Ruthenium nitrosyl complexes with NO release capability: the use of fluorene as an antenna.

A ruthenium nitrosyl complex of formula [RuII(fluorene(C6)CH2O-terpy)(bipy)(NO)]3+ (AC) in which fluorene(C6) is the 9,9-dihexylfluorene, terpy the 2,2';6',2''-terpyridine, and bipy the 2,2'-bipyridine is presented with its related [RuII(MeO-terpy)(bipy)(NO)]3+ (C) and 9,9-dihexylfluorene 2-hydroxymethylfluorene (A) building blocks. The reference complex C undergoes NO release capabilities under irradiation at λ = 365 nm. The effect of the introduction of the fluorescent A antenna within the resulting AC complex is discussed both experimentally and theoretically. The importance of the encaging parameter defined as ϕAC·IAC, in which IAC is the quantity of light absorbed by AC and ϕAC the quantum yield of NO release is evidenced and found to be concentration dependent. The conditions of optimization of the antenna approach to maximize ϕAC·IAC are discussed. The crystal structure of [RuII(fluorene(C6)CH2O-terpy)(bipy)(NO2)](PF6), the last intermediate in the synthesis of AC is also presented.

Photorelease of Nitric Oxide (NO) in Mono- and Bimetallic Ruthenium Nitrosyl Complexes: A Photokinetic Investigation with a Two-Step Model.

Two monometallic and three bimetallic ruthenium acetonitrile (RuMeCN) complexes are presented and fully characterized. All of them are built from the same skeleton [FTRu(bpy)(MeCN)]2+, in which FT is a fluorenyl-substituted terpyridine ligand and bpy is the 2,2'-bipyridine. The crystal structure of [FTRu(bpy)(MeCN)](PF6)2 is presented. A careful spectroscopic analysis allows establishing that these 5 RuMeCN complexes can be identified as the product of the photoreaction of 5 related RuNO complexes, investigated as efficient nitric oxide (NO) donors. Based on this set of complexes, the mechanism of the NO photorelease of the bimetallic complexes has been established through a complete investigation under irradiations performed at 365, 400, 455, and 490 nm wavelength. A two-step (A → B → C) kinetic model specially designed for this purpose provides a good description of the mechanism, with quantum yields of photorelease in the range 0.001-0.029, depending on the irradiation wavelength. In the first step of release, the quantum yields (ϕAB) are always found to be larger than those of the second step (ϕBC), at any irradiation wavelengths.

Acetylacetonate Ruthenium Nitrosyls: A Gateway to Nitric Oxide Release in Water under Near-Infrared Excitation by Two-Photon Absorption.

A fundamental challenge for phototriggered therapies is to obtain robust molecular frameworks that can withstand biological media. Photoactivatable nitric oxide (NO) releasing molecules (photoNORMs) based on ruthenium nitrosyl (RuNO) complexes are among the most studied systems due to several appealing features that make them attractive for therapeutic applications. Nevertheless, the propensity of the NO ligand to be attacked by nucleophiles frequently manifests as significant instability in water for this class of photoNORMs. Our approach to overcome this limitation involved enhancing the Ru-NO π-backbonding to lower the electrophilicity at the NO by replacing the commonly employed 2,2'-bipyridine (bpy) ligand by an anionic, electron-rich, acetylacetonate (acac). A versatile and convenient synthetic route is developed and applied for the preparation of a large library of RuNO photoNORMs with the general formula [RuNO(tpy)(acac)]2+ (tpy = 2,2':6',2″-terpyridine). A combined theoretical and experimental analysis of the Ru-NO bonding in these complexes is presented, supported by extensive single-crystal X-ray diffraction experiments and by topological analyses of the electron charge density by DFT. The enhanced π-back-bonding, systematically evidenced by several techniques, resulted in a remarkable stability in water for these complexes, where significant NO release efficiencies were recorded. We finally demonstrate the possibility of obtaining sophisticated water-stable multipolar NO-delivery platforms that can be activated in the near-IR region by two-photon absorption (TPA), as demonstrated for an octupolar complex with a TPA cross section of 1530 GM at λ = 800 nm and for which NO photorelease was demonstrated under TPA irradiation in aqueous media.

A Trojan horse approach for enhancing the cellular uptake of a ruthenium nitrosyl complex.

Ruthenium nitrosyl (RuNO) complexes continue to attract significant research interest due to several appealing features that make these photoactivatable nitric oxide (NO˙) donors attractive for applications in photoactivated chemotherapy. Interesting examples of molecular candidates capable of delivering cytotoxic concentrations of NO˙ in aqueous media have been discussed. Nevertheless, the question of whether most of these highly polar and relatively large molecules are efficiently incorporated by cells remains largely unanswered. In this paper, we present the synthesis and the chemical, photophysical and photochemical characterization of RuNO complexes functionalized with 17α-ethinylestradiol (EE), a semisynthetic steroidal hormone intended to act as a molecular Trojan horse for the targeted delivery of RuNO complexes. The discussion is centered around two main molecular targets, one containing EE (EE-Phtpy-RuNO) and a reference compound lacking this biological recognition fragment (Phtpy-RuNO). While both complexes displayed similar optical absorption profiles and NO˙ release efficiencies in aqueous media, important differences were found regarding their cellular uptake towards dermal fibroblasts, with EE-Phtpy-RuNO gratifyingly displaying a remarkable 10-fold increase in cellular uptake when compared to Phtpy-RuNO, thus demonstrating the potential drug-targeting capabilities of this biomimetic steroidal conjugate.

"Click" Chemistry for the Functionalization of Graphene Oxide with Phosphorus Dendrons: Synthesis, Characterization and Preliminary Biological Properties.

Two families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified-GO and GO-dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses. In addition, the free dendrons and the dendrons grafted to GO were tested toward cancerous (HCT116) and non-cancerous (RPE1) cell lines.

Etching suppression as a means to Pt dendritic ultrathin nanosheets by seeded growth.

2D ultrathin metal nanostructures are emerging materials displaying distinct physical and chemical properties compared to their analogues of different dimensionalities. Nanosheets of fcc metals are intriguing, as their crystal structure does not favour a 2D configuration. Thanks to their increased surface-to-volume ratios and the optimal exposure of low-coordinated sites, 2D metal nanostructures can be advantageously exploited in catalysis. Synthesis approaches to ultrathin nanosheets of pure platinum are scarce compared to other noble metals and to Pt-based alloys. Here, we present the selective synthesis of Pt ultrathin nansosheets by a simple seeded-growth method. The most crucial point in our approach is the selective synthesis of Pt seeds comprising planar defects, a main driving force for the 2D growth of metals with fcc structure. Defect engineering is employed here, not in order to disintegrate, but for conserving the defect comprising seeds. This is achieved by in situ elimination of the principal etching agent, chloride, which is present in the PtCl2 precursor. As a result of etching suppression, twinned nuclei, that are selectively formed during the early stage of nucleation, survive and grow to multipods comprising planar defects. Using the twinned multipods as seeds for the subsequent 2D overgrowth of Pt from Pt(acac)2 yields ultrathin dendritic nanosheets, in which the planar defects are conserved. Using phenylacetylene hydrogenation as a model reaction of selective hydrogenation, we compared the performance of Pt nanosheets to that of a commercial Pt/C catalyst. The Pt nanosheets show better stability and much higher selectivity to styrene than the commercial Pt/C catalyst for comparable activity.

Bimetallic Ruthenium Nitrosyl Complexes with Enhanced Two-Photon Absorption Properties for Nitric Oxide Delivery.

One monometallic and three bimetallic ruthenium nitrosyl (RuNO) complexes are presented and fully characterized in reference to a parent monometallic complex of formula [FTRu(bpy)(NO)]3+ , where FT is a fluorenyl-substituted terpyridine ligand, and bpy the 2,2'-bipyridine. These new complexes are built with the new ligands FFT, TFT, TFFT, and TF-CC-TF (where an alkyne C≡C group is inserted between two fluorenes). The crystal structures of the bis-RuNO2 and bis-RuNO complexes built from the TFT ligand are presented. The evolution of the spectroscopic features (intensities and energies) along the series, at one-photon absorption (OPA) correlates well with the TD-DFT computations. A spectacular effect is observed at two-photon absorption (TPA) with a large enhancement of the molecular cross-section (σTPA ), in the bimetallic species. In the best case, σTPA is equal to 1523±98 GM at 700 nm, in the therapeutic window of transparency of biological tissues. All compounds are capable of releasing NO⋅ under irradiation, which leads to promising applications in TPA-based drug delivery.

Crystal structure of 1,1'-(pyridine-2,6-di-yl)bis-[N-(pyridin-2-ylmeth-yl)methanaminium] dichloride dihydrate.

In the title compound, C19H23N5 2+·2Cl-·2H2O, the two pyridine side arms are not coplanar, with the terminal pyridine rings subtending a dihedral angle of 26.45 (6)°. In the crystal, hydrogen bonds, inter-molecular C-H⋯Cl contacts and a weak C-H⋯O inter-action connect the mol-ecule with neighbouring chloride counter-anions and lattice water mol-ecules. The crystal packing also features by π-π inter-actions with centroid-centroid distances of 3.4864 (12) and 3.5129 (13) Å.

Polarizability is a key parameter for molecular electronics.

Identifying descriptors that govern charge transport in molecular electronics is of prime importance for the elaboration of devices. The effects of molecule characteristics, such as size, bulkiness or charge, have been widely reported. Herein, we show that the molecule polarizability can be a crucial parameter to consider. To this end, platinum nanoparticle self-assemblies (PtNP SAs) are synthesized in solution, including a series of polyoxometalates (POMs). The charge of the POM unit can be modified according to the nature of the central heteroatom while keeping its size constant. POM hybrids that display remote terminal thiol functions strongly anchor the PtNP surface to form robust SAs. IV curves, recorded by conductive AFM, show a decrease in Coulomb blockade as the dielectric constant of the POMs increases. In this system, charge transport across molecular junctions can be interpreted as variations in polarizability, which is directly related to the dielectric constant.

Multistep Photochemical Reactions of Polypyridine-Based Ruthenium Nitrosyl Complexes in Dimethylsulfoxide.

The photorelease of nitric oxide (NO·) has been investigated in dimethylsulfoxide (DMSO) on two compounds of formula [Ru(R-tpy)(bpy)(NO)](PF6)3, in which bpy stands for 2,2'-bipyridine and R-tpy for the 4'-R-2,2':6',2″-terpyridine with R = H and MeOPh. It is observed that both complexes are extremely sensitive to traces of water, leading to an equilibrium between [Ru(NO)] and [Ru(NO2)]. The photoproducts of formula [Ru(R-tpy)(bpy)(DMSO)](PF6)2 are further subjected to a photoreaction leading to a reversible linkage isomerization between the stable Ru-DMSO(S) (sulfur linked) and the metastable Ru-DMSO(O) (oxygen linked) species. A set of 4 [Ru(R-tpy)(bpy)(DMSO)]2+ complexes (R = H, MeOPh, BrPh, NO2Ph) is investigated to characterize the ratio and mechanism of the isomerization which is tentatively related to the difference in absorbance between the Ru-DMSO(S) and Ru-DMSO(O) forms. In addition, the X-ray crystal structures of [Ru(tpy)(bpy)(NO)](PF6)3 and [Ru(MeOPh-tpy)(bpy)(DMSO(S))](PF6)2 are presented.

Chemical and photochemical behavior of ruthenium nitrosyl complexes with terpyridine ligands in aqueous media.

The synthesis and behavior in water of a set of various cis(Cl,Cl)-[R-tpyRuCl2(NO)](PF6) and trans(Cl,Cl)-[R-tpyRuCl2(NO)](PF6) (R = fluorenyl, phenyl, thiophenyl; tpy = 2,2':6',2''-terpyridine) complexes are presented. In any case, one chlorido ligand is substituted by a hydroxo ligand and the final species arises as a single trans(NO,OH) isomer, whatever the nature of the starting cis/trans(Cl,Cl) complexes. Six X-ray crystal structures are presented for cis(Cl,Cl)-[thiophenyl-tpyRuCl2(NO)](PF6) (cis-3a), trans(Cl,Cl)-[thiophenyl-tpyRuCl2(NO)](PF6) (trans-3a), trans(NO,OH)-[phenyl-tpyRu(Cl)(OH)(NO)](PF6) (4a), trans(NO,OH)-[thiophenyl-tpyRu(Cl)(OH)(NO)](PF6) (4b), trans(NO,OEt)-[phenyl-tpyRu(Cl)(OEt)(NO)](PF6) (5a), and trans(NO,OH)-[phenyl-tpyRu(Cl)(OEt)(NO)](PF6) (5b) compounds. The different cis/trans(Cl,Cl) complexes exhibit an intense low-lying transition in the λ = 330-390 nm range, which appears to be slightly blue-shifted after Cl → OH substitution. In water, both cis/trans(Cl,Cl) isomers are converted to a single trans(NO,OH) isomer in which one chlorido- is replaced by one hydroxo-ligand, which avoids tedious separation workout. The water stable trans(NO,OH)-species all release NO with quantum yields of 0.010 to 0.075 under irradiation at 365 nm. The properties are discussed with computational analysis performed within the framework of Density Functional Theory.

Author Correction: Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

Antibiotic resistance is becoming a global scourge with 700,000 deaths each year and could cause up to 10 million deaths by 2050. As an example, Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. S. epidermidis can form biofilms, which contribute to its pathogenicity when present in intravascular devices. These staphylococci, embedded in the biofilm matrix, are resistant to methicillin, which had long been the recommended therapy and which has nowadays been replaced by less toxic and more stable therapeutic agents. Moreover, current reports indicate that 75 to 90% of Staphylococcus epidermidis isolates from nosocomial infections are methicillin-resistant strains. The challenge of successfully combating antibiotics resistance in biofilms requires the use of compounds with a controlled mode of action that can act in combination with antibiotics. Ruthenium nitrosyl complexes are potential systems for NO release triggered by light. The influence of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) on Staphylococcus epidermidis resistant to methicillin is described. The results show a 50% decrease in cell viability in bacteria treated with low concentrations of NO. When combined with methicillin, this low dose of NO dramatically decreases bacterial resistance and makes bacteria 100-fold more sensitive to methicillin.