Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.     

Morphology of anisotropic polymer-dispersed liquid crystals and the effect of monomer functionality

The morphology of transmission gratings with varying Bragg spacings formed using polymer-dispersed liquid crystals were examined using high-resolution scanning electron microscopy and image analysis techniques. The effect on the morphology of small changes in the overall functionality of the prepolymer syrup was observed. An increase in the amount of monofunctional compound resulted in small, nearly spherical domains (<100 nm in diameter) confined in well-defined lamellae for samples with a 0.49 μm Bragg spacing. A decrease in concentration (an effective increase in monomer functionality) at this Bragg spacing resulted in larger domains (100–200 nm) with much greater distribution of sizes and shapes. The local volume fractions of discrete liquid crystalline (LC) domains was considerably larger in the latter case. An increase in the Bragg spacing to 1.35 μm also resulted in well-defined lamellae of LC domains, although much more coalescence into irregularly shaped individual domains was observed. Surprisingly, the local volume fraction of LC increased in the larger Bragg spacing samples. The morphology results are discussed qualitatively in terms of liquid–gel demixing where the inherent crosslink density and elasticity of the polymeric host must be considered in phase separation processes on the nanoscale. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35: 2825–2833, 1997     

Representations of infinite permutations by words (II)

We present an argument (due originally to R. C. Lyndon) which completes the proof of the following theorem: Every free group word which is not a proper power can represent any permutation of an infinite set.

     

Self-chemical ionization of diethylzinc

The self-chemical ionization of diethylzinc is examined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and semiempirical molecular orbital calculations. Electron impact of diethylzinc neutral produces the radical cation, C(4)H(15)Zn(+) (m/z x 122), which reacts further with the neutral (C(2)H(5))(2)Zn to give the following product ions: Zn(+) (m/z x 64), C(2)H(5)Zn(+) (m/z x 93), C(4)H(9)Zn(+) (m/z x 121), C(4)H(11)Zn(2)(+) (m/z x 187), and C(6)H(15)Zn(2)(+) (m/z x 215). To determine the structure and pathways for production of these ions, monoisotopic (12)C(4)H(15)(64)Zn(+), (64)Zn(+) and (12)C(2)H(5)(64)Zn(+) were individually isolated and reacted with the neutral background. We also performed semiempirical molecular orbital calculations (ZINDO/1). The molecular orbital calculations and experimental data are consistent in predicting that the ethyl group on the diethylzinc cation carries the positive charge. Copyright 1999 John Wiley & Sons, Ltd.     

The Crystal Structure of a Potassium Channel— A New Era in the Chemistry of Biological Signaling

The similarity to crown ethers is apparent when the arrangement of the oxygen atoms of the carbonyl groups of the protein backbone in the structure of the potassium channel (see schematic drawing of a section of the structure) found in the bacterium Streptomyces lividans is considered. This particular part of the channel pore acts as the selectivity filter, with the permeability of the channel for K⁺ being as much as 10 000 times greater than for the Na⁺ ion. In fact, in this area of the structure two K⁺ ions are located, a feature that enables high flux through the channel.     

Results of theoretical and experimental studies of solar wind and active galactic nuclei on LFVN VLBI network using S2 recording system

We discuss the results of two sessions of observations at the Low-Frequency VLBI Network (LFVN), carried out in 1999 (INTAS99.4) and 2000 (INTAS00.3) at a wavelength of 18 cm using the S2 recording system and processed using the correlator system in Pentictone, Canada. In different configurations of the experiments on studying the solar wind and active galactic nuclei, the antennas at the following sites were employed: Medvezhji Ozera (RT-64, Special Engineering Bureau of Moscow Power Engineering Institute, Russia), Pushchino (RT-22, Pushchino Radio Astronomy Observatory, Russia), Hartebeesthoek (RT-25, South Africa), Noto (RT-32, Italy), Shanghai (RT-25, China), Pune (RT-45, India), Svetloe (RT-32, Institute of Applied Astronomy RAS, Russia). The work resulted in successful testing of the method of radio probing of the solar-wind plasma by radiation of extragalactic sources, supplemented with the method of radio interferometric reception. Spectral analysis of the obtained data allowed us to estimate the index of spatial spectrum of the electron number density.uctuations and the transfer velocity of the solar-wind inhomogeneities on the sounding path. We present and discuss the retrieved images of STA-102 quasar and the BL Lacertae object 1418+546 with millisecond angular resolution and demonstrate the results of modeling the structure of these sources. __________ Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Radiofizika, Vol. 50, No. 4, pp. 275–299, April 2007     

Formation of secondary phases during crystal growth of Pb5Ge3O11

Studies of secondary phases formed during the Czochralski growth of lead germanate crystals (Pb₅Ge₃O₁₁) show that these phases form inclusions in the crystal, thereby reducing its optical quality, and can also cause twinning and cracking. Results of differential thermal analysis, energy dispersive X-ray fluorescence analysis, and X-ray diffraction studies of secondary phases are presented. The narrow stability range for Pb₅Ge₃O₁₁ shown in the phase diagram, the thermal instability of this compound, and its pronounced supercooling during crystallization suggest that equilibrium conditions are difficult to sustain and that other compounds of the PbO-GeO₂ family may form, although Pb₅Ge3O₁₁ is melting congruently. It is shown that Pb₃GeO₅ and PbGeO₃, which are both reported to melt congruently, can crystallize during the growth of Pb₅Ge₃O₁₁ forming inclusions in the crystal. The successful synthesis of these three compounds is reported. The compound Pb₃Ge₂O₇, reported in the literature, is identified as a mixture of Pb₅Ge₃O₁₁ and PbGeO₃. Experimental conditions are presented for growing single phase Pb₅Ge₃O₁₁ crystals of uniform composition and high optical quality. This paper is based on a presentation at the Conference on Preparation and Properies of Electronic Materials, Princeton, N. J., August 1975.