The development of a boron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boron-based Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base. This advance allows the limits of FLP's hydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls. This metal-free catalytic variant displays a notably broad chemoselectivity and generality.

Nuclear magnetic resonance (NMR) spectroscopy is an analytical technique that gives information on the local magnetic field around atomic nuclei. Since the local magnetic field of the nucleus is directly influenced by such features of the molecular structure as constitution, configuration, conformation, intermolecular interactions, etc., NMR can provide exhaustive information on the chemical structure, which is unrivaled by any other analytical method. Starting from the 1950s, NMR spectroscopy first revolutionized organic chemistry and became an indispensable tool for the structure elucidation of small, soluble molecules. As the technique evolved, NMR rapidly conquered other disciplines of chemical sciences. When the analysis of macromolecules and solids also became feasible, the technique turned into a staple in materials characterization, too. All aspects of NMR spectroscopy, including technical and technological development, as well as its applications in natural sciences, have been growing exponentially since its birth. Hence, it would be impossible to cover, or even touch on, all topics of importance related to this versatile analytical tool. In this tutorial, we aim to introduce the reader to the basic principles of NMR spectroscopy, instrumentation, historical development and currently available brands, practical cost aspects, sample preparation, and spectrum interpretation. We show a number of advanced techniques relevant to materials characterization. Through a limited number of examples from different fields of materials science, we illustrate the immense scope of the technique in the analysis of materials. Beyond our inherently limited introduction, an ample list of references should help the reader to navigate further in the field of NMR spectroscopy.

Background and Purpose:Mitragyna speciosa extract and kratom alkaloids decrease alcohol consumption in mice at least in part through actions at the δ-opioid receptor (δOR). However, the most potent opioidergic kratom alkaloid, 7-hydroxymitragynine, exhibits rewarding properties and hyperlocomotion presumably due to preferred affinity for the mu opioid receptor (µOR). We hypothesized that opioidergic kratom alkaloids like paynantheine and speciogynine with reduced µOR potency could provide a starting point for developing opioids with an improved therapeutic window to treat alcohol use disorder.Experimental Approach: We characterized paynantheine, speciociliatine, and four novel kratom-derived analogs for their ability to bind and activate δOR, µOR, and κOR. Select opioids were assessed in behavioral assays in male C57BL/6N WT and δOR knockout mice.Key Results: Paynantheine (10 mg∙kg−1, i.p.) produced aversion in a limited conditioned place preference (CPP) paradigm but did not produce CPP with additional conditioning sessions. Paynantheine did not produce robust antinociception but did block morphine-induced antinociception and hyperlocomotion. Yet, at 10 and 30 mg∙kg−1 doses (i.p.), paynantheine did not counteract morphine CPP. 7-hydroxypaynantheine and 7-hydroxyspeciogynine displayed potency at δOR but limited µOR potency relative to 7-hydroxymitragynine in vitro, and dose-dependently decreased voluntary alcohol consumption in WT but not δOR in KO mice. 7-hydroxyspeciogynine has a maximally tolerated dose of at least 10 mg∙kg−1 (s.c.) at which it did not produce significant CPP neither alter general locomotion nor induce noticeable seizures.Conclusion and Implications: Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window.

The development of ab oron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boronbased Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base.T his advance allows the limits of FLPsh ydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls.T his metal-free catalytic variant displays an otably broad chemoselectivity and generality.

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