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Levulinic acid, which can be obtained from biomass, has sparked great interest as a biologically-based chemical building block with wide versatility and potential. Its esterification with alcohols of different chain lengths is a promising valorization process for obtaining esters with various applications in the areas of biofuels/biolubricants, food and cosmetics, among others. In this work, the enzymatic esterification of levulinic acid and 1-octanol using a biocatalyst derived from Araujia sericifera latex was studied in systems with and without solvent. The influence of the molar ratio between alcohol and acid (ranging from 2:1-1:9), the biocatalyst loading (between 7.5 % and 17.5 % relative to the acid), the volume of n-heptane used as reaction solvent (from 0 to 4 ml), and the reaction time (6 hours) were investigated. The activity and stability of the biocatalyst in successive uses were also analyzed. A conversion of 49 % was achieved when the reaction was carried out in a solvent-free system, using an alcohol/acid molar ratio of 1:7 and after 5 h of reaction. On the other hand, the conversion was 65.1 % when the reaction was conducted in a system containing 1 ml of n-heptane as solvent, an alcohol/acid molar ratio of 1:8, and 5 h of reaction. In both cases, a temperature as low as 30 °C and an agitation speed of 300 RPM were used., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel Sanchez reports financial support was provided by National Agency for the Promotion of Research Technological Development and Innovation. Gabriela Tonetto reports financial support was provided by National Scientific and Consejo Nacional de Investigaciones Científicas y Técnicas. Gabriela Tonetto reports financial support was provided by National University of the South Department of Chemical Engineering. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Soret effect is a significant factor in various scenarios, with thermodiffusion in binary systems serving as a common method for the study. Most research focuses rarely on the distribution characteristics of components in diffusion systems; and Soret coefficients in the porous media could not be obtained by typical methods based on the thermodiffusion column, which are particularly important in the field of oil and gas development. Moreover, experiments on ground conditions have struggled to determine the Soret coefficient accurately due to the convective effect caused by gravity differentiation. The thermodiffusion behavior of n-pentane (C5) and n-heptane (C7) binary mixtures in both bulk and porous media conditions have been investigated, aiming to provide corrected coefficients that mitigate the influence of gravity using theoretical derivation. A new method was proposed to calculate the Soret coefficients in this work by establishing a model based on gas chromatography technology. Dynamic variation of component concentration along the path was studied, and the corresponding Soret coefficients were calculated and analyzed in parallel. The results indicate that the concentration and temperature exhibit a logarithmic relationship with the distance from the heat source. The Soret coefficient values obtained from measurements in porous media are closer to the theoretically corrected values, which do not account for gravity effects. Additionally, as the permeability decreases, the counteracting effect of porous media on convection becomes more pronounced. Therefore, it presents a novel method for accurately measuring the Soret coefficient that ignores convection to some extent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The separation and purification of plant-based Active Pharmaceutical Ingredients (API) from extracts is a crucial part in pharmaceutical process development. For the purification of the antimalarial drug component artemisinin (ARTE) from an Artemisia anna L. toluene extract, antisolvent crystallization is considered. Solubilities of ARTE in binary solvent mixtures of toluene and two potential antisolvents, n-heptane and ethanol, were determined at temperatures from 278.15 K to 313.15 K. The experimental work was supported by the application of various models, utilizing varying amounts of experimental input data. The goal was the identification of models that are able to predict solubilities in binary solvent mixtures sufficiently accurate and, thus, can help to reduce the experimental effort for future solvent screenings. In this study, we applied the PC-SAFT model both with and without fitting the binary interaction parameter k ij between ARTE and the respective solvent, as well as the empirical Jouyban-Acree model. From the experiments, n-heptane demonstrated to be a promising antisolvent, while ethanol acted more as a cosolvent. All models tested were capable of distinguishing between effective and ineffective antisolvents. The purely predictive PC-SAFT model applied with k ij = 0 exhibited the largest deviation from the experimental data. This was followed by the PC-SAFT model including fitted k ij values, based on at least four experimental data points. The Jouyban-Acree model fitted the data most accurately. Its parametrization required a minimum of ten experimental data points., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index. The E descriptor for compounds solid at 20 °C and the S, A, and B descriptors are experimental properties traditionally assigned from chromatographic, liquid-liquid partition, and solubility measurements. In this report liquid-liquid partition constants in totally organic and aqueous biphasic systems are evaluated as a standalone technique for descriptor assignments. Using six totally organic biphasic systems the S, A, and B descriptors were assigned with an average absolute deviation (AAD) of about 0.04, 0.03, and 0.04, respectively, compared with the best estimate of the true descriptor values for 65 compounds. The E descriptor for compounds solid at 20 °C can only be estimated with an AAD of approximately 0.1. For six aqueous biphasic systems the B descriptor is assigned with a lower AAD of 0.028 and higher AAD of 0.08 and 0.05 for the S and A descriptors, respectively, than for the totally organic biphasic systems for compounds with a reliable value for the E descriptor. The preferred system for descriptor assignments utilizes both totally organic biphasic systems (heptane-1,1,1-trifluoroethanol, isopentyl ether-propylene carbonate, isopentyl ether-ethanolamine, heptane-ethylene glycol, heptane-formamide, and 1,2-dichloroethane-ethylene glycol) and aqueous biphasic systems (octanol-water, cyclohexane-water) with the possible substitution of some systems with alternative systems of similar selectivity. For 55 varied compounds this combination of eight organic and aqueous biphasic systems resulted in an AAD of approximately 0.03, 0.02, and 0.02 for the S, A, and B descriptors compared to the best estimate of the true descriptor value. For 30 compounds solid at 20 °C the AAD for the E descriptor of 0.11 is poorly assigned. The relative average absolute deviation in percent (RAAD) corresponds to 9.7 %, 3.1 %. 4.0 % and 8.3 % for E, S, A, and B, respectively, for the eight biphasic systems. Liquid-liquid partition is compared to reversed-phase liquid and gas chromatography as a standalone technique for descriptor assignments., Competing Interests: Declaration of competing interest The author declares that he has no conflicts of interest in connection with this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of synthetic strategies for the preparation of bioisosteric compounds is a demanding undertaking in medicinal chemistry. Numerous strategies have been developed for the synthesis of bicyclo[1.1.1]pentanes (BCPs), bridge-substituted BCPs, and bicyclo[2.1.1]hexanes. However, progress on the synthesis of bicyclo[3.1.1]heptanes, which serve as meta-substituted arene bioisosteres, has not been previously explored. Herein, we disclose the first photoinduced [3σ + 2σ] cycloaddition for the synthesis of trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes and cyclopropylamines. This transformation not only uses mild and operationally simple conditions but also provides unique meta-substituted arene bioisosteres. The applicability of this method is showcased by simple derivatization reactions.

Small-ring cage hydrocarbons are popular bioisosteres (molecular replacements) for commonly found para-substituted benzene rings in drug design 1 . The utility of these cage structures derives from their superior pharmacokinetic properties compared with their parent aromatics, including improved solubility and reduced susceptibility to metabolism 2,3 . A prime example is the bicyclo[1.1.1]pentane motif, which is mainly synthesized by ring-opening of the interbridgehead bond of the strained hydrocarbon [1.1.1]propellane with radicals or anions 4 . By contrast, scaffolds mimicking meta-substituted arenes are lacking because of the challenge of synthesizing saturated isosteres that accurately reproduce substituent vectors 5 . Here we show that bicyclo[3.1.1]heptanes (BCHeps), which are hydrocarbons for which the bridgehead substituents map precisely onto the geometry of meta-substituted benzenes, can be conveniently accessed from [3.1.1]propellane. We found that [3.1.1]propellane can be synthesized on a multigram scale, and readily undergoes a range of radical-based transformations to generate medicinally relevant carbon- and heteroatom-substituted BCHeps, including pharmaceutical analogues. Comparison of the absorption, distribution, metabolism and excretion (ADME) properties of these analogues reveals enhanced metabolic stability relative to their parent arene-containing drugs, validating the potential of this meta-arene analogue as an sp 3 -rich motif in drug design. Collectively, our results show that BCHeps can be prepared on useful scales using a variety of methods, offering a new surrogate for meta-substituted benzene rings for implementation in drug discovery programmes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We communicate a versatile synthetic approach to C-3 disubstituted 2-oxa-5-azabicyclo[2.2.1]heptanes as carbon-atom bridged morpholines, starting with 4 R -hydroxy-l-proline as a chiron. Attaching an acetic acid moiety on the C-3 carbon of the 2-oxa-5-azabicyclo[2.2.1]heptane core reveals the framework of an embedded γ-amino butyric acid (GABA). Variations in the nature of the substituent on the tertiary C-3 atom with different alkyls or aryls led to backbone-constrained analogues of the U.S. Food and Drug Administration-approved drugs baclofen and pregabalin.

Experimental studies on the reactive extraction of fumaric acid with Amberlite LA-2 from Rhizopus oryzae suspensions using three solvents with different dielectric constants varying from 9.08 to 1.90 (dichloromethane, n-butyl acetate, and n-heptane, respectively) underlined the particular behavior of the extraction system in the presence of fungal biomass. The interfacial mass flow of the reaction product was found to be significantly affected by the biomass, due mainly to its adsorption onto the phase separation interface, this leading to the appearance of a physical barrier against the solute's transfer. However, the magnitude of the adsorption phenomenon was found to depend on Rhizopus oryzae 's affinity for the solvent phase, which increased significantly from dichloromethane to n-heptane. The negative influence of the biomass on the interfacial mass transfer can be partially counteracted by adding 1-octanol into the organic phase, improving the solvent's ability to solve the fumaric acid-Amberlite LA-2 complex and simplifying the reactive extraction mechanism, effects that were found to be more important for low-polar solvents. Consequently, for the same mixing intensity, the maximum amplification factor was reached for n-heptane, its value being almost 5-6 times higher than that obtained for dichloromethane and over 2 times higher than that obtained with n-butyl acetate.

The safety of food contact plastic materials, including PP, PE, PET, PCT, PLA, PBT and cross-linked polyester, was assessed with regard to migrated substances. The migrated concentrations of overall migrants (OMs), terephthalic acid, acetaldehyde, 1,4-butanediol and lead, were determined according to the standards and specifications for utensils, containers and packages in Korea. Food simulants of 4% acetic acid, water and n-heptane were used for the analysis of the substances. The dietary exposures of terephthalic acid, acetaldehyde and 1,4-butanediol were assessed using the dietary concentrations and the food consumption data. As a result, the dietary exposures were considered to be safe comparing to the health-based guidance values. In the case of lead, the margin of exposure (MOE) approach was applied. The MOEs calculated using the UB concentration and mean consumption data were ranged from 3 to 1000, which indicated low concern for health risk. Moreover, in this study, the dietary exposures were estimated by the Korean MFDS and U.S. FDA methods, respectively. As a result, the assessed risks were considered to be low in both cases. Based on the results of current exposure assessments, it could be considered that the food contact plastic materials are properly controlled by the regulatory authorities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the last decade, the nature of the nonpolar solvents that can be part of reverse micelles (RMs) has been the topic of several investigations to improve their applications. In this sense, the hydrolysis of 1-naphthyl phosphate catalyzed by the enzyme alkaline phosphatase (AP) was used as a probe to investigate the effect of the change of the external solvent on RMs formulated with the anionic surfactant sodium diethylhexyl sulfosuccinate (AOT). As external nonpolar solvents, two biocompatible lipophilic esters, isopropyl myristate and methyl laurate, and the traditional nonpolar solvents, n-heptane and benzene, were used. The results were compared among the RMs investigated and with the reaction in homogeneous media. Thus, the effect of the nanoconfinement as well as the impact of the replacement of a conventional external nonpolar solvent by biocompatible solvents were analyzed. The results indicate that the catalytic efficiency in the AOT RMs is larger than that in homogeneous media, denoting a different hydration level over the AP enzyme, which is directly related to the different degrees of nonpolar solvent penetration to the RM interface. Our findings demonstrated that toxic solvents such as n-heptane and benzene can be replaced by nontoxic ones (isopropyl myristate or methyl laurate) in AOT RMs without affecting the performance of micellar systems as nanoreactors, making them a green and promising alternative toward efficient and sustainable chemistry.

Nitrogen-containing flame retardants have been extensively applied due to their low toxicity and smoke-suppression properties; however, their poor charring ability restricts their applications. Herein, a representative nitrogen-containing flame retardant, polyheptanazine, was investigated. Two novel, cost-effective phosphorus-doped polyheptazine (PCN) and cobalt-anchored PCN (Co@PCN) flame retardants were synthesized via a thermal condensation method. The X-ray photoelectron spectroscopy (XPS) results indicated effective doping of P into triazine. Then, flame-retardant particles were introduced into thermoplastic polyurethane (TPU) using a melt-blending approach. The introduction of 3 wt% PCN and Co@PCN could remarkably suppress peak heat release rate (pHRR) (48.5% and 40.0%), peak smoke production rate (pSPR) (25.5% and 21.8%), and increasing residues (10.18 wt%→17.04 wt% and 14.08 wt%). Improvements in charring stability and flame retardancy were ascribed to the formation of P-N bonds and P=N bonds in triazine rings, which promoted the retention of P in the condensed phase, which produced additional high-quality residues.

Experimental and theoretical studies on thermodynamic properties of quinolinium-based ionic liquids (ILs) based on bis(trifluoromethylsulfonyl)imide anion (namely N -butyl-quinoloinium bis(trifluoromethylsulfonyl)imide, [BQuin][NTf 2 ], N -hexylquinoloinium bis(trifluoromethyl-sulfonyl)imide, [HQuin][NTf 2 ], and N -octylquinoloinium bis(trifluoromethyl-sulfonyl)imide, [OQuin][NTf 2 ]) with aromatic sulfur compounds and heptane, as a model compound of fuel were examined in order to assess the applicability of the studied ionic liquids for desulfurization of fuels. With this aim, the temperature-composition phase diagrams of 13 binary mixtures composed of organic sulfur compounds (thiophene, benzothiophene, or 2-methylthiophene) or heptane and ionic liquid (IL) were investigated at ambient pressure. A dynamic method was used to determine the (solid-liquid) equilibrium phase diagrams in binary systems over a wide composition range and temperature range from T = 255.15 to 365.15 K up to the fusion temperature of ILs. The immiscibility gap with an upper critical solution temperature (UCST) was observed for each binary system under study. The influence of the alkane chain length of the substituent on the IL cation and of the sulfur compounds (the aromaticity of the solvent) was described. The experimental (solid + liquid) phase equilibrium dataset were successfully correlated using the well-known NRTL equation.

The functionality of biopolymer aerogels is inherently linked to its microstructure, which in turn depends on the synthesis protocol. Detailed investigations on the macroscopic size change and nanostructure formation during chitosan aerogel synthesis reveal a new aspect of biopolymer aerogels that increases process flexibility. Formaldehyde-cross-linked chitosan gels retain a significant fraction of their original volume after solvent exchange into methanol (50.3 %), ethanol (47.1 %) or isopropanol (26.7 %), but shrink dramatically during subsequent supercritical CO 2 processing (down to 4.9 %, 3.5 % and 3.7 %, respectively). In contrast, chitosan gels shrink more strongly upon exchange into n-heptane (7.2 %), a low affinity solvent, and retain this volume during CO 2 processing. Small-angle X-ray scattering confirms that the occurrence of the volumetric changes correlates with mesoporous network formation through physical coagulation in CO 2 or n-heptane. The structure formation step can be controlled by solvent-polymer and polymer-drying interactions, which would be a new tool to tailor the aerogel structure., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The effect of simulants, repeated use, washing, and oiling on the release of toxic metals from metallic kitchen utensils was investigated. The release of As, Cd, Cr, Ni, and Pb from kitchen utensils composed of stainless steel, aluminum, copper alloy, and cast iron into food simulants was quantified using inductively coupled plasma-mass spectrometry. The results show that this release of toxic metals was highly dependent on pH. Generally, the release of toxic metals tended to decrease with repeated use, and the release of Cr and Ni from stainless steel samples was significantly higher in the first test, compared to the third test. The washing conditions affected the release of As and Cr, whose release levels were higher when washing only with water and with a steel wool pad, respectively. Furthermore, oiling cast iron cookware reduced the release of As, Cd, Cr, and Ni into acidic simulants by 66%, 83%, 71%, and 15%, respectively. The margin of exposure (MOE) was calculated for each toxic metal; the calculated MOE values indicated that it is improbable that the current level of exposure from metallic kitchen utensils would pose a health risk in Korea., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The purpose of this investigation was to systematically assess the effect of residual solvents on the physical properties of a silicone adhesive-based transdermal system (TDS) containing n-heptane and o-xylene as residual solvents. The processing temperature was varied in this study to obtain various contents of residual solvents in the TDS. The adhesion performance was determined by evaluating the tack, shear, and peel of these TDS at week 0 and week 2. The adhesion measurements showed significant changes in tack values with a decrease in the contents of residual solvents, but the changes in peel and shear were insignificant. The rheological characteristics such as linear viscoelastic region, loss modulus and storage modulus were also measured. The outcome of the rheological measurements was found to be more sensitive to the changes in the contents of residual solvents in comparison to adhesion measurements. These results show that the residual solvent content may affect TDS performance and should be controlled from a product quality and performance perspective., (Published by Elsevier B.V.)

Homogeneous Charge Compression Ignition (HCCI) combustion is a potential candidate for dealing with the stringent regulations on vehicle emissions while still providing very good energy efficiency. Despite the promising results obtained in preliminary studies, the lack of autoignition control has delayed its launch in the engine industry. In the development of the HCCI concept, the availability of reliable computer models has proved extremely valuable, due to their flexibility and lower cost compared with experiments using real engines. In order to obtain the best formulation of a fuel surrogate formulated with n-heptane, toluene and cyclohexane that efficiently estimate the autoignition behaviour, regression adjustments are made to the Root-Mean-Square Errors (RMSE) of experimental Starts of Combustion (SOC) from the modeled SOC. The canonical form of the Scheffé polynomials is widely used to fit the data from mixture experiments, however the experimenter might have only partial knowledge. In this paper we present the adaptation of the robust methodology for possibly misspecified blending model and an algorithm to obtain tailor-made optimal designs for mixture experiments, instead of using standard designs which are indiscriminately employed, to make good estimations of the parameters blending model. We maximize the determinant of the mean squared error matrix of the least square estimator over a realistic neighbourhood of the fitted regression mixture model. The maximized determinant is then minimized over the class of possible designs, yielding an optimal design. Thus, the computed desings are robust to the exact form of the true blending model. Standard mixture designs, as the simplex lattice, are around 25% efficient for estimation purposes compared with the designs obtained in this work when deviances from the considered model occur during the experiments. Once an optimal-robust design was selected (based on the level of certainty about model adequacy), we computed the optimal mixture that best reproduces the combustion property to be imitated. Optimal mixtures obtained when the considered model is inadequate agree with the results achieved in empirical studies, which validates the methodology proposed in this work., Competing Interests: The authors have declared that no competing interests exist.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are high nutritional components. Evidence for unique effects of them is increasing. Further understanding of their independent biological functions urgently needs more efficient separation techniques. Nowadays, most of the commercially available fish oil products are the mixture of eicosapentaenoic acid ethyl ester (EPAEE) and docosahexaenoic acid ethyl ester (DHAEE). It will be convenient to directly separate esterified EPA and DHA without saponification pretreatment. However, it is of great challenge to separate EPAEE and DHAEE because of their extremely fat-soluble nature and the equivalent chain length rule. In this research, the suitability of green guanidinium ionic liquid (IL) in countercurrent chromatography (CCC) solvent system for the separation of them was evaluated for the first time. Compared with imidazolium IL and phosphonium IL, guanidinium IL based non-aqueous biphasic system showed more outstanding separation performance. The separation mechanism was elucidated in depth through quantum mechanical calculations. It was found that guanidinium IL acted a crucial role in the CCC separation, which resulted in difference of partition behavior of EPAEE and DHAEE via different hydrogen-bonding affinity. EPAEE and DHAEE were successfully separated by solvent system (n-heptane/methanol/propylguanidinium chloride ([C 3 Gun]Cl, 1:1:5%, v/v/m)) with high purity (>95%) in one step, which was not achieved beforehand. Moreover, an easy recycling procedure of IL had also been devised, which significantly reduced waste generated. It opens up a new way for reasonable design water-free two-phase solvent system for efficient separation of very non-polar lipid compounds., Competing Interests: Declaration of Competing Interests The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Encapsulation of crocin (CN), having large nonlinear optical (NLO) properties, can be utilized in studies of photodynamic therapy (PDT). For this purpose, photo-physical and NLO properties of CN encapsulation with and without cell culture medium (CCM) were investigated. As well, nonlinear absorption (NLA) coefficient and nonlinear refractive (NLR) indices were found to be 10 -7 (cm W -1 ) and 10 -12 (cm 2  W -1 ); respectively. The results revealed that NLO properties of CN had changed through its dipole moment. Reflecting on the theory of Bilot and Kawski, it was evidenced that the dipole moment of CN could change with a nano-droplet size. Furthermore, it was demonstrated that RPMI-1640 as a growth medium had failed to change NLO properties of CN encapsulated in nano-droplet. Accordingly, the encapsulated CN in nano-droplet in the form of a photosensitizer (PS) was suggested as a good candidate to examine PDT under in-vitro conditions.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small honorarium for time spent reviewing the subject work.

We introduce an integrated chip-approach for a postcolumn segmentation of normal phase liquid chromatography. This is achieved by the seamless integration of a chiral NP-chip-HPLC column, a flow-focusing droplet generator, and a segmented flow channel in a single microfluidic glass chip. This allows a continuous segmentation of the eluent into droplets which are picked up and transported via an immiscible continuous phase. The combination of NP-chip-HPLC and droplet microfluidics enables to fractionate and conserve chromatographic runs for further downstream processes at picoliter scale. An essential aspect is the proper choice of the continuous phase concerning polarity, wetting properties and viscosity. For this purpose, ethylene glycol is introduced which facilitates this first combination of normal phase chromatography and droplet microfluidics. By adjusting the flow rates and varying the generator geometry, the size and frequency of the droplets could be precisely controlled., (Copyright © 2019 Elsevier B.V. All rights reserved.)

( S )-5-Methylhept-2-en-4-one is a key flavour compound in hazelnuts. We have performed its chiral-pool-based chemoenzymatic synthesis with 39% overall yield (73% ee ). The four-step aldol-based sequence avoids the use of highly reactive and/or toxic reagents, does not require anhydrous conditions and uses only distillation as the purification method. Thus, such methodology represents a green and scalable alternative to only two stereoselective approaches towards this natural product known so far. In addition, we have designed and prepared a set of new (di)enones as achiral synthetic analogues of the title compound. The results of their sensory analyses clearly show that relatively minor structural changes of the natural molecule significantly alter its olfactory properties. Thus, simple (poly)methylation completely changes the original hazelnut aroma of ( S )-5-methylhept-2-en-4-one and shifts the odour of its analogues to eucalyptus, menthol, camphor, and sweet aroma., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Linear and non-linear tetranuclear ruthenium(ii) complexes containing the bridging ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(ii) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that both tetranuclear complexes had significant antimicrobial activity, with the non-linear (branched) species (Rubb 7 -TNL) having slightly higher activity than the corresponding linear analogue (Rubb 7 -TL). The corresponding toxicity against three eukaryotic cell lines - BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma) - have also been determined. Interestingly, both Rubb 7 -TNL and Rubb 7 -TL were as toxic to the eukaryotic cells as they were to the bacteria, a rarity for kinetically-inert cationic polypyridylruthenium(ii) complexes, and exhibited lower IC 50 values than cisplatin over 24-, 48- or 72-hour incubation times. Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). Rubb 7 -TNL and Rubb 7 -TL exhibited strong HSA binding, with equilibrium binding constants in the order of 10 7 M -1 . Confocal microscopy was used to examine the cellular localisation of Rubb 7 -TNL in BHK cells. The results indicated that the ruthenium complex localised in the nucleolus. Significant accumulation was also observed in the cytoplasm, but not in the mitochondria. Taken together, the results of this study suggest that Rubb 7 -TNL is an unlikely candidate as an antimicrobial agent, but may have potential as an anticancer drug.

Uncommon retention behavior of a series of n-alkylbenzene homologues as well as the effect of different sample solvents on chromatographic efficiency were studied in supercritical fluid chromatography. After testing various columns, an alkylamide stationary phase was selected for detailed studies. The results showed that even a small amount of methanol originating only from the sample, overloaded the column and competitive adsorption was induced between the analytes and the sample solvent for adsorption on the stationary phase. This was indicated by the changes in column efficiency, retention and peak widths. The concentration of the analytes in the sample was negligible compared to the amount of methanol - but their adsorption was influenced by the solvent - while the adsorption of methanol remained unaffected by the n-alkylbenzenes. First, the competition was described by determining the single-component adsorption isotherms for both the analytes and their solvent, then competitive isotherms were calculated. Based on the peak profiles, bi-Langmuir and competitive bi-Langmuir isotherms were assumed. The solvent effect was modeled by a numerical method created in-house where the differential mass balance equation given by the equilibrium-dispersive (ED) model was integrated using the Rouchon algorithm. The experimental observations were confirmed by in silico experiments and additional cases involving two hypothetical analytes were studied as well., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A simultaneous headspace-gas chromatography/mass spectrometry (HS-GC/MS) method was developed and validated to determine the migration of 12 volatile organic compounds (methanol, acetone, methylethylketone, ethylacetate, isopropylalcohol, benzene, toluene, ethylbenzene, xylene, cumene, propylbenzene, and styrene) from food contact materials into food simulants (water, 4% acetic acid, 50% ethanol, and n-heptane). The limits of detection and quantification were 0.007-0.201 mg L -1 and 0.023-0.668 mg L -1 , respectively. The method was applied to 205 samples of paper/paperboard, polyethylene, polypropylene, polystyrene, and polyethylene terephthalate. The estimated daily intake (EDI) was calculated using the migration results. Exposure assessments were carried out to compare the EDI to the tolerable daily intake (TDI); the results indicated that the EDI of styrene represented only a small percentage (8.0%) of the TDI. This analytical method will be a useful tool to examine levels of various volatile compounds migrating from food packaging to food simulants using HS-GC/MS method.

New 1'-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine ( 5 ) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds ( 6j and 6d ) had lower IC 50 (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC 50 (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides., Competing Interests: The authors declare no conflict of interest.

We have developed a transgenic mouse model of Type 1 Diabetes (T1D) in which human GAD65 is expressed in pancreatic β-cells, and human MHC-II is expressed on antigen presenting cells. Induced GAD65 antigen presentation activates T-cells, which initiates the downstream events leading to diabetes. In our humanized mice, we have shown downregulation of eukaryotic translation initiation factor 5 A (elF5A), expressed only in actively dividing mammalian cells. In-vivo inhibition of elF5A hypusination by deoxyhypusine synthase (DHS) inhibitor "GC7" was studied; DHS inhibitor alters the pathophysiology in our mouse model by catalyzing the crucial hypusination and the rate-limiting step of elF5A activation. In our mouse model, we have shown that inhibition of eIF5A resets the pro-inflammatory bias in the pancreatic microenvironment. There was: (a) reduction of Th1/Th17 response, (b) an increase in Treg numbers, (c) debase in IL17 and IL21 cytokines levels in serum, (d) lowering of anti-GAD65 antibodies, and (e) ablation of the ER stress that improved functionality of the β-cells, but minimal effect on the cytotoxic CD8 T-cell (CTL) mediated response. Conclusively, immune modulation, in the case of T1D, may help to manipulate inflammatory responses, decreasing disease severity, and may help manage T1D in early stages of disease. Our study also demonstrates that without manipulating the CTLs mediated response extensively, it is difficult to treat T1D.

The Pseudomonas sp. have been long recognized for their exogenous lipolytic activities yet the genus still contains a lot of unexplored strains. Due to the versatile metabolic machinery and their potential for adaptation to fluctuating environmental conditions Pseudomonas sp. are of great interest for biotechnological applications. In this study, a new extracellularly produced lipolytic enzyme from Pseudomonas sp. (P. reinekei) was purified and characterized. The production of lipase from P. reinekei (H1) was enhanced 10-fold by optimizing the nitrogen source. The 50 kDa H1 lipase was purified using negative and positive mode anion exchange chromatography. The purified lipase was active over a broad pH range (5.0-9.0) and was stable for 24 h at 40 °C. The lipase showed significant stability, and indeed activation, in the presence of organic solvents with log P ≥ 2.0. These features render this lipase of interest as a biocatalyst for applications such as biodiesel production, detergent formulations and biodegradation of oil in the environment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study demonstrates a simple method for one-step isolation of the main secondary metabolites of a hydroalcoholic extract of Crocus sativus stigmas (saffron) using step-gradient centrifugal partition chromatography. The analysis was performed in dual and elution-extrusion mode, using five biphasic systems of the solvents heptane/ethyl acetate/butanol/ethanol/water in ratios of 4:10:0:4:10, 1:13:0:4:10, 1:12:1:4:10, 1:10:3:4:10, and 1:7:6:4:10. Five major crocins, picrocrocin, and crocetin were directly isolated in one step. Scaling up to preparative level, allowed the recovery of significantly high quantities of pure compounds, especially trans-crocin-4, saffron's principal crocin. Comparing dual-mode and elution-extrusion, in dual-mode, the trans-crocin-4 containing fractions were co-eluted with a high amount of free β-d-glucose. In contrast, absence of free β-d-glucose was observed in the corresponding trans-crocin-4 fractions obtained by the second method denoting its superiority against dual-mode. Initiating analysis with the 4 th solvent-system afforded selective isolation of trans-crocin-4, with reduction in experimental time and solvent consumption. Structure elucidation was performed by nuclear magnetic resonance spectroscopy, liquid chromatography with mass spectrometry, and high-resolution tandem mass spectrometry. The proposed methodology comprises an integrated approach for the purification and characterization of biologically active saffron components in a fast, selective, and environmentally friendly manner., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This comprehensive review of filbertone, a principal flavor compound of hazelnut, evaluates the current state of the art of all relevant aspects of the title molecule: its occurrence and properties, laboratory preparation and bulk synthesis, analytical issues regarding stereochemistry and purity, sensory evaluation, and practical uses. Comparisons are made between different synthetic approaches, and a critical assessment of various applications is presented.

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dose of DPHP per kg body weight., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Using an emulsion liquid membrane based on edible oils is investigated for removing cationic dyes from aqueous solutions. There is a great potential for using edible oils in food industry extraction processes. The parameters affecting the stability of the emulsion and the extraction rate were studied. These parameters were the emulsification time, the stirring speed, the surfactant concentration, the internal phase concentration, the feed phase concentration, the volume ratio of internal phase to organic phase and the treat ratio. In order to stabilize the emulsion without using a carrier, edible paraffin oil and heptane are used at an 80:20 ratio. The optimum conditions for the extraction of methylene blue (MB), crystal violet and methyl violet (CV and MV) cationic dyes using edible paraffin oil as an environment friendly solvent are represented. A removal percentage of 95% was achieved for a mixture of dyes. The optimum concentration of sodium hydroxide in the internal phase, which results a stabile emulsion with a high stripping efficiency of 96%, was 0.04 M. An excellent membrane recovery was observed and the extraction of dyes did not decrease up to seven run cycles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The estrogen receptor (ER), a member of the nuclear receptor (NR) family, is involved in the regulation of physiological effects such as reproduction and bone homeostasis. Approximately 70% of human breast cancers are hormone-dependent and ERα-positive, and, thus, ER antagonists are broadly used in breast cancer therapy. We herein designed and synthesized a set of ER antagonists with a 4-heterocycle-4-phenylheptane skeleton., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The characterization and identification of compounds in complex real-world samples is quite difficult and new concepts and workflows are highly desirable. Retention indices (RIs) are widely used in gas chromatography (GC) to support the identification of unknown compounds. Several attempts have been made to introduce a similar concept for the second dimension in comprehensive two-dimensional (2D) GC (GC × GC) but, an easily applicable and robust system remains elusive. In the present study, a new RI system for GC × GC was developed. Polyethylene glycols (PEGs) were used in combination with a simple linear regression, with n-alkanes as reference points for virtually unretained compounds and PEG homologs as reference compounds for second-dimension RIs (PEG- 2 I). The n-alkanes were assigned a PEG- 2 I of zero and the distance between consecutive PEG homologs from PEG-2 (diethylene glycol) and higher were assigned a PEG- 2 I value of 10. We used ethylene glycol and PEG-2 through PEG-10 as reference compounds, thereby covering a PEG- 2 I range from 20.0 for ethylene glycol, over 50.0 for diethylene glycol (PEG-2) to 130.0 for decaethylene glycol (PEG-10); additional PEGs can be added to cover a wider polarity range. The PEG- 2 I system was initially evaluated using a 30 m × 0.25 mm non-polar (5% phenyl, 0.25 μm film thickness) first-dimension column and a 1.6 m × 0.18 mm polar (50% phenyl, 0.18 μm film thickness) second-dimension column. This system was validated for use with non-polar first-dimension columns and a semi-polar (50% phenyl) second-dimension column, and exhibited robustness to changes in the carrier gas flow velocity, oven temperature ramping rate, and secondary oven temperature offset. An average relative standard deviation of 2.7%, equal to a 95% confidence interval of 1.27 PEG- 2 I units, was obtained for the PEG- 2 I values of 72 environmental pollutants. Additionally, the system was found to be applicable over a wide range of boiling points (in the current case, from n-heptane to n-dotriacontane (C 7 -C 32 )) and can be used with various column dimensions. Changing the second-dimension column to either a narrower 0.1 mm column or a wider 0.25 mm column, yielded similar 95%-percentiles to that of the 0.18 mm column, differing by only 3.20 and 2.80 PEG- 2 I units, respectively. Moreover, methods for improving the system were suggested., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The surface modification of titanium and its alloys with amino group plasma-enhanced chemical vapor deposition has been proven to enhance the performance of implants on initial osteoblast bioactivity in vitro. However, scarce information on the effect of this kind of surface modification on nerve regeneration exists. In this study, the surface chemistry of pure Ti disks and surface-modified disks was examined using X-ray photoelectron spectroscopy. Cell counting kit 8 assay, 4,6-diamidino-2-phenylindole staining, flow cytometry, and scanning electron microscopy showed that either the p30% or cw + p30% mode-mediated surface significantly promote Schwann cell adhesion without any cytotoxicity compared with the pure Ti surface, and the cw + p30% group showed the best performance on cell adhesion. However, results of polymerase chain reaction and Western blot analyses showed that the mRNA and protein levels of glial cell-derived neurotrophic factor and nerve growth factor of the p30% and cw + p30% groups were lower than those of the Ti group at some time points. Generally, the results indicate that amino-functionalized Ti surfaces can promote Schwann cell adhesion without cytotoxicity, but this modification, in fact, inhibited the expression of the key growth factors GDNF and NGF of Schwann cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 265-271, 2018., (© 2017 Wiley Periodicals, Inc.)

This Minireview describes a presentation made at the XXIV National Meeting in Medicinal Chemistry (NMMC) held in Perugia (Italy), September 11-14, 2016. It relates to the discovery of novel templates of the so-called "amino" region of dopamine D 3 receptor antagonists. Moving from the early scaffolds, which were modified in the amine portion, this review discusses the variations that led to the discovery of new systems published in 2016, which allowed the identification of compounds endowed with great selectivity over the dopamine D 2 receptor and the human ether-à-go-go-related gene (hERG) ion channel. The main efforts in characterizing these compounds were devoted not only to determining their potency and selectivity relative to closely associated targets (e.g., the dopamine D 2 receptor), but to ensure a large therapeutic window versus liability points such as hERG. In particular, we present examples of derivatives with selectivities greater than 2000-fold. Furthermore, much focus is devoted to the overall developability of the scaffolds, ensuring that appropriate physicochemical and pharmacokinetic parameters are present in all compounds progressing through the screening cascade., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs), however, their spirocyclic analogues remain unknown. Described here is the synthesis of spirocyclic analogues for 2-substituted piperidines and a demonstration of their validation in drug discovery., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Synthesis of a novel 2'-deoxy-guanine carbocyclic nucleoside 4 constructed with spiro[2.4]heptane core structure in the aglycon moiety was carried out. Radical-mediated 5-exo-dig mode cyclization and following cyclopropanation proceeded efficiently to furnish the spiro alcohol 10. Subsequent Mitsunobu-type glycosylation between 13 and 14, deoxygenation of the 2'-hydroxyl group of 16 and deprotection of 17 gave the title compound 4. Compound 4 demonstrated moderate anti-HBV activity (EC 50 value of 0.12 ± 0.02 µM) and no cytotoxicity against HepG2 cells was observed up to 100 µM.

Solvent systems are not readily available for the separation of very nonpolar compounds by countercurrent chromatography (CCC). In this study we therefore evaluated the suitability of room temperature ionic liquids (IL) in organic solvents for the CCC separation of the extremely nonpolar lipid compounds tripalmitin (PPP) and cholesteryl stearate (CS). The four IL tested were [C 10 mim][OTf], [C 2 mim][NTf 2 ], [P66614][NTf 2 ], and [P66614][Cl]. Search for a CCC-suited solvent system started with solubility studies with fourteen organic solvents. Following this, combinations were made with one organic solvent miscible and one organic solvent immiscible with IL (147 combinations). Twenty-four initially monophasic mixtures of two organic solvents became biphasic by adding IL. Several unexpected results could be observed. For instance, n-hexane and n-heptane became biphasic with [P66614][Cl]. Further nine systems became biphasic although the IL was not miscible in any of the two components. These 33 solvent systems were investigated with regard to phase ratio, settling time, share of IL in the upper phase and last not least the K U/L values of PPP and CS, which were 8.1 and 7.7 respectively. The most promising system, n-heptane/chloroform/[C 10 mim][OTf] (3:3:1, v/v/v) allowed a partial separation of PPP and CS by CCC which was not achieved beforehand., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The synthesis and X-ray crystal structures of syn and anti 4-N-Boc-aminobicyclo[3.2.0]heptane-1-carboxylic acids are described. The placement of the N-Boc-amino groups in the two stereoisomers in either pseudo-equatorial or pseudo-axial positions renders the molecules conformationally locked, with N-Boc-protected γ-aminobutyric acid (GABA) embedded within the bicyclic core. Despite the different conformations of the urethane and distinct crystal packing, the bicyclic core units of the two stereoisomers adopt virtually identical structures. They correspond to in silico models of the parent bicyclic core and a systematic array of disubstituted derivatives. The study documents an intrinsic property of the bicyclo[3.2.0]heptane core to favor adoption of a boat-like conformation, which is largely unaffected by various substitution patterns. The structural concepts are useful in the design of molecules with spatial and directional fixation of pharmacophoric groups., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the present work, a 0.4nm nickel cluster has been theoretically studied. Its equilibrium structural parameters have been calculated by the DFT method based on the PBEH1PBE hybrid functional and split-valence basis set Lanl2DZ including effective core potentials. We have systematically considered diverse spin states of this cluster and find out its ground state. The relative stability of these states depends on the HOMO-LUMO gap. The interaction of the Ni 6 with 4-propylheptane С 10 Н 22 has been studied to simulate the process of catalytic cracking of hydrocarbons. The optimization of this structure has been performed by the ωPBE/Lanl2DZ_ecp method (the TeraChem V.1.9 program package) with no symmetry restrictions; the electron shells of the metal were described by effective core pseudopotentials. For visualization and quantitative estimation of the bonding bonds between the nickel nanocluster and 4-propylheptane, the analysis of weak interactions based on RGD has been performed. To confirm the proposition about the formation of Ni-H bonds, we have scrutinized critical points of electronic density. Values of laplasian of electronic density and Bader atomic charge distribution in the global minimum of the total energy have been estimated by the AIMAll 15.05.18 program suite. Finally, we have simulated interaction of Ni 6 with 4-propylheptane in terms of the Born-Oppenheimer ab initio molecular dynamics. The results of the molecular dynamics simulation provide pair radial distribution function CH at 1500°C and a detailed picture of the processes occurring in the system., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We have measured the concentration of hydroxyl radicals (OH) produced in the gas phase by a commercially available purifier for air and surfaces, using the time rate of decay of n-heptane added to an environmental chamber. The hydroxyl generator, an Odorox® BOSS™ model, produces the OH through 185-nm photolysis of ambient water vapor. The steady-state concentration of OH produced in the 120 m 3 chamber is, with 2σ error bars, (3.25 ± 0.80) × 10 6 cm -3 . The properties of the hydroxyl generator, in particular the output of the ultraviolet lamps and the air throughput, together with an estimation of the water concentration, were used to predict the amount of OH produced by the device, with no fitted parameters. To relate this calculation to a steady-state concentration, we must estimate the OH loss rate within the chamber owing to reaction with the n-heptane and the 7 ppb of background hydrocarbons that are present. The result is a predicted steady-state concentration in excellent agreement with the measured value. This shows we understand well the processes occurring in the gas phase during operation of this hydroxyl radical purifier., Implications: Hydroxyl radical air purifiers are used for cleaning both gaseous contaminants, such as volatile organic compounds (VOCs) or hazardous gases, and biological pathogens, both airborne and on surfaces. This is the first chemical kinetic study of such a purifier that creates gas-phase OH by ultraviolet light photolysis of H 2 O. It shows that the amount of hydroxyls produced agrees well with nonparameterized calculations using the purifier lamp output and device airflow. These results can be used for designing appropriate remediation strategies.

Two novel diphenylheptanes, 2,3- dihydro-2 - (4' - hydroxy-phenylethyl) - 6 - [(3″,4″ - dihydroxy-5" - methoxy) phenyl] -4 - pyrone (CG-A) and 4 - dihydro-2 - (4' - hydroxy-phenylmethyl) -6 - [(3",4″ - dihydroxy-5″ - methoxyphenyl) methylene]-pyran-3, 5 - dione (CG-B), were isolated from the dried fruits of Amomum tsaoko, a commercially important spice. This study was designed to investigate their protective effects against H 2 O 2 -induced nerve injury, using PC-12 cells to determine the cell cytotoxicity and cell viability. The inhibitory effect on (nitric oxide) NO production was also determined in (lipopolysaccharide) LPS-stimulated macrophage RAW 264.7 cells. The results showed that CG-A and CG-B displayed significant neuroprotective effect and exhibited anti-inflammatory activity in a dose-dependent manner. These findings suggest that CG-A and CG-B are very important nutritional ingredients responsible for the neuroprotective and anti-inflammatory health benefits of A. tsaoko.

This paper is focused on the determination of phthalates (PAEs), compounds "plausibly" endocrine disruptors, in baby food products by means of a method based on ultrasound-vortex-assisted liquid-liquid microextraction coupled with GC-IT/MS (UVALLME-GC-IT/MS). Particularly, the whole procedure allows the determination of six phthalates such as DMP, DEP, DBP, iBcEP, BBP and DEHP. After dissolution of 0.1g product sample and addition of anthracene as Internal Standard, 250μL of n-heptane are used as extraction solvent. The solution, held for 5min on the vortex mixer and for 6min in an ultrasonic bath at 100W for favoring the solvent dispersion and consequently the analyte extraction, is centrifuged at 4000rpm for 30min. About 100μL of heptane are recovered and 1μL is injected into the GC-IT/MS. All the analytical parameters investigated are deeply discussed: under the best conditions, the percentage recoveries range between 96.2 and 109.2% with an RSD ≤10.5% whereas the Limit of Detections (LODs) and the Limit of Quantifications (LOQs) are below 11 and 20ngg -1 , respectively, for all the PAEs except for iBcEP (23 and 43ngg -1 , respectively). The linear dynamic range of this procedure is between 10 and 5000ngg -1 with R 2 ≥0.92. The method has been applied to real commercial freeze-dried samples (chicken and turkey meats) available on the Italian pharmaceutical market: three PAEs were preliminary identified, i.e. DEP (14ngg -1 ), DBP (11ngg -1 ) and DEHP (64ngg -1 )., (Copyright © 2016. Published by Elsevier B.V.)

A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.

In this study, equilibria, breakthrough curves, and breakthrough times were predicted for three binary mixtures of four volatile organic compounds (VOCs) using a model based on partial differential equations of dynamic adsorption coupling a mass balance, a simple Linear Driving Force (LDF) hypothesis to describe the kinetics, and the well-known Extended-Langmuir (EL) equilibrium model. The model aims to predict with a limited complexity, the BTCs of respirator cartridges exposed to binary vapor mixtures from equilibria and kinetics data obtained from single component. In the model, multicomponent mass transfer was simplified to use only single dynamic adsorption data. The EL expression used in this study predicted equilibria with relatively good accuracy for acetone/ethanol and ethanol/cyclohexane mixtures, but the prediction of cyclohexane uptake when mixed with heptane is less satisfactory. The BTCs given by the model were compared to experimental BTCs to determine the accuracy of the model and the impact of the approximation on mass transfer coefficients. From BTCs, breakthrough times at 10% of the exposure concentration t10% were determined. All t10% were predicted within 20% of the experimental values, and 63% of the breakthrough times were predicted within a 10% error. This study demonstrated that a simple mass balance combined with kinetic approximations is sufficient to predict lifetime for respirator cartridges exposed to VOC mixtures. It also showed that a commonly adopted approach to describe multicomponent adsorption based on volatility of VOC rather than adsorption equilibrium greatly overestimated the breakthrough times.

Bacterial infections, caused by Mycobacterium tuberculosis and other problematic bacterial pathogens, continue to pose a significant threat to global public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic diarylheptanoids with diverse amine, amide, urea, and sulfonamide functionalities. Results of this study have produced macrocyclic geranylamine and 4-fluorophenethylamine substituted derivatives, exhibiting moderate to good activity against M. tuberculosis and selected Gram-positive bacterial pathogens., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The interfacial properties of pure reverse micelles (RMs) are a consequence of the magnitude and nature of noncovalent interactions between confined water and the surfactant polar head. Addition of a second surfactant to form mixed RMs is expected to influence these interactions and thus affect these properties at the nanoscale level. Herein, pure and mixed RMs stabilized by sodium 1,4-bis-2-ethylhexylsulfosuccinate and tri-n-octyl phosphine oxide (TOPO) surfactants in n-heptane were formulated and studied by varying both the water content and the TOPO mole fraction. The microenvironment generated was sensed by following the solvatochromic behavior of the 1-methyl-8-oxyquinolinium betaine probe and (31) P NMR spectroscopy. The results reveal unique properties of mixed RMs and we give experimental evidence that free water can be detected in the polar core of the mixed RMs at very low water content. We anticipate that these findings will have an impact on the use of such media as nanoreactors for many types of chemical reactions, such as enzymatic reactions and nanoparticle synthesis., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photoinduced initiators for continuous activator regeneration atom transfer radical polymerization (ATRP) of hydrophilic monomers in heptane/ethanol latent-biphasic system for copper catalyst separation and recycling have been realized for the first time at room temperature with different wavelengths of visible light LED (green, blue, purple, and white LED) as external stimulus, using 2-bromophenylacetate as the ATRP initiator and camphorquinone/triethylamine as the photoinitiator. In this system, hybrid catalyst complex (HCc) is synthesized as a novel nonpolar catalyst, which is preferentially dissolved in heptane. The hydrophilic polymers obtained catalyzed by HCc in heptane/ethanol mixture solvent show typical "living" features, for example, the values of Mn,GPC increase linearly with monomer conversion up to quantitative level (>96%) and the molecular weight distributions were kept narrow (Mw /Mn < 1.20) throughout the polymerization process. It should be noted that the excellent controllability of this novel polymerization system can be achieved even after 5 catalyst recycling experiments under LED irradiation., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)