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.     

Pointwise convergence of the iterates of a harris-recurrent Markov operator

LetP be a Markov operator recurrent in the sense of Harris, withσ-finite invariant measureμ. (1) Ifμ is finite andP aperiodic, then forf ∈L ₁(μ),P ⁿf →f fdμ a.e. (2) Ifμ is infinite,P ⁿf → 0 a.e. for everyf ∈L _p (μ), 1≦p <∞.     

The hausdorff dimension of the sample path of a subordinator

The Hausdorff dimension of the range of an arbitrary subordinator is exactly determined in terms of the rate of linear drift and the Levy measure of the subordinator. This generalizes the result of Blumenthal and Getoor: that for a stable subordinator of indexσ, the dimension of the range isσ.     

Flavonoids of citrus—VIII Synthesis of Limocitrol, limocitrin and spinacetin

Allan-Robinson syntheses of limocitrol (3,5,7,4′-tetrahydroxy-6,8,3′-trimethoxyflavone), limocitrin (3,5,7,4′-tetrahydroxy-8,3′-dimethoxyflavone) and spinacetin (3,5,7,4′-tetrahydroxy-6-3′- dimethoxyflavone) are described. The direction of ring closure to give limocitrin or spinacetin is determined by the blocking group (benzyl or benzoyl) at the 4-position of the B-ring component.     

Water as buffer material for gold nanocluster growth

Water molecules adsorbed on SiO2/Si(100) at 140 K to form amorphous solid water (ASW) layers were utilized as a buffer for assisting the growth of gold nanoclusters. It was shown that the average height and diameter of the clusters deposited on the silicon oxide substrate following the buffer annealing/desorption increase as the buffer layer becomes thicker and as more gold is deposited. The clusters' height and diameter were determined by tapping mode AFM and high-resolution SEM imaging, respectively. Typical heights were between 0.5 and 4.5 nm, and the diameters were in the range of 3-9 nm for ASW layer thickness of 7-100 ML and gold deposition in the range of 0.2-1.2 A. The density of the clusters decreased from 65 x 10(10) to 8 x 10(10) cm (-2) in the same buffer layer thickness range. Significantly different morphology of the clusters is obtained when compared to those formed by direct deposition of gold on the silicon oxide surface and to those grown on top of Xe as buffer material.