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Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [ 18 F]-labelled analog of the highly affine and selective α3β4 ligand ( S )-3-(4-(4-fluorophenyl)-1 H -1,2,3-triazol-1-yl)quinuclidine (( S )- T1 ). ( S )-[ 18 F] T1 was synthesized from ethynyl-4-[ 18 F]fluorobenzene ([ 18 F] 5 ) and ( S )-azidoquinuclidine by click reaction. After a synthesis time of 130 min ( S )-[ 18 F] T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of ( S )-[ 18 F] T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of ( S )-[ 18 F] T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001 . These findings make ( S )-[ 18 F] T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET. [ABSTRACT FROM AUTHOR]

Abstract: Both enantiomers of the epibatidine analogue flubatine display high affinity towards the α4β2 nicotinic acetylcholine receptor (nAChR) in vitro, accompanied by negligible interactions with diverse off-target proteins. Extended single dose toxicity studies in rodent indicated a NOEL (No Observed Effect Level) of 6.2μg/kg for (−)-flubatine and 1.55μg/kg for (+)-flubatine. We developed syntheses for both flubatine enantiomers and their corresponding precursors for radiolabeling. The newly synthesized trimethylammonium precursors allowed for highly efficient 18F-radiolabelling in radiochemical yields >60% and specific activities >750GBq/μmol, thus making the radioligands practical for clinical investigation. [Copyright &y& Elsevier]

Abstract: (−)-[18F]flubatine is a promising agent for visualization by PET of cerebral α4β2 nicotinic acetylcholine receptors (nAChRs), which are implicated in psychiatric and neurodegenerative disorders. Here, we describe a substantially improved two-step radiosynthesis strategy for (−)-[18F]flubatine, based on the nucleophilic radiofluorination of an enantiomerically pure precursor followed by deprotection of the intermediate. An extensive leaving group/protecting group library of precursors was tested. Application of a trimethylammonium-iodide precursor with a Boc-protecting group provided the best results: labeling efficiencies of 80–95%, RCY of 60±5%, radiochemical purity of >98%, and a specific activity of >350GBq/μmol. The radiosynthesis is easily transferable to an automated synthesis module. [Copyright &y& Elsevier]

Abstract: In this report, never-dried regenerated celluloses, i.e. cellulose II, from their NaOH/urea/H2O solutions were subjected to TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) or 4-acetamide-TEMPO-mediated oxidation. Water-soluble and -insoluble fractions of carboxyl cellulose (COC) were obtained and their DO were determined to be between 0.08 and 0.85. Apart from conductometric titration, complexometric titration with EDTA was used to analyze the DO of COC. The conductometric titration can be used for lowly or highly oxidized celluloses, while the complexometric titration with EDTA is only adequate for COC with DO lower than 0.6. FT Raman spectroscopy represents characteristic bands of carboxyl and carboxylate groups. It demonstrates the feasibility of establishing novel analyzing methods for DO of COC with high correlation coefficients of up to 0.9867. Moreover, long oxidation duration, high temperature and high amounts of oxidizing agents are important for the synthesis of COC with high DO and yields. [Copyright &y& Elsevier]

Abstract: Aminocyclohexyl indoles bind with high affinity and specificity toward the serotonin transporter (SERT). Based on this structural lead, we designed fluoroalkoxydihydroisoquinoline-cyclohexyl indole carbonitriles for future application as 18F-labeled tracers for SERT imaging by PET. Six compounds, three pairs of cis- and trans-isomer derivatives, respectively, were synthesized and evaluated in vitro. The chemistry of the new compounds, their affinity and specificity data, the general route to the phenolic precursor for labeling, and the successful 18F-fluoroalkylation of one pair of compounds are described herein. [Copyright &y& Elsevier]

The synthesis and characterization of novel cellulose sulfate derivatives was reported. Various cellulose ethers were prepared in a homogeneous reaction with common sulfating agents. The received product possess different properties in dependence on the reaction conditions like sulfating agent, solvent, reaction time and reaction temperature. The cellulose ether sulfates are all soluble in water, they rheological behavior could be determined by viscosity measurements and the determination of the sulfur content by elemental analysis lead to a resulting degree of substitution ascribed to sulfate groups (DS Sul ) of the product. A wide range of products from DS Sul 0.1 to DS Sul 2.7 will be obtained. Furthermore the cellulose sulfate ethers could be characterized by Raman spectroscopy. [ABSTRACT FROM AUTHOR]

Cellulose microspheres (CMS) are a type of spherical regenerated cellulose particles with versatile properties which have been used as carrier materials in medical and technical applications. The integration of CMS into paper products opens up novel application scenarios for paper products in a wide range of fields. However, the incorporation of CMS carriers into paper products is challenging and hitherto no reports do exist in literature. Here, we present a feasibility study to incorporate up to 50 w.% CMS in paper hand sheets using retention aids. Our primary observations highlight the successful formation of uniform paper hand sheets retaining its tensile strengths at elevated CMS concentrations. Sheets with high CMS contents exhibit an increase in density and display enhanced surface smoothness — an outcome of a CMS layer forming atop the fiber base — which effectively bridges voids and rectifies surface irregularities as supported by Gurley testing, infinite focus microscopy and scanning electron microscopy. While our primary objective centered on the general feasibility to manufacture CMS-containing papers, the resulting composite scaffold carries significant potential as a platform for innovative, functional paper-based materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: [ 18 F]NS14490, a new potential radiotracer for neuroimaging of α7 nicotinic acetylcholine receptors (α7 nAChRs), was synthesized and evaluated in vitro and in vivo. Radioligand binding studies using [3H]methyllycaconitine and NS14490 as competitor showed a good target affinity (K i,α7 =2.5nM) and a high selectivity towards other nAChRs. Radiosynthesis of [ 18 F]NS14490 was performed by two different labelling procedures: a two-step synthesis using a prosthetic group, which led to 7% labelling yield, and the convenient direct nucleophilic substitution of the corresponding tosylate precursor, which resulted in 70% labelling yield. After optimisation of the isolation, purification and formulation process, biodistribution studies were performed in CD-1 mice. The brain uptake of [ 18 F]NS14490 was comparably low (0.16% IDg−1 wet weight at 5min p.i.). The radiotracer showed a high metabolic stability in plasma and brain. Also, the target specificity was proven by pre-administration of a highly affine α7 ligand providing a rationale basis for further in vivo evaluation. [Copyright &y& Elsevier]

Abstract: Monostarch monophosphates with different phosphorus contents were prepared via reacting starch with a mixture of primary and secondary sodium phosphates under weak acidic conditions in a semi-dry process. For a structural characterisation of starch phosphates 31P NMR and FT Raman spectra were recorded. The degrees of substitution (DSP) of modified starch were determined using a standard wet chemistry method. By recording the FT Raman spectra of starch phosphates a characteristic band at ∼975cm−1 was found whose intensity depends on the degree of phosphorylation of starch. The integrated areas of this C–O–P stretching vibration were plotted versus the degree of substitution DSP of starch phosphates obtained from standard photometric method. A strong linear correlation was derived which is suitable to determine the level of phosphorylation of starch phosphates with unknown DSP value by Raman spectroscopy as a rapid and non-destructive method. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Gamma amino butyric acid type A (GABAA) receptors are involved in a variety of neurological and psychiatric diseases, which have promoted the development and use of radiotracers for positron emission tomography imaging. Radiolabeled benzodiazepine antagonists such as flumazenil have most extensively been used for this purpose so far. Recently, the non-benzodiazepine pyrazolopyrimidine derivative indiplon with higher specificity for the α1 subtype of the GABAA receptor has been introduced for treatment of insomnia. The aim of this study was the development and biological evaluation of an 18F-labeled derivative of indiplon. Methods: Both [18F]fluoro-indiplon and its labeling precursor were synthesized by two-step procedures starting from indiplon. The radiosynthesis of [18F]fluoro-indiplon was performed using the bromoacetyl precursor followed by multiple-stage purification using semipreparative HPLC and solid phase extraction. Stability, partition coefficients, binding affinities and regional brain binding were determined in vitro. Biodistribution and radiotracer metabolism were studied in vivo. Results: [18F]Fluoro-indiplon was readily accessible in good yields (38–43%), with high purity and high specific radioactivity (>150 GBq/μmol). It displays high in vitro stability and moderate lipophilicity. [18F]Fluoro-indiplon has an affinity to GABAA receptors comparable to indiplon (K i=8.0 nM vs. 3.4 nM). In vitro autoradiography indicates high [18F]fluoro-indiplon binding in regions with high densities of GABAA receptors. However, ex vivo autoradiography and organ distribution studies show no evidence of specific binding of [18F]fluoro-indiplon. Furthermore, the radiotracer is rapidly metabolized with high accumulation of labeled metabolites in the brain. Conclusions: Although [18F]fluoro-indiplon shows good in vitro features, it is not suitable for in vivo imaging studies because of its metabolism. Structural modifications are needed to develop derivatives with higher in vivo stability. [Copyright &y& Elsevier]

[Display omitted] • Binding of lignosulfonate hydrogels to oxidic surfaces. • Shrinking and swelling process of the hydrogel dependence of the ion and ionic strength. • Repeatable response over several cycles. The manufacturing of sensors based on sustainable and renewable materials is becoming increasingly important to achieve independence from fossil raw materials. It is known that hydrogels based on lignin, the polyphenolic biopolymer in lignocellulosic biomass, are able to react to environmental influences such as pH value, temperature or ion concentration. This effect can be used for sensor applications. For this purpose, ligninsulfonate hydrogel was simultaneously generated and bound to glass surfaces via a two-step synthesis. First, the etched oxide substrates were silanized using (3-acryloxypropyl)methyldimethoxysilane (APMDMS). Thereafter, the hydrogel was bound to the surface via a radical polymerization process. Here, the lignosulfonate solution, which included the crosslinker polyethyleneglycoldiacrylate (PEGDA) and ascorbic acid, was applied directly to the functionalized surface. The functionalized surface was analyzed using XPS, AFM, SEM, ATR-IR, profilometer, contact angle, and QCM. The layer thickness was found to vary between 1.8–8.6 µm as a function of the amount of precursor lignin solution applied. The porous structure exhibited pore sizes of 4–6 µm. For the sensor tests, solutions of sodium(I) and magnesium(II) salts at different concentrations were used. The hydrogels reacted with shrinking and swelling processes, depending on the selected cation and its concentration. This effect was reproducible over several cycles and the initial state could be reestablished at the end of the tests. [ABSTRACT FROM AUTHOR]

In this issue, different chemical (alkaline and sulfite pulping, ozonolysis) and mechanical (vibratory ball milling) pre-treatments were utilized for activating wheat straw and beech sawdust prior to carboxymethylation. Detailed analysis by a range of methods, including Klason-lignin, cellulose and hemicellulose quantification, Powder-X-ray diffraction (PXRD) and attenuated total reflection (ATR) IR spectroscopy, enabled the investigation of material alterations. Subsequently, carboxymethylation was carried out with both untreated and activated materials, allowing the evaluation of activation steps by determining degrees of substitution with carboxymethyl groups ( DS CM ). Moreover, carboxymethylation conditions were optimized, realizing high DS CM of up to 1.05. Results further revealed that ball milling enhanced the subsequent conversion; whereas chemical pre-treatments did not effectively increase material accessibilities. Further studies on chemically untreated materials emphasized that a highly reactive surface was already generated in the course of the carboxymethylation, inter alia through the concomitant dissolution of matrix components. [ABSTRACT FROM AUTHOR]

Intrinsic cross-linking is not only useful for increasing stability, but also for tailoring mechanical properties of polyelectrolyte multilayers (PEM) on implants and tissue engineering scaffolds. Here, a novel route for synthesizing thiolated chitosan (t-Chi) based on the application of 3,3′-dithiodipropionic acid was applied, while thiolated chondroitin sulfate (t-CS) was conjugated by 3,3′-dithiobis (propanoic hydrazide). Both products were subsequently reduced to obtain the free thiols. The thiol content, structural changes and degree of substitution were studied by UV–vis, FTIR, Raman and 1 H NMR spectroscopy, respectively. Chi and CS can be used for PEM formation with the layer-by-layer method, due to the cationic nature of Chi at pH values below 5.0 and the anionic character of CS. Comparative studies on the formation of native Chi/CS versus t-Chi/t-CS PEM with surface plasmon resonance and ellipsometry revealed higher layer mass. We also found that the PEM composed of t-Chi/t-CS had superior cell adhesion properties for human keratinocytes in comparison to the native PEM. [ABSTRACT FROM AUTHOR]

Radiopharmacological investigations of [ 18 F]NS14490 have proven that this radiotracer could be a potential PET radiotracer for imaging of alpha7 nicotinic acetylcholine receptor particularly with regard to vulnerable plaques of diseased vessels. For further optimisation of the previously automated one-pot radiosynthesis of [ 18 F]NS14490 using a tosylate precursor, precursors with other leaving groups (nosylate and mosylate) were synthesized and compared with the tosylate with respect to their reactivities towards [ 18 F]fluoride. The use of these different precursors resulted in comparable labelling yields of [ 18 F]NS14490. A novel mosylate precursor was synthesized and evaluated, which has revealed a higher stability during a storage period of five months compared to the corresponding tosylate and nosylate. [ABSTRACT FROM AUTHOR]

The limited availability and the increasing demands of [ 18 O]H 2 O force the reuse of bombarded [ 18 O]H 2 O for the production of [ 18 F]F − at least for the purposes of research. Therefore, inorganic and organic contaminants have to be removed from the [ 18 O]H 2 O after bombardment. We present a simple, effective, easy-handling and reliable method of [ 18 O]H 2 O purification including oxidation and distillation. The obtained recycled [ 18 O]H 2 O had comparable quality to commercially distributed [ 18 O]water. This was confirmed by a detailed comparison of produced radionuclides and their activities and the application of [ 18 F]F − for the automated synthesis of [ 18 F]fluspidine. [ABSTRACT FROM AUTHOR]

[ 18 F]NS10743, a promising and highly competitive α7 nAChR radioligand has been synthesized so far by microwave irradiation using a manual single-mode device followed by a palladium-catalyzed reduction of remaining nitro-precursor for HPLC separation purposes. For further preclinical and clinical use, regulated production of [ 18 F]NS10743 by fully automated radiosynthesis is a crucial requirement. Therefore, we chose a commercial synthesis module and developed the automated radiosynthesis of [ 18 F]NS10743. Besides evaluation of several radiosynthesis procedures, we performed an extensive HPLC study for quantitative separation of [ 18 F]NS10743 from the corresponding nitro precursor. After implementation of the optimized procedure on a TRACERlab TM FX F-N synthesis module, [ 18 F]NS10743 was obtained in high radiochemical purity (≥99%) with an overall radiochemical yield of 32.2±7% ( n =3). The specific activities at the end of the synthesis were 571±17 GBq/µmol ( n =3). [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) with varying degree of sulfation were chemically modified to obtain thiolated analogues (tGAGs) for subsequent surface grafting on vinyl-terminated self-assembled monolayers. Thiolation was achieved by the use of the disulfide containing crosslinker 3,3‘-dithiobis(propanoic hydrazide) and subsequent reduction of the disulfide with dithiothreitol. Two different molar ratios of the crosslinker were used for conjugation. The tGAGs were characterized by 1 H-NMR, Raman and flow-field-flow-fractionation (A4F) to determine the chemical composition, structure and molecular weight of the products. Ellman‘s reagent was used to quantify the thiol concentration of tGAGs. The tGAGs were immobilized onto vinyl-terminated glass and silicon via thiol-ene reaction. This was achieved by homogeneous immobilization from solution as well as with microcontact printing and exposure to UV light. The results of water contact angle measurement (WCA), ellipsometry and confocal laser scanning microscopy (CLSM) demonstrated that the resulting surface coverage was dependent on the degree of thiolation of GAGs. [ABSTRACT FROM AUTHOR]

Wheat straw was subjected to three different processes prior to saccharification, namely alkaline pulping, natural pulping and autohydrolysis, in order to study their effect on the rate of enzymatic hydrolysis. Parameters like medium concentration, temperature and time have been varied in order to optimize each method. Milling the raw material to a length of 4 mm beforehand showed the best cost–value-ratio compared to other grinding methods studied. Before saccharification the pulp can be stored in dried form, leading to a high yield of glucose. Furthermore the relation of pulp properties (i.e. intrinsic viscosity, K lason -lignin and hemicelluloses content, crystallinity, morphology) to cellulose hydrolysis is discussed. [ABSTRACT FROM AUTHOR]

Introduction: (−)-[18 F]Flubatine is a PET tracer with high affinity and selectivity for the nicotinic acetylcholine α4β2 receptor subtype. A clinical trial assessing the availability of this subtype of nAChRs was performed. From a total participant number of 21 Alzheimer’s disease (AD) patients and 20 healthy controls (HCs), the following parameters were determined: plasma protein binding, metabolism and activity distribution between plasma and whole blood. Methods: Plasma protein binding and fraction of unchanged parent compound were assessed by ultracentrifugation and HPLC, respectively. The distribution of radioactivity (parent compound+metabolites) between plasma and whole blood was determined ex vivo at different time-points after injection by gamma counting after separation of whole blood by centrifugation into the cellular and non-cellular components. In additional experiments in vitro, tracer distribution between these blood components was assessed for up to 90min. Results: A fraction of 15%±2% of (−)-[18 F]Flubatine was found to be bound to plasma proteins. Metabolic degradation of (−)-[18 F]Flubatine was very low, resulting in almost 90% unchanged parent compound at 90min p.i. with no significant difference between AD and HC. The radioactivity distribution between plasma and whole blood changed in vivo only slightly over time from 0.82±0.03 at 3min p.i. to 0.87±0.03 at 270min p.i. indicating the contribution of only a small amount of metabolites. In vitro studies revealed that (−)-[18 F]Flubatine was instantaneously distributed between cellular and non-cellular blood parts. Discussion: (−)-[18 F]Flubatine exhibits very favourable characteristics for a PET radiotracer such as slow metabolic degradation and moderate plasma protein binding. Equilibrium of radioactivity distribution between plasma and whole blood is reached instantaneously and remains almost constant over time allowing both convenient sample handling and facilitated fractional blood volume contribution assessment. [ABSTRACT FROM AUTHOR]

The radiosynthesis of [18F]Fluspidine, a potent σ1 receptor imaging probe for pre-clinical/clinical studies, was implemented on a TRACERlabTM FX F-N synthesizer. [18F]2 was synthesized in 15min at 85°C starting from its tosylate precursor. Purification via semi-preparative RP-HPLC was investigated using different columns and eluent compositions and was most successful on a polar RP phase with acetonitrile/water buffered with NH4OAc. After solid phase extraction, [18F]Fluspidine was formulated and produced within 59±4min with an overall radiochemical yield of 37±8%, a radiochemical purity of 99.3±0.5% and high specific activity (176.6±52.0GBq/µmol). [ABSTRACT FROM AUTHOR]

Abstract: A fully automatized radiosynthesis of (+)- and (−)-[18F]Flubatine ((+)- and (−)NCFHEB) by means of a commercially available synthesis module (TRACERlab FX FN) under GMP conditions is reported. Radiochemical yields of 30% within an overall synthesis time of 40min were achieved in more than 70 individual syntheses. Specific activities were approximately 3000GBq/μmol and radiochemical purity was determined to be at least 97%. [Copyright &y& Elsevier]

Abstract: The spirocyclic σ1 receptor ligand 1 (1′-benzyl-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4′-piperidine]) was prepared in four steps starting from methoxy derivative 5. Due to its high σ1 affinity (K i =0.74nM) and selectivity against several other relevant targets, 1 was investigated as 18F-labeled PET tracer and its biological properties were compared with those of homologous fluoroalkyl derivatives 2–4. The fluoromethyl derivative 1 was faster metabolized in vitro than homologs 2–4. In contrast to the radiosynthesis of [18F]2–4, the nucleophilic substitution of the tosylate 15 using the K[18F]F–K222–carbonate complex required heating to 150°C in DMSO to achieve high labeling efficiencies. Whereas radiometabolites of [18F]2–4 were not detected in vivo in the brain of mice, two radiometabolites of [18F]1 were found. Analysis of ex vivo autoradiography images provided rather low target-to-nontarget ratio for [18F]1 compared with [18F]2–4. [18F]1 showed a fast uptake in the brain, which decreased continuously over time. The brain-to-plasma ratio of the radiotracer [18F]1 was only exceeded by the fluoroethyl tracer [18F]2. [Copyright &y& Elsevier]

Abstract: The synthesis and characterisation of cellulose sulfates were reported. Various cellulose sulfates with diverse degrees of substitution ascribed to sulfate groups (DSS) between 0.21 and 2.59 were prepared through acetosulfation or direct sulfation of two celluloses. The number-average degrees of polymerisation (DP n ) of these cellulose sulfates were determined to be in the range of 59 and 232 via size exclusion chromatography (SEC). Accordingly, the molecular weight of cellulose was remarkably decreased during the sulfation. The use of high amount of sulfating agent and high sulfation temperature led to stronger reduction of the DP n in comparison to low amount of sulfating agent and low temperature. The morphology of cellulose sulfate was analysed via scanning electron microscopy (SEM) and wide-angle X-ray diffraction (WAXD). Obtained cellulose sulfates demonstrated different surface properties from cellulose and became more amorphous than starting celluloses. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and characterization of sulfoethyl cellulose (SEC) exhibiting low degrees of substitution ascribed to sulfoethyl groups (DSSE) were reported. The effects of reaction temperature, duration, reaction mediums as well as sulfoethylating agents on DSSE were investigated. The total DSSE was determined via elemental analysis and the structure of SEC was elucidated by FT Raman, one- (1D-) and two-dimensional (2D-) NMR spectroscopy. Based on the characterization, SEC with diverse total DSSE up to 0.65 were obtained and the primary hydroxyl groups were found to be preferably substituted. Finally, the feasibility of using FT Raman spectroscopy with the band at 1044, 811 or 747cm−1 as marker band to determine total DSSE of SEC was presented. [ABSTRACT FROM AUTHOR]

Abstract: Synthesis and spectroscopic characterisation of cellulose sulfate (CS) were reported. Various CS exhibiting diverse degrees of sulfation (DSS) were prepared through acetosulfation or direct sulfation of cellulose. During the acetosulfation, intermediate product – cellulose acetate sulfate (CAS) – was formed after the comparative esterification and subsequent deacetylation of CAS led to CS. The direct sulfation proceeded quasi-homogeneously and heterogeneously in N,N-dimethylformamide (DMF) or homogeneously in N,N-dimethylacetamide (DMAc)/LiCl mixture. The total DSS between 0.21–2.59 and partial DSS6 as well as DSS2 of up to 1 were determined via elemental analysis and 13C NMR spectroscopy. Besides, solid-state CP/MAS 13C NMR could characterise CS regarding the sulfation. Subsequently, FT Raman investigation of obtained CS was conducted with the aim to establish analysis methods quantifying the total DSS. The intensities of Raman bands ascribed to the vibrations of Oh name="dbnd" />O and C–O–S groups were used as analysis parameters, yielding calibration curves with high correlation coefficients of more than 0.96. [ABSTRACT FROM AUTHOR]

Abstract: Chitosan sulfates (CHS) exhibiting various total degrees of substitution ascribed to sulfate groups (DSS) were synthesized. The sulfation could be under homogeneous or non-homogeneous conditions. The obtained CHS were characterized and total DSS of up to 1.73 were determined. Using chlorosulfonic acid as sulfating agent, CS with total DSS between 0.86 and 1.67 were obtained and the total DSS can be regulated by varying the sulfation parameters. Using other sulfating agents, CS with distinct total DSS of up to 1.73 were prepared. By means of FT Raman spectroscopy, marker bands at 1070cm−1 or 1014cm−1 attributed to vibrations of sulfation groups can be applied for quantifying the total DSS of CHS. Calibration curves with correlation coefficients of more than 0.95 were established, suggesting the feasibility of Raman spectroscopy for quantifying the total DSS of CHS. Finally, the capacity of CHS to improve the osteogenic activity of bone morphogenetic protein-2 (BMP-2) was presented. [ABSTRACT FROM AUTHOR]

Abstract: Chitosan sulfates (CHS) were prepared with chlorosulfonic acid homogeneously and non-homogeneously. The total degrees of substitution (DS) ascribed to sulfate groups (DSS) were determined with elemental analysis and the partial DS at 6-O-position was estimated via 13C NMR. CHS with diverse total DSS and sulfation patterns were obtained according to the analysis. The effects of selected reaction parameters that can influence the distribution of sulfate groups were examined. The structure of CHS was then characterized with various NMR techniques, i.e. one- (1D-) and two-dimensional (2D-) NMR, and FT Raman spectroscopy. It was found that the primary hydroxyl groups were always predominantly sulfated for CHS prepared under homogeneous or non-homogeneous conditions and no sulfate groups at 2-N-position could be detected. Finally, the feasibility of using FT Raman spectroscopy as another alternative for determining the total DSS of CHS was presented. [ABSTRACT FROM AUTHOR]

Abstract: Both sulfate and carboxyl groups are found in many glycosaminoglycans exhibiting diverse biological activities, such as heparin. Present study reports on the preparation of cellulose derivatives containing both sulfate and carboxyl groups that were regioselectively introduced into anhydroglucose units (AGU) of cellulose. The products – carboxyl cellulose sulfates (COCS) – with various contents of both functional groups were obtained by two synthesis routes. One way started with sulfation of cellulose yielding cellulose sulfate (CS) and was followed by TEMPO-mediated oxidation of CS. In another way, cellulose at first underwent TEMPO-mediated oxidation yielding carboxyl cellulose (COC). Subsequently, acetosulfation of the COC was carried out. The products were characterized by diverse analysis methods, and the amounts of both functional groups in CS, COC and COCS were determined. Finally, the biological activity of COCS was examined. [Copyright &y& Elsevier]

Abstract: Several 3H-spiro[[2]benzofuran-1,4′-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF3·OEt2 catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure–affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar σ1 affinity (K i =0.18nM, 0.79nM, 0.86nM) and high selectivity against the σ2 subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [18F]2a and [18F]2e two different radiosynthetic approaches were followed. [Copyright &y& Elsevier]

Abstract: Phenylpiperidinyl-octahydro-benzo[1,4]oxazines represent a new class of conformationally restrained vesamicol analogues. Derived from this morpholine-fused vesamicol structure, a new fluorine-18-labeled 4-fluorobenzoyl derivative ([18F]FBMV) was synthesized with an average specific activity of 75 GBq/μmol and a radiochemical purity of 99%. The radiolabeling method included an exchange reaction of a 4-nitro group of the precursor by fluorine-18, a reduction procedure to eliminate excess of the nitro compound, followed by a high-performance liquid chromatography purification. [18F]FBMV demonstrates (i) a moderate lipophilic character with a logDpH7.0 1.8±0.10; (ii) a considerable binding affinity to the vesicular acetylcholine transporter (VAChT) (K i=27.5 nM), as determined using PC12 cells transfected with a VAChT cDNA, and a low affinity to σ1,2 receptors (K i >3000 nM); (iii) a good uptake into the rat and pig brains; (iv) a typical accumulation in the VAChT-containing brain regions; and (v) an approximately 20% reduction in cortical tracer binding after a specific cholinergic lesion using 192IgG-saporin. [18F]FBMV exhibits another PET marker within the group of vesamicol derivatives that demonstrates potentials in imaging brain cholinergic deficits, while its usefulness in clinical practice must await further investigation. [Copyright &y& Elsevier]

Abstract: With the aim of producing selective radiotracers for in vivo imaging of the vesicular acetylcholine transporter (VAChT) using positron mission tomography (PET), here, we report synthesis and analysis of a new class of conformationally constrained vesamicol analogues with moderate lipophilicity. The sequential ring opening on trans-1,4-cyclohexadiene dioxide enabled an approach to synthesize 6-arylpiperidino-octahydrobenzo[1,4]oxazine-7-ols [morpholino vesamicols]. The radiosynthesis of the [18F]fluoroacetyl-substituted derivative ([18F]FAMV) was achieved starting from a corresponding bromo precursor [2-Bromo-1-[7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazin-4-yl]-ethanone] and using a modified commercial computer-controlled module system with a radiochemical yield of 27±4%, a high radiochemical purity (99%) and a specific activity of 35 GBq/μmol. In competitive binding assays using a PC12 cell line overexpressing VAChT and [3H]-(−) vesamicol, 2-fluoro-1-[7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazin-4-yl]-ethanone (FAMV) demonstrated a high selectivity for binding to VAChT (K i: 39.9±5.9 nM) when compared to its binding to sigma1/2 receptors (K i>1500 nM). The compound showed a moderate lipophilicity (logD(pH 7)=1.9) and a plasma protein binding of 49%. The brain uptake of [18F]FAMV was about 0.1% injected dose per gram at 5 min after injection and decreased continuously with time. Notably, an increasing accumulation of radioactivity in the lateral brain ventricles was observed. After 1 h, the accumulation of [18F]FAMV, expressed as ratio to the cerebellum, was 4.5 for the striatum, 2.0 for the cortical and 1.5 for the hippocampal regions, measured on brain slices using ex vivo autoradiography. At the present time, 75% of [18F]FAMV in the plasma was shown to be metabolized to various hydrophilic compounds, as detected by high-performance liquid chromatography. The degradation of [18F]FAMV was also detected in brain extracts as early as 15 min post injection (p.i.) and increased to 50% at 1 h postinjection. In conclusion, although the chemical properties of [18F]FAMV and the selectivity of binding to VAChT appear to be promising indicators of a useful PET tracer for imaging VAChT, a low brain extraction, in combination with only moderate specific accumulation in cholinergic brain regions and an insufficient in vivo stability prevents the application of this compound for neuroimaging in humans. [Copyright &y& Elsevier]

Abstract: Neuroimaging of GABAA receptors offers the potential for a better diagnosis of diseases related to a dysfunction of the GABAergic neurotransmission. A series of potent fluorinated analogues of the pyrazolopyrimidine Indiplon has been synthesized and evaluated in vitro as potential agents for imaging the GABAA receptor by means of positron emission tomography (PET). The most promising compound N-(3-fluoropropyl)-N-[3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl]-acetamide (5b) showed an IC50 value of 2.78±0.63nM comparable to the lead compound Indiplon (IC50 3.29±0.37nM), thus making it an interesting candidate for further investigations. In addition to the fluorinated reference compounds, suitable precursors for 18F-radiolabelling studies have been synthesized. [Copyright &y& Elsevier]

Abstract: The function of γ-aminobutyric acid type A receptors (GABAA receptors) is enhanced by various clinically important drugs including benzodiazepines that act on an allosteric site formed at the interface between the α and γ subunits. In contrast to classical benzodiazepines, the novel pyrazolopyrimidine indiplon (N-methyl-N-{3-[7-(thiophene-2-carbonyl)-1,5,9-triazabicyclo[4.3.0]nona-2,4,6,8-tetraen-2-yl]phenyl}acetamide; N-methyl-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide) demonstrates relative binding selectivity for the α1 subunit containing receptor subtypes, which are the most frequently expressed in the mammalian central nervous system. To investigate the pharmacological properties at GABAA receptors and to promote the development of α1 subunit selective radiotracers for positron emission tomography imaging, we have started with the evaluation of various fluorinated indiplon derivatives. Binding affinities were determined in homogenates from newborn and adult rats suggesting an α1 preference of the reference compounds indiplon, zaleplon as well as for all newly synthesized indiplon derivatives. In homogenated cerebellar tissue obtained from adult rat brain, known to primarily express α1 containing GABAA receptors, the high affinity of the basic indiplon structure was only slightly affected by an elongation of the alkyl substituent of the amide N from methyl (indiplon; K i 3.1 nM) via ethyl (2a, N-(2-fluoro-ethyl)-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide; K i 5.4 nM) to propyl (2b, N-(3-fluoro-propyl)-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide; K i 2.4 nM). Whole cell patch-clamp recordings at neuronal and recombinant GABAA receptors indicated that the fluorinated derivatives 2a and 2b have a high potency at α1β3γ2L isoforms comparable to indiplon (EC50: 105, 158, and 81 nM, respectively), with 2b displaying the most pronounced efficacy at α3β3γ2L subtypes. In conclusion, the affinity profiles and functional properties of the newly synthesised fluorinated indiplon derivatives make compounds 2a and 2b suitable for the development of [18F]-labelled ligands at GABAA receptors containing the α1 subunit. [Copyright &y& Elsevier]

Abstract: A series of fluorinated diphenylchalcogen derivatives, possessing a sulfur or an oxygen bridge, has been prepared with the aim to get a suitable radiotracer to image the SERT in vivo using positron emission tomography (PET). The compounds were synthesized and assayed toward the serotonin (SERT), dopamine (DAT), and norepinephrine (NET) transporters. Among the developed series, five compounds display a high SERT affinity (K i: 0.27–2.91nM range) and can be labeled either with carbon-11 or fluorine-18. [Copyright &y& Elsevier]

• Oxalic acid treatment improves surface roughness better compared to NaOH. • Agro-waste soy stem fiber is used as reinforcement. • Silane treatment improved the mechanical performance. • Chemical treatment influences the dimensional stability of composites. Present days, the world needs more sustainable and eco-friendly materials to replace and reduce the use of synthetic materials to prevent pollution. In this regard, the agro-waste after soy cultivation is identified as a sustainable resource of raw material and can be used as reinforcement in polymer matrices. The current research focuses on the effect of surface modification in agro-waste soy stem fibers and their composites. The fibers were collected, cleaned, processed, and subjected to chemical treatment. The chemical analysis showed an increased ratio of cellulose % in the soy fibers when compared to untreated fibers. The silane treatment showed improvement in the thermal stability of soy fibers and reduced the coefficient of thermal expansion in silane treated composite. The X-ray diffraction test shows that there was a 22.57% increase in the crystalline index due to oxalic acid treatment. The chemical treatments also influenced the crystal size of the soy fibers which had direct impact on the water absorption nature of the developed composites. The mechanical performance of the composites is evaluated through tensile, flexural, impact, and interlaminar shear strength according to the ASTM. The silane treated fibers in the composites showed a better mechanical performance compared to untreated and other chemical treatment. However, oxalic acid treatment showed better mechanical performance when compared to traditional NaOH treatment. The increase in wettability nature influenced the mechanical strength and water-resistant nature of the composite. The complete results state that the silane treatment on the soy stem fiber showed the best performance followed by the oxalic acid and alkali treatment when compared to the raw fibers. From the results, it is observed that the Agro-waste soy fiber is a sustainable and renewable resource of raw material that can be used as reinforcements in polymer matrices for lightweight structural applications. [ABSTRACT FROM AUTHOR]

The production of 85 Sr by irradiation of a Rb-target at a cyclotron was investigated. The purification of the radionuclide was performed by a Sr-selective resin. 85 Sr was separated in no-carrier-added aqueous solution with a recovery of 98% and a concentration up to 6.6 MBq in 200 µl. [ABSTRACT FROM AUTHOR]