Metal nanoclusters: from fundamental aspects to electronic properties and optical applications.

Monolayer-protected noble metal clusters, also called nanoclusters, can be produced with the atomic precision and in large-scale quantity and are playing an increasingly important role in the field of nanoscience. To outline the origin and the perspectives of this new field, we overview the main results obtained on free metal clusters produced in gas phase including mainly electronic properties, the giant atom concept, the optical properties, briefly the role of the metal atom (alkali, divalent, noble metal) and finally the atomic structure of clusters. We also discuss the limitations of the free clusters. Then, we describe the field of monolayer-protected metal clusters, the main results, the new offered perspectives, the added complexity, and the role of the ligand beyond the superatom concept.

Hydrogen-Induced Adsorption of Carbon Monoxide on the Gold Dimer Cation: A Joint Experimental and DFT Investigation.

It is demonstrated, using tandem mass spectrometry and radio frequency ion trap, that the adsorption of a H atom on the gold dimer cation, Au2H+, prevents its dissociation and allows for adsorption of CO. Reaction kinetics are measured by employing a radio frequency ion trap, where Au2+ and CO interact for a given reaction time. The effect of a hydrogen atom is evaluated by comparing reaction rate constants measured for Au2+ and Au2H+. The theoretical results for the adsorption of CO molecules and their reaction characteristics with Au2+ and Au2H+ are found to agree with the experimental findings. The joint investigations provide insights into hydrogen atom adsorption effects and consequent reaction mechanisms.

Plasmon resonances tailored by Fano profiles in silver-based core-shell nanoparticles.

The optical absorption of bimetallic nanoparticles M-Ag involving silver as an active plasmonic compound has been the subject of very extensive experimental studies, both for a large range of sizes and a large variety of associated metals. Considering the most commonly encountered core-shell segregated configuration M@Ag involving a transition metal M, the spectral response is found to be weakly discriminating with regard to the chemical order and composition and is characterized by a large unstructured plasmon resonance in the 2 eV to 4 eV range. The plasmon band is essentially shaped by the scars made in the absorption continuum of metal M by Fano-like induced resonances and is surprisingly little sensitive to the exact nature of this metal, giving birth to a "quasi universal" optical signature for M@Ag systems. In this paper, we show how this generic behaviour arises from the specific plasmonic response of silver and stress the role of interband transitions of both metals through their coupling with the free electron oscillation modes. This theoretical discussion will be illustrated through selected experimental results.

Plasmon spectroscopy of small indium-silver clusters: monitoring the indium shell oxidation.

Owing to the very different electrovalences of indium and silver, nanoparticles made of these elements are among the simplest examples of hybrid plasmonic systems retaining a full metallic character. The optical properties of small indium-silver clusters are investigated here for the first time in relation to their structural characterization. They are produced in the gas phase by a laser vaporization source and co-deposited in a silica matrix. The optical absorption of fresh samples is dominated by a strong surface plasmon resonance (SPR) in the near UV, in an intermediate position between those of pure elements. A combination of SPR analysis and electron microscopy imaging provides evidence for the favourable surface segregation of indium. After a prolonged exposure to ambient air and because of the silica matrix porosity, changes in the SPR reflect the spontaneous formation of a dielectric indium oxide shell around a metallic silver core. The metallic character of indium can nevertheless be recovered by annealing under a reducing atmosphere. The reversibility of these processes is directly mirrored in optical measurements through SPR shifts and broadenings as supported by multi-shell Mie theory calculations. By controlling their oxidation level, In-Ag clusters can be considered as new candidates to extend SPR spectroscopy in the UV range and model plasmonic systems consisting of a silver particle of potentially very small size, fully protected by a dielectric oxide shell.

Silver cluster-biomolecule hybrids: from basics towards sensors.

We focus on the functional role of small silver clusters in model hybrid systems involving peptides in the context of a new generation of nanostructured materials for biosensing. The optical properties of hybrids in the gas phase and at support will be addressed with the aim to bridge fundamental and application aspects. We show that extension and enhancement of absorption of peptides can be achieved by small silver clusters due to the interaction of intense intracluster excitations with the π-π* excitations of chromophoric aminoacids. Moreover, we demonstrate that the binding of a peptide to a supported silver cluster can be detected by the optical fingerprint. This illustrates that supported silver clusters can serve as building blocks for biosensing materials. Moreover, the clusters can be used simultaneously to immobilize biomolecules and to increase the sensitivity of detection, thus replacing the standard use of organic dyes and providing label-free detection. Complementary to that, we show that protected silver clusters containing a cluster core and a shell liganded by thiolates exhibit absorption properties with intense transitions in the visible regime which are also suitable for biosensing applications.

Profiling an electrospray plume by laser-induced fluorescence and Fraunhofer diffraction combined to mass spectrometry: influence of size and composition of droplets on charge-state distributions of electrosprayed proteins.

We investigated how physico-chemical properties of charged droplets are affected by the electrospray process, using simultaneous in situ measurements by laser-induced fluorescence (LIF), Fraunhofer diffraction and mass spectrometry. For this purpose, we implemented a laser-induced-fluorescence profiling setup in conjunction with a fast, high-resolution particle sizing scheme on a modified Agilent Jet Stream electrospray source coupled to a single quadrupole mass analyser. The optical setup permits us to profile the solvent fractionation and the size of the droplets as they evaporate in an electrospray plume by measuring both the angular scattering pattern and emission spectra of a solvatochromic fluorescent dye. Mass spectra are recorded simultaneously. These mass spectrometry and optical spectroscopy investigations allow us to study the relation between the observed charge-state distributions of protein anions and physico-chemical properties of evaporating droplets in the spray plume. By mixing water with methanol, a refolding of cytochrome C is observed as the water percentage increases in the plume due to the preponderant evaporation of volatile methanol.

Binding motifs of silver in prion octarepeat model peptides: a joint ion mobility, IR and UV spectroscopies, and theoretical approach.

Transition metal-ion complexation is essential to the function and structural stability of many proteins. We studied silver complexation with the octarepeat motif ProHisGlyGlyGlyTrpGlyGln of the prion protein, which shows competitive sites for metal chelation including amide, indole and imidazole groups. This octapeptide is known as a favourable transition metal binding site in prion protein. We used ion mobility spectrometry (IMS), infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory calculations (DFT) to identify the binding motifs of a silver cation on HisGlyGlyGlyTrp peptide as well as on peptide subsequences. Ultra-violet photodissociation (UVPD) and collision induced dissociation mass spectrometry together with the time-dependent density functional method was then exploited to study the influence of binding sites on optical properties and on the ground and excited states reactivity of the peptide. We show that the metal cation is bound to the π-system of the indole group and a nitrogen atom of the imidazole group and that charge transfers from the indole group to the silver cation occur in excited electronic states.

UV spectroscopy of DNA duplex and quadruplex structures in the gas phase.

UV absorption spectroscopy is one of the most widely used methods to monitor nucleic acid folding in solution, but the absorption readout is the weighted average contribution of all species present in solution. Mass spectrometry, on the other hand, is able to separate constituents of the solution based on their mass, but methods to probe the structure of each constituent are needed. Here, we explored whether gas-phase UV spectroscopy can give an indication of DNA folding in ions isolated by electrospray mass spectrometry. Model DNA single strands, duplexes, and G-quadruplexes were extracted from solution by electrospray; the anions were stored in a quadrupole ion trap and irradiated by a tunable laser to obtain the UV action spectra of each complex. We found that the duplex and quadruplex spectra are significantly different from the spectra of single strands, thereby suggesting that electronic spectroscopy can be used to probe the DNA gas-phase structure and obtain information about the intrinsic properties of high-order DNA structure.

Probing elasticity at the nanoscale: Terahertz acoustic vibration of small metal nanoparticles.

The acoustic response of surface-controlled metal (Pt) nanoparticles is investigated in the small size range, between 1.3 and 3 nm (i.e., 75-950 atoms), using time-resolved spectroscopy. Acoustic vibration of the nanoparticles is demonstrated, with frequencies ranging from 1.1 to 2.6 THz, opening the way to the development of THz acoustic resonators. The frequencies, measured with a noncontact optical method, are in excellent agreement with the prediction of a macroscopic approach based on the continuous elastic model, together with the bulk material elastic constants. This demonstrates the validity of this model at the nanoscale and the weak impact of size reduction on the elastic properties of a material, even for nanoparticles formed by less than 100 atoms.

Optical and structural properties of copper-oxytocin dications in the gas phase.

We present a joint experimental and theoretical investigation of the structural and optical properties of copper-oxytocin dications in the gas phase. Ion mobility and UV photodissociation experiments were performed, allowing the investigation of the influence of the Cu(2+) ion on the structural and optical properties of oxytocin. Density functional theory calculations were performed to find low energy structures for the bare and complexed peptide and to characterize optical spectral features. Copper complexation induces a drastic change in the structure of the oxytocin peptide. In particular, we predict a 4N chelation of the copper cation which leads to a contraction of the oxytocin ring. The gas phase lowest-energy structures are compared with the X-ray crystal structure of the oxytocin molecule bound to its receptor protein. The optical spectrum of oxytocin complexed with the copper cation displays a global enhancement of the photofragmentation yield as compared to the one recorded for the doubly protonated oxytocin. Moreover, experimental and calculated optical spectra of protonated tyrosine have also been determined, since its leading features are present in oxytocin as well.

Optical properties of isolated hormone oxytocin dianions: ionization, reduction, and copper complexation effects.

Trapped oxytocin (OT) peptide dianions and copper-oxytocin complex dianions are subjected to electron detachment when irradiated by a UV light. Electron photodetachment experiments as a function of the laser wavelength were performed on the native disulfide-containing ring oxytocin, the reduced dithiol oxytocin, and the Cu(II)-oxytocin complex. The electron detachment yield was used to monitor the excited electronic spectrum of the trapped ions. The spectra can be used as a fingerprint of the ionization state of the tyrosine chromophore under different structural environments. In gas-phase oxytocin dianion [OT-2H](2-), the tyrosine is deprotonated while it is neutral for the reduced form of oxytocin [OT(SH)-2H](2-). Optical spectra for the copper complex dianion [OT-4H+Cu](2-) are in favor of a neutral tyrosine in the complex. A structure with the metal cation chelated to four deprotonated amide groups is proposed for this complex.

Electron photodetachment from gas phase peptide dianions. Relation with optical absorption properties.

Electron detachment from peptide dianions is studied as a function of the laser wavelength. The first step for the detachment is a resonant electronic excitation of the dianions. Electronic excitation spectra are reported for three peptides, including gramicidin. A comparative study of the detachment yield for 13 peptides was performed at 260 nm and at 220 nm. At 260 nm, the detachment yield is mainly driven by the sum of the absorption coefficients of the aromatic amino acids that are contained in the peptide. At 220 nm, no direct relation is observed between the electron photodetachement yields and the sum of absorption efficiencies. At this wavelength, the sequence and the structure of the peptide may have an influence on the photodetachment process.

Electron photodetachment dissociation of DNA anions with covalently or noncovalently bound chromophores.

Double stranded DNA multiply charged anions coupled to chromophores were subjected to UV-Vis photoactivation in a quadrupole ion trap mass spectrometer. The chromophores included noncovalently bound minor groove binders (activated in the near UV), noncovalently bound intercalators (activated with visible light), and covalently linked fluorophores and quenchers (activated at their maximum absorption wavelength). We found that the activation of only chromophores having long fluorescence lifetimes did result in efficient electron photodetachment from the DNA complexes. In the case of ethidium-dsDNA complex excited at 500 nm, photodetachment is a multiphoton process. The MS(3) fragmentation of radicals produced by photodetachment at lambda = 260 nm (DNA excitation) and by photodetachment at lambda > 300 nm (chromophore excitation) were compared. The radicals keep no memory of the way they were produced. A weakly bound noncovalent ligand (m-amsacrine) allowed probing experimentally that a fraction of the electronic internal energy was converted into vibrational internal energy. This fragmentation channel was used to demonstrate that excitation of the quencher DABSYL resulted in internal conversion, unlike the fluorophore 6-FAM. Altogether, photodetachment of the DNA complexes upon chromophore excitation can be interpreted by the following mechanism: (1) ligands with sufficiently long excited-state lifetime undergo resonant two-photon excitation to reach the level of the DNA excited states, then (2) the excited-state must be coupled to the DNA excited states for photodetachment to occur. Our experiments also pave the way towards photodissociation probes of biomolecule conformation in the gas-phase by Förster resonance energy transfer (FRET).

Specific UV photodissociation of tyrosyl-containing peptides in multistage mass spectrometry.

UV photodissociation (UVPD) at 262 nm has been carried out on protonated tyrosyl-containing peptides formed by trypsin digestion of apo-transferrin. Under UVPD, the main event is the fragmentation of the C(alpha)-C(beta) bond of the tyrosyl residues leading to a radical ion 107 Da below the precursor ion. The dissociation rate of this specific cleavage appears to be strongly dependent on the peptide sequence and is more prominent on the singly protonated species than on the doubly protonated state. The fragmentation spectra resulting from collisional activation of the protonated even-electron native peptides and of the odd-electron radical species prepared by UVPD are dominated by y-type backbone cleavages. A comparison of their respective y-ion pattern shows complementarities since the combination of both increases the sequence coverage of the peptide sequence. The specific detection of the neutral loss of 107 Da from peptides witnesses the content of at least one tyrosyl residue and, though preliminary, is proposed as a potential new filtering strategy during protein database searching.

Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis.

Cystinosis is an autosomal recessive disorder characterized by an accumulation of intralysosomal cystine. The causative gene, CTNS, encodes cystinosin, a seven-transmembrane-domain protein, which we recently showed to be a lysosomal cystine transporter. The most severe and frequent form of cystinosis, the infantile form, appears around 6 to 12 months, with a proximal tubulopathy (de Toni-Debré-Fanconi syndrome) and ocular damage. End-stage renal failure is reached by 10 years of age. Accumulation of cystine in all tissues eventually leads to multisystemic disease. Treatment with cysteamine, which reduces the concentration of intracellular cystine, delays disease progression but has undesirable side effects. We report the first Ctns knockout mouse model generated using a promoter trap approach. We replaced the last four Ctns exons by an internal ribosome entry site-betagal-neo cassette and showed that the truncated protein was mislocalized and nonfunctional. Ctns(-/-) mice accumulated cystine in all organs tested, and cystine crystals, pathognomonic of cystinosis, were observed. Ctns(-/-) mice developed ocular changes similar to those observed in affected individuals, bone defects and behavioral anomalies. Interestingly, Ctns(-/-) mice did not develop signs of a proximal tubulopathy, or renal failure. A preliminary therapeutic trial using an oral administration of cysteamine was carried out and demonstrated the efficiency of this treatment for cystine clearance in Ctns(-/-) mice. This animal model will prove an invaluable and unique tool for testing emerging therapeutics for cystinosis.

Fano Transparency in Rounded Nanocube Dimers Induced by Gap Plasmon Coupling.

Homodimers of noble metal nanocubes form model plasmonic systems where the localized plasmon resonances sustained by each particle not only hybridize but also coexist with excitations of a different nature: surface plasmon polaritons confined within the Fabry-Perot cavity delimited by facing cube surfaces (i.e., gap plasmons). Destructive interference in the strong coupling between one of these highly localized modes and the highly radiating longitudinal dipolar plasmon of the dimer is responsible for the formation of a Fano resonance profile and the opening of a spectral window of anomalous transparency for the exciting light. We report on the clear experimental evidence of this effect in the case of 50 nm silver and 160 nm gold nanocube dimers studied by spatial modulation spectroscopy at the single particle level. A numerical study based on a plasmon mode analysis leads us to unambiguously identify the main cavity mode involved in this process and especially the major role played by its symmetry. The Fano depletion dip is red-shifted when the gap size is decreasing. It is also blue-shifted and all the more pronounced that the cube edge rounding is large. Combining nanopatch antenna and plasmon hybridization descriptions, we quantify the key role of the face-to-face distance and the cube edge morphology on the spectral profile of the transparency dip.

Plasmonic coupling with most of the transition metals: a new family of broad band and near infrared nanoantennas.

In this article, we show for the first time, both theoretically and empirically, that plasmonic coupling can be used to generate Localized Surface Plasmon Resonances (LSPRs) in transition metal dimeric nano-antennas (NAs) over a broad spectral range (from the visible to the near infrared) and that the spectral position of the resonance can be controlled through morphological variation of the NAs (size, shape, interparticle distance). First, accurate calculations using the generalized Mie theory on spherical dimers demonstrate that we can take advantage of the plasmonic coupling to enhance LSPRs over a broad spectral range for many transition metals (Pt, Pd, Cr, Ni etc.). The LSPR remains broad for low interparticle distances and masks the various hybridized modes within the overall resonance. However, an analysis of the charge distribution on the surface of the nanoparticles reveals these modes and their respective contributions to the observed LSPR. In the case of spherical dimers, the transfer of the oscillator strengths from the "dipolar" mode to higher orders involves a maximum extinction cross-section for intermediate interparticle distances of a few nanometers. The emergence of the LSPR has been then experimentally illustrated with parallelepipedal NAs (monomers and dimers) made of various transition metals (Pt, Pd and Cr) and elaborated by nanolithography. Absolute extinction cross-sections have been measured with the spatial modulation spectroscopy technique over a broad spectral range (300-900 nm) for individual NAs, the morphology of which has been independently characterized by electron microscopy imaging. A clear enhancement of the LSPR has been revealed for a longitudinal excitation and plasmonic coupling has been clearly evidenced in dimers by an induced redshift and broadening of the LSPR compared to monomers. Furthermore, the LSPR has been shown to be highly sensitive to slight modifications of the interparticle distance. All the experimental results are well in agreement with finite element method (FEM) calculations in which the main geometrical parameters characterizing the NAs have been derived from electron microscopy imaging analysis. The main advantage of dimers as compared to monomers lies in the generation of a well-defined and highly enhanced electromagnetic field (the so-called "hot spots") within the interparticle gap that can be exploited in photo-catalysis, magneto-plasmonics or nano-sensing.

Long-term social outcome of children after kidney transplantation.

BACKGROUND: There are few data concerning the social outcome at adult age of children who received a kidney transplant. The aim of this study was to collect information on this outcome in a cohort of 366 children who underwent transplantation between 1973 and 1985. METHODS: Information was obtained through a simple questionnaire in 244 patients. The mean age of the patients was 31.7 years, and they had undergone grafting at a mean age of 11.9 years. RESULTS: As of December 2000 or at last visit, 77% had a functioning graft. The mean height was 156.6 cm for male patients and 147.4 cm for female patients. The distribution of educational level was lower than national averages: 27.4% were at the lowest level versus 3% of the general population, 41.4% were at the middle level, 31.2% had reached the baccalaureate level, and 11% had followed a university cursus. Activity was similar to the general population: 73% had paid employment versus 72%, 6.5% were unemployed versus 10.5%, and 18.7% received a disablement pension. Among the 149 male patients, 39 (27%) had a marital life and 12 (8.3%) had children, whereas among the 95 female patients, 48 (50%) had a marital life and 26 (27%) had at least one child. Lodging was the parent's home in 46% and independent in 54%. Multivariate analysis showed a significant correlation between educational level, paid activity, marital life, and independent housing with final height. CONCLUSIONS: The long-term social outcome of patients who underwent grafting in childhood more than 15 years previously is encouraging. The importance of reaching a normal height is stressed.

A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.

BACKGROUND: The pharmacokinetics and immunodynamics of basiliximab were assessed in 39 pediatric de novo kidney allograft recipients to rationally chose a dose regimen for this age group. METHODS: In study part 1, patients were given 12 mg/m(2) of basiliximab by bolus intravenous injection before surgery and on day 4. An interim pharmacokinetic evaluation supported a fixed-dose approach for study part 2 in which infants and children received two 10-mg doses and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for analysis of basiliximab and soluble interleukin-2 receptor concentrations, flow cytometry, and screening for anti-idiotype antibodies. RESULTS: Basiliximab clearance in infants and children (n=25) was reduced by approximately half compared with adults from a previous study and was independent of age (1-11 years), weight (9-37 kg), and body surface area (0.44-1.20 m(2) ). Clearance in adolescents (12-16 years, n=14) approached or reached adult values. CD25-saturating basiliximab concentrations were maintained for 31+/-12 days in study part 1 with mg/m(2) dosing and for 36+/-14 days in study part 2 based on the fixed-dose regimen ( P=0.31). A single patient experienced a rejection episode during CD25 saturation. The duration of CD25 saturation in patients who experienced a rejection episode after desaturation did not differ from those who remained rejection-free for the full 6-month period: 34+/-6 days (n=6) vs. 35+/-14 days (n=33 patients); P=0.74. Anti-idiotype antibodies were detected in two patients; however, this did not influence the clearance of basiliximab or the duration of CD25 saturation. CONCLUSIONS: To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients <35 kg should receive two 10-mg doses and those > or =35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose is given before surgery and the second on day 4 after transplantation.