Incorporation Of Methyl Groups Research Articles

1,4-D-Glucan block copolymers: synthesis and comprehensive structural characterization

Multi-block glucans comprising permethylated and partially methylated blocks are compounds of interest. In order to monitor their formation by transglycosylation of corresponding starting glucans, a method has been developed and applied to model compounds. This method allows determining the average length of the blocks and the progress of incorporation of methyl blocks in partially methylated sequences with a random distribution. The method, comprising liquid chromatography mass spectrometry (LC-MS) and electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MSn) measurements of two types of peralkylated glucans representing derivatives of the target compounds, is comprehensively described and discussed. ESI-MSn allows looking into the sequences of oligomeric domains. In addition, transglycosylation is followed by attenuated total reflection FTIR and NMR spectroscopy.Graphical abstract

A novel stable isotope tracer method to simultaneously quantify skeletal muscle protein synthesis and breakdown

Background/aimsMethodological challenges have been associated with the dynamic measurement of muscle protein breakdown (MPB), as have the measurement of both muscle protein synthesis (MPS) and MPB within the same experiment. Our aim was to use the transmethylation properties of methionine as proof-of-concept to measure rates of MPB via its methylation of histidine within skeletal muscle myofibrillar proteins, whilst simultaneously utilising methionine incorporation into bound protein to measure MPS. ResultsDuring the synthesis measurement period, incorporation of methyl[D3]-13C-methionine into cellular protein in C2C12 myotubes was observed (representative of MPS), alongside an increase in the appearance of methyl[D3]-methylhistidine into the media following methylation of histidine (representative of MPB). For further validation of this approach, fractional synthetic rates (FSR) of muscle protein were increased following treatment of the cells with the anabolic factors insulin-like growth factor-1 (IGF-1) and insulin, while dexamethasone expectedly reduced MPS. Conversely, rates of MPB were reduced with IGF-1 and insulin treatments, whereas dexamethasone accelerated MPB. ConclusionsThis is a novel stable isotope tracer approach that permits the dual assessment of muscle cellular protein synthesis and breakdown rates, through the provision of a single methionine amino acid tracer that could be utilised in a wide range of biological settings.

Ring-opening carbonyl-olefin metathesis of norbornenes.

A computational and experimental study of the hydrazine-catalyzed ring-opening carbonyl–olefin metathesis of norbornenes is described. Detailed theoretical investigation of the energetic landscape for the full reaction pathway with six different hydrazines revealed several crucial aspects for the design of next-generation hydrazine catalysts. This study indicated that a [2.2.2]-bicyclic hydrazine should offer substantially increased reactivity versus the previously reported [2.2.1]-hydrazine due to a lowered activation barrier for the rate-determining cycloreversion step, a prediction which was verified experimentally. Optimized conditions for both cycloaddition and cycloreversion steps were identified, and a brief substrate scope study for each was conducted. A complication for catalysis was found to be the slow hydrolysis of the ring-opened hydrazonium intermediates, which were shown to suffer from a competitive and irreversible cycloaddition with a second equivalent of norbornene. This problem was overcome by the strategic incorporation of a bridgehead methyl group on the norbornene ring, leading to the first demonstrated catalytic carbonyl–olefin metathesis of norbornene rings.

Fabrication of hydrophobic PP/CH3SiO2 composite hollow fiber membrane for membrane contactor application

Polymeric membrane wetting by liquid absorbent is one of the major challenges of the gas- liquid membrane contactors. In order to overcome this issue, composite polypropylene (PP) hollow fiber membranes were prepared by incorporation of methyl grafted silica nanoparticles (CH3-g-silica NPs) via two treatment approaches including blending the NPs with dope solution before membrane fabricating (approach 1), and also coating the NPs on the surface of the prepared membrane (approach 2). The fabricated membranes were characterized by using ATR-FTIR, FESEM, TEM, AFM, porosity, contact angle, mechanical strength, breakthrough pressure, wetting resistance and gas permeation test. The obtained results from ATR-FTIR spectra confirmed the successful formation of the PP-CH3SiO2 composite hollow fiber membranes. It was seen that for composite membranes fabricated with approaches 1 and 2 the average contact angle increased from 124° to 145° and 168°, respectively. The fabricated membranes were also investigated for CO2 absorption process in gas- liquid membrane contactors. As a result, the gentle decrease in flux of composite membranes compare to the sharp flux drop of neat one confirmed the effective improvement in the non-wetting property of the membranes in the presence of inorganic particles.

Advances in chronic myelomonocytic leukemia and future prospects: Lessons learned from precision genomics.

In the latest World Health Organization classification of myeloid neoplasms, chronic myelomonocytic leukemia (CMML) exists as a separate entity under the category of myelodysplastic/myeloproliferative (MDS/MPN) overlap syndromes. Outcomes remain uniformly poor with a median overall survival of ~2 years and an inherent risk of transformation into acute myeloid leukemia (15-20% over 5 years). Due to unique biologic characteristics such as overlapping features of myelodysplasia and myeloproliferation, and clinical diversity despite relative genomic homogeneity, CMML represents a unique model to study chronic myeloid tumor biology. Recent advances have focused on understanding the role of putative genomic abnormalities, in particular, clonal evolution of pathogenic alterations in genes regulating the epigenome (TET2), chromatin architecture (ASXL1), spliceosome complex (SRSF2, SF3B1) and cell signaling (NRAS, KRAS, CBL, JAK2). Disease prognostication has evolved from purely clinical prognostic models to those incorporating pathogenic gene variations. Therapeutic options in this disease remain dismal with only two agents approved by the United States Food and Drug Administration, namely 5-azacitidine and decitabine. Allogeneic hematopoietic stem cell transplantation remains the sole curative option in this disease; however is associated with substantial treatment-related morbidity and mortality. Future areas of research include opportunities to further improve disease prognostication by employing novel technologies such as machine learning, incorporation of methylation and cytokine signatures, in addition to gene mutations; insights into clonal origins of this disease, and novel therapeutic strategies.

(Micro)structure, thermal behavior and mechanical properties of ethylene–propylene–1-octadecene terpolymers from chain-walking polymerization of 1-octadecene

This paper reports the polymerization of 1-octadecene catalyzed by a series of α-diimine Ni(II) complex, with methyl ligand backbone and different substituents in the ortho and para aryl positions, in combination with Et2AlCl. We obtained semicrystalline ethylene–propylene–1-octadecene terpolymers with high molecular weight and narrow molecular weight distribution. The formation of such terpolymers is due to the numerous combinations of insertion and chain-walking pathways. The effect of the type of ligand and monomer feedstock concentration on the activity, regioselectivity, polymers (micro)structure, and structure/properties is thoroughly investigated by NMR, DSC, WAXD and SAXS. The thermal behavior and the crystal structure of the polymers are strongly influenced by the level of incorporation of methyl and longer alkyl branches. The chain heterogeneity of the polymers is investigated by successive self-nucleation and annealing thermal fractionation evaluating the crystallizable sequence length, and the lamellar thickness.

The methylation effect in prolonging the pure organic room temperature phosphorescence lifetime.

Prolonging the phosphorescence lifetime of pure organic phosphorescent materials by a methyl-substitution strategy is described. We present a chemical strategy for improving the phosphorescence lifetime of triplet excitons under ambient conditions by incorporating methyl groups into the chemical structures. This is observed by a long-lived phosphorescence lifetime of up to 0.83s detected for methylated 9-(4-(mesitylsulfonyl)phenyl)-9H-carbazole (3M), compared to 0.36 s for 9-(4-(phenylsulfonyl)phenyl)-9H-carbazole (0M) without any methyl groups. Additionally, enhanced phosphorescence efficiency can be obtained at an appropriate methylation degree, because of the smaller ΔE ST (singlet and triplet energy gap) and ΔE TT* (normal phosphorescence and long-lived phosphorescence energy gap). A comprehensive investigation on the packing mode in the crystalline state reveals that the methyl groups occupy the free volume and result in a suppression of non-radiative decay, accounting for the enhanced phosphorescence lifetime.

Hexamethyldisiloxane cold plasma treatment and amylose content determine the structural, barrier and mechanical properties of starch-based films

In this study, the effect of amylose content and cold plasma treatment on starch films properties was investigated. Films from normal (30%) and high amylose (50 and 70%) starches were subjected to hexamethyldisiloxane (HMDSO) cold plasma treatment. Morphological, structural, mechanical and barrier properties of the films were evaluated. The amount of remnant starch granules (RSG) in the films depended on the amylose content and on the gelatinization extent of the starch. This behavior was corroborated on the films from starch with 50% amylose, where the loss of RSG resulted in poor barrier properties and high hydrophilicity. Moreover, HMDSO cold plasma treatment incorporated methyl groups improving the hydrophobic properties and favored the helix ordering of the starch components resulting in a limited water-film interaction. Furthermore, the simultaneous effect of HMDSO coating and the ordering of the structures reinforced the surface of the films, improving the mechanical properties.

ATIM-13. ASUNERCEPT PLUS RADIOTHERAPY IN RELAPSED GLIOBLASTOMA. UPDATE ON FIVE YEARS OVERALL SURVIVAL OF STUDY NCT01071837 AND DEVELOPMENT OF A POPULATION-PK - TUMOR GROWTH INHIBITION - SURVIVAL MODEL

Asunercept (APG101) is an Fc-fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of IgG1. Asunercept is in clinical development for glioblastoma (GB). Based on PK-data from study NCT01071837 a population pharmacokinetic (PopPK) - tumor growth inhibition (TGI) model was developed and extended to a survival model describing the effect of radiotherapy (RT) or RT + asunercept on the overall survival (OS) of GB-patients. The objective of the model was to identify the best descriptor (i.e. asunercept exposure, tumor size determined by MRT) for survival and to quantify the effect of CpG2 methylation in the CD95 ligand promoter on patient survival. Model development was performed using non-linear mixed effects modeling with NONMEM 7.3 in a stepwise procedure. Firstly, a PopPK–TGI model was developed. Several tumor growth models were tested (e.g. exponential, sequential exponential-linear). Secondly, a survival model was developed and linked to the PopPK-TGI model. For the PopPK-TGI model, data from 84 patients were available contributing to 314 tumor measurements. Glioblastoma growth was best described by an exponential growth model with an average doubling time of 90 days. Asunercept exposure showed a significant inhibitory effect on the tumor growth rate. Tumor size was identified to significantly influence survival. Incorporation of CpG2 CD95L promotor methylation further improved the model: the survival in asunercept-treated patients was prolonged with lower CpG2 methylation status. A PopPK-TGI-Survival model for asunercept and radiotherapy treated patients was developed. A clear inhibitory effect of asunercept exposure was observable on tumor growth resulting in an increased survival. A recent update on OS of study NCT01071837 revealed that 7% of Asunercept+RT treated 2nd-line GB patients were alive after 5 years compared to 0% in patients treated with RT alone.

Establishment of regulatory elements during erythro-megakaryopoiesis identifies hematopoietic lineage-commitment points

BackgroundEnhancers and promoters are cis-acting regulatory elements associated with lineage-specific gene expression. Previous studies showed that different categories of active regulatory elements are in regions of open chromatin, and each category is associated with a specific subset of post-translationally marked histones. These regulatory elements are systematically activated and repressed to promote commitment of hematopoietic stem cells along separate differentiation paths, including the closely related erythrocyte (ERY) and megakaryocyte (MK) lineages. However, the order in which these decisions are made remains unclear.ResultsTo characterize the order of cell fate decisions during hematopoiesis, we collected primary cells from mouse bone marrow and isolated 10 hematopoietic populations to generate transcriptomes and genome-wide maps of chromatin accessibility and histone H3 acetylated at lysine 27 binding (H3K27ac). Principle component analysis of transcriptional and open chromatin profiles demonstrated that cells of the megakaryocyte lineage group closely with multipotent progenitor populations, whereas erythroid cells form a separate group distinct from other populations. Using H3K27ac and open chromatin profiles, we showed that 89% of immature MK (iMK)-specific active regulatory regions are present in the most primitive hematopoietic cells, 46% of which contain active enhancer marks. These candidate active enhancers are enriched for transcription factor binding site motifs for megakaryopoiesis-essential proteins, including ERG and ETS1. In comparison, only 64% of ERY-specific active regulatory regions are present in the most primitive hematopoietic cells, 20% of which containing active enhancer marks. These regions were not enriched for any transcription factor consensus sequences. Incorporation of genome-wide DNA methylation identified significant levels of de novo methylation in iMK, but not ERY.ConclusionsOur results demonstrate that megakaryopoietic profiles are established early in hematopoiesis and are present in the majority of the hematopoietic progenitor population. However, megakaryopoiesis does not constitute a “default” differentiation pathway, as extensive de novo DNA methylation accompanies megakaryopoietic commitment. In contrast, erythropoietic profiles are not established until a later stage of hematopoiesis, and require more dramatic changes to the transcriptional and epigenetic programs. These data provide important insights into lineage commitment and can contribute to ongoing studies related to diseases associated with differentiation defects.

Experimental Design and Bioinformatic Analysis of DNA Methylation Data.

DNA methylation is a crucial regulatory mechanism of gene expression, affected in many human pathologies. Therefore, it is not surprising that nowadays, in the era of high-throughput methods, a lot of data sets representing DNA methylation in various conditions are available and the amount of such data keeps growing. In this chapter, we discuss those aspects of experiment planning and data analysis, which we consider the most important for reliability and reproducibility of DNA methylation studies: usage of replicates, data quality control at various stages, selection of a statistical model, and incorporation of DNA methylation into the multi-omics analysis.

Ruthenium(II)–arene complexes of diimines: Effect of diimine intercalation and hydrophobicity on DNA and protein binding and cytotoxicity

A series of half‐sandwich Ru(II)–arene complexes [Ru(η6‐benzene)(diimine)Cl](PF6) (1–4), where diimine is 1,10‐phenanthroline (1), 5,6‐dimethyl‐1,10‐phenanthroline (2), dipyrido[3,2‐a:2′,3′‐c]phenazine (3) or 11,12‐dimethyldipyrido[3,2‐a:2′,3′‐c]phenazine (4), have been isolated and characterized using analytical and spectral methods. Complex 2 possesses a familiar pseudo‐octahedral ‘piano‐stool’ structure. The intrinsic DNA binding affinity of the complexes depends upon the diimine ligand: 3 (dppz) > 4 (11,12‐dmdppz) > 2 (5,6‐dmp) > 1 (phen). The π‐stacking interaction of extended planar ring of coordinated dppz (3) in between the DNA base pairs is more intimate than that of phen (1), and the incorporation of methyl groups on the dppz ring (4) discourages the stacking interaction leading to a lower DNA binding affinity for 4 than 3. Docking studies show that all the complexes bind in the major groove of DNA. Interestingly, 3 shows an ability to convert supercoiled DNA into nicked circular DNA even at 20 μM concentration beyond which complete oxidative DNA degradation is observed. The protein binding affinity of the complexes decreases in the order 4 > 3 > 2 > 1, and the higher protein binding affinity of 4 illustrates the strong involvement of methyl groups on dppz ring in hydrophobic interaction with protein. Also, 4 cleaves protein more efficiently than the other complexes in the presence of H2O2. It is notable that 2, 3 and 4 display cytotoxicity against human cervical cancer cell lines (SiHa) with potency higher than the currently used drug cisplatin. Acridine orange/ethidium bromide staining studies reveal that 3 induces apoptosis in cancer cells much more efficiently than 4.

Heat Stress Dictates Microbial Lipid Composition along a Thermal Gradient in Marine Sediments.

Temperature exerts a first-order control on microbial populations, which constantly adjust the fluidity and permeability of their cell membrane lipids to minimize loss of energy by ion diffusion across the membrane. Analytical advances in liquid chromatography coupled to mass spectrometry have allowed the detection of a stunning diversity of bacterial and archaeal lipids in extreme environments such as hot springs, hydrothermal vents and deep subsurface marine sediments. Here, we investigated a thermal gradient from 18 to 101°C across a marine sediment field and tested the hypothesis that cell membrane lipids provide a major biochemical basis for the bioenergetics of archaea and bacteria under heat stress. This paper features a detailed lipidomics approach with the focus on membrane lipid structure-function. Membrane lipids analyzed here include polar lipids of bacteria and polar and core lipids of archaea. Reflecting the low permeability of their ether-linked isoprenoids, we found that archaeal polar lipids generally dominate over bacterial lipids in deep layers of the sediments influenced by hydrothermal fluids. A close examination of archaeal and bacterial lipids revealed a membrane quandary: not only low permeability, but also increased fluidity of membranes are required as a unified property of microbial membranes for energy conservation under heat stress. For instance, bacterial fatty acids were composed of longer chain lengths in concert with higher degree of unsaturation while archaea modified their tetraethers by incorporation of additional methyl groups at elevated sediment temperatures. It is possible that these configurations toward a more fluidized membrane at elevated temperatures are counterbalanced by the high abundance of archaeal glycolipids and bacterial sphingolipids, which could reduce membrane permeability through strong intermolecular hydrogen bonding. Our results provide a new angle for interpreting membrane lipid structure-function enabling archaea and bacteria to survive and grow in hydrothermal systems.

Density functional theory calculations of charge transport properties of ‘plate-like’ coronene topological structures

Charge transport rate is one of the key parameters determining the performance of organic electronic devices. In this paper, we used density functional theory (DFT) at the M06-2X/6−31 $$+$$ G(d) level to compute the charge transport rates of nine coronene topological structures. The results show that the energy gap of these nine coronene derivatives is in the range 2.90–3.30 eV, falling into the organic semiconductor category. The size of the conjugate ring has a large influence on the charge transport properties. Incorporation of methyl groups on the rigid core of tetrabenzocoronene and hexabenzocoronene is more conducive to the hole transport of the molecule than incorporating methoxyl groups. The derivatisation of a ‘long plate-like’ coronene with methoxyl groups facilitates both hole and electron transport. This class of molecules can thus be used in the design of ambipolar transport semiconductor materials. JCSC-D-16-01407 SYNOPSIS Density functional theory was used to compute the charge transport rates of three series nine coronene topological structures at the M06-2X/6−31+G(d) level. Tetrabenzocoronene (series a) and hexabenzocoronene (series b) could be candidates for a hole-transporting (p-type) organic semiconductor material, and ‘long plate-like’ coronene topological structures (series c) could be used as an ambipolar transport material.

Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population.

Metastases in the later stages of hepatocellular carcinoma (HCC) cause the majority of deaths associated with the disease, making early detection crucial to patient survival. Risk models assessing HCC risk in the general population can be used for risk stratification for further HCC surveillance, however, none have been validated externally. Methylation of circulating DNA shows potential for non-invasive diagnosis of HCC. We conducted a prospective case-control study nested within a community-based cohort. We measured methylation levels in six genes (CDKN2A, RASSF1A, STEAP4, TBX2, VIM and ZNF154) which were identified in our previous work, using pre-diagnostic plasma DNA from 237 HCC cases and 257 matched controls. We found TBX2 hypermethylation was associated with increased HCC risk, with ORs (95% CI) of 3.2 (1.8-6.0). The associations were mainly among high-risk subjects; among subjects infected with HBV/HCV, the OR (95% CI) of TBX2 methylation was 5.3 (2.2-12.7). Among subjects with high risk scores, the ORs (95% CIs) were 7.8 (1.5-38.6) for Wen-HCC model ≥16, 5.8 (2.2-15.5) for Hung-HCC ≥15 and 7.5 (2.2-26.0) for Michikawa-HCC ≥8. Adding TBX2 methylation improved the accuracy of risk models for a high-risk population, with the area under the curve (AUC) of 76% for Wen-HCC score with TBX2 methylation compared with 69% with Wen-HCC alone. The AUCs were 63% for Hung-HCC score plus TBX2 methylation, and 53% for Hung-HCC alone, 65% for Michikawa-HCC score plus TBX2 methylation and 58% for Michikawa-HCC alone. Our findings suggest the potential increase in risk assessment discrimination and accuracy from incorporation of DNA methylation.

Abstract 2747: Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population

Abstract Metastases in the later stages of hepatocellular carcinoma (HCC) cause the majority of deaths associated with the disease, making early detection crucial to patient survival. Risk models that assess HCC risk in the general population can be used for risk stratification for further HCC surveillance, however, none have been validated externally. Methylation of circulating DNA shows potential for noninvasive and early diagnosis of HCC. Most evidence, however, comes from cross-sectional studies raising concerns about temporality. We conducted a prospective case-control study nested within a community-based cohort. We measured methylation levels in of 6 genes (CDKN2A, RASSF1A, STEAP4, TBX2, VIM, and ZNF154) using pre-diagnostic plasma DNA from 237 HCC cases and 257 matched controls. We found TBX2 hypermethylation was associated with increased HCC risk, with ORs (95%CI) of 3.7 (1.9-7.2). The associations were mainly among high-risk subjects; among subjects infected with HBV/HCV, the OR (95%CI) of TBX2 methylation was 5.3 (2.2-12.7). Among subjects with high risk, the ORs (95%CIs) were 8.9 (1.0-73.9) for Wen-HCC score ≥16, 5.6 (2.1-14.6) for Hung-HCC score ≥15, and 7.2 (2.1-24.4) for Michikawa-HCC ≥8. Adding information on TBX2 methylation improved the accuracy of risk models for a high risk population, with the area under the curve (AUC) of 74% for TBX2 methylation and Wen-HCC score compared with 64% with Wen-HCC score alone. The AUCs were 63% for Hung-HCC score and TBX2 methylation, 53% for Hung-HCC score alone, 65% for Michikawa-HCC score and TBX2 methylation and 59% for Michikawa-HCC risk alone. Our findings suggest the potential increase in risk assessment discrimination and accuracy from incorporation of DNA methylation. Citation Format: Hui-Chen Wu, Hwai-I Yang, Qiao Wang, Chien-Jen Chen, Regina M. Santella. Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2747. doi:10.1158/1538-7445.AM2017-2747

Biochemical Investigation into Novel Activities of Yeast SPOUT‐Superfamily RNA Methyltransferases

The SPOUT superfamily of S‐adenosyl‐L‐methionine (SAM) dependent methyltransferases are involved in post‐transcriptional RNA modifications. Nep1, a SPOUT superfamily member, methylates rRNA at the N1 position of a post‐transcriptionally incorporated pseudouridine in the 18S rRNA of Saccharomyces cerevisiae (yeast) and in humans is implicated in cases of Diamond‐Blackfan anemia. We found that Nep1 can bind and methylate a specific pseudouridine found in the U2 snRNA in vitro, suggesting that Nep1 may also play a role in splicing regulation. Given this finding, other SPOUT proteins may also be able to modify snRNAs and be involved in splicing regulation. YGR283C and YMR310C are two other yeast SPOUT methyl transferases whose specific biological functions are not known but are known to interact with the U2 snRNP yeast protein, Lea1, and the yeast homolog of dyskerin, a protein involved in pseudouridylation of the U2 snRNA. We have expressed yeast YGR283C in E. coli and purified the protein for biochemical and structural characterization. Fluorescence polarization assays and electrophoretic mobility shift assays will be conducted to quantify YGR283C binding affinities for snRNAs. Filter binding assays will be used to quantify [3H]‐methyl incorporation from SAM into snRNA substrates. Together these studies will elucidate the function of these previously uncharacterized SPOUT superfamily members.

Tuning of Second-Order Nonlinear Optical Response Properties of Aryl-Substituted Boron-Dipyrromethene Dyes: Unidirectional Charge Transfer Coupled with Structural Tailoring

Controlling the nonlinear optical (NLO) response properties at the molecular level is a key to develop strong NLO active materials for technological applications. In this paper, we report quantum chemical investigation of NLO response properties of select aryl-substituted Boron-Dipyrromethene (BODIPY) dyes, a class of intramolecular charge transfer (ICT) probes. Density functional theory (DFT) with long-range corrected CAM-B3LYP functional and cc-pVTZ, 6-31G(d,p) and 6-31+G(d,p) basis sets are employed to compute the electronic structures and NLO response of the aforesaid molecules. Calculations at the second order M{\o}ller-Plesset perturbation (MP2) level of theory are performed for comparison. The results suggest that the charge transfer process in these molecules is mostly unidirectional and the total first hyperpolarizability (\b{eta}total) values of these molecules are dominantly dictated by the response in the direction of charge transfer. Alteration of conjugation strength through donor/acceptor substitution as well as twisting of the phenyl ring obtained through incorporation of methyl groups affect the NLO response of thesemolecules. The vector components of first hyperpolarizability (\b{eta}vec) of the probe molecules are also studied to analyze the angle between the vector components of \b{eta}vec and the dipole moment vector. The results presented here are expected to shed light on the origin of NLO response of several aryl-substituted BODIPY dyes and provide means to optimizing it for future technological applications.

Continued optimization of the M5 NAM ML375: Discovery of VU6008667, an M5 NAM with high CNS penetration and a desired short half-life in rat for addiction studies

This letter describes the continued optimization of M5 NAM ML375 (VU0483253). While a valuable in vivo tool compound, ML375has an excessively long elimination half-life in rat (t1/2=80h), which can be problematic in certain rodent addiction paradigms (e.g., reinstatement). Thus, we required an M5 NAM of comparable potency to ML375, but with a rat t1/2 of less than 4h. Steep SAR plagued this chemotype, and here we detail aniline replacements that offered some improvements over ML375, but failed to advance. Ultimately, incorporation of a single methyl group to the 9b-phenyl ring acted as a metabolic shunt, providing (S)-11 (VU6008667), an equipotent M5 NAM, with high CNS penetration, excellent selectivity versus M1–4 and the desired short half-life (t1/2=2.3h) in rat.

Ionic behavior modification of cation exchange ED membranes by using CMC-co-Fe3O4 nanoparticles for heavy metals removal from water

A new mixed matrix polyvinyl chloride-based heterogeneous cation exchange membrane was prepared by incorporation of carboxy methyl cellulose-co-Fe3O4 nanoparticles through solution casting technique. The effect of simultaneous using of carboxy methyl cellulose and iron oxide nanoparticles in the casting solution on the physicochemical properties of membranes was studied. SOM images showed uniform particles distribution and uniform surfaces for the membranes relatively. The SEM images exhibited regular direction/spatial orientation for the CMC-co-Fe3O4 nanoparticles in the membrane matrix. XRD patterns showed that membrane heterogeneity was enhanced by using of Fe3O4 nanoparticles. Membrane ion exchange capacity, membrane surface hydrophilicity, membrane potential, surface charge density, transport number, selectivity, and ionic flux were increased by using CMC/Fe3O4 nanoparticles in membrane matrix. Results showed that membrane areal electrical resistance was declined up to 3.8 Ω cm2 by utilizing CMC/Fe3O4 nanoparticles in the casting solution. Also PVC/CMC-co-Fe3O4 membrane showed higher transport number, selectivity, flux, and electrical conductivity compared to PVC/CMC membrane and unmodified ones. Electrodialysis experiment in laboratory scale showed higher dialytic rate in lead ions removal for PVC/CMC-co-Fe3O4 nanoparticle-mixed matrix ion exchange membrane compared to PVC/CMC membrane and pristine one.