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.     

REDISTRIBUTION AND VIRUS INACTIVATION EFFICACY OF A SILICON PHTHALOCYANINE IN RED BLOOD CELL CONCENTRATES AS A FUNCTION OF DELIVERY VEHICLE

The silicon phthalocyanine, HOSiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂ (Pc 4), is a new photosensi-tizer that can inactivate lipid-enveloped viruses in red blood cell concentrates (RBCC) upon exposure to red light. Because Pc 4 is insoluble in water, it was delivered either as an emulsion in saline and cremophor EL (CRM) or as a solution in dimethyl sulfoxide (DMSO). In RBCC, Pc 4 added in either vehicle distributed between the plasma and red blood cells (RBC) in a ratio of 4:6, similar to the ratio of these components in RBCC 3:7 (i.e. a hematocrit of 70%). Light exposure did not affect this distribution and caused only marginal degradation of Pc 4 at a light dose that inactivates >5 log,₀ vesicular stomatitis virus (VSV). Among human plasma proteins, Pc 4 bound mainly (about 70%) to lipoproteins and to a lesser extent to albumin and lower molecular weight proteins when delivered in DMSO. When delivered in CRM, distribution between lipoproteins and albumin became more even. Among the lipoproteins Pc 4 bound almost exclusively to very low-density lipoproteins (VLDL) when delivered in DMSO and to both VLDL and low-density lipoproteins when added in CRM. The rate of VSV inacti-vation was independent of the delivery vehicle but there was less RBC damage, as measured by hemolysis during storage, when Pc 4 was added in CRM. These results indicate that using CRM as emulsifier can enhance the specificity of Pc 4-induced photochemical decontamination of RBCC for transfusion.     

A Dinuclear Cobalt Cryptate as a Homogeneous Photocatalyst for Highly Selective and Efficient Visible-Light Driven CO2 Reduction to CO in CH3CN/H2O Solution

A dinuclear cobalt complex [Co₂(OH)L¹](ClO₄)₃ ( 1 , L¹=N[(CH₂)₂NHCH₂(m-C₆H₄)CH₂NH(CH₂)₂]₃N) displays high selectivity and efficiency for the photocatalytic reduction of CO₂ to CO in CH₃CN/H₂O (v/v=4:1) under a 450 nm LED light irradiation, with a light intensity of 100 mW cm⁻². The selectivity reaches as high as 98 %, and the turnover numbers (TON) and turnover frequencies (TOF) reach as high as 16896 and 0.47 s⁻¹, respectively, with the calculated quantum yield of 0.04 %. Such high activity can be attributed to the synergistic catalysis effect between two Co^II ions within 1 , which is strongly supported by the results of control experiments and DFT calculations.     

A Dinuclear Cobalt Cryptate as a Homogeneous Photocatalyst for Highly Selective and Efficient Visible‐Light Driven CO2 Reduction to CO in CH3CN/H2O Solution

A dinuclear cobalt complex [Co₂(OH)L¹](ClO₄)₃ ( 1 , L¹=N[(CH₂)₂NHCH₂(m ‐C₆H₄)CH₂NH(CH₂)₂]₃N) displays high selectivity and efficiency for the photocatalytic reduction of CO₂ to CO in CH₃CN/H₂O (v/v=4:1) under a 450 nm LED light irradiation, with a light intensity of 100 mW cm⁻². The selectivity reaches as high as 98 %, and the turnover numbers (TON) and turnover frequencies (TOF) reach as high as 16896 and 0.47 s⁻¹, respectively, with the calculated quantum yield of 0.04 %. Such high activity can be attributed to the synergistic catalysis effect between two Co^II ions within 1 , which is strongly supported by the results of control experiments and DFT calculations.     

Synthèse de complexes du tungstène,du chrome et du rhénium contenant un ligand 1,4-bidenté carbéne-alcéne

A general synthesis of alkene-carbene complexes of tungsten, chromium and rhenium, containing a six-membered ring system, is outlined and the crystal structure of two new complexes of this type, (CO)₄WC(OEt)(CH)(η²-CH₂CHCH₂) (CH₂CHCH₂) and (CO)₉Re₂(OCH₂CH₃(CH₂(CH₂(CH₂CHCH₂), is described.     

Thermodynamics of Bromo-Adamantane and Carbon Tetrabromide Under Pressure

Excess molar volumes at 298.15 K of the ternary system {CH₃(CH₂)₂CO₂(CH₂)₃CH₃+ CH₃(CH₂)₇OH+CH₃(CH₂)₆CH₃} and the binary mixtures {CH₃(CH₂)₂CO₂(CH₂)₃CH₃+ CH₃(CH₂)₇OH}, {CH₃(CH₂)₂CO₂(CH₂)₃CH₃+CH₃ (CH₂)₆CH₃} and {CH₃(CH₂)₇OH+ CH₃(CH₂)₆CH₃} were determined using an Anton Paar DMA 60/602 densimeter. All experimental values were compared with the results obtained with empirical expressions for estimation of the ternary properties from the binary data. Variable-degree polynomials were fitted to the results. This revised version was published online in July 2006 with corrections to the Cover Date.     

Reaction products between sodium diphenyl -amine-4-sulfonate and hydrated LaCl3

This paper presents the reactions of synthesis between the ligand sodium diphenylamine-4-sulfonate and the lanthanum(III) chloride hydrated. The compounds (LaCl₃)₂·(C₁₂H₁₀NSO₃Na)₃·2(CH₃CH₂OH) (A) and (LaCl₃)·(C₁₂H₁₀NSO₃Na)·(CH₃CH₂OH)·12H₂O (B) were obtained using the solvents ethanol and methanol (synthesis A) and ethanol and water (synthesis B). The produced compounds and the ligand were characterized by thermogravimetric and differential thermogravimetric analysis, IR spectroscopy and elemental analysis of sodium, carbon, hydrogen, nitrogen, sulfur, chlorine and lanthanum, whereas the residues from thermal decomposition were investigated by X-ray diffractometry. This revised version was published online in August 2006 with corrections to the Cover Date.     

Synthesis and characterization of tri-block fluorinated-n-alkanes

A series of triblock semifluorinated n-alkanes of general formula F(CF₂)_n(CH₂)_m(CF₂)_nF (n = 6, 8 and m = 4, 6, 8) have been synthesized and characterized. The synthesis of triblock compounds was performed in two different ways according to the length of the hydrogenated moiety. Coupling of two molecules of β-(perfluoro-n-alkyl)ethyl iodides leads to the triblock materials F(CF₂)₆(CH₂)₄(CF₂)₆F and F(CF₂)₈(CH₂)₄(CF₂)₈F. The synthesis of compounds with larger hydrogenated part is accomplished in two steps by the addition of perfluoro-n-alkyl iodide F(CF₂)_nI to 1,5-hexadiene and 1,7-octadiene, respectively to give the diiodo-adducts which are subsequently deiodinated to the final triblock products F(CF₂)₆(CH₂)₆(CF₂)₆F, F(CF₂)₆(CH₂)₈(CF₂)₆F, F(CF₂)₈(CH₂)₆(CF₂)₈F and F(CF₂)₈(CH₂)₈(CF₂)₈F. The obtained triblock semifluorinated n-alkanes are characterized by low surface free energies with good lubricant properties usable as additives in ski-wax formulations.     

Photopolymerization of vinyl monomers in the presence of chlorosilane compounds

The photopolymerization of vinyl monomers (methyl methacrylate and styrene) was investigated in the presence of chlorosilane compounds. It was found that these additives acted as photosensitizers. In the case of the photopolymerization of methyl methacrylate, the rate of polymerization was found to be proportional to the concentration of methyl methacrylate and to the square root of the chlorosilane concentration. The chain-transfer constants of these photosensitizers, SiCl₄, CH₃SiCl₃, (CH₃)₂SiCl₂, (CH₃)₃-SiCl, and (CH₃)₄Si, with ultraviolet irradiation were 25.6 × 10^?3, 18.4 × 10^?3, 17.5 × 10^?3, 14.4 × 10^?3 and 0.5 × 10^?3, respectively, for methyl methacrylate.     

Highly soluble tetra lauryl alcohol substituted phthalocyanines; synthesis,electrochemistry, spectroelectrochemistry

The tetra peripherally β-substituted 2(3),9(10),16(17),23(24)-tetrakis undecyloxy phthalocyanine derivatives, M{Pc[O-(CH₂)₁₁CH₃)]₄} Pc: Phthalocyanine, [M: Zn(II)(2), Ga(III)(3), and Ti(IV)(4)], have been synthesized and characterized using FT-IR, ¹H, and ¹³CNMR, MS (MALDI-TOF), UV–vis, atomic force microscopy, electro and spectroelectro chemical and elemental analysis. The new synthesized complexes are soluble in both polar solvents and nonpolar solvents, such as THF, DMF, CHCl₃, CH₂Cl_2, benzene, and even hexane. Electrochemical and spectroelectrochemical measurements give common metal-based and/or Pc ring-based redox processes which support the proposed structures of the complexes. While titanium phthalocyanine exhibits metal- and Pc ring-based reduction and/or oxidation couples, gallium and zinc phthalocyanines give only Pc ring-based electron transfer processes.     

Ionic complexes simultaneously containing fullerene anions and coordination structures of metal phthalocyanines with I<Superscript>−</Superscript> and EtS<Superscript>−</Superscript> anions

The ionic complexes simultaneously containing negatively charged coordination structures of metal phthalocyanines and fullerene anions, viz., {Mn^IIPc(CH₃CH₂S^?) _x ·(I^?)_1?x }·(C₆₀ ^·?)· ·(PMDAE⁺)₂·C₆H₄Cl₂ (PMDAE is N,N,N′,N′,N′-pentamethyldiaminoethane, x = 0.87, 1) and {Zn^IIPc(CH₃CH₂S^?)_y·(I^?)_1?y }₂·(C₆₀ ^?)₂·(PMDAE⁺)₄·(C₆H₄Cl₂) (y = 0.5, 2) were synthesized. The both compounds were obtained as single crystals, which made it possible to study their crystal structures. In complex 1, the fullerene radical anions form honeycomb-like layers in which each fullerene has three neighbors with center-to-center interfullerene distances of 10.13–10.29 Å. Rather long distances between the C₆₀ ^·? radical anions results in the retention of monomeric C₆₀ ^·? in this complex down to the temperature of 110(2) K. In complex 2, fullerenes form dimers (C₆₀ ^?)₂ bonded by one C-C bond. The dimers are packed in corrugated honeycomb-like layers with interfullerene center-to-center distances of 9.90–10.11 Å. Manganese(II) and zinc(II) phthalocyanines coordinate iodide and ethanethiolate anions to the central metal atom to form unusual negatively charged coordination structures M^IIPc(An^?) (An^? is anion) packed in dimers {M^IIPc(An^?)}₂ with a short distance between the phthalocyanine planes (3.14 Å in 1 and 3.27 Å in 2). The pthalocyanine dimers also form layers with the PMDAE⁺ cations, and these layers alternate with the fullerene layers. The packing of spherical fullerenes with planar phthalocyanine molecules is attained by the insertion of fullerenes between the phenylene groups of phthalocyanines. The π-π-interactions of the porphyrin macrocycle with five- or six-membered fullerene rings are characteristic of the earlier studied ionic porphyrin and fullerene complexes. Such interactions are not observed for ionic complexes 1 and 2.     

NH<Subscript>3</Subscript>(CH<Subscript>2</Subscript>)<Subscript>5</Subscript>NH<Subscript>3</Subscript>BiCl<Subscript>5</Subscript>: an efficient and recyclable catalyst for the synthesis of benzoxazole,benzimidazole and benzothiazole heterocycles

In this work, the condensation of aromatic aldehydes with different two-substituted aniline catalyzed by NH₃(CH₂)₅NH₃BiCl₅ as heterogeneous and recyclable catalyst was reported. It was demonstrated that NH₃(CH₂)₅NH₃BiCl₅ can act as an efficient and active catalyst and is reusable for six runs without a significant loss of their catalytic activity. Simple preparation of the catalyst, high catalytic activity and good reusability are noteworthy advantages of this catalytic system in the synthesis of benzoxazole, benzimidazole and benzothiazole heterocycles at room temperature under solvent-free conditions.     

Bis(cyclopentadienyl)methan-verbrückte Zweikernkomplexe: II. Synthese und Reaktionen ringverbrückter Cobalt-Zweikernkomplexe mit zwei nucleophilen Metallzentren

The dinuclear cobalt complex [CH₂(C₅H₄)₂][Co(PMe₃)₂]₂ (2), which is prepared from CoCl(PMe₃)₃ and [CH₂(C₅H₄)₂]Li₂, reacts with NH₄PF₆ and CH₃I to form the protonated and methylated dications {[CH₂(C₅H₄)₂][CoR(PMe₃)₂]₂}²⁺ (R = H, CH₃). Treatment of {[CH₂(C₅H₄)₂][CoCH₃(PMe₃)₂]₂}I₂ (4) with LiCH₃ affords the neutral compound [CH₂(C₅H₄)₂][Co(CH₃)₂(PMe₃)]₂ (5). Ligand substitution of [CH₂(C₅H₄)₂][Co(CO)₂]₂ (6) with P₂Me₄ and 1,2-C₂H₄(PMe₂)₂(dmpe) gives the doubly-bridged complexes [CH₂(C₅H₄)₂][Co₂(CO)₂(μ-P₂Me₄)] (7) and [CH₂(C₅H₄)₂][Co₂(CO)₂(μ-dmpe)] (8), respectively. Similarly, [CH₂(C₅H₄)₂][Co-(CO)(PMe₃)]₂ (9) is obtained from the reaction of 6 with PMe₃. Oxidation of 6 with iodine gives [CH₂(C₅H₄)₂][Co(CO)I₂]₂ (11) which is transformed via {[CH₂(C₅H₄)₂][Co(PMe₂H)₃]₂}I₄ (12) into the triply-bridged cobalt(II) complex [CH₂(C₅H₄)₂][CO₂(μ-PMe₂)₂] (13).     

Chalcogen-Bonding Interactions in Telluroether Heterocycles [Te(CH2)m]n (n=1–4; m=3–7)

The Te ⋅⋅⋅ Te secondary bonding interactions (SBIs) in solid cyclic telluroethers were explored by preparing and structurally characterizing a series of [Te(CH₂)_m]_n (n=1–4; m=3–7) species. The SBIs in 1,7-Te₂(CH₂)₁₀, 1,8-Te₂(CH₂)₁₂, 1,5,9-Te₃(CH₂)₉, 1,8,15-Te₃(CH₂)₁₈, 1,7,13,19-Te₄(CH₂)₂₀, 1,8,15,22-Te₄(CH₂)₂₄ and 1,9,17,25-Te₄(CH₂)₂₈ lead to tubular packing of the molecules, as has been observed previously for related thio- and selenoether rings. The nature of the intermolecular interactions was explored by solid-state PBE0-D3/pob-TZVP calculations involving periodic boundary conditions. The molecular packing in 1,7,13,19-Te₄(CH₂)₂₀, 1,8,15,22-Te₄(CH₂)₂₄ and 1,9,17,25-Te₄(CH₂)₂₈ forms infinite shafts. The electron densities at bond critical points indicate a narrow range of Te ⋅⋅⋅ Te bond orders of 0.12–0.14. The formation of the shafts can be rationalized by frontier orbital overlap and charge transfer.     

Methyl group exchange in methyllithiumlithium bromide solutions in diethyl ether

The 220 MHz ¹H NMR spectrum of an ether solution of CH₃Li and LiBr in 10–1 ratio has been examined as a function of temperature. At low temperature distinct resonances, assignable to Li₄(CH₃)₄ and Li₄(CH₃)₃Br, are seen. Methyl group exchange between the two tetramers is observed in the NMR spectra in the temperature interval ?32 to 0°. The exchange is shown to be much slower than the dissociation of Li₄(CH₃)₄ tetramer, measured in other work. It is proposed that the rate-determining step is dissociation of Li₄(CH₃)₃Br to form Li₂(CH₃)₂ and Li₂(CH₃)Br. The rate constant for dissociation, k₂, obeys the equation ln k₂ = 36.0?83303/T.     

INACTIVATION OF Trypanosoma cruzi TRYPOMASTIGOTE FORMS IN BLOOD COMPONENTS BY PHOTODYNAMIC TREATMENT WITH PHTHALOCYANINES

Abstract— -Three phthalocyanine dyes HOSiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂ (Pc 4), HOSiPc-OSi(CH₃)₂(CH₂)₃N+(CH₃)3I- (Pc 5) and aluminum tetrasulfophthalocyanine hydroxide (AlOHPcS₄) were evaluated for their ability to inactivate the trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red blood cell concentrates (RBCC). The compound Pc 4 was found to be highly effective in killing T. cruzi, Pc 5 less effective and AlOHPcS₄ ineffective. With FFP as the medium, a complete loss of parasite infectivity in vitro (≥5 log₁₀) was found to occur with 2 μ M Pc 4 after irradiation with red light (>600 nm) at a fiuence of 7.5 J/cm², while with RBCC as the medium, a complete loss was found to occur at a fiuence of 15 J/cm². Even without illumination, Pc 4 at 2 μ M also killed about 3.7-4.1 log₁₀ of T. cruzi in FFP during 30 min. Observed differences in T. cruzi killing by the various phthalocyanines may relate to differences in binding; Pc 4 binds to the parasites about twice as much as Pc 5. Ultrastructural analysis of treated parasites suggests that mitochondria are a primary target of this photodynamic treatment. The data indicate that Pc 4 combined with exposure to red light could be used to eliminate bloodborne T. cruzi parasites from blood components intended for transfusion. The inactivation of T. cruzi by Pc 4 in the dark suggests a possible therapeutic application.     

Halogen displacement chemistry with silver and alkali metal salts: Preparation of SF5-esters, alcohols, aliphatic olefins, acids and an iodide

It has been found that treatment of SF₅-alkyl halides, especially SF₅(CH₂)₂Br, with silver salts such as CH₃C(O)OAg, p-CH₃C₆H₄SO₃Ag, CF₃SO₃Ag and AgNO₃ provides convenient pathways for preparing the following ester compounds: SF₅CH₂CH₂R (R = CH₃COO, TosO, CF₃SO₃, NO₃), SF₅(CH₂)₃OTos, and SF₅(CF₂)₄(CH₂)₂OAc. Important derivatives prepared from these esters include SF₅(CH₂)₂OH; SF₅(CF₂)₄(CH₂)₂OH. Several alkenes SF₅C(Br)CH₂ and SF₅CH₂(COOCH₃)CCHC(O)OCH₃ are obtained using silver salts. The use of alkali metals salts with SF₅(CH₂)₃Br is studied and yields SF₅(CH₂)₃I; also, a pathway has been developed that extends for SF₅(CH₂)₃₋ the chain by two-carbon atoms and also produces the first SF₅-containing malonic acid.     

Mono‐ and heterodi‐nuclear complexes of aluminium: synthesis,characterization and antifungal activity

Some new types of mononuclear derivatives, AlL(1–4)L(1–4)H ( 1a–1d ) of aluminium were synthesized by the reaction of Al(OPrⁱ)₃ and LH₂ [XC(NYOH)CHC(R)OH], X = CH₃, Y = (CH₂)₂, R = CH₃(L1H₂); X = C₆H₅, Y = (CH₂)₂, R = CH₃(L2H₂); X = CH₃, Y = (CH₂)₃, R = CH₃(L3H₂); X = C₆H₅, Y = (CH₂)₃, R = CH₃(L4H₂) in 1:2 molar ratio in refluxing benzene. Reactions of AlL(1–4)L(1–4)H with hexamethyldisilazane in 2:1 molar ratio yielded some new ligand bridged heterodinuclear derivatives AlL(1–4)L(1–4)SiMe₃ ( 2a – 2d ). All these newly synthesized derivatives were characterized by elemental analysis and molecular weight measurements. Tentative structures were proposed on the basis of IR and NMR spectra (¹H, ¹³C, 27 Al and ²⁹Si) and FAB‐mass studies. Schiff base ligands and their mono‐ and heterodi‐nuclear derivatives with aluminium have been screened for fungicidal activities. These compounds showed significant antifungal activity against Aspergillus niger and A. flavus. Copyright © 2007 John Wiley & Sons, Ltd.     

ansa-Metallocene derivatives: VIII. Syntheses and crystal structures of ethylene-bridged titanocene and zirconocene derivatives with permethylated ring ligands

Ethylene-bridged titanocene and zirconocene derivatives with permethylated ring ligands, C₂H₄(C₅(CH₃)₄)₂TiCl₂ and C₂H₄(C₅(CH₃)₄)₂ZrCl₂, have been synthesized and their crystal structures determined.     

Pressure‐Assisted Hetero‐ and Homodialkylation of Sulfide in [Pt2(μ‐S)2(dppp)2]: One‐Pot Conversion of {Pt2(μ‐S)2} into {Pt2(SR)2} and {Pt2(SR)(SR′)}

Heterodialkylation of [Pt₂(μ‐S)₂(dppp)₂] (dppp=Ph₂P(CH₂)₃PPh₂) was achieved under high pressure (10 kbar). This enabled the synthesis of rare diplatinum complexes with structurally diverse thiolate bridges, such as [Pt₂(μ‐SC₅H₁₀CO₂CH₂CH₃)(μ‐SC₃H₇)‐(dppp)₂](PF₆)₂, which was crystallographically identified. Complete homodialkylation was also achieved under similar conditions (6 kbar at room temperature), thus permitting the isolation of [Pt₂(μ‐SC₂H₄CO₂CH₂CH₃)₂(dppp)₂]‐(PF₆)₂. The isolation of these complexes extends the applications of high‐pressure chemistry to thiolato homo‐ and heterobridged complexes that are otherwise not accessible.