Synthesis, photophysical characterization, and aerobic redox reactivity of electron-rich tellurorhodamine photocatalysts.

Tellurorhodamine dyes are a class of self-sensitizing chromophores that we have previously shown can photocatalytically oxidize a variety of organic and inorganic compounds with visible light, oxygen, and water. A new series of tellurorhodamine chromophores containing electron donating moieties were synthesized to explore how different electron donating groups affect photophysical properties and catalyst function. The synthesized complexes 1B, 1C, and 1D contain increasingly electron-donating substituents (Me, t-Butyl, OMe) on the xylene ring. 1A, containing an unsubstituted xylene, was synthesized for use as a control. UV-Vis spectroscopy was used to determine the photophysical properties of the dyes and for kinetic and thermodynamic studies. With visible light irradiation all dyes could be oxidized at room temperature to their corresponding telluroxides 2A, 2B, 2C, and 2D, as confirmed by mass spectroscopy. Comparative reduction studies using our previously established silane oxidation reaction showed that decreasing the electron density of the xylene moiety increased the rate of reduction, corresponding to a decrease in the experimental ΔG. 2D has the smallest energy barrier to silane oxidation, and a linear increase in rate with increasing substituent electron withdrawing nature was observed at low temperatures, and non-linearity at high temperatures.

The multifunctional dopamine D2/D3 receptor agonists also possess inhibitory activity against the full-length tau441 protein aggregation.

Neurodegeneration leads to variety of diseases which are linked to aberrant protein or peptide aggregation, as a one possible mechanism. Hence, small drug molecules targeting aggregation are of interest. Tau protein aggregation is one of the biomarkers of neurodegenerative diseases and is a viable drug target. Toward multifunctional inhibitors, we aim to incorporate structural elements in a potential drug in order to preserve dopamine agonist activity, which elevates disease symptoms associated with motor skills, and promote inhibitory activity against aggregation of the full-length tau (2N4R, tau441) protein. In our design, we introduced various moieties (catechol, non-catechol, biphenyl, piperazine, and thiazole) to determine which functional group leads to the greatest aggregation inhibition of tau. In vitro, tau aggregation was induced by heparin and monitored by using fluorescence aggregation assay, transmission electron microscopy and 4,4'-Dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt (Bis-ANS) fluorescence spectroscopy. The catechol containing compounds, D-519 and D-520, prevented aggregation of tau. By contrast, non-catechol and thiazole containing compounds (D-264 and D-636) were poor inhibitors. The Bis-ANS studies revealed that the potent inhibitors bound solvent-exposed hydrophobic sites. Based on the density functional theory calculations on inhibitors tested, the compounds characterized with the high polarity and polarizability were more effective aggregation inhibitors. These findings could lead to the development of small multifunctional drug inhibitors for the treatment of tau-associated neurodegeneration.

Tellurorhodamine photocatalyzed aerobic oxidation of organo-silanes and phosphines by visible-light.

Tellurorhodamine, 9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate (1), photocatalytically oxidizes aromatic and aliphatic silanes and triphenyl phosphine under mild aerobic conditions. Under irradiation with visible light, 1 can react with self-sensitized 1O2 to generate the active telluroxide oxidant (2). Silanes are oxidized to silanols and triphenyl phosphine is oxidized to triphenyl phoshine oxide either using 2, or 1 with aerobic irradiation. Kinetic experiments coupled with a computational study elucidate possible mechanisms of oxidation for both silane and phosphine substrates. First-order rates were observed in the oxidation of triphenyl phosphine and methyldiphenyl silane, indicating a substitution like mechanism for substrate binding to the oxidized tellurium(iv). Additionally, these reactions exhibited a rate-dependence on water. Oxidations were typically run in 50 : 50 water/methanol, however, the absence of water decreased the rates of silane oxidation to a greater degree than triphenyl phosphine oxidation. Parallel results were observed in solvent kinetic isotope experiments using D2O in the solvent mixture. The rates of oxidation were slowed to a greater degree in silane oxidation by 2 (kH/kD = 17.30) than for phosphine (kH/kD = 6.20). Various silanes and triphenyl phosphine were photocatalytically oxidized with 1 (5%) under irradiation with warm white LEDs using atmospheric oxygen as the terminal oxidant.