A new undergraduate organic chemistry laboratory experiment has been developed to determine the absolute configuration of enantioenriched secondary alcohols with the competing enantioselective conversion (CEC) method. The CEC method uses both enantiomers of a chiral kinetic resolution reagent in parallel reactions to identify the fast-reacting reagent and thus the configuration of the alcohol. Students working in pairs are given one of three enantioenriched secondary alcohols with an unknown absolute configuration. They assign the molecular structure using the corresponding 1H NMR spectrum and determine the absolute configuration via the CEC method. The parallel reactions are run at room temperature for 1 h using small quantities of solvent, substrate, and catalyst. Students use thin-layer chromatography (TLC) to analyze the parallel reactions and determine the fast reaction qualitatively. The free program ImageJ is used with a picture of the TLC plate to carry out a quantitative analysis of reaction conversion. Data collected in the spring 2013 laboratory course (n = 1036) show that 93.6% of students determined the absolute configuration of their unknown correctly with just a qualitative analysis of the TLC plate. This experiment provides a platform for discussions of stereochemistry, mechanism, kinetics, energy diagrams, and transition states.

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Background: Preparation of mini buccal tablets incorporating either of the Alzheimer's drugs, rivastigmine tartrate or donepezil hydrochloride, were developed for patients who have difficulty swallowing as a source of effervescence, by pairing the less commonly used malic acid with sodium bicarbonate in an experimentally determined (1:2) stochiometirc ratio. Methods: To avoid premature reaction of the acid and the base during compounding, the tablet ingredients were mixed in the following order: acid, sweetener, binder, drug, preservative, base, and anti-adherent/lubricant. Results: An accelerated thermal stability study at 40°C and 25% relative humidity showed that the integrity of the effervescent tablets containing rivastigmine tartrate were superior to that of donepezil HCl tablets. FT-IR spectrometry confirmed the presence of water of hydrate in donepezil HCl crystals. This water was absent in the IR after one-month storage at accelerated thermal stability, but was present at room temperature. This behavior was not observed in the tablet made from rivastigmine tartrate powder. Differential scanning calorimetry of donepezil hydrochloride showed two thermal events: the first was associated with the loss of the water, and the second, at much higher temperature, was the melting of theanhydrous drug. Such behavior was not observed in the rivastigmine tartrate powder. Conclusions: Hidden water which may function as catalyst to induce premature effervescence during storage.

Hindlimb unweighting (HLU) of rats is a model used to mimic the cephalic fluid shift potentially involved in the orthostatic intolerance experienced by astronauts. Certain arteries in these rats exhibit a decreased contractile response to adrenergic agonists. It was shown previously that this may be caused by changes in thick filament regulation (Summers et al., Vascul Pharmacol 48: 208-214, 2008). In the present study, it was hypothesized that HLU also modifies thin filament regulation by effects on p38(MAPK) and ERK. Abdominal aorta rings from 20-day HLU rats and untreated controls were subjected to phenylephrine and phorbol 12,13-dibutyrate (PDBU) concentration response curves in the presence and absence of two inhibitors: the p38(MAPK) inhibitor SB-203580 and the MEK inhibitor U-0126. SB-203580 decreased control sensitivity to both agonists, but HLU sensitivity was not significantly affected. U-0126, which blocks enzymes immediately upstream of ERK, affected sensitivity to both agonists equally between control and HLU. Western blot analysis revealed no change in total levels of p38(MAPK) and its downstream target heat shock protein 27 but did reveal a decrease in phosphorylated levels of both after stimulation with PDBU and phenylephrine after HLU treatment. Neither total ERK nor phosphorylated levels after stimulation were affected by HLU. Total levels of caldesmon, a molecule downstream of both pathways, were decreased, but phosphorylated levels after stimulation were decreased by roughly twice as much. The results of this study demonstrate that HLU downregulates p38(MAPK), but not ERK, signaling. In turn, this may decrease actin availability for contraction.