Divalent ansa-Octaphenyllanthanocenes: Synthesis, Structures, and EuII Luminescence.

Reductive dimerization of fulvenes using low-valent metal precursors is a straightforward one-step approach to access ethylene-bridged metallocenes. This process has so far mainly been employed with fulvenes carrying one or two substituents in the exocyclic position. In this work, a new synthesis of the unsubstituted exocyclic 1,2,3,4-tetraphenylfulvene (1), its full structural characterization by NMR spectroscopy and single-crystal X-ray diffraction, as well as some photophysical properties and its first use in reductive dimerization are described. This fulvene reacted with different lanthanoid metals in thf to provide the divalent ansa-octaphenylmetallocenes [Ln(C5Ph4CH2)2(thf)n] (Ln = Sm, n = 2 (2); Ln = Eu, n = 2 (3); and Ln = Yb, n = 1 (4)). These complexes were characterized by X-ray diffraction, laser desorption/ionization time of flight mass spectrometry, and, in the case of Sm and Yb, multinuclear NMR spectroscopy, showing the influence of the ansa-bridge on solution and solid-state structures compared to previously reported unbridged metallocenes. Furthermore, the luminescence properties of the Eu ansa complex 3 were studied in solution and the solid state, revealing significant differences with the known octa- and deca-phenyleuropocenes, [Eu(C5Ph4H)2(dme)] and [Eu(C5Ph5)2].

Unprecedented Self-Organized Monolayer of a Ru(II) Complex by Diazonium Electroreduction.

A new heteroleptic polypyridyle Ru(II) complex was synthesized and deposited on surface by the diazonium electroreduction process. It yields to the covalent grafting of a monolayer. The functionalized surface was characterized by XPS, electrochemistry, AFM, and STM. A precise organization of the molecules within the monolayer is observed with parallel linear stripes separated by a distance of 3.8 nm corresponding to the lateral size of the molecule. Such organization suggests a strong cooperative process in the deposition process. This strategy is an original way to obtain well-controlled and stable functionalized surfaces for potential applications related to the photophysical properties of the grafted chromophore. As an exciting result, it is the first example of a self-organized monolayer (SOM) obtained using diazonium electroreduction.

Optical and photophysical properties of anisole- and cyanobenzene-substituted perylene diimides.

One- and two-photon absorption cross-sections and spectra and the photophysical properties of eight perylenetetracarboxy-3,4:9,10-diimide (PDI) derivatives are reported and analyzed. The investigated compounds are characterized by direct binding of the phenyl rings of the substituents to the bay positions of the perylene core. They have been designed to test the effects of differences in the electronic nature - electron donating (anisole) or accepting (cyanobenzene) - and binding topology (cis or trans, meta or para disubstitution or tetrasubstitution) of the bay substituents on the above optical and photophysical observables. (TD)DFT and Hückel MO calculations have provided theoretical information on the ground-state geometries, the MOs and the electronic spectra of several model compounds. For tetrasubstituted and cis disubstituted derivatives, strong steric interactions in the bay area determined the preferred conformations, with perylene cores distorted near the substituted bay(s) and a 42-44° twisting of the substituent rings relative to the core, quite irrespective of the electronic nature of the substituents. On the other hand, in trans-disubstituted PDI steric hindrance in the bay areas was much weaker and similar in the cyanobenzene and the anisole derivatives. So, the large differences found in the conformational preferences were completely attributable to electronic effects. With electron-accepting cyanobenzene, the substituent rings were found normal to the central planar perylene core, thus enabling the assignment of the moderate spectroscopic effects to inductive interactions. The DFT analysis of the PDI trans-disubstituted with electron-donating anisoles gave quite strongly distorted perylene-core geometries and less twisted (59°) substituent rings. The corresponding increased substituent/core conjugative interactions resulted in new CT allowed electronic transitions and an extremely pronounced solvent-polarity dependence of the emission spectra and intensities. All anisole substituted PDI feature a very fast radiationless decay path in polar solvents, likely related to a relaxation to a charge-separated configuration in the lowest excited-state.

Two-photon Absorption Engineering of 5-(Fluorenyl)-1,10-phenanthroline-based Ru(II) Complexes.

This study deals with the fine tuning of the photophysical characteristics, and especially two-photon absorption (2PA) properties, of several homo- and heteroleptic ruthenium(II) complexes involving 5-substituted-1,10-phenanthroline ligands. The 2PA spectra of the complexes were determined in the 700-930 nm range by investigating their two-photon excited luminescence (2PEL). Structure - linear and nonlinear optical properties correlations are discussed, and potential applications (therapy and optical power limiting in the near infrared) can be anticipated.

A 5-(difluorenyl)-1,10-phenanthroline-based Ru(II) complex as a coating agent for potential multifunctional gold nanoparticles.

The synthesis and photophysical properties of small gold nanoparticles (NPs, AuNP-[Ru-PFF]) surface functionalized by 5-substituted-1,10-phenanthroline-ligand based Ru(II) complexes are described. Luminescence of the grafted and confined Ru(II) complexes is totally quenched on the gold surface. Nonlinear optical properties were determined via Z-scan measurements in the range 600-1300 nm for both the free Ru(II) complex and the related NPs. In the short wavelength range (around 600 nm) the behaviour switches from that of two-photon absorption (2PA) for the complex to saturable absorption for the NPs. 2PA applications such as optical power limiting or two-photon dioxygen sensitization can be anticipated for these nanoplatforms.

A top-down synthesis route to ultrasmall multifunctional Gd-based silica nanoparticles for theranostic applications.

New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd(3+) chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd(3+) by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, (29)Si solid-state NMR, (1)H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s(-1) mM(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd(3+) is strongly chelated to DOTAGA (complexation constant logß110 =24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.

Impact of mucus and biofilm on antimicrobial photodynamic therapy: Evaluation using Ruthenium(II) complexes.

The biofilm lifestyle of bacterial pathogens is a hallmark of chronic lung infections such as in cystic fibrosis (CF) patients. Bacterial adaptation to the complex conditions in CF-affected lungs and repeated antibiotherapies lead to increasingly tolerant and hard-to-treat biofilms. In the context of growing antimicrobial resistance and restricted therapeutic options, antimicrobial photodynamic therapy (aPDT) shows great promise as an alternative to conventional antimicrobial modalities. Typically, aPDT consists in irradiating a non-toxic photosensitizer (PS) to generate reactive oxygen species (ROS), which kill pathogens in the surrounding environment. In a previous study, we reported that some ruthenium (II) complexes ([Ru(II)]) can mediate potent photodynamic inactivation (PDI) against planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus clinical isolates. In the present work, [Ru(II)] were further assayed to evaluate their ability to photo-inactivate such bacteria under more complex experimental conditions better recapitulating the microenvironment in lung infected airways. Bacterial PDI was tentatively correlated with the properties of [Ru(II)] in biofilms, in mucus, and following diffusion across the latter. Altogether, the results obtained demonstrate the negative impacting role of mucus and biofilm components on [Ru(II)]-mediated PDT, following different possible mechanisms of action. Technical limitations were also identified that may be overcome, making this report a pilot for other similar studies. In conclusion, [Ru(II)] may be subjected to specific chemical engineering and/or drug formulation to adapt their properties to the harsh micro-environmental conditions of the infected respiratory tract.

Ruthenium(II) Polypyridyl Complexes for Antimicrobial Photodynamic Therapy: Prospects for Application in Cystic Fibrosis Lung Airways.

Antimicrobial photodynamic therapy (aPDT) depends on a variety of parameters notably related to the photosensitizers used, the pathogens to target and the environment to operate. In a previous study using a series of Ruthenium(II) polypyridyl ([Ru(II)]) complexes, we reported the importance of the chemical structure on both their photo-physical/physico-chemical properties and their efficacy for aPDT. By employing standard in vitro conditions, effective [Ru(II)]-mediated aPDT was demonstrated against planktonic cultures of Pseudomonas aeruginosa and Staphylococcus aureus strains notably isolated from the airways of Cystic Fibrosis (CF) patients. CF lung disease is characterized with many pathophysiological disorders that can compromise the effectiveness of antimicrobials. Taking this into account, the present study is an extension of our previous work, with the aim of further investigating [Ru(II)]-mediated aPDT under in vitro experimental settings approaching the conditions of infected airways in CF patients. Thus, we herein studied the isolated influence of a series of parameters (including increased osmotic strength, acidic pH, lower oxygen availability, artificial sputum medium and biofilm formation) on the properties of two selected [Ru(II)] complexes. Furthermore, these compounds were used to evaluate the possibility to photoinactivate P. aeruginosa while preserving an underlying epithelium of human bronchial epithelial cells. Altogether, our results provide substantial evidence for the relevance of [Ru(II)]-based aPDT in CF lung airways. Besides optimized nano-complexes, this study also highlights the various needs for translating such a challenging perspective into clinical practice.

A novel ruthenium(II) complex for two-photon absorption-based optical power limiting in the near-IR range.

In this article, the synthesis of a novel high-conjugated ligand and its corresponding Ru(II) complex PTFTF:Ru is reported, along with the linear and nonlinear optical characterizations. Two-photon absorption based optical power limiting properties (OPL), especially in the near infrared, are described and compared to those of the analogous complexes previously published. Combined with a preliminary theoretical approach, this allows us to highlight several key parameters for OPL optimization in such molecular systems and more particularly the spectral overlap between TPA and excited-state absorption.

Molecular engineering for optical properties of 5-substituted-1,10-phenanthroline-based Ru(II) complexes.

A series of homo- and heteroleptic Ru(ii) complexes [Ru(phen)3-n(phen-X)n](PF6)2 (n = 0-3, X = CN, epoxy, H, NH2) were prepared and characterized. The influence of electron-withdrawing or electron-releasing substituents of the 1,10-phenanthroline ligands on the photo-physical properties was evaluated. It reveals fundamental interests in the fine tuning of redox potentials and photo-physical characteristics, depending both on the nature of the substitution of the ligand, and on the symmetry of the related homo- or heteroleptic complex. These complexes exhibit linear absorption and two-photon absorption (2PA) cross-sections over a broad range of wavelength (700-900 nm) due to absorption in the intra-ligand charge transfer (ILCT) and the metal-to-ligand charge transfer (MLCT) bands. These 2PA properties were more particularly investigated in the 700-1000 spectral range for a family of complexes bearing electro-donating ligands (phen-NH2).

Covalent Grafting of Ruthenium Complexes on Iron Oxide Nanoparticles: Hybrid Materials for Photocatalytic Water Oxidation.

The present environmental crisis prompts the search for renewable energy sources such as solar-driven production of hydrogen from water. Herein, we report an efficient hybrid photocatalyst for water oxidation, consisting of a ruthenium polypyridyl complex covalently grafted on core/shell Fe@FeOx nanoparticles via a phosphonic acid group. The photoelectrochemical measurements were performed under 1 sun illumination in 1 M KOH. The photocurrent density of this hybrid photoanode reached 20 µA/cm2 (applied potential of +1.0 V vs reversible hydrogen electrode), corresponding to a turnover frequency of 0.02 s-1. This performance represents a 9-fold enhancement of that achieved with a mixture of Fe@FeOx nanoparticles and a linker-free ruthenium polypyridyl photosensitizer. This increase in performance could be attributed to a more efficient electron transfer between the ruthenium photosensitizer and the Fe@FeOx catalyst as a consequence of the covalent link between these two species through the phosphonate pendant group.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies.

Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlights the current state of the art of curative or preventive aPDT applications with relevant clinical trials. In addition, the most recent developments in photochemistry and photophysics as well as advanced carrier systems in the context of aPDT are provided, with a focus on the latest generations of efficient and versatile PSs and the progress towards hybrid-multicomponent systems. In particular, deeper insight into combinatory aPDT approaches is afforded, involving non-radiative or other light-based modalities. Selected aPDT perspectives are outlined, pointing out new strategies to target and treat microorganisms. Finally, the review works out the evolution of the conceptually simple PDT methodology towards a much more sophisticated, integrated, and innovative technology as an important element of potent antimicrobial strategies.

A rational design of catechol-based compounds: an experimental and theoretical study of optical properties.

The synthesis and optical properties of 4,5-disubstituted (tert-butyldimethylsilyloxy)-protected catechol derivatives are reported. One or two carbon-carbon triple bond functions were introduced through the Sonogashira cross-coupling reaction. The effects on the optical properties of monosubstitution at the 4-position or disubstitution at the 4- and 5-positions of these catechol derivatives with electron-withdrawing or -donating substituents have been investigated. The experimental chemical-structure-polarisability relationship has been studied by using the Lippert-Mataga correlation and compared with the results of a theoretical study carried out with DFT calculations. These compounds are promising candidates for the fine-tuning of internal charge transfer, but also as potential non-linear chromophores and ligands within multifunctional coordination complexes.

Gold hollow spheres obtained using an innovative emulsion process: towards multifunctional Au nanoshells.

The tremendous development of materials with fine tuning of their composition, shape, size and chemical functionalities at the nanometer scale has opened a wide range of applications, particularly in medicine. Metallic nanoparticles are extremely interesting for such developments. The fundamental study of surface plasmon resonance (SPR) versus the shape/size of a particle is an important challenge. In this field, we propose a synthetic strategy using an original biphasic emulsion process linked to chemo-reduction of gold salt HAuCl(4). This method allows the preparation of new functional nanocapsules. These nanomaterials are fully characterized.

One-Dimensional Double Wires and Two-Dimensional Mobile Grids: Cobalt/Bipyridine Coordination Networks at the Solid/Liquid Interface.

Various architectures have been generated and observed by STM at a solid/liquid interface resulting from an in situ chemical reaction between the bipyridine terminal groups of a ditopic ligand and Co(II) ions. Large monodomains of one-dimensional (1D) double wires are formed by Co(II)/ligand coordination, with polymer lengths as long as 150 nm. The polymers are organized as parallel wires 8 nm apart, and the voids between wires are occupied by solvent molecules. Two-dimensional (2D) grids, showing high surface mobility, coexist with the wires. The wires are formed from linear chain motifs where each cobalt center is bonded to two bipyridines. 2D grids are generated from a bifurcation node where one cobalt bonds to three bipyridines. Surface reconstruction of the grids and of the 1D wires was observed under the STM tip. As an exciting result, analysis of these movements strongly indicates surface reactions at the solid/liquid interface.

High-Relaxivity Gd(III)-Hemicryptophane Complex.

The polytopic hemicryptophane cage HC1 combining a cyclotriveratrylene (CTV) unit and a tris(2-aminoethyl)amine (tren) moiety connected by three 2-hydroxyisophthalamide linkers was synthesized in 12 steps. The resulting highly functionalized covalent host is soluble in aqueous medium and has been used to complex Gd(III) ion. The Gd(III)@HC1 complex presents promising relaxivity properties when compared to the clinically used Dotarem MRI agent.

Ruthenium(II) Polypyridyl Complexes as Photosensitizers for Antibacterial Photodynamic Therapy: A Structure-Activity Study on Clinical Bacterial Strains.

As a growing public health concern, the worldwide spread of antimicrobial resistance urges the development of new therapies. Antibacterial photodynamic therapy (a-PDT) may be an alternative to conventional antibiotic therapy. Herein we report the synthesis and characterization of seven original reactive oxygen species (ROS)-producing ruthenium(II) polypyridyl complexes. These are part of a collection of 17 derivatives varying in terms of the nature of the substituent(s), molecular symmetry, electrical charge, and counterions. They were characterized by considering 1) their physical properties (absorption coefficient at irradiation wavelength, 1 O2 generation quantum yield, luminescence) and 2) their antibacterial activity in a series of photodynamic assays using Gram-positive and Gram-negative bacteria of clinical relevance. The results unveiled some structure-activity relationships: one derivative that combines multiple beneficial features for a-PDT was effective against all the bacteria considered, regardless of their Gram status, species, or antibiotic resistance profile. This systematic study could guide the design of next-generation ruthenium-based complexes for enhanced antibacterial photodynamic strategies.

Silica-Based Nanoparticles as Bifunctional and Bimodal Imaging Contrast Agents.

New bifunctional and bimodal nanoparticles (NPs) have been elaborated and characterised. They are based on silica NPs that incorporate a silylated ruthenium tris-bipyridine complex. The resulting suspension of amine-modified NPs with diameters of 20 nm was post-functionalised with a stable gadolinium ion complex. Interest in these NPs lies mainly in the confinement of optical and magnetic imaging agents (Ru and Gd complexes, respectively) within the NP volume. Their potential use as a bimodal probe (luminescence/magnetic resonance imaging) and theranostic agent (photodynamic therapy/imaging) is described. The biological potential of these NPs has been studied on HCT-116 cells and microscopy and cytotoxicity results are given.