An efficient method for the selective isotopic labeling of carboxylic acids is reported. By reacting an amino acid with excess carbodiimide and (18)OH(2), a kinetically enhanced multiple turnover reaction provides the (18)O-labeled product in high yield and excellent isotopic enrichment. This reaction is fully compatible with standard Fmoc, Boc, Trt, and OtBu protecting groups and provides a means to selectively label the alpha-carboxylic acids of functionalized amino acids with stable oxygen isotopes.

Metal-free hemiporphyrazine (HpH2) is a notoriously insoluble material possessing interesting photophysical properties. Here we report the synthesis, structure, and photophysical properties of an octahedral zinc trans-ditriflate hemiporphyrazine complex "HpH2Zn(OTf)2" that contains a neutral hemiporphyrazine ligand. The photophysical properties of hemiporphyrazine are largely unaffected by introduction of zinc(II) triflate, but a dramatic increase in solubility is observed. HpH2Zn(OTf)2 therefore provides a convenient model system to evaluate the impact of aggregation on the photophysical properties of hemiporphyrazine. Soluble aggregates and crystalline materials containing planar hemiporphyrazines exhibit relatively strong absorbance of visible light (450-600 nm) and red luminescence (600-700 nm). Hemiporphyrazine monohydrate (HpH2·H2O), in contrast, has a nonplanar "saddleshaped" conformation that exhibits very little absorbance of visible light in solution or in the solid state. Upon photoexcitation at 380 nm, HpH2Zn(OTf)2 and HpH2 exhibit multiwavelength emissions centered at 450 and 650 nm. Emissions at 450 nm are highly anisotropic, while emissions at 650 nm are fully depolarized with respect to a plane-polarized excitation source. Taken together, our results suggest that excitonic coupling of aggregated and crystalline hemiporphyrazines results in increased absorbance and emission of visible light from S0 S1 transitions that are usually symmetry forbidden in isolated species. In contrast to previously proposed theories involving excited-state intramolecular proton transfer, we propose that the multiple-wavelength luminescent emissions of HpH2Zn(OTf)2 and HpH2 are due to emissive S1 and S2 states in aggregated and crystalline hemiporphyrazines. These results may provide a better understanding of the nonlinear optical properties of these materials in solution and in the solid state.

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.

Thiazole derivatives R 0260 Chemoselectivity of the [2 + 3]-Cycloaddition of Thiocarbonyl Ylides with 5-Benzylidene-3-phenylrhodanine. -The reaction of title ylides, generated in situ from compounds (I), (VI), and (IX), is studied. -(SEYFRIED, M. S.; LINDEN, A.; MLOSTON, G.; HEIMGARTNER*, H.; Pol.