PHOTODYNAMIC EFFECTS OF NEW SILICON PHTHALOCYANINES: In vitro STUDIES UTILIZING RAT HEPATIC MICROSOMES AND HUMAN ERYTHROCYTE GHOSTS AS MODEL MEMBRANE SOURCES

Abstract— Photodynamic therapy (PDT) of cancer is a modality that relies upon the irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphasis to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic effects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed significant destruction of cytochrome P-450 and monooxygenase activities, and enhancement of lipid peroxidation, when added to microsomal suspension followed by irradiation with ∼ 675 nm light. These two Pc named SiPc IV (HOSiPcOSi[CH₃]₂[CH₂]₃N[CH₃]₂) and SiPc V (HOSiPcOSi[CH₃]₂[CH₂]₃N[CH₃]₃¹ I) showed dose-dependent photodestruction of cytochrome P-450 and monooxygenase activities in liver microsomes, and photoenhancement of lipid peroxidation, lipid hydroperoxide formation and lipid fluorescence in rnicrosomes and erythrocyte ghosts. Compared to chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V produced far more pronounced photodynamic effects. Sodium azide, histidine, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded highly significant protection against SiPc IV- and SiPc V-mediated photodynamic effects. However, to a lesser extent, the quenchers of superoxide anion, hydrogen peroxide and hydroxyl radical also showed some protective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer.     

Study of the energy and charged multiplicity dependence of inclusiveπ− production in π−p interactions up to fermilab energies

Using new data from 100 $\text{GeV}\text{c π}{}^{\mathrm{?}}$ interactions, we find the energy dependence of the invariant cross-section in the target fragmentation (central) region to be consistent with an $\text{A + Bs}{}^{\mathrm{<mtext>?</mtext><mtext>1</mtext><mtext>2</mtext>}}\text{(C + Ds}{}^{\mathrm{<mtext>?</mtext><mtext>1</mtext><mtext>4</mtext>}}\text{)}$ behavior. The leading particle peak near x = + 1 exhibits a width in x which becomes smaller with increasing energy and an integrated cross section which is approximately energy independent.     

Time‐Resolved Phase Transitions of the Nanocrystalline Cubic to Submicron Monoclinic Phase in Mn2O3‐ZrO2

The nanocrystalline cubic phase of zirconia was found to be thermally stabilized by the addition of 3 to 40 mol % manganese. The nanocrystalline cubic, tetragonal and monoclinic phases of zirconia stabilized with manganese (III)oxide (Mn‐Stabilized Zirconia) were prepared by thermal decomposition of carbonate and hydroxide precursors. Both the crystallization and isothermal phase transitions associated with Mn‐SZ were studied using high temperature x‐ray diffraction and x‐ray diffraction of quenched samples. Cubic Mn‐SZ initially crystallized and progressively transformed to tetragonal, and monoclinic structures above 700°C. The nanocrystalline cubic Mn‐SZ containing 25 mol % Mn was found to have the greatest thermal stability, retaining its cubic form at temperatures as high as 800°C for periods up to 25 hours. Higher than 40 mol %, cubic Mn₂O₃ was found to coexist with cubic Mn‐SZ. The crystallite sizes observed for the cubic, tetragonal and monoclinic Mn‐SZ phases ranged from 50 to 137, 130 to 220, and 195 to 450 Å respectively, indicating, for ZrO₂, that particle size was a primary factor in determining its polymorphs. The classical Avrami equation for nucleation and growth was applied to the observed phase transformations.     

Study of phase separation in polyurethane using paramagnetic labels. Effect of soft segment molecular weight,structure, and thermal history

The morphology of segmented polyurethane (PU) elastomers was studied by means of ESR at various temperatures ranging from 100K-450K. The PU's were based on 4,4'-diphenylmethane diisocyanate (MDI), poly (oxytetramethylene) glycols (PTMO) and hydroxyl-terminated random compolymers of tetrahydrofuran and 3-methyl-tetrahydrofuran (THF/Me-THF). Purified 1,4-butanediol (BD) was used as a chain extender. The nitroxide probe, 4-hydroxy-2-2',6-6'-tetramethylpiperidine-1-oxyl (TEMPOL), was used to label the polyurethanes by reaction with an NCO group of MDI. Analysis of the electron spin resonance (ESR) spectra suggested that the label situates at heterogeneous sites, which means that a two-phase domain is present. The morphologies at 300K and 400K were compared. It was found from ESR spectra that polyurethanes made from soft segments having higher MW exhibited greater phase separation at 300K than their corresponding elastomers made from lower MW soft segments. However, at 400K the more isotropic ESR spectra for the PUs containing higher MW soft segments suggested that the PUs were more mobile than their analogs having lower MW soft segments. The introduction of 3-methyl side groups decreased the phase mixing at 400K due to steric hindrance.     

Photophysical behavior of open-shell first-row transition-metal octabutoxynaphthalocyanines: CoNc(OBu)8 and CuNc(OBu)8 as case studies

Ultrafast photodynamics and density functional theory/time-dependent density functional theory (DFT/TDDFT) results for complexes of Co and Cu with 5,9,14,18,23,27,32,36-octabutoxynaphthalocyanine [CoNc(OBu)8 and CuNc(OBu)8] are reported. As a basis for this work, details concerning the syntheses of these complexes and the corresponding Zn complex (used as a reference) are given. Transient absorption spectrometry with femtosecond time resolution combined with a detailed DFT/TDDFT analysis has been employed to construct a complete picture of the excited-state dynamics after Q-band excitation of the Co and Cu complexes and to gain an understanding of the relationship between the nature of the metal center and the excited-state lifetime. The Co complex was shown to return to its ground state via two competing channels: a (2)T1(pi, pi*) state that decayed with a lifetime of 1 ps and a low-lying (2)(d, d) state that repopulated the ground-state surface with a lifetime of 15 ps. CuNc(OBu)8 showed ground-state repopulation from the (2)T1(pi, pi*) state via a lower-lying ligand-to-metal charge-transfer (LMCT) state that was completed within a few nanoseconds. The photophysical behavior of the cobalt and copper complexes was compared to that previously reported for the nickel analog in an effort to highlight the effect of the central metal on the nature and rates of the deactivation pathways. The results described in this work provide basic knowledge that is relevant to the use of these compounds as photothermal sensitizers in cancer therapy.     

The path relation for directed planar graphs in rectangles, and its relation to the free diad

In this paper, we define the path relation of a directed graph to be the relation which relates two vertices if there is a path from the first to the second. We study the restriction of this relation to paths from sources to sinks, and consider the question of when two finite graphs embedded in a rectangle give the same relation. We find a set of local changes to these graphs which can be used to get between any two graphs for which this relation is the same. Furthermore, we classify the relations which can arise as this relation for a finite directed graph embedded in a rectangle as the triconvex relations between finite ordinals (defined in this paper).This work originated from some of the author’s work on category theory. It turns out that the category of finite ordinals and relations that can be the path relation of a directed graph embedded in a rectangle, is relevant to the study of diads—introduced by the author as a common generalisation of monads and comonads (note that the terms diad and dyad have been used to mean different things by other authors). More specifically, the referee of one of the author’s papers suggested that it would be useful to identify the category which plays the role for diads that the category of finite ordinals and order-preserving functions plays for monads. It turns out that the category of finite ordinals and relations that can be path relations of graphs embedded in a rectangle, is exactly the category that plays this role.     

Transient studies of carbon monoxide oxidation over platinum catalyst

The applicability of transient techniques to the study of the catalytic oxidation of carbon monoxide is discussed. It is shown that at 100–150°C adsorption and desorption equilibria between the gas phase and catalyst cannot be assumed, and an elementary step formulation may be used to predict both multiple steady states and transient behaviour.     

NEW PHTHALOCYANINES FOR PHOTODYNAMIC VIRUS INACTIVATION IN RED BLOOD CELL CONCENTRATES

Abstract Cationic phthalocyanines with either aluminum or silicon as the central metal were evaluated for their ability to inactivate viruses in red blood cell concentrates (RBCC) photodynamically. In addition, the virucidal potential of a substituted anionic phthalocyanine, aluminum dibenzodisulfophthalocyanine hydroxide (AlN₂SB₂POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (AIPcS₄OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitisvirus (VSV), the viruci dal potential of these phthalocyanines was: HOSiP_COSi(CH₃)₂(CH₂)₃N⁺(CH₃)₃I- (Pc 5) = SiPC[OSi(CH₃)₂-(CH₂)₃N⁺(CH₃)₃I-]₂ (Pc 6) > AIP_COSi(CH,)₂(CH₂)_?N⁺(CH₃)₂(CH_?)₁₁CH₃I- (Pc 21) = A1N₂SB₂POH = AlPcS₄ > HOSiPc[OSi(CH₃)₂(CH₂)₃N⁺(CH₃)₂(CH₂)₁₁CH₃1–]₂(Pc 14) > AIPcOSi(CH₃)₂(CH₂)₃N+(CH_S)₃I- (Pc 2). Phthalocy anine ligand 14 and Pc 21 are new phthalocyanines, made by quaternizing known amino analogues. Compared to VSV, the rate of inactivation of Sindbis virus (another model lipid-enveloped virus) was identical when treated in red blood cells (RBC) with Pc 5 and slightly higher when treated with Pc 6 and AlPcS₄OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or AlPcS₄OH required 15 min of irradiation to inactivate (>5 log₁₀ reduction) the virus. The extent of HIV-1 inactivation with AlN₂SB₂POH was 3.7 log₁₀ after 60 min of red light exposure. The RBC integrity after photosensitization was measured by the ability of the cells to bind to plates coated with poly-L-lysine, (which reflects the retention of the RBC surface negative charges) and hemolysis of the cells over a 7 day storage period. The RBC damage using these criteria was most pronounced with Pc 5 and Pc 6 but could be reduced when treatment was in plasma instead of buffer. These data indicate that lipid-enveloped viruses differ in their sensitivity to phthalocyanine photosensitization. Therefore, for virus sterilization of RBCC for transfusion the ability to inactivate human pathogenic viruses completely will have to be evaluated for each virus. The cationic Pc 5 appears to be a potentially useful virucidal agent.     

Multiparticle rapidity clustering in 200 GeV/cπ−p interactions

A study of multiparticle rapidity clustering is made using a generalized rapidity-gap method. The data for events with ?6 charged particles are compared to what would be expected from uncorrelated particle production. We find clear evidence for cluster production. The data are consistent with ～ 20% of all charged particles being produced in clusters of two charged particles; clusters of higher multiplicity are not required.