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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).)

Photoresponsive materials offer excellent spatiotemporal control over biological processes and the emerging phototherapeutic methods are expected to have significant effects on targeted cancer therapies. Recent examples show that combination of photoactivatable approaches with bioorthogonal chemistry enhances the precision of targeted phototherapies and profound implications are foreseen particularly in the treatment of disperse/diffuse tumors. The extra level of on-target selectivity and improved spatial/temporal control considerably intensified related bioorthogonally assisted phototherapy research. The anticipated growth of further developments in the field justifies the timeliness of a brief summary of the state of the art., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Herein, we present high-yielding, concise access to a set of xanthenium-derived, water-soluble, low-molecular-weight photocages allowing light-controlled cargo release in the green to red region. Very importantly, these new photocages allow installation of various payloads through ester, carbamate, or carbonate linkages even at the last stage of the synthesis. Payloads were uncaged with high efficiency upon green, orange, or red light irradiation, leading to the release of carboxylic acids, phenols, and amines. The near-ideal properties of a carboxanthenium derivative were further evaluated in the context of light-controlled drug release using a camptothecin-derived chemotherapeutic drug, SN38. Notably, the caged drug showed orders of magnitude lower efficiency in cellulo , which was reinstated after red light irradiation. The presented photocages offer properties that facilitate the translation of photoactivated chemotherapy toward clinical applications.

An energy transfer-based signal amplification relay concept enabling transmission of bioorthogonally activatable fluorogenicity of blue-excitable coumarins to yellow/red emitting cyanine frames is presented. Such relay mechanism resulted in improved cyanine fluorogenicities together with increased photostabilities and large apparent Stokes-shifts allowing lower background fluorescence even in no-wash bioorthogonal fluorogenic labeling schemes of intracellular structures in live cells. These energy transfer dyads sharing the same donor moiety together with their parent donor molecule allowed three-color imaging of intracellular targets using one single excitation source with separate emission windows. Sub-diffraction imaging of intracellular structures using the bioorthogonally activatable FRET dyads by STED microscopy is also presented., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The supramolecular complexes of three strongly solvatochromic dyes, Brooker's merocyanine (M1) and its two derivatives (M2, M3) with carboxylato pillar[6]arene (WP6) were studied in aqueous solutions. The dye-WP6 mixtures were described in terms of four equilibrium reactions: the acidic dissociations of the pyridinium phenols into the zwitterionic phenolates, the acidic dissociations of the complexed phenols, the bindings of the phenol form dyes to WP6 and the bindings of the phenolates to WP6. The equilibrium constants were determined by an analysis of the absorption spectra. It was found that the acidity of the phenol form merocyanines were largely reduced on complexation, pK a shifts of 1.1-1.6 units were observed. In neutral solutions, the complexes of the phenol forms of M1 and M2 were dominant, in contrast to the more acidic M3 (a dibromo derivative), of which the phenolate complex was more stable. Comparing the spectral properties, the binding constants and the pK a -s of the dye-WP6 complexes, the complex M3⋅WP6 was chosen to be tested as a displacement assay. It was demonstrated that this complex functioned as a colorimetric indicator displacement assay which discriminated trimethyl lysine from other lysine derivatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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 proof of concept for conditionally activatable photocages is demonstrated on a new vinyltetrazine-derivatized coumarin. The tetrazine form is disabled in terms of light-induced cargo release, however, bioorthogonal transformation of the modulating tetrazine moiety results in fully restored photoresponsivity. Irradiation of such a "click-armed" photocage with blue light leads to fast and efficient release of a set of caged model species, conjugated via various linkages. Live-cell applicability of the concept was also demonstrated by the conditional release of a fluorogenic probe using mitochondrial pretargeting.

Easily accessible green-light activatable (>500 nm) photocages based on red-shifted, π-extended coumarin scaffolds are developed with uncaging efficiencies similar to those of recently introduced BODIPY derivatives. The photocages possess increased aqueous solubility, high absorption coefficients within the 450-600 nm range, and exceptionally high two-photon cross sections.

The irreproducibility of the standard potential ( E °) is probably the last major challenge for the commercialization of solid-contact ion-selective electrodes (SCISEs) as single-use or wearable sensors. To overcome this issue, we are introducing for the first time a perfluorinated alkanoate side chain functionalized poly(3,4-ethylenedioxythiophene) (PEDOTF) as a hydrophobic SC in potassium-selective electrodes (K-SCISEs) based on plasticized poly(vinyl chloride). The SC incorporates the tetrakis(pentafluorophenyl)borate (TFAB - ) anion, which is also present as a lipophilic additive in the ion-selective membrane (ISM), thus ensuring thermodynamic reversibility at the SC/ISM interface and improving the potential reproducibility of the electrodes. We show here that the PEDOTF-TFAB solid contact, which was prepolarized prior to the ISM deposition to either its half or fully conducting form (i.e. different oxidation states) in acetonitrile containing 0.01 M KTFAB, had a very stable open-circuit potential and an outstanding potential reproducibility of only ±0.5 mV ( n = 6) for 1 h in the same solution after the prepolarization. This shows that the oxidation state of the highly hydrophobic PEDOTF-TFAB film (water contact angle 133°) is stable over time and can be precisely controlled with prepolarization. The SC was also not light sensitive, which is normally a disadvantage of conducting polymer SCs. After the ISM deposition, the standard deviation of the E ° of the K-SCISEs prepared on glassy carbon was ±3.0 mV ( n = 5), which is the same as that for conventional liquid contact K-ISEs. This indicates that the ISM deposition is the main source for the potential irreproducibility of the K-SCISEs, which has been overlooked previously.

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.)

The fluorescence properties of 4'-diethylamino-3-hydroxyflavone (FET), a dye probe sensitive to the polarity as well as the hydrogen bonding ability of its environment, have been studied in acetone-water mixtures by measuring spectra and decay curves over the whole composition range and analyzing the results on the basis of theoretical calculations. In acetone, like in most of organic solvents, the dye showed dual fluorescence, due to an excited state intramolecular proton transfer (ESIPT), in which a quasi-equilibrium between the two excited species, N* and T*, was reached. In acetone-water mixtures with lower molar fractions of water, where the water molecules are largely dispersed, only one type of hydrate could be detected, a complex with 1:1 composition, showing only N* emission, but with a high (0.45) fluorescence quantum yield. At higher water concentrations, the interaction of FET with the hydrogen-bonded water clusters resulted in fluorescence quenching. In neat water the fluorescence quantum yield fell to ~0.001. Theoretical calculations on a FET-acetone complex, a FET-water complex and a FET-water-acetone triple complex (the latter as model for the samples with low water concentrations) concluded that ESIPT was energetically favored in all the models, but the E(N*)-E(T*) energy difference for the water complexes was much lower. The kinetic barrier of ESIPT was found greatly higher in the FET-water complex than in the isolated solute. The intermolecular hydrogen bonds in the water complexes became significantly stronger following the excitation, stabilizing the N* form of the hydrated dye., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The excited state processes in N-propyl-4-piperidinyl-1,8-naphthalimide have been studied by measuring its fluorescence spectra and decay curves in solvents of different polarity and viscosity and also in a frozen solvent glass. The results unanimously proved the formation of a dark twisted intramolecular charge transfer (TICT) state from the emissive charge transfer (CT) species, the direct product of excitation. The rate coefficients of the TICT process and the deactivations of the CT and TICT species were determined, using a reversible two-state kinetic model. The temperature dependence of the kinetic data was consistent with a kinetic barrier consisting of three terms, the inherent barrier of the reaction, and the contributions of the solute-solvent interactions related to the solvent viscosity and polarity. The potential energy surfaces were calculated in the S0 and the S1 states along the coordinate of turning motion which was conclusive concerning the direction of the twisting and indicated a possible conformational change of the piperidinyl unit. The theoretical calculations confirmed that the TICT species is dark and has a stronger charge transfer character compared to the CT state.

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.

A novel functionality was introduced in the pillararene family by the Claisen rearrangement of monoallyl pillar[5]arene. This new key derivative can lead to the formation of a 10 + 1 functionalized derivative, a useful scaffold for further derivatization. Except for the previously known monodeprotection reaction, all steps proceed efficiently with high yields and easy separation. In addition, a solvent-responsive pseudo[1]rotaxane was synthesized based on this novel functionality.

The photolysis reactions of 4'-diethylamino-3-hydroxyflavone (D), a versatile fluorescent probe showing excited-state intramolecular proton transfer (ESIPT), and the magnesium chelate of D (MgD(2+)) have been studied in acetonitrile solution. Upon UV irradiation both species were oxidized into O-4-diethylaminobenzoyl salicylic acid, differently from the photoreaction of the parent compound 3-hydroxyflavone (3HF) which was described to undergo rearrangement to 3-hydroxy-3-phenyl-indan-1,2-dione. The photooxygenation of the Mg(2+) complex was found to be significantly faster than the reaction of the pure dye. As the kinetic analysis of the absorption spectra of samples under irradiation showed, the rate coefficients for the oxygenations of the excited state dye and complex have close values, kox(D*) = 2.4 × 10(7) min(-1), kox(MgD(2+)*) = 3.9 × 10(7) min(-1); the difference arises from the higher photooxygenation quantum yield of the complex, Φ(MgD(2+)) = 2.3 × 10(-3), than the respective value for the pure dye, Φ(D) = 1.5 × 10(-4). The potential energy surface of the photooxygenation of D was calculated assuming a reaction path in which the phototautomer formed from Dvia ESIPT, reacts in its triplet state with triplet molecular oxygen O2, a mechanism similar to that suggested for the photoreaction of the parent 3HF. The moderate values for the transition state energies confirmed the plausibility of the hypothetical mechanism.