RESUMO
Indium arsenide quantum dots, which typically emit in the near-infrared, have been utilized in various optoelectronics and biomedical applications, such as covert illumination, optical communication, and deep-tissue imaging. While theory predicts that further quantum confinement through size reduction could enable visible light emission, systems with larger optical bandgaps have not been realized. Here, we report a method of preparing highly luminescent, visible-light-emitting In(Zn)As/ZnSe/ZnS QD, using a low-temperature nanocluster synthesis approach. Each QD contains an ultraconfined In(Zn)As nanocluster and fluoresces at tunable wavelengths between 538 and 640 nm with a high photoluminescence quantum efficiency of 58%. We confirm, through DFT and spectroscopic analysis, that the strong confinement effects in the few-atom-wide In(Zn)As nanoclusters are responsible for the significant spectral shift from the near-infrared to the visible region. These findings suggest that broader-than-expected optical tuning may now be achievable in other quantum-confined semiconductor systems, which could lead to a wider scope of functional applications in optoelectronics.
Assuntos
Arsenicais , Pontos Quânticos , Índio , LuminescênciaRESUMO
The synthesis of a library of bacterial phosphoglycolipid, PGL-1, is described. Key features of the synthesis include regioselective esterification of the primary alcohol of the diacylglycerol moiety and an H-phosphonate method to install the phosphate in PGL-1 in comparison with earlier reported procedures. A representative set of PGL-1 analogues was prepared and evaluated for their biological activities. Results showed that the immunological activity of PGL-1 is dependent on the chain lengths of the fatty acids.
Assuntos
Glicolipídeos/farmacologia , Bactérias Gram-Negativas/química , Fatores Imunológicos/farmacologia , Organofosfatos/farmacologia , Animais , Relação Dose-Resposta a Droga , Glicolipídeos/síntese química , Glicolipídeos/química , Fatores Imunológicos/síntese química , Fatores Imunológicos/química , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Organofosfatos/síntese química , Organofosfatos/química , Estereoisomerismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.
Assuntos
Diterpenos/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Linhagem Celular Tumoral , Sistemas Computacionais , Diterpenos/síntese química , Diterpenos/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Imageamento Tridimensional , Cinética , Reprodutibilidade dos TestesRESUMO
Andrographolide (1) is a diterpenoid lactone with an α,ß-unsaturated lactone group that inhibits NF-κB DNA binding. Andrographolide reacts with the nucleophilic Cys62 of NF-κB p50 through a Michael addition at the Δ(12(13)) exocylic double bond to form a covalent adduct. Using computer docking, site-directed mutagenesis, and mass spectrometry, the noncovalent interactions between andrographolide and additional binding site residues other than Cys62 were found to be essential for the covalent incorporation of andrographolide. Furthermore, the addition reaction of andrographolide on Cys62 was highly dependent on the redox conditions and on the vicinity of nearby, positively charged Arg residues in the conserved RxxRxR motif. The reaction mechanisms of several of the analogues were determined, showing that 14-deoxy-11,12-didehydroandrographolide (8) reacts with NF-κB p50 via a novel mechanism distinct from andrographolide. The noncovalent interaction and redox environment of the binding site should be considered, in addition to the electrophilicity, when designing a covalent drug. Analogues similar in structure appear to use distinct reaction mechanisms and may have very different cytotoxicities, e.g., compound 6.