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.     

Comparison of Yield,Chemical Composition and Antimicrobial Activity of Distichochlamys citrea Rhizome Essential Oils Obtained by Different Extraction Methods

Moscow University Chemistry Bulletin - Hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydrodistillation (MAHD) extraction methods were assessed for their effects on yield,...     

Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.     

Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation

Matching of symmetry at interfaces is a fundamental obstacle in molecular assembly. Virus‐like particles (VLPs) are important vaccine platforms against pathogenic threats, including Covid‐19. However, symmetry mismatch can prohibit vaccine nanoassembly. We established an approach for coupling VLPs to diverse antigen symmetries. SpyCatcher003 enabled efficient VLP conjugation and extreme thermal resilience. Many people had pre‐existing antibodies to SpyTag:SpyCatcher but less to the 003 variants. We coupled the computer‐designed VLP not only to monomers (SARS‐CoV‐2) but also to cyclic dimers (Newcastle disease, Lyme disease), trimers (influenza hemagglutinins), and tetramers (influenza neuraminidases). Even an antigen with dihedral symmetry could be displayed. For the global challenge of influenza, SpyTag‐mediated display of trimer and tetramer antigens strongly induced neutralizing antibodies. SpyCatcher003 conjugation enables nanodisplay of diverse symmetries towards generation of potent vaccines.     

Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation

Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from Artemisia capillaris were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in db/db mice without elevation of insulin levels.     

Positively charged liposomes consisting of the KTTKS pentapeptide conjugated with rhodamine increase rhodamine toxicity in E. coli and zebrafish embryo

Liposomes composed of cell‐penetrating peptide derivatives increased transport across the cell membrane. Conjugating rhodamine to a cell‐penetrating peptide increased the toxicity of rhodamine in E. coli and zebrafish embryos. A similar total protein inhibition pattern with different intensities, indicating that the interaction pathways of the rho‐KTTKS‐CONH₂ monomer and liposomes were the same. It suggests that the rho‐KTTKS‐CONH₂ liposomes showed higher toxicity because better transport across the cell membrane increased the effective concentration inside cells. The staining of zebrafish embryos using rho‐KTTKS‐CONH₂ liposomes showed a longer retention time, suggesting that it can penetrate deeper tissues or organs in zebrafish.     

Biosynthesis of Streptolidine Involved Two Unexpected Intermediates Produced by a Dihydroxylase and a Cyclase through Unusual Mechanisms

Streptothricin‐F (STT‐F), one of the early‐discovered antibiotics, consists of three components, a β‐lysine homopolymer, an aminosugar D ‐gulosamine, and an unusual bicyclic streptolidine. The biosynthesis of streptolidine is a long‐lasting but unresolved puzzle. Herein, a combination of genetic/biochemical/structural approaches was used to unravel this problem. The STT gene cluster was first sequenced from a Streptomyces variant BCRC 12163, wherein two gene products OrfP and OrfR were characterized in vitro to be a dihydroxylase and a cyclase, respectively. Thirteen high‐resolution crystal structures for both enzymes in different reaction intermediate states were snapshotted to help elucidate their catalytic mechanisms. OrfP catalyzes an Fe^II‐dependent double hydroxylation reaction converting L ‐Arg into (3R,4R)‐(OH)₂‐L ‐Arg via (3S)‐OH‐L ‐Arg, while OrfR catalyzes an unusual PLP‐dependent elimination/addition reaction cyclizing (3R,4R)‐(OH)₂‐L ‐Arg to the six‐membered (4R)‐OH‐capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT‐F by a feeding experiment.     

Molecular Engineering of Push–Pull Porphyrin Dyes for Highly Efficient Dye‐Sensitized Solar Cells: The Role of Benzene Spacers

Porphyrins have drawn much attention as sensitizers owing to the large absorption coefficients of their Soret and Q bands in the visible region. In a donor and acceptor zinc porphyrin we applied a new strategy of introducing 2,1,3‐benzothiadiazole (BTD) as a π‐conjugated linker between the anchoring group and the porphyrin chromophore to broaden the absorption spectra to fill the valley between the Soret and Q bands. With this novel approach, we observed 12.75 % power‐conversion efficiency under simulated one‐sun illumination (AM1.5G, 100 mW cm^?2). In this study, we showed the importance of introducing the phenyl group as a spacer between the BTD and the zinc porphyrin in achieving high power‐conversion efficiencies. Time‐resolved fluorescence, transient‐photocurrent‐decay, and transient‐photovoltage‐decay measurements were employed to determine the electron‐injection dynamics and the lifetime of the photogenerated charge carriers.     

Redox Chemistry of a Hydroxyphenyl‐Substituted Borane

Chemical reduction of a hydroxyphenyl‐substituted borane triggers a sequential electron‐ and intramolecular hydrogen‐atom‐transfer process to afford a hydridoborate phenoxide dianion. On the other hand, hydrogen‐atom abstraction of the borane leads to the isolation of a neutral borylated phenoxyl radical, which can be transformed to the corresponding benzoquinone borataalkene derivative by reduction with cobaltocene.