Phase-change metasurfaces for dynamic control of chiral quasi-bound states in the continuum.

Chiral quasi-bound states in the continuum (QBIC) offer novel mechanisms to achieve intrinsic chiroptical responses. However, current studies on chiral QBIC metasurfaces are restricted to the excitation of intrinsic chirality and fail to dynamically control its circular dichroism (CD) responses. Herein, we construct a phase-change metasurface based on paired Ge2Sb2Te5 (GST) bars to demonstrate the dynamic control of the CD responses of chiral QBIC. The modified coupled mode theory (CMT) is proposed to evaluate the intrinsic chirality, and the predicted results are in good agreement with the finite-difference time-domain (FDTD) results. The maximal intrinsic chirality is associated with the spin-selected dipole mode, i.e., the coupled magnetic dipole (MD) QBIC mode for the left-handed circularly polarized (LCP) light and the decoupled electric dipole (ED) QBIC mode for the right-handed circularly polarized (RCP) light. By varying the volume fraction of GST, the location of chiral BIC can be tuned linearly, and the corresponding chiral response can be switched.

Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans.

Candida albicans (C. albicans) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N)2(tpphz)](PF6) (C-N = 2-phenylpyridine (ppy, in Ir1), 2-(2-thienyl)pyridine (thpy, in Ir2), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N)2(tpphz)](PF6)2 (N-N = 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3)), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

Heteronuclear Ru(II)-Re(I) complexes as potential photodynamic anticancer agents with anti-metastatic and anti-angiogenic activities.

Herein, three heterometallic Ru(II)-Re(I) complexes, [Ru(NN)2(tpphz)Re(CO)3Cl](PF6)2 (N-N = 2,2'-bipyridine (bpy, in RuRe1), 1,10-phenanthroline (phen, in RuRe2), 4,7-diphenyl-1,10-phenanthroline (DIP, in RuRe3), tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2″',3″'-j]phenazine), using tpphz as a bridging ligand to connect Ru(II) polypyridyl moiety and Re(I) tricarbonyl moiety were designed and synthesized. Cytotoxicity tests revealed that RuRe1-3 exhibited high phototoxicities against several cancer cell lines tested, with IC50 values ranging from 0.8 to 6.8 µM. Notably, RuRe2 exhibited the most significant increase in cytotoxicity against human prostate cancer (PC3) cells under light (450 nm) irradiation, with phototoxicity index (PI) value increasing by >112.3-fold. Further mechanistic studies of RuRe2 revealed that RuRe2-mediated PDT could induce tumor cell apoptosis through the mitochondrial pathway. Moreover, RuRe2-mediated PDT could inhibit PC3 cell scratch healing and reduce the expression levels of matrix metalloproteinases 2 (MMP-2), matrix metalloproteinases 9 (MMP-9) and vascular endothelial growth factor receptor VEGFR2. Finally, angiogenic activity assays performed in human umbilical vein endothelial cells (HUVECs) showed that RuRe2 exerted an anti-angiogenesis effect. Our study demonstrated that RuRe1-3 were promising PDT antitumor agents with potential anti-metastatic and anti-angiogenic activities.

Lysosome-targeted cyclometalated iridium(III) complexes: JMJD inhibition, dual induction of apoptosis, and autophagy.

A series of cyclometalated iridium(III) complexes with the formula [Ir(C^N)2 L](PF6) (C^N = 2-phenylpyridine (ppy, in Ir-1), 2-(2-thienyl)pyridine (thpy, in Ir-2), 2-(2,4-difluorophenyl)pyridine (dfppy, in Ir-3), L = 2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)quinolin-8-ol) were designed and synthesized, which utilize 8-hydroxyquinoline derivative as N^N ligands to chelate the cofactor Fe2+ of the Jumonji domain-containing protein (JMJD) histone demethylase. As expected, the results of UV/Vis titration analysis confirm the chelating capabilities of Ir-1-3 for Fe2+, and molecular docking studies also show that Ir-1-3 can interact with the active pocket of JMJD protein, and treatment of cells with Ir-1-3 results in significant upregulation of trimethylated histone 3 lysine 9 (H3K9Me3), indicating the inhibition of JMJD activity. Meanwhile, Ir-1-3 exhibit much higher cytotoxicity against the tested tumor cell lines compared with the clinical chemotherapeutic agent cisplatin. And Ir-1-3 can block the cell cycle at the G2/M phase and inhibit cell migration and colony formation. Further studies show that Ir-1-3 can specifically accumulate in lysosomes, damage the integrity of lysosomes, and induce apoptosis and autophagy. Reduction of mitochondrial membrane potential and elevation of reactive oxygen species also contribute to the antitumor effects of Ir-1-3. Finally, Ir-1 can inhibit tumor growth effectively in vivo and increase the expression of H3K9Me3 in tumor tissues. Our study demonstrates that these iridium(III) complexes are promising anticancer agents with multiple functions, including the inhibition of JMJD and induction of apoptosis and autophagy.

8-Hydroxyquinoline-modified ruthenium(II) polypyridyl complexes for JMJD inhibition and photodynamic antitumor therapy.

As an ideal scaffold for metal ion chelation, 8-hydroxyquinoline (8HQ) can chelate different metal ions, such as Fe2+, Cu2+, Zn2+, etc. Here, by integrating 8HQ with a ruthenium(II) polypyridyl moiety, two Ru(II)-8HQ complexes (Ru1 and Ru2), [Ru(N-N)2L](PF6)2 (L = 2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)quinolin-8-ol; N-N: 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2)) were designed and synthesized. In both complexes, ligand L is an 8HQ derivative designed to chelate the cofactor Fe2+ of jumonji C domain-containing demethylase (JMJD). As expected, Ru1 and Ru2 could inhibit the activity of JMJD by chelating the key cofactor Fe2+ of JMJD, resulting in the upregulation of histone-methylation levels in human lung cancer (A549) cells, and the upregulation was more pronounced under light conditions. In addition, MTT data showed that Ru1 and Ru2 exhibited lower dark toxicity, and light irradiation could significantly enhance their antitumor activity. The marked photodynamic activities of Ru1 and Ru2 could induce the elevation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP), and activation of caspases. These mechanistic studies indicated that Ru1 and Ru2 could induce apoptosis through the combination of JMJD inhibitory and PDT activities, thereby achieving dual antitumor effects.

Synthesis, Characterization and Antitumor Mechanism Investigation of Heterometallic Ru(â ¡)-Re(â ) Complexes.

The development of heteronuclear metal complexes as potent anticancer agents has received increasing attention in recent years. In this study, two new heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes, [Ru(bpy)2LRe(CO)3(DIP)](PF6)3 and [Ru(phen)2LRe(CO)3(DIP)](PF6)3 [RuRe-1 and RuRe-2, L = 2-(4-pyridinyl)imidazolio[4,5-f][1,10]phenanthroline, bpy = 2,2'-bipyridine, DIP = 4,7-diphenyl-1,10-phenanthroline, phen = 1,10-phenanthroline], were synthesized and characterized. Cytotoxicity assay shows that RuRe-1 and RuRe-2 exhibit higher anticancer activity than cisplatin, and exist certain selectivity toward human cancer cells over normal cells. The anticancer mechanistic studies reveal that RuRe-1 and RuRe-2 can induce apoptosis through the regulation of cell cycle, depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS), and caspase cascade. Moreover, RuRe-1 and RuRe-2 can effectively inhibit cell migration and colony formation. Taken together, heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes possess the prospect of developing new anticancer agents with high efficacy.

Novel heterobimetallic Ir(III)-Re(I) complexes: design, synthesis and antitumor mechanism investigation.

The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the anticancer field. Herein, three heterobimetallic Ir(III)-Re(I) complexes, [Ir(C^N)2LRe(CO)3DIP](PF6)2 (C^N = 2-phenylpyridine (ppy, in IrRe-1), 2-(2-thienyl)pyridine (thpy, in IrRe-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, in IrRe-3); L = pyridylimidazo[4,5-f][1,10]phenanthroline; DIP = 4,7-diphenyl-1,10-phenanthroline), were designed and synthesized. The heterobimetallic IrRe-1-3 complexes show pH-sensitive emission properties, which can be used for specific imaging of lysosomes. Additionally, IrRe-1-3 display higher cytotoxicity against tested tumor cell lines than the clinical chemotherapeutic drug cisplatin. Further mechanisms indicate that IrRe-1-3 can induce apoptosis and autophagy, increase intracellular reactive oxygen species (ROS), depolarize the mitochondrial membrane (MMP), block the cell cycle at the G0/G1 phase and inhibit cell migration. To the best of our knowledge, this is the first example of the synthesis of heterobimetallic Ir(III)-Re(I) complexes with superior anticancer activities and evaluation of their anticancer mechanisms.

Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety.

Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N)2bpy(4-CH3-4'-CH2OART)](PF6)2 (Ru-ART-1-3) and [Ru(N^N)2bpy(4-CH2OART-4'-CH2OART)](PF6)2 (Ru-ART-4-6) (N^N = 2,2'-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4), 1,10-phenanthroline (phen, in Ru-ART-2 and Ru-ART-5) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-ART-3 and Ru-ART-6)), were synthesized and characterized. Among them, Ru-ART-1-3 and Ru-ART-4-6 carry one and two ART moieties, respectively. Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result, Ru-ART-3 and Ru-ART-6 induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. In this work, six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) have been synthesized and characterized. Among them, Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy.

Phosphorescent rhenium(I) complexes conjugated with artesunate: Mitochondrial targeting and apoptosis-ferroptosis dual induction.

Cell death is essential for cancer, which can be induced through multiple mechanisms. Ferroptosis, a newly emerging form of non-apoptotic cell death, involves the generation of iron-dependent reactive oxygen species (ROS). In this study, we designed and synthesized two artesunate (ART) conjugated phosphorescent rhenium(I) complexes (Re(I)-ART conjugates), [Re(N^N)(CO)3(PyCH2OART)](PF6) (Re-ART-1 and Re-ART-2) (Py = pyridine, N^N = 1,10-phenanthroline (phen, in Re-ART-1) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Re-ART-2)) that can specifically locate in the mitochondria of human cervical carcinoma (HeLa). Mechanism studies show that Re-ART-1 and Re-ART-2 exhibit high cytotoxicity against cancer cells lines and can induce both apoptosis and ferroptosis in HeLa cells through mitochondrial damage, caspase cascade, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation and lipid peroxidation accumulation. As a result, this work presents the rational design of Re(I)-ART conjugates as a promising strategy to induce both apoptosis and ferroptosis and improve therapeutic efficiency of cancer treatment.

Synergetic effect of efficient energy transfer and 3D pi-pi stack for white emission based on the block copolymers containing nonconjugated spacer.

A series of block copolymers containing nonconjugated spacer and 3D pi-pi stacking structure with simultaneous blue-, green-, and yellow-emitting units has been synthesized and characterized. The dependence of the energy transfer and electroluminescence (EL) properties of these block copolymers on the contents of oligo(phenylenevinylene)s has been investigated. The block copolymer (GEO8-BEO-YEO4) with 98.8% blue-emitting oligomer (BEO), 0.8% green-emitting oligomer (GEO), and 0.4% yellow-emitting oligomer (YEO) showed the best electroluminescent performance, exhibiting a maximum luminance of 2309 cd/m(2) and efficiency of 0.34 cd/A. The single-layer-polymer light-emitting diodes device based on GEO2-BEO-YEO4 emitted greenish white light with the CIE coordinates of (0.26, 0.37) at 10 V. The synergetic effect of the efficient energy transfer and 3D pi-pi stack of these block copolymers on the photoluminescent and electroluminescent properties are investigated.