Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

Strain‑Induced Surface Interface Dual Polarization Constructs PML‑Cu/Bi_(12)O_(17)Br_(2) High‑Density Active Sites for CO_(2) Photoreduction

The insufficient active sites and slow interfacial charge trans-fer of photocatalysts restrict the efficiency of CO_(2) photoreduction.The synchronized modulation of the above key issues is demanding and chal-lenging.Herein,strain-induced strategy is developed to construct the Bi–O-bonded interface in Cu porphyrin-based monoatomic layer(PML-Cu)and Bi_(12)O_(17)Br_(2)(BOB),which triggers the surface interface dual polarization of PML-Cu/BOB(PBOB).In this multi-step polarization,the built-in electric field formed between the interfaces induces the electron transfer from con-duction band(CB)of BOB to CB of PML-Cu and suppresses its reverse migration.Moreover,the surface polarization of PML-Cu further promotes the electron converge in Cu atoms.The introduction of PML-Cu endows a high density of dispersed Cu active sites on the surface of PBOB,significantly promoting the adsorption and activation of CO_(2) and CO desorption.The conversion rate of CO_(2) photoreduction to CO for PBOB can reach 584.3μmol g-1,which is 7.83 times higher than BOB and 20.01 times than PML-Cu.This work offers valuable insights into multi-step polarization regulation and active site design for catalysts.

A cobalt(Ⅱ)porphyrin with a tethered imidazole for efficient oxygen reduction and evolution electrocatalysis

Electrocatalytic oxygen reduction and evolution reactions are involved in new energy conversion and storage technologies,such as various fuel cells and metal-air batteries and also water splitting devices[1,2].However,both reactions are very slow in kinetics,and thus catalysts are required[3,4].

Radicals on the silica surface:probes for studying dynamics by means of fast field cycling relaxometry and dynamic nuclear polarization

Determining the dynamics of adsorbed liquids on nanoporous materials is crucial for a detailed understanding of interactions and processes on the solid-liquid interface in many materials and porous systems.Knowledge of the influence of the presence of paramagnetic species on the surface or within the porous matrices is essential for fundamental studies and industrial processes such as catalysts.Magnetic resonance methods,such as electron paramagnetic resonance(EPR),nuclear magnetic resonance(NMR)and dynamic nuclear polarization(DNP),are powerful tools to address these questions and to quantify dy-namics,electron-nuclear interaction features and their relation to the physical-chemical parameters of the system.This paper presents an NMR study of the dynamics of polar and nonpolar adsorbed liquids,represented by water,n-decane,deuterated water and nonane-d20,on the native silica surface as well as silica modified with vanadyl porphyrins.The analysis of the frequency dependence of the nuclear spin-lattice relaxation time is carried out by separating the intra-and intermolecular contributions,which were analyzed using reorientations mediated by translational displacements(RMTD)and force-free-hard-sphere(FFHS)models,respectively.

Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters

BACKGROUND Radionuclides produce Cherenkov radiation(CR),which can potentially activate photosensitizers(PSs)in phototherapy.Several groups have studied Cherenkov energy transfer to PSs using optical imaging;however,cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge.Many laboratories face the need for expensive dedicated equipment.AIM To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs.METHODS The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs.To mitigate the need for expensive dedicated equipment and achieve the aim of the study,we developed a method that utilizes a chargecoupled device optical imaging system and appropriate long-pass filters of different wavelengths(manual sequential application of long-pass filters of 515,580,645,700,750,and 800 nm).Tetrakis(4-carboxyphenyl)porphyrin(TCPP)was utilized as a model PS.Different doses of copper-64(^(64)CuCl_(2))(4,2,and 1 mCi)were used as CR-producing radionuclides.Imaging and data acquisition were performed 0.5 h after sample preparation.Differential image analysis was conducted by using ImageJ software(National Institutes of Health)to visually evaluate TCPP fluorescence.RESULTS The maximum absorbance of TCPP was at 390-430 nm,and the emission peak was at 670 nm.The CR and CRinduced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above.The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity(total flux)difference between^(64)CuCl_(2)+TCPP and^(64)CuCl_(2).Moreover,the differential fluorescence images of TCPP were obtained by subtracting the^(64)CuCl_(2)image from the^(64)CuCl_(2)+TCPP image.The experimental results considering different^(64)CuCl_(2)doses showed a dosedependent trend.These results demonstrate that a bioluminescence imaging device coupled with different longpass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP.CONCLUSION This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

几种水溶性Porphyrin在电化学处理的银表面上的表面增强拉曼光谱(英文)

利用波长为632．8nm激光激发的拉曼光谱仪，测定了三种水溶性porphyrin在电化学粗糙银表面上的表面增强拉曼光谱（SERS）．这些光谱非常相似，但也有一些重要的差别．实验还表明：当Sn（Ⅳ）TMPyP（4）吸附在Ag表面上时，Sn-N键仍稳定存在，而且吸附分子的表面浓度不同，其在表面的取向也不同．

Metabolic analyses reveal different mechanisms of leaf color change in two purple-leaf tea plant (Camellia sinensis L.) cultivars

Purple-leaf tea plants,as anthocyanin-rich cultivars,are valuable materials for manufacturing teas with unique colors or flavors.In this study,a new purple-leaf cultivar“Zixin”(“ZX”)was examined,and its biochemical variation and mechanism of leaf color change were elucidated.The metabolomes of leaves of“ZX”at completely purple,intermediately purple,and completely green stages were analyzed using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOF-MS).Metabolites in the flavonoid biosynthetic pathway remained at high levels in purple leaves,whereas intermediates of porphyrin and chlorophyll metabolism and carotenoid biosynthesis exhibited high levels in green leaves.In addition,fatty acid metabolism was more active in purple leaves,and steroids maintained higher levels in green leaves.Saponin,alcohol,organic acid,and terpenoid-related metabolites also changed significantly during the leaf color change process.Furthermore,the substance changes between“ZX”and“Zijuan”(a thoroughly studied purple-leaf cultivar)were also compared.The leaf color change in“Zijuan”was mainly caused by a decrease in flavonoids/anthocyanins.However,a decrease in flavonoids/anthocyanins,an enhancement of porphyrin,chlorophyll metabolism,carotenoid biosynthesis,and steroids,and a decrease in fatty acids synergistically caused the leaf color change in“ZX”.These findings will facilitate comprehensive research on the regulatory mechanisms of leaf color change in purple-leaf tea cultivars.

In Situ Coupling Strategy for Anchoring Monodisperse Co_9S_8 Nanoparticles on S and N Dual?Doped Graphene as a Bifunctional Electrocatalyst for Rechargeable Zn–Air Battery

An in situ coupling strategy to prepare Co_9S_8/S and N dual?doped graphene composite(Co_9S_8/NSG) has been proposed. The key point of this strategy is the function?oriented design of organic compounds. Herein, cobalt porphyrin derivatives with sulfo groups are employed as not only the coupling agents to form and anchor Co_9S_8 on the graphene in situ, but also the heteroatom?doped agent to generate S and N dual?doped graphene. The tight coupling of multiple active sites endows the composite materials with fast electrochemical kinetics and excellent stability for both oxygen reduction reaction(ORR) and oxygen evolution reaction(OER). The obtained electrocatalyst exhibits better activity parameter(ΔE = 0.82 V) and smaller Tafel slope(47.7 mV dec^(-1) for ORR and 69.2 mV dec^(-1) for OER) than commercially available Pt/C and RuO_2. Most importantly, as electrocatalyst for rechargeable Zn–air battery, Co_9S_8/NSG displays low charge–discharge voltage gap and outstanding long?term cycle stability over 138 h compared to Pt/C–RuO_2. To further broaden its application scope, a homemade all?solid?state Zn–air battery is also prepared, which displays good charge–discharge performance and cycle performance. The function?oriented design of N_4?metallomacrocycle derivatives might open new avenues to strategic construction of high?performance and long?life multifunctional electrocatalysts for wider electro?chemical energy applications.

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin＇s accumulation selectively in tumor, the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects. These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield, and the constructions of all these new compounds were characterized by UV, IR, MS, ^1H NMR spectra and elementary analysis. Their anticancer activities were evaluated by MTT assay; the results indicated that the anticancer activities of compounds 4a-e were twice as high as that of ftorafur.

Facile preparation of N-doped corncob-derived carbon nanofiber efficiently encapsulating Fe2O3 nanocrystals towards high ORR electrocatalytic activity

Facile preparation of cost-effective and durable porous carbon-supported non-precious-metal/nitrogen electrocatalysts for oxygen reduction reaction(ORR)is extremely important for promoting the commercialized applications of such catalysts.In this work,the FeCl3-containing porphyrinato iron-based covalent porous polymer(FeCl3·FeP or-CPP)was fabricated in-situ onto porous corncob biomass supports via a simple one-pot method.Subsequent thermal-reduction pyrolysis at 700℃-900℃with CO2 gas as an activating agent resulted in Fe2O3-decorated and N-doped graphitic carbon composite Fe2O3@NC&bio-C with a high degree of graphitization of Fe-involved promotion during pyrolysis(Fe2O3=FeCl3·FePor-CPP derived Fe2O3;NC=N-doped graphene analog;bio-C=the corncob-derived hierarchically porous graphitic biomass carbon framework).The derivedα-Fe2O3 andγ-Fe2O3 nanocrystals(5-10 nm particle diameter)were all immobilized on the N-doped bio-C micro/nanofibers.Notably,the Fe2O3@NC&bio-C obtained at the pyrolysis temperature of 800℃(Fe2O3@NC&bio-C-800),exhibited unusual ORR catalytic efficiency via a 4-electron pathway with the onset and half-wave potentials of 0.96 V and 0.85 V vs.RHE,respectively.In addition,Fe2O3@NC&bio-C-800 also exhibited a high and stable limiting current density of-6.0 mA cm-2,remarkably stability(larger than 91%retention after 10000 s),and good methanol tolerance.The present work represents one of the best results for iron-based biomass material ORR catalysts reported to date.The high ORR activity is attributed to the uniformly distributedα-Fe2O3 andγ-Fe2O3 nanoparticles on the N-enriched carbon matrix with a large specific surface area of 772.6 m^2 g^-1.This facilitates favor faster electron movement and better adsorption of oxygen molecules on the surface of the catalyst.Nevertheless,comparative studies on the structure and ORR catalytic activity of Fe2O3@NC&bioC-800 with Fe2O3@bio-C-800 and NC&bio-C-800 clearly highlight the synergistic effect of the coexisting Fe2O3 nanocrystals,NC,and bio-C on the ORR performance.

Occurrence and distribution of metals and porphyrins in Nigerian coal minerals

The metal contents of Nigerian coal minerals were analyzed using an atomic absorption spectrophotometer. Calcium, Na, and Fe occurred as the major elements with concentrations ranging from 9 782 μg/g for Ca to 432 μg/g for Na whereas K, Mg, Mn, Ni, Cr, Zn, Pb, and Cu, which occurred at trace levels ranged from 673.73 μg/g for Mg to 2.97 μg/g for Mn. The results of the quantitative analysis of porphyrins extracted from the coal minerals showed that Onyeama coal has the highest amount of porphyrins (ca～0.96 μg/g) while Okpara has the lowest (ca～0.30 μg/g). The porphyrins were qualitatively characterized by a combination of thin layer chromatography (TLC), infrared, and ultraviolet-visible spectrophotometers. The results of the mid infrared analysis (MIR) showed the presence of absorption bands at 3 440 cm～1～3 450 cm-1 and 1 640 cm-1～1 680 cm-1 , which are owing to the stretching vibrations of N ─ H and C─ C of aromatics, with C─ H out of plane (oop) bending vibrations at wavenumbers less than 900 cm-1, all of which are characteristic absorptions of porphyrin free base. The ultraviolet-visible data showed prominent peaks at ～400 nm(Soret band) and at wavelength ranges of 535 nm～550 nm(β-band) and 565 nm～ 600 nm (α-band) for the coal porphyrins analyzed. The geochemical significance of the metals and porphyrins in coal minerals are discussed.

Covalent sulfur as stable anode for potassium ion battery

The potassium bis(fluoro-sulfonyl)imide(KFSI)-based electrolyte has great application prospects in potassium ion batteries (PIBs). However, their development has been limited by the decomposition of electrolytes and the corrosion of Al foils (current collector) at high potential. Here, a N-doping, sulfur-rich chemically bonded porphyrin organic framework (SPOF) with a high potential plateau were synthesized as an anode to lower the redox potential of full cells and further inhibit the corrosion of Al foils. SPOF as anode delivers high reversible capacity (557 mAh g^(−1) at 50 mA g^(−1)), excellent cycling performance (94% capacity retention over 1000 cycles at 500 mA g^(−1)), and superior rate performance. Meanwhile, the ex-situ FTIR, Raman, and HRTEM revealed the stability of N-doping and the reversible covalent sulfur and S–S bonds changes during potassiation/depotassiation. In addition, full cells using SPOF anode and PTCDA cathode showed outstanding performance (high capacity of 300 mAh g^(−1) at 200 mA g^(−1)). And the Al current collector of the full cell was not corroded after 150 cycles. Yet, the Al foils with PTCDA as cathode were seriously corroded. This work provides a new strategy for realizing ultra-high reversible capacity and cyclic stability of PIBs, and also accelerates the process of early commercial application of PIBs.

A New 3-D Lanthanide Porphyrin: Synthesis,Structure and Photophysical Properties

A new lanthanide porphyrin, [Smm（H3TPPSHI）]n-nH20 （1, H6TPPS = tetra（4- sulfonatophenyl）porphyrin）, has been synthesized through a hydrothermal reaction and structurally characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in the P4/mcc space group of tetragonal system： a = 15.3683（12）, c = 9.895（2）/k, V = 2337.0（5） A3, C44H29N4OI3SaSm, Mr = 1100.30, Z = 2, Dc = 1.564 g/cm3, S = 1.063,μ（MoKa） = 1.502 mm-1, F（000） = 1102, R = 0.0583 and wR = 0.1666. Compound 1 is characteristic of a three-dimensional （3-D） framework with a slightly distorted square-antiprism eight-coordinated Sm3＋ ion. Fluorescent study revealed that compound 1 exhibits an emission in the red region. The fluorescence quantum yield and lifetime of 1 were determined to be 3.5% and 9.1 ns, respectively. UV-vis absorption spectra were also investigated.

Synthesis,spectroscopic and electrochemical property of an unsymmetrical porphyrin and its Zn compound

In this article,a new 5-（p-maleicaminophenyl）-10,15,20-triphenylporphyrin（H_2P） and relative zinc compound（ZnP） were synthesized and characterized by means of elemental analyses,UV-vis,IR,MS and 1H NMR spectroscopies.Furthermore,we have investigated the fluorescence spectroscopy of these compounds.The oxidation and reduction properties of the compounds were studied by the cyclic voltarnmetry,the oxidation-reduction potentials were obtained.

The formation of crystalline lithium sulfide on electrocatalytic surfaces in lithium-sulfur batteries

Lithium-sulfur(Li-S)battery is highly regarded as a promising next-generation energy storage device but suffers from sluggish sulfur redox kinetics.Probing the behavior and mechanism of the sulfur species on electrocatalytic surface is the first step to rationally introduce polysulfide electrocatalysts for kinetic promotion in a working battery.Herein,crystalline lithium sulfide(Li_(2)S)is exclusively observed on electrocatalytic surface with uniform spherical morphology while Li_(2)S on non-electrocatalytic surface is amorphous and irregular.Further characterization indicates the crystalline Li_(2)S preferentially participates in the discharge/charge process to render reduced interfacial resistance,high sulfur utilization,and activated sulfur redox reactions.Consequently,crystalline Li_(2)S is proposed with thermodynamic and kinetic advantages to rati on alize the superior performances of Li-S batteries.The evoluti on of solid Li_(2)S on electrocatalytic surface not only addresses the polysulfide electrocatalysis strategy,but also inspires further investigation into the chemistry of energy-related processes.

Cobalt porphyrins supported on carbon nanotubes as model catalysts of metal-N_(4)/C sites for oxygen electrocatalysis

Transition-metal based M-N_4/C catalysts are appealing for electrocatalytic oxygen reduction reaction(ORR) and oxygen evolution reaction(OER). Employing model catalysts, which have well-defined molecular structures and coordination environments, to investigate electrocatalytic performance of M-N_4/C sites for ORR and OER is of fundamental significance. Herein, we reported the use of Co tetra(phenyl)porphyrin 1 and Co tetra(pentafluorophenyl)porphyrin 2 as models to probe the role of Co-N_4/C sites for oxygen electrocatalysis. We showed that Co porphyrin 1 is more efficient than its structural analogue 2 for oxygen electrocatalysis in alkaline aqueous solutions, indicating that the electronrich Co-N_4/C site is more favored when noncovalently adsorbed on carbon supports. This work inspires rational design of reaction-oriented catalysts for sustainable energy storage and conversion technologies.

SINGLET OXYGEN QUANTUM YIELDS OF PORPHYRIN-BASED PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

The major cytotoxic agent with most current photosensitizers used in photodynamic therapy(PDT)is widely believed to be singlet oxygen(^(1)O_(2)).Determination of the ^(1)O_(2) quantum yields for porphyrin-based photosensitizers,including hematoporphyrin derivative(HiPorfin),hematoporphyrin monomethyl ether(HMME)and photocarcinorin(PsD-007)in air-saturated dimethylformamide(DMF)solutions were performed by the direct measurement of their near-infrared luminescence.In addition,^(1)O_(2) quencher sodium azide was employed to confirm the ^(1)O_(2) generation from the investigated photosensitizers.The maximal ^(1)O_(2) luminescence occurs at about 1280 nm with full width at half maximum of 30 nm.The ^(1)O_(2) quantum yields were found to be 0.61±0.03,0.60±0.02 and 0.59±0.03 for HiPorfin,HMME and PsD-007,respectively.These results provide that these porphyrin-based photosensitizers produce ^(1)O_(2) under irradiation,which is of significance for the study of their photodynamic action in PDT.

Synthesis and Liquid Crystal Properties of Transition Metal Complexes of Meso-tetra(4-n-myristyloxyphenyl)porphyrin

Transition metal complexes of meso-tetra(4-myristyloxyphenyl)porphyrin TMPPM [M =Mn, Fe, Co, Ni, Cu, Zn; TMPP=mesotetra(4-myristyloxyphenyl)porphyrin] have been synthesized and characterized by means of elemental analyses, UV-Vis spectra, infrared photoacoustic spectra, 1H NMR spectra, molar conductance and differential scanning calorimetry(DSC). The ligand and the Zn complex show liquid crystalline behavior. According to the DSC thermogram of the Zn complex, it exhibits a lower phase transition temperature -7.453 ℃ and a wide mesophase temperature span, 77 ℃.

Enhanced electrocatalytic activity of iron amino porphyrins using a flow cell for reduction of CO_(2) to CO

The flexibility of molecular catalysts is highly coveted for the electrochemical reduction of carbon dioxide(CO_(2)) to carbon monoxide(CO) in both homogeneous and heterogeneous systems.While the electrocatalytic activity of molecular catalysts has been widely studied in H-cells;their less studied capabilities in more efficient flow cell reactors have the potential to rival that of heterogeneous catalysts.In this work,a comparative study of amino functionalized iron-tetraphenylporphyrins(amino-Fe-TPPs) immobilized onto carbonaceous materials in both H-cells and flow cells was conducted to selectively reduce CO_(2) to CO.In a flow cell set up operating in alkaline media,the resulting hybrid catalyst exhibits 87% faradaic efficiency(FE) with extraordinary current density(j) of 119 mA/cm^(2) and turnover frequency(TOF) of 14 s^(-1) at-1.0 V vs.RHE.This remarkable catalytic activity was achieved through thoughtful combination of molecular and flow cell design that provides an effective strategy for future immobilized heterogeneous approaches toward CO_(2) reduction reactions(CO_(2) RRs).