Monitoring of the Pre-Equilibrium Step in the Alkyne Hydration Reaction Catalyzed by Au(III) Complexes: A Computational Study Based on Experimental Evidences

The coordination ability of the [(ppy)Au(IPr)]²⁺ fragment [ppy = 2-phenylpyridine, IPr = 1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene] towards different anionic and neutral X ligands (X = Cl⁻, BF₄⁻, OTf⁻, H₂O, 2-butyne, 3-hexyne) commonly involved in the crucial pre-equilibrium step of the alkyne hydration reaction is computationally investigated to shed light on unexpected experimental observations on its catalytic activity. Experiment reveals that BF₄⁻ and OTf⁻ have very similar coordination ability towards [(ppy)Au(IPr)]²⁺ and slightly less than water, whereas the alkyne complex could not be observed in solution at least at the NMR sensitivity. Due to the steric hindrance/dispersion interaction balance between X and IPr, the [(ppy)Au(IPr)]²⁺ fragment is computationally found to be much less selective than a model [(ppy)Au(NHC)]²⁺ (NHC = 1,3-dimethylimidazol-2-ylidene) fragment towards the different ligands, in particular OTf⁻ and BF₄⁻, in agreement with experiment. Effect of the ancillary ligand substitution demonstrates that the coordination ability of Au(III) is quantitatively strongly affected by the nature of the ligands (even more than the net charge of the complex) and that all the investigated gold fragments coordinate to alkynes more strongly than H₂O. Remarkably, a stabilization of the water-coordinating species with respect to the alkyne-coordinating one can only be achieved within a microsolvation model, which reconciles theory with experiment. All the results reported here suggest that both the Au(III) fragment coordination ability and its proper computational modelling in the experimental conditions are fundamental issues for the design of efficient catalysts.     

Synthesis and Transformations of NH-Sulfoximines

Recent years have seen a marked increase in the occurrence of sulfoximines in the chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximine containing compounds into clinical trials and the concurrent development of powerful synthetic methods. This review covers recent developments in the synthesis of sulfoximines concentrating on developments since 2015. This includes extensive developments in both S−N and S−C bond formations. Flow chemistry processes for sulfoximine synthesis are also covered. Finally, subsequent transformations of sulfoximines, particularly in N-functionalization are reviewed, including N−S, N−P, N−C bond forming processes and cyclization reactions.     

Stability Monitoring of Electrolytic Conductivity Reference Materials Under Repeated Use Conditions by the Primary Measurement Method

This work presents the results from stability studies for several electrolytic conductivity (EC) reference materials submitted to repeated use conditions, as required by the last version of the ISO 17034 standard. Eight batches of reference materials, composed of water or water/n-propanol and HCl or KCl (at different concentrations), were studied, with nominal EC values ranging from 5 to 12,825 µS·cm−1. The materials were submitted to a simulation of repeated use, with the manipulation of bottles once a week and their storage under refrigeration with air gaps inside them. They were then analyzed once a month by the EC primary measurement method. The measurement results were evaluated to check for deviations from conventional long-term stability monitoring and for variation trends using normalized error and linear regression statistical tests. The results indicated that the repeated use simulation caused deviations in the EC for the 100 and 500 µS·cm−1 reference materials and variation trends in the EC for the 5000 and 12,825 µS·cm−1 reference materials. From the results, the uncertainty related to stability monitoring under repeated use conditions was calculated for each reference material.     

Theoretical and Experimental Analysis of Protoporphyrin IX Photodegradation Using Multi-Wavelength Light Sources

Photodynamic procedures have been used in many applications, ranging from cancer treatment to microorganism inactivation. Photodynamic reactions start with the activation of a photosensitizing molecule with light, leading to the production of cytotoxic molecules that promote cell death. However, establishing the correct light and photosensitizer dosimetry for a broadband light source remains challenging. In this study, we proposed a theoretical mathematical model for the photodegradation of protoporphyrin IX (PpIX), when irradiated by multi-wavelength light sources. The theoretical model predicts the experimental photobleaching (temporal change in PpIX concentration) of PpIX for different light sources. We showed that photobleaching occurs independently of the light source wavelengths but instead depends only on the number of absorbed photons. The model presented here can be used as an important mathematical approach to better understand current photodynamic therapy protocols and help achieve optimization of the doses delivered.     

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.     

Paper spray tandem mass spectrometry: A rapid approach for the assay of parabens in cosmetics and drugs

A fast methodology for the assay of parabens in drug and cosmetic preparations has been presented. The procedure developed is based on paper spray tandem mass spectrometry and isotope dilution approach. For each investigated paraben, the corresponding labeled standard has been used in order to improve the accuracy and reproducibility of the analyses. The MS experiments have been performed under MRM conditions, monitoring the transitions [M‐H]^? → m/z 92 and [M‐H]^? → m/z 98, respectively, for each analyte and the corresponding labeled internal standard. The quantitative assay has been performed using a calibration curve built from 2 to 15 mg/L. The method accuracy, in all case near 100%, was evaluated using fortified samples at two concentration levels, which are representative of the lower and the higher portion of calibration curve. The good values of LOQ, LOD, and reproducibility confirm the consistency of the developed approach.     

Accurate Modelling of Group Electrostatic Potential and Distributed Polarizability in Dipeptides

Within the scope of accurate structure-property correlations in biomolecules, this work investigates how conformations and electronic configurations of biologically relevant macromolecules affect their intermolecular potentials. With the purpose of testing the suitability of a simple and universal model, the dipeptides are made from the assembly of their building blocks, namely the amino acid residuals or, more finely tuned, the individual functional groups. The model makes use of functional-group electrostatic potentials (GEP) and distributed polarizabilities (GDP), which enable an in depth analysis of the correlation between structural features and property build-up. GEPs and GDPs are calculated for various conformers and protonation states of L-alanyl-L-alanine, glycyl-L-alanine, L-alanylglycine, and glycylglycine, which are prototypic molecules to model the pertinent functional groups. The model provides GEPs that reproduce the exact potential to an average accuracy of ca. 0.05 au. The good agreement between the properties estimated with the simple model and those calculated with state-of-the-art quantum chemical methods encourages further testing of the predictive power of this model, simulating for example interaction energies and optoelectronic properties.