syn-3-(4-Chlorobenzyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol

In the title compound, C16H23ClN2O, both six-membered rings adopt chair conformations, thus allowing the formation of an intramolecular N—H...N hydrogen bond. In the crystal, adjacent molecules are combined into chains running along the ac diagonal via O—H...N hydrogen bonds

Photoprocesses in Derivatives of 1,4- and 1,3-Diazadistyryldibenzenes

Photoprocesses in 1,4-diazadistyrylbenzene (1) and 1,3-diazadistyrylbenzene derivative (2) diperchlorates in MeCN were studied by absorption, luminescence, and kinetic laser spectroscopies. For compound 1, trans-cis-photoisomerization and intersystem crossing to a triplet state are observed. For compound 2, photoelectrocyclization is suggested. Quantum chemical calculations of diazadistyrylbenzene structures in the ground and excited states were carried out. The schemes for photoreactions were proposed

Plier Ligands for Trapping Neurotransmitters into Complexes for Sensitive Analysis by SERS Spectroscopy

Catecholamines–dopamine, noradrenaline and adrenaline are important biomarkers of neurotransmitter metabolism, indicating neuroendocrine tumors and neurodegenerative diseases. Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique with unprecedented multiplexing capabilities. However, not all important analytes exhibit strong SERS signals on stable and robust nanostructured substrates. In this work, we propose a novel indicator system based on the formation of mixed ligand complexes with bispidine-based bis-azole ligands which can serve as pliers to trap Cu(II) ions and stabilize its complexes with catecholamines. Four synthesized ligands with different functional groups: carboxyl, amino, benzyl, and methoxybenzyl, were applied for forming stable complexes to shift maximum absorbance of catecholamines from the ultraviolet region to 570–600 nm. A new absorbance band in the visible range resonates with the local surface plasmon resonance (LSPR) band of metal nanoparticles and most used laser wavelengths. This match allowed use of Molecular Immobilization and Resonant Raman Amplification by Complex-Loaded Enhancers (MIRRACLE) methodology to measure intense Raman signals on a nanostructured silver-based SERS-active substrate. The synthesized plier-like ligands fixed and stabilized catecholamine complexes with Cu(II) on the SERS sensor surface, which facilitated the determination of dopamine in a 3.2 × 10−12–1 × 10−8 M concentration range

A First-in-Class β-Glucuronidase Responsive Conjugate for Selective Dual Targeted and Photodynamic Therapy of Bladder Cancer

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

Novel Bispidine-Monoterpene Conjugates—Synthesis and Application as Ligands for the Catalytic Ethylation of Chalcones

A number of new chiral bispidines containing monoterpenoid fragments have been obtained. The bispidines were studied as ligands for Ni-catalyzed addition of diethylzinc to chalcones. The conditions for chromatographic analysis by HPLC-UV were developed, in which the peaks of the enantiomers of all synthesized chiral products were separated, which made it possible to determine the enantiomeric excess of the resulting mixture. It was demonstrated that bispidine-monoterpenoid conjugates can be used as the ligands for diethylzinc addition to chalcone C=C double bond but not as inducers of chirality. Besides products of ethylation, formation of products of formal hydrogenation of the chalcone C=C double bond was observed in all cases. Note, that this formation of hydrogenation products in significant amounts in the presence of such catalytic systems was found for the first time. A tentative scheme explaining the formation of all products was proposed