In Vivo Imaging of Tumor Hypoxia by Maintaining Green Fluorescence of 9-Aminoanthracene Under Hypoxic Conditions.

In this study, 9-aminoanthracene (9AA) was used as a new fluorescence reagent for the in vivo imaging of tumor hypoxia by taking advantage of the maintenance of its green fluorescence under hypoxic conditions. As 9AA is insoluble in water, polyethylene glycol (PEG)-400 was used to dissolve 9AA in saline. Each organ was successfully stained with 9AA, as observed by green fluorescence using in vivo imaging, following intragastric administration of a 9AA PEG-saline solution in mice. Therefore, the intragastric administration of 9AA can be used for in vivo imaging of normal mice. Tumor hypoxia staining using the 9AA fluorescence method was evaluated by in vivo imaging of mice subcutaneously transplanted with Ehrlich ascites carcinoma cells and compared with conventional pimonidazole (PIMO) staining under hypoxic conditions. The tumor sections were stained with green fluorescence derived from 9AA and the same sections corresponded to hypoxic areas upon immunohistochemical staining with PIMO.

Observation and Stereochemistry of Betaine Intermediates in the Reaction of Phosphonium Ylide Containing a Phosphaboratatriptycene Skeleton with Benzaldehyde.

Betaine intermediates, rather than the corresponding 1,2-oxaphosphetanes, were observed in the reaction of the phosphonium ylide containing a phosphaboratatriptycene skeleton with PhCHO in THF. Their chemical shifts were -4.56, -4.92, -7.32, and -11.1 ppm at -10 °C in variable temperature (VT) 31P{1H} NMR experiments. These signals were observed by the deprotonations of ß-hydroxyalkylphosphonium salts with lithium hexamethyldisilazide (LiHMDS) and sodium hexamethyldisilazide (NaHMDS). Their signals were assigned to betaine lithium complexes and salt-free betaines, respectively. The betaine lithium complexes were thermodynamically stable even at 25 °C and were converted to ß-hydroxyalkylphosphonium salts by protonation, whereas the salt-free betaines were unstable, providing the corresponding ethylphosphonium salt and PhCHO at 0 °C, instead of olefins and phosphine oxide. The potential structures of the betaine lithium complexes and salt-free betaines were investigated by optimizing the expected stereoisomers and estimating the phosphorus chemical shifts by density functional theory (DFT) calculations. The results indicated that the erythro-syn- and threo-syn-betaines were more stable than their anti-forms. Erythro-syn-betaines were the most thermodynamically stable among the expected stereoisomers in both lithium complexes and salt-free betaines. The estimated phosphorus-31 signals were in good agreement with those experimental values.