Simultaneous atmospheric nitrous oxide, methane and water vapor detection with a single continuous wave quantum cascade laser.

A continuous wave (CW) quantum cascade laser (QCL) based absorption sensor system was demonstrated and developed for simultaneous detection of atmospheric nitrous oxide (N(2)O), methane (CH(4)), and water vapor (H(2)O). A 7.73-µm CW QCL with its wavelength scanned over a spectral range of 1296.9-1297.6 cm(-1) was used to simultaneously target three neighboring strong absorption lines, N(2)O at 1297.05 cm(-1), CH(4) at 1297.486 cm(-1), and H(2)O at 1297.184 cm(-1). An astigmatic multipass Herriott cell with a 76-m path length was utilized for laser based gas absorption spectroscopy at an optimum pressure of 100 Torr. Wavelength modulation and second harmonic detection was employed for data processing. Minimum detection limits (MDLs) of 1.7 ppb for N(2)O, 8.5 ppb for CH(4), and 11 ppm for H(2)O were achieved with a 2-s integration time for individual gas detection. This single QCL based multi-gas detection system possesses applications in environmental monitoring and breath analysis.

Atmospheric CH4 and N2O measurements near Greater Houston area landfills using a QCL-based QEPAS sensor system during DISCOVER-AQ 2013.

A quartz-enhanced photoacoustic absorption spectroscopy (QEPAS)-based gas sensor was developed for methane (CH4) and nitrous-oxide (N2O) detection. The QEPAS-based sensor was installed in a mobile laboratory operated by Aerodyne Research, Inc. to perform atmospheric CH4 and N2O detection around two urban waste-disposal sites located in the northeastern part of the Greater Houston area, during DISCOVER-AQ, a NASA Earth Venture during September 2013. A continuous wave, thermoelectrically cooled, 158 mW distributed feedback quantum cascade laser emitting at 7.83 µm was used as the excitation source in the QEPAS gas sensor system. Compared to typical ambient atmospheric mixing ratios of CH4 and N2O of 1.8 ppmv and 323 ppbv, respectively, significant increases in mixing ratios were observed when the mobile laboratory was circling two waste-disposal sites in Harris County and when waste disposal trucks were encountered.

Double acoustic microresonator quartz-enhanced photoacoustic spectroscopy.

Quartz-enhanced photoacoustic spectroscopy (QEPAS) based on double acoustic microresonators (AmRs) is developed and experimentally investigated. The double AmR spectrophone configuration exhibits a strong acoustic coupling between the AmR and the quartz tuning fork, which results in a ∼5 ms fast response time. Moreover, the double AmRs provide two independent detection channels that allow optical signal addition or cancellation from different optical wavelengths and facilitate rapid multigas sensing measurements, thereby avoiding laser beam combination.

A compact QCL based methane and nitrous oxide sensor for environmental and medical applications.

A methane (CH4) and nitrous oxide (N2O) sensor based on a sensitive, selective and well established technique of quartz enhanced photoacoustic spectroscopy (QEPAS) was developed for environmental and biomedical measurements. A thermoelectrically cooled (TEC) distributed feedback quantum cascade laser (DFB-QCL), capable of continuous wave (CW) mode hop free emission in the 7.83 µm wavelength range, was used as an excitation source. For the targeted CH4 and N2O absorption lines located at 1275.04 cm(-1) and 1275.49 cm(-1) detection limits (1σ) of 13 ppbv and 6 ppbv were achieved with a 1 second data acquisition time, respectively. Environmental data of CH4 and N2O mixing ratios acquired using the QEPAS sensor system are also reported.

Discovery of Novel Non-Nucleoside Inhibitors Interacting with Dizinc Ions of CD73.

High extracellular concentrations of adenosine triphosphate (ATP) in the tumor microenvironment generate adenosine by sequential dephosphorylation of CD39 and CD73, resulting in potent immunosuppression to inhibit T cell and natural killer (NK) cell function. CD73, as the determining enzyme for adenosine production, has been shown to correlate with poor clinical tumor prognosis. Conventional inhibitors as analogues of adenosine 5'-monophosphate (AMP) may have a risk of further metabolism to adenosine analogues. Here, we report a new series of malonic acid non-nucleoside inhibitors coordinating with zinc ions of CD73. Compound 12f was found to be a superior CD73 inhibitor (IC50 = 60 nM) by structural optimization, and its pharmacokinetic properties were investigated. In mouse tumor models, compound 12f showed excellent efficacy and reversal of immunosuppression in combination with chemotherapeutic agents or checkpoint inhibitors, suggesting that it deserves further development as a novel CD73 inhibitor.

Discovery and optimization of 4-anilinoquinazoline derivatives spanning ATP binding site and allosteric site as effective EGFR-C797S inhibitors.

Epidermal growth factor receptor (EGFR) is an effective drug target for the treatment of non-small cell lung cancer (NSCLC). However, a tertiary point mutation (C797S) at the ATP binding pocket of the EGFR induces resistance to the third-generation EGFR inhibitors, due to the loss of covalent interaction with Cys797. Here, we designed a series of 4-anilinoquinazoline derivatives that simultaneously occupied the ATP binding pocket and the allosteric site. The newly-synthesized compounds displayed high potency against EGFR-C797S resistance mutation. Among them, compound 14d presented high anti-proliferative effect against BaF3-EGFRL858R/T790M/C797S (IC50 = 0.75 µM) and BaF3-EGFR19del/T790M/C797S (IC50 = 0.09 µM) cells. Moreover, 14d resulted in obvious inhibition activities against EGFR and its downstream signaling pathways in a dose-dependent manner in BaF3-EGFR19del/T790M/C797S cells. Finally, 14d significantly inhibited tumor growth in BaF3-EGFR19del/T790M/C797S xenograft model (30 mg/kg, TGI = 67.95%). These results demonstrated that 14d is a novel and effective EGFR-C797S inhibitor which spanning the ATP binding pocket and the allosteric site and effective both in vitro and in vivo.

Discovery of Novel Small-Molecule Antiangiogenesis Agents to Treat Diabetic Retinopathy.

Diabetic retinopathy is the leading cause of blindness which is associated with excessive angiogenesis. Using the structure of wondonin marine natural products, we previously created a scaffold to develop a novel type of antiangiogenesis agent that possesses minimized cytotoxicity. To overcome its poor pharmaceutical properties, we further modified the structure. A new scaffold was derived in which the stereogenic carbon was changed to nitrogen and the 1,2,3-triazole ring was replaced by an alkyl chain. By comparing the bioactivity versus cytotoxicity, compound 31 was selected, which has improved aqueous solubility and an enhanced selectivity index. Mechanistically, 31 suppressed angiopoietin-2 (ANGPT2) expression induced by high glucose in retinal cells and exhibited in vivo antiangiogenic activity in choroidal neovascularization and oxygen-induced retinopathy mouse models. These results suggest the potential of 31 as a lead to develop antiangiogenic small-molecule drugs to treat diabetic retinopathy and as a chemical tool to elucidate new mechanisms of angiogenesis.

Modulation of Excited State Property Based on Benzo[a, c]phenazine Acceptor: Three Typical Excited States and Electroluminescence Performance.

Throwing light upon the structure-property relationship of the excited state properties for next-generation fluorescent materials is crucial for the organic light emitting diode (OLED) field. Herein, we designed and synthesized three donor-acceptor (D-A) structure compounds based on a strong spin orbit coupling (SOC) acceptor benzo[a, c]phenazine (DPPZ) to research on the three typical types of excited states, namely, the locally-excited (LE) dominated excited state (CZP-DPPZ), the hybridized local and charge-transfer (HLCT) state (TPA-DPPZ), and the charge-transfer (CT) dominated state with TADF characteristics (PXZ-DPPZ). A theoretical combined experimental research was adopted for the excited state properties and their regulation methods of the three compounds. Benefiting from the HLCT character, TPA-DPPZ achieves the best non-doped device performance with maximum brightness of 61,951 cd m-2 and maximum external quantum efficiency of 3.42%, with both high photoluminescence quantum efficiency of 40.2% and high exciton utilization of 42.8%. Additionally, for the doped OLED, PXZ-DPPZ can achieve a max EQE of 9.35%, due to a suppressed triplet quenching and an enhanced SOC.

Preparation and properties of CA/ATP-g-CDs gel fibers for simultaneous detection and adsorption of methylene blue.

To detect and adsorb methylene blue (MB) from wastewater simultaneously, a solid fluorescent and absorbent material was designed by immobilizing attapulgite (ATP) on calcium alginate (CA) and reacting with carbon dots (CDs) which were modified by the activation of γ-(2,3-epoxypropoxy) propyltrimethoxysilane (KH-560), then the CA/ATP-g-CDs gel fibers were prepared. The problem of CDs easily falling out of materials was solved. The structures of the gel fibers were characterized by field emission scanning electron microscopy (FE-SEM), specific surface area (BET) and X-ray photoelectron spectroscopy (XPS). The thermal properties were analyzed by thermogravimetry (TG). The adsorption capacity was measured and the effect of initial pH was investigated. The results showed that ATP was successfully reacted with CA and the adsorption capacity was enhanced with the increase of the pH value. CA/ATP-g-CDs gel fibers were favorable materials to detect and adsorb MB simultaneously, and MB could be adsorbed by gel fibers and also the fluorescence of CA/ATP-g-CDs was weakened. At low concentrations of MB (1 µg L-1), the removal efficiency could even be as high as 100%.