Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Intensified and safe ozonolysis of fatty acid methyl esters in liquid CO2 in a continuous reactor

We demonstrate a continuous reactor for performing the ozonolysis of fatty acid methyl esters (FAMEs) using liquid CO₂ as solvent. The fast reaction kinetics allows the use of small‐volume reactors to completely convert the FAMEs, forming secondary ozonides as the primary products. The short residence times also help maximize the yields of the secondary ozonides by minimizing over‐oxidation and the formation of oligomeric products. The liquid CO₂ medium promotes safe reactor operation by providing an essential fraction of overall reactor cooling and by diluting the vapor phase organics. We also demonstrate a continuous stirred reactor for the safe thermal decomposition of the secondary ozonides to their corresponding acids and aldehydes. Using a lumped kinetic model for the thermal decomposition of the ozonolysis products, we estimate activation energy values of 108.6 ± 0.6 kJ mol^?1 for the decomposition of secondary ozonides and 122 ± 3 kJ mol^?1 for the decomposition of the undesired oligomeric species. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2819–2826, 2017     

烯烃臭氧化反应中两性离子反应新进展

介绍了烯烃臭氧化反应,论述了臭氧化反应中生成的两性离子与醇、氧化胺、水、路易斯酸的反应以及两性离子的异构化反应及其在合成相关化工、医药、香料产物方面的应用,并对近十年来两性离子反应的研究进展进行了综述。     

Ozonide ions on the surface of MgO nanocrystals

The adsorption properties of oxygen radicals on the surface of polycrystalline oxides can provide relevant information about the functionality of specific surface sites in oxidation catalysis. Using electron paramagnetic resonance spectroscopy, we investigated O₂ adsorption at MgO nanocrystal surfaces which were previously enriched with O⁻ radicals i.e. trapped hole centers. On dehydroxylated particle surfaces, two ozonide radical types O ₃ ⁻ were isolated as adsorbates and the related energies for O₂ adsorption were found to be 55 ± 5 kJ mol⁻¹ and 100 ± 5 kJ mol⁻¹. The respective adsorption sites are assigned to hole centers trapped on oxygen terminated corners and cation vancancies, respectively. In addition, O ₃ ⁻ ions were also employed as probes for electron trapping sites on partially hydroxylated sample surfaces. Five types of O⁻ radicals emerge from surface colour centre bleaching with N₂O, but only two of them adsorb O₂ at room temperature. A connection between the well-characterized (H⁺)(e^-) defect – an electron trapped in close vicinity of a nearby proton [Chiesa et al. J. Phys. Chem. B 109 (2005) 7314] – and one ozonide type which exhibits significant magnetic coupling with an adjacent proton, was established on the basis of their production parameter dependence. Although the g tensor of an O₃ ⁻ species reflects the properties of the radical itself rather than the structure of the adsorption site, the related signatures are proposed to serve also as spectroscopic fingerprints for catalytically relevant surface anion environments.     

Synthesis of pinonic acid esters from ozonolysis of α-pinene

以天然产物松节油的主要成分α-蒎烯和醇为原料,二氯甲烷为溶剂,经臭氧氧化制得α-蒎烯臭氧化物,臭氧化物不加分离直接在三乙胺（TEA）催化下经乙酸酐重排（AA）裂解,一锅法合成了6种蒎酮酸酯类化合物。考察了乙酸酐用量、三乙胺用量、反应时间和反应温度等条件对蒎酮酸酯收率的影响,并通过正交试验对合成条件进行了优化。优化的实验条件为：nAA/nα-蒎烯 = 3.0∶1,nTEA/nα-蒎烯 = 0.75∶1,反应时间为60 min,反应温度为30 ℃,在该条件下合成的6种蒎酮酸酯收率均在60%以上,并采用1H NMR、13C NMR、IR、MS对6种化合物的结构进行了表征。该方法操作简便,条件温和,且收率高,是合成蒎酮酸酯类化合物的一种简易可行的方法。     

α-蒎烯臭氧化反应合成蒎酮酸酯

以天然产物松节油的主要成分α-蒎烯和醇为原料,二氯甲烷为溶剂,经臭氧氧化制得α-蒎烯臭氧化物,臭氧化物不加分离直接在三乙胺(TEA)催化下经乙酸酐重排(AA)裂解,一锅法合成了6种蒎酮酸酯类化合物。考察了乙酸酐用量、三乙胺用量、反应时间和反应温度等条件对蒎酮酸酯收率的影响,并通过正交试验对合成条件进行了优化。优化的实验条件为:nAA/nα-蒎烯=3.0∶1,nTEA/nα-蒎烯=0.75∶1,反应时间为60 min,反应温度为30℃,在该条件下合成的6种蒎酮酸酯收率均在60%以上,并采用1H NMR、13C NMR、IR、MS对6种化合物的结构进行了表征。该方法操作简便,条件温和,且收率高,是合成蒎酮酸酯类化合物的一种简易可行的方法。