5 μM to 1.5 mM), sulfite (5 μM to 1.0 mM), thiosulfate (1 μM to 1.5 mM), elemental sulfur (2 μM to 32 mM) and sulfate (5 μM to >1 mM).