On-Surface Synthesis and Real-Space Visualization of Aromatic P3N3

On-surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on-surface synthesis of the structurally elusive cyclotriphosphazene (P₃N₃), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e., voltage pulse-induced sextuple dechlorination of an ultra-small (about 6 Å) hexachlorophosphazene P₃N₃Cl₆ precursor by the tip of a scanning probe microscope. Real-space atomic-level imaging of cyclotriphosphazene reveals its planar D_3h-symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P₃N₂₁ via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy.     

Reduction of Platinum(IV) Prodrug Hemoglobin Nanoparticles with Deeply Penetrating Ultrasound Radiation for Tumor-Targeted Therapeutically Enhanced Anticancer Therapy

The development of Pt^IV prodrugs that are reduced into the therapeutically active Pt^II species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of Pt^IV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of Pt^IV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.     

Engineering Graphdiyne for Solar Photocatalysis

Graphdiyne (GDY) with a direct band gap, excellent carrier mobility and uniform pores, is regarded as a promising photocatalytic material for solar energy conversion, while the research on GDY in photocatalysis is a less developed field. Herein, the distinctive structure, adjustable band gap, and electronic properties of GDY for photocatalysis is firstly summarized. The construction and progress of GDY-based photocatalysts for solar energy conversion, including H₂ evolution reaction (HER), CO₂ reduction reaction (CO₂RR) and N₂ reduction reaction (NRR) are then elaborated. At last, the challenges and perspectives in developing GDY-based photocatalysts for solar fuel production are discussed. It is anticipated that a timely Minireview will be helpful for rapid progress of GDY in solar energy conversion.     

Synthesis of the N-Amykitanosyl Tetramic Acid Moiety of Amycolamicin

An improved five-step synthetic route from l -fucose to an N-glycosyl l -valine methyl ester has been developed. The new route involves glycosidation of l -fucose with phenol in a β-selective manner without protection/deprotection steps and one-pot stereochemical inversion of a secondary alcohol intermediate and is superior to our previous one both in the number of steps and in overall yield. An N-glycosyl l -valine benzyl ester, prepared from l -fucose in an analogous way, has been elaborated into an N-amykitanosyl tetramic acid derivative, Li's synthetic intermediate for amycolamicin, via a four-step sequence which features the utilization of Bestmann's ylide to stereoconvergently construct an N-glycosyl tetramic acid intermediate in a single step, opening of a cyclic carbonate ring with an amine to regioselectively install a carbamate functionality, and visible light-mediated oxidative debenzylation of an N,N-dibenzyl carbamate.     

Light-Driven Catalyst-Free Access to Phthalazines: Entry to Antiviral Model Drugs by Merging Domino Reactions**

We report the development of a metal-free four-step one-pot synthetic strategy to access high-value functionalized phthalazines using o-methyl benzophenones as starting compounds. Combining a light-mediated enolization of o-methyl benzophenones/Diels-Alder reaction domino process with a subsequent deprotection/aromatization domino reaction in one-pot leads to sustainable and efficient organic synthesis. The tangible advantages, i. e., absence of catalysts or additives, utilization of commercially available and/or easily accessible substrates, mild reaction conditions, simplicity, and single work-up procedure, make this combined process highly appealing for the direct construction of various 1-aryl-phthalazines. Importantly, in vitro bioactivity evaluation of these newly prepared heterocyclic compounds demonstrated a strong antiviral efficacy against major human pathogens like HCMV and SARS-CoV-2.     

Gold(I)-Catalyzed and PTSA-Promoted Cycloisomerization of Ynamides to Access Pyrrole Substituted α,β-Unsaturated Ketones**

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold-catalyzed and para-toluenesulfonic acid (PTSA)-assisted cascade cycloisomerization reaction for the synthesis of β-pyrrole substituted α,β-unsaturated ketones. Notably, the reaction is stereoselective, offering E-isomer as major product with low to moderate yield.     

Direct Synthesis of Disubstituted 3-Isoquinolinone Derivatives through the Construction of C−N,C=O,and C(sp2)−C(sp3) Bonds under Transition-Metal-Free Conditions

The efficient three-component cascade coupling reaction of 3-haloisoquinolines, haloalkanes, and sp³-carbon nucleophiles (acetophenone or nitromethane) led to a series of structurally novel 1,2-disubstituted-3-isoquinolinones through the formation of C(sp³)−C(sp²), C−N, and C=O bonds. The NaOAc-promoted reaction described in this work is simple to operate, environment friendly, and highly selective.     

Selective Formal Carbene Insertion into Carbon-Boron Bonds of Diboronates by N-Trisylhydrazones

Bisborylalkanes play important roles in organic synthesis as versatile bifunctional reagents. The two boron moieties in these compounds can be selectively converted into other functional groups through cross-coupling, oxidation or radical reactions. Thus, the development of efficient methods for synthesizing bisborylalkanes is highly demanded. Herein we report a new strategy to access bisborylalkanes through the reaction of N-trisylhydrazones with diboronate, in which the bis(boryl) methane is transformed into 1,2-bis(boronates) via formal carbene insertion. Since the N-trisylhydrazones can be readily derived from the corresponding aldehydes, this strategy represents a practical synthesis of 1,2-diboronates with broad substrate scope. Mechanistic studies reveal an unusual neighboring group effect of 1,1-bis(boronates), which accounts for the observed regioselectivity when unsymmetric 1,1-diboronates are applied.     

Clustering Six Electrons within “Dawson-Like” Polyoxometalate: An Open Route toward Its Post-functionalization

Super-reduction of polyoxometalates (POMs) in solution is of fundamental interest for designing innovative energy storage systems. In this article, we show that the “Dawson-like” POM can undergo a disproportionation process during its massive electron uptake, leading to species containing three metal-metal bonds as evidenced by X-ray diffraction, multi-nuclear magnetic resonance spectroscopy (¹H and ¹⁸³W NMR), extended X-ray absorption fine structure (EXAFS), UV/Vis, and voltammetry techniques. This result indicates that electron storing within metal-metal bonds is not a unique property of Keggin-type POM as postulated since the 70s. Besides, we demonstrate that the presence of an electron-rich triad in the “Dawson-like” POM allows its post-functionalization with additional tungstate ions, generating a chiral molecule that is also the largest W^IV-containing POMs known to date.     

Neuroprotective Bioorthogonal Catalysis in Mitochondria Using Protein-Integrated Hydrogen-Bonded Organic Frameworks

Mitochondria-targeted bioorthogonal catalysis holds promise for controlling cell function precisely, yet achieving selective and efficient chemical reactions within organelles is challenging. In this study, we introduce a new strategy using protein-integrated hydrogen-bonded organic frameworks (HOFs) to enable synergistic bioorthogonal chemical catalysis and enzymatic catalysis within mitochondria. Utilizing catalytically active tris(4,4′-dicarboxylicacid-2,2′-bipyridyl) ruthenium(II) to self-assemble with [1,1′-biphenyl]-4,4′-biscarboximidamide, we synthesized nanoscale RuB-HOFs that exhibit high photocatalytic reduction activity. Notably, RuB-HOFs efficiently enter cells and preferentially localize to mitochondria, where they facilitate bioorthogonal photoreduction reactions. Moreover, we show that RuB-HOFs encapsulating catalase can produce hydrogen sulfide (H₂S) in mitochondria through photocatalytic reduction of pro-H₂S and degrade hydrogen peroxide through enzymatic catalysis simultaneously, offering a significant neuroprotective effect against oxidative stress. Our findings not only introduce a versatile chemical toolset for mitochondria-targeted bioorthogonal catalysis for prodrug activation but also pave the way for potential therapeutic applications in treating diseases related to cellular oxidative stress.