Macrocyclic Dual-Locked "Turn-On" Drug for Selective and Traceless Release in Cancer Cells.

Drug safety and efficacy due to premature release into the bloodstream and poor biodistribution remains a problem despite seminal advances in this area. To circumvent these limitations, we report drug cyclization based on dynamic covalent linkages to devise a dual lock for the small-molecule anticancer drug, camptothecin (CPT). Drug activity is "locked" within the cyclic structure by the redox responsive disulfide and pH-responsive boronic acid-salicylhydroxamate and turns on only in the presence of acidic pH, reactive oxygen species and glutathione through traceless release. Notably, the dual-responsive CPT is more active (100-fold) than the non-cleavable (permanently closed) analogue. We further include a bioorthogonal handle in the backbone for functionalization to generate cyclic-locked, cell-targeting peptide- and protein-CPTs, for targeted delivery of the drug and traceless release in triple negative metastatic breast cancer cells to inhibit cell growth at low nanomolar concentrations.

Buckling behavior of ternary one-dimensional van der Waals heterostructures.

One-dimensional van der Waals heterostructures (1D vdWHs) may suffer from external compression when applied in field-effect, light-emitting and photovoltaic devices. Ternary 1D vdWHs were recently reported to be successfully synthesized (Xianget al2020Science367, 537). In present work, the buckling behavior of ternary 1D vdWH consisting of an inner carbon nanotube, a middle boron nitride nanotube and an outer molybdenum disulfide nanotube is extensively investigated by using molecular dynamics simulations. We find that the composite can effectively enhance the capability of axial compression of the inner nanotubes. The 1D vdWH gradually loses its stability under uniaxial compression and the critical stress of buckling decreases as the temperature increases. Slenderness ratioαof 4.8 ≤α≤ 7.2 has a slight influence on the strength and stability of ternary 1D vdWH under axial compression. To obtain a 1D vdWH with best compressive stability and strength, there is an optimal diameter existing for any specific length. Our work provides guidance for the design of 1D vdWH with desired compressive stability.

Effect of nitrilotriacetic acid and tea saponin on the phytoremediation of Ni by Sudan grass (Sorghum sudanense (Piper) Stapf.) in Ni-pyrene contaminated soil.

Phytoremediation is commonly used in the remediation of soils co-contaminated by heavy metals and polycyclic aromatic hydrocarbons (PAHs) because of its economy and effectiveness. Sudan grass (Sorghum sudanense (Piper) Stapf.) has well-developed roots and strong tolerance to heavy metals, so it has been widely concerned. In this study, nitrilotriacetic acid (NTA) and tea saponin (TS) were used as enhancers and combined with Sudan grass for improving the remediation efficiency of Ni-pyrene co-contaminated soil. The results of the pot experiment in soils showed that enhancers promoted the enrichment of Ni in plants. With the function of enhancers, more inorganic and water-soluble Ni were converted into low-toxic phosphate-bonded and residual Ni, so as to reinforce the tolerance of Sudan grass to Ni. In the pot experiment based on vermiculite, it was found that enhancers increased the accumulation of Ni in cell wall by 49.71-102.73%. Enhancers also had the positive effect on the relative abundance of Proteobacteria, Patescibacteria and Bacteroidetes that could tolerate heavy metals at phylum level. Simultaneously, the study found that pyrene reduced the exchangeable Ni in soils. More Ni entered the organelles and transfer to more high-toxic forms in Sudan grass when pynere coexisted. The study manifested that enhancers improved the phytoremediation effect of Ni significantly, yet the co-existence of pyrene weakened the process. Our results provided meaningful references for remediating actual co-contaminated soil of heavy metals and PAHs.

Polymer-Encapsulated Cobalt/Gold Bimetallic Nanoclusters as Stimuli-Responsive Chemiluminescent Nanoprobes for Reactive Oxygen Species.

A stimuli-responsive chemiluminescent nanocomposite was developed based on bimetallic nanoclusters encapsulated in a reactive oxygen species (ROS)-responsive polymer for a highly sensitive determination of ROS (i.e., H2O2) in biological samples. Cobalt/gold bimetallic nanoclusters (GSH@Co-AuNCs) were synthesized using glutathione (GSH) as a reducing-cum-protecting reagent. The GSH-coated nanoclusters were covalently bound to N-(4-aminobutyl)-N-ethylisoluminol (ABEI) to form the GSH@Co-AuNCs-ABEI, which was further encapsulated in polymeric ROS-sensitive boronic ester modified dextran (Oxi-Dex) nanospheres through hydrophobic interactions. The stimulation of H2O2, as a model ROS, led to a sustainable structural cleavage of the Co-AuNCs-ABEI@Oxi-Dex nanocomposites and release of internal GSH@Co-AuNCs-ABEI, accompanied by intense chemiluminescence (CL). On this basis, an enzyme-free and reagent-free CL sensor was developed for a highly sensitive and selective determination of H2O2 with a detection limit of 35.8 pM in biological samples. It is of great application potential for the determination of ROS related to various diseases.

Csp(3)-P versus Csp(2)-P Bond Formation: Catalyst-Controlled Highly Regioselective Tandem Reaction of Ene-Yne-Ketones with H-Phosphonates.

Under copper-catalyzed or base-promoted conditions, a wide range of ene-yne-ketones react with H-phosphonates to afford various phosphorylated furans in good yields. A copper carbene generation or a Michael addition is proposed as the key step in the selective construction of the Csp(3)-P or Csp(2)-P bond, which is supported by carbene capture reactions and interval (31)P NMR experiments. Furthermore, this method features inexpensive metal catalysts, no usage of oxidant, and high atom economy, which make it attractive and practical.