Main Ligand Research Articles

Chiral ruthenium(II) complexes as stabilizers for an RNA triplex: In contrast to Λ-enantiomer, Δ-enantiomer stabilizes the Watson-Crick duplex and the Hoogsteen strand without significant preference

To further determine the factors governing the triplex stabilization by chiral ruthium(II) polypyridyl complexes, two new dppz-beased binding reagents, Δ-[Ru(bpy)2(6-NO2-dppz)]2+ (Δ-1; bpy = 2,2′-bipyridine; 6-NO2-dppz = 6-nitro-dipyrido-3,2-a,2′,3′-c]phenazine) and Λ-[Ru(bpy)2(6-NO2-dppz)]2+ (Λ-1), have been synthesized and characterized in this work. Binding properties of the two enantiomers Δ-1 and Λ-1 with the RNA poly(U)•poly(A)*poly(U) triplex have been studied by spectroscopic technologies and viscosity measurements as well as melting measurements. Spectral titrations and viscosity experiments as well as light-scattering experiments show that although the two enantiomers bind to the triplex through an intercalative mode, the binding affinity of Δ-1 toward the triplex is slightly higer than that of Λ-1. Moreover, melting measurements show that the two enantiomers exhibit different stabilization effects on the triplex under the same conditions. The enantiomer Δ-1 stabilizes the triplex without significant preference, thereby almost equally stabilizing the Watson-Crick base-paired duplex (the template duplex) and the Hoogsteen base-paired strand (third-strand) of the triplex. In contrast to Δ-1, Λ-1 shows preference for stabilizing the template duplex rather than third-strand to a large extent. This suggests that the racemic complex [Ru(bpy)2(6-NO2-dppz)]2+ is similar as a non-specific metallointercalator for the triplex investigated in this study. The results obtained in this work show that in addition to chiralities of Ru(II) polypyridyl complexes, substituent effects of the main ligands also play important roles in altering the ability and selectivity of the metal complex enantiomers to stabilize the triplex.

Simple Synthesis of Red Iridium(III) Complexes with Sulfur-Contained Four-Membered Ancillary Ligands for OLEDs

Phosphorescent iridium(III) complexes have been widely researched for the fabrication of efficient organic light-emitting diodes (OLEDs). In this work, three red Ir(III) complexes named Ir-1, Ir-2, and Ir-3, with Ir-S-C-S four-membered framework rings, were synthesized efficiently at room temperature within 5 min using sulfur-containing ancillary ligands with electron-donating groups of 9,10-dihydro-9,9-dimethylacridine, phenoxazine, and phenothiazine, respectively. Due to the same main ligand of 4-(4-(trifluoromethyl)phenyl)quinazoline, all Ir(III) complexes showed similar photoluminescence emissions at 622, 619, and 622 nm with phosphorescence quantum yields of 35.4%, 50.4%, and 52.8%, respectively. OLEDs employing these complexes as emitters with the structure of ITO (indium tin oxide)/HAT-CN (dipyra-zino[2,3-f,2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile, 5 nm)/TAPC (4,4′-cyclohexylidenebis[N,N-bis-(4-methylphenyl)aniline], 40 nm)/TCTA (4,4″,4″-tris(carbazol-9-yl)triphenylamine, 10 nm)/Ir(III) complex (10 wt%): 2,6DCzPPy (2,6-bis-(3-(carbazol-9-yl)phenyl)pyridine, 10 nm)/TmPyPB (1,3,5-tri(mpyrid-3-yl-phenyl)benzene, 50 nm)/LiF (1 nm)/Al (100 nm) achieved good performance. In particular, the device based on complex Ir-3 with the phenothiazine unit showed the best performance with a maximum brightness of 22,480 cd m−2, a maximum current efficiency of 23.71 cd A−1, and a maximum external quantum efficiency of 18.1%. The research results suggest the Ir(III) complexes with a four-membered ring Ir-S-C-S backbone provide ideas for the rapid preparation of Ir(III) complexes for OLEDs.

A Double-Antibody Sandwich ELISA for Sensitive and Specific Detection of Swine Fibrinogen-Like Protein 1.

Fibrinogen-like protein 1 (FGL1), a member of the fibrinogen family, is a specific hepatocyte mitogen. Recently, it has been reported that FGL1 is the main inhibitory ligand of lymphocyte activating gene 3 (LAG3). Furthermore, the FGL1-LAG3 pathway has a synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway and is regarded as a promising immunotherapeutic target. However, swine FGL1 (sFGL1) has not been characterized and its detection method is lacking. In the study, the sFGL1 gene was amplified from the liver tissue of swine and then inserted into a prokaryotic expression vector, pQE-30. The recombinant plasmid pQE30-sFGL1 was transformed into JM109 competent cells. The recombinant sFGL1 was induced expression by isopropyl-β-d-thiogalactoside (IPTG) and the purified sFGL1 was used as an antigen to produce mouse monoclonal antibody (mAb) and rabbit polyclonal antibody (pAb). After identification, a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) for sensitive and specific detection of sFGL1 was developed. Swine FGL1 in samples was captured by anti‐sFGL1 mAb followed by detection with anti‐sFGL1 rabbit pAb and HRP-conjugated goat anti-rabbit IgG. The limit of detection of the developed sFLG1-DAS-ELISA is 35 pg/ml with recombinant sFLG1. Besides, it does not show cross‐reactivity with the control protein. Then serum samples of PRRSV-negative and -positive pigs were tested with the established DAS-ELISA and calculated according to the equation of y=0.0735x+0.0737. The results showed that PRRSV infection enhanced the serum FGL1 levels significantly. Our research provides a platform for the research on the functional roles of swine FGL1.

Targeted exosomes for co-delivery of siFGL1 and siTGF-β1 trigger combined cancer immunotherapy by remodeling immunosuppressive tumor microenvironment

Immune checkpoint therapy encounters significant challenges in clinic, including low response rate, acquired resistance and immune-related adverse events. Combination immunotherapy targeting multiple independent but complementary pathways in immune evasion has the potential to enhance therapeutic efficacy. Herein, a combination therapeutic strategy that dually inhibiting FGL1, a recently discovered main ligand for immune checkpoint LAG-3, and TGF-β1, an immunosuppressive cytokine, is firstly reported for colorectal cancer immunotherapy by blocking immune checkpoint and modulating tumor microenvironment simultaneously. We established a cRGD-modified exosome with high siFGL1 and siTGF-β1 loading efficiency (cRGD-Exo/siMix) to realize the co-silence of FGL1 and TGF-β1. The constructed cRGD-Exo/siMix showed a significant anti-tumor effect both in vitro and in vivo. Analysis of the tumor immune microenvironment demonstrated an increased number of tumor infiltration CD8+ T cells while a decreased number of immunosuppressive cells, implying that this therapeutic approach boosted anti-tumor immunity by reshaping the tumor microenvironment. This work provides a new strategy for siRNA delivery and its applications in combined cancer immunotherapy.

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates.

ABSTRACTThe mechanisms underlying the cellular response to extracellular matrices (ECMs) that consist of multiple adhesive ligands are still poorly understood. Here, we address this topic by monitoring specific cellular responses to two different extracellular adhesion molecules – the main integrin ligand fibronectin and galectin-8, a lectin that binds β-galactoside residues − as well as to mixtures of the two proteins. Compared with cell spreading on fibronectin, cell spreading on galectin-8-coated substrates resulted in increased projected cell area, more-pronounced extension of filopodia and, yet, the inability to form focal adhesions and stress fibers. These differences can be partially reversed by experimental manipulations of small G-proteins of the Rho family and their downstream targets, such as formins, the Arp2/3 complex and Rho kinase. We also show that the physical adhesion of cells to galectin-8 was stronger than adhesion to fibronectin. Notably, galectin-8 and fibronectin differently regulate cell spreading and focal adhesion formation, yet act synergistically to upregulate the number and length of filopodia. The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed.This article has an associated First Person interview with the first author of the paper.

Substituent effects on the interactions of ruthenium(II) polypyridyl complexes [Ru(bpy)2(6-R-dppz)]2+ (R = hydroxy and fluorine) with the RNA triplex poly(rU)·poly(rA) × poly(rU)

Two new ruthenium(II) polypyridyl complexes, [Ru(bpy)2(6-OH-dppz)]2+ (Ru1, bpy = 2,2′-bipyridine, 6-OH-dppz = 6-hydroxydipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(bpy)2(6-F-dppz)]2+ (Ru2, 6-F-dppz = 6-fluorodipyrido[3,2-a:2′,3′-c]-phenazine), have been synthesized and characterized in this work. The interactions of Ru1 and Ru2 with the RNA triplex poly(rU)·poly(rA) × poly(rU) have been investigated by spectroscopic and viscometric techniques. Spectral titrations and viscosity experiments show that the binding modes of Ru1 and Ru2 to the triplex are intercalation, with the binding affinity for Ru2 being greater than that for Ru1. Fluorescence titrations indicate that Ru2, unlike Ru1, can act as a “molecular light switch” for the triplex. Furthermore, thermal denaturation experiments suggest that Ru1 and Ru2 stabilize the Hoogsteen base-paired strand (third-strand) of the triplex without significant differences, while the two complexes exhibit different selective stabilizing effects toward the triplex. In contrast to Ru1, Ru2 shows a preference for stabilizing the template duplex under the conditions used in this study. Results of the present work demonstrate that the electronic effects of substituents on the main ligands can significantly affect the binding and stabilization effects of Ru(II) polypyridyl complexes toward the RNA triplex poly(rU)·poly(rA) × poly(rU).

Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay

For the COVID-19 pandemic caused by SARS-CoV-2, there are currently no effective drugs or vaccines to treat this coronavirus infection. In this study, we focus on the main protease enzyme of SARS-CoV-2, 3CLpro, which is critical for viral replication. We employ explicit solvent molecular dynamics simulations of about 150 compounds docked into 3CLpro’s binding site and that had emerged as good main protease ligands from our previous in silico screening of over 1.2 million compounds. By incoporating protein dynamics and applying a range of structural descriptors, such as the ability to form specific contacts with the catalytic dyad residues of 3CLpro and the structural fluctuations of the ligands in the binding site, we are able to further refine our compound selection. Fourteen compounds including estradiol shown to be the most promising based on our calculations were procured and screened against recombinant 3CLpro in a fluorescence assay. Eight of these compounds have significant activity in inhibiting the SARS-CoV-2 main protease. Among these are corilagin, a gallotannin, and lurasidone, an antipsychotic drug, which emerged as the most promising natural product and drug, respectively, and might thus be candidates for drug repurposing for the treatment of COVID-19. In addition, we also tested the inhibitory activity of testosterone, and our results reveal testosterone as possessing moderate inhibitory potency against the 3CLpro enzyme, which may thus provide an explanation why older men are more severely affected by COVID-19.

Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia: a genetic and functional study.

To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. A case-control study. Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. The most significantly pre-eclampsia-linked CR3 variant M441K (P=4.27E-4, OR=1.401, 95%CI=1.167-1.682) displayed a trend of increased adhesion to iC3b (P=0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia.

Differential effects of reduced mineralocorticoid receptor activation by unilateral adrenalectomy vs mineralocorticoid antagonist treatment in patients with primary aldosteronism - Implications for depression and anxiety

The mineralocorticoid receptor (MR) and its ligand aldosterone have been found to play a major role in the pathophysiology of depression. Both could be targets of therapeutic interventions. We analyzed laboratory data and questionnaires evaluating anxiety (using GAD-7 questionnaire) and depression (using PHQD questionnaire) of up to 210 patients with primary aldosteronism (PA) (82 females, 54.7 ± 12.0yrs; 128 males, 48.7 ± 12.8yrs) before and one year after initiation of specific treatment of PA by either adrenalectomy (ADX) or treatment with mineralocorticoid receptor antagonists (MRA). After ADX normalization of aldosterone excess was observed. This was associated with a significant reduction of depressive symptoms, but no significant change in GAD-7 score. MRA treatment was accompanied with persistent high aldosterone levels, but led to a significant improvement of anxiety, but no significant changes in PHQD scores. These data suggest different mechanistic pathways for depression and anxiety mediated via the MR. For treatment of depression a reduction of aldosterone levels might be relevant at CNS locations specific for aldosterone, whereas MRA targets MR more broadly, including areas, where cortisol is the main ligand. MRA may be useful in treatment of anxiety related behavior.

KIR2DL4 genetic diversity in a Brazilian population sample: implications for transcription regulation and protein diversity in samples with different ancestry backgrounds

KIR2DL4 is an important immune modulator expressed in natural killer cells; HLA-G is its main ligand. We have characterized the KIR2DL4 genetic diversity by considering the promoter, all exons, and all introns in a highly admixed Brazilian population sample and by using massively parallel sequencing. We introduce a molecular method to amplify and to sequence the complete KIR2DL4 gene. To avoid the mapping bias and genotype errors commonly observed in gene families, we have developed and validated a bioinformatic pipeline designed to minimize these errors and applied it to survey the variability of 220 individuals from the State of São Paulo, southeastern Brazil. We have also compared the KIR2DL4 genetic diversity in the Brazilian cohort with the diversity previously reported by the 1000Genomes consortium. KIR2DL4 presents high linkage disequilibrium throughout the gene, with coding sequences associated with specific promoters. There are few but divergent promoter haplotypes. We have also detected many new KIR2DL4 sequences, all bearing nucleotide exchanges in introns and encoding previously described proteins. Exons 3 and 4, which encode the external domains, are the most variable. The ancestry background influences the KIR2DL4 allele frequencies and must be considered for association studies regarding KIR2DL4.

BIS(PYRIDYL) ANCILLARY LIGANDS AND PYRAZINE SULFONIC ACID IN THE SYNTHESIS OF TWO Ag(I) SUPRAMOLECULAR STRUCTURES AND FLUORESCENT PROPERTIES OF THE LATTER

The coordination behavior of metal ions coordinated with heterocyclic sulfonic acid is of great significance for the construction of functional sulfonate polymers and the exploration of their potential application. In this study, two novel Ag(I)-based supramolecular structures, namely {[Ag2(4,4′-bipy)2][Ag2(P–SO3)4]·H2O}n (1) and {[Ag(dpp)](P–SO3)·H2O}n (2) (4,4′-bipy = 4,4′-bipyridine, dpp = 1,3-di(4-pyridyl)propane, and P–SO3H = pyrazine sulfonic acid) are synthesized using bis(pyridyl) ancillary ligands to assist the P–SO3H main ligand by the solvent evaporation method. The single crystal X-ray diffraction data indicate that the as-synthesized polymers belong to P-1 and P21/n space groups, respectively. In particular, the application of bis(pyridyl) ancillary ligands specifically improves the rigidity and coordination ability of pyrazine sulfonate, and then, it combines with the generated weak interaction to further extend the structure to higher dimensions. Powder X-ray diffraction results and related data, including Raman spectra, thermal stability and solid-state fluorescence characterizations, are also discussed.

The effect of benzene ring substituent at different position of main ligand on electronic structure and photophysical properties of a series of iridium(III) complexes

The electronic structure and photophysical properties of a series of iridium(III) complexes have been theoretically explored by DFT/TDDFT calculations. Ionization potential, electron affinities, and reorganization energy have been calculated to evaluate the charge transfer and balance properties between hole and electron for the three complexes. The lowest lying absorption of 3 is obviously blue-shifted in contrast to those of 1 and 2, which is consistent with the variation of the energy gap between of LUMO and HOMO values. The calculated lowest energy emissions of complexes 1, 2 and 3 are located at 607, 634 and 698 nm, respectively.

Synthesis and Optoelectronic Properties of Cationic Iridium(III) Complexes with o-Carborane-Based 2-Phenyl Benzothiazole Ligands.

A series of cationic cyclometalated iridium(III) complexes with o-carborane cage on the main ligand of 2-phenylbenzothiazole were synthesized. The prepared iridium complexes (C1-C6) were fully characterized by UV-vis, NMR, and FT-IR spectra. The exact molecular structure of complex C1 was further studied by single crystal X-ray diffraction analysis. The different substitution position of o-carborane on the 2-phenylbenzothiazole ring lead to obvious differences in the emission properties of the synthesized complexes. The o-carboranyl unit results in a bathochromic shift of 10 nm in the fluorescence emission spectrum of C2. In addition, the presence of an o-carborane fragment promoted the strong fluorescence intensity of C1 and C4, which can be used as a tool to effectively boost the intensity of fluorescence properties. The emission fluorescent behavior of iridium(III) complexes can be facilely tuned by structural variations in the main ligands of these materials.

Photoluminescence performance of green light emitting terbium (III) complexes with β-hydroxy ketone and nitrogen donor ancillary ligands.

An efficient and cost-effective technique, solution precipitation approach is adopted to synthesize five bright green luminescent terbium (III) complexes by employing the main β-hydroxy ketone ligand, 2-hydroxy-4-ethoxyacetophenone, and ancillary ligands like bathophenanthroline, 5,6-dimethyl-1,10-phenanthroline, 1,10-phenanthroline, and 2,2-bipyridyl. The elemental compositions and binding mode of ligand to terbium (III) ion can be validated by using energy dispersive X-ray analysis, elemental analysis, Fourier transform infrared, and proton nuclear magnetic resonance spectroscopy. The complexes are thermally stable up to 158°C and possess the cubic shaped particles as confirmed by thermogravimetric analysis and scanning electron microscopic study, respectively. The band-gap energy (3.02-2.92 eV) of complexes is reckoned through diffuse reflectance spectra, which tailors them as potential candidates in the field of military radars. The photoluminescence studies unveil that the complexes exhibit the bright green luminescence corresponding to 5 D4 → 7 F5 transition of Tb3+ ion (548 nm) under the excitation wavelength of 395 or 397 nm. The Commission International de I'Eclairage chromaticity coordinates (x, y) and color purity substantiates the green emission of complexes. The energy transfer mechanism elucidates that the main ligand and ancillary ligands sensitize Tb3+ ion, which in turn enhances the luminescence efficiency of the emissive layer of white organic light emitting diodes. The results reveal that the complexes are considered as good contenders in the field of display devices and laser technology. Lastly, in vitro antimicrobial and antioxidant activity proclaim the potent antimicrobial and antioxidant actions of complexes via tube dilution and 2, 2-diphenyl-1-picrylhydrazyl assays, respectively.

High Serum Soluble Fas Ligand Levels in Non-survivor Traumatic Brain Injury Patients.

Soluble Fas Ligand (sFasL) is one of the main ligands that activates the apoptosis extrinsic pathway. Higher expression of FasL in brain samples and higher cerebrospinal fluid FasL concentrations in traumatic brain injury (TBI) patients than in controls have been found. However, the potential association between blood sFasL concentrations and TBI mortality has not been reported. Therefore, the objective of this study was to determine whether that association exists. We included patients with a severe isolated TBI, defined as < 9 points in Glasgow Coma Scale (GCS) and < 10 non-cranial aspects points in Injury Severity Score in this observational and prospective study performed in 5 Intensive Care Units. We measured serum sFasL concentrations on day 1 of TBI. We found that 30-day survivor (n = 59) in comparison to non-survivor patients (n = 24) had higher GCS (p = 0.001), lower age (p = 0.004), lower APACHE-II score (p < 0.001), lower intracranial pressure (ICP) (p = 0.01), lower computer tomography (CT) findings of high risk of death (p = 0.02) and lower serum sFasL concentrations (p < 0.001). The area under the curve for mortality prediction by serum sFasL levels was of 75% (95% CI = 63%-87%; p < 0.001). In Kaplan-Meier analysis was found that patients with serum sFasL levels > 29.2pg/mL had a higher mortality rate (Hazard ratio = 6.2; 95% CI = 2.6-14.8; p < 0.001). Multiple logistic regression analysis found an association between serum sFasL levels and mortality after controlling for GCS, age and CT findings (OR = 1.055; 95% CI = 1.018-1.094; p = 0.004), and after controlling for APACHE-II, ICP and CT findings (OR = 1.048; 95% CI = 1.017-1.080; p = 0.002). The association between serum sFasL levels and 30-day mortality in TBI patients was the major novel finding of our study; however, future validation could be interesting to confirm those results.

Differential Contribution of Cadm1-Cadm3 Cell Adhesion Molecules to Peripheral Myelinated Axons.

Cell adhesion proteins of the Cadm (SynCAM/Necl) family regulate myelination and the organization of myelinated axons. In the peripheral nervous system (PNS), intercellular contact between Schwann cells and their underlying axons is believed to be mediated by binding of glial Cadm4 to axonal Cadm3 or Cadm2. Nevertheless, given that distinct neurons express different combinations of the Cadm proteins, the identity of the functional axonal ligand for Cadm4 remains to be determined. Here, we took a genetic approach to compare the phenotype of Cadm4 null mice, which exhibit abnormal distribution of Caspr and Kv1 potassium channels, with mice lacking different combinations of Cadm1-Cadm3 genes. We show that in contrast to mice lacking the single Cadm1, Cadm2, or Cadm3 genes, genetic ablation of all three phenocopies the abnormalities detected in the absence of Cadm4. Similar defects were observed in double mutant mice lacking Cadm3 and Cadm2 (i.e., Cadm3-/-/Cadm2-/-) or Cadm3 and Cadm1 (i.e., Cadm3-/-/Cadm1-/-), but not in mice lacking Cadm1 and Cadm2 (i.e., Cadm1-/-/Cadm2-/-). Furthermore, axonal organization abnormalities were also detected in Cadm3 null mice that were heterozygous for the two other axonal Cadms. Our results identify Cadm3 as the main axonal ligand for glial Cadm4, and reveal that its absence could be compensated by the combined action of Cadm2 and Cadm1.SIGNIFICANCE STATEMENT Myelination by Schwann cells enables fast conduction of action potentials along motor and sensory axons. In these nerves, Schwann cell-axon contact is mediated by cell adhesion molecules of the Cadm family. Cadm4 in Schwann cells regulates axonal ensheathment and myelin wrapping, as well as the organization of the axonal membrane, but the identity of its axonal ligands is not clear. Here, we reveal that Cadm mediated axon-glia interactions depend on a hierarchical adhesion code that involves multiple family members. Our results provide important insights into the molecular mechanisms of axon-glia communication, and the function of Cadm proteins in PNS myelin.

Synthesis, crystal structures, DNA interactions, and antitumor activity of two new dinuclear copper(ii) complexes with thiazole ligand.

Two new dinuclear copper(ii) complexes, [Cu(ambt)2(cnba)4] (1) and [Cu(ambt)2(clba)4] (2) were synthesized with 2-amino-6-methoxybenzothiazole (ambt) as the main ligand. The structures of the two complexes were characterized by single-crystal XRD. The binding between CT-DNA (calf thymus DNA) and the complexes was evaluated by viscometry, electronic absorption, and fluorescence spectroscopy, and the binding constants were calculated using the Stern–Volmer equation. The complexes were intercalatively bound to CT-DNA, and [Cu(ambt)2(clba)4] having a greater binding constant than [Cu(ambt)2(cnba)4]. The two complexes had better antitumor properties against HepG2 (human hepatocellular carcinoma), A549 (human lung carcinoma), and HeLa (human cervical carcinoma) tumor cell lines than their respective ligands and cisplatin. Furthermore, [Cu(ambt)2(clba)4] had a stronger inhibitory ability on the three types of tumor cells than [Cu(ambt)2(cnba)4], which is congruent with the binding power of the complexes with DNA. Flow cytometry revealed that [Cu(ambt)2(cnba)4] and [Cu(ambt)2(clba)4] could trigger apoptosis or necrosis, arrest the HepG2 cell cycles, and cause G0/G1-phase cells to accumulate.

Synthesis of pH-responsive cyclometalated iridium(III) complex and its application in the selective killing of cancerous cells.

Cyclometalated iridium(III) complexes are promising candidates as photosensitizers (PSs) in photodynamic therapy (PDT). The challenge in PDT is the selective killing of cancerous cells over the neighboring normal cells. In this work, a pH-responsive cyclometalated iridium(III) complex (probe 1) was designed and synthesized as an effective PS to selectively kill cancerous cells, with 3-(2-pyridyl)benzaldehyde used as the main ligand and 1-(2-pyridyl)-β-carboline used as an ancillary ligand. Probe 1 shows enhanced photoluminescence emission and higher 1O2 quantum yield in an acidic environment compared to a neutral solution, which led to remarkable phototoxicity toward cancerous cells and high selectivity for killing cancerous cells over normal cells within 10 min. This work demonstrates that the cyclometalated iridium(III) complex with acidic pH-responsive photoluminescence emission and high 1O2 generation is an effective alternative PS for selectively killing cancerous cells.

Coordination chemistry of the bench-stable tris-2-pyridyl pnictogen ligands [E(6-Me-2-py)3] (E = As, As[double bond, length as m-dash]O, Sb).

Tripodal ligands with main group bridghead units are well established in coordination chemistry and single-site organometallic catalysis. Although a large number of tris(2-pyridyl) main group ligands [E(2-py)3] (E = main group element, 2-py = 2-pyridyl) spanning across the whole p-block are now synthetically acessible, only limited work has been done on the coordination chemistry on the tris(2-pyridyl) group 15 ligands for the heavier elements (As, Sb). In the current study we investigate the coordination chemistry of the ligand family E(6-Me-2-py)3 (E = As, Sb) and of the As(v) ligand O[double bond, length as m-dash]As(6-Me-2-py)3. The air- and mositure-stability of all of these main group ligands makes them especially attractive in future catalytic applications.

Cyclometalated Ir(III) complexes as potential electron acceptors for organic solar cells.

Cyclometalated iridium(iii) complexes have been investigated as promising electron donor (D) materials in organic solar cells (OSCs) due to their unique octahedral configuration for optimized morphology and their significantly long lifetimes potentially for enhanced exciton dissociation. However, the application as electron acceptor (A) materials has never been reported. In order to fill this blank, herein, two cyclometalated heteroleptic Ir complexes, TRIr and 2TRIr, based on electron donating-accepting type organic ligands with different π-conjugation lengths are reported as electron acceptor materials in comparison with their corresponding main organic ligands. The two Ir complexes exhibit suitable HOMO/LUMO energy levels of -5.55/-3.47 eV and -5.44/-3.48 eV, which are ∼0.1 eV higher in the HOMO and ∼0.15 eV deeper in the LUMO than the TR and 2TR ligands, respectively. 2TRIr with extended ligand π-conjugation displays a poor triplet feature, while TRIr demonstrates obvious metal-to-ligand charge transfer (MLCT) transition absorption, with a triplet component photoluminescence (PL) lifetime of 85 ns in neat films. When blended with PBDB-T in bulk heterojunction (BHJ) OSCs, the power conversion efficiencies (PCEs) are 2-3 times higher than their relevant ligands, with values of 1.20% and 1.62% for TRIr and 2TRIr, and 0.58% and 0.47% for the TR and 2TR ligand-based devices, respectively. TRIr and 2TRIr based active layer blends exhibit poorer hole and electron mobilities, whereas compared with their relatively linear planar ligands, both of the two octahedral Ir complexes exhibit an optimized surface morphology for less bimolecular recombination and more efficient exciton dissociation, thus contributing to improved photovoltaic performance.