NEW PHTHALOCYANINE PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

Six new aluminum and silicon phthalocyanines have been synthesized and their photocytotoxicity toward V79 cells has been studied. The compounds that have been prepared are: AIPcOSi(CH₃)₂(CH₂),N(CH₃)₂, I; AIPcOSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?, II; CH₃SiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, III; HOSiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, IV; HOSiPcOSi(CH₃)₂(CH₂)₃)₃(CH₃)₃⁺I^?, V; and SiPc[OSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?]₂, VI. Relative growth delay values for compounds I-VI and relative cytotoxicity values for compounds I, II, IV, V and VI have been determined. Compounds I and II have been shown to be comparable in photocytotoxicity to what is presumed to be AIPcOH.xH₂O, and compound IV has been shown to have greater activity. The classes of compounds to which these six compounds belong appear to have potential for photodynamic therapy.     

VERDINS: NEW PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

The in vivo cytotoxic effect of verdins was determined by histological methods, using the FANFT-induced urothelial tumor line (AY-27). The results indicate that the verdins may be good alternatives to hematoporphyrin derivative for photodynamic therapy.     

双节奏和三重稳定性现象的一个自催化反应模型

远离平衡的化学反应系统即使在恒温和均相条件下也能产生各种各样复杂的动力学现象。从理论和实际应用的角度来说,其中的多重稳定性现象,尤其是双节奏现象和三重稳定性现象特别引起人们的兴趣。最近,这类现象已经在某些简单的恒温反应系统中观察到,一个代表性的例子是BrO_3~--ClO_2~--I~-系统。然而迄今还没有一个简单的恒温反应模型可以模拟这类现象。     

A TEST OF DIFFERENT PHOTOSENSITIZERS FOR PHOTODYNAMIC TREATMENT OF CANCER IN A MURINE TUMOR MODEL

Abstract The efficiency of different sensitizers for photodynamic therapy (PDT) was tested using a model system with a C3H mammary carcinoma growing subcutaneously on the dorsal side of mouse feet. Growth curves were constructed from which growth delay and doubling time in the regrowth phase were calculated. As PDT induced oedema in the mouse foot, this model system also allowed assessment of normal tissue response.
The following sensitizers were tested: hematoporphyrin derivative (HpD), Photofrin II (PII), tetraphenylporphinetetrasulfonate (TPPS₄), acridine orange (AO), phthalocyanine tetrasulfonate (PCTS), Al- and Zn-phthalocyanine tetrasulfonate (A1PCTS and ZnPCTS). For tumor control, the following sensitizer efficiencies were found: PII > HpD > AIPCTS > TPPS₄ >>> ZnPCTS, PCTS, AO. With regard to sensitizing normal-tissue damage: PII > AIPCTS, TPPS₄ > HpD, ZnPCTS, PCTS. The results suggest that AIPCTS should be further evaluated for use in PDT.     

UPTAKE KINETICS AND INTRACELLULAR LOCALIZATION OF HYPOCRELLIN PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY: A CONFOCAL MICROSCOPY STUDY

Hypocrellins are naturally occurring compounds with photosensitizing properties in biological systems. We have prepared synthetic derivatives of hypocrellin B, which have promise as photosensitizers in the clinical application of photodynamic therapy. The intracellular localization and uptake kinetics of hypocrellin B and several selected hypocrellin congeners were determined semiquantitatively by fluorescence confocal microscopy in monolayer cultures of EMT6/Ed murine tumor cells. Each compound had unique uptake kinetics. Although no compound tested to date has demonstrated nuclear labeling, most could be detected in lysosomes, Golgi, endoplasmic reticulum and, to a minor extent, in cellular membranes. No two compounds gave identical labeling distributions. The differences are assumed to originate in physicochemical properties characteristic of each compound, which may ultimately impact upon the primary modality of phototoxicity.     

A NEW MODEL OF FROST HEAVE PREDICTION FOR CLAYEY SOILS

After analysing the results of systematic experimental research on frost susceptibility tests, a new frost heave prediction model, including the heave ratio η and rate R, is first proposed in this paper. Six main factors influencing frost heave are considered: initial water content W, initial dry unit weight γd, frost penetration rate Vf, groundwater level Hw, plasticity index Ip and ion content S. The model could be expressed by: η= B0WB1γBd2VB31·exp(B4Hw)exp(B5Ip)exp(B6S) and R = B'0WB'1γB'2dexp(B'3Hw)exp(B'4Ip)exp(B'5S) with a good reliability, where B0 to B6 and B'0 to B'5 are the characteristic constants of clayey soils. The effect of each factor on frost susceptibility of soils is discussed also.     

A NEW MODEL FOR CONCENTRATION DEPENDENCE OF POLYMER CHAIN DIMENSIONS

A new model for concentration dependence of polymer chain dimensions over the wholeconcentration range was proposed. The hydrodynamic volume of a solvated macromoleculewas found to be a universal function of the degree of coil overlapping (c/c~*). The radiusof gyration (R_g) and the expansion coefficient (α) of polymer in solution or in bulk. pre-dicted by this model are much better in agreement with the experimental data of small angleX-ray scattering and neutron scattering from literature, than with the values predicted byother models and theories.     

AGGREGATION OF 2,3-DIHYDROXY-ETIOCHLORIN I. AN AMPHIPHILIC MODEL COMPOUND FOR PHOTODYNAMIC THERAPY AND GREEN HEME d

The crystal structure of 2,3-dihydroxy-etiochlorin I has been determined to obtain information on its aggregation behavior. Cis -dihydroxychlorins serve as model compounds for green heme d and show promising photonecrotic activity in photodynamic therapy. The compound shows strong aggregation in the solid state facilitated by intramolecular hydrogen bonding between one hydroxy group and pyrrole nitrogens of neighboring molecules. This novel type of aggregation leads to chain-type aggregates in the crystal. The title compound 4 crystallized in the monoclinic space group Ia (Z = 4) with unit cell dimensions a = 9.902(4) Å, b = 26.430(9) Å, c = 10.823(5), β= 104.47(3) Å, V = 2743(2) ų. The structure was refined to an R -value of 0.097 on the basis of 1150 reflections with F > 4.0σ (F) (130 K).     

AN INDIRECT METHOD FOR DETERMINATION OF PARAMETERS IN THE FORECAST MODEL

An indirect method for determining some parameters in a forecast model has been developed, by which the program of the original model with little modification can be used as a subroutine of the inversion system and the optimum estimate of the parameters can be obtained by calling the subroutine time after time. It is specially useful for the sophisticated numerical weather prediction model. It may also be utilized to improve the forecast timely in case of obvious differences between the recent observations and the forecasts. The effect of the method is verified by numerical simulation tests with simple models.     

THE PREPARATION AND SURFACE CHARACTERIZATION OF AN IDEAL MODEL COLLOID

ABSTRACT

Monodisperse polystyrene latexes were prepared with and without emulsifier using persulfate initiator. The latexes were ion-exchanged with purified Dowex 50W(H⁺)-Dowex 1(0H^?) mixed resin to remove solute electrolyte and adsorbed emulsifier and to convert acidic surface groups to the H⁺ form. Conductometric titration showed that all latexes contained only strong-acid surface groups, presumably the sulfate endgroups of the polymer chains introduced by the persulfate initiator. The sulfate-stabilized latexes (H⁺ form) were hydrolyzed to the hydroxyl form after 2–8 weeks at room temperature or 48–120 hours at 363°K. The rate of the acid-catalyzed hydrolysis is enhanced by increasing the glass contact surface area, by adding Pyrex glass beads. Conductometric titration of the hydrolyzed latexes after ion exchange showed no titratable groups, indicating that the latexes were stabilized by hydroxyl groups. The latexes were oxidized to the carboxyl form by heating the hydroxyl-stabilized latex with persulfate and traces of heavy metal ions or the sulfate-stabilized latex in contact with Pyrex glass beads. For example, latex 520′ prepared without emulsifier using persulfate initiator and bicarbonate buffer contained only strong-acid surface groups after cleaning, no titratable groups after hydrolysis, and only carboxyl groups in the same number as the original sulfate groups after oxidation. Thus the three forms of the latex provide ideal model colloids, rigid monodisperse spheres stabilized with the same number of chemically bound surface groups of three types —strong-acid sulfate, weak- acid carboxyl, and uncharged hydroxyl.     

CHLORIN AND PORPHYRIN DERIVATIVES AS POTENTIAL PHOTOSENSITIZERS IN PHOTODYNAMIC THERAPY

In order to find a photosensitizer with better optical properties and pharmacokinetics than Photofrin II, a series of new photosensitizers related to methyl pheophorbide-a and chlorin-e6 were synthesized. These compounds absorb at substantially longer wavelengths (lambda max 660 nm) than does Photofrin II (630 nm) and show promise for use in photodynamic therapy. Among the porphyrins, we observed that long carbon chain ether derivatives are better photosensitizers than their ester analogs. These sensitizers were tested for in vivo photosensitizing activity vis-a-vis Photofrin II, using the standard screening system of DBA/2 mice bearing transplanted SMT/F tumors. Most of these photosensitizers were found to have better tumoricidal photosensitizing activity than Photofrin II and demonstrated more rapid attenuation of normal tissue photosensitivity with time after administration vis-a-vis Photofrin II.     

PHOTOINDUCED BIREFRINGENCE AND NUMERICAL SOLUTION OF A NEW DYNAMIC MODEL IN AN AMORPHOUS COPOLYMER CONTAINING AZOBENZENE GROUPS*

Photoinduced birefringence is investigated in a new amorphous copolymer containing azobenzene groups. Thelevels of birefringence signal are found to depend on the polarization angle between the pump beam and the probe beam, andon the ellipticity of the pump beam. Both the growth and decay processes of the birefringence signal can be described byknown biexponential equations. The rate constants and the amplitudes associated with the growth process of thephotoinduced birefringence are observed to display a linear dependence with the pump beam intensity. A new dynamicmodel of the photoinduced birefringence is presented taking into account the contributions of both the trans and cis isomersof azobenzene groups and the local polymer segments. The numerical treatment of this model shows good agreement with theexperimental data in the whole writing-erasing processes of the photoinduced birefringence conducted in our polymersamples.     

INACTIVATION OF LIPID-CONTAINING VIRUSES BY HYDROPHOBIC PHOTOSENSITIZERS AND NEAR-ULTRAVIOLET RADIATION

Abstract—The hydrophobic photosensitizers acridine and phenothiazine inactivate the lipid-contnining viruses PM2,φ6, and herpes simplex when samples are illuminated with near-UV radiation. φ23–1- a . which is insensitive to organic solvents and presumably contains no lipids. is not inactivated under comparable conditions. For acridinc, the inactivation of virus requires that oxygen be present and is inhibited by sodium azide, implicating the involvement of singlet oxygen. For phenothiazine, oxygen is not required for photosensitized inactivation. Treatment of PM2 with acridine and near-UV light caused a complete disruption of the virion, as determined by sucrose gradient analysis of treated and untreated samples. These data and related observations suggest that lipid-containing viruses are inactivated through photosensitized membrane damage.     

AN S- AND P-CONTAINING FLAME RETARDANT FOR POLYPROPYLENE

A novel charring agent,bis(1-oxo-4-hydroxymethyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane) phenylphosphine sulfide (BCPPS),has been synthesized,and it is combined with ammonium polyphosphate (APP) and melamine phosphate (MP) to impart flame retardance and dripping resistance for polypropylene (PP).The fire performance of the treated PP is investigated by limiting oxygen index (LOI),vertical burning test (UL-94) and cone calorimeter,and the thermal stability and thermal oxidative stability of the compos...     

PHOTOSENSITIZERS IN ORGANIZED MEDIA: SINGLET OXYGEN PRODUCTION AND SPECTRAL PROPERTIES

Abstract— Measurement of singlet oxygen production by porphyrin-type photosensitizers in simple buffer solutions show that TPPS is more efficient than PII (Photofrin II) or than hematoporphyrin. This behavior was observed using three independent analytical detection methods for ¹O₂: RNO bleaching, tryptophan degradation, and oxygen consumption. Similar results were obtained when irradiating with a classical light source or with a pulsed dye laser. Addition of EPC liposomes to the buffer solution caused a decrease of efficiency for TPPS and an increase for PII. Addition of BSA shows the same relative pattern: a small increase of efficiency for TPPS and a tenfold increase for PII. These changes can be ascribed to specific interactions between the sensitizer molecules and the organized medium. Since changes in the fluorescence properties are also due to interactions with the medium, we monitored the emission of the sensitizers as a function of the environment. The fluorescence peak positions (at 648, 705 nm for TPPS and at 615, 677 nm for PII) were all red shifted. The intensities show an increase, particularly for PII in liposomes, due to a marked change in the microviscosity.     

光学活性的醛酮鉴定试剂

醛酮鉴定试剂很多,利用肼基与羰基缩合的尤其常用,如苯肼、氨基脲等等。     

OCTA-ALKYL ZINC PHTHALOCYANINES: POTENTIAL PHOTOSENSITIZERS FOR USE IN THE PHOTODYNAMIC THERAPY OF CANCER

The synthesis, characterization and electronic spectra of a series of nine 1,4,8,11,15,18,22,25-octa-alkyl zinc phthalocyanines (ZnPc), potential photosensitizers for the photodynamic therapy of cancer, are described. The substituents on the phthalocyanine (Pc) macrocycle “red-shift” the absorbance maximum, in cyclohexane, of all nine members of this series to a value of 703 ± 2 nm, with a corrected fluorescence emission maximum for the octadecyl derivative of 715 nm. The solubilities and degree of aggregation of six examples in cyclohexane have been measured. The highest homologue, the octadecyl derivative, remains essentially unaggregated to a concentration of 1.5 ± 10^?4 mol dm^?3. The photostability of this Pc has been examined and the compound shown to be sensitive to photooxidation processes, which lead to its decomposition to 3,6-fcw-decylphthalimide. Known singlet oxygen quenchers inhibit the photodecomposition. In a comparative study, the octadecyl ZnPc underwent a more rapid photodecomposition than the corresponding metal-free derivative.     

AN ANALYSIS OF A TRIPLET EXCITON MODEL FOR THE DELAYED LIGHT IN CHLORELLA*

Abstract— The time dependence of the delayed light in the green alga Chlorella pyrenoidosa has been examined quantitatively in the 1 to 12 msec range after excitation with light pulses (A = 6328 Å) of 100 μsec and 4.5 msec duration. We have confirmed the data of Tollin, Ruby, and Bertsch et al., on the time course of the delayed light in the msec range. New experiments, with 100 μsec flash excitation, on the time dependence of the delayed light emitted by Chlorella treated with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DMU), hydroxylamine, methyl violgen, and various combinations of these chemicals are presented. Also, data on the dependence of the delayed light intensity on the intensity of the excitation light in the 1.5 and 5.0 msec range are reported. The square law dependence, reported by Jones, in the 140 and 250 msec range is confirmed in the 1.5 and 5.0 msec range at very low light levels. The experimental data on delayed light has been analyzed in terms of a model which incorporates triplet exciton fusion. The following major points result from this analysis: (1) A triplet exciton kinetic model can explain both the time dependence and the excitation intensity dependence of the delayed light emitted by Chlorella. (2) The density of triplet excitons predicted by the model from the observed delayed light intensity is much less than that which can be detected by flash photolysis measurements. Therefore, the failure of such measurements to detect triplet states in vivo does not disprove the model. (3) The possibility of changes in the rate of electron transfer reactions of photosynthesis is included in the kinetic model. The predictions from the model are compared with the effects of chemical additives on the time dependence of the delayed light decay. (4) The proposed triplet exciton model predicts that the delayed light intensity may, under certain specific conditions, be affected by a magnetic field. The negative result of an attempt to observe this effect is reported and discussed. (5) It is concluded that the proposed triplet ‘fusion’ model is a valid alternative to the electron-hole recombination model.     

等离子体热解煤及模型化合物的热力学分析

在等离子体反应器中煤及石墨热解生成乙炔研究的基础上,选取了与挥发物相类似的气态脂肪族及液态芳香族模型化合物以及设计了与这些模型化合物生成乙炔有关的反应,通过计算这些热解反应在不同温度下的Gibbs函数变化ΔG°,对其进行了热力学分析。根据上述实验和理论研究,更进一步证实了煤释放出的挥发分是生成乙炔的主要来源,同时也得出了乙炔在高温时易生成是由于熵效应。这些研究为探索煤在等离子体热解反应器中生成乙炔的机理提供了有用的信息。