Institute of Advanced Chemistry of Catalonia

The structural and electronic properties of MXenes were investigated by means of a finite-system approach using all-electron Density Functional Theory-based calculations. Pristine (M2C)n flakes and their O-terminated counterparts (M2CO2)n (M = Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo and W; 12 ≤ n ≤ 216) were computationally modelled. Surface-like behaviour is lost for n ≤ 90, corresponding to ca. 3 nm wide flakes, where finite-size effects become increasingly relevant. While the flake structure at the core is very similar to that found in extended periodic models, the edges are often deformed due to structural defects, which impact their electronic properties. Pristine M2C flakes are metallic, while the O-terminated M2CO2 counterparts present bandgaps exceeding 1 eV for metals of Groups III and IV when neglecting low-populated gap states near the Fermi level. The alignment of the valence and conduction bands for these systems evolves favourably to nearly include the water splitting half-reactions within the bandgap for the largest flakes. Overall, our results show that Sc, Y, Zr, and Hf O-functionalised MXenes are the best suited for photocatalytic water splitting, obtaining energy gaps within the visible spectrum for several flake sizes, and band alignments closer to water oxidation and hydrogen reduction reactions.

ZUSAMMENFASSUNG Die Photopharmakologie entwickelt lichtresponsive Wirkstoffe zur gezielten Modulation von Proteinaktivitäten, die präzise und dynamische Untersuchungen ihrer Funktionen in Gesundheit und Krankheit ermöglichen. Adrenerge Rezeptoren sind hierfür besonders geeignete Ziele, da sie prototypische G‐Protein‐gekoppelte Rezeptoren mit hoher klinischer Relevanz für bronchiale und kardiovaskuläre Erkrankungen darstellen. In dieser Studie kombinierten wir die azobenzenbasierte Verbindung Photoazolol‐1 mit zeitaufgelöster serieller Kristallographie an Röntgen‐Freie‐Elektronen‐Lasern, um die molekularen Mechanismen aufzuklären, durch die photoschaltbare β‐Blocker die Aktivität des β 2 ‐Adrenozeptors (β 2 AR) modulieren. Zeitaufgelöste Strukturen des Rezeptors in Komplexen mit trans‐Photoazolol‐1 (vor der Photokonversion), einem gespannten Zwischenzustand im Nanosekundenbereich sowie vollständig photoisomerisiertem cis‐Photoazolol‐1 zeigen, wie die Isomerisierung der Azobenzeneinheit unterschiedliche konformationelle Veränderungen innerhalb der orthosterischen Ligandenbindetasche induziert. Innerhalb von Sekunden nimmt lichtangeregtes Photoazolol‐1 eine neue Bindepose ein, wodurch Wechselwirkungen mit der extrazellulären Schleife 2 verändert und die Positionen der Transmembranhelices 5, 6 und 7 verschoben werden. Funktionelle Assays des β 2 AR in zellulären Membranen belegen, dass Photoazolol‐1 als Wirksamkeits‐Photoschalter fungiert, der sich bei der Isomerisierung von einem inversen Agonisten zu einem neutralen Antagonisten wandelt, ohne die Bindetasche zu verlassen. Zusammengenommen weisen diese Ergebnisse auf einen molekularen Mechanismus der Aktivitätsmodulation durch Wirksamkeits‐Photoschalter hin und liefern einen konzeptionellen Rahmen für das Design von Liganden, die lichtgetriebene Übergänge innerhalb der Bindetasche zur räumlichen und zeitlichen Kontrolle der Rezeptorfunktion nutzen.

Fragile X Syndrome (FXS) is the leading monogenic cause of autism spectrum disorder (ASD). To date, no approved pharmacological treatment alleviates social impairments in patients with FXS. Since D1 and D2 dopamine receptor-expressing striatal projection neurons (SPNs) were shown to regulate ASD-sensitive behaviors, we explored whether the balance of activity between D1- and D2-SPNs would be biased in the Fmr1-/- mouse model of FXS. We evaluated striatal function in Fmr1-/- and Fmr1+/+ mice under pharmacological challenge and performed RNAscope® in situ hybridization following social interaction to assess the activity of SPNs in the nucleus accumbens (NAc) and dorsal striatum (DS). We evidenced a decrease in D1-SPN activity, biasing the D1/D2-SPN balance towards an excessive weight of D2-SPN outputs. We then evaluated the effects of compounds that repress D2-SPN activity on behavioral impairments in Fmr1-/- mice. Systemically facilitating mGlu4 or blocking A2A receptor activity relieved behavioral deficits in this model. Finally, we tested the hypothesis that a tilt of the D1/D2-SPN balance in Fmr1-/- mice may contribute to their social deficit by facilitating mGlu4 activity directly in the projection site of NAc D2-SPNs. Social interaction in Fmr1-/- mice was fully rescued by photopharmacological activation of mGlu4 in the ventral pallidum (VP), where NAc D2-SPNs project. This result supports our hypothesis of excessive D2-SPN outputs and highlights the contribution of the VP in controlling social behavior. In conclusion, pharmacological compounds that repress D2-SPN activity demonstrate a promising therapeutic potential to relieve ASD-like deficits in FXS.

BN-isosterism, the replacement of carbon-carbon units with boron-nitrogen pairs in organic frameworks, offers a powerful means to create novel compounds, yet methods to access larger BN-containing polyaromatic cores remain scarce. Leveraging our recently developed multigram-scale synthesis of BN-naphthalene, we now combine it with a Catellani-type arene extension (Pd(OAc)2/P(2-furyl)3, norbornene) to rapidly access diverse extended BN-embedded polyaromatic cores. This strategy delivers BN-embedded benzo[c]phenanthridines and curved 8- and 7-membered ring-fused derivatives, as well as BN-embedded benzofluorenones in both normal and inverse BN-vector orientations. Importantly, the ability to access both directional BN isomers, in addition to the parent C═C core, provides a rare opportunity to directly interrogate the effect of the presence and sense of the BN moiety. Most notably, light-induced singlet oxygen (1O2) generation promoted by the benzofluorenone core shows a more than 10-fold enhancement in the "boron-up" BN isostere, while dropping to negligible levels upon inversion of the BN unit. This work thus offers a blueprint for experimental electronic tuning of optically responsive organic materials through BN-mapping.

The yerba mate tree Ilex paraguariensis is widelyconsumed in South America, and the limited recommendation for pesticideuse highlights the need for alternative pest-management strategies. Thelosia camina is an important defoliator whose damageseverely reduces yields. This study investigated the sex-pheromonesystem of T. camina as a basis for pheromone-mediatedcontrol. Female pheromone glands were extracted and analyzed by gaschromatography-electroantennographic detection, revealing nine antennallyactive compounds. Structural elucidation identified three major components(13Z,15Z)-octadeca-13,15-dienal(4), (13Z,15Z)-octadeca-13,15-dien-1-ol(5) and (13Z,15Z)-octadeca-13,15-dien-1-ylacetate (9). Remaining components were stereoisomersand related monoenes consistent with the same double-bond system.All isomers were synthesized, field bioassays showed that both theternary blend (4,5 and 9) andthe acetate (9) alone attracted males at levels significantlyhigher than controls. These results confirm conjugated C18 dienesas key pheromone components of T. camina and providea foundation for pheromone-based, sustainable management in yerbamate cultivation.

Chemodivergent C–H annulation of aliphatic amides with maleimides has been achieved under cobalt-catalysis, enabling access to distinct (4 + 1) and (3 + 2) outcomes.