Molecular mobility in hydrogels based on poly(acrylic acid) and macrodiisocyanates

Partially water-swellable polymer networks were synthesized on the basis of poly(acrylic acid) and various macrodiisocyanates. Hydrophilic and hydrophobic local regions were revealed in swollen networks (hydrogels) by means of the spin probe technique. The local mobility in hydrophobic regions depends on the macrodiisocyanate structure; however, it is substantially lower than that in hydrophilic regions for all gels. It was assumed that the presence of hydrophobic and hydrophilic regions and the difference in their local dynamics must have a substantial effect on the pharmacokinetics of release of drugs immobilized in these hydrogels.     

Crystal structure and magnetic properties of two new cobalt selenite halides: Co5(SeO3)4X2 (X=Cl, Br)

Two new isostructural cobalt selenite halides Co₅(SeO₃)₄Cl₂ and Co₅(SeO₃)₄Br₂ have been synthesized. They crystallize in the triclinic system space group P−1 with the following lattice parameters for Co₅(SeO₃)₄Cl₂: a=6.4935(8) Å, b=7.7288(8) Å, c=7.7443(10) Å, α=66.051(11)°, β=73.610(11)°, γ=81.268(9)°, and Z=1. The crystal structures were solved from single-crystal X-ray data, R1=3.73 and 4.03 for Co₅(SeO₃)₄Cl₂ and Co₅(SeO₃)₄Br₂, respectively. The new compounds are isostructural to Ni₅(SeO₃)₄Br₂.Magnetic susceptibility measurements on oriented single-crystalline samples show anisotropic response in a broad temperature range. The anisotropic susceptibility is quantitatively interpreted within the zero-field splitting schemes for Co²⁺ and Ni²⁺ ions. Sharp low-temperature susceptibility features, at T_N=18 and 20 K for Co₅(SeO₃)₄Cl₂ and Co₅(SeO₃)₄Br₂, respectively, are ascribed to antiferromagnetic ordering in a minority magnetic subsystem. In isostructural Ni₅(SeO₃)₄Br₂ magnetically ordered subsystem represents a majority fraction (T_N=46 K). Nevertheless, anisotropic susceptibility of Ni₅(SeO₃)₄Br₂ is dominated at low temperatures by a minority fraction, subject to single-ion anisotropy effects and increasing population of S_z=0 (singlet) ground state of octahedrally coordinated Ni²⁺.     

Cyclic trihydroxamic acid derivatives

In the crystal structures of two cyclic trihydroxamic acid derivatives containing the same substructure unit, viz. 1,3,5‐trihydroxy‐1,3,5‐triazinane‐2,4,6‐trione dihydrate, C₃H₃N₃O₆·2H₂O, (I), and 1,3,5‐benz­yloxy‐1,3,5‐triazinane‐2,4,6‐trione, C₂₄H₂₁N₃O₆, (II), there is no significant difference in the geometric parameters. In (I), there are 11 hydrogen bonds of the O—H⋯O type inter­connecting the mol­ecules in a three‐dimensional network, while in (II) there are only two weak C—H⋯O hydrogen bonds. The results of IR spectroscopic analysis are in good agreement with the crystallographic study.     

Unified quantum logic

Unified quantum logic based on unified operations of implication is formulated as an axiomatic calculus. Soundness and completeness are demonstrated using standard algebraic techniques. An embedding of quantum logic into a new modal system is carried out and discussed.On leave of absence from Department of Mathematics, University of Zagreb, Pot. Pret. 165, YU-41001 Zagreb, Yugoslavia.     

Protein-coated β-ferric hydrous oxide particles: An electrokinetic and electrooptic study

Using microelectrophoresis and electric light scattering techniques, we investigated the adsorption characteristics, surface coverage and surface electric parameters of superstructures from two isoforms of plastocyanin, PCa and PCb, in an oxidized state adsorbed on β-ferric hydrous oxide particles. The surface electric charge and electric dipole moments of the composite particles and the thickness of the protein adsorption layer are determined in a wide pH range, at different ionic strengths and concentration ratios of PC to β-FeOOH. The adsorption of the two proteins was found to shift the particles’ isoelectric point and to alter the total electric charge and the electric dipole moments of the oxide particles to different extent. A “reversal” in the direction of the permanent dipole moment is observed at lower pH for PCb- than for PCa-coated oxide particles. Strict correlation is found between the changes in the electrokinetic charge of the composite particles and the variation in their “permanent” dipole moments. Data suggest that the adsorption of the proteins is driven by electrostatic and/or hydrophobic interactions with the oxide surfaces dependent on pH. The adsorption behaviour is consistent with the involvement of the “eastern” and “northern” patches of the plastocyanin molecules in their adsorption on the oxide surfaces that are differently charged depending on pH.     

Base-line model for identifying the bioaccumulation potential of chemicals

The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important mitigating factor was found to be metabolism. Accordingly, a simulator for fish liver was used in the model, which has been trained to reproduce fish metabolism based on related mammalian metabolic pathways. Other significant mitigating factors, depending on the chemical structure, e.g. molecular size and ionization were also taken into account in the model. The results (r(2)=0.84) obtained for a training set of 511 chemicals demonstrate the usefulness of the BCF base line concept. The predictability of the model was evaluated on the basis of 176 chemicals not used in the model building. The correctness of predictions (abs(logBSF(Obs)-logBCF(Calc))=0.75)) for 59 chemicals included within the model applicability domain was 80%.     

Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer

In current clinical practice, photodynamic therapy (PDT) is carried out with prescribed drug doses and light doses as well as fixed drug-light intervals and illumination fluence rates. This approach can result in undesirable treatment outcomes of either overtreatment or undertreatment because of biological variations between different lesions and patients. In this study, we explore the possibility of improving PDT dosimetry by monitoring drug photobleaching and photoproduct formation. The study involved 60 mice receiving the same drug dose of a novel verteporfin-like photosensitizer, QLT0074, at 0.3 mg/kg body weight, followed by different light doses of 5, 10, 20, 30, 40 or 50 J/cm2 at 686 nm and a fluence rate of 70 mW/cm2. Photobleaching and photoproduct formation were measured simultaneously, using fluorescence spectroscopy. A ratio technique for data processing was introduced to reliably detect the photoproduct formed by PDT on mouse skin in vivo. The study showed that the QLT0074 photoproduct is stable and can be reliably quantified. Three new parameters, photoproduct score (PPS), photobleaching score (PBS) and percentage photobleaching score (PBS%), were introduced and tested together with the conventional dosimetry parameter, light dose, for performance on predicting PDT-induced outcome, skin necrosis. The statistical analysis of experimental results was performed with an ordinal logistic regression model. We demonstrated that both PPS and PBS improved the prediction of skin necrosis dramatically compared to light dose. PPS was identified as the best single parameter for predicting the PDT outcome.