Iminoamido chelated iridium(III) and ruthenium(II) anticancer complexes with mitochondria-targeting ability and potential to overcome cisplatin resistance.

A diverse set of neutral half-sandwich iminoamido iridium and ruthenium organometallic complexes is synthesized through the utilization of Schiff base pro-ligands with N˄N donors. Notably, these metal complexes with varying leaving groups (Cl- or OAc-) are formed by employing different quantities of the deprotonating agent NaOAc, and exhibit promising cytotoxicity against various cancer cell lines such as A549 and cisplatin-resistant A549/DDP lung cancer cells, as well as HeLa cells, with IC50 values spanning from 9.26 to 15.98 µM. Cytotoxicity and anticancer selectivity (SI: 1.9-2.4) of these metal complexes remain unaffected by variations in the metal center, leaving group, and ligand substitution. Further investigations reveal that these metal complexes specifically target mitochondria, leading to the depolarization of the mitochondrial membrane and instigating the production of intracellular reactive oxygen species. Furthermore, the metal complexes are found to induce late apoptosis and disrupt the cell cycle, leading to G2/M cell cycle arrest specifically in A549 cancer cells. In light of these findings, it is evident that the primary mechanism contributing to the anticancer effectiveness of these metal complexes is the redox pathway.

Three-Dimensional Cuprous Iodide Framework with Intrinsic Broadband Red-to-Near-Infrared Light Emission.

Herein, a new organic-inorganic hybrid cuprous iodide of [(Me)2-DABCO]Cu6I8 was prepared and structurally characterized with a novel three-dimensional (3D) [Cu6I8]2- framework. Significantly, this 3D cuprous iodide displays infrequent broadband red-to-near-infrared light emission (600-1000 nm) stemming from the radiative recombination of self-trapped excitons.

Preparation and Bioactivity of Iridium(III) Phenanthroline Complexes with Halide Ions and Pyridine Leaving Groups.

A series of half-sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl- , Br- , I- ) and pyridine leaving groups ([(η5 -CpX )Ir(Phen)Z](PF6 )n , Cpx : electron-rich cyclopentadienyl group, Z: leaving group) have been prepared. Target complexes, especially the Cpxbiph (biphenyl-substituted cyclopentadienyl)-based one, showed favourable anticancer activity against human lung cancer (A549) cells; the best one (Ir8) was almost five times that of cisplatin under the same conditions. Compared with complexes involving halide ion leaving groups, the pyridine-based one did not display hydrolysis but effectively caused lysosomal damage, leading to accumulation in the cytosol, inducing an increase in the level of intracellular reactive oxygen species and apoptosis; this indicated an anticancer mechanism of oxidation. Additionally, these complexes could bind to serum albumin through a static quenching mechanism. The data highlight the potential value of half-sandwich iridium(III) phenanthroline complexes as anticancer drugs.

Broadband White-Light Emission in One-Dimensional Organic-Inorganic Hybrid Silver Halide.

In the past few decades, organic-inorganic hybrid metal halides acting as single-component white light emission diodes (LEDs) have attracted extensive attentions, but most of the studies concentrate on the low-dimensional lead perovskites. Here, by using the nontoxic silver as optically active metal center, a series of hybrid silver halides based on one-dimensional structures were constructed and realized broadband white light emission. Compounds [H2DABCO][Ag2X4(DABCO)] (X = Br (1), I (2)) feature one-dimensional [Ag2X4(DABCO)]2- structures charged balanced by [H2DABCO]2+ cations. Compound 1 exhibits an efficient broadband white-light emission with photoluminescence quantum efficiency (PLQE) of about 2.1% and excellent photochemical stability, while compound 2 gives a broadband yellow-white emission centered at 556 nm. [HDABCO]3Ag5Cl8 (3) gives a strong broadband yellow emission (585 nm) with high PLQE of 6.7%, which can be easily fabricated as a white light emitting device. Based on the temperature-dependent, particle-size-dependent, and time-resolved PL measurements as well as other detailed studies, the broadband white-light emissions are ascribed to the synergetic effects of the organic and inorganic components. Our work provides a unique structural assembly method to explore lead-free single-component white-light illuminants from molecular level.

Triphenylamine-appended cyclometallated iridium(III) complexes: Preparation, photophysical properties and application in biology/luminescence imaging.

Four triphenylamine (TPA)-appended cyclometallated iridium(III) complexes were designed and synthesized. Photophysical properties of these complexes were studied, and density functional theory (DFT) was utilized to analyze the influence of the ancillary ligands (TPA-modified bipyridine) to these complexes. The introduction of TPA units could effectively adjust the lipid solubility of complexes (logP), and endowed complexes with potential bioactivity (anticancer, antibacterial and bactericidal activity), especially in the field of anticancer (the best value of IC50 is 4.34±0.01µM). Interestingly, complexe 4 show some selectivity for cancer cells versus normal cells. Meanwhile, complexes could effectively prevent the metastasis of cancer cells. Complexes can be transported by serum albumin and followed by the static quenching mechanism (Kq: 1013M-1s-1), disturb cell cycle at G0/G1 phase, and induce apoptosis. The favorable fluorescence property confirmed these complexes followed by an energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (PCC: >0.95) and induced lysosomal damage, and eventually leaded to cell death. Our study demonstrates that these complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage.

Organic-Inorganic Hybrid Heterometallic Halides with Low-Dimensional Structures and Red Photoluminescence Emissions.

In recent years, although low-dimensional hybrid lead halides have received great attention due to the fascinating photoluminescent (PL) properties, the research is still on the early stage and only limited phases have been explored and characterized. Here, by introducing heterometals as mixed structural compositions and optical activity centers, we prepared a series of low-dimensional hybrid heterometallic halides, namely as, [(Me)-DABCO]2Cu2PbI6, [(Me)2-DABCO]2M5Pb2I13 (M = Cu and Ag) and [(Me)2-DABCO]Ag2PbBr6 (Me = methyl group, DABCO = 1,4-diazabicyclo[2.2.2]octane). These hybrid halides feature a low-dimensional 0D [Cu2PbI6]2- cluster, a 1D [M5Pb2I13]4- chain, and a 2D [Ag2PbBr6]2- layer, respectively, on the basis of corner-, edge- and face-sharing connecting of [MX4] tetrahedrons, [PbX5] quadrangular pyramids, and [PbX6] octahedrons. Under the photoexcitation, these hybrid heterometallic halides exhibit deep-red luminescent emissions from 711 to 801 nm with the largest Stocks shift of 395 nm. The temperature-dependent PL emissions, PL lifetime, and theoretical calculations are also investigated to probe into the intrinsic nature of photoluminescent emissions. This work affords new types of hybrid halides by introducing different metal centers to probe into the structural evolution and photoluminescent properties.

Transition metal complex dye-sensitized 3D iodoplumbates: syntheses, structures and photoelectric properties.

Here, we prepared the first series of 3D hybrid iodoplumbates with novel porous frameworks of [Pb8I21]5- directed by transition metal complex (TMC) cationic dyes of [TM(2.2-bipy)3]2+. The microporous materials exhibit outstanding visible light-driven photoelectric properties due to the effective photosensitization of the TMC dyes. The coexistence of stronger face- and weaker corner-shared connecting manners affords the feasibility of tailoring the 3D framework into low-dimensional skeletons, which provide a new structural prototype to modify the semiconducting properties similar to those of classic perovskites.

The Multiple Promotion Effects of Ammonium Phosphate-Modified Ag3PO4 on Photocatalytic Performance.

Phosphate ( PO 4 3 - ) modification of semiconductor photocatalysts such as TiO2, C3N4, BiVO4, and etc. has been shown positive effect on the enhancement of photocatalytic performance. In the present study, we demonstrate a novel one-pot surface modification route on Ag3PO4 photocatalyst by ammonium phosphate [(NH4)3PO4], which combines PO 4 3 - modification with ammonium ( NH 4 + ) etching to show multiple effects on the structural variation of Ag3PO4 samples. The modified Ag3PO4 photocatalysts exhibit much higher photocatalytic performance than bare Ag3PO4 for the degradation of organic dye solutions under visible light irradiation. It is indicated that the NH 4 + etching favors the surface transition from Ag3PO4 to metallic Ag nanoparticles, resulting in the fast capture of photogenerated electrons and the followed generation of O 2 · - radicals. The strongly adsorbed PO 4 3 - on the Ag3PO4 surfaces can further provide more negative electrostatic field, which improves the separation of photogenerated electron-hole pairs by inducing the holes to directly flow to the surface and then enhances the formation of reactive ·OH radicals. Furthermore, the photocatalytic performance of the modified Ag3PO4 photocatalysts can be optimized by monitoring the concentration of (NH4)3PO4 that is 1 mM.

Design and fabrication of clustered rugged ZnO nanotube films with condensate microdrop self-propelling function.

We design and fabricate a type of condensate microdrop self-propelling (CMDSP) clustered rugged nanotube film, which is achieved by two-step electrodeposition and low-surface-energy silane modification. This work offers an avenue for developing CMDSP surfaces with self-cleaning, antifrosting, and antidewing functions.

Prevalence and risk factors of Giardia doudenalis in dogs from China.

The aim of this study was to carry out a survey for the presence of Giardia duodenalis infection in canine using ELISA and PCR and to identify risk factors for infection. Samples from 318 dogs' feces living in nine cities in China were used in the present study. Each sample was tested for the presence of G. duodenalis-specific antigens using ELISA and 197 out of 318 samples were further examined for the presence of G. duodenalis using PCR. The overall rate of canines infected with giardiasis in the present study was 16.04% and 15.22% using ELISA and PCR, respectively. No significant difference was found between sex and Giardia positivity. Young dogs (up to one year) and living in communities were identified as risk factors for infection by multivariate logistic regression analysis. In conclusion, giardiasis in dogs was present in nine cities in China; as risk factors, young dogs (up to one year) and living in communities were of great significance. Giardia-infected canine should be treated for hygienic management to prevent transmission of the infection from dog to human.

Molecular dynamics simulations of mutated Mycobacterium tuberculosis L-alanine dehydrogenase to illuminate the role of key residues.

L-Alanine dehydrogenase from Mycobacterium tuberculosis (L-MtAlaDH) catalyzes the NADH-dependent interconversion of l-alanine and pyruvate, and it is considered to be a potential target for the treatment of tuberculosis. The experiment has verified that amino acid replacement of the conserved active-site residues which have strong stability and no great changes in biological evolutionary process, such as His96 and Asp270, could lead to inactive mutants [Ågren et al., J. Mol. Biol. 377 (2008) 1161-1173]. However, the role of these conserved residues in catalytic reaction still remains unclear. Based on the crystal structures, a series of mutant structures were constructed to investigate the role of the conserved residues in enzymatic reaction by using molecular dynamics simulations. The results show that whatever the conserved residues were mutated, the protein can still convert its conformation from open state to closed state as long as NADH is present in active site. Asp270 maintains the stability of nicotinamide ring and ribose of NADH through hydrogen bond interactions, and His96 is helpful to convert the protein conformation by interactions with Gln271, whereas, they would lead to the structural rearrangement in active site and lose the catalytic activity when they were mutated. Additionally, we deduce that Met301 plays a major role in catalytic reaction due to fixing the nicotinamide ring of NADH to prevent its rotation, and we propose that Met301 would be mutated to the hydrophobic residue with large steric hindrance in side chain to test the activity of the protein in future experiment.

Genetic diversity and phylogenetic analysis of Tams1 of Theileria annulata isolates from three continents between 2000 and 2012.

Theileria annulata, which is part of the Theileria sergenti/Theileria buffeli/Theileria orientalis group, preferentially infects cattle and results in high mortality and morbidity in the Mediterranean, Middle East, and Central Asia. The polypeptide Tams1 is an immunodominant major merozoite piroplasm surface antigen of T. annulata that could be used as a marker for epidemiological studies and phylogenetic analysis. In the present study, a total of 155 Tams1 sequences were investigated for genetic diversity and phylogenetic relationships through phylogenetic analysis. Results showed that the Tams1 sequences were divided into two major groups and that distribution for some isolates also exhibited geographic specificity. As targeting polymorphic genes for parasite detection may result in underestimation of infection, polymerase chain reaction (PCR) assay using two different probes targeting tams-1 genes of these two groups can be more credible. In addition, the direction of the spread of the disease was discovered to be from the Mediterranean or the tropical zone to the Eurasian peninsula, Middle East, Southern Asia, and Africa, particularly for Group 2. A similar occurrence was also found between the Ms1 gene of Theileria lestoquardi and the Tams1 gene of T. annulata, which explains cross-immunogenicity to a certain extent. However, no potential glycosylation site in the Tams1 of T. annulata was found in this study, which illustrated that instead of N-glycosylation, other modifications have more significant effects on the immunogenicity of the Tams1 protein.

Molecular dynamics simulations of isoleucine-release pathway in GAF domain of N-CodY from Bacillus Subtilis.

The GAF domain located in the N-terminal motifs of CodY (N-CodY) is responsible for increasing the affinity of CodY to its target sites on DNA by its interaction with the branched chain amino acids (BCAAs) involving isoleucine, leucine and valine. The study of the interaction of GAF domain with isoleucine gains much attention in recent years, but the mechanism of isoleucine release still remains unclear. In this paper, a conventional molecular dynamics (MD) and force probe molecular dynamics (FPMD) simulations have been performed with the aim to understand how the isoleucine ligand escapes from the GAF domain of N-CodY from Bacillus subtilis. The MD results reveal that the ligand release is a gradual process, which is accompanied by the movement of the loop between ß3 and ß4. During the periods of ligand escaping from the bottom to the top of binding pocket, isoleucine forms hydrogen bonds one after another with series of residues, such as ARG61, THR96, PHE98, VAL100, GLU101 and ASN102, under the mediation of hydrophobic contacts. The FPMD results show that the easiest way to pull ligand out of the cavity is along x direction (i.e. the direction is opposite to MET62).

Molecular dynamics simulations of the coenzyme induced conformational changes of Mycobacterium tuberculosis L-alanine dehydrogenase.

Mycobacterium tuberculosis L-alanine dehydrogenase (L-MtAlaDH) catalyzes the NADH-dependent reversible oxidative deamination of L-alanine to pyruvate and ammonia. L-MtAlaDH has been proposed to be a potential target in the treatment of tuberculosis. Based on the crystal structures of this enzyme, molecular dynamics simulations were performed to investigate the conformational changes of L-MtAlaDH induced by coenzyme NADH. The results show that the presence of NADH in the binding domain restricts the motions and conformational distributions of L-MtAlaDH. There are two loops (residues 94-99 and 238-251) playing important roles for the binding of NADH, while another loop (residues 267-293) is responsible for the binding of substrate. The opening/closing and twisting motions of two domains are closely related to the conformational changes of L-MtAlaDH induced by NADH.

Spectroscopic analysis on the resveratrol-DNA binding interactions at physiological pH.

The interaction of resveratrol with calf thymus deoxyribonucleic acid (ctDNA) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) was studied by spectroscopy, fluorescence spectroscopy and viscosity measurement method, respectively. Results indicated that a complex of resveratrol with ctDNA was formed with a binding constant of K(17°C) = 5.49×10(3) L mol(-1) and K(37°C) = 1.90×10(4) L mol(-1). The fluorescence quenching mechanism of acridine orange (AO)-ctDNA by resveratrol was shown to be a static quenching type. The thermodynamic parameters of the complex were calculated by a double reciprocal method: Δ(r)H(m)(s) = 4.64×10(4) J mol(-1), Δ(r)S(m)(s) = 231.8 J K(-1) mol(-1) and Δ(r)G(m)(s) = -2.54×10(4) J mol(-1) (37°C). Spectroscopic techniques together with viscosity determination provided evidences of intercalation mode of binding for the interaction between resveratrol and ctDNA.

Electrocatalytic properties of platinum nanoparticles supported on fluorine tin dioxide/multi-walled carbon nanotube composites for methanol electrooxidation in acidic medium.

Fluorine tin oxide (FTO) and multi-walled carbon nanotube (MWCNT) composites synthesized by a sol-gel process followed by a hydrothermal treatment process have been explored as a support for Pt nanoparticles (Pt-FTO/MWCNTs). X-ray diffraction analysis and high resolution transmission electron microscopy show that the Pt and FTO nanoparticles with crystallite size of around 4-8 nm are highly dispersed on the surface of MWCNTs. Pt-FTO/MWCNT catalyst is evaluated in terms of the electrochemical catalytic activity for methanol electrooxidation using cyclic voltammetry, steady state polarization experiments, and electrochemical impedance spectroscopy technique in acidic medium. The Pt-FTO/MWCNT catalyst exhibits a higher intrinsic catalytic activity for methanol electrooxidation with high stability during potential cycling than Pt nanoparticles supported on tin dioxide/multi-walled carbon nanotube composites. The results suggest that FTO/MWCNT composites could be considered as an alternative support for Pt-based electrocatalysts in direct alcohol fuel cells.