Charge-charge and cation-<Emphasis Type="Italic">π</Emphasis> interactions in ligand binding to G protein-coupled receptors

To study the importance of charge–charge and cation-π interactions for the binding of positively charged amine ligands to their receptors, the energies of interaction between [(CH₃)₄–N]⁺, [(CH₃)₃–NH]⁺, and [(CH₃)₄–NH₃]⁺ and acetate, as a model of Asp and Glu, and with benzene, as a model of aromatic side chains, were obtained at the MP2/aug-cc-pVDZ level of theory. The free energies of solvation in water were also calculated for the different amines. It was found that, although primary amines form stronger charge–charge interactions with acetate than tertiary or quaternary amines, the difference is not large enough to compensate their higher solvation energy. Quaternary amines show the weakest interaction with acetate. However, their alkyl groups can interact with various aromatic groups, enhancing ligand binding to the receptor. The analysis was completed with MD calculations on amine binding to the G protein-coupled receptors β₂AR and CCR5. The calculations on the model systems were found to be in good agreement with the simulations of the ligand-receptor complexes. Contribution to the Serafin Fraga Memorial Issue.     

Photostability of a photochromic naphthopyran dye in different sol-gel prepared ormosil coatings

A photochromic naphthopyran derivative was embedded in sol-gel prepared thin ormosil films. The resulting samples show high transparency and exhibit a strong red colouration upon irradiation with UV light. The photostability of the photochromic molecules is strongly related to the nature of the embedding ormosil matrix. The introduction of organic functional groups into the inner pore surface of the matrix allows tailoring the chemical environment where the dye molecules will be allocated, in terms of the effectiveness of the interaction between the photochromic molecules and the Si-OH groups on the surface of the pores, affecting the stability of the molecules upon prolonged exposition to UV light. The photostability of the molecules was increased in matrices functionalized with larger organic groups, or with larger amount of modifying groups. In this way the photodegradation of the photochromic molecules could be reduced by a factor of 5, as compared with the photodegradation of the molecules in unfunctionalized silica matrix.     

Comparison of the performance of three ion mobility spectrometers for measurement of biogenic amines

The performance of three different types of ion mobility spectrometer (IMS) devices: GDA2 with a radioactive ion source (Airsense, Germany), UV-IMS with a photo-ionization source (G.A.S. Germany) and VG-Test with a corona discharge source (3QBD, Israel) was studied. The gas-phase ion chemistry in the IMS devices affected the species formed and their measured reduced mobility values. The sensitivity and limit of detection for trimethylamine (TMA), putrescine and cadaverine were compared by continuous monitoring of a stream of air with a given concentration of the analyte and by measurement of headspace vapors of TMA in a sealed vial. Preprocessing of the mobility spectra and the effectiveness of multivariate curve resolution techniques (MCR-LASSO) improved the accuracy of the measurements by correcting baseline effects and adjusting for variations in drift time as well as enhancing the signal to noise ratio and deconvolution of the complex data matrix to their pure components. The limit of detection for measurement of the biogenic amines by the three IMS devices was between 0.1 and 1.2 ppm (for TMA with the VG-Test and GDA, respectively) and between 0.2 and 0.7 ppm for putrescine and cadaverine with all three devices. Considering the uncertainty in the LOD determination there is almost no statistically significant difference between the three devices although they differ in their operating temperature, ionization method, drift tube design and dopant chemistry. This finding may have general implications on the achievable performance of classic IMS devices.     

One-Pot Synthesis and Applications of N-Heteroaryl Iodonium Salts

An efficient one-pot synthesis of N-heteroaryl iodonium triflates from the corresponding N-heteroaryl iodide and arene has been developed. The reaction conditions resemble our previous one-pot syntheses, with suitable modifications to allow N-heteroaryl groups. The reaction time is only 30 min, and no anion exchange is required. The obtained iodonium salts were isolated in a protonated form, these salts can either be employed directly in applications or be deprotonated prior to use. The aryl groups were chosen to induce chemoselective transfer of the heteroaryl moiety to various nucleophiles. The reactivity and chemoselectivity of these iodonium salts were demonstrated by selectively introducing a pyridyl moiety onto both oxygen and carbon nucleophiles in good yields.     

Access to Optically Active 3‐Substituted Piperidines by Ring Expansion of Prolinols and Derivatives

The ring expansion of prolinols via an aziridinium intermediate gives C3‐substituted piperidines in good yields and enantiomeric excess, the substituent at the C3 position being derived from the most reactive nucleophile in the reaction mixture. Depending on the nucleophile, the reaction proceeds under thermodynamic or kinetic control. The regioselectivity of attack of nucleophiles on the aziridinium intermediate depends on the nature of the substituents on the nitrogen atom and the C4 position of the starting prolinols.     

Mechanically Interlocked Single‐Wall Carbon Nanotubes

Extensive research has been devoted to the chemical manipulation of carbon nanotubes. The attachment of molecular fragments through covalent‐bond formation produces kinetically stable products, but implies the saturation of some of the C? C double bonds of the nanotubes. Supramolecular modification maintains the structure of the SWNTs but yields labile species. Herein, we present a strategy for the synthesis of mechanically interlocked derivatives of SWNTs (MINTs). In the key rotaxane‐forming step, we employed macrocycle precursors equipped with two π‐extended tetrathiafulvalene SWNT recognition units and terminated with bisalkenes that were closed around the nanotubes through ring‐closing metathesis (RCM). The mechanically interlocked nature of the derivatives was probed by analytical, spectroscopic, and microscopic techniques, as well as by appropriate control experiments. Individual macrocycles were observed by HR STEM to circumscribe the nanotubes.     

Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB2 Receptor**

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB₂ receptor. These compounds selectively target CB₂ versus CB₁ receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis.