Optical modulation of cell nucleus penetration and singlet oxygen release of a switchable platinum complex.

The activation of anticancer molecules with visible light constitutes an elegant strategy to target tumors and to improve the selectivity of treatments. In this context, we report here a visible-light activatable bis-platinum complex () incorporating an organic photo-switchable ligand based on the dimethyldihydropyrene moiety. Illumination of this metal complex with red light (660 nm) under air readily produces the corresponding endoperoxide form ().

Design and synthesis of 4-amino-2',4'-dihydroxyindanone derivatives as potent inhibitors of tyrosinase and melanin biosynthesis in human melanoma cells.

Melanogenesis inhibition constitutes a privileged therapeutic solution to treat skin hyperpigmentation, a major dermatological concern associated with the overproduction of melanin by human tyrosinase (hsTYR). Despite the existence of many well-known TYR (tyrosinase) inhibitors commercialized in skin formulations, their hsTYR-inhibition efficacy remains poor since most of them were investigated over mushroom tyrosinase (abTYR), a model with low homology relative to hsTYR. Considering the need for new potent hsTYR inhibitors, we designed and synthesized a series of indanones starting from 4-hydroxy compound 1a, one of the two most active derivatives reported to date against the human enzyme, together with marketed thiamidol.

Acylhydrazones as sensitive fluorescent sensors for discriminative detection of thorium (IV) from uranyl and lanthanide ions.

Thorium, as a radioactive element, is always associated with rare earth in nature. So it is an exacting challenge to recognize thorium ion (Th) in the presence of lanthanide ions because of their overlapping ionic radii. Here three simple acylhydrazones (AF, AH and ABr, with the functional group fluorine, hydrogen and bromine, respectively) are explored for Th detection.

All Visible Light Photoswitch Based on the Dimethyldihydropyrene Unit Operating in Aqueous Solutions with High Quantum Yields.

Molecular systems and devices whose properties can be modulated using light as an external stimulus are the subject of numerous research studies in the fields of materials and life sciences. In this context, the use of photochromic compounds that reversibly switch upon light irradiation is particularly attractive. However, for many envisioned applications, and in particular for biological purposes, illumination with harmful UV light must be avoided and these photoactivable systems must operate in aqueous media.

Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells.

Human tyrosinase (hsTYR) catalyzes the key steps of melanogenesis, making it a privileged target for reducing melanin production in vivo. However, very few hsTYR inhibitors have been reported so far in the literature, whereas thousands of mushroom tyrosinase (abTYR) inhibitors are known. Yet, as these enzymes are actually very different, including at their active sites, there is an urgent need for new true hsTYR inhibitors in order to enable human-directed pharmacological and dermocosmetic applications without encountering the inefficiency and toxicity issues currently triggered by kojic acid or hydroquinone.

Bioactive Aurones, Indanones, and Other Hemiindigoid Scaffolds: Medicinal Chemistry and Photopharmacology Perspectives.

Hemiindigoids comprise a range of natural and synthetic scaffolds that share the same aromatic hydrocarbon backbone as well as promising biological and optical properties. The encouraging therapeutic potential of these scaffolds has been unraveled by many studies over the past years and uncovered representants with inspiring pharmacophoric features such as the acetylcholinesterase inhibitor donezepil and the tubulin polymerization inhibitor indanocine. In this review, we summarize the last advances in the medicinal potential of hemiindigoids, with a special attention to molecular design, structure-activity relationship, ligand-target interactions, and mechanistic explanations covering their effects.

Copper(II) and zinc(II) complexation with -ethylene hydroxycyclams and consequences on the macrocyclic backbone configuration.

We report a series of four cyclams and cross-bridged cyclams, -functionalized by one hydroxyethyl arm, which may incorporate additional methyl(s) group(s). The Cu(II) and Zn(II) complexes of these ligands were synthesized and fully characterized. The investigation of the metal complexes in solid-state and in solution was carried X-ray diffraction, NMR, EPR, absorption spectroscopy and DFT calculations.

New Insights into the Redox Properties of Pyridinium Appended 1,2-Dithienylcyclopentenes.

The optical and redox properties of a methyl pyridinium appended 1,2-dithienylethene photochromic derivative have been thoroughly investigated. A complex multi-step photo/redox mechanism is proposed for the closed isomer on the ground of spectro-electrochemical and theoretical data. The generated compounds are not stable over the time because of chemical reactions associated to the redox processes and a new dithienylethene derivative incorporating a seven-membered ring has been isolated and characterized.

Synthesis of Redox-Active Photochromic Phenanthrene Derivatives.

A phenanthrene unit has been functionalized by several methylthiophene units in order to bring it a photochromic behavior. These compounds were characterized by NMR, absorption and emission spectroscopies, theoretical calculations as well as cyclic voltammetry. The association of a phenanthrene group with a photochromic center could open the door to a new generation of organic field-effect transistors.

Synthesis of a Negative Photochrome with High Switching Quantum Yields and Capable of Singlet-Oxygen Production and Storage.

A dimethyldihydropyrene (DHP) photochromic unit has been functionalized by donor (triphenylamine group) and acceptor (methylpyridinium) substituents. This compound was characterized by NMR, absorption and emission spectroscopies as well as cyclic voltammetry, and its properties were rationalized by theoretical calculations. The incorporation of both electron-donor and -withdrawing groups at the photochromic center allows i) an efficient photo-isomerization of the system when illuminated at low energy (quantum yield: Φ =13.

Complexation of -Functionalized Cyclams with Copper(II) and Zinc(II): Similarities and Changes When Compared to Parent Cyclam Analogues.

Herein, we report a comprehensive coordination study of the previously reported ligands , , , , and and of their -functional analogues, , , , , and . This group of ligands includes , cross-bridged , their di- or tetramethylated derivatives, and the analogues bearing an additional hydroxyethyl group on one β-N position of the ring. The Cu(II) and Zn(II) complexes of these macrocycles have been highlighted previously for the biological interest, but the details of their structures in the solid state and in solution remained largely unexplored.

Photo-/Electroinduced Irreversible Isomerization of 2,2'-Azobispyridine Ligands in Arene Ruthenium(II) Complexes.

Novel arene Ru complexes containing 2,2'-azobispyridine ligands were synthesized and characterized by using H and C NMR spectroscopy, UV/vis spectroscopy, electrochemistry, DFT calculations and single-crystal X-ray diffraction. Z-configured complexes featuring unprecedented seven-membered chelate rings involving the nitrogen atom of both pyridines were isolated and were shown to undergo irreversible isomerization to the corresponding E-configured five-membered chelate complexes in response to light or electrochemical stimulus.

Dependency of the Dimethyldihydropyrene Photochromic Properties on the Number of Pyridinium Electron-Withdrawing Groups.

Photochromic dimethyldihydropyrenes substituted with electron-withdrawing pyridinium groups have shown an increase of photo-induced ring-opening efficiency and a light sensitivity that is red shifted relative to the unsubstituted compound. However, a recently synthesized tetrapyridinium derivative showed a considerable decrease of the photo-isomerization quantum yield relative to the monopyridinium and bispyridinium derivatives. We provide a rationale for this unexpected photochemical behavior based on the comparative theoretical investigations of the relevant excited states of these systems.

Redox-Responsive Colloidal Particles Based on Coordination Polymers Incorporating Viologen Units.

Colloidal particles based on supramolecular polymers are emerging as promising functional materials because of their intrinsic dynamic features and the possibility of stimuli responsivity. In this work, ≈200 nm self-assembled redox-responsive colloidal particles made of 1D-coordination polymers were readily prepared. In these metallopolymers, organic entities made of bis(viologen) groups covalently associated with terpyridine units are spontaneously bridged by Zn cations through the formation of coordination bonds.

Structural Study of Polystyrene--poly(acrylic acid) Micelles Complexed with Uranyl: A SAXS Core-Shell Model Analysis.

The interactions between natural colloidal organic matter and actinides in solutions are complex and not fully understood. In this work, a crew-cut polystyrene--poly(acry1ic acid) (PS--PAA) micelle is proposed as a model particle for humic acid (HA) colloid with the aim to better understand the sequestration, aggregation, and mobility of HA colloids in the presence of uranyl ions. The effects of uranyl ions on the structure of PS--PAA micelles in aqueous solution were mainly investigated by synchrotron small-angle X-ray scattering.

All Visible Light Switch Based on the Dimethyldihydropyrene Photochromic Core.

Two photoswitchable compounds that can operate under visible light irradiation are prepared and investigated using spectroscopic and computational studies. These all-visible systems are based on the dimethyldihydropyrene (DHP)/cyclophanediene (CPD) photochromic couple connected either to a bipyridine (bpy) unit or to a (tris(bpy)ruthenium(II)) complex through a pyridinium bridge. In these compounds, the DHP to CPD isomerization and the reverse CPD to DHP conversion can be triggered by illumination with red (>630 nm) and blue (460 nm) lights, respectively.

Electronic Excited States and UV-Vis Absorption Spectra of the Dihydropyrene/Cyclophanediene Photochromic Couple: a Theoretical Investigation.

Dihydropyrene (DHP)/cyclophanediene (CPD) is a fascinating photoswitchable organic system displaying negative photochromism. Upon irradiation in the visible region, the colored DHP can be converted to its open-ring CPD colorless isomer, which can be converted back to DHP by UV light. DHP and CPD thus possess very different absorption spectra whose absorption bands have never been assigned in detail so far.

Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo.

Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer.

Dynamic Molecular Metamorphism Involving Palladium-Assisted Dimerization of π-Cation Radicals.

A dynamic supramolecular approach is developed to promote the π-dimerization of viologen radicals at room temperature and in standard concentration ranges. The approach involves cis- or trans-protected palladium centers serving as inorganic hinges linking two functionalized viologens endowed with metal-ion coordinating properties. Based on detailed spectroscopic, electrochemical and computational data, we show that the one-electron electrochemical reduction of the viologen units in different dynamic metal/ligand mixtures leads to the formation of the same intramolecular π-dimer, regardless of the initial environment around the metallic precursor and of the relative ratio between metal and ligand initially introduced in solution.

Redox-Induced Molecular Metamorphism Promoting a Sol/Gel Phase Transition in a Viologen-Based Coordination Polymer.

We have developed a strategy enabling control over the organization of ditopic molecular tectons within a palladium-based self-assembled system. The key electron-responsive sub-unit is a viologen-based mechanical hinge that can toggle under electric stimulation between a folded and a stretched position, the driving force of the folding motion being the π-dimerisation of the electrogenerated viologen cation radicals. The title ditopic tecton features two planar, N2-type, triazole/pyridine-based bidentate binding units, providing the tecton with the ability to chelate two palladium ions both in its folded and in its elongated conformations.

Redox-Triggered Folding of Self-Assembled Coordination Polymers incorporating Viologen Units.

We report the study of stimuli-responsive Zn and Fe coordination polymers (MC3 or MC2 with M=Fe or Zn ). These soluble metallopolymers were formed spontaneously by reaction of an organic ligand (C3 or C2 ) with one molar equivalent of metal ions. The C3 and C2 ligands incorporate two chelating terpyridine groups bridged by a redox responsive hinge featuring two viologen units (viologen=N,N'-dialkyl-4,4'-bipyridinium) linked either with propyl (C3 ) or ethyl (C2 ) chains.

Conductance in a bis-terpyridine based single molecular breadboard circuit.

Controlling charge flow in single molecule circuits with multiple electrical contacts and conductance pathways is a much sought after goal in molecular electronics. In this joint experimental and theoretical study, we advance the possibility of creating single molecule breadboard circuits through an analysis of the conductance of a bis-terpyridine based molecule (). The molecule can adopt multiple conformations through relative rotations of 7 aromatic rings and can attach to electrodes in 61 possible single and multi-terminal configurations through 6 pyridyl groups.

Efficient Photoswitch System Combining a Dimethyldihydropyrene Pyridinium Core and Ruthenium(II) Bis-Terpyridine Entities.

Terpyridine ruthenium complexes linked to the dimethyldihydropyrene (DHP) photochromic unit have been synthesized and fully characterized by cyclic voltammetry and absorption and emission spectroscopy. The study of the photoisomerization reaction undergone by the DHP motif under visible light irradiation is reported. In comparison to previous work, the introduction of an electron-withdrawing pyridinium spacer between the chelating terpyridine unit and the DHP skeleton has considerably tuned the photochromic properties of the free ligands and their corresponding complexes in term of time response and photoreversibility.

Light Control of Charge Transfer and Excitonic Transitions in a Carbon Nanotube/Porphyrin Hybrid.

Carbon nanotube-chromophore hybrids are promising building blocks in order to obtain a controlled electro-optical transduction effect at the single nano-object level. In this work, a strong spectral selectivity of the electronic and the phononic response of a chromophore-coated single nanotube transistor is observed for which standard photogating cannot account. This paper investigates how light irradiation strongly modifies the coupling between molecules and nanotube within the hybrid by means of combined Raman diffusion and electron transport measurements.