Indoleamine 2,3-dioxygenase (IDO), an immune checkpoint protein, can cause the depletion of tryptophan (Trp) and accumulation of its metabolite of kynurenine (Kyn) in cancer cells, and generates the immunosuppressive microenvironment that supports tumor cell growth. A novel immunoregulatory prodrug micelle based on polyethylene glycol-derivatized an IDO-selective inhibitor of 1-methyltryptophan (1-MT), PEG-Fmoc-1-MT, was developed for inhibiting the IDO activity of the conversion of Trp to Kyn in tumor microenvironments. To investigate the 1-MT distribution and Trp/Kyn ratios in mice tumors with PEG-Fmoc-1-MT prodrug micelles treatment, a HPLC–MS/MS method for simultaneous determination of 1-MT and IDO biomakers of Trp and Kyn in mouse tumors was developed and validated. Triple-quadrupole mass spectrometry with positive electrospray ionization as source ionization in multiple reaction monitoring at m/z 219.0?→?160.1, 205.0?→?118.2, 209.0?→?146.1 and 249.3?→?148.3 was used for determination of 1-MT, Trp, Kyn and matrine (internal standard). The method demonstrated good linearity at the concentrations ranging from 10 to 10,000 ng/mL and lower limits of quantitation of 1 ng/mL for 1-MT, Trp and Kyn, respectively. The validated method was successfully applied to 1-MT tumor biodistribution and Trp/Kyn ratio studies in 4T1 tumor bearing mice i.v. with PEG-Fmoc-1-MT prodrug micelles. The mice tumors with PEG-Fmoc-1-MT prodrug micelles treatment exhibited higher 1-MT accumulation and lower Trp/Kyn ratio, in comparison with those of mice with 1-MT solution treatment. The developed PEG-Fmoc-1-MT prodrug micelles could be a promising IDO immunoregulatory prodrug micelles for cancer immunotherapy.
Treatment of Ru3(CO)12 with salicylaldimines [2-HOC6H4-CH?=N–C6H4-4-R] [R?=?Me; Cl; Br; OMe; CF3] in refluxing toluene gave three novel binuclear ruthenium carbonyl complexes {[µ-?2-2-OC6H4-CH=N-C6H4-4-R)][µ-?2-2-CH2-OC6H4][µ-?-NH-C6H4-4-R]}Ru2(CO)4 [R?=?Me (1), Cl (2), Br (3)] and three mononuclear carbonyl complexes [2-OC6H4-CH=N-C6H4-4-R][2-OC6H4-CH2NH-C6H4-4-R]Ru(CO)2 [R?=?Me (4), OMe (5), CF3 (6)], respectively. The structures of 1–6 were fully characterized using IR and NMR spectroscopy, elemental analysis and single-crystal X-ray diffraction. These results suggest that the substituent group on the phenyl of salicylaldimine has a significant effect on the structure of the Ru complex.
Both racemate and enantiomer of a novel double helix,binaphthylcyclooctaterthiophene(BN-COTh),which is a DNA-like molecule constructed by two single helices intertwined with each other via covalent bonds,have been synthesized with two building blocks,cycloocta-tetrathiophene(COTh) and cyclooctadinaphthyldithiophene(CONT) fused together via Negishi coupling reaction.Another homologue,dinaphthylcyclooctaterthiophene(DN-COTh) has been employed together as a model compound.Besides the synthetic work,BN-COTh and DN-COTh have been investigated by studying their crystal structures,spectroscopic behaviors,chiral resolution and chiral characteristics,including circular dichroism(CD) spectra and optical rotations.In addition,the novel crystal of enantiomer of(R,R,R)-BN-COTh has been explored.The enantiomer molecules packing along b-axis to form a larger and extended assembly packing due to intermolecular interactions between the enantiomer molecules and chloroform molecules in crystal. 相似文献
g-C3N4 have been widely used in the fields of photocatalytic hydrogen production,photocatalytic degradation of dyes and oxidative degradation of toxic gases due to their excellent performance.It has attracted extensive attention in recent years due to its highly efficient photocatalytic capacity of hydrogen generation,water oxidation,carbon dioxide reduction and degradation of organic pollutants.Because of the abundant carbon and nitrogen composition of the earth,large-scale production and industrial applications of this material are possible.The modification of this material makes its performance more excellent so that this new material can obtain a steady stream of vitality.These outstanding works have become important materials and milestones on the road to mankind's photocatalytic hydrogen production.This review will begin with the basic idea of designing,synthesizing and improving g-C3N4 based photocatalytic materials,and introduce the latest development of g-C3N4 photocatalysts in hydrogen production from four aspects of controlling the carbon/nitrogen ratio,morphology,element doping and heterojunction structure of g-C3N4 materials. 相似文献
The effect of gold nanoparticle-decorated molybdenum sulfide (AuNP-MoS2) nanocomposites on amyloid-β-40 (Aβ40) aggregation was investigated. The interesting discovery was that the effect of AuNP-MoS2 nanocomposites on Aβ40 aggregation was contradictory. Low concentration of AuNP-MoS2 nanocomposites could enhance the nucleus formation of Aβ40 peptides and accelerate Aβ40 fibrils aggregation. However, although high concentration of AuNP-MoS2 nanocomposites could enhance the nucleus formation of Aβ40 peptides, it eventually inhibited Aβ40 aggregation process. It might be attributed to the interaction between AuNP-MoS2 nanocomposites and Aβ40 peptides. For low concentration of AuNP-MoS2 nanocomposites, it was acted as nuclei, resulting in the acceleration of the nucleation process. However, the structural flexibility of Aβ40 peptides was limited as the concentration of AuNP-MoS2 nanocomposites was increased, resulting in the inhibition of Aβ40 aggregation. These findings suggested that AuNP-MoS2 nanocomposites might have a great potential to design new multifunctional material for future treatment of amyloid-related diseases. 相似文献
Luminescent conjugated network polymer is one of the most promising chemo-sensors owing to their good chemical/optical stability and multiple functionalization.Herein,three conjugated network polymers were prepared by using aggregation-induced emission active 1,1,2,2-tetrakis(4-formyl-(1,1'-biphenyl))-ethane(TFBE) unit as monomer and hydrazine as linker.Through regulating the synthetical condition,the polyme ric network can form either unifo rm two-dimensional azine-linked nanosheets(ANS),conjugated microporous polymers(A-CMP) or covalent organic frameworks(A-COF).All of these polymers exhibited good stability and high fluorescence quantum efficiency with the quantum yield of6.31% for A-NS,5.26% for A-CMP,and 5.80% for A-COF,as well as fast and selective fluorescence quenching response to 2,4,6-trinitrophenol(TNP).And the best TNP sensing performance with the Stern-Volmer constants(K_(sv)) values up to 8 × 10~5 L/mol and a detection limit of 0.09 μmol/L was obtained for A-NS.The study explores various strategies to construct conjugated polymers with different nanoarchitectures based on the same building block for sensitive detection of explosives. 相似文献
Here,the selective adsorption behaviors of guest molecule COR in two hexamer host grids were investigated by means of scanning tunnelling microscope(STM).The assembled structures of small functional organic molecules TTBTA and TATBA were thermodynamically stable.Interestingly,the introduction of the guest molecule COR destroyed the original hexamer structure of TTBTA and combined with it to form a new triangular host-guest system.Different from TTBTA,the introduction of the guest molecule COR did not affect the six-membered ring structure of TATBA.Furthermore,the co-assembly structure of TTBTA/TATBA/COR was established and the guest molecule COR showed preferential adsorption to the TATBA host grid.Density functional theory(DFT) calculations had been performed to disclose the mechanism of the involved assemblies. 相似文献
An interlocked M_4 L_8 coordination cage was synthesized by coordination-driven self-assembly of palladium(Ⅱ) ions with aromatic amide bidentate ligands.The reaction of the ligand and the metal at 2:1 ratio led to the monomeric M_2 L_4 cage as the kinetic product,while the thermodynamic product M_4 L_8 cage was obtained by prolongating the reaction.This conve rsion and the interlocked structure was clearly revealed by using ~1 H NMR,mass spectrometry and X-ray crystallography.The driving force of interlocking was mainly attributed to the interactions(hydrogen bonding,aromatic stacking and electrostatic interaction) arising from the aptitude of flexibility of the amide ligand. 相似文献