We reported herein efficient economic high-pressure synthesis procedures for the synthesis of bis(azoles) and bis(azines) by utilizing the bis(enaminone) intermediate. Bis(enaminone) reacted with hydrazine hydrate, hydroxylamine hydrochloride, guanidine hydrochloride, urea, thiourea, and malononitrile to form the desired bis azines and bis azoles. A combination of elemental analyses and spectral data was used to confirm the structures of the products. Compared with conventional heating, the high-pressure Q-Tube method promotes reactions in a short period of time and provides high yields.

Two bis-(imidazolium–vanillylidene)-(R,R)-diaminocyclohexane ligands (H₂(VAN)₂dach, H₂L_1,2) and their Pd(II) complexes (PdL₁ and PdL₂) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL₁LNP and PdL₂LNP), which are physicochemically and morphologically characterized. PdL₁LNP and PdL₂LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd_1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd_1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL₁LNP and PdL₂LNP to downregulate TGFβ1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

This study presents an efficient synthetic strategy for heterocycles using silica-supported sodium carbonate as a reusable heterogeneous catalyst under both conventional and Q-Tube high-pressure conditions. The distinct product outcomes observed under conventional reflux and Q-Tube-assisted conditions indicate that the reaction environment influences product selectivity. Because temperature and autogenous pressure vary together in the Q-Tube system, we cannot distinguish their individual contributions in these experiments. Accordingly, the divergent formation of thiazole and 1,3-oxathiole derivatives is attributed to the combined reaction conditions rather than to pressure alone. Green chemistry metrics, including atom economy, reaction mass efficiency, process mass intensity, E-factor, and EcoScale, were evaluated for representative reactions to assess the material efficiency and waste profile of each protocol. This work provides a quantitative and balanced assessment of the SSC/Q-Tube approach for selective heterocycle synthesis.

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