Integrated Hollow Mesoporous Silica Nanoparticles for Target Drug/siRNA Co‐Delivery

A hollow mesoporous silica nanoparticle (HMSNP) based drug/siRNA co‐delivery system was designed and fabricated, aiming at overcoming multidrug resistance (MDR) in cancer cells for targeted cancer therapy. The as‐prepared HMSNPs have perpendicular nanochannels connecting to the internal hollow cores, thereby facilitating drug loading and release. The extra volume of the hollow core enhances the drug loading capacity by two folds as compared with conventional mesoporous silica nanoparticles (MSNPs). Folic acid conjugated polyethyleneimine (PEI‐FA) was coated on the HMSNP surfaces under neutral conditions through electrostatic interactions between the partially charged amino groups of PEI‐FA and the phosphate groups on the HMSNP surfaces, blocking the mesopores and preventing the loaded drugs from leakage. Folic acid acts as the targeting ligand that enables the co‐delivery system to selectively bind with and enter into the target cancer cells. PEI‐FA‐coated HMSNPs show enhanced siRNA binding capability on account of electrostatic interactions between the amino groups of PEI‐FA and siRNA, as compared with that of MSNPs. The electrostatic interactions provide the feasibility of pH‐controlled release. In vitro pH‐responsive drug/siRNA co‐delivery experiments were conducted on HeLa cell lines with high folic acid receptor expression and MCF‐7 cell lines with low folic acid receptor expression for comparison, showing effective target delivery to the HeLa cells through folic acid receptor meditated cellular endocytosis. The pH‐responsive intracellular drug/siRNA release greatly minimizes the prerelease and possible side effects of the delivery system. By simultaneously delivering both doxorubicin (Dox) and siRNA against the Bcl‐2 protein into the HeLa cells, the expression of the anti‐apoptotic protein Bcl‐2 was successfully suppressed, leading to an enhanced therapeutic efficacy. Thus, the present multifunctional nanoparticles show promising potentials for controlled and targeted drug and gene co‐delivery in cancer treatment.     

Synthesis and characterization of dithienobenzothiadiazole-based donor–acceptor conjugated polymers for organic solar cell applications

New donor–acceptor conjugated polymers (P1 and P2) containing a fused-ring dithienobenzothiadiazole (DT-BTD building block) were synthesized by using the Stille copolymerization method. The synthesized polymers were characterized by ¹H NMR, GPC, and elemental analysis. The optical band gaps of the polymers were found to be 1.86 and 1.9 eV, respectively, as calculated from their film onset absorption edge. Upon annealing both produced a distinct shoulder peak in their film absorption spectra. The electrochemical studies of P1 and P2 revealed that the HOMO and LUMO energy levels of the polymer were −5.3, −5.1 eV, and −3.4, −3.2 eV, respectively. The polymers are thermally stable up to 250–350 °C.     

Macrocycle Dynamics in a Branched [8]Catenane Controlled by Three Different Stimuli in Three Different Regions

A branched [8]catenane from an efficient one-pot synthesis (72 % HPLC yield, 59 % isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril-mediated azide–alkyne cycloaddition (CBAAC) for ring-closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non-influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid-base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non-obvious supramolecular interactions in the synthesis of high-order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.     

Unusual Acetylation‐Dependent Reaction Cascade in the Biosynthesis of the Pyrroloindole Drug Physostigmine

Physostigmine is a parasympathomimetic drug used to treat a variety of neurological disorders, including Alzheimer’s disease and glaucoma. Because of its potent biological activity and unique pyrroloindole skeleton, physostigmine has been the target of many organic syntheses. However, the biosynthesis of physostigmine has been relatively understudied. In this study, we identified a biosynthetic gene cluster for physostigmine by genome mining. The 8.5 kb gene cluster encodes eight proteins (PsmA–H), seven of which are required for the synthesis of physostigmine from 5‐hydroxytryptophan, as shown by in vitro total reconstitution. Further genetic and enzymatic studies enabled us to delineate the biosynthetic pathway for physostigmine. The pathway features an unusual reaction cascade consisting of highly coordinated methylation and acetylation/deacetylation reactions.     

[RhIII(Cp*)]‐Catalyzed ortho‐Selective Direct C(sp2)H Bond Amidation/Amination of Benzoic Acids by N‐Chlorocarbamates and N‐Chloromorpholines. A Versatile Synthesis of Functionalized Anthranilic Acids

A Rh^III‐catalyzed direct ortho‐C?H amidation/amination of benzoic acids with N‐chlorocarbamates/N‐chloromorpholines was achieved, giving anthranilic acids in up to 85 % yields with excellent ortho‐selectivity and functional‐group tolerance. Successful benzoic acid aminations were achieved with carbamates bearing various amide groups including NHCO₂Me, NHCbz, and NHTroc (Cbz=carbobenzyloxy; Troc=trichloroethylchloroformate), as well as secondary amines, such as morpholines, piperizines, and piperidines, furnishing highly functionalized anthranilic acids. A stoichiometric reaction of a cyclometallated rhodium(III) complex of benzo[h]quinoline with a silver salt of N‐chlorocarbamate afforded an amido–rhodium(III) complex, which was isolated and structurally characterized by X‐ray crystallography. This finding confirmed that the C?N bond formation results from the cross‐coupling of N‐chlorocarbamate with the aryl–rhodium(III) complex. Yet, the mechanistic details regarding the C?N bond formation remain unclear; pathways involving 1,2‐aryl migration and rhodium(V)– nitrene are plausible.     

A Small‐Molecule FRET Reporter for the Real‐Time Visualization of Cell‐Surface Proteolytic Enzyme Functions

Real‐time imaging of cell‐surface‐associated proteolytic enzymes is critical to better understand their performances in both physiological and pathological processes. However, most current approaches are limited by their complexity and poor membrane‐anchoring properties. Herein, we have designed and synthesized a unique small‐molecule fluorescent probe, which combines the principles of passive exogenous membrane insertion and Förster resonance energy transfer (FRET) to image cell‐surface‐localized furin‐like convertase activities. The membrane‐associated furin‐like enzymatic cleavage of the peptide probe leads to an increased fluorescence intensity which was mainly localized on the plasma membrane of the furin‐expressed cells. This small‐molecule fluorescent probe may serve as a unique and reliable reporter for real‐time visualization of endogenous cell‐surfaceassociated proteolytic furin‐like enzyme functions in live cells and tissues using one‐photon and two‐photon microscopy.     

Neo‐Fused Hexaphyrin: A Molecular Puzzle Containing an N‐Linked Pentaphyrin

The first neo‐confused hexaphyrin(1.1.1.1.1.0) was synthesized by oxidative ring closure of a hexapyrrane bearing two terminal “confused” pyrroles. The new compound displays a folded conformation with a short interpyrrolic C???N distance of 3.102 Å, and thus it readily underwent ring fusion to afford a neo‐fused hexaphyrin with an unprecedented 5,5,5,7‐tetracyclic ring structure. Furthermore, coordination of Cu^II triggered a ring opening/contracting reaction to afford a Cu^II complex of an N‐linked pentaphyrin derivative. The roles of reactive N? C bonds in the porphyrinoid macrocycles were demonstrated.