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The complex formation of the cationic stilbene-type photoswitch CP with the anionic macrocycles carboxylato-pillar[5]arene (WP5) and carboxylato-pillar[6]arene (WP6) has been investigated in aqueous solution by optical spectroscopic, NMR and isothermal calorimetric experiments and theoretical calculations. Subsequently, the photoisomerization reactions of the supramolecular complexes formed have been studied. CP consists of a 7-diethylamino-coumarin fluorophore and an N -methylpyridinium unit, which are connected via an ethene bridge. The trans isomer of CP is fluorescent, and its cis isomer is dark. The binding constants of the WP6 complexes of the two photoisomers of CP are larger by 2 orders of magnitude than those of the respective complexes with WP5, and trans -CP forms more stable complexes with the individual pillararenes than the cis isomer. As shown by NMR spectroscopic measurements and theoretical calculations, the two isomers of CP form external complexes with WP5 and inclusion complexes with WP6. On complexation with WP6, the quantum yields of both the trans -to- cis and cis -to- trans photoisomerization reactions of CP increase significantly, and the fluorescence quantum yield of trans -CP is also enhanced. These changes are due to the suppression of the TICT deactivation process, which is characteristic of 7-dialkylamino-coumarin derivatives., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The aim of this work is to incorporate lanthanide-cored upconversion nanoparticles (UCNP) into the surface of microengineered biomedical implants to create a spatially controlled and optically releasable model drug delivery device in an integrated fashion. Our approach enables silicone-based microelectrocorticography (ECoG) implants holding platinum/iridium recording sites to serve as a stable host of UCNPs. Nanoparticles excitable in the near-infrared (lower energy) regime and emitting visible (higher energy) light are utilized in a study. With the upconverted higher energy photons, we demonstrate the induction of photochemical (cleaving) reactions that enable the local release of specific dyes as a model system near the implant. The modified ECoG electrodes can be implanted in brain tissue to act as an uncaging system that releases small amounts of substance while simultaneously measuring the evoked neural response upon light activation. In this paper, several technological challenges like the surface modification of UCNPs, the immobilization of particles on the implantable platform, and measuring the stability of integrated UCNPs in in vitro and in vivo conditions are addressed in detail. Besides the chemical, mechanical, and optical characterization of the ready-to-use devices, the effect of nanoparticles on the original electrophysiological function is also evaluated. The results confirm that silicone-based brain-machine interfaces can be efficiently complemented with UCNPs to facilitate local model drug release.

There has been a surge of interest in covalent inhibitors for protein kinases in recent years. Despite success in oncology, the off-target reactivity of these molecules is still hampering the use of covalent warhead-based strategies. Herein, we disclose the development of precision-guided warheads to mitigate the off-target challenge. These reversible warheads have a complex and cyclic structure with optional chirality center and tailored steric and electronic properties. To validate our proof-of-concept, we modified acrylamide-based covalent inhibitors of c-Jun N-terminal kinases (JNKs). We show that the cyclic warheads have high resilience against off-target thiols. Additionally, the binding affinity, residence time, and even JNK isoform specificity can be fine-tuned by adjusting the substitution pattern or using divergent and orthogonal synthetic elaboration of the warhead. Taken together, the cyclic warheads presented in this study will be a useful tool for medicinal chemists for the deliberate design of safer and functionally fine-tuned covalent inhibitors., (© 2024. The Author(s).)

In order to explore how cucurbituril hosts accommodate an N -phenyl-pyridinium derivative guest, the complexation of the solvatochromic dye, 4-(4-(dimethylamino)styryl)-1-phenylpyridinium iodide (PhSt) with , ' , δ M , δ ' -tetramethyl-cucurbit[6]uril (Me 4 M K a = 6.0 × 10 6 M - 1 ) than the complex with Me 4 CB6 ( K a = 1.1 × 10 6 M - 1 ). As revealed by NMR experiments and confirmed by theoretical calculations, CB7 encapsulates the whole phenylpyridinium entity of the PhSt cation guest, whereas the cavity of Me 4 CB6 includes only the phenyl ring, the pyridinium ring is bound to the carbonyl rim of the host. The binding of PhSt to cucurbiturils is accompanied by a strong enhancement of the fluorescence quantum yield due to the blocking of the deactivation through a twisted intramolecular charge transfer (TICT) state. The TICT mechanism in PhSt was characterized by fluorescence experiments in polyethylene glycol (PEG) solvents of different viscosities. The PhSt-CB7 system was tested as a fluorescence indicator displacement (FID) assay, and it recognized trimethyl-lysine selectively over other lysine derivatives., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The complexation of three cationic fluorescent dye guests with the anionic host carboxylato-pillar[6]arene (WP6) was investigated by optical and NMR spectroscopy. Among the selected indicators - a stilbazolium dye (i1) and two naphthalimide derivatives with positively charged 'anchor' groups (i2 and i3) - i1 gave a large turn-on, i2 and i3 a large turn-off fluorescence response to the complexation. The size selectivity of the complex formation of pillararenes was demonstrated by comparing the binding constants of the complexes of the three indicators with WP6 and its smaller homologue, WP5. The systems WP6·i1 and WP6·i2 were tested as indicator displacement assays for the sensing of monoamine neurotransmitters. The WP6·i1 system functioned as a turn-off, the WP6·i2 system as a turn-on sensor for neurotransmitters, and both assays showed a good selectivity to histamine over the other neurotransmitter analytes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Nucleotides are essential molecules in living systems due to their paramount importance in various physiological processes. In the past years, numerous attempts were made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of a uracil nucleobase to the known 4'-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy. Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum.