RESUMO
We have synthesized a collection of quinolizinium fluorescent dyes for the purpose of cell imaging. Preliminary biological studies in human U2OS osteosarcoma cancer cells have shown that different functional groups appended to the cationic quinolizinium scaffold efficiently modulate photophysical properties but also cellular distribution. While quinolizinium probes are known nuclear staining reagents, we have identified a particular quinolizinium derivative salt that targets the lysosomal compartment. This finding raises the question of predictability of specific organelle targeting from structural features of small molecules.
Assuntos
Corantes Fluorescentes/farmacologia , Quinolizinas/farmacologia , Antraquinonas/metabolismo , Artemisininas/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Endocitose/efeitos dos fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Lisossomos/metabolismo , Imagem Molecular , Quinolizinas/síntese química , Quinolizinas/químicaRESUMO
Charged chromophores based on heteroaromatic cations were prepared by reaction of alkylazinium salts with N-heteroarylstannanes under Stille conditions. This approach provides easy access to potential single donor D-A(+) chromophores in which the acceptor moiety A(+) is the pyridinium cation and the donors are different π-excessive N-heterocycles. The ß hyperpolarizabilities were measured in hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis that combines a variety of computational procedures, including density functional theory and correlated Hartree-Fock-based methods. In some chromophores, the absence of a bridge between donor and acceptor fragments increases the NLO properties.
RESUMO
Two total syntheses of the indolo[2,3-a]quinolizinium cation have been accomplished through the application of two ring-closing metathesis reactions to form the pyridinium ring. One of these approaches provides the tetracyclic cation in only five steps from commercially available harmane. Fluorescence-based thermal denaturation experiments, as well as spectrofluorimetric titration, circular dichroism measurements, and theoretical simulations, showed a consistent DNA-binding capacity by intercalation with a marked preference for AT-rich sequences.