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Atomically precise gold nanoclusters display properties that are unseen in larger nanoparticles. When the number of gold atoms is sufficiently small, the clusters exhibit molecular properties. Their study requires extensive use of classic molecular physical chemistry and, thus, methods such as vibrational spectroscopies, electrochemistry, density functional theory and molecular dynamics calculations, and of course nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopies. NMR and EPR studies have been mostly carried out on the benchmark, stable molecules Au-25(SR)(18), AU(38)(SR)(24), Au-102(SR)(44), and Au-144(SR)(60) (where SR = thiolate). In this Account, we showcase examples primarily taken from our previous and ongoing NMR and EPR studies, which we hope will trigger further interest in the use of these sensitive, though often underutilized, techniques. Indeed, 1D and 2D NMR spectra of pure, atomically precise clusters can be very detailed and informative. Molecular clusters are molecules and, thus, have discrete energy levels and undergo stepwise oxidation or reduction. The effect of the charge state on the chemical shifts and line shapes is a function of the ligand type (ligands differ due to specific bonds with different Au atom types) and the position of the chemical group along the ligand backbone: for groups near the Au core, they can be very dramatic. Ligand-protected gold clusters are hard-soft molecules where a hard metal core is surrounded by a dynamic molecular layer. The latter provides a nanoenvironment that interfaces the cluster core with the surrounding environment and can be permeated by molecules and ions. NMR spectroscopy is especially useful to assess its structure. For example, the data show that whereas long alkanethiolates form bundles, shorter chains exhibit more conformational freedom and are quite folded. NMR spectroscopy allows studying diastereotopic effects and provides information on possible hydrogen bonds of ligands with sulfur or surface gold atoms. EPR spectroscopy is a very precise technique to check and characterize the magnetic state of gold clusters or clusters doped with foreign-metal atoms. Electron nuclear double resonance (ENDOR) provides a powerful tool to assess the interaction of an unpaired electron with nuclei, as we showed for Au-197 and H-1. It can be used as a sensitive probe of the spin-density distribution in nanoclusters: for example, it showed that the singly occupied molecular orbital may span outside the Au core by nearly 6 angstrom. Solid-state EPR spectroscopy has provided compelling evidence that the specific ligands and the crystallinity degree are very important factors in determining the interactions between clusters in the solid state. Depending on the condition, paramagnetic, superparamagnetic, ferromagnetic, or antiferromagnetic behavior can be observed. Time-resolved EPR was successfully tested to determine the efficiency of singlet-oxygen generation via sensitization of Au-25 clusters. This Account thus demonstrates some of the remarkable insights that can be gained into the properties of atomically precise clusters through detailed NMR and EPR studies.

Protein phosphorylation has a key role in cell regulation. Oxidation of proteins, in turn, is related to many diseases and to aging, but the effects of phosphorylation on the oxidation of proteins and peptides have been rarely studied. The aim of this study was to examine the mechanistic effect of phosphorylation on peptide oxidation induced by titanium dioxide photo catalysis. The effect of phosphorylation was compared between nonphosphorylated and tyrosine phosphorylated peptides using electrospray tandem mass spectrometry. We observed that tyrosine was the most preferentially oxidized amino acid, but the oxidation reaction was significantly inhibited by its phosphorylation. The study also shows that titanium dioxide photocatalysis provides a fast and easy method to study oxidation reactions of biomolecules, such as peptides.

Radiative transitions between the three lowest-lying electronic states of molecular oxygen have long provided a model to study how collision-dependent perturbations influence forbidden processes. In an isolated oxygen molecule, transitions between the O-2(X-3 Sigma(-)(g)), O-2(a(1)Delta(g), and O-2(b(1)Sigma(+)(g)) states are forbidden as electric-dipole processes. For oxygen dissolved in organic solvents, the probabilities of radiative transitions between these states increase appreciably. Attempts to interpret solvent-dependent changes in the radiative rate constants have principally relied on O-2(b(1)Sigma(+)(g)) and O-2(a(1)Delta(g)) emission experiments. However, the dominant nonradiative deactivation channels of O-2(b(1)Sigma(+)(g)) make it difficult to quantify solvent effects on the O-2(b(1)Sigma(+)(g)) -> O-2(a(1)Delta(g)) radiative process. Thus, an appreciable amount of important information has heretofore not been available. In the present study, we examined the effect of 17 common organic solvents on the O-2(a(1)Delta(g)) -> O-2(b(1)Sigma(+)(g)) absorption transition at similar to 5200 cm(-1) (i.e., similar to 1925 nm). The solvent-dependent absorption coefficients at the band maximum, em, range from 5 to 50 M-1 cm(-1) and correlate reasonably well with the solvent refractive index; emax is largest in solvents with the largest refractive index. This observation is consistent with a model in which oxygen is perturbed to a greater extent by solvents with a large electronic polarizability. Through the Strickler-Berg equation, we also used these absorption data to obtain the radiative rate constant for the O-2(b(1)Sigma(+)(g)) -> O-2(a(1)Delta(g)) transition, and the results are consistent with a model in which the O-2(a(1)Delta(g)) -> O-2(X-3 Sigma(-)(g)) transition is said to steal intensity from the O-2(b(1)Sigma(+)(g)) -> O-2(a(1)Delta(g)) transition.

The use of organic photocatalysts for the oxidation of pollutants and model compounds, with special emphasis on the involved concepts and mechanistic aspects, is reviewed. Photoinduced electron transfer involving the singlet excited state of phthalocyanines has been postulated in the photodegradation of phenols. The reactivity of OH - radical with different pollutants has been quantitatively determined by competition experiments, looking at the decrease of the typical transient absorption of the stilbene adduct at 390 nm. As regards heterogeneous media, after excitation at 355 nm of phthalocyanines immobilized in zeolites, the characteristic singlet oxygen luminiscence is monitored at 1270 nm. TPP has been included within extralarge pore zeolitic aluminosilicates, such as MCM-41. These materials provide an adequate balance between moderate cage effect and facilitation of molecular traffic through the mesopores., Financial support from the Spanish Government (CTQ2009- 13699, CTQ2009-13459-C05-03/PPQ, RIRRAF RETICS), and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged. Dedicated to Prof. Avelino Corma on the occasion of his 60th birthday.

The protein phosphatase calcineurin has been gradually revealing itself as the central controller of our immune response, although it is involved in a wide array of signaling pathways related to cellular development and cell cycle progression. As such, calcineurin is an attractive, yet delicate, therapeutic target for the prevention of allograft rejection and treatment of several inflammatory skin conditions. However, calcineurin activity is not only sensitive to immunosuppressants such as cyclosporin A and tacrolimus, but also subject to modulation by reactive oxygen species. We have recently shown, both in vivo and in vitro, that UVA1 radiation suppresses calcineurin activity. In this paper, we present evidence that this activity loss is due to singlet oxygen and superoxide generated by photosensitization and show that a closely related phosphatase, PP2A, is not affected. Furthermore, a survey of this damage reveals oxidation of several Met and Cys residues as well as an overall conformational change. These findings provide a mechanistic basis for the hypothesis that UVA1 and calcineurin inhibitors both affect the same signal transduction pathway in skin. (C) 2011 Elsevier Inc. All rights reserved.

Cinacalcet (CIN) is a calcimimetic drug, which contains a naphthalene chromophore and binds almost quantitatively to human serum albumin (HSA). In the present work, the excited states of CIN have been characterized in order to obtain relevant information about complexation of CIN with HSA. The fluorescence spectrum in acetonitrile, at lambda(exc) = 290 nm, displayed two bands with maxima at 332 and 439 nm, assigned to the monomer and exciplex emission. Upon protonation of the amino group, the exciplex band disappeared, with a concomitant increase of the monomer emission intensity. Time-resolved fluorescence evidenced an intramolecular dynamic quenching, attributed to exciplex formation and/or photoinduced electron transfer, in agreement with the favorable thermodynamics predicted by the Rehm-Weller equations. Diffusion controlled dynamic quenching of CINH(+) fluorescence by oxygen was observed. The emission properties in PBS were similar to those obtained for CINH(+) in acetonitrile. Laser flash photolysis (LFP) of CIN and CINH(+) in aCetonitrile/N(2), at lambda(exc) = 308 nm, gave rise to the naphthalene-like triplet excited states, with maxima at 420 nm and lifetimes of 4 and 7 mu s; they were efficiently quenched by oxygen. No significant singlet excited state interaction was observed in CINH(+)/HSA complexes, as revealed by the emission spectra, which were roughly explained taking into account the relative contributions of drug and protein in the absorption spectra. Upon LFP of the complexes, triplet excited states were generated; the decays monitored at 420 nm were satisfactorily fitted using a function containing two monoexponential terms, corresponding to a Short-lived (tau(1) = 8 mu s) and a long-lived (tau(2) = 37 mu s) component. This indicates that the drug is incorporated into two different binding sites of HSA. Despite the long triplet lifetimes of the CINH(+)/HSA complexes, the rate constant of quenching by oxygen was found to be 2 orders of magnitude lower than that determined in acetonitrile, which can be attributed to the relative slower diffusion rates in this microheterogeneous system. Therefore, the protein microenvironment protects cinacalcet from attack by oxygen; this prevents the phototoxic effects caused by formation of singlet oxygen and results in an enhanced photosafety of the drug., Financial support from the MICINN (Grant CTQ2007-67010), from the Generalitat Valenciana (Prometeo Program, ref 2008/090) and from Carlos III Institute of Health (Grant RIRAAF, RETICS program) is gratefully acknowledged.

Eight complexes with the formula [M(N-N)(DHBA)] (where M=Pd(II) or Pt(II), N-N is 2,2'-bipyridine (BPY), 2,2'-biquinoline (BIQ), 1,10-phenanthroline (PHEN), 4,7-diphenyl-1,10-phenanthroline (DPP) and DHBA is 3,4-dihydroxybenzoic acid dianion) were found to photosensitize the oxidation of 2,2,6,6-tetramethyl-4-piperidinol (NH) in NN-dimethylformamide (DMF) to the nitroxide radical. This photo-oxidation reaction involves singlet molecular oxygen (O-1(2)) as an intermediate and its presence was confirmed by quenching studies using bis(diethyldithiocarbamato)nickel(II), a well known O-1(2) quencher. The ability of these complexes to photosensitize the above photo-oxidation reaction follows the order, [Pt(PHEN)(DHBA)] . H2O > [Pt(DPP)(DHBA)] . H2O > [Pt(BIQ)(DHBA)] > [Pd(PHEN)(DHBA)] > [Pt(BPY)(DHBA)] > [Pd(DPP)(DHBA)] > [Pd(BPY)(DHBA)] . CH3OH > [Pd(BIQ)(DHBA)]. This order depends on the metal ion, the nature of the alpha-diimine ligand and the geometry of the metal complex.

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with Tc-99m. When this Tc-99m-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment. (C) 1997

Intensive research has been focused on the synthesis of N-modified TiO2 materials having visible light absorption in order to get higher solar photocatalytic degradation rates of pollutants in water. However, an exhaustive revision of the topic underlines several controversial issues related to N-modified TiO2 materials; these issues concern (a) the methodology used for preparation, (b) the assessment of the structural characteristics, (c) the mechanistic action modes and (d) the raisons argued to explain the limited performances of the prepared materials for organic and biological targets photodegradation in water. Taking advantage of last year's progress in analytical chemistry and in material characterization methods, the authors show, for example, that some works in the literature controversially attribute the term nitrogen doping without enough analytical evidence. Additionally, some papers describe N-modified TiO2 photocatalysts as being able to generate holes with enough oxidative potential to form hydroxyl radicals under visible light. This last assertion often derives from a no pertinent use of illumination sources, light filters, or targets or a limited understanding of the thermodynamic aspects of the studied systems. None of N-containing materials prepared by herein presented methods leads, under solar light, to a significant enhancement in pollutants degradation and microorganism's inactivation kinetics.

An eye lens is constantly exposed to the solar UV radiation, which is considered the most important external source of age-related changes to eye lens constituents. The accumulation of modifications of proteins and lipids with age can eventually lead to the development of progressive lens opacifications, such as cataracts. Though the impact of solar UV radiation on the structure and function of proteins is actively studied, little is known about the effect of photodamage on plasma membranes of lens cells. In this work we exploit Fluorescence Lifetime Imaging Microscopy (FLIM), together with viscosity-sensitive fluorophores termed molecular rotors, to study the changes in viscosity of plasma membranes of porcine eye lens resulting from two different types of photodamage: Type I (electron transfer) and Type II (singlet oxygen) reactions. We demonstrate that these two types of photodamage result in clearly distinct changes in viscosity - a decrease in the case of Type I damage and an increase in the case of Type II processes. Finally, to simulate age-related changes that occur in vivo, we expose an intact eye lens to UV-A light under anaerobic conditions. The observed decrease in viscosity within plasma membranes is consistent with the ability of eye lens constituents to sensitize Type I photodamage under natural irradiation conditions. These changes are likely to alter the transport of metabolites and predispose the whole tissue to the development of pathological processes such as cataracts.