The ongoing depletion of fossil fuels has led to an intensive search for additional renewable energy sources. Solar-based technologies could provide sufficient energy to satisfy the global economic demands in the near future. Photovoltaic (PV) cells are the most promising man-made devices for direct solar energy utilization. Understanding the charge separation and charge transport in PV materials at a molecular level is crucial for improving the efficiency of the solar cells. Here, we use light-induced EPR spectroscopy combined with DFT calculations to study the electronic structure of charge separated states in blends of polymers (P3HT, PCDTBT, and PTB7) and fullerene derivatives (C60-PCBM and C70-PCBM). Solar cells made with the same composites as active layers show power conversion efficiencies of 3.3% (P3HT), 6.1% (PCDTBT), and 7.3% (PTB7), respectively. Under illumination of these composites, two paramagnetic species are formed due to photo-induced electron transfer between the conjugated polymer and the fullerene. They are the positive, P+, and negative, P-, polarons on the polymer backbone and fullerene cage, respectively, and correspond to radical cations and radical anions. Using the high spectral resolution of high-frequency EPR (130 GHz), the EPR spectra of these species were resolved and principal components of the g-tensors were assigned. Light-induced pulsed ENDOR spectroscopy allowed the determination of 1H hyperfine coupling constants of photogenerated positive and negative polarons. The experimental results obtained for the different polymer-fullerene composites have been compared with DFT calculations, revealing that in all three systems the positive polaron is distributed over distances of 40 - 60 Å on the polymer chain. This corresponds to about 15 thiophene units for P3HT, approximately three units PCDTBT, and about three to four units for PTB7. No spin density delocalization between neighboring fullerene molecules was detected by EPR. Strong delocalization of the positive polaron on the polymer donor is an important reason for the efficient charge separation in bulk heterojunction systems as it minimizes the wasteful process of charge recombination. The combination of advanced EPR spectroscopy and DFT is a powerful approach for investigation of light-induced charge dynamics in organic photovoltaic materials.

Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related structures, and screened them for in vitro cytotoxicity and antiparasitic activity against T. gondii and C. parvum . We identified one compound (GMG-1-09), and four compounds (JS-1-09, JS-2-20, JS-2-35 and JS-2-49) with efficacy against C. parvum and T. gondii , respectively, at low micromolar concentrations and showed appreciable selectivity in human host cells. Among the four compounds with efficacy against T. gondii , JS-1-09 representing the diacyl urea scaffold was the most effective, with an anti- Toxoplasma IC 50 concentration (1.21 μM) that was nearly 53-fold lower than its cytotoxicity IC 50 concentration, indicating that this compound has a good selectivity index. The other three compounds (JS-2-20, JS-2-35 and JS-2-49) were structurally more divergent from JS-1-09 as they represent the acyl urea and acyl carbamate scaffold. This appeared to correlate with their anti- Toxoplasma activity, suggesting that these compounds’ potency can likely be enhanced by selective structural modifications. One compound, GMG-1-09 representing acyl carbamate scaffold, depicted in vitro efficacy against C. parvum with an IC 50 concentration (32.24 μM) that was 14-fold lower than its cytotoxicity IC 50 concentration in a human intestinal cell line. Together, our studies unveil a series of novel synthetic acyl/diacyl urea and acyl carbamate scaffold-based small molecule compounds with micromolar activity against T. gondii and C. parvum that can be explored further for the development of the much-needed novel anti-protozoal drugs.

A wide range of chemicals such as amides, hydrazides, amines, alcohols, carbazate, and sulfonate were reacted with acyl isocyanates generated by the reaction of primary amides with oxalyl chloride to give symmetrical and unsymmetrical diacyl urea derivatives, acyl ureas/carbamates/thiocarbamates, and related compounds. This method provides means for convenient one-pot, two-step synthesis of compounds bearing urea, carbamate, and other functional groups from cheap and commercially available starting reagents. It is expected that the results presented in this report will expand the medicinal chemist's toolbox.

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Fatty acid amide hydrolase (FAAH) is a serine hydrolase enzyme that metabolizes various lipophilic transmitters, including oleamide, anandamide, and 2‐arachidonyl glycerol. These neurotransmitters are part of the endocannabinoid system (ECS) that comprises a neuromodulatory network involved in regulation of various physiological functions, including appetite, pain, reward, motor control, memory, and mood. Previous studies have shown that enhancing the ECS offers a potential therapeutic target for various psychiatric disorders. An FAAH inhibitor provides indirect modulation of the system, with the added advantage of avoiding undesirable adverse effects associated with the direct receptor agonists. The objective of this study was to synthesize various oleamide analogs and evaluate them for FAAH inhibition. A total of fifty one compounds (1–51) were synthesized using a one‐pot two‐step synthetic scheme. All compounds were evaluated in the in vitro FAAH inhibition assay using human recombinant FAAH enzyme, at 2–100 uM concentrations. Of these compounds, ten analogs showed >50% FAAH inhibition activity at the 50 uM concentration. These compounds serve as leads for structure activity relationship studies to optimize the inhibitory activity and to help design potent and effective FAAH inhibitors to be evaluated in vivo in various animal models of neuropsychiatric disorders.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.