PTC-174, a positive allosteric modulator of NMDA receptors containing GluN2C or GluN2D subunits.

NMDA receptors are ionotropic glutamate receptors that mediate excitatory neurotransmission. The diverse functions of these receptors are tuned by deploying different combinations of GluN1 and GluN2 subunits (GluN2A-D) to form either diheteromeric NMDA receptors, which contain two GluN1 and two identical GluN2 subunits, or triheteromeric NMDA receptors, which contain two GluN1 and two distinct GluN2 subunits. Here, we characterize PTC-174, a novel positive allosteric modulator (PAM) of receptors containing GluN2C or GluN2D subunits. PTC-174 potentiates maximal current amplitudes by 1.8-fold for diheteromeric GluN1/2B receptors and by > 10-fold for GluN1/2C and GluN1/2D receptors. PTC-174 also potentiates responses from triheteromeric GluN1/2B/2D and GluN1/2A/2C receptors by 4.5-fold and 1.7-fold, respectively. By contrast, PTC-174 produces partial inhibition of responses from diheteromeric GluN1/2A and triheteromeric GluN1/2A/2B receptors. PTC-174 increases potencies of co-agonists glutamate and glycine by 2- to 5-fold at GluN1/2C and GluN1/2D receptors, and NMDA receptor activation facilitates allosteric modulation by PTC-174. At native NMDA receptors in GluN2D-expressing subthalamic nucleus neurons, PTC-174 increases the amplitude of responses to NMDA application and slows the decay of excitatory postsynaptic currents (EPSCs) evoked by internal capsule stimulation. Furthermore, PTC-174 increases the amplitude and slows the decay of EPSCs in hippocampal interneurons, but has not effect on the amplitudes of NMDA receptor-mediated EPSCs in hippocampal CA1 pyramidal neurons. Thus, PTC-174 provides a useful new pharmacological tool to investigate the molecular pharmacology and physiology of GluN2C- and GluN2D-containing NMDA receptors.

Photocatalytic antifouling graphene oxide-mediated hierarchical filtration membranes with potential applications on water purification.

Graphene oxide-based filtration membranes with photocatalytic antifouling function have been successfully synthesized by a two-step method for the first time. First, graphene oxide particles composite sheets are prepared by decorating graphene oxide sheets with appropriate amount of TiO2 nanoparticles, which can be assembled into filtration membranes with suitable permeation and retention rates. Then, an additional TiO2 particle layer (P25) with strong photocatalysis activity is coated on these films by filtration, forming hierarchical structure membranes. The filtration properties of the as-obtained films are investigated by treating dye solution, and the results demonstrate that these membranes possess favorable photocatalytic antifouling function under UV light irradiation, which can maintain the clean films and their filtration properties, broadening the horizon for the vast use of these graphene-involved films in water purification.

Synthetic and Mechanistic Aspects of the Reaction of 1,1-Difluoro-2,2-bis(dimethylamino)ethene with Ethyl Propiolate.

1,1-Difluoro-2,2-bis(dimethylamino)ethene undergoes a [2 + 2] cycloaddition with ethyl propiolate at -25 degrees C [DeltaH() = 4.2 (+/-0.4) kcal/mol and DeltaS() = -56.7 (+/-0.9) cal/mol.K], and the cyclobutene product undergoes electrocyclic ring opening at +15 degrees C [DeltaH() = 18.5 (+/-0.6) kcal/mol and DeltaS() = -9.7 (+/-1.0) cal/mol.K]. The resultant diene undergoes Diels-Alder reactions with electron-deficient dienophiles to give aromatic products. A complementary computational study addresses the issue of the [2 + 2] cycloaddition mechanism.