ABSTRACT
Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.
ABSTRACT
Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.
Subject(s)
Hyaluronic Acid , Nanoparticles , Reactive Oxygen Species , Hyaluronic Acid/chemistry , Doxorubicin/chemistry , Molecular Dynamics Simulation , Pharmaceutical Preparations , Drug Delivery Systems , Nanoparticles/chemistry , Hyaluronan Receptors , Cell Line, TumorABSTRACT
Construction of C-N bond continues to be one part of the most significant goals in organic chemistry because of the universal applications of amines in pharmaceuticals, materials and agrochemicals. However, E2 elimination through classic SN2 substitution of alkyl halides lead to generation of alkenes as major side-products. Thus, formation of a challenging C(sp3)-N bond especially on tertiary carbon center remains highly desirable. Herein, we present a practical alternative to prepare primary, secondary and tertiary alkyl amines with high efficiency between alkyl iodides and easily accessible diazonium salts. This robust transformation only employs Cs2CO3 promoting halogen-atom transfer (XAT) process under transition-metal-free reaction conditions, thus providing a rapid method to assemble diverse C(sp3)-N bonds. Moreover, diazonium salts served as alkyl radical initiator and amination reagent in the reaction. Mechanism studies suggest this reaction undergo through halogen-atom transfer process to generate active alkyl radical which couples with diazonium cations to furnish final products.
ABSTRACT
A novel approach for high efficient conversion of the CO(2)-rich bio-syngas into the CO-rich bio-syngas was carried out by using biomass char and Ni/Al(2)O(3) catalyst, which was successfully applied for production of bio-methanol from bio-oil. After the bio-syngas conditioning, the CO(2)/CO ratio prominently dropped from 6.33 to 0.01-0.28. The maximum CO yield in the bio-syngas conditioning process reached about 1.96 mol/(mol CO(2)) with a nearly complete conversion of CO(2) (99.5%). The performance of bio-methanol synthesis was significantly improved via the conditioned bio-syngas, giving a maximum methanol yield of 1.32 kg/(kg(catalyst)h) with a methanol selectivity of 99%. Main reaction paths involved in the bio-syngas conditioning process have been investigated in detail by using different model mixture gases and different carbon sources.
