Ab initio study of organic mixed valency

A series of six radical cations of the type (D L D)⁺ was investigated at the ab initio unrestricted Hartree–Fock level. One localized and one delocalized conformation were systematically searched by full geometry optimization. At both nuclear arrangements, mostly found as being minima in the symmetry‐restrained Hartree–Fock framework, excitation energies were calculated through the expansion of the wave function on single electronic excitations of the Hartree–Fock fundamental determinant and at the unrestricted Hartree–Fock or at the multiconfigurational self consistent field levels. Few calculations were also performed by taking into account some part of the electronic correlation. Except for N,N,N′,N′‐tetramethyl p‐phenylenediamine, all the studied compounds are localized stable cations, at the symmetry‐restrained Hartree–Fock level. However, the reoptimization of their wave function changes this observation since only three of them seem to conserve a localized stable conformation. Most of the studied systems are characterized by one or two excited electronic states very close to the fundamental one and should thus present an unresolved broadened first absorption band in the near‐infrared region. These features are in agreement with the available experimental data. Strong Hartree–Fock instabilities are found for the delocalized structure and put in relation with the existence of the large nonadiabatic coupling in this conformational region. The solvent influence is discussed in the Onsager dipolar reaction field framework. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 76: 552–573, 2000     

Hartree–Fock instabilities and electronic properties

Hartree–Fock instabilities are investigated for about 80 compounds, from acetylene to mivazerol (27 atoms) and a cluster of 18 water molecules, within a double ζ basis set. For most conjugated systems, the restricted Hartree–Fock wave function of the singlet fundamental state presents an external or so‐called triplet instability. This behavior is studied in relation with the electronic correlation, the vicinity of the triplet and singlet excited states, the electronic delocalization linked with resonance, the nature of eventual heteroatoms, and the size of the systems. The case of antiaromatic systems is different, because they may present a very large internal Hartree–Fock instability. Furthermore, the violation of Hund's rule, observed for these compounds, is put in relation with the fact that the high symmetry structure in its singlet state has no feature of a diradical‐like species. It appears that the triplet Hartree–Fock instability is directly related with the spin properties of nonnull orbital angular momentum electronic systems. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 483–504, 2000     

On the particle inertia-free collision with a partially contaminated spherical bubble

The collision between a contaminated spherical bubble and fine particles in suspension is considered for r_p/r_b ? 1 (r_p being the radius of the particles in suspension and r_b the radius of the bubble). The collision probability or efficiency is defined as the number of particles colliding the bubble surface to the number of particles initially present in the volume swept out by the bubble. In this note we show that the collision probability can be expressed as P_c(r_p/r_b,Re) = g(r_p/r_b)f(Re) for both mobile and immobile interfaces. For partially contaminated bubbles a linear or quadratic dependency in r_p/r_b is found depending on the level of contamination and the value of r_p/r_b. These behaviors are given by the flux of particles near the surface which is controlled by the tangential velocity for mobile interfaces and by the velocity gradient for immobile interfaces. The threshold value (r_p/r_b)_th between the r_p/r_b and (r_p/r_b)² evolution is shown to vary as sin^n(Re)(θ_clean/n(Re))sin(3θ_clean/4), θ_clean being the angle describing the front clean part of the bubble and n(Re) varying from n = 2 to n = 1 from small to large Reynolds number.     

Liquid/liquid dispersion in a chaotic advection flow

Mixing by chaotic advection in a twisted-pipe flow is used here to investigate the efficiency of this flow in the liquid/liquid dispersion process. This study focuses on water/oil dispersions produced by continuous water injection into a main oil flow, for small Dean numbers. The drop sizes obtained with the chaotic-advection twisted-pipe flow are compared with those in a straight pipe and a helically coiled flow for the same conditions. It is found that the resulting dispersions are finer and more mono-dispersed in the chaotic advection flow. These results are compared with the theoretical maximum diameter _dmax$d_{\text{max}}$ determined by the Grace theory in which the viscous stress controls the breakup phenomena. For this purpose, the kinematic field is computed from the theoretical formulae for Dean flow. The strain rate fields in the pipe cross-section are then analytically computed and used to predict the maximum drop diameter. The theoretical values are identical for the three configurations (straight, helically coiled, and twisted pipe) up to a critical Dean number, where the secondary flow becomes significant. Beyond this value, the shear stress is enhanced in the twisted-pipe flow compared with the straight-pipe flow, and the predicted drop diameters are smaller. An interpretation of the higher dispersive performance of the chaotic flow is provided by the Lagrangian trajectories of the particles.     

Time-dependent complexation of glucose-reduced gold nanoparticles with octadecylamine Langmuir monolayers

We report on the reduction of aqueous chloroaurate ions by glucose to form gold nanoparticles of uniform size. We further demonstrate the complexation of these particles with octadecylamine (ODA) monolayers at the air-water interface. Pressure-area (pi-A) isotherms as a function of time of complexation revealed a significant expansion of the monolayer. Surface pressure variation with time for constant areas after spreading of the monolayer was carried out to observe the kinetics of complexation of the colloidal particles at the interface. The kinetics of complexation of the particles at the interface was also monitored by Brewster angle microscopy (BAM) measurements. Langmuir-Blodgett films of the particles complexed with ODA were formed at a subphase pH of 9 onto different substrates. Quartz crystal microgravimetry (QCM) was used to quantify the amount of particles deposited per immersion cycle of the quartz crystal. The LB films were further characterized by UV-vis and transmission electron microscopy (TEM) measurements. TEM measurements indicate a close packed and equidistant arrangement of colloidal particles in the LB film, probably due to hydrogen-bonding interactions.     

Protein Delivery System Containing a Nickel‐Immobilized Polymer for Multimerization of Affinity‐Purified His‐Tagged Proteins Enhances Cytosolic Transfer

Recombinant proteins with cytosolic or nuclear activities are emerging as tools for interfering with cellular functions. Because such tools rely on vehicles for crossing the plasma membrane we developed a protein delivery system consisting in the assembly of pyridylthiourea‐grafted polyethylenimine (πPEI) with affinity‐purified His‐tagged proteins pre‐organized onto a nickel‐immobilized polymeric guide. The guide was prepared by functionalization of an ornithine polymer with nitrilotriacetic acid groups and shown to bind several His‐tagged proteins. Superstructures were visualized by electron and atomic force microscopy using 2 nm His‐tagged gold nanoparticles as probes. The whole system efficiently carried the green fluorescent protein, single‐chain antibodies or caspase 3, into the cytosol of living cells. Transduction of the protease caspase 3 induced apoptosis in two cancer cell lines, demonstrating that this new protein delivery method could be used to interfere with cellular functions.     

A New Stereoselective Synthesis of Acitretin (=Soriatane®, Neotigason®)

A new synthesis of acitretin via a C₁₅+C₅ route is reported. The C₁₅ unit is the key step, involving a procedure that provides the required (all‐E)‐C₁₅‐aldehyde with high stereoselectivity.     

An object-oriented hybrid symbolic/numerical approach for the development of finite element codes

The association of object-oriented programming and symbolic computation techniques introduces certain changes in finite element code organization. The purpose of this approach is to speed up the design of new formulations. Previous papers have described the basic concepts of the method. In this paper, the focus is placed on functional aspects of symbolic tools for the development of finite element formulations. Two practical examples are used to illustrate this point. The first is a space-time formulation for an incompressible flow driven by the Navier–Stokes equations, and the second is a finite element derivation of the total potential energy for linear elasticity.     

Estimating the Analytical Performance of Raman Spectroscopy for Quantification of Active Ingredients in Human Stratum Corneum

Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo) human stratum corneum (SC), using systematically varied doses of resorcinol, as model compound, and the performance is quantified according to key figures of merit defined by regulatory bodies (ICH, FDA, and EMA). A methodology is thus demonstrated to establish the limit of detection (LOD), precision, accuracy, sensitivity (SEN), and selectivity (SEL) of the technique, and the performance according to these key figures of merit is compared to that of similar established methodologies, based on studies available in literature. First, principal components analysis (PCA) was used to examine the variability within the spectral data set collected. Second, ratios calculated from the area under the curve (AUC) of characteristic resorcinol and proteins/lipids bands (1400–1500 cm⁻¹) were used to perform linear regression analysis of the Raman spectra. Third, cross-validated PLSR analysis was applied to perform quantitative analysis in the fingerprint region. The AUC results show clearly that the intensities of Raman features in the spectra collected are linearly correlated to resorcinol concentrations in the SC (R² = 0.999) despite a heterogeneity in the distribution of the active molecule in the samples. The Root Mean Square Error of Cross-Validation (RMSECV) (0.017 mg resorcinol/mg SC), The Root Mean Square of Prediction (RMSEP) (0.015 mg resorcinol/mg SC), and R² (0.971) demonstrate the reliability of the linear regression constructed, enabling accurate quantification of resorcinol. Furthermore, the results have enabled the determination, for the first time, of numerical criteria to estimate analytical performances of CRM, including LOD, precision using bias corrected mean square error prediction (BCMSEP), sensitivity, and selectivity, for quantification of the performance of the analytical technique. This is one step further towards demonstrating that Raman spectroscopy complies with international guidelines and to establishing the technique as a reference and approved tool for permeation studies.     

Cytotoxic and Antioxidant Activities of Imine Analogs of Trans-Resveratrol towards Murine Neuronal N2a Cells

Trans-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans-resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans-resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC₆(3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2′-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans-resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans-resveratrol.