Bonding and redox properties of [Os(3)(CO)(9)(tmbp)(L)] (tmbp=4,4',5,5'-tetramethyl-2,2'-biphosphinine; L=CO, PPh(3)) clusters with an unprecedented electron-deficient metallic core and doubly bridging biphosphinine dianion

Herein we describe in detail the bonding properties and electrochemical behavior of the first known triosmium carbonyl clusters with a coordinated redox-active ligand 4,4',5,5'-tetramethyl-2,2'-biphosphinine (tmbp), the phosphorus derivative of 2,2'-bipyridine. The clusters investigated were [Os(3)(CO)(10)(tmbp)] (1) and its derivative [Os(3)(CO)(9)(PPh(3))(tmbp)] (2). The crystal structures of both clusters are compared with those of relevant compounds; they served as the basis for density functional theory (DFT and time-dependent DFT) calculations. The experimental and theoretical data reveal an unexpected and unprecedented bridging coordination mode of tmbp, with each P atom bridging two metal atoms. The tmbp ligand is formally reduced by transfer of two electrons from the triangular cluster core that consequently lacks one of the metal-metal bonds. Both 1 and 2 therefore represent 50e(-) clusters with a coordinated 8e(-) donor, [tmbp](2-). The HOMO and LUMO of 1 and 2 possess a predominant contribution from different pi*(tmbp) orbitals, implying that the lowest energy excited state possesses a significant intraligand character. This is in agreement with the photostability of these clusters. DFT calculations also predict the experimentally observed structure of 1 to be the most stable one in a series of several plausible structural isomers. Stepwise two-electron electrochemical reduction of 1 and 2 results in dissociation of CO and PPh(3), respectively, and formation of the [Os(3)(CO)(9)(tmbp)](2-) ion. The initially produced radical anions of the parent clusters, in which the odd electron is predominantly localized on the tmbp ligand, are sufficiently stable at low temperatures and can be observed with IR spectroelectrochemistry. The electron-deficiency of the cluster core in 1 permits facile electrocatalytic substitution of a CO ligand by tertiary phosphane and phosphite donors.     

Hyperpigmentation induced by topical 5-aminolaevulinic acid plus visible light

Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an alternative tool for the treatment of superficial non-melanoma skin cancers. Recently ALA-PDT has been employed with encouraging results also for warts, condylomata and psoriasis. In this study the effects of topical ALA plus irradiation with visible light on intact human skin have been evaluated. Five skin areas (A, B, C, D, and E) on the inner upper part of the arms of five healthy volunteers (skin types III and IV) were treated with (A) ALA 20% in base cream without irradiation, (B) only the vehicle (base cream) without ALA, (C, D and E) ALA cream at the concentrations of 5, 10 and 20%, respectively; all treatments were applied with an occlusive dressing. Four hours after ALA or vehicle application areas B, C, D and E were irradiated with a fixed dose of 40 J/cm(2). ALA penetration through the intact skin was evaluated by in vivo fluorescence determination. The effects on healthy skin were evaluated by clinical and chromometric examinations, light microscopy, immunohistochemistry and electron microscopy. RESULTS: (1) in vivo fluorescence demonstrated that ALA is able to penetrate through the intact skin, when applied with occlusive dressing and induces a classical fluorescence peak due to Protoporphyrin IX (PpIX) formation, which is the active photosensitiser. (2) Skin areas receiving ALA plus irradiation showed erythema and swelling just after the irradiative session and hyperpigmentation 48-72 h later. (3) Colourimetric data confirmed significant skin colour changes: values a* (representing the erythematous changes) increased only on the skin areas where ALA+irradiation were applied and during the 48 h after irradiation, thereafter a* began to decrease; values L* (pigmentation) increased during the 2 weeks following treatment. (4) Histopathological, immunohistochemical (S100, HMB-45) and electron microscopic findings showed an absolute increment of the number of melanocytes, which appeared clearly activated. In conclusion the application of ALA cream followed by irradiation is able to induce a pigmentation response in healthy human skin, at least in skin types III and IV. This melanocytic activation could have a potential for the treatment of skin disorders characterised by hypopigmentation.     

Langmuir monolayers of the zwitterionic surfactant hexadecyl 1-N-L-tryptophan glycerol ether

We report the formation of Langmuir monolayers of pure zwitterionic hexadecyl 1-N-L-tryptophan glycerol ether (C(16)-TGE) surfactant and mixed monolayers of cationic-zwitterionic surfactant obtained modifying the pH of the subphase. The pressure-area and surface potential-area isotherms and fluorescence microscopy measurements have been used to characterize the surface phase transitions in the monolayers. These transitions appeared at larger areas as the pH decreased from 6.0 to 2.0 and almost disappeared as the pH decreased further. The analysis of the surface potential and the infrared reflection-absorption spectroscopy data suggests that the phase transition is associated with a change of orientation of both the hydrocarbon chain and the aromatic group of the surfactant with respect to the air-water surface. The surface rheology of the monolayers was studied by quasielastic light scattering and by the oscillatory barrier technique. The results indicate that there is at least one relaxation process in the monolayer.     

Interaction of antimicrobial arginine-based cationic surfactants with liposomes and lipid monolayers

The present work examines the relationship between the antimicrobial activity of novel arginine-based cationic surfactants and the physicochemical process involved in the perturbation of the cell membrane. To this end, the interaction of these surfactants with two biomembrane models, namely, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multilamellar lipid vesicles (MLVs) and monolayers of DPPC, 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] sodium salt (DPPG), and Escherichia coli total lipid extract, was investigated. For the sake of comparison, this study included two commercial antimicrobial agents, hexadecyltrimethylammonium bromide and chlorhexidine dihydrochloride. Changes in the thermotropic phase transition parameters of DPPC MLVs in the presence of the compounds were studied by differential scanning calorimetry analysis. The results show that variations in both the transition temperature (Tm) and the transition width at half-height of the heat absorption peak (deltaT1/2) were consistent with the antimicrobial activity of the compounds. Penetration kinetics and compression isotherm studies performed with DPPC, DPPG, and E. coli total lipid extract monolayers indicated that both steric hindrance effects and electrostatic forces explained the antimicrobial agent-lipid interaction. Overall, in DPPC monolayers single-chain surfactants had the highest penetration capacity, whereas gemini surfactants were the most active in DPPG systems. The compression isotherms showed an expansion of the monolayers compared with that of pure lipids, indicating an insertion of the compounds into the lipid molecules. Owing to their cationic character, they are incorporated better into the negatively charged DPPG than into zwitterionic DPPC lipid monolayers.     

FLAVIN-MEDIATED PRODUCTION OF HYDROGEN PEROXIDE IN PHOTOELECTROCHEMICAL CELLS

A photoelectrochemical cell for hydrogen peroxide production using flavin photosystems is described. The anodic solution, which is kept free of oxygen by passing an Ar stream through it, contains the photoreceptor (flavin mononucleotide or lumiflavin) and the electron donor (EDTA, semicarbazide or hydroxylamine), while the peroxide is formed at the electrode of the cathodic solution, whose oxygen content is increased by bubbling with pure oxygen. Among several electrode metals that have been tested (Ag, Pt and Hg), Hg is the most efficient. The pH of the anodic and cathodic solutions should be adjusted to 14 and 1, respectively, for optimum results.     

Time-resolved gas-phase kinetic and quantum chemical studies of the reaction of silylene with nitric oxide

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by laser flash photolysis of phenylsilane, have been carried out to obtain rate constants for its bimolecular reaction with NO. The reaction was studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas at five temperatures in the range 299-592 K. The second-order rate constants at 10 Torr fitted the Arrhenius equation log(k/cm3 molecule(-1) s(-1)) = (-11.66 +/- 0.01) + (6.20 +/- 0.10 kJ mol(-1))/RT ln 10 The rate constants showed a variation with pressure of a factor of ca. 2 over the available range, almost independent of temperature. The data could not be fitted by RRKM calculations to a simple third body assisted association reaction alone. However, a mechanistic model with an additional (pressure independent) side channel gave a reasonable fit to the data. Ab initio calculations at the G3 level supported a mechanism in which the initial adduct, bent H2SiNO, can ring close to form cyclo-H2SiNO, which is partially collisionally stabilized. In addition, bent H2SiNO can undergo a low barrier isomerization reaction leading, via a sequence of steps, ultimately to dissociation products of which the lowest energy pair are NH2 + SiO. The rate controlling barrier for this latter pathway is only 16 kJ mol(-1) below the energy of SiH2 + NO. This is consistent with the kinetic findings. A particular outcome of this work is that, despite the pressure dependence and the effects of the secondary barrier (in the side reaction), the initial encounter of SiH2 with NO occurs at the collision rate. Thus, silylene can be as reactive with odd electron molecules as with many even electron species. Some comparisons are drawn with the reactions of CH2 + NO and SiCl2 + NO.     

NMR J-based analysis of nitrogen-containing moieties and application to dysithiazolamide, a new polychlorinated dipeptide from Dysidea sp.

The methodology of J-based analysis applied to 1,3-methylcarboamido systems allowed us to deduce the relative configurations of the two leucine-like fragments of a new tetrachloro amino acid derivative dysithiazolamide, which was isolated from an unidentified sponge of the genus Dysidea. Furthermore, the absolute configuration was also proposed by comparison with analogous systems.     

Time shift correction in second-order liquid chromatographic data with iterative target transformation factor analysis

When the generalized rank annihilation method (GRAM) is applied to liquid chromatographic data with diode-array detection, an important problem is the time shift of the peak of the analyte in the test sample. This problem leads to erroneous predictions. This time shift can be corrected if a time window is selected so that the chromatographic profile of the analyte in the test sample is trilinear with the peak of the analyte in the calibration sample. In this paper we present a new method to determine when this condition is met. This method is based on the curve resolution with iterative target transformation factor analysis (ITTFA). The calibration and test matrices are independently decomposed into profiles and spectra, and aligned before GRAM is applied. Here we study two situations: first, when the calibration matrix has one analyte and second, when it has two analytes. When the calibration matrix has two analytes, we selectively determine the time window for the analyte to be quantified. There were considerably fewer prediction errors after correction.     

Homogeneous pyrolysis kinetics of ethyl 3-hydroxy-3-methylbutanoate in the gas phase

The pyrolysis kinetics of ethyl 3-hydroxy-3-methylbutanoate have been examined over the temperature range of 286–330°C and pressure range of 29–108 Torr. In a seasoned vessel and in the presence of the free radical inhibitor cyclohexene or toluene the reaction is homogeneous, unimolecular and obeys a first-order rate law. The elimination products are mainly acetone and ethyl acetate, and very small amounts of ethyl 3-butenoate, acetic acid, ethylene and H₂O. The rate coefficient is expressed by the following equation: log k₁(s^–1)=(12.39±0.46)–(174.5±5.2) kJ mol^–1 (2.303RT)^–1. The mechanism appears to proceed via a six-membered cyclic transition state, where polarization of the (CH₃)C(OH)^+...-CH₂COOCH₂CH₃ bond is rate determining.     

In situ tissue pathology from spatially encoded mass spectrometry classifiers visualized in real time through augmented reality

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available.

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data.