Regulation mechanism of human insulin fibrillation by L-lysine carbon dots: low concentration accelerates but high concentration inhibits the fibrillation process.

The fibrillation process of human insulin (HI) is closely related to the therapy for type II diabetes (T2D). Due to changes in the spatial structure of HI, the fibrillation process of HI takes place in the body, which leads to a significant decrease in normal insulin levels. L-Lysine CDs with a size of around 5 nm were synthesized and used to adjust and control the fibrillation process of HI. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CDs showed the role of HI fibrillation from the perspective of the kinetics of HI fibrillation and regulation. Isothermal titration calorimetry (ITC) was used to explore the regulatory mechanism of CDs at all stages of HI fibrillation from the perspective of thermodynamics. Contrary to common sense, when the concentration of CDs is less than 1/50 of the HI, CDs will promote the growth of fibres, while a high concentration of CDs will inhibit the growth of fibres. The experimental results of ITC clearly prove that different concentrations of CDs will correspond to different pathways of the combination between CDs and HI. CDs have a strong ability to combine with HI during the lag time, and the degree of combination has become the main factor influencing the fibrillation process.

Inhibition mechanism of human insulin fibrillation by Bodipy carbon polymer dots and photothermal defibrillation effect of Bodipy carbon polymer dots modified by ThT.

Fibrillation process of human insulin (HI) is closely related to type 2 diabetes (T2D). In the present work, Carbon Polymer Dots (CPDs) was synthesized by Bodipy to control the process of insulin fibrillation. The inhibition process of insulin fibrillation with the existence of CPDs was completed investigated. The hydrophobic interaction of CPDs and insulin was used to inhibit the change of insulin's secondary structure in the lag phase and growth period. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CPDs were used to explore the kinetics of insulin fibrillation and regulation process by CPDs. Isothermal titration calorimetry (ITC) was applied to explore the regulatory mechanism by CPDs at all stages of the insulin fibrillation process. ThT was used to complete the chemical modification of CPDs by Friedel-Crafts alkylation, which made the CPDs maintain the characteristics of photothermal effect and also obtain the ability to bind specifically to the fibers. Finally, the process of defibrillation of human insulin fibers under the Near-infrared light's irradiation was realized. In this work, we clarified the mechanism of the regulation process by Bodipy CPDs and made CPDs able to defibrillate the insulin fibers by chemical modification.

Highly Enantioselective Asymmetric Hydrogenation of Carboxy-Directed α,α-Disubstituted Terminal Olefins via the Ion Pair Noncovalent Interaction.

The t-Bu-Wudaphos was successfully applied into Rh-catalyzed asymmetric hydrogenation of α,α-disubstituted terminal olefins bearing a carboxy-directed group with excellent reactivities and enantioselectivities via the ion pair noncovalent interaction (up to >99% conversion, 98% yield, 98% ee) under mild reaction conditions without base. In addition, control experiments were conducted, and the results demonstrated that the ion pair noncovalent interaction between ligand and substrate played an important role in achieving an outstanding performance in this asymmetric hydrogenation.