Chemical biology investigation of a triple-action,smart-decomposition antimicrobial booster based-combination therapy against“ESKAPE”pathogens

The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic membranes.This study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition mechanism.OA1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme inhibition.This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial resistance.Furthermore,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione levels.These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.

Modulation of the cobalt species state on zincosilicate to maximize propane dehydrogenation to propylene

Dispersing metals from nanoparticles into clusters or single atoms often exhibits unique properties such as the inhibition of structure-sensitive side reactions.Here,we reported the use of ion exchange(IE)methods and direct hydrogen reduction to achieve high dispersion of Co species on zincosilicate.The obtained 2Co/Zn-4-IE catalyst achieved an initial propane conversion of 41.4%at a temperature of 550℃in a 25%propane and 75%nitrogen atmosphere for propane dehydrogenation.Visualization of the presence of Co species within specific rings(alpha-α,beta-βand delta-δ)was obtained by aberration-corrected scanning transmission electron microscopy.A series of Fourier transform infrared spectra confirmed the anchoring of Co by specific hydroxyl groups in zincosilicate and the specific coordination environment of Co and its presence in the rings essentially as a single site.The framework Zn for the modulation of the microenvironment and the presence of Co species as Lewis acid active sites(Co-O4)was also supported by density functional theory calculations.

Palladium-Catalyzed Desulfinative Cross-Coupling of Polyhalogenated Aryl Triflates with Aryl Sulfinate Salts:Inversion of Traditional Chemoselectivity

Comprehensive Summary This paper presents the first general examples of palladium-catalyzed desulfinative cross-coupling reaction of polyhalogenated aryl triflates with aryl sulfinate salts showing an inversion of the conventional reactivity order of C-Br>C-Cl>C-OTf.The catalyst system,comprising of Pd(OAc)_(2)and tBuPhSelectPhos,exhibited excellent catalytic reactivity and chemoselectivity toward this reaction.This reaction had a wide range of substrate scopes and provided a simple and efficient method for the construction of functionalized biaryl motifs.Notably,the C-H···Pd interaction from the methine hydrogen of the C2-cyclohexyl group of the indolyl phosphine ligand with the Pd center may contribute a key factor in reactivity and chemoselectivity.Assisting with density functional theory(DFT)calculations,the results revealed that the oxidative addition step in this reaction was a controlling-chemoselectivity step.

Transition-Metal-Free Allylic Defluorination Cross-Electrophile Coupling Employing Rongalite

Comprehensive Summary The conversion of CF3-alkenes to gem-difluoroalkenes using reductive cross-coupling strategy has received much attention in recent years,however,the use of green and readily available reducing salt to mediate these reactions remains to be explored.In this work,a concise construction of gem-difluoroalkenes,which requires neither a catalyst nor a metal reducing agent,was established.Rongalite,a safe and inexpensive industrial product,was employed as both a radical initiator and reductant.This procedure was compatible with both linear and cyclic diaryliodonium salts,enabling a wide variety of substrates(>70 examples).The utility of this approach was demonstrated through gram-scale synthesis and efficient late-stage functionalizations of anti-inflammatory drugs.

I_(2)-DMSO mediated tetra-functionalization of enaminones for the construction of novel furo[2,3:4,5]pyrimido[1,2-b]indazole skeletons via in situ capture of ketenimine cations

The first-ever synthesis of the unknown furo[2,3:4,5]pyrimido[1,2-b]indazole skeleton was demonstrated based on the undiscovered tetra-functionalization of enaminones,with simple substrates and reaction conditions.The key to realizing this process lies in the multiple trapping of the in situ generated ketenimine cation by the 3-aminoindazole,which results in the formation of four new chemical bonds and two new rings in one pot.Moreover,the products of this new reaction were found to exhibit aggregationinduced emission(AIE)without modification.

Fine-tune chiroptical activity in discrete chiral Au nanorods

Accurate researches on the surface plasmon resonance(SPR)-based applications of chiral plasmonic metal nanoparticles(NPs)still remain a great challenge.Herein,a series of chiral plasmonic metal NPs,e.g.,chiral Au nanorods(c-Au NRs),c-Au@Ag core–shell,and c-Au@TiO_(2) core–shell NRs,with different chiroptical activities have been produced.Plasmonic circular dichroism(PCD)bands of c-Au NRs can be precisely tailored by tuning the longitudinal SPR(LSPR)and amount of Au NRs as seeds.Besides,a shift of PCD bands within ultraviolet–visible–near infrared ray(UV–vis–NIR)region can also be achieved through the functionalization of a shell of another metal or semiconductor.Interestingly,chirality transfer from c-Au core to Ag shell leads to new PCD bands at the near-UV region.The tuning of PCD bands and chirality transfer are confirmed by our developed theoretical model.Developing chiral Au NRs-based chiral plasmonic nanomaterials with tunable chiroptical activities will be helpful to understand the structure-direct PCD and to extend circularly polarized-based applications.

CircTUBD1: A Novel Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis

Citation of this article:Gu CY,Lee TKW.CircTUBD1:A Nov-el Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis.J Clin Transl Hepatol 2022;10(4):571-573.doi:10.14218/JCTH.2022.00132.Primary liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide.1 Liver transplantation and surgical resection are two curative therapeutic options for liver cancer patients at the early stages.However,most patients are diagnosed at advanced stages.