Pharmacological intervention in young adolescents rescues synaptic physiology and behavioural deficits in Syngap1+/- mice.

Haploinsufficiency in SYNGAP1 is implicated in intellectual disability (ID) and autism spectrum disorder (ASD) and affects the maturation of dendritic spines. The abnormal spine development has been suggested to cause a disbalance of excitatory and inhibitory (E/I) neurotransmission at distinct developmental periods. In addition, E/I imbalances in Syngap1+/- mice might be due to abnormalities in K+-Cl- co-transporter function (NKCC1, KCC2), in a maner similar to the murine models of Fragile-X and Rett syndromes. To study whether an altered intracellular chloride ion concentration represents an underlying mechanism of modified function of GABAergic synapses in Dentate Gyrus Granule Cells of Syngap1+/- recordings were performed at different developmental stages of the mice. We observed depolarised neurons at P14-15 as illustrated by decreased Cl- reversal potential in Syngap1+/- mice. The KCC2 expression was decreased compared to Wild-type (WT) mice at P14-15. The GSK-3ß inhibitor, 6-bromoindirubin-3'-oxime (6BIO) that crosses the blood-brain barrier, was tested to restore the function of GABAergic synapses. We discovered that the intraperitoneal administration of 6BIO during the critical period or young adolescents [P30 to P80 (4-week to 10-week)] normalised an altered E/I balance, the deficits of synaptic plasticity, and behavioural performance like social novelty, anxiety, and memory of the Syngap1+/- mice. In summary, altered GABAergic function in Syngap1+/- mice is due to reduced KCC2 expression leading to an increase in the intracellular chloride concentration that can be counteracted by the 6BIO, which restored cognitive, emotional, and social symptoms by pharmacological intervention, particularly in adulthood.

Designing dendronic-Raman markers for sensitive detection using surface-enhanced Raman spectroscopy.

Surface-Enhanced Raman Spectroscopy (SERS) is well-established as a tool for bio-diagnostics but is often limited by analyte sensitivity and the need for specialized substrates. Signal enhancement can be achieved by attaching multiple Raman markers to a single analyte. Dendronic frameworks with multiple Raman markers attached to the periphery offer an opportunity to examine this idea. In this article, dendrons with thiophenol groups on their periphery were synthesized and tested as a SERS analyte. For this study, simple gold nanoparticles (∼60 nm) were used as a substrate. A 102 fold enhancement in detection was observed upon going from a mono-thiophenol (MT) to a tetra-thiophenol (TT). Dendronic Raman markers increased the probability of SERS occurrence at lower concentrations when compared to a single Raman active molecule. This strategy extends the applicability of SERS, as these analyte molecules can be just mixed or drop-casted on any kind of SERS substrate.

Activation of Benzyl Aryl Carbonates: The Role of Cation-π Interactions.

Benzyl aryl carbonates can react with a nucleophile to yield an activated electrophile and an aryloxide anion. Previously, we had utilized this in the synthesis of α-nitro esters from nitroalkanes. To further understand the process of activation of these carbonates by nucleophiles, we have performed kinetic studies on the hydrolysis of carbonates using nucleophiles. Rate constants for the hydrolysis were obtained under pseudo-first-order conditions with DABCO as the nucleophile. A comparison of rate constant for hydrolysis of isobutyl phenyl carbonate with benzyl phenyl carbonate shows that the presence of benzyl group results in a 16-fold acceleration of hydrolysis rate. This indicates that the transition state for activation of carbonate is stabilized by cation-π interactions. A comparison of the rate constant for various aromatic rings indicates that electron-donating substituents on the benzyl groups accelerate the rate of hydrolysis. Studies were also carried out with DMAP as nucleophile and the results are presented. Our studies show that stable carbonates can be activated using nucleophiles. Activated acyl groups generated from acid anhydrides have been used in several enantioselective reactions. Our studies show that carbonates can be stable alternatives to acid anhydrides.

A Comparison of Charge Separation Dynamics in Organic Blend Films Employing Fullerene and Perylene Diimide Electron Acceptors.

We report a comparison of charge carrier dynamics and device performance for low band gap polymer PBDTTT-CT in blends with the fullerene acceptor PC71BM and a PDI derivative with similar electron affinities. Charge separation and recombination dynamics are found to be remarkably similar for these two acceptors, with both blends exhibiting efficient, ultrafast charge separation (time constants of 1.6 and 1.4 ps, respectively). The lower device performance for the PDI acceptor (1.75% compared to 3.5% for the equivalent PC71BM device) is shown to result from slower charge transport, increasing nongeminate recombination losses during charge collection.

Ferroelectric Polymer Matrix for Probing Molecular Organization in Perylene Diimides.

Ferroelectric films of poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) provide a controlled environment to study the aggregation tendency of functional molecules such as perylene diimides (PDIs). The local electric field and free volume confinement parameters offered by the matrix are tailored to study the organizational and assembly characteritics of molecular acceptors. The optical properties of planar and nonplanar PDIs in the ferroelectric polymer matrix were studied systematically over a wide range that encompassed the ferroelectric transition temperature. This approach provides valuable insight into the properties of molecular materials used in applications ranging from bulk heterostructure-based photovoltaics to nonlinear optical materials.

Unusual reactivity of nitronates with an aryl alkyl carbonate: synthesis of α-amino esters.

The monoanions of nitroalkanes are ambident nucleophiles that react with carbonate electrophiles through the oxygen atom. Products arising from reactivity at the carbon atom will yield α-nitro esters, which are precursors for α-amino esters. We demonstrate this in the reactions of nitroalkanes with benzyl phenyl carbonate and DABCO where α-nitro esters are obtained instead of nitrile oxides. The products are readily reduced to α-amino esters. This pathway could be a safe alternative to the Strecker reaction.

Nonplanar Perylene Diimides as Potential Alternatives to Fullerenes in Organic Solar Cells.

Perylene diimides (PDIs) are attractive alternatives to fullerenes as electron transporters because of their optoelectronic properties, durability, and ease of synthesis. Belying this promise, devices that utilize PDIs as electron acceptors have low efficiencies. The primary deficiency in such cells is the low short circuit current density (JSC), which is traceable to the crystallinity of PDIs. Therefore, disrupting the crystallinity without adversely impacting the charge-transfer properties of PDIs is proposed as an important design principle. This has been achieved using a nonplanar perylene. In combination with a hole transporting polymer, a device efficiency of 2.77% has been achieved. A 10-fold increase in JSC is observed in comparison with a planar PDI, resulting in one of the highest JSC values for a solution processed device featuring a PDI. Indeed, this is one of the highest efficiencies for devices featuring a nonfullerene as the electron transporter.

Design of hydrogen bond catalysts based on a modular oxazoline template: application to an enantioselective hetero Diels-Alder reaction.

[reaction: see text] A catalyst system that displays two hydrogen bond donating arms from a rigid oxazoline backbone and its utility in a hydrogen bond promoted enantioselective hetero Diels-Alder reaction are described.

Catalytic enantioselective oxidations using molecular oxygen.

The use of molecular oxygen as an atom-efficient, environmentally benign and inexpensive oxidant has increasingly gained consideration in catalysis. This review will specifically highlight catalytic enantioselective oxidations that utilize molecular oxygen as a terminal oxidant. The topics covered herein include aerobic enantioselective variants of alcohol oxidation, Baeyer-Villiger oxidation, dihydroxylation, epoxidation, oxidative biaryl coupling and sulfoxidation.

Modular synthesis of amine-functionalized oxazolines.

Substituted oxazoline amines have been prepared in high yield from beta-amino alcohols and Fmoc-protected alpha-amino acids using CCl(4), PPh(3), and Hünig's base in a one-pot procedure followed by base-mediated deprotection. [reaction: see text]