We present a highly efficient strategy for the assembly of bispidine-isoxazolidine-fused multicyclic structures via [3+2] cycloaddition of alkenes to a nitrone-functionalized bispidine framework. The reaction smoothly delivers diverse hybrid heterocycles featuring complex stereochemistry at the isoxazolidine-bispidine junction point in high yields and good selectivity. This approach opens a straightforward pathway to new synthetic analogues of natural compounds (primarily lupine alkaloids) and may prove to be useful for the discovery of new bioactive molecules and ligands for catalysis.

Lanthanide complexes are widely used in both luminescent thermometry and catalysis, yet their integration into a single material remains a major challenge. Herein, we report novel terbium and europium complexes with a bispidine-based ligand conjugated to benzoic acid via a triazole linker. These complexes exhibit dual functionality: they act as homogeneous catalysts for the Michael addition reaction and simultaneously serve as ratio-metric luminescent thermometers. The mixed-metal complex (Eu0.1Tb0.9)(L)(TFA)2 center dot H2O demonstrates bright emission with quantum yields up to 56 %, and europium lifetime-based thermometry shows a relative sensitivity of 1.7 %/ degrees C with a temperature uncertainty below 0.5 degrees C. Notably, the catalytic activity arises only in the metalligand complex form, as neither the ligand nor lanthanide salts alone promote the reaction. To the best of our knowledge, this is the first report of a rare-earth complex combining homogeneous catalysis with luminescent thermometry in solution.

The photophysical processes and photochemical reactions of 1,4-di(azastyryl)benzene (1) derivative {[(E,E)-1](ClO4)2} were investigated by absorption, luminescence, and laser kinetic spectroscopy in the water solution. The observed photo processes include dimerization, E-Z isomerization, and intersystem crossing to the triplet state, as well as the complexation [(E,E)-1](ClO4)2 with cucurbit[7]uril (CB[7]). The [(E,E)-1](ClO4)2 dye dimerization was shown to be energetically more favorable in the excited state than in the ground state. The reversible photoinduced migration of the dye dication in the CB[7] cavity takes place as a result of partial exit of the [(E,E)-1]2+ from the cavity and its subsequent conversion to the (E,Z)-isomer in the excited state, which undergoes conversion to the initial complex of {[(E,E)-1]@CB[7]}2+ after returning to the ground state. This photoprocess is of interest in relation to the scientific problem of designing photocontrolled supramolecular machines.

Motivated by the task to replace toxic lead halide perovskites with lead-free environmentally benign light-harvesting materials for photovoltaics, we have synthesized two new hybrid bromometallates, (AH2)4[Sb2Br10(SbBr6)2(Br)2] (1) and (AH2)2[(BiBr6)(SbBr6)]·2H2O (2), where A = 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane. Their crystal structures show combinations of Sb3+/Sb5+ (1) or Bi3+/Sb5+ (2) centers each surrounded by six Br- anions forming distorted (Sb3+ or Bi3+) or almost regular (Sb5+) octahedra. These octahedra are arranged in the crystal structure in a perfectly ordered way owing to weak Br⋯Br interactions within the inorganic anionic part and to hydrogen bonds linking inorganic anions and organic cations. The electronic structures of both compounds are alike in that they have M3+/Br- states (M = Sb or Bi) dominating the top of the valence band and acceptor in-gap states formed by the Sb5+/Br- interactions. Such an electronic structure leads to the reduced band gap of 1.27 (1) and 1.58 eV (2), favorable for creating light-harvesting materials for photovoltaics. We support our data by powder and single-crystal X-ray diffraction study, 121Sb Mossbauer spectroscopy, and optical spectroscopy. We infer that tailoring the band gap is a very important step on the way to lead-free light-harvesting materials for photovoltaic applications.

Skin wrinkles formation is caused by reactive oxygen species (ROS) which induce degradation of collagens and fibroblasts. While antioxidants like ascorbic acid (AA) and retinoic acid (RA) aid skin rejuvenation, their delivery is hindered by skin barrier. Here AA and RA loaded cyanobacteria-inspired ROS-responsive core-shell hydrogel microneedles (AR-CSMNs) were developed from methacrolyl hydroxypropyl chitosan (HPCMA) as base material and N,N bis(acryloyl)-cystamine (BAC) as ROS-responsive crosslinker. These microneedles had pyramidal shape and sufficient mechanical strength for skin penetration. Equilibrium AA release from AR-CSMNs was 89 %, in neutral environment while RA release from these microneedles was 95 % in H2O2 solution and only 66 % without H2O2. Finally, the microneedles were utilized for wrinkles treatment in Sprague-Dawley (SD) rats. AR-CSMNs visually reduced wrinkles in rats within four days and nearly completely removed wrinkles in seven days. These microneedles demonstrated effective skin penetration and targeted drug release for therapeutic applications.

The complexation ability of one of the new promising analgesics, thiowurtzine (TW), with a number of cyclodextrin (CD) host molecules was studied using electron and 1H NMR spectroscopy in methanol and confirmed by quantum-chemical and molecular dynamics calculations. Spectrophotometric and fluorescence titration methods determined the 1 : 1 stoichiometry and stability of the resulting complexes with γ-cyclodextrin derivatives (for TW@HP-γ-CD log K1:1 = 3.0).

The search for new anticancer drugs is still a very important task for modern chemistry. Some of the most intensively studied objects are metal complexes, in particular complexes of platinum, ruthenium, iridium and osmium. To address this issue, novel organometallic ruthenium complexes with thiophene-based imines containing a Ru-C bond were synthesized and tested against cancer cell lines. The scaffold is designed to allow the generation of a broad library of cyclometallated compounds from commercially available substrates. Compounds were characterized using spectroscopic, electrochemical, and X-ray diffraction techniques. They were found to have a very good cytotoxicity among ruthenium complexes against A2780, A549 and MCF-7 cancer cells and against HEK cells.

A new tricationic organic supramolecular tecton has been designed and synthesized. Contrary to known mono- and dicationic species, this new molecule, being a "three-way connector", allows assembling infinite supramolecular sheets and nets upon interaction with appropriate inorganic counterpart complex anions. In this work, triprotonated 6-amino-5,7-dimethyl-1,3-diazaadamantane, comprising two secondary and one primary nitrogen atoms, is used as a trication to form hybrid compounds with iodometallate anions by forming five hydrogen bonds at a time. It is shown that the bulky cation works simultaneously as a spacer and a connector, such that the positions of inorganic [MI6]3- anions (M = Sb or Bi) in the crystal structures are defined by five hydrogen bonds and are well-separated from each other. The latter is considered as a prerequisite for the hybrid compounds to exhibit optical properties originating from the undisturbed electronic structure of individual inorganic anions.

INTRODUCTION:The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials. AREAS COVERED:This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors. The search was conducted using SciFinder, Cortellis Drug Discovery Intelligence Database, and Espacenet. After filtering, 44 records were identified for further analysis. This paper also discusses the recent progress in the clinical trials and development history. EXPERT OPINION:ATM kinase is a promising target for cancer therapy. Small-molecule ATM kinase inhibitors hold significant potential in cancer treatment by enhancing the efficacy of existing DNA-damaging therapies. Patent analysis revealed that the majority of these compounds contain imidazo[4,5-c]quinolinone scaffold or its bioisosteric variations which are optimal in terms of good ATM inhibitory activity and selectivity over closely related enzymes. Clinical trials explore combinations with RT or DNA-targeted compounds like PARP inhibitors, which induce DSBs. The medicinal chemistry field anticipates that these therapeutic options will soon be available on the pharmaceutical market.

In this report, we developed novel chlorin/arylaminoquinazoline conjugates for targeted photodynamic therapy of cancer. The synthesized photosensitizers consisted of chlorin-e6 metallocomplexes (Zn, In, or Pd) conjugated with arylaminoquinazoline ligands with high affinity for epidermal growth factor receptors (EGFR). Additionally, the selectivity and antitumor properties of the conjugates were investigated in the EGFR-expressing A431 human tumor cell line in vitro. Among the tested molecules, the In-containing conjugate effectively inhibited tumor cell proliferation at nanomolar concentrations, a rare property for conventional photosensitizers. In in vivo experiments, the conjugates rapidly accumulated at the tumor site in nude mice bearing A431 xenograft tumors. Subsequent distribution analysis among different tissues was carried out using fluorescence imaging and elemental analysis. Finally, we demonstrated that the most promising In-containing conjugate was capable of inhibiting xenograft tumor growth in mice through combinational therapy. This therapeutic approach, combined with the conjugate's confirmed safety profile, highlights its potential for effective and safe cancer treatment.

Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: 1H and 13C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by 64Cu in mild conditions. In vitro studies of the labeled conjugate [64Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with 64Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with 64Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.

Gout has gradually become the second-largest metabolic disease, which requires long-term anti-inflammatory and uric acid-lowering treatment. Because of the characteristics of recurrent gout, its management and treatment costs are very high. Traditional administration methods (oral or injection) require patients to take drugs frequently, which leads to uncontrollable drug concentration in the blood and may cause a series of side effects. Therefore, a safe and convenient way of administration is significant for the long-term self-management of gout patients. Compared with the normal physiological environment, the pH value at the focus of gouty arthritis is acidic, so we can design pH-responsive MNs according to this difference to realize the intelligent release of drugs. Here, pH-responsive microneedles (MNs) based on 4-carboxy-3-fluorophenylboronic acid modification of hydroxypropyl chitosan were prepared, which were loaded with anti-inflammatory drugs colchicine (Col) and urate-lowering drugs urate oxidase (UOX) for long-term self-management of gout patients. Based on dynamic phenyl borate ester bonds and electrostatic interactions, it has been proved that the MNs can respond to the weak acid environment at the attack site of gouty arthritis and release drugs intelligently, which can relieve gout in two ways: anti-inflammation and uric acid reduction. The pH-responsive MNs can achieve 48 hours of transdermal drug release. Compared with the normal pH environment, the MNs increased the transdermal release rate of Col to 2.67 times and UOX to 1.66 times in the slightly acidic environment. The pH-responsive MNs achieved rapid swelling reduction within 12 hours in the gout rat model. Generally speaking, the swellable pH-responsive MNs loaded with Col and UOX have great potential in treating gouty arthritis.

In contrast to hypervalent iodine compounds, the chemistry of their sulfur analogues has been considerably less explored. Herein, we report the direct C-H bond thiolation of electron-rich heterocycles, arenes, and 1,3-dicarbonyls by dichlorosulfuranes under mild conditions. Mechanistic studies and density functional theory calculations suggest the radical chain mechanism of the disclosed transformation. The key to success is attributed to a strikingly low S-Cl bond dissociation energy, which enables the generation of radical species upon exposure to daylight.

Nowadays PSMA ligands are widely used for radiotheragnostic purposes of prostate cancer. The goal of this study was to synthesize and estimate stability in vitro of copper complex with diacetate bispidine ligand (Bisp1), its bifunctional derivative (Bisp-alkyne) and its conjugate – bispidine-PSMA ligand (PSMA-Bisp) to evaluate the possibility of applying one as radiotheragnostic agent. The synthesis for PSMA-Bisp conjugate was developed and realized with good yields. All newly synthesized compounds were characterized by a set of physicochemical methods: 1H and 13C NMR, HRMS and LCMS (for final molecules). Subsequently, Bisp1 and Bisp-alkyne and its derivative PSMA-Bisp were labelled by 64Cu at mild conditions. In vitro studies of the labelled conjugate [64Cu]Cu-PSMA-Bisp have shown the great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to well-known PSMA-617 conjugate labelled with 64Cu and they have showed similar stability in excess of bovine serum (BVS), and at the same time labelling PSMA-Bisp with 64Cu is characterized by extremely high kinetics at mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C) [PMCID: PMC5435610]. Thus, the conjugate PSMA-Bisp could be promising candidate for further investigations expanded in vitro and in vivo investigations.

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e6 photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a β-glucuronidase-responsive linker. Upon activation by β-glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells. This activation was accompanied by the recovery of its fluorescence and the generation of reactive oxygen species. Investigation of photodynamic and dark toxicity in vitro revealed that the novel conjugate had an excellent safety profile and was able to inhibit tumor cells proliferation at submicromolar concentrations. Additionally, combined therapy effects were also observed in 3D models of tumor growth, demonstrating synergistic suppression through the activation of both photodynamic and targeted therapy.

Heterobimetallic lanthanide conjugates were obtained by click-reaction between two monometallic lanthanide complexes with Schiff bases for the first time. For that, novel azido- and ethynyl-substituted ligands, as well as their lanthanide complexes, were obtained and characterised; two new crystal structures were obtained. Click-reaction between ligands and complexes was performed, and the latter was demonstrated to result in the conjugates {Ln1-Ln2} formation. Among the obtained conjugates, {Yb-Nd} and {Yb-Er} demonstrated intense NIR emission with temperature sensitivity in the physiological range of up to 3%/K.

The first example of intramolecular diastereoselective domino reaction of ferrocene 1,1'-bis-enone to [5]ferrocenophane initiated with sodium ethoxide was found. The product is [5]ferrocenophane with two pyridyl and one ethoxy substituents arranged asymmetrically in a five-carbon bridge. Diffraction studies showed that ferrocene is in almost ideal eclipsed conformation. The fan conformation found in the crystal is also preserved in solution, which was determined by NMR spectroscopy.

Conjugates of bispidines and free radicals of the (2,2,6,6-tetramethylpiperidin-1-yl)-oxyl type were synthesized for the first time. The conjugates were obtained by the alkylation reaction of NH-bispidines with electrophilic chloro derivatives containing a free radical. The structure of the latter was established by X-ray diffraction analysis. The products obtained were characterized by IR spectroscopy, ESR spectroscopy, and high-resolution mass spectrometry.

he halogen bonding in molecular crystals and supramolecular assemblies has been widely investigated. Special attention is given to the molecular structures capable of simultaneously exhibiting different types of non-covalent interactions, including conventional hydrogen bonds and halogen bonds. This paper systematically analyzes crystalline peroxosolvates of bispidine-based bis-amide derivatives, containing haloacetic acid residues, namely previously reported 1,1 '-(1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(2-iodooethanone) peroxosolvate C13H20I2N2O2H2O2 (1) and four new crystalline compounds, 1,1 '-(1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(2-bromoethanone) peroxosolvate C13H20Br2N2O2H2O2 (2), 1,1 '-(9-hydroperoxy-9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(2-iodoethanone) peroxosolvate C13H20I2N2O50.5H(2)O(2) (3), 1,1 '-(9-hydroperoxy-9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(2-bromoethanone) peroxosolvate C13H20Br2N2O5H2O2 (4), and 1,1 '-(9-hydroperoxy-9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane-3,7-diyl)bis(2-chloroethanone) peroxosolvate C13H20Cl2N2O5H2O2 (5). Compounds 2-5 were synthesized for the first time and their crystal structures were determined by single-crystal X-ray diffractometry (SCXRD). To the best of our knowledge, 3-5 are unprecedented crystalline hydrogen peroxide adducts of organic hydroperoxides (R-OOH). Short intermolecular contacts between halogen and hydroperoxo oxygen atoms were found in 1-3. The halogen bonding of C-I(Br) fragments with dioxygen species in compounds 1-3 as well as in the previously reported cocrystal of diacetone diperoxide with triodotrinitrobenzene (6) was identified through reduced density gradient analysis, Hirshfeld surface analysis, and Bader analysis of crystalline electron density. The interactions were quantified using the electron density topological properties acquired from the periodic DFT calculations and evaluated to lie in the range of 9-19 kJ mol(-1). A distinctive spectral feature was revealed for this type of interaction, involving a red shift of the characteristic O-O stretching vibration by about 6 cm(-1), which appeared in IR spectra as a narrow low-intensity band in the region 837-872 cm(-1).