Photoabsorption and photofragmentation of isolated cationic silver cluster-tryptophan hybrid systems

We present a theoretical study of the size and structure selective absorption properties of cationic silver cluster-tryptophan Trp-Ag(n)(+) (n = 2-5,9) hybrid systems supported by photofragmentation experiments. Our time-dependent density functional theory calculations provide insight into the nature of excitations in interacting nanoparticle-biomolecule subunits and allow to determine characteristic spectral features as fingerprints of two different classes of structures: charge solvated and zwitterionic. Moreover, different types of charge transfer transitions have been identified. Charge transfer from pi system of tryptophan to silver cluster occurs for charge solvated structures while charge transfer from silver to the NH(3) (+) group takes place for zwitterionic structures. This has been confirmed by experimentally measured photofragmentation channels and molecular dynamics simulations. Our findings provide fundamental insight into the structure- and size-dependent mechanism responsible for the enhanced absorption and emission in nanoparticle-biomolecular hybrid systems.     

New access to H-phosphonates via metal-catalyzed phosphorus-oxygen bond formation

A novel approach to H-phosphonates from hypophosphorous acid using a transfer hydrogenation process was developed. This method is atom-economical, environmentally friendly, catalytic, and efficient, leading easily to H-phosphonate monoesters or ammonium salt in moderate to good yields.     

Alkoxyallene‐ynes: Selective Preparation of Bicyclo[5.3.0] Ring Systems Including a δ‐Alkoxy Cyclopentadienone

The development of an intramolecular rhodium(I)‐catalyzed Pauson–Khand reaction of alkoxyallene‐ynes with a proximal alkoxy group is reported. This reaction, in the presence of a [Rh(cycloocta‐1,5‐diene)Cl]₂/propane‐1,3‐diylbis(diphenylphosphane) system under a CO atmosphere, constitutes a powerful tool for selectively accessing carbo‐ and heterobicyclo[5.3.0] frameworks featuring an enol ether moiety. Through this procedure, a straightforward access to guaiane skeletons with a tertiary hydroxy group at the C10 position was achieved.     

A Highly Reactive Geminal P/B Frustrated Lewis Pair: Expanding the Scope to C−X (X=Cl,Br) Bond Activation

The geminal frustrated Lewis pair tBu₂PCH₂B(Fxyl)₂ ( 1 ; Fxyl=3,5‐(CF₃)₂C₆H₃) is accessible in 65 % yield from tBu₂PCH₂Li and (Fxyl)₂BF. According to NMR spectroscopy and X‐ray crystallography, 1 is monomeric both in solution and in the solid state. The intramolecular P ??? B distance of 2.900(5) Å and the full planarity of the borane site exclude any significant P/B interaction. Compound 1 readily activates a broad variety of substrates including H₂, EtMe₂SiH, CO₂/CS₂, Ph₂CO, and H₃CCN. Terminal alkynes react with heterolysis of the C?H bond. Haloboranes give cyclic adducts with strong P?BX₃ and weak R₃B?X bonds. Unprecedented transformations leading to zwitterionic XP/BCX₃ adducts occur on treatment of 1 with CCl₄ or CBr₄ in Et₂O. In less polar solvents (C₆H₆, n‐pentane), XP/BCX₃ adduct formation is accompanied by the generation of significant amounts of XP/BX adducts. FLP 1 catalyzes the hydrogenation of PhCH=NtBu and the hydrosilylation of Ph₂CO with EtMe₂SiH.     

Design of original bioactive formulations based on sugar-surfactant/non-steroidal anti-inflammatory catanionic self-assemblies: a new way of dermal drug delivery

A new kind of catanionic assembly was developed that associates a sugar-based surfactant with a non-steroidal anti-inflammatory drug (NSAID). Three different assemblies using indomethacin, ibuprofen and ketoprofen as NSAIDs were easily obtained in water by an acid-base reaction. These assemblies formed new amphiphilic entities because of electrostatic and hydrophobic effects in water and led to the spontaneous formation of vesicles. These catanionic vesicles were then tested as potential NSAID delivery systems for dermatological application. The anti-inflammatory activity was evaluated in vivo, and this study clearly showed an improved therapeutic effect for NSAIDs that were formulated as catanionic vesicles. These vesicles ensured a slower diffusion of the NSAID through the skin. This release probably increased the time of retention of the NSAID in the targeted strata of the skin. Thus, the present study suggests that this catanionic bioactive formulation could be a promising dermal delivery system for NSAIDs in the course of skin inflammation treatment.     

Metalation of cyclic pseudopeptidic thiosulfinates with Ni(II) and Zn(II) after ring opening: a mechanistic investigation

Thiosulfinates are an emerging class of oxidized sulfur species that are frequently supposed to be involved in biochemical processes. Reaction of 12- and 10-membered ring pseudopeptidic thiosulfinates 1a (4,4,7,7-tetramethyl-1,3,4,7,8,10-hexahydro-5,6,1,10-benzodithiadiazacyclododecine-2,9-dione 5-oxide) and 1b (3,3,6,6-tetramethyl-1,8-dihydro-4,5,1,8-benzodithiadiazecine-2,7(3H,6H)-dione 4-oxide) with a Ni(II) salt leads after ring cleavage under alkaline conditions to the isolation of diamidato/thiolato/sulfinato complexes. These two thiolato/sulfinato complexes of nickel, which can also be prepared by dioxygen oxidation of the parent diamidato/dithiolato complexes, were characterized by X-ray crystallography. They show a square-planar geometry with a S-bonded sulfinato ligand. A similar reaction between 1b and a Zn(II) salt leads to a thiolato/sulfinato complex with an O-bonded sulfinate via the intermediate formation of a mixed thiolato/sulfinic ester. On the basis of 1H NMR, IR, and mass analyses, the sulfinic ester in the intermediate is proposed to be O-bonded to the zinc center. Then, an in-depth study of the cleavage of these thiosulfinates with the oxyanions RO- and HO- was performed. This led, after trapping of the open species with CH3I, to the identification of three polyfunctionalized products containing a methyl thioether, with either an isothiazolidin-3-one S-oxide, a methyl sulfone, or a methyl sulfinic ester. All of these products arise from a selective nucleophilic attack at the sulfinyl sulfur, promoted either directly by RO- or HO- or by an internal peptidic nitrogen of the thiosulfinate after deprotonation with RO- or HO-.     

Modeling the inhibition of peptide deformylase by hydroxamic acids: influence of the sulfur donor

The first complexes containing both a sulfur atom and a hydroxamate moiety coordinated to a biologically relevant transition metal were synthesized as models for the structure of inhibited peptide deformylases. Two of these [(N(2)S)Zn(hydroxamate)] complexes were characterized by X-ray crystallography. The first contains a thioether and a simple hydroxamate, the second a thiolate and a N-substituted hydroxamate. Isolation of a complex with a thiolate and a simple hydroxamate group was not possible.     

FTIR spectroscopy in medical mycology: applications to the differentiation and typing of <Emphasis Type="Italic">Candida</Emphasis>

The incidence of fungal infections, in particular candidiasis and aspergillosis, has considerably increased during the last three decades. This is mainly due to advances in medical treatments and technologies. In high risk patients (e.g. in haematology or intensive care), the prognosis of invasive candidiasis is relatively poor. Therefore, a rapid and correct identification of the infectious agent is important for an efficient and prompt therapy. Most clinical laboratories rely on conventional identification methods that are based on morphological, physiological and nutritional characteristics. However, these have their limitations because they are time-consuming and not always very accurate. Moreover, molecular methods may be required to determine the genetic relationship between the infectious strains, for instance in Candida outbreaks. In addition, the latter methods require time, expensive consumables and highly trained staff to be performed adequately. In this study, we have applied the FTIR spectroscopic approach to different situations encountered in routine mycological diagnosis. We show the potentials of this phenotypic approach, used in parallel with routine identification methods, for the differentiation of 3 frequently encountered Candida species (C. albicans, C. glabrata and C. krusei) by using both suspensions and microcolonies. This approach, developed for an early discrimination, may help in the initial choice of antifungal treatment. Furthermore, we demonstrate the feasibility of the method for intraspecies comparison (typing) of 3 Candida species (C. albicans, C. glabrata and C. parapsilosis), particularly when an outbreak is suspected.     

Optimization of a liquid chromatography ion mobility-mass spectrometry method for untargeted metabolomics using experimental design and multivariate data analysis

High-resolution mass spectrometry coupled with pattern recognition techniques is an established tool to perform comprehensive metabolite profiling of biological datasets. This paves the way for new, powerful and innovative diagnostic approaches in the post-genomic era and molecular medicine. However, interpreting untargeted metabolomic data requires robust, reproducible and reliable analytical methods to translate results into biologically relevant and actionable knowledge. The analyses of biological samples were developed based on ultra-high performance liquid chromatography (UHPLC) coupled to ion mobility - mass spectrometry (IM-MS). A strategy for optimizing the analytical conditions for untargeted UHPLC-IM-MS methods is proposed using an experimental design approach. Optimization experiments were conducted through a screening process designed to identify the factors that have significant effects on the selected responses (total number of peaks and number of reliable peaks). For this purpose, full and fractional factorial designs were used while partial least squares regression was used for experimental design modeling and optimization of parameter values. The total number of peaks yielded the best predictive model and is used for optimization of parameters setting.