Xiaoming Miao

Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys‐Xxx‐Gly‐SEt)₂ form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6–12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single‐crystal X‐ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model “removal” reaction. These results indicate that even not template‐assisted autocatalytic production combined with competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre‐Darwinian stages of molecular evolution.

Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys‐Xxx‐Gly‐SEt)₂ form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6–12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single‐crystal X‐ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model “removal” reaction. These results indicate that even not template‐assisted autocatalytic production combined with competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre‐Darwinian stages of molecular evolution.

Janus nanoparticles possess amphiphilic properties and thus exhibit vast applications in the field of catalysis, drug delivery, displays, and surface/interface stabilizers. Despite several successful approaches, that were developed for micro‐sized Janus particle fabrication, the achievement of nano‐sized Janus particles is still facing challenges due to the difficulty with nanoscale processing. Here, new options for the preparation of Janus nanoparticles are demonstrated from strawberry‐like hierarchical composites with designed surface functional groups for both “satellites” and spherical “core.” The “satellites” of the hierarchical composites can be freely varied, from iron oxide to silica nanoparticles. Results from transmission electron microscopy, fourier transform infrared spectroscopy, and thermal gravimetric analysis measurements clearly prove the successful production of hybrid Janus silica nanoparticles coated by polystyrene and poly(acrylic acid). This technique demonstrates the vast flexibility of the abovementioned technique in terms of size, type, and surface chemistry design of Janus nanoparticles, which thus offers an additional approach to the current synthesis library of hybrid Janus nanoparticles.

Oridonin (1) is a complex ent-kaurane diterpenoid exhibiting remarkable antitumor activity. However, the detailed mechanism or cellular target that underlies this activity has not yet been identified. Herein, we report an efficient approach for exploring the anticancer mechanism of oridonin through development of the potent fluorescent analogues. A series of novel fluorescent oridonin probes linked with coumarin moieties were designed, synthesized, and characterized. Fluorescence microscopy and confocal imaging studies suggested that fluorescent oridonin probe 17d was rapidly taken up into tumor cells and the mitochondrion was the main site of its accumulation. Moreover, we confirmed that cytochrome c played an important role in oridonin induced mitochondrion-mediated apoptosis and α,β-unsaturated ketone is the active moiety of oridonin, which is crucial to its uptake, localization, and cytotoxicity. Our results provide new insights on the molecular mechanism of oridonin and would be useful for its further development into an antitumor agent.

In addition to the widely used polymeric hydrogels, molecular hydrogels are also emerging as promising biomaterials. However, molecular hydrogels typically suffer from poor mechanical properties and relatively low in vivo stability. Here we report on the preparation of two hybrid hydrogels (Hgel I and Hgel II) by the combination of two molecular hydrogelators and alginate, respectively. First, the molecular hydrogelator and sodium alginate were dissolved in water, and then a hydrogel was formed upon triggering by enzymes or reductants. Afterward the resulting hydrogel was soaked in calcium ion solution to form the hybrid hydrogel. The preparation process was easy and mild which allowed the resulting hybrid hydrogels to act as carriers for biomacromolecules such as enzymes. Both Hgel I and Hgel II had better stabilities and mechanical properties than the calcium alginate gel (CAgel) alone. Hgel I had exceptional stability compared with Hgel II and CAgel. The reason we propose is that molecular hydrogelators in Hgel I interacted with alginate more strongly than molecular hydrogelators in Hgel II according to the fluorescence results of these gels. Unlike the porous microstructure of molecular hydrogels, the microstructure of two hybrid hydrogels was almost the same as that of CAgel (film-like morphology) except with some nanofibers embedded. We found that Hgel I was an ideal carrier for enzyme immobilization with high recyclable properties and excellent preservation of enzyme activities due to its good mechanical strength. However, Hgel II was not suitable as a carrier for immobilized lactase probably due to poor affinity between Hgel II and the substrate. Combining the advantages of molecular hydrogels and polymeric hydrogels would broaden the applications of both kinds of hydrogels in the future.