Amorphous drug nanosuspensions. 2. Experimental determination of bulk monomer concentrations

A simple turbidimetric method was developed to measure the bulk concentration of drug in nanosuspensions. The bulk concentrations measured were in the range from 1 microM to 1 mM. The accuracy of the method was checked by determination of the bulk concentration of crystalline nanosuspensions, i.e., the crystalline solubility, which compared favorably to solubilities measured by a conventional method. Results obtained for amorphous nanosuspensions agreed with predictions using a theory describing the relative solubility between a supercooled liquid and a crystal. Further, it was found that the bulk concentration in Ostwald ripening inhibited amorphous nanosuspensions and could be lowered by incorporation of higher amounts of the inhibitor, in agreement with predictions using the Bragg-Williams theory of nonideal solutions.     

Detection and spectroscopy of gold nanoparticles using supercontinuum white light confocal microscopy

We combine confocal microscopy using supercontinuum laser illumination and an interferometric detection technique to identify single nanoparticles of diameter below 10 nm. Spectral analysis of the signal allows us to record the plasmon resonance of a single nanoparticle. Our results hold great promise for fundamental studies of the optical properties of single metal clusters and for their use in biophysical applications.     

Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05–6 μg mL⁻¹) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20–160-fold) than with DAPPI (typically 2–15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC–MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.     

High-sensitivity piezoelectric tube sensor for shear-force detection in scanning near-field optical microscopy

An easy-to-implement non-optical shear-force detection setup for tip–sample distance regulation in scanning near-field optical microscopy is demonstrated. The detection method is based on attaching the near-field probe to a piezoelectric tube resulting in excellent mechanical contact between tip and detector. The main advantages of the method are good signal-to-background contrast and thus potential for high sensitivity. The method is demonstrated by obtaining approach curves of silicon surfaces. The suitability for optical experiments is further shown by measuring the near-field intensity distribution of the emission of a semiconductor laser.     

In silico prediction of drug solubility: 1. Free energy of hydration

As a first step in the computational prediction of drug solubility the free energy of hydration, DeltaG*(vw) in TIP4P water has been computed for a data set of 48 drug molecules using the free energy of perturbation method and the optimized potential for liquid simulations all-atom force field. The simulations were performed in two steps, where first the Coulomb and then the Lennard-Jones interactions between the solute and the water molecules were scaled down from full to zero strength to provide physical understanding and simpler predictive models. The results have been interpreted using a theory assuming DeltaG*(vw) = A(MS)gamma + E(LJ) + E(C)/2 where A(MS) is the molecular surface area, gamma is the water-vapor surface tension, and E(LJ) and E(C) are the solute-water Lennard-Jones and Coulomb interaction energies, respectively. It was found that by a proper definition of the molecular surface area our results as well as several results from the literature were found to be in quantitative agreement using the macroscopic surface tension of TIP4P water. This is in contrast to the surface tension for water around a spherical cavity that previously has been shown to be dependent on the size of the cavity up to a radius of approximately 1 nm. The step of scaling down the electrostatic interaction can be represented by linear response theory.     

Heavy quarks and squarks fromW-gluon fusion

We discussWg-fusion as a source heavy quark and squark pairs at very high energy hadron colliders. EffectiveW approximation is used to calculate the cross-sections analytically in the forward scattering configuration; good agreement is obtained with exact numerical calculations.W-gluon fusion is found to be not nearly as important a production mechanism of heavy squarks as it is of heavy quarks. This is especially true when the mass-splitting within theSU(2) _L doublet is small.     

Direct photon production beyond leading order in QCD

The significance of the quark-quark scattering process (quark+quark→quark+quark+photon) for the production of large-q_T real photons is discussed in the framework of perturbative QCD. To extract the finite contribution of this process to the differential cross section dσ/dy d²q_T (hadron 1+hadron 2→photon+anything) we define the gluon distribution and the quark-to-photon fragmentation function beyond the leading approximation. The calculations are performed consistently in the dimensional regularization scheme. Our numerical estimates show the resulting finite qq→qqγ contribution to be a small (order α_s/2π) correction in comparison with the basic QCD subprocesses.     

Solvent effects on the acid-catalyzed hydrolysis of tetramethylurea

Tetramethylurea was hydrolyzed in aqueous hydrochloric acid at temperatures of 80, 90, and 100°C. All reactions were carried out in an excess of both tetramethylurea and water, with first-order dependence on acid concentration being observed. As the concentration of water was increased, the rate of hydrolysis decreased until equimolar amounts of water and tetramethylurea were present. Subsequent addition of water had no effect on the observed rate.     

Assessment of UV Biological Spectral Weighting Functions for Phenolic Metabolites and Growth Responses in Silver Birch Seedlings

In research concerning stratospheric ozone depletion, action spectra are used as biological spectral weighting functions (BSWFs) for describing the effects of UV radiation on plant responses. Our aim was to evaluate the appropriateness of six frequently used BSWFs that differ in effectiveness with increasing wavelength. The evaluation of action spectra was based on calculating the effective UV radiation doses according to 1–2) two formulations of the generalized plant action spectrum, 3) a spectrum for ultraviolet induced erythema in human skin, 4) a spectrum for the accumulation of a flavonol in Mesembryanthemum crystallinum , 5) a spectrum for DNA damage in alfalfa seedlings and 6) the plant growth action spectrum. We monitored effects of UV radiation on the concentration of individual UV absorbing metabolites and chlorophyll concentrations in leaves and growth responses of silver birch ( Betula pendula ) seedlings. Experiments were conducted outdoors using plastic films attenuating different parts of the UV spectrum. Chlorophyll concentrations and growth were not affected by the UV treatments. The response to UV radiation varied between and within groups of phenolics. In general, the observed responses of phenolic groups and individual flavonoids were best predicted by action spectra extending into the UV-A region with moderate effectiveness.