Construction of 5-Fluorouracil and Gallium Corrole Conjugates for Enhanced Photodynamic Therapy.

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.

Azide-modified corrole phosphorus complexes for endoplasmic reticulum-targeted fluorescence bioimaging and effective cancer photodynamic therapy.

Study on corrole photosensitizers (PSs) for photodynamic therapy (PDT) has made remarkable progress. Targeted delivery of PSs is of great significance for enhancing therapeutic efficiency, decreasing the dosage, and reducing systemic toxicity during PDT. The development of PSs that can be specifically delivered to the subcellular organelle is still an attractive and challenging work. Herein, we synthesize a series of azide-modified corrole phosphorus and gallium complex PSs, in which phosphorus corrole 2-P could not only precisely target the endoplasmic reticulum (ER) with a Pearson correlation coefficient (PCC) up to 0.92 but also possesses the highest singlet oxygen quantum yields (ΦΔ = 0.75). This renders it remarkable PDT activity at a very low dosage (IC50 = 23 nM) towards HepG2 tumor cell line while ablating solid tumors in vivo with excellent biosecurity. Furthermore, 2-P exhibits intense red fluorescence (ΦF = 0.25), outstanding photostability, and a large Stokes shift (190 nm), making it a promising fluorescent probe for ER. This study provides a clinically potential photosensitizer for cancer photodynamic therapy and a promising ER fluorescent probe for bioimaging.

Gallium(III) Amide Corroles: DNA Interaction and Photodynamic Activity in Cancer Cells.

A series of gallium(III) amide corroles including meso-5,15-bis(pentafluorophenyl)-10-(4-Pyridinamide-phenyl)corrole gallium (III) (1-Ga), meso-5,15-bis(pentafluorophenyl)-10-(4-Furamide-phenyl)corrole gallium(III) (2-Ga) and meso-5,15-bis(pentafluorophenyl)-10-(4-Thiophenamide-phenyl)corrole gallium(III) (3-Ga) were synthesized. The interaction of these complexes with DNA and their photodynamic antitumor activities have been studied. UV spectra titration showed that these gallium(III) corroles interact with calf thymus DNA (CT-DNA) through an external binding mode. All three gallium(III) corroles can effectively generate singlet oxygen under illumination and have good photostability. Among the three gallium(III) corroles, 2-Ga exhibited excellent photodynamic antitumor activity against the tested tumor cell lines under light irradiation (625±2 nm, 0.3 mW/cm2 , 1.08 J/cm2 ). The best phototoxicity was observed by 2-Ga against HepG2 cells (IC50 =6.3±0.9), which is even better than temoporfin (IC50 =8.4±1.8). It could block HepG2 cells in the sub-G0 phase and effectively induce apoptosis of HepG2 cells under 625 nm light irradiation.

Non-Metallic Phosphorus Corrole as Efficient Electrocatalyst in Hydrogen Evolution Reaction.

The economical consideration of using an electrocatalyst in energy-related field, composed of non-precious/sustainable elements is quite noteworthy. In this work, the phosphorus(V) complex of tris-(pentafluorophenyl)corrole [(TPFC)PV (OH)2 ] was reported as electrocatalyst for the hydrogen evolution reaction (HER). The electrochemical studies revealed that the HER experienced a ECEC pathway (E: electron transfer step, C: chemical step), and the possible intermediate [PV ]-H species was suggested. (TPFC)PV (OH)2 displayed excellent HER activity in dimethylformamide (DMF) with trifluoroacetic acid (TFA) as the proton source, and the turnover frequency (TOF) reached 31.75 s-1 at an overpotential of 900 mV. Interestingly, the HER electrocatalytic performance remained extraordinary even applying water as a proton source in acetonitrile/water (v/v=2 : 3), with a TOF of 18.40 mol H 2 ${{_{{\rm H}{_{2}}}}}$ molcat -1 h-1 at an overpotential of 900 mV.

Photodynamic Antitumor Activity of 5,15-Bis(perfluorophenyl)-10-(4-carboxyphenyl)corrole and its Gallium(III) and Phosphorus(V) Complexes.

This work reports the preparation and characterization of an A2 B corrole 5,15-bis(perfluorophenyl)-10-(4-carboxyphenyl)corrole and its gallium(III) and phosphorus(V) complexes. Their in-vitro photodynamic anticancer activities against A549, MDA-MB-231, B16, HepG2, and Hela cell lines were also investigated. Among three compounds, phosphorus(V) complexexhibits the best photostability, highest fluorescence quantum yields (ΦF =0.138), and the highest singlet-oxygen quantum yields (ΦΔ =0.87). Also, the phosphorus(V) complex exhibits the best photodynamic antitumor activity against MDA-MB-231 cells with a low IC50 (0.08 µM) upon light irradiation at 625±2 nm, which is much lower than commercial PDT drug Temoporfin (0.1 µM) at the same conditions. The cellular localization assay confirmed that the phosphorus(V) complexis mainly distributed in the cytoplasm and have a good ability to produce reactive oxygen species (ROS) under light illumination, which would further cause oxidative damage to tumor cells and finally result in the apoptosis. After PDT treatment, phosphorus(V) complex may cause tumor cell arrest at the G2/M stage. The preliminary results showed phosphorus(V) corrole complex is a good candidate for photodynamic therapy (PDT) of tumors.

Direct bromocarboxylation of arynes using allyl bromides and carbon dioxide.

An unprecedented three-component coupling involving arynes, allyl bromides, and CO2 is described, providing efficient and facile access to structurally diverse ortho-brominated aryl esters. Unlike the conventional role played in organic synthesis as electrophiles, organic bromides served as nucleophiles in this reaction, affording a new approach to multicomponent reactions (MCRs) involving aryne intermediates. Additionally, Hammett analysis suggests that two reaction mechanisms exist, depending on the electronic nature of the cinnamyl bromides used.

Switchable Reactivity between Vinyl Azides and Terminal Alkyne by Nano Copper Catalysis.

A novel nano copper-catalyzed substrate-dependent chemodivergent transformation of vinyl azides with a terminal alkyne is disclosed. 2,5-Disubstituted pyrroles were selectively obtained in high yield with aryl alkynes and aliphatic alkynes, whereas 2,3,4-trisubstituted pyrroles were formed with silylated alkynes. This switchable method provides a controllable and facile access to both multisubstituted pyrrole scaffolds with high efficiency, excellent regioselectivity, and good functional group compatibility.

A Three-Phase Four-Component Coupling Reaction: Selective Synthesis of o-Chloro Benzoates by KCl, Arynes, CO2, and Chloroalkanes.

A transition-metal-free three-phase four-component coupling reaction (3P-4CR) involving KCl, arynes, chloroalkanes and CO2 has been reported for the first time, enabling the incorporation of both chloro and CO2 into an aryne simultaneously. The reactions for the synthesis of different types of o-chloro benzoates can be selectively modulated by the chloroalkane utilized. The corresponding products can be alternatively transformed for postsynthetic functionalizations conveniently.

Direct Assembly of 4-Substituted Quinolines with Vinyl Azides as a Dual Synthon via C═C and C-N Bond Cleavage.

An unprecedented Zn-promoted selective cleavage of vinyl azides for the synthesis of 4-substituted quinolines is developed. In this conversion, vinyl azides function as a dual synthon via C═C and C-N bond cleavage with two C═C bonds and one C═N bond formation in a one-step manner. The reaction is appreciated for its readily accessible substrates, high step economy, mild conditions, and use of air as the sole oxidant.

Copper-catalyzed synthesis of thiazol-2-yl ethers from oxime acetates and xanthates under redox-neutral conditions.

A novel copper-catalyzed annulation of oxime acetates and xanthates for the synthesis of thiazol-2-yl ethers with remarkable regioselectivity has been developed. Various oxime acetates, whether derived from aryl ketones or alkyl ketones, or natural product cores are suitable for this conversion. Unique dihydrothiazoles were also obtained when both reaction sites were methine. Mechanistic studies indicated that imino copper(iii) intermediates were involved. In addition, this protocol proceeded under redox-neutral conditions and did not require additives or ligands.

Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "CN" Source.

A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.

One-pot regiospecific synthesis of imidazo[1,2-a]pyridines: a novel, metal-free, three-component reaction for the formation of C-N, C-O, and C-S bonds.

A novel transition-metal-free three-component reaction for the construction of imidazo[1,2-a]pyridines has been developed. It represents a facile approach for the formation of C-N, C-O, and C-S bonds from ynals, pyridin-2-amines, and alcohols or thiols.

Copper-catalyzed C-O bond formation: an efficient one-pot highly regioselective synthesis of furans from (2-furyl)carbene complexes.

A convenient one-pot Cu(I)-catalyzed strategy for regioselective synthesis of trisubstituted furan derivatives has been developed via (2-furyl) carbene complexes. This process has opened a new synthetic route to a variety of α-carbonyl furans using air as the oxidant affording furans in good yields.