Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered“valve-off”starvation therapy

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy.However,conventional starvation therapy,such as glucose exhaustion and vascular thrombosis,can lead to systemic toxicity and exacerbate tumor hypoxia.Herein,we developed a new“valve-off”starvation tactic,which was accomplished by closing the valve of glucose transporter protein 1(GLUT1).Specifically,dihydroartemisinin(DHA),2,20-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AI),and Ink were co-encapsulated in a sodium alginate(ALG)hydrogel.Upon irradiation with the 1064 nm laser,AI rapidly disintegrated into alkyl radicals(R·),which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate(ATP).Simultaneously,the production of R·facilitated DHA-induced starvation therapy by suppressing GLUT1,which in turn reduced glucose uptake.Systematic in vivo and in vitro results suggested that this radical-enhanced“valveoff”strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels.This integrated strategy induces tumor starvation with efficient tumor suppression,creating a new avenue for controlled,precise,and concerted tumor therapy.

Alkyl Radical Initiated Cyclization/Cascade for Synthesizing Lactam-Substituted Alkyl Sulfones

An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite(K_(2)S_(2)O_(5))as a connector is developed for the synthesis of various lactam-substituted alkyl sulfones.Notably,this process does not require a metal catalyst or metal powder reductant,highlighting its environmentally friendly features.The reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional groups.Furthermore,the biologically active molecules and commercially available drugs with a late-stage modification are also highly compatible with this transformation.Mechanistic studies revealed that the reaction proceeds through a single-step process involving intramolecular radical cyclization,"SO_(2)"insertion,and external alkyl incorporation.

Precise electro-reduction of alkyl halides for radical defluorinative alkylation

Reported here is a precise electro-reduction strategy for radical defluorinative alkylation towards the synthesis of gem-difluoroalkenes from α-trifluoromethylstyrenes. According to the redox-potential difference of the radical precursors, direct or indirect electrolysis is respectively adopted to realize the precise reduction. An easy-to-handle, catalyst-and metal-free condition is developed for the reduction of alkyl radical precursors that are generally easier to be reduced than α-trifluoromethylstyrenes,while a novel electro-Ni-catalytic system is established for the electro-reduction of alkyl bromides or chlorides towards the electrochemical synthesis of gem-difluoroalkenes. The merit of this protocol is exhibited by its mild conditions, wide substrate scope, and scalable preparation. Mechanistic studies and DFT calculations proved that the coordination of α-trifluoromethylstyrenes to Ni-catalyst prevents the direct reduction of the alkene and, in turn, promotes the activation of alkyl bromide through halogen atom transfer mechanism.

Decarboxylative Amination with Nitroarenes via Synergistic Catalysis

In this paper,we have developed a decarboxylative amination of carboxylic acids with nitroarenes for the synthesis of secondary amines.The protocol is performed at mild conditions without the use of noble metals as catalysts.A wide range of structurally diverse secondary amines could be obtained in good yields(up to 94%)with good functional group tolerance.This transformation shows good to excellent selectivity,avoiding the generation of over alkylated byproducts.

Recent advances in synthesis of organosilicons via radical strategies

Organosilicon compounds play an important role in the fields of materials science,pharmacy,and organic synthesis.The development of effective approaches for the preparation of these compounds have also become a research focus in organic synthesis.In recent years,free radical synthesis of organosilicons has been vigorously developed,which generally has the advantages of milder synthesis conditions,higher yields and selectivity,and free of precious metal catalysts compared with traditional strategies.This article reviews research progresses in the synthesis of organosilico n compounds by free radical pathways since 2016.In most cases,the radical silylation is achieved based on the reaction of silyl radicals,which are triggered by four routes including peroxide,transition-metal-induced peroxide decomposition,alkali,photocatalysis.The alkyl radicals can also initiate the radical silylation for the generation of C(sp^(3))—Si bonds.

Alkylation of Sulfur Ligand in Cysteinate-Iron Chelates by a 1,2,4,5-Tetraoxane

Reaction of a 1,2,4,5-tetraoxane with cysteinate-iron in the presence of excess methyl cysteinate led to formation of sulfur-alkylated methyl cysteinate in 33% yield, illustrating a possible mechanism for tetraoxanes' antimalarial action.

Deoxygenative alkylation of tertiary amides using alkyl iodides under visible light

It is an unceasing goal for organic chemists to develop new catalytic methodologies for functional group transformations of widespread molecular structures. Amides are readily available from simple and reliable reactions, which are common structural units found in biologically active compounds. Consequently, they are attractive to be exploited in amine synthesis by reductive cross coupling. However, deoxygenative functionalization of amides is a long-standing challenge owing to the inertness of the resonance-stabilized amide C=O bond. In this work, a deoxygenative alkylation strategy was demonstrated, which combines amides and alkyl iodides to build structurally diverse tertiary alkylamines in a single step. Compared with previous deoxygenative alkylation of amides using organometallic reagents as functional partner, this work uses stable and easily available alkyl halides as functionalization reagents. The versatile and flexible strategy plus structural and functional diversity of readily available amides and alkyl iodides renders it highly appealing for the streamlined synthesis of tertiary amines and would be of much interest in areas such as pharmaceutical and agrochemical research.

An Oxygen-Independent Photodynamic Therapy Nanoplatform for Combating Anaerobic Infection

Anaerobic bacteria infections remain a major threat to humans.Oxidative stress mediated by photodynamic therapy(PDT)has shown great potential in antimicrobial applications,attributing to its controllability and non-resistance.However,the hypoxic infection microenvironment severely compromises the therapeutic outcomes.Here,we designed a nanoplatform comprising the initiator of alkyl radicals(R-),2,2’-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AIPH)-loaded oxidized mesoporous carbon nanoparticles(OMCN)and then coated with a phase change material(PCM)nanoparticle for oxygen-independent PDT to combat anaerobic infections.Upon near-infrared(NIR)light irradiation,OMCN mediates the generation of heat to melt PCM,which could trigger the liberation and decomposition of AIPH to produce R.and further induce the oxidative damage to bacteria,and cooperate with optothermal effects to eradicate anaerobic bacteria.As results,the nanoplatform displays strong synergistic antibacterial behavior,effectively eliminating anaerobic Propionibacterium acnes(P.acnes)in vitro under hypoxic conditions,and successfully treating P.acnes-infected cutaneous abscess in mice models.Moreover,no distinct toxicity appears through the entire course of treatment.Collectively,this light-activated oxygen-independent PDT offers a novel approach to combat anaerobic bacteria infections.

Degradable Hybrid CuS Nanoparticles for Imaging-Guided Synergistic Cancer Therapy via Low-Power NIR-II Light Excitation

Near-infrared(NIR)-II light-excitable photonic agents capable of generating tumor hyperthermia and cytotoxic free radicals are promising for synergistic phototherapy of tumors.However,the lack of NIR-II excitable agents makes it challenging to achieve combinational tumor phototherapy.Here,the authors have reported on a tumor-targeting and degradable hybrid copper sulfide(CuS)nanoparticle(AIBA@CuS-FA)via loading a hydrophilic Azo initiator(AIBA)into an amphiphilic lipid-encapsulating CuS nanoparticle.AIBA@CuS-FA shows high photothermal conversion efficiency(PCE≈47.5%)at 1064 nm,enabling heat production to trigger tumor hyperthermia and thermal decomposition of AIBA into cytotoxic free alkyl radicals upon irradiation with a 1064-nm laser under low-power density(0.5 W/cm2).Moreover,alkyl radicals can drive degradation of AIBA@CuS-FA and embedded CuS nanodisks,releasing Cu^(2+)ions that can catalyze a Fenton-like reaction for hydroxyl radical(•OH)production to promote tumor therapy.Findings demonstrate promise for combinational photothermal therapy(PTT),oxygen-independent alkyl radical therapy,and chemodynamic therapy(CDT)of tumors.

Photoactivatable nanogenerators of reactive species for cancer therapy

In recent years,reactive species-based cancer therapies have attracted tremendous attention due to their simplicity,controllability,and effectiveness.Herein,we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy.First,we summarized the most widely explored reactive species,such as singlet oxygen,superoxide radical anion(O2●-),nitric oxide(●NO),carbon monoxide,alkyl radicals,and their corresponding secondary reactive species generated by interaction with other biological molecules.Then,we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation,followed by their anticancer effect,and the synergetic principles with other therapeutic modalities.This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.