Resonance‐Assisted Intramolecular Chalcogen–Chalcogen Interactions?

High-level B3LYP/6-311+G(3df,2p) density functional calculations have been carried out for a series of saturated chalcogenoaldehydes: CH(X)-CH(2)-CH(2)YH (X, Y=O, S, Se, Te). Our results indicate that in CH(X)-CH(2)-CH(2)YH (X=Y=O, S, Se) the X-H...X intramolecular hydrogen bond (IHB) competes in strength with the X...XH chalcogen-chalcogen interaction, while the opposite is found for the corresponding tellurium-containing analogues. For those derivatives in which X does not equal Y, X being the more electronegative atom, the situation is more complicated due to the existence of two non-equivalent X-H and Y-H tautomers. The Y-H tautomer is found to be lower in energy than the X-H tautomer, independently of the nature of X and Y. For X=O, S, Se and Y=S, Se the most stable conformer b is the one exhibiting a Y-H...X IHB. Conversely when Y=Te, the chelated conformer d, stabilized through a X...YH chalcogen-chalcogen interaction is the global minimum of the potential energy surface. Systematically the IHB and the chalcogen-chalcogen interactions observed for saturated compounds are much weaker than those found for their unsaturated analogues. This result implies that the nonbonding interactions involving chalcogen atoms, mainly Se and Te, are not always strongly stabilizing. This conclusion is in agreement with the fact that intermolecular interactions between Se and Te containing systems with bases bearing dative groups are very weak. We have also shown that these interactions are enhanced for unsaturated compounds, through an increase of the charge delocalization within the system, in a mechanism rather similar to the so call Resonance Assisted Hydrogen Bonds (RAHB). The chalcogen-chalcogen interactions will be also large, due to the enhancement of the X-->Y dative bond, if the molecular environment forces the interacting atoms X and Y to be close each other.     

Use of LC–HRMS in full scan‐XIC mode for multi‐analyte urine drug testing – a step towards a ‘black‐box’ solution?

The influx of new psychoactive substances (NPS) has created a need for improved methods for drug testing in toxicology laboratories. The aim of this work was to design, validate and apply a multi‐analyte liquid chromatography–high‐resolution mass spectrometry (LC–HRMS) method for screening of 148 target analytes belonging to the NPS class, plant alkaloids and new psychoactive therapeutic drugs. The analytical method used a fivefold dilution of urine with nine deuterated internal standards and injection of 2 μl. The LC system involved a 2.0 μm 100 × 2.0 mm YMC‐UltraHT Hydrosphere‐C₁₈ column and gradient elution with a flow rate of 0.5 ml/min and a total analysis time of 6.0 min. Solvent A consisted of 10 mmol/l ammonium formate and 0.005% formic acid, pH 4.8, and Solvent B was methanol with 10 mmol/l ammonium formate and 0.005% formic acid. The HRMS (Q Exactive, Thermo Scientific) used a heated electrospray interface and was operated in positive mode with 70 000 resolution. The scan range was 100–650 Da, and data for extracted ion chromatograms used ± 10 ppm tolerance. Product ion monitoring was applied for confirmation analysis and for some selected analytes also for screening. Method validation demonstrated limited influence from urine matrix, linear response within the measuring range (typically 0.1–1.0 μg/ml) and acceptable imprecision in quantification (CV <15%). A few analytes were found to be unstable in urine upon storage. The method was successfully applied for routine drug testing of 17 936 unknown samples, of which 2715 (15%) contained 52 of the 148 analytes. It is concluded that the method design based on simple dilution of urine and using LC–HRMS in extracted ion chromatogram mode may offer an analytical system for urine drug testing that fulfils the requirement of a ‘black box’ solution and can replace immunochemical screening applied on autoanalyzers. Copyright © 2017 John Wiley & Sons, Ltd.     

Can collision‐induced negative‐ion fragmentations of [M–H]– anions be used to identify phosphorylation sites in peptides?

A joint experimental and theoretical investigation of the fragmentation behaviour of energised [M-H](-) anions from selected phosphorylated peptides has confirmed some of the most complex rearrangement processes yet to be reported for peptide negative ions. In particular: pSer and pThr (like pTyr) may transfer phosphate groups to C-terminal carboxyl anions and to the carboxyl anion side chains of Asp and Glu, and characteristic nucleophilic/cleavage reactions accompany or follow these rearrangements. pTyr may transfer phosphate to the side chains of Ser and Thr. The reverse reaction, namely transfer of a phosphate group from pSer or pThr to Tyr, is energetically unfavourable in comparison. pSer can transfer phosphate to a non-phosphorylated Ser. The non-rearranged [M-H](-) species yields more abundant product anions than its rearranged counterpart. If a peptide containing any or all of Ser, Thr and Tyr is not completely phosphorylated, negative-ion cleavages can determine the number of phosphated residues, and normally the positions of Ser, Thr and Tyr, but not which specific residues are phosphorylated. This is in accord with comments made earlier by Lehmann and coworkers.     

One‐ or Two‐Electron Transfer? The Ambiguous Nature of the Discharge Products in Sodium–Oxygen Batteries

Rechargeable lithium–oxygen and sodium–oxygen cells have been considered as challenging concepts for next‐generation batteries, both scientifically and technologically. Whereas in the case of non‐aqueous Li/O₂ batteries, the occurring cell reaction has been unequivocally determined (Li₂O₂ formation), the situation is much less clear in the case of non‐aqueous Na/O₂ cells. Two discharge products, with almost equal free enthalpies of formation but different numbers of transferred electrons and completely different kinetics, appear to compete, namely NaO₂ and Na₂O₂. Cells forming either the superoxide or the peroxide have been reported, but it is unclear how the cell reaction can be influenced for selective one‐ or two‐electron transfer to occur. In this Minireview, we summarize available data, discuss important control parameters, and offer perspectives for further research. Water and proton sources appear to play major roles.     

Is the Hoveyda–Grubbs Complex a Vinylogous Fischer‐Type Carbene? Aromaticity‐Controlled Activity of Ruthenium Metathesis Catalysts

Three naphthalene-based analogues (4 a-c) of the Hoveyda-Grubbs metathesis catalyst exhibited immense differences in reactivity. Systematic structural and spectroscopic studies revealed that the ruthenafurane ring present in all 2-isopropoxyarylidene chelates possesses some aromatic character, which inhibits catalyst activity. This aromatic stabilization within the chelate ring may be controlled by variation of the polycyclic core topology as was demonstrated for tetraline and phenanthrene derivatives (4 d, e). General conclusions about a new mode of ligand-structure tuning in catalytic systems are presented.     

Generating CuII–Oxyl/CuIII–Oxo Species from CuI–α‐Ketocarboxylate Complexes and O2: In Silico Studies on Ligand Effects and C?H‐Activation Reactivity

Theoretically speaking : The mechanistic details associated with the generation and reaction of [CuO]⁺ species from Cu^I–α‐ketocarboxylate complexes, especially with respect to modifications of the ligand supporting the copper center, were investigated (see scheme). Theoretical models were used to characterize the electronic structures of different [CuO]⁺ species and their reactivity in C? H activation and O‐atom transfer reactions.

     

In Search of Organic Zeolites – Does Modern Information Retrieval Inevitably Become a ‘Sieving‐the‐Desert' Exercise?

Information retrieval for planning and executing research projects and for publishing results is considered a routine task that is usually neither mentioned explicitly in a scientific publication nor described in any detail. In the information searches for the preceding publication (‘Building an Organic Zeolite from a Macrocyclic TADDOL Derivative or How to Teach an Old Dog New Tricks'), we were confronted with so many problems during retrieval of the desired information about related work that we decided to deviate from this tradition. We had to use the Cambridge Structural Database, the Chemical Abstracts structure and literature databases, and the Beilstein database to the full extent of their contents, indexing, and search facilities to retrieve the necessary information about ‘organic zeolites'. In the process, we found important limitations and deficiencies in any one of these databases, and we had to conceive search procedures that we considered rather unusual even after more than 20 years of experience in searching chemistry databases. The results and, particularly, the problems encountered underline the necessity for enhanced integration of individual compound and property databases and improved standardization as a prerequisite for this.     

Intramolecular Methylacridan–Methylacridinium Complexes with a Phenanthrene‐4,5‐diyl or Related Skeleton: Geometry–Property Relationships in Isolable C?H Bridged Carbocations

Bridging the gap : Snapshots of 1,6‐H‐shift precursors indicate that a narrower C? H???C⁺ separation (D in the ORTEP diagram) in the title complexes induces faster degenerate rearrangement of 1 ⁺. A contact distance of less than 2.7 Å is necessary to realize the organic three‐center two‐electron bond of [C? H? C]⁺, as indicated by extrapolation of the X‐ray data.

     

The Liebeskind–Srogl C?C Cross‐Coupling Reaction

New kid on the block : The cross‐coupling of thioorganic compounds with boronic acids under neutral conditions in the presence of catalytic palladium(0) and a stoichiometric amount of a copper(I) oxygenate has emerged as a very useful method for the construction of C C bonds (see scheme). This intriguing and mechanistically unprecedented base‐free coupling has distinct advantages, in particular when traditional Pd⁰‐catalyzed cross‐coupling is not possible.

     

A Straightforward Synthesis of 2‐[1‐Alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic Acid Derivatives via Domino Michael Addition?Cyclization Reaction

A new and efficient synthesis of 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives by a one‐pot three‐component reaction between primary amine, dialkyl acetylenedicarboxylate, and itaconic anhydride (=3,4‐dihydro‐3‐methylidenefuran‐2,5‐dione) is reported. The reaction was performed without catalyst and under solvent‐free conditions with excellent yields. Notably, the ready availability of the starting materials, and the high level of practicability of the reaction and workup make this approach an attractive complementary method to access to unknown 2‐[1‐alkyl‐5,6‐bis(alkoxycarbonyl)‐1,2,3,4‐tetrahydro‐2‐oxopyridin‐3‐yl]acetic acid derivatives. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of domino Michael addition? cyclization reaction is proposed (Scheme 2).