Copper (I) Chloride-Catalyzed Photoredox Synthesis of Multifunctionalized Compounds at Room Temperature and Their Antifungal Activities.

A simple visible-light-induced CuCl-catalyzed synthesis was developed for highly functionalized carbon-centered compounds (α-alk/aryloxy-α-diaryl/alkylaryl-acetaldehydes/ketones) at room temperature using benzoquinone, alkyl/aryl alcohol, and alkyl/aryl terminal/internal alkynes. Late-stage functionalized compounds show good antifungal activities, especially against Candida krusei fungal strain, in in vitro experiments (the Broth microdilution method). Moreover, toxicity tests (zebrafish egg model experiments) indicated that these compounds had negligible cytotoxicity. The green chemistry metrics (E-factor value is 7.3) and eco-scale (eco-scale value is 58.8) evaluations show that the method is simple, mild, highly efficient, eco-friendly, and environmentally feasible.

Computer-Aided Design and Synthesis of (Functionalized quinazoline)-(α-substituted coumarin)-arylsulfonate Conjugates against Chikungunya Virus.

Chikungunya virus (CHIKV) has repeatedly spread via the bite of an infected mosquito and affected more than 100 countries. The disease poses threats to public health and the economy in the infected locations. Many efforts have been devoted to identifying compounds that could inhibit CHIKV. Unfortunately, successful clinical candidates have not been found yet. Computations through the simulating recognition process were performed on complexation of the nsP3 protein of CHIKV with the structures of triply conjugated drug lead candidates. The outcomes provided the aid on rational design of functionalized quinazoline-(α-substituted coumarin)-arylsulfonate compounds to inhibit CHIKV in Vero cells. The molecular docking studies showed a void space around the ß carbon atom of coumarin when a substituent was attached at the α position. The formed vacancy offered a good chance for a Michael addition to take place owing to steric and electronic effects. The best conjugate containing a quinazolinone moiety exhibited potency with EC50 = 6.46 µM, low toxicity with CC50 = 59.7 µM, and the selective index (SI) = 9.24. Furthermore, the corresponding 4-anilinoquinazoline derivative improved the anti-CHIKV potency to EC50 = 3.84 µM, CC50 = 72.3 µM, and SI = 18.8. The conjugate with 4-anilinoquinazoline exhibited stronger binding affinity towards the macro domain than that with quinazolinone via hydrophobic and hydrogen bond interactions.

Domino Reaction for the Synthesis of Polysubstituted Pyrroles and Lamellarin R.

A three-component annulation reaction was developed for the synthesis of pyrroles, a class of compounds with various properties valuable to biomedical and polymer industries. Treatment of α-silylaryl triflates, Schiff bases, and alkynes generated polysubstituted pyrroles in good yields (61-86%) with regioselectivity. This domino reaction involved completion of five sequential steps in a single flask, which comprised aryne formation through 1,2-elimination, their alkylation by Schiff bases through 1,2-addition, 1,4-intramolecular proton transfer, Hüisgen 1,3-dipolar cycloaddition, and dehydrogenative aromatization. It was then successfully applied as the key step in the synthesis of the natural product lamellarin R. This new reaction represents an efficient, sustainable process for the production of chemical materials.

Copper Photoredox Catalyzed A3' Coupling of Arylamines, Terminal Alkynes, and Alcohols through a Hydrogen Atom Transfer Process.

The first successful example of the three-component coupling of N-alkylanilines, terminal alkynes, and alcohols was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox hydrogen-atom transfer process. This method allows preparation of propargylamines through uniquely selective α-C-H bond activation of unactivated alkylalcohols. Preliminary studies indicate that formation of α-oxy radical is operative. This approach facilitates rapid access to biologically important propargylamines from methanol as an abundant feedstock.

Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C≡C Triple Bond Cleavage.

Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C≡C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.

Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus.

A series of new conjugated compounds with a -SCH2- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 µM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

Preparation, cytotoxicity and in vivo bioimaging of highly luminescent water-soluble silicon quantum dots.

Designing various inorganic nanomaterials that are cost effective, water soluble, optically photostable, highly fluorescent and biocompatible for bioimaging applications is a challenging task. Similar to semiconducting quantum dots (QDs), silicon QDs are another alternative and are highly fluorescent, but non-water soluble. Several surface modification strategies were adopted to make them water soluble. However, the photoluminescence of Si QDs was seriously quenched in the aqueous environment. In this report, highly luminescent, water-dispersible, blue- and green-emitting Si QDs were prepared with good photostability. In vitro studies in monocytes reveal that Si QDs exhibit good biocompatibility and excellent distribution throughout the cytoplasm region, along with the significant fraction translocated into the nucleus. The in vivo zebrafish studies also reveal that Si QDs can be evenly distributed in the yolk-sac region. Overall, our results demonstrate the applicability of water-soluble and highly fluorescent Si QDs as excellent in vitro and in vivo bioimaging probes.

Photoinduced Copper-Catalyzed Regioselective Synthesis of Indoles: Three-Component Coupling of Arylamines, Terminal Alkynes, and Quinones.

The first successful example of a visible-light-induced copper-catalyzed process for C-H annulation of arylamines with terminal alkynes and benzoquinone is described. This three-component reaction allows use of a variety of commercial terminal alkynes as coupling partners for the one-step regioselective synthesis of functionalized indoles. Moreover, the current process represents a sustainable and atom-economical approach for the preparation of complex indoles from easily accessible starting materials under visible-light irradiation, without the need for expensive metals and harsh reaction conditions.

Aryne-Induced Novel Tandem 1,2-Addition/(3+2) Cycloaddition to Generate Imidazolidines and Pyrrolidines.

A new "single-flask" method was developed for the synthesis of imidazolidines and pyrrolidines with high stereoselectivity. First, a Schiff base was arylated with an aryne. Second, an intramolecular proton transfer took place from the methylene position to the anionic aryne ring. Third, the resultant ylide reacted with a second equivalent of the same Schiff base in situ or an electron-deficient alkene through a (3+2) cycloaddition. These sequential tandem 1,2-addition/(3+2) cycloaddition reactions led to the desired heterocycles in 63-88% yields.

First demonstration of gold nanorods-mediated photodynamic therapeutic destruction of tumors via near infra-red light activation.

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1-48 W/cm²) irradiation, leading to hyperthermia-induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs-mediated PTT and organic photosensitizers-mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O2) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs-mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti-cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon-induced fluorescence to illustrate their in vivo locations/distribution.

Mid-IR Light-Activatable Full Spectrum LaB6 Plasmonic Photocatalyst.

Photocatalysts as long-lasting, benign reagents for disinfection of bacteria in hospitals and public areas/facilities/transportation vehicles are strongly needed. A common limitation for all existing semiconductor photocatalysts is the requirement of activation by external UV-vis-near-infrared (NIR) light with wavelengths shorter than ≈1265 nm. None of the existing photocatalysts can function during nighttime in the absence of external light. Herein, an unprecedented LaB6 plasmonic photocatalyst is reported, which can absorb UV-vis-NIR light and mid-IR (3900 nm) light to split water and generate hydrogen and hydroxyl radicals for the decomposition of organic pollutants, as well as kill multidrug-resistant Escherichia coli bacteria. Mid-IR light (≈2-50 µm) is readily available from the natural environments via thermal radiation of warm/hot objects on the earth including human bodies, animals, furnances, hot/warm electrical devices, and buildings.

Photocatalytic Dinitrogen Reduction to Ammonia over Biomimetic FeMoSx Nanosheets.

Reduction of atmospheric dinitrogen (N2) to ammonia (NH3) using water and sunlight in the absence of sacrificial reducing reagents at room temperature is very challenging and is considered an eco-friendly approach to meet the rapidly increasing demand for nitrogen storage, fertilizers, and a sustainable society. Currently, ammonia production via the energy-intensive Haber-Bosch process causes ∼350 million tons of carbon dioxide (CO2) emission per year. Interestingly, natural N2 fixation by the nitrogenase enzyme occurs under ambient conditions. Unfortunately, N2 fixation on biomimetic catalysts has rarely been studied. To mimic biological nitrogen fixation, herein, we synthesized the novel iron molybdenum sulfide (FeMoSx) micro-/nanosheets via a simple hydrothermal approach for the first time. Further, we successfully demonstrated the photochemical conversion of N2 to NH3 over a biomimetic FeMoSx photocatalyst. The estimated yield is around 99.79 ± 6.0 µmol/h/g photocatalyst with a quantum efficiency of ∼0.028% at 532 nm visible-light wavelength. Besides, we also systematically studied the influence of key factors to further improve NH3 yields. Overall, this study paves a new pathway to fabricate carbon-free, photochemical N2 fixation materials for future applications.

Visible-light-induced, copper(I)-catalysed C-N coupling between o-phenylenediamine and terminal alkynes: one-pot synthesis of 3-phenyl-2-hydroxy-quinoxalines.

Visible-light-initiated aerobic direct C-N coupling between o-phenylenediamines and terminal acetylenes was performed using simple copper(I) chloride as a catalyst for the synthesis of quinoxaline derivatives. The current method works well for a wide range of electron rich as well as electron poor group-substituted o-phenylenediamines and phenylacetylenes. The key component in the reaction is the direct photo-excitation of in situ generated copper arylacetylide (λ(abs) = 420-480 nm). Moreover, as compared to the literature reports (thermal process), the current photochemical method is simple, mild, high yielding, and more viable towards the construction of biologically important quinoxaline derivatives from easily accessible raw materials, without the need of ligands and strong oxidants.

Photosensitization of singlet oxygen and in vivo photodynamic therapeutic effects mediated by PEGylated W(18)O(49) nanowires.

Upon excitation with near-infrared light (980 nm), PEGylated W18 O49 nanowires can sensitize the formation of singlet oxygen and thus reactive oxygen species (ROS). The resulting photodynamic therapy (PDT) effect can cause the destruction of tumors in the absence of organic photosensitizers. PEG=poly(ethylene glycol), PTT=photothermal therapy.

A high-index facet gold 12 tip nanostar for an improved electrocatalytic alcohol oxidation reaction with superior CO tolerance.

Direct alcohol fuel cells have a long and promising future, which will require the development of highly active electrocatalysts for alcohol electrooxidation reactions. To this end, high-index facet nanomaterial-based electrocatalysts provide significant promise for the successful oxidation of alcohols. However, the fabrication and exploration of high-index facet nanomaterials are seldom reported, especially in electrocatalytic applications. Herein, we successfully synthesized a high index facet {711} Au 12 tip nanostructure for the first time using a single-chain cationic TDPB surfactant. Electrooxidation results demonstrate that a {711} high-index facet Au 12 tip exhibited much higher electrocatalytic activity (∼10-fold higher) than the {111} low-index facet Au nanoparticles (Au NPs) without being poisoned by CO under identical conditions. Besides, Au 12 tip nanostructures offer appreciable stability and durability. The high electrocatalytic activity with excellent CO tolerance is due to the spontaneous adsorption of the negatively charged -OH on the high-index facet Au 12 tip nanostars, as evidenced by the isothermal titration calorimetry (ITC) analysis. Our findings suggest that high-index facet Au nanomaterials are ideal candidate electrode materials for the electrooxidation reaction of ethanol in fuel cells.

Combined Gadolinium and Boron Neutron Capture Therapies for Eradication of Head-and-Neck Tumor Using Gd10B6 Nanoparticles under MRI/CT Image Guidance.

Eradication of head-and-neck (H&N) tumors is very difficult and challenging because of the characteristic feature of frequent recurrence and the difficulty in killing cancer stem cells. Neutron capture therapy (NCT) is emerging as a noninvasive potential modality for treatments of various types of tumors. Herein, we report that 98.5% 10B-enriched anti-EGFR-Gd10B6 nanoparticles can not only deliver large doses of 158 µg 10B/g tumor tissues as well as 56.8 µg 157Gd/g tumor tissues with a very high tumor-to-blood (T/B) 10B ratio of 4.18, but also exert very effective CT/MRI image-guided combined GdBNCT effects on killing cancer stem cells and eradication of recurrent head-and-neck (H&N) tumors. This leads to a long average half-lifespan of 81 days for H&N tumor-bearing mice, which is a record-making result, and surpasses the best result reported in the literature using combined radiotherapy and T cell-mediated immunotherapy (70 d).

Advances of medical nanorobots for future cancer treatments.

Early detection and diagnosis of many cancers is very challenging. Late stage detection of a cancer always leads to high mortality rates. It is imperative to develop novel and more sensitive and effective diagnosis and therapeutic methods for cancer treatments. The development of new cancer treatments has become a crucial aspect of medical advancements. Nanobots, as one of the most promising applications of nanomedicines, are at the forefront of multidisciplinary research. With the progress of nanotechnology, nanobots enable the assembly and deployment of functional molecular/nanosized machines and are increasingly being utilized in cancer diagnosis and therapeutic treatment. In recent years, various practical applications of nanobots for cancer treatments have transitioned from theory to practice, from in vitro experiments to in vivo applications. In this paper, we review and analyze the recent advancements of nanobots in cancer treatments, with a particular emphasis on their key fundamental features and their applications in drug delivery, tumor sensing and diagnosis, targeted therapy, minimally invasive surgery, and other comprehensive treatments. At the same time, we discuss the challenges and the potential research opportunities for nanobots in revolutionizing cancer treatments. In the future, medical nanobots are expected to become more sophisticated and capable of performing multiple medical functions and tasks, ultimately becoming true nanosubmarines in the bloodstream.

Rational design of fluorescent phosgene sensors.

Phosgene is a very toxic gas, which was used as a chemical weapon in World War I, and is currently widely used in industrial processes. So far, no any phosgene fluorescent sensor has been reported. In this study, we report rational design of unimolecular fluorescent phosgene sensors for the first time. Phosgene was used to initiate intramolecular cyclization and convert nonfluorescent molecules to highly fluorescent products. Bright blue fluorescence of phosgene reaction products can be easily visualized by naked eye. The detection limit for phosgene is as low as 1 nM in solutions at room temperature.

Reusable amperometric biosensor for measuring protein tyrosine kinase activity.

This work presents a simple, low-cost and reusable label-free method for detecting protein tyrosine kinase activity using a tyrosinase-based amperometric biosensor (tyrosine kinase biosensor). This method is based on the observation that phosphorylation can block the tyrosinase-catalyzed oxidation of tyrosine or tyrosyl residue in peptides. Therefore, the activity of p60c-src protein tyrosine kinase (Src) on the developed tyrosine kinase biosensor could be quickly determined when its specific peptide substrate, p60c-src substrate I, was used. The tyrosine kinase biosensor was highly sensitive to the activity of Src with a linear dynamic range of 1.9-237.6 U/mL and the lowest detection limit of 0.23 U/mL. Interestingly, the tyrosine kinase activity can be measured using the developed tyrosine kinase biosensor repetitively without regeneration. The inhibitory effect of various kinase inhibitors on the Src activity could be determined on the tyrosine kinase biosensor. Src-specific inhibitors, PP2 and Src inhibitor I, effectively suppressed Src activity, whereas PD153035, an inhibitor of the epidermal growth factor receptor, was ineffective. Staurosporine, a universal kinase inhibitor, inhibited Src activity in an ATP concentration-dependent manner. These results suggests that the activities of tyrosine kinases and their behaviors toward various reagents can be effectively measured using the developed tyrosine kinase biosensor.

Nitrate ion promoted formation of Ag nanowires in polyol processes: a new nanowire growth mechanism.

In polyol processes, it was widely accepted that Ag nanowires (NWs) were formed via uniaxial growth of multiple twinned decahedral particles (MTPs) along the {111} facets. Herein, we show that the above MTP uniaxial growth mechanism for growth of nanorods (NRs) and short nanowires (NWs) is different from that for the growth of long Ag NWs. We provide experimental evidence to show that polycrystalline long Ag NWs (up to ~100 µm) could be formed in high yield (~90%) by a completely different growth mechanism via self-assembly of Ag NPs/NRs. Transmission electron microscope (TEM) measurements show that long Ag NWs are composed of crystalline Ag NPs and NRs with multiple crystal orientations, and many NRs have crystalline structures with pentagonal cross section. Solution phase in situ X-ray diffraction (XRD) measurements show that a strained face-centered tetragonal (fct) phase was gradually formed during the formation and growth of long Ag NWs, in addition to the normal face-centered cubic (fcc) phase. The strained fct phase disappears after partial etching by HAuCl(4) and Fe(NO(3))(3). The working conditions for the MTP uniaxial growth mechanism and the current nitrate-promoted self-assembly growth mechanism will be compared and discussed.