以微孔β沸石为硅铝源合成强酸性介孔分子筛

以微孔β沸石为硅铝源,通过碱处理和以十六烷基三甲基溴化铵为模板剂,合成了具有较强酸性的六方结构介孔分子筛材料B-MCM-41,并采用XRD、N₂吸附脱附、FT-IR、²7Al MAS NMR、HRTEM和水热处理等手段对其进行了结构表征,采用NH₃-TPD对其进行了酸性表征。实验结果表明,B-MCM-41具有明显强于常规介孔分子筛的酸性,且在C⁺₁0混合芳烃加氢脱烷基化反应中表现出了良好的催化性能。这主要是由于碱溶液将β沸石降解为沸石结构单元,在表面活性剂作用下五元环次级结构单元被引入了介孔铝硅酸盐B-MCM-41的结构。     

A hand-held fiber-optic implement for the site-specific delivery of photosensitizer and singlet oxygen

We have constructed a fiber optic device that internally flows triplet oxygen and externally produces singlet oxygen, causing a reaction at the (Z)-1,2-dialkoxyethene spacer group, freeing a pheophorbide sensitizer upon the fragmentation of a reactive dioxetane intermediate. The device can be operated and sensitizer photorelease observed using absorption and fluorescence spectroscopy. We demonstrate the preference of sensitizer photorelease when the probe tip is in contact with octanol or lipophilic media. A first-order photocleavage rate constant of 1.13 h(-1) was measured in octanol where dye desorption was not accompanied by readsorption. When the probe tip contacts aqueous solution, the photorelease was inefficient because most of the dye adsorbed on the probe tip, even after the covalent ethene spacer bonds have been broken. The observed stability of the free sensitizer in lipophilic media is reasonable even though it is a pyropheophorbide-a derivative that carries a p-formylbenzylic alcohol substituent at the carboxylic acid group. In octanol or lipid systems, we found that the dye was not susceptible to hydrolysis to pyropheophorbide-a, otherwise a pH effect was observed in a binary methanol-water system (9:1) at pH below 2 or above 8.     

Hematoporphyrin as a photosensitizer of tumors

Abstract— The ability of hematoporphyrin (Hp) to act as a photosensitizer of cells in vitro or in vivo is a matter of dispute, while hematoporphyrin derivative (Hpd), a mixture of porphyrins including hematoporphyrin, has been consistently found to be an effective photosensitizer both in vitro and in vivo. Until recently the actual component of the Hpd mixture responsible for these effects had not been identified. We have found that those preparations of Hp which contain, as an impurity, a porphyrin similar to that found to be responsible for the tumor photosensitizing ability of Hpd, may be effective photosensitizers of tumors but are generally of low efficacy. This material accounts for the entire photosensitizing activity of both Hp and Hpd in the SMT-F mammary carcinoma in DBA/2 HeHa mice.     

A simple synthesis of a targeted drug delivery system with enhanced cytotoxicity

A simple synthesis of a targeted drug delivery system with enhanced cytotoxicity to (epidermal growth factor receptor) EGFR(+) cancer cells.     

Synthesis and DNA interactions of a bis-phenothiazinium photosensitizer

We report the synthesis and characterization of N,N-bis[(7-dimethylamino)phenothiazin-5-ium-3-yl]-4,4-ethylenedipiperidine diiodide (3), consisting of two photosensitizing phenothiazinium rings attached to a central ethylenedipiperidine linker. At all time points (10, 30, 60 min) and all wavelengths (676, 700, 710 nm) tested, photocleavage of pUC19 plasmid DNA (22 degrees C and pH 7.0) was markedly enhanced by 1 microM of 3 in comparison to 1 microM of the parent phenothiazine methylene blue (MB). At concentrations of phenothiazine ranging from 5 to 0.5 microM, the photocleavage levels produced by compound 3 were consistently higher than the cleavage produced using approximately twice the amount of MB (e.g., 710 nm irradiation of 5 microM of 3 and 10 microM of MB cleaved the plasmid DNA in 93% and 71% yields, respectively). Scavenger assays provided evidence for the involvement of singlet oxygen and, to a lesser extent, hydroxyl radicals in DNA damage. Analysis of photocleavage products at nucleotide resolution revealed that direct strand breaks and alkaline-labile lesions occurred predominantly at guanine bases. While compound 3 and MB were both shown to stabilize duplex DNA, the DeltaTm values of calf thymus (CT) and C. perfringens DNAs were approximately three fold higher in the presence of compound 3. Finally, viscometric data indicated that CT DNA interacts with compound 3 and MB by a combination of groove binding and monofunctional intercalation, and with compound 3 by a third, bisintercalative binding mode.     

Direct electrodeposition of Pt nanotube arrays and their enhanced electrocatalytic activities

Ordered Pt nanotube arrays have been fabricated by one-step electrodeposition utilizing nanochannel alumina templates. The electro-oxidation of ethanol on Pt nanotube arrays in acidic medium has been investigated by cyclic voltammetry. The oxidation peak currents on the Pt nanotube array electrode for ethanol oxidation are about 1.7 times those on the commercial PtRu/C electrode. The high electrocatalytic activities of the Pt nanotube array towards the oxidation of ethanol made it an excellent platform for direct ethanol fuel cell applications.     

Type-II CdS nanoparticle-ZnO nanowire heterostructure arrays fabricated by a solution process: enhanced photocatalytic activity

We report a two-step, solution-based synthetic method to fabricate CdS nanoparticles-sensitized ZnO nanowire heterostructure arrays which showed enhanced photocatalytic activities in comparison with bare ZnO nanowire arrays.     

Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket

Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5' terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5'-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.     

Polarized surface enhanced Raman and absorbance spectra of aligned silver nanorod arrays

Polarized surface-enhanced Raman scattering (SERS) and UV-vis absorbance spectra were measured for a nonplanar Ag nanorod array substrate prepared by oblique angle vapor deposition. The anisotropy of the SERS polarization was shown to differ from that of the polarized UV-vis absorbance. The maximum SERS intensity was observed in the polarization direction perpendicular to the long axis of the Ag nanorods, while the UV-vis absorbance was strongly polarized along the direction of the long axis of the nanorod array. Analysis of the polarization data showed that molecular orientation was not the cause of the anisotropic SERS scattering. Rather, the SERS anisotropy was primarily attributed to the lateral arrangement of the three-dimensional tilted nanorod lattice in which highly localized plasmon modes are created by strong electromagnetic coupling between adjacent metallic nanorods.     

Electrically enhanced percutaneous delivery of delta-aminolevulinic acid using electric pulses and a DC potential

Selectivity of photodynamic therapy can be improved with localized photosensitizer delivery, but topical administration is restricted by poor diffusion across the stratum corneum. We used electric pulses to increase transdermal transport of delta-aminolevulinic acid (ALA), a precursor to the photosensitizer protoporphyrin IX (PpIX). ALA-filled electrodes were attached to the surface of excised porcine skin or the dorsal surface of mice. Pulses were administered and, in some in vivo cases, a continuous DC potential (6 V) was concomitantly applied. For in vitro 14C ALA penetration, 10 microm layers parallel to the stratum corneum were assayed by liquid scintillation analysis, and 10 microm cross sections were examined autoradiographically. As the electrical dose (voltage x frequency x pulse width x treatment duration) increased, there was an increase in penetration depth. In vivo delivery was assayed by measuring the fluorescence of PpIX in skin samples. A greater than two-fold enhancement of PpIX production with electroporative delivery was seen versus that obtained with passive delivery. Superimposition of a DC potential resulted in a nearly three-fold enhancement of PpIX production versus passive delivery. Levels were higher than the sum of PpIX detected after pulse-alone and DC-alone delivery. Electroporation and electrophoresis are likely factors in electrically enhanced delivery.     

Synthesis of a hypocrellin B-polyamide conjugate as DNA-targeting photosensitizer

A new hypocrellin B （HB） derivative bearing a bispyrrolecarboxamide-containing side chain was synthesized, which presents improved absorptivity in phototherapeufic window than HB and affinity feature towards dsDNA.     

Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon

Colon‐residing bacteria, such as vancomycin‐resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit^®‐based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso‐tetra(N‐methyl‐4‐pyridyl)porphine tetra‐tosylate (TMP), or 5‐aminolevulinic acid hexyl‐ester (h‐ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen‐releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6‐h period. For TMP and h‐ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon‐residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.     

Nonenzymic polycyclization of analogues of oxidosqualene with a preformed C-ring

Some nonenzymic epoxide-initiated polyolefin cyclization are reported. The presented molecules are partially constrained analogues of (3S)-oxidosqualene, the natural substrate to many important cyclase enzymes. These model compounds feature a preformed C-ring with built-in stereochemical information. The experimental results allow for an instructive comparison with the enzymic processes, particularly those of the cyclases in steroid biosynthesis (i.e. lanosterol synthase).     

Mutagenicity and dark toxicity of the second-generation photosensitizer bacteriochlorin a

Bacteriochlorin a (BCA) is an effective second-generation photosensitizer both in vitro and in vivo. BCA has a high molecular absorption coefficient (32,000 M-1 cm-1) at 760 nm. At this wavelength tissue penetration of light is almost optimal and melanin absorption is relatively low. BCA is preferentially retained in a number of tumour model systems and is rapidly cleared from non-cancerous tissues, thus inducing no or minor skin photosensitivity. Mutagenicity of BCA has been tested using the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA104. In all tester strains used, BCA induces, in the dark, a minute increase in the number of revertants. No linear correlation between the number of revertants and the BCA dose is observed. Incubation of isolated rat hepatocytes with BCA, in the dark, does not result in increased cell death as measured by leakage of cytosolic lactate dehydrogenase. A convenient bioassay to test possible genotoxicity in vivo is the established Somatic Mutation and Recombination Test (SMART) on Drosophila melanogaster. Bacteriochlorin was tested for induction of loss of heterozygosity in the white/white+ eye mosaic assay, which predominantly measures homologous mitotic recombination in somatic cells of Drosophila after treatment of larval stages. BCA did not induce loss of heterozygosity above the level of the incorporated controls, with or without illumination. Based on these results, obtained in prokaryotic and eukaryotic cells and in vivo, we are inclined to conclude that the dark toxicity and mutagenic properties of BCA, as measured by the applied bioassays, are negligible.     

Photo-properties of a silicon naphthalocyanine: a potential photosensitizer for photodynamic therapy

Abstract— The photoproperties of derivatized silicon naphthalocyanine have been investigated in order to assess its potential as a photosensitizer for photo-dynamic therapy. Absorption, fluorescence, phosphorescence and triplet absorption spectra have been measured. Oxygen quenching of the triplet state formed singlet oxygen in significant yields.     

Tumor vascular area correlates with photosensitizer uptake: analysis of verteporfin microvascular delivery in the Dunning rat prostate tumor

The parameters that limit supply of photosensitizer to the cancer cells in a solid tumor were systematically analyzed with the use of microvascular transport modeling and histology data from frozen sections. In particular, the vascular permeability transport coefficient and the effective interstitial diffusion coefficient were quantified for Verteporfin-for-Injection delivery of benzoporphyrin derivative (BPD). Orthotopic tumors had higher permeability and diffusion coefficients (Pd = 0.036 microm/s and D = 1.6 microm(2)/s, respectively) as compared to subcutaneously grown tumors (Pd = 0.025 microm/s and D = 0.9 microm2/s, respectively), likely due to the fact that the vessel patterns are more homogeneous orthotopically. In general, large intersubject and intratumor variability exist in the verteporfin concentration, in the range of 25% in plasma concentration and in the range of 20% for tissue concentrations, predominantly due to these microregional variations in transport. However, the average individual uptake of photosensitizer in tumor tissue was only correlated to the total vascular area within the tumor (R2 = 64.1%, P < 0.001). The data are consistent with a view that microregional variation in the vascular permeability and interstitial diffusion rate contribute the spatial heterogeneity observed in verteporfin uptake, but that average supply to the tissue is limited by the total area of perfused blood vessels. This study presents a method to systematically analyze micro-heterogeneity as well as possible methods to increase delivery and homogeneity of photosensitizer within tumor tissue.     

Substituted thiazolamide coupled to a redox delivery system: a new gamma-secretase inhibitor with enhanced pharmacokinetic profile

Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic A beta peptides, is an attractive approach for the treatment of Alzheimer's disease. We have designed a new gamma-secretase thiazolamide inhibitor bearing a dihydronicotinoyl moiety as Redox Delivery System which allows specific delivery of the drug to the brain. Through, on the one hand, A beta peptide production measurements by specific in vitro assays (gamma-secretase Cell Free assay and Cell Based assay on HEK 293 APP transfected cells) and, on the other hand, pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent gamma-secretase inhibitory activity in vitro. From the obtained results, it is expected that drug will be mainly delivered to the CNS with low diffusion in the peripheral tissues. Consequently the side effects of this gamma-secretase inhibitor on the immune cells could be reduced.     

Needle-like cobalt phosphide arrays grown on carbon fiber cloth as a binder-free electrode with enhanced lithium storage performance

Cobalt phosphide(CoP) is a promising anode candidate for lithium-ion batteries(LIBs) due to its high specific capacity and low working potential.However,the poor cycling stability and rate performance,caused by low electrical conductivity and huge volume variation,impede the further practical application of CoP anode materials.Herein,we report an integrated binder-free electrode featuring needle-like CoP arrays grown on carbon fiber cloth(CC) for efficient lithium storage.The as-prepared CoP/CC electrode integrates the advantages of 1 D needle-like CoP arrays for efficient electrolyte wettability and fast cha rge transpo rtation,and 3 D CC substrate for superior mechanical stability,flexibility and high conductivity.As a result,the CoP/CC electrode delivers an initial specific capacity of 1283 mAh/g and initial Coulombic effeciencies of 85.4%,which are much higher than that of conventional CoP electrode.Notably,the Co P/CC electrode shows outstanding cycling performance up to 400 cycles at 0.5 A/cm² and excellent rate performance with a discharge capacity of 549 mAh/g even at 5 A/cm².This work demonstrates the great potential of integrated CoP/CC hybrid as efficient bind-free and freestanding electrode for LIBs and future flexible electronic devices.