Novel energetic CNO oxidizer: Pernitro-substituted pyrazolyl-furazan framework

There is a need for dense energetic oxidizers whose composition is restricted to carbon, hydrogen, nitrogen and oxygen atoms as chlorine-free alternative to current oxidizers of energetic materials such as explosives, propellants and pyrotechnics. High nitrogen heterocyclic frameworks containing trinitromethyl units are an attractive and increasingly important class of oxygen-rich compounds. Herein, for the first time, a synthetic method has been developed for the preparation of a new (pyrazole-3-yl)furazan framework bearing a nitro group in the furazan ring. From this framework, 3-nitro-4-(4-nitro-1-(trinitromethyl)-1H-pyrazol-3-yl)furazan (15) and 3-(3,4-dinitro-1-(trinitromethyl)-1H-pyrazol-5-yl)-4-nitrofurazan (16) have been produced. The combination of positive enthalpy of formation, high density, favorable physical and thermal properties, and reasonable sensitivity with the promising theoretical energetic performance of these oxygen-rich compounds offers materials not only of fundamental interest, but also for potential practical applications, for example, as promising candidates to new environmentally benign rocket propellants

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