一种新型细胞摄取增强的两亲性卟啉类光敏剂及肿瘤光动力治疗研究

光敏剂能否被肿瘤细胞高效吸收是影响光动力治疗效率的重要因素。亲脂性光敏剂易于被肿瘤组织摄取,但会使光敏剂发生自猝灭;亲水性光敏剂则有利于光敏剂在体内的转运,但肿瘤细胞摄取率会下降。本工作通过亲酯性的乙二醇缩合支链和亲水性季膦基团与卟啉相连接,成功制备一种新型两亲性卟啉锌化合物(ZnTP-TP),实验表明该化合物具有较高的单线态氧量子产率和良好的两亲性,可被细胞快速摄取,并表现出较低的细胞毒性和良好的肿瘤光动力治疗效应。     

Vibrational and electronic circular dichroism study of the interactions of cationic porphyrins with (dG-dC)10 and (dA-dT)10

The interactions of two different porphyrins, without axial ligands-5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin-Cu(II) tetrachloride (Cu(II)TMPyP) and with bulky meso substituents-5,10,15,20-tetrakis(N,N,N-trimethylanilinium-4-yl)porphyrin tetrachloride (TMAP), with (dG-dC)10 and (dA-dT)10 were studied by combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopy at different [oligonucleotide]/[porphyrin] ratios, where [oligonucleotide] and [porphyrin] are the concentrations of oligonucleotide per base-pair and porphyrin, respectively. The combination of VCD and ECD spectroscopy enables us to identify the types of interactions, and to specify the sites of interactions: The intercalative binding mode of Cu(II)TMPyP with (dG-dC)(10), which has been well described, was characterized by a new VCD "marker" and it was shown that the interaction of Cu(II)TMPyP with (dA-dT)10 via external binding to the phosphate backbone and major groove binding caused transition from the B to the non-B conformer. TMAP interacted with the major groove of (dG-dC)10, was semi-intercalated into (dA-dT)10, and caused significant variation in the structure of both oligonucleotides at the higher concentration of porphyrin. The spectroscopic techniques used in this study revealed that porphyrin binding with AT sequences caused substantial variation of the DNA structure. It was shown that VCD spectroscopy is an effective tool for the conformational studies of nucleic acid-porphyrin complexes in solution.     

Silk fibroin hydrogels for potential applications in photodynamic therapy

In this study, we prepared translucid hydrogels with different concentrations of silk fibroin, extracted from raw silk fibers, and used them as a matrix to incorporate the photosensitizer 5-(4-aminophenyl)-10,15,20-tris-(4-sulphonatophenyl) porphyrin trisodium for application in photodynamic therapy (PDT). The hydrogels obtained were characterized by rheology, spectrophotometry, and scattering techniques to elucidate the factors involved in the formation of the hydrogel, and to characterize the behavior of silk fibroin (SF) after incorporating of the porphyrin to the matrix. The rheology results demonstrated that the SF hydrogels had a shear thinning behavior. In addition, we were able to verify that the structure of the material was able to be recovered over time after shear deformation. The encapsulation of porphyrins in hydrogels leads to the formation of self-assembled peptide nanostructures that prevent porphyrin aggregation, thereby greatly increasing the generation of singlet oxygen. Also, our findings suggest that porphyrin can diffuse out of the hydrogel and permeate the outer skin layers. This evidence suggests that SF hydrogels could be used as porphyrin encapsulation and as a drug carrier for the sustained release of photosensitizers for PDT.     

Microbial Community Analysis and Effects of Fe(II)/Mn(II) Ratio on Denitrification in the Mixotrophic Biological Reactor

In this study, the denitrification performance of the mixotrophic biological reactor was investigated under varying Fe(II)/Mn(II) molar ratio conditions. Results indicate that the optimal nitrate removal ratio occurred at an Fe(II)/Mn(II) molar ratio of 9:1, pH of 7, with an HRT of 10?h. When the reactor was performing under optimal conditions, the nitrate removal reached 100.00% at a rate of 0.116?mmol·L^?1·h^?1. The proportion of oxidized Fe(II) and Mn(II) reached 99.29% and 21.88%, respectively. High-throughput sequencing results show that Pseudomonas was the dominant species in the mixotrophic biological reactor. Furthermore, the relative abundance of Pseudomonas and denitrification performance was significantly influenced by variation in the Fe(II)/Mn(II) molar ratio.     

Determination of the absolute configuration of Anisotome irregular diterpenes: application of CD and NMR methods

Several Anisotome diterpene derivatives were synthesized in an attempt to obtain a crystalline compound for X-ray analysis. Although we were unable to obtain a suitable crystal, the absolute configuration of the irregular diterpene skeleton was determined using two other techniques: a circular dichroism (CD) protocol based on a tetraarylporphyrin molecular tweezer that allowed prediction of the absolute stereochemistry on a microscale level, and a method employing differences in NMR shifts from derivatization of the naturally occurring acid 1 with enantiomers of a phenylglycine methyl ester (PGME) chiral anisotropic reagent. The excellent agreement between the CD and NMR methods led to the assignment of a 2S-absolute configuration for anisotomenoic acid 1.     

Recent advances in chlorophyll biosynthesis and breakdown in higher plants

Chlorophyll (Chl) has unique and essential roles in photosynthetic light-harvesting and energy transduction, but its biosynthesis, accumulation and degradation is also associated with chloroplast development, photomorphogenesis and chloroplast-nuclear signaling. Biochemical analyses of the enzymatic steps paved the way to the identification of their encoding genes. Thus, important progress has been made in the recent elucidation of almost all genes involved in Chl biosynthesis and breakdown. In addition, analysis of mutants mainly in Arabidopsis, genetically engineered plants and the application of photo-reactive herbicides contributed to the genetic and regulatory characterization of the formation and breakdown of Chl. This review highlights recent progress in Chl metabolism indicating highly regulated pathways from the synthesis of precursors to Chl and its degradation to intermediates, which are not longer photochemically active.     

Iron porphyrin treatment extends survival in a transgenic animal model of amyotrophic lateral sclerosis

Oxidative damage, produced by mutant Cu/Zn superoxide dismutase (SOD1), may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating motor neuron degenerative disease. A novel approach to antioxidant therapy is the use of metalloporphyrins that catalytically scavenge a wide range of reactive oxygen and reactive nitrogen species. In this study, we examined the therapeutic potential of iron porphyrin (FeTCPP) in the G93A mutant SOD1 transgenic mouse model of ALS. We found that intraperitoneal injection of FeTCPP significantly improved motor function and extended survival in G93A mice. Similar results were seen with a second group of mice wherein treatment with FeTCPP was initiated at the onset of hindlimb weakness-roughly equivalent to the time at which treatment would begin in human patients. FeTCPP-treated mice also showed a significant reduction in levels of malondialdehyde (a marker of lipid peroxidation), in total content of protein carbonyls (a marker of protein oxidation), and increased neuronal survival in the spinal cord. These results therefore provide further evidence of oxidative damage in a mouse model of ALS, and suggest that FeTCPP could be beneficial for the treatment of ALS patients.     

One electron oxidation of benzyltrialkylsilanes catalysed by lignin peroxidase: comparison with the oxidation induced by chemical oxidants

Lignin peroxidase catalyses the H(2)O(2)-induced oxidation of 4-methoxybenzyltrimethylsilane by an electron transfer mechanism. The intermediate radical cation undergoes preferentially C(alpha)[bond]H deprotonation to give 4-methoxybenzaldehyde whereas C(alpha)[bond]Si bond cleavage is a minor fragmentation pathway and leads to 4-methoxybenzyl alcohol. Similar results are obtained in the oxidation catalysed by the water soluble model compound 5,10,15,20-tetra(N-methyl-4-pyridyl)porphyrinatoiron(III) pentachloride. Instead, in the oxidation promoted by the genuine one-electron transfer oxidant potassium dodecatungstocobalt(III)ate C(alpha)[bond]Si bond cleavage is the exclusive fragmentation process of the intermediate radical cation. It is suggested that in the enzymatic and biomimetic oxidations of 4-methoxybenzyltrimethylsilane the deprotonation of the intermediate radical cation is promoted by the reduced form [PorFe(IV)[double bond]O] of the active oxidant, which is an iron-oxo porphyrin radical cation.     

Manganese supplementation relieves the phenotypic deficits seen in superoxide-dismutase-null Escherichia coli

Escherichia coli, lacking cytoplasmic superoxide dismutases, exhibits a variety of oxygen-dependent phenotypic deficits. Enrichment of the growth medium with Mn(II) relieved those deficits. Extracts of cells grown on Mn(II)-rich medium exhibited superoxide dismutase-like activity that was due partially to low-molecular-weight and partially to high-molecular-weight complexes. The high-molecular-weight activity was sensitive to proteolysis. Hence this activity is likely associated with low-affinity binding of Mn to proteins.     

SS Bond-activation of diorganyl disulfide by anionic [Mn(CO)5]: crystal structures of [Mn(SC5H4NO)3] and [(CO)3Mn(μ-SR)3Co(μ-SR)3Mn(CO)3] (R=C6H4NHCOPh)

The SS bond-activation of diorganyl disulfide by the anionic metal carbonyl fragment [Mn(CO)₅]⁻ gives rise to an extensive chemistry. Oxidative decarbonylation addition of 2,2′-dithiobis(pyridine-N-oxide) to [Mn(CO)₅]⁻, followed by chelation and metal-center oxidation, led to the formation of [Mn^II(SC₅H₄NO)₃]⁻ (1). The effective magnetic moment in solid state by SQUID magnetometer was 5.88 μ_B for complex 1, which is consistent with the Mn^II having a high-spin d⁵ electronic configuration in an octahedral ligand field. The average Mn(II)S, SC and NO bond lengths of 2.581(1), 1.692(4) and 1.326(4) Å, respectively, indicate that the negative charge of the bidentate 1-oxo-2-thiopyridinato [SC₅H₄NO]⁻ ligand in complex 1 is mainly localized on the oxygen atom. The results are consistent with thiolate-donor [SC₅H₄NO]⁻ stabilization of the lower oxidation state of manganese (Mn(I)), while the O,S-chelating [SC₅H₄NO]⁻ ligand enhances the stability of manganese in the higher oxidation state (Mn(II)). Activation of SS bond as well as OH bond of 2,2′-dithiosalicylic acid by [Mn(CO)₅]⁻ yielded [(CO)₃Mn(μ-SC₆H₄C(O)O)₂Mn(CO)₃]²⁻ (4). Oxidative addition of bis(o-benzamidophenyl) disulfide to [Mn(CO)₅]⁻ resulted in the formation of cis-[Mn(CO)₄(SR)₂]⁻ (R=C₆H₄NHCOPh) which was employed as a chelating metallo ligand to synthesize heterotrinuclear [(CO)₃Mn(μ-SR)₃Co(μ-SR)₃Mn(CO)₃]⁻ (8) possessing a homoleptic hexathiolatocobalt(III) core.