Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy.

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT.

Intra- vs Intermolecular Aurophilic Contacts in Dinuclear Gold(I) Compounds: Impact on the Population of the Triplet Excited State.

Two series of dinuclear gold(I) complexes that contain two Au-chromophore units (chromophore = dibenzofurane or dimethylfluorene) connected through a diphosphane bridge that differs in the flexibility and length (diphosphane = dppb for 1,4-bis(diphenylphosphino)butane, DPEphos for bis[(2-diphenylphosphino)phenyl]ether, xanthphos for 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and BiPheP for 2,2'-bis(diphenylphosphino)-1,1'-biphenyl) have been synthesized and structurally characterized. Their photophysical properties have been carefully investigated, paying attention to the role of the presence, or absence, of aurophilic contacts and their nature (intra- or intermolecular character). This analysis was permitted due to the X-ray crystallographic determination of all of the structures of the compounds discussed herein. The quantum yields of the triplet population, ϕT, have been calculated by nanosecond-laser flash photolysis measurements, and we could determine the main role of the character of the aurophilic contacts in the resulting ϕT, being especially favored in the presence of intermolecular contacts. Time-dependent density functional theory (TD-DFT) calculations support the absorption and emission assignments and the shorter distance between S1 and the closest triplet excited state energy in the case of the compounds with a higher triplet-state population.

Development of gold(I) phosphorescent tweezers for sensing applications.

The synthesis of the gold(I) alkynyl-fluorene compound 2 containing a diphosphane (dppb = 1,4-bisdiphenylphosphanebutane) has been easily achieved by the treatment of the previously synthesized [2-ethynylfluorene-Au]n polymer (1) and the corresponding dppb diphosphane in an adequate 2 : 1 stoichiometry. Compound 2 shows a boat-tweezer conformation that makes it ideal for being used as a host in molecular recognition processes. Different polyaromatic hydrocarbons (PAHs) and polyfluorinated compounds (PFCs) have been used as guests and a stronger interaction has been detected for PAHs, especially for anthracene, in agreement with spectrofluorometric titrations and the calculated values of the association constants, which is confirmed by DFT calculations. Compound 2 has then been immobilized in different organic matrices, in order to enhance room temperature phosphorescence (RTP). This promotes sensing with dual emission and furthermore in the case of the analytes under investigation, phosphorescence is observed in a range of wavelengths that do not coincide with the fluorescence emission of PAHs and PFCs.

Aggregation versus Biological Activity in Gold(I) Complexes. An Unexplored Concept.

The aggregation process of a series of mono- and dinuclear gold(I) complexes containing a 4-ethynylaniline ligand and a phosphane at the second coordination position (PR3-Au-C≡CC6H4-NH2, complexes 1-5, and (diphos)(Au-C≡CC6H4-NH2)2, complexes 6-8), whose biological activity was previously studied by us, has been carefully analyzed through absorption, emission, and NMR spectroscopy, together with dynamic light scattering and small-angle X-ray scattering. These experiments allow us to retrieve information about how the compounds enter the cells. It was observed that all compounds present aggregation in fresh solutions, before biological treatment, and thus they must be entering the cells as aggregates. Inductively coupled plasma atomic emission spectrometry measurements showed that mononuclear complexes are mainly found in the cytosolic fraction; the dinuclear complexes are mainly found in a subsequent fraction composed of nuclei and cytoskeleton. Additionally, dinuclear complex 8 affects the actin aggregation to a larger extent, suggesting a cooperative effect of dinuclear compounds.

Comprehensive Investigation of the Photophysical Properties of Alkynylcoumarin Gold(I) Complexes.

Six gold(I) complexes (R3P-Au-Coum) containing three different alkynylcoumarin chromophores (Coum) with different electron-donating and electron-withdrawing characteristics and two different water-soluble phosphanes (PR3 = PTA (a) and DAPTA (b)) have been synthesized (1a,b, unsubstituted coumarin; 2a,b, 4-methyl substituted coumarin; 3a,b, 3-chloro and 4-methyl substituted coumarin). A comprehensive study of the photophysical properties of the R3P-Au-Coum, together with their propynyloxycoumarin precursors 1-3, was performed in solution at room and low temperatures. Spectral and photophysical characteristics of the R3P-Au-Coum essentially depend on the electronic characteristics of the propynyloxycoumarin ligand. The presence of the Au(I) atom was found to be responsible for an increase of the intersystem crossing, with triplet state quantum yield values, ϕT, ranging from ∼0.05 to 0.35 and high coumarin phosphorescence quantum yield values for derivatives 1 and 2; fluorescence dominates the deactivation in derivatives 3. Efficient singlet oxygen photosensitization was observed for the new compounds 3a,b. From TDDFT calculations, the relevant HOMO and LUMO of the compounds, i.e., those involved in the transitions, are dominated by the frontier orbitals associated with the coumarin core. The Au(I)-phosphane structure introduces a new transition assigned to an intraligand transition involving the phosphane ligand, and π(C≡C) system, to the p orbitals of phosphorus and gold atoms.

Antioxidant Potential of the Bio-Based Fucose-Rich Polysaccharide FucoPol Supports Its Use in Oxidative Stress-Inducing Systems.

Reactive oxygen species (ROS) are dangerous sources of macromolecular damage. While most derive from mitochondrial oxidative phosphorylation, their production can be triggered by exogenous stresses, surpassing the extinction capacity of intrinsic antioxidant defense systems of cells. Here, we report the antioxidant activity of FucoPol, a fucose-rich polyanionic polysaccharide produced by Enterobacter A47, containing ca. 17 wt% of negatively charged residues in its structure. Ferric reducing antioxidant power (FRAP) assays coupled to Hill binding kinetics fitting have shown FucoPol can neutralize ferricyanide and Fe3+-TPTZ species at an EC50 of 896 and 602 µg/mL, respectively, with positive binding cooperativity (2.52 ≤ H ≤ 4.85). This reducing power is greater than most polysaccharides reported. Moreover, an optimal 0.25% w/v FucoPol concentration shown previously to be cryo- and photoprotective was also demonstrated to protect Vero cells against H2O2-induced acute exposure not only by attenuating metabolic viability decay, but also by accentuating post-stress proliferation capacity, whilst preserving cell morphology. These results on antioxidant activity provide evidence for the biopolymer's ability to prevent positive feedback cascades of the radical-producing Fenton reaction. Ultimately, FucoPol provides a biotechnological alternative for implementation in cryopreservation, food supplementation, and photoprotective sunscreen formula design, as all fields benefit from an antioxidant functionality.

New 3-Ethynylaryl Coumarin-Based Dyes for DSSC Applications: Synthesis, Spectroscopic Properties, and Theoretical Calculations.

A set of 3-ethynylaryl coumarin dyes with mono, bithiophenes and the fused variant, thieno [3,2-b] thiophene, as well as an alkylated benzotriazole unit were prepared and tested for dye-sensitized solar cells (DSSCs). For comparison purposes, the variation of the substitution pattern at the coumarin unit was analyzed with the natural product 6,7-dihydroxycoumarin (Esculetin) as well as 5,7-dihydroxycomarin in the case of the bithiophene dye. Crucial steps for extension of the conjugated system involved Sonogashira reaction yielding highly fluorescent molecules. Spectroscopic characterization showed that the extension of conjugation via the alkynyl bridge resulted in a strong red-shift of absorption and emission spectra (in solution) of approximately 73-79 nm and 52-89 nm, respectively, relative to 6,7-dimethoxy-4-methylcoumarin (λabs = 341 nm and λem = 410 nm). Theoretical density functional theory (DFT) calculations show that the Lowest Unoccupied Molecular Orbital (LUMO) is mostly centered in the cyanoacrylic anchor unit, corroborating the high intramolecular charge transfer (ICT) character of the electronic transition. Photovoltaic performance evaluation reveals that the thieno [3,2-b] thiophene unit present in dye 8 leads to the best sensitizer of the set, with a conversion efficiency (η = 2.00%), best VOC (367 mV) and second best Jsc (9.28 mA·cm-2), surpassed only by dye 9b (Jsc = 10.19 mA·cm-2). This high photocurrent value can be attributed to increased donor ability of the 5,7-dimethoxy unit when compared to the 6,7 equivalent (9b).

Using Room Temperature Phosphorescence of Gold(I) Complexes for PAHs Sensing.

The synthesis of two new phosphane-gold(I)-napthalimide complexes has been performed and characterized. The compounds present luminescent properties with denoted room temperature phosphorescence (RTP) induced by the proximity of the gold(I) heavy atom that favors intersystem crossing and triplet state population. The emissive properties of the compounds together with the planarity of their chromophore were used to investigate their potential as hosts in the molecular recognition of different polycyclic aromatic hydrocarbons (PAHs). Naphthalene, anthracene, phenanthrene, and pyrene were chosen to evaluate how the size and electronic properties can affect the host:guest interactions. Stronger affinity has been detected through emission titrations for the PAHs with extended aromaticity (anthracene and pyrene) and the results have been supported by DFT calculation studies.

Gold(i)-doped films: new routes for efficient room temperature phosphorescent materials.

The synthesis of four novel gold(i)-phosphane complexes coordinated to 9-phenanthrene chromophore has been carried out through the reaction of 9-phenanthreneboronic acid and the corresponding AuClPR3 (PR3 = PPh3 for triphenylphosphane (1a); 1,4-bis(diphenylphosphanyl)butane or dppb (2b); bis(diphenylphosphanyl)acetylene or dppa (2c); (AuCl)2(diphos) (diphos = bis(diphenylphosphanyl)methane or dppm (3)) sources. The X-ray crystal structures of compounds 1a and 2b show the existence of MOF-like intermolecular assemblies that contain empty inner cavities in the absence of aurophilic contacts. In contrast, the formation of a tetranuclear complex with intramolecular aurophilic interactions was evidenced for 3. Photophysical characterization indicates dual emission in all gold(i) complexes when oxygen is removed from the sample, while only fluorescence emission is recorded for the uncoordinated ligand. The introduction of the compounds within PMMA and Zeonex was assayed, and luminescent films containing gold(i) complexes where phosphorescence is the sole pathway for emission are obtained, instead of the dual emission (with significant fluorescence contribution) recorded in solution.

Effect of Gold(I) on the Room-Temperature Phosphorescence of Ethynylphenanthrene.

The synthesis of two series of gold(I) complexes with the general formulae PR3 -Au-C≡C-phenanthrene (PR3 =PPh3 (1 a/2 a), PMe3 (1 b/2 b), PNaph3 (1 c/2 c)) or (diphos)(Au-C≡C-phenanthrene)2 (diphos=1,1-bis(diphenylphosphino)methane, dppm (1 d/2 d), 1,4-bis(diphenylphosphino)butane, dppb (1 e/2 e)) has been realized. The two series differ in the position of the alkynyl substituent on the phenanthrene chromophore, being at the 9-position (9-ethynylphenanthrene) for the L1 series and at the 2-position (2-ethynylphenanthrene) for the L2 series. The compounds have been fully characterized by 1 H, 31 P NMR, and IR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction resolution in the case of compounds 1 a, 1 e, 2 a, and 2 c. The emissive properties of the uncoordinated ligands and corresponding complexes have been studied in solution and within organic matrixes of different polarity (polymethylmethacrylate and Zeonex). Room-temperature phosphorescence (RTP) is observed for all gold(I) complexes whereas only fluorescence can be detected for the pure organic chromophore. In particular, the L2 series presents better luminescent properties regarding the intensity of emission, quantum yields, and RTP effect. Additionally, although the inclusion of all the compounds in organic matrixes induces an enhancement of the observed RTP owing to the decrease in non-radiative deactivation, only the L2 series completely suppresses the fluorescence, giving rise to pure phosphorescent materials.

Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors.

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.

Dinuclear Cu(I) Halides with Terphenyl Phosphines: Synthesis, Photophysical Studies, and Catalytic Applications in CuAAC Reactions.

Several dinuclear terphenyl phosphine copper(I) halide complexes of composition [CuX(PR2Ar')]2 (X = Cl, Br, I; R = hydrocarbyl, Ar' = 2,6-diarylterphenyl radical), 1-5, have been isolated from the reaction of CuX with 1 equiv of the phosphine ligand. Most of them have been characterized by X-ray diffraction studies in the solid state, thus allowing comparative discussions of different structural parameters, namely, Cu···Cu and Cu···Aryl separations, conformations adopted by coordinated phosphines, and planarity of the Cu2X2 cores. Centrosymmetric complexes [CuI(PMe2ArXyl2)]2, 1c, and [CuI(PEt2ArMes2)]2, 3c, despite their similar structures, show very distinct photoluminescence (PL) in powder form at room temperature. The photophysical behavior of these compounds in liquid solution, solid-solid Zeonex solution and powder samples at room temperature and 77 K have been investigated and supported by DFT calculation. Identification of vibronic coupling modes, done by group theory calculations and the technique of projection operators, shows that the manifestation of these modes is conditioned by crystal packing. Complexes [CuI(PMe2ArXyl2)]2, 1c, and [CuI(PEt2ArMes2)]2, 3c, display remarkable activity in copper-catalyzed azide-alkyne cycloaddition reactions involving preformed and in situ-made azides. Reactions are performed in H2O, under aerobic conditions, with low catalyst loadings and tolerate the use of iodoalkynes as substrates.

Microwave Synthesis of Silver Sulfide and Silver Nanoparticles: Light and Time Influence.

Silver sulfide (Ag2S) is a low band gap material, which absorbs near-infrared light and is of great importance in areas such as nanotechnology and biomedicine. We report the influence of the starting reagents, synthesis time, and light radiation on the geometry and size of silver sulfide nanoparticles and on the fraction of metallic Ag obtained in a microwave reactor. The X-ray diffraction diffractograms confirmed that Ag2S is the main product if the reaction's precursor contains silver in the oxidation state of +1 and mostly metallic silver (Ag°) when it is +2. Small nanoparticles (∼6 nm) of spherical geometry are present in the transmission electron microscopy images for the synthesis performed with the lamp light ON, while with the light switched OFF, wider and hundreds of nanometers longer particles are observed. This discriminative effect occurs with shorter synthesis time duration (<10 min) but when the time of reaction is extended, the particles coalesce for both light and dark conditions. Overall, it was observed by photoluminescence that crystalline Ag and Ag2S 4-8 nm nanoparticles obtained in 15 min and light irradiation during synthesis have a clear relative increase of the radiative recombination channels of the charged carriers, which are typical of materials characterized by the involvement of low density of states inside the band gap.

Assessment of Dimethoate in Olive Oil Samples Using a Dual Responsive Molecularly Imprinting-Based Approach.

A new generation of advanced materials developed by molecular imprinting technology showing a stimuli-responsive functionality are emerging. The switchable ability to control the uptake/release of the target analyte by action of external stimulus combined with a remarkable selectivity and specificity, makes these functional materials very attractive for sample preparation purposes. In this work, the usefulness of a sample preparation tool for the selective enrichment/pre-concentration of dimethoate from olive oil spiked samples based on "tailor-made" dual responsive magnetic and photonic molecularly imprinted polymers as sorbents is explored. To achieve this goal, a smart molecularly imprinted polymer (MIP) possessing magnetic and photonic responsiveness was successfully synthesized, and its physico-chemical and morphological characterization was assessed. Further, the trace analysis of dimethoate in spiked olive oil samples was validated and successfully implemented using smart-MIPs as sorbents in the sample preparation step, with high recoveries (83.5 ± 0.3%) and low detection limit (0.03µg·mL-1).

Room-Temperature Phosphorescence and Efficient Singlet Oxygen Production by Cyclometalated Pt(II) Complexes with Aromatic Alkynyl Ligands.

The synthesis of five novel cyclometalated platinum(II) compounds containing five different alkynyl-chromophores was achieved by the reaction of the previously synthesized Pt-Cl cyclometalated compound (1) with the corresponding RC≡CH by a Sonogashira reaction. It was observed that the spectral and photophysical characteristics of the cyclometalated platinum(II) complexes (Pt-Ar) are essentially associated with the platinum-cyclometalated unit. Room-temperature emission of the Pt-Ar complexes was attributed to phosphorescence in agreement with DFT calculations. Broad nanosecond (ns)-transient absorption spectra were observed with decays approximately identical to those obtained from the emission of the triplet state. From the femtosecond-transient absorption (fs-TA) data, two main excited-state decay components were identified: one in the order of a few picoseconds was assigned to fast intersystem crossing to populate the triplet excited-state and the second (hundreds of ns) was associated with the decay of the transient triplet state. In general, efficient singlet oxygen photosensitization quantum yields were observed from the triplet state of these complexes.

Facile morphology control of gold(0) structures from aurophilic assemblies.

Different gold microstructures have been synthesized by using supramolecular gold(i) organometallic compounds as templates and Ag nanoparticles as reducing agents. The use of fibers resulting from supramolecular assemblies of neutral gold(i) compounds gives rise to the formation of microrods. The use of supramolecular assemblies from ionic molecules results in spherical or square-based prism gold microstructures, depending on the shape of the supramolecular gold(i) precursor assembly. In addition to temperature and reaction time, solvents exert a strong influence on the formation and morphology of gold structures, as borne out by the example that well-defined star-like morphologies have been obtained in chloroform.

Luminescent Tetranuclear Gold(I) Dibenzo[g,p]chrysene Derivatives: Effect of the Environment on Photophysical Properties.

A new 2,7,10,15-tetraethynyldibenzo[g,p]chrysene ligand (1) and two tetranuclear gold(I) derivatives containing PPh3 (3) and PMe3 (4) phosphines were synthesized and characterized by 1H and 31P NMR, IR spectroscopy, and high-resolution mass spectrometry. The compounds were studied in order to analyze the effect of the introduction of gold(I) on the supramolecular aggregation and photophysical properties. Absorption and emission spectra displayed broad bands due to the establishment of π π interactions as an indication of intermolecular contacts and the formation of aggregates. A decrease of the recorded quantum yield (QY) of the gold(I) derivatives was observed compared to the uncomplexed ligand. The introduction of the complexes into poly methyl methacrylate (PMMA) and Zeonex 480R matrixes was analyzed, and an increase of the measured QY of 4 in Zeonex was observed. No phosphorescent emission was detected.

Aggregation induced emission of a new naphthyridine-ethynyl-gold(i) complex as a potential tool for sensing guanosine nucleotides in aqueous media.

A new organometallic alkynyl-gold(i) complex capable of exhibiting aggregation induced emission was designed and synthesized. The linear complex structure possesses a central Au(i) atom, bearing two axial ligands: (1) 1,3,5-triaza-7-phosphaadamantane and (2) 2-acetamido-7-ethynyl-1,8-naphthyridine. While the former accounts for its partial solubility in an aqueous environment, the latter acts as a receptor unit for binding guanosine nucleotides and derivatives via multiple hydrogen bonding interactions. At high concentrations, aggregation of the complex was observed by the formation of new absorption (λmax∼ 400 nm) and emission bands (550-700 nm). Formation of aggregates of ca. 60 nm diameter was confirmed by Small Angle X-ray Scattering (SAXS). Disruption of the aggregates in the presence of guanosine derivatives resulted in a ratiometric signal with apparent association constants in the order of 105 M-1 and high sensitivity (around 63% signal change) which are, to the best of our knowledge, in line with the highest values recorded for nucleotide sensors based on hydrogen bonding and capable of working in water. Computational studies indicate the presence of additional hydrogen bonding interactions that account for the strong binding of the Au(i) complex to phosphorylated guanosine nucleotides.

Experimental Evaluation of the Thermal Polarization in Direct Contact Membrane Distillation Using Electrospun Nanofiber Membranes Doped With Molecular Probes.

Membrane distillation (MD) has recently gained considerable attention as a valid process for the production of fresh-water due to its ability to exploit low grade waste heat for operation and to ensure a nearly feed concentration-independent production of high-purity distillate. Limitations have been related to polarization phenomena negatively affecting the thermal efficiency of the process and, as a consequence, its productivity. Several theoretical models have been developed to predict the impact of the operating conditions of the process on the thermal polarization, but there is a lack of experimental validation. In this study, electrospun nanofiber membranes (ENMs) made of Poly(vinylidene fluoride) (PVDF) and doped with (1, 10-phenanthroline) ruthenium (II) Ru(phen)3 were tested at different operating conditions (i.e., temperature and velocity of the feed) in direct contact membrane distillation (DCMD). The temperature sensitive luminophore, Ru(phen)3, allowed the on-line and non-invasive mapping of the temperature at the membrane surface during the process and the experimental evaluation of the effect of the temperature and velocity of the feed on the thermal polarization.

Facile Microwave-assisted Synthesis Manganese Doped Zinc Sulfide Nanoparticles.

Undoped and manganese doped zinc sulfide nanoparticles were produced by a fast, one-step and two-component microwave-assisted synthesis method. The solid phase retains around 78% of the initial Mn concentration, as revealed by Particle Induced X-ray Emission analysis. X-ray diffraction patterns confirmed zinc blende structure and in the transmission electron microscopy images, nanoparticles with triangular prism and cube shapes were observed, respectively with an average particle size around 7 nm and 13 nm. Dried powders of zinc sulfide nanoparticles, doped with 0.1 mol% and 0.7 mol% of Mn ions, show highest brilliance of luminescence under UV light. Increasing dopant levels resulted in a diminishing emission that vanishes above 4% of dopant concentration. The synthesis of ZnS was monitored and two main events were detected, one at 145 °C corresponding to the sol-gel phase formation and another after ~3 min at 300 °C where the precipitation of the zinc sulfide nanoparticles occurs.