We study responses of thermally annealed ultrathin films deposited on silicon substrates and containing polyzwitterions to applied electric fields by using specular neutron reflectometry (NR). In particular, we applied 7 kV under vacuum at 150 °C on the films containing poly(1-(3-sulfonatopropyl)-2-vinylpyridinium) (P2VPPS) and its blends with either a deuterated ionic liquid (EMIMBF4-d11), potassium bromide (KBr), or deuterated sodium polystyrenesulfonate (NaPSS-d7). The voltage was applied over an air gap, and the in situ neutron reflectivity measurements allowed us to measure changes in the films. In all the cases, we measured decreases in thicknesses of the films, which varied up to ∼8% depending on the added salt. Posteriori X-ray reflectivity (XRR) measurements on the same films at room temperature reveal that these films were highly hygroscopic, which led to the presence of water in these films. Analysis of the NR and the XRR revealed that the decrease in the thickness of the films in the neutron reflectivity experiments on heating resulted from the loss of water and the ionic liquid but not from electrostrictive effects. The in situ NR and posteriori XRR experiments revealed not only the hygroscopic nature of these films but also depth-resolved structural rearrangements due to the applied electric fields in the films containing electrolytes and polyelectrolytes. This work shows that a combination of NR and XRR can be used to distinguish between mass loss and electrostriction in films containing charged polymers such as polyzwitterions.

A catalytic metal-free approach for the H/D exchange in aromatic compounds using D2O as the terminal deuterating reagent has been developed. This metal-free protocol employs a triaryl carbenium as the mediator and showcases a wide applicability in the late-stage deuteration of various natural products and small-molecule drugs. Gram-scale deuteration was successfully demonstrated with β-Estradiol, highlighting the method\'s practicability. Detailed mechanistic insights, supported by DFT calculations, unveiled the essential role of in-situ generated acidic species in this electrophilic aromatic substitution process. This newly developed method offers a sustainable and versatile alternative to traditional metal-catalyzed H/D exchange techniques, addressing challenges such as the use of expensive metals, impurity formation, and the necessity for residual metal removal from the final products.

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.

Electron-rich heteroaromatics, such as furan, thiophene and pyrrole, as well as their benzo-condensed derivatives, are of great interest as components of natural products and as starting substances for various products including high-tech materials. Although their reactions with Brønsted and Lewis acids play important roles, in particular as the primary step of various transformations, they are often disregarded and mechanistically not understood. The present publication gives a first overview about this chemistry focusing on the parent compounds. It comprises reactions with strong Brønsted acids forming adducts that can undergo intramolecular proton and/or substituent transfer reactions, ring openings or ring transformations into other heterocycles, depending on their structure. Interactions with weak Brønsted acids usually initiate oligomerizations/polymerizations. A similar behaviour is observed in reactions of these heteroaromatics with Lewis acids. Special effects are achieved when the Lewis acids are activated through primary protonation. Deuterated Brønsted acids allow straight forward deuteration of electron-rich heteroaromatics. Mercury salts as extremely weak Lewis acids cause direct metalation in a straight forward way replacing ring H-atoms yielding organomercury heterocycles. This review will provide comprehensive information about the chemistry of adducts of such heterocycles with Brønsted and Lewis acids enabling chemists to understand the mechanisms and the potential of this field and to apply the findings in future syntheses.

Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from the nature of the photoswitch itself (e.g. azobenzenes, dithienylethenes, hemithioindigo) to fine-tuning of aromatic units and substituents. Herein, we present deuterated azobenzene photoswitches as a general means of enhancing the performance of photopharmacological molecules. Deuteration can improve azobenzene performance in terms of light sensitivity (higher molar extinction coefficient), photoswitch efficiency (higher photoisomerization quantum yield), and photoswitch kinetics (faster macroscopic rate of photoisomerization) with minimal alteration to the underlying structure of the photopharmacological ligand. We report synthesized deuterated azobenzene-based ligands for the optimized optical control of ion channel and G protein-coupled receptor (GPCR) function in live cells, setting the stage for the straightforward, widespread adoption of this approach.

The peripherical protons of the dye molecule hypericin can undergo structural interconversion (tautomerization) between different isomers separated by a low energy barrier with rates that depends sensitively on the interaction with local chemical environment defined by the nature of host material. We investigate the deuterium (D) isotope effect of hypericin tautomerism at the single-molecule level to avoid ensemble averaging in different polymer matrices by a combined spectroscopic and computational approach. In the \'innocent\' PMMA matrix only intramolecular isotope effects on the internal conversion channel and tautomerization are observed; while PVA specifically interacts with the probe via H- and D-bonding. This establishes a single molecular picture on intra- and intermolecular nano-environment effects to control chromophore photophysics and -chemistry.

Constrained by a limited understanding of the structure and luminescence mechanisms of carbon dots (CDs), achieving precise enhancement of their photoluminescence (PL) performance without altering the emission wavelength and color remains a challenge. In this work, a deuterated CD is first achieved by simply replacing the reaction solvent from H2O to D2O. The substitution of D atoms for H atoms is not limited on the surface but also within the internal structure of CDs. Deuteration affects the formation of the π-conjugated network structure by altering the content of sp2 carbon and sp3 carbon, ultimately inducing a reconstruction for energy level structure of CDs. Both the intrinsic state and surface state emission, including quantum yield, emission intensity and lifetime, are significantly enhanced after deuteration. It benefits from the reduction in non-radiative transitions, since the lowered vibrational frequencies of D atoms and optimized local energy level distribution in CDs structure. The deuterated CDs are applied in the fabrication of white-light-emitting diodes to show their application potential. This work provides a highly versatile route for improving and controlling photoluminescence performance of CDs and has opportunities to guide the development of CDs for practical applications.

The conjugation of proteins with polymers offers immense biotechnological potential by creating novel macromolecules. This article presents experimental findings on the structural properties of maltose-binding protein (MBP) conjugated with linear biodegradable polyphosphoester polymers with different molecular weights. We studied isotopic effects on both proteins and polymers. Circular dichroism and fluorescence spectroscopy and small-angle neutron scattering reveal that the conjugation process destabilizes the protein, affecting the secondary more than the tertiary structure, even at room temperature, and that the presence of two domains in the MBP may contribute to its observed instability. Notably, unfolding temperatures differ between native MBP and the conjugates. In particular, this study sheds light on the complex interplay of factors such as the deuteration influencing protein stability and conformational changes in the conjugation processes. The perdeuteration influences the hydrogen bond network and hydrophobic interactions in the case of the MBP protein. The perdeuteration of the protein influences the hydrogen bond network and hydrophobic interactions. This is evident in the decreased thermal stability of deuterated MBP protein, in the conjugate, especially with high-molecular-mass polymers.

Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an N-alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular N-alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug market rapidly. In response to the large number of SCRAs that have been detected, pharmacological evaluation of this NPS class has become increasingly common. Adamantane-derived SCRAs have consistently appeared throughout the market since 2011, and as such, a systematic set of these derivatives was synthesized and pharmacologically evaluated. Deuterated and fluorinated adamantane derivatives were prepared to evaluate typical hydrogen bioisosteres, as well as evaluation of the newly detected AFUBIATA.

Deuterated drugs (heavy drugs) have recently been spotlighted as a new modality for small-molecule drugs because the pharmacokinetics of pharmaceutical drugs can be enhanced by replacing C-H bonds with more stable C-D bonds at metabolic positions. Therefore, deuteration methods for drug candidates are a hot topic in medicinal chemistry. Among them, the H/D exchange reaction (direct transformation of C-H bonds to C-D bonds) is a useful and straightforward method for creating novel deuterated target molecules, and over 20 reviews on the synthetic methods related to H/D exchange reactions have been published in recent years. Although various deuterated drug candidates undergo clinical trials, approved deuterated drugs possess CD3 groups in the same molecule. However, less diversification, except for the CD3 group, is a problem for future medicinal chemistry. Recently, we developed various deuterated alkyl (dn-alkyl) sulfonium salts based on the H/D exchange reaction of the corresponding hydrogen form using D2O as an inexpensive deuterium source to introduce CD3, CH3CD2, and ArCH2CD2 groups into drug candidates. This concept summarises recent reviews related to H/D exchange reactions and novel reagents that introduce the CD3 group, and our newly developed electrophilic dn-alkyl reagents are discussed.