A Fluorogenic Probe for Cell Surface Phosphatidylserine Using an Intramolecular Indicator Displacement Sensing Mechanism.

The detection of externalized phosphatidylserine (PS) on the cell surface is commonly used to distinguish between living, apoptotic, and necrotic cells. The tools of choice for many researchers to study apoptosis are annexin V-fluorophore conjugates. However, the use of this 35 kDa protein is associated with several drawbacks, including temperature sensitivity, Ca2+ dependence, and slow binding kinetics. Herein, a fluorogenic probe for cell surface PS, P-IID, is described, which operates by an intramolecular indicator displacement (IID) mechanism. An intramolecularly bound coumarin indicator is released in the presence of cell surface PS, leading to a fluorescence "turn-on" response. P-IID demonstrates superior performance when compared to annexin V, for both fluorescence imaging and flow cytometry. This allows P-IID to be used in time-lapse imaging of apoptosis using confocal laser scanning microscopy and demonstrates the utility of the IID mechanism in live cells

Quantum chemical prediction of equilibrium acidities of ureas, deltamides, squaramides, and croconamides

Robust quantum chemical methods are employed to predict the pKa's of several families of dual hydrogen-bonding organocatalysts/anion receptors, including deltamides and croconamides as well as their thio derivatives. The average accuracy of these predictions is ∼1 pKa unit and allows for a comparison of the acidity between classes of receptors and for quantitative studies of substituent effects. These computational insights further explain the relationship between pKa and chloride anion affinity of these receptors that will be important for designing future anion receptors and organocatalysts