Synthesis and Biological Evaluation of a New Biphenyl-Based Organogold(III) Complex with In Vitro and In Vivo Anticancer Activity.

Despite recent advances in cancer treatment, there is still a need for novel compounds with antineoplastic activity. Among 11 biphenyl-based organogold(III) -heterocyclic carbene (NHC) (BGC) complexes of general formula [(C^C)Au(NHC-pyr)X], where (C^C) = 4,4'-ditertbutylbiphenyl, X = Cl or phenylacetylide, and (NHC-pyr) is a pyridyl-substituted NHC ligand, the complex bearing a 4-CF-pyridyl substituent and a chloride ligand showed promising antineoplastic activity on the triple negative breast cancer cell line. was able to induce cell apoptosis but had no effect on the cell cycle.

Post-metallation functionalization of the [(C^C)Au(P^P)] scaffold through a hydrothiolation reaction.

Complex 1 [(C^C)Au(dppv)]PF (dppv = -1,2-diphenylphosphinoethylene) is reported to react efficiently and selectively with aliphatic and aromatic thiols in the presence of a base. This methodology enables the smooth introduction of various functional groups on the [(C^C)Au(P^P)] scaffold.

Are Redox-Active Centers Bridged by Saturated Flexible Linkers Systematically Electrochemically Independent?

The extent to which electrophores covalently bridged by a saturated linker are electrochemically independent was investigated considering the charge/spin duality of the electron and functionality of the electrophore as a spin carrier upon reduction. By combining computational modeling with electrochemical experiments, we investigated the mechanism by which tethered electrophores react together within 4,4'-oligo[n]methylene-bipyridinium assemblies (with n=2 to 5). We show that native dicationic electrophores (redox state Z=+2) are folded prior to electron injection into the system, allowing the emergence of supra-molecular orbitals (supra-MOs) likely to support the process of the reductive σ bond formation giving cyclomers.

Synthesis of New Bodipy Hydrazide Fluorescent Probes for the Detection of Carbonylated Proteins Generated by Oxidative Stress.

Oxidative stress is a cellular disorder implicated in various severe diseases and redox biology and represents an important field of research for the last decades. One of the major consequences of oxidative stress is the carbonylation of proteins, which is also a reliable marker to assess protein oxidative modifications. Accumulation of carbonylated proteins has been associated with aging and age-related diseases and can ultimately causes cell death.

Identification of Cellular Protein Targets of a Half-Sandwich Iridium(III) Complex Reveals Its Dual Mechanism of Action via Both Electrophilic and Oxidative Stresses.

Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C∧N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high-affinity targets.

Development of furan-2,5-dicarboxylic acid (FDCA)-based organogelators.

Organogels are used in a wide range of applications for which the development of new bio-based organogelators is highly desirable. While furan-2,5-dicarboxylic acid (FDCA) is a promising molecule for the synthesis of bio-based polyesters, it has never been used in the context of organogels. This study explores the possibility to design FDCA-based organogelators that self-assemble into fibrillar networks stabilized by hydrogen bonding.

Binuclear Biphenyl Organogold(III) Complexes: Synthesis, Photophysical and Theoretical Investigation, and Anticancer Activity.

A series of four binuclear complexes of general formula [(C^C)Au(Cl)(L^L)(Cl)Au(C^C)], where C^C is 4,4'-diterbutylbiphenyl and L^L is either a bridging diphosphine or 4,4'-bipyridine, are synthetized with 52 to 72 % yield and structurally characterized by X-ray diffraction. The use of the chelating 1,2-diphenylphosphinoethane ligand in a 1 : 2 (P^P):Au stoichiometry leads to the near quantitative formation of a gold double-complex salt of general formula [(C^C)Au(P^P)][(C^C^)AuCl ]. The compounds display long-lived yellow-green phosphorescence with λ in the range of 525 to 585 nm in the solid state with photoluminescence quantum yields (PLQY) up to 10 %.

Bond-Dissociation Energies to Probe Pyridine Electronic Effects on Organogold(III) Complexes: From Methodological Developments to Application in π-Backdonation Investigation and Catalysis.

In this work, we report on the synthesis of several organogold(III) complexes based on 4,4'-diterbutylbiphenyl (C^C) and 2,6-bis(4-terbutylphenyl)pyridine (C^N^C) ligands and bond with variously substituted pyridine ligands (pyrR). Altogether, 33 complexes have been prepared and studied with mass spectrometry using higher-energy collision dissociation (HCD) in an Orbitrap mass spectrometer. A complete methodology including the kinetic modeling of the dissociation process based on the Rice-Ramsperger-Kassel-Marcus (RRKM) statistical method is proposed to obtain critical energies of the pyrR loss for all complexes.

Biphenyl Au(III) Complexes with Phosphine Ancillary Ligands: Synthesis, Optical Properties, and Electroluminescence in Light-Emitting Electrochemical Cells.

A series of ten cationic complexes of the general formula [(C^C)Au(P^P)]X, where C^C = 4,4'-di--butyl-1,1'-biphenyl, P^P is a diphosphine ligand, and X is a noncoordinating counteranion, have been synthesized and fully characterized by means of chemical and X-ray structural methods. All the complexes display a remarkable switch-on of the emission properties when going from a fluid solution to a solid state. In the latter, long-lived emission with lifetime τ = 1.

CO Electroreduction in Water with a Heterogenized C-Substituted Nickel Cyclam Catalyst.

Molecular catalysis for selective CO electroreduction into CO can be achieved with a variety of metal complexes. Their immobilization on cathodes is required for their practical implementation in electrolytic cells and can benefit from the advantages of a solid material such as easy separation of products and catalysts, efficient electron transfer to the catalyst, and high stability. However, this approach remains insufficiently explored up to now.

Reactant-induced photoactivation of in situ generated organogold intermediates leading to alkynylated indoles via Csp-Csp cross-coupling.

Photosensitization of organogold intermediates is an emerging field in catalysis. In this context, an access to 2,3-disubstituted indoles from o-alkynyl aniline and iodoalkyne derivatives via a gold-catalyzed sequence under visible-light irradiation and in the absence of an exogenous photocatalyst was uncovered. A wide scope of the process is observed.

Synthesis and Reactivity of Martin's Spirosilane-Derived Chloromethylsilicate.

Pentacoordinate silicon derivatives with a chloromethyl ligand are versatile compounds that are usually obtained from the corresponding tetravalent trialkoxy- or trihalogeno(chloromethyl)silane. We describe herein the synthesis of a chloromethylsilicate bearing two Martin's ligands readily obtained by addition of in situ generated chloromethyllithium to a spirosilane. The reactivity of this new species was evaluated and it has been established that the chloride is displaced by strong nucleophiles such as alkyllithiums and (hetero)aryllithiums.

Synthesis and Optical Resolution of Configurationally Stable Zwitterionic Pentacoordinate Silicon Derivatives.

Stereogenic silicon centres in functionalised tetracoordinated organosilanes generally exhibit very high configurational stability under neutral conditions. This stability drops completely when higher coordination states of the silicon centre are reached due to rapid substituent exchange. Herein we describe the synthesis of chiral and neutral pentacoordinate silicon derivatives with high configurational stability.

On the Supra-LUMO Interaction: Case Study of a Sudden Change of Electronic Structure as a Functional Emergence.

The synergistic functioning of redox-active components that emerges from prototypical 2,2'-di(N-methylpyrid-4-ylium)-1,1'-biphenyl is described. Interestingly, even if a trans conformation of the native assembly is expected, due to electrostatic repulsion between cationic pyridinium units, we demonstrate that cis conformation is equally energy-stabilized on account of a peculiar LUMO (SupLUMO) that develops through space, encompassing the two pyridiniums in a single, made-in-one-piece, electronic entity (superelectrophoric behavior). This SupLUMO emergence, with the cis species as superelectrophore embodiment, originates in a sudden change of electronic structure.

[(C C)Au(N N)] Complexes as a New Family of Anticancer Candidates: Synthesis, Characterization and Exploration of the Antiproliferative Properties.

A library of eleven cationic gold(III) complexes of the general formula [(C C)Au(N N)] when C C is either biphenyl or 4,4'-ditertbutyldiphenyl and N N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison.

Novel luminescent benzopyranothiophene- and BODIPY-derived aroylhydrazonic ligands and their dicopper(II) complexes: syntheses, antiproliferative activity and cellular uptake studies.

Two novel unsymmetrical binucleating aroylhydrazonic ligands and four dicopper(II) complexes carrying fluorescent benzopyranothiophene (BPT) or boron dipyrromethene (BODIPY) entities were synthesized and fully characterized. Complex 1, derived from the BPT-containing ligand HL1, had its crystal structure elucidated through X-ray diffraction measurements. The absorption and fluorescence profiles of all the compounds obtained were discussed.

Indolizy Carbene Ligand. Evaluation of Electronic Properties and Applications in Asymmetric Gold(I) Catalysis.

We report herein a new family of carbene ligands based on an indolizine-ylidene (Indolizy) moiety. The corresponding gold(I) complexes are easily obtained from the gold(I)-promoted cyclization of allenylpyridine precursors. Evaluation of the electronic properties by experimental methods and also by DFT calculations confirms strong σ-donating and π-accepting properties of these ligands.

A Bis-Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents.

The two independent and coordination sites of a newly synthesized bis[2-(hydroxyphenyl)-1,2,4-triazole] platform have been exploited to prepare four monometallic neutral ()Pt complexes carrying DMSO, pyridine, triphenylphosphine, or N-heterocyclic carbene as the fourth ligand. Then, the second coordination site was used to introduce an IR-active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral Pt /Re complexes, as well as a cationic Pt /Re derivative. X-ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers.

Isoxazole-Derived Aroylhydrazones and Their Dinuclear Copper(II) Complexes Show Antiproliferative Activity on Breast Cancer Cells with a Potentially Alternative Mechanism Of Action.

This paper reports the design, synthesis and cytotoxicity studies of two new isoxazole-derived aroylhydrazone ligands and their dinuclear copper(II) complexes. Compounds were fully characterized by various spectroscopic and analytical techniques. The molecular structures of four derivatives were confirmed by X-ray crystallography.

Optimizing Group Transfer Catalysis by Copper Complex with Redox-Active Ligand in an Entatic State.

Metalloenzymes use earth-abundant non-noble metals to perform high-fidelity transformations in the biological world. To ensure chemical efficiency, metalloenzymes have acquired evolutionary reactivity-enhancing tools. Among these, the entatic state model states that a strongly distorted geometry induced by ligands around a metal center gives rise to an energized structure called entatic state, strongly improving the reactivity.