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Peter D.r. Moeller - One of the best experts on this subject based on the ideXlab platform.
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the effect of ph on the toxicity of Fatty Acids and Fatty Acid Amides to rainbow trout gill cells
Aquatic Toxicology, 2014Co-Authors: Matthew J. Bertin, Delia Voronca, Robert W Chapman, Peter D.r. MoellerAbstract:Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of Fatty Acid Amides and Fatty Acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of Fatty Acid Amides and Fatty Acids. Our results demonstrate that increasing pH levels increases the toxicity of Fatty Acid Amides and inhibits the toxicity of Fatty Acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the Fatty Acid Amides and Fatty Acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on Fatty Acid Amides and Fatty Acids.
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Identification of toxic Fatty Acid Amides isolated from the harmful alga Prymnesium parvum carter
Harmful Algae, 2012Co-Authors: Matthew J. Bertin, Kevin R. Beauchesne, Kevin M. Huncik, Paul V Zimba, Peter D.r. MoellerAbstract:Abstract The golden alga Prymnesium parvum has been implicated in fish and aquatic animal kills globally for over a century. In addition to widespread ecological impacts through the loss of entire fish populations within lakes, an economic burden is also felt by state and local agencies due to year class losses of fish raised for stocking lakes as well as loss of fishing and recreational use of the affected water. Multiple compounds have been implicated in P. parvum toxicity, but the unequivocal identification and characterization of all P. parvum toxins remained to be accomplished. To unambiguously characterize these toxins, we analyzed laboratory-cultured cells exposed to limited nitrogen and phosphorus concentrations, uni-algal wild cells collected from an ichthytoxic bloom event at Lake Wichita, TX, and the water from both cultured and field-collected algae. A bioassay-guided fractionation process was employed to chemically isolate P. parvum toxins using both mammalian cells and larval fish. The results of these assays revealed that there was a distinct similarity in the toxic compounds characterized as seven primary Fatty Acid Amides (myristamide, palmitamide, linoleamide, oleamide, elaidamide, stearamide, and erucamide) and one hydroxamic Acid (linoleyl hydroxamic Acid). These compounds display cytotoxic and ichthytoxic activity and have not yet been reported in P. parvum toxicity or in the toxicity of harmful algal species.
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the contribution of Fatty Acid Amides to prymnesium parvum carter toxicity
Harmful Algae, 2012Co-Authors: Matthew J. Bertin, Kevin R. Beauchesne, Kevin M. Huncik, Peter D.r. Moeller, Paul V ZimbaAbstract:Abstract It is well known that toxic blooms of Prymnesium parvum result in widespread fish mortalities. An assemblage of Fatty Acid Amides (FAAs) has been shown to be toxic metabolites of P. parvum. Several compounds and compound classes have been implicated in P. parvum toxicity, but unlike FAAs, thus far none have been shown to accumulate to lethal levels at ichthyotoxic bloom events. The purpose of this study is to characterize the hemolytic activity, cytotoxicity, and ichthyotoxicity of the Fatty Acid Amides identified from P. parvum using mammalian red blood cells, mouse neuroblastoma cells, and rainbow trout gill cells. We also investigate the effect of abiotic factors (divalent cations and pH) on Fatty Acid amide toxicity. Samples from P. parvum bloom events with fish kills were analyzed in order to demonstrate that Fatty Acid Amides are found in lethal levels at fish kills. Hemolytic and cytoxicity assays were completed with the introduction of abiotic factors to assess Fatty Acid Amides toxicity. Our results show that Fatty Acid Amides are detected in toxicologically significant quantities in samples from at least one fish kill event. We also show that the toxicity of oleamide and linoleamide in cell culture is increased in the presence of divalent cations and increasing pH, demonstrating that multiple abiotic factors affect the toxicity of Fatty Acid Amides. Fatty Acid Amides possess the hemolytic and cytotoxic properties previously attributed to P. parvum toxins throughout history. After Fatty Acid Amides have been released into the environment, multiple abiotic factors can increase their toxicity.
Benjamin F Cravatt - One of the best experts on this subject based on the ideXlab platform.
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evaluation of Fatty Acid Amides in the carrageenan induced paw edema model
Neuropharmacology, 2008Co-Authors: Laura E Wise, Roberta Cannavacciulo, Billy F Martin, Benjamin F Cravatt, Andrew H LichtmanAbstract:While it has long been recognized that Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of Fatty Acid amide hydrolase (FAAH), the enzyme responsible for degradation of Fatty Acid Amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (−/−) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (−/−) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild-type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (−/−) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.
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A FAAH-regulated class of N-acyl taurines that activates TRP ion channels.
Biochemistry, 2006Co-Authors: Alan Saghatelian, Michele K. Mckinney, Michael Bandell, And Ardem Patapoutian, Benjamin F CravattAbstract:Fatty Acid amide hydrolase (FAAH) is an integral membrane enzyme that catabolizes several bioactive lipids in vivo. Most of the physiological substrates of FAAH characterized to date belong to the N-acyl ethanolamine (NAE) class of Fatty Acid Amides, including the endocannabinoid anandamide, the anti-inflammatory lipid N-palmitoyl ethanolamine, and the satiating factor N-oleoyl ethanolamine. We recently identified a second structural class of Fatty Acid Amides regulated by FAAH in vivo: the N-acyl taurines (NATs). Global metabolite profiling revealed high concentrations of long chain (≥C20) saturated NATs in the central nervous system (CNS) of FAAH(−/−) mice. Here, we use metabolite profiling to characterize the FAAH−NAT system in peripheral mouse tissues. Livers and kidneys of FAAH(−/−) mice possessed dramatic elevations in NATs, which, in contrast to those detected in the CNS, were enriched in polyunsaturated acyl chains (e.g., C20:4, C22:6). Peripheral NATs rose more than 10-fold within 1 h following ...
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Structure-based design of a FAAH variant that discriminates between the N-acyl ethanolamine and taurine families of signaling lipids.
Biochemistry, 2006Co-Authors: Michele K. Mckinney, Benjamin F CravattAbstract:Fatty Acid amide hydrolase (FAAH) inactivates a large and diverse class of endogenous signaling lipids termed Fatty Acid Amides. Representative Fatty Acid Amides include the N-acyl ethanolamines (NAEs) anandamide, which serves as an endogenous ligand for cannabinoid receptors, and N-oleoyl and N-palmitoyl ethanolamine, which produce satiety and anti-inflammatory effects, respectively. Global metabolite profiling studies of FAAH (−/−) mice have recently identified a second class of endogenous FAAH substrates: the N-acyl taurines (NATs). To determine the metabolic and signaling functions performed by NAEs and NATs in vivo, a FAAH variant that discriminates between these two substrate classes would be of value. Here, we report the structure-guided design of a point mutant in the active site of FAAH that selectively disrupts interactions with NATs. This glycine-to-aspartate (G268D) mutant was found to exhibit wild-type kinetic parameters with NAEs, but more than a 100-fold reduction in activity with NATs att...
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Characterization of the sleep-wake patterns in mice lacking Fatty Acid amide hydrolase.
Sleep, 2004Co-Authors: Salvador Huitron-resendiz, Benjamin F Cravatt, Manuel Sanchez-alavez, Derek N. Wills, Steven J. HenriksenAbstract:Study Objectives: Oleamide and anandamide are Fatty Acid Amides implicated in the regulatory mechanisms of sleep processes. However, due to their prompt catabolism by Fatty Acid amide hydrolase (FAAH), their pharmacologic and behavioral effects, in vivo, disappear rapidly. To determine if, in the absence of FAAH, the hypnogenic Fatty Acid Amides induce an increase of sleep, We characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation. Design: FAAH (-/-), FAAH (+/-), and FAAH (+/+) mice were implanted chronically for sleep, body temperature (Tb), and locomotor activity (LMA) recordings. Sleep-wake states were recorded during a 24-hour baseline session followed by 8 hours of sleep deprivation. Recovery recordings were done during the 16 hours following sleep deprivation. Total amount of wake, slow-wave sleep, and rapid eye movement sleep were calculated and compared between genotypes. The electroencephalographic spectral analysis was performed by fast Fourier transform analysis. Telemetry recordings of Tb and LMA were carried out continuously during 4 days under baseline conditions. Setting: N/A. Patients or Participants: FAAH (-/-) mice and their heterozygote (+/-) and control (+/+) littermates were used. Interventions: Sleep deprivation. Measurements and Results: FAAH (-/-) mice possess higher values of slow-wave sleep and more intense episodes of slow-wave sleep than do control littermates under baseline conditions that are not related to differences in Tb and LMA. A rebound of slow-wave sleep and rapid eye movement sleep as well an increase in the levels of slow-wave activity were observed after sleep deprivation in all genotypes. Conclusion: These findings support the role of Fatty Acid Amides as possible modulators of sleep and indicate that the homeostatic mechanisms of sleep in FAAH (-/-) mice are not disrupted.
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pharmacological activity of Fatty Acid Amides is regulated but not mediated by Fatty Acid amide hydrolase in vivo
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Andrew H Lichtman, Gregory E Hawkins, Graeme Griffin, Benjamin F CravattAbstract:Fatty Acid Amides (FAAs) represent a class of neuromodulatory lipids that includes the endocannabinoid anandamide and the sleep-inducing substance oleamide. Both anandamide and oleamide produce behavioral effects indicative of cannabinoid activity, but only anandamide binds the cannabinoid (CB1) receptor in vitro. Accordingly, oleamide has been proposed to induce its behavioral effects by serving as a competitive substrate for the brain enzyme Fatty Acid amide hydrolase (FAAH) and inhibiting the degradation of endogenous anandamide. To test the role that FAAH plays as a mediator of oleamide activity in vivo, we have compared the behavioral effects of this FAA in FAAH(+/+) and (−/−) mice. In both genotypes, oleamide produced hypomotility, hypothermia, and ptosis, all of which were enhanced in FAAH(−/−) mice, were unaffected by the CB1 antagonist N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-di-chlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide hydrochloride (SR141716A) and occurred in CB1(−/−) mice. Additionally, oleamide displayed negligible binding to the CB1 receptor in brain extracts from either FAAH(+/+) or (−/−) mice. In contrast, anandamide exhibited a 15-fold increase in apparent affinity for the CB1 receptor in brains from FAAH(−/−) mice, consistent with its pronounced CB1-dependent behavioral effects in these animals. Contrary to both oleamide and anandamide, monoacylglycerol lipids exhibited equivalent hydrolytic stability and pharmacological activity in FAAH(+/+) and (−/−) mice. Collectively, these results indicate that FAAH is a key regulator, but not mediator of FAA activity in vivo. More generally, these findings suggest that FAAs represent a family of signaling lipids that, despite sharing similar chemical structures and a common pathway for catabolism, produce their behavioral effects through distinct receptor systems in vivo.
Matthew J. Bertin - One of the best experts on this subject based on the ideXlab platform.
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the effect of ph on the toxicity of Fatty Acids and Fatty Acid Amides to rainbow trout gill cells
Aquatic Toxicology, 2014Co-Authors: Matthew J. Bertin, Delia Voronca, Robert W Chapman, Peter D.r. MoellerAbstract:Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of Fatty Acid Amides and Fatty Acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of Fatty Acid Amides and Fatty Acids. Our results demonstrate that increasing pH levels increases the toxicity of Fatty Acid Amides and inhibits the toxicity of Fatty Acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the Fatty Acid Amides and Fatty Acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on Fatty Acid Amides and Fatty Acids.
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Identification of toxic Fatty Acid Amides isolated from the harmful alga Prymnesium parvum carter
Harmful Algae, 2012Co-Authors: Matthew J. Bertin, Kevin R. Beauchesne, Kevin M. Huncik, Paul V Zimba, Peter D.r. MoellerAbstract:Abstract The golden alga Prymnesium parvum has been implicated in fish and aquatic animal kills globally for over a century. In addition to widespread ecological impacts through the loss of entire fish populations within lakes, an economic burden is also felt by state and local agencies due to year class losses of fish raised for stocking lakes as well as loss of fishing and recreational use of the affected water. Multiple compounds have been implicated in P. parvum toxicity, but the unequivocal identification and characterization of all P. parvum toxins remained to be accomplished. To unambiguously characterize these toxins, we analyzed laboratory-cultured cells exposed to limited nitrogen and phosphorus concentrations, uni-algal wild cells collected from an ichthytoxic bloom event at Lake Wichita, TX, and the water from both cultured and field-collected algae. A bioassay-guided fractionation process was employed to chemically isolate P. parvum toxins using both mammalian cells and larval fish. The results of these assays revealed that there was a distinct similarity in the toxic compounds characterized as seven primary Fatty Acid Amides (myristamide, palmitamide, linoleamide, oleamide, elaidamide, stearamide, and erucamide) and one hydroxamic Acid (linoleyl hydroxamic Acid). These compounds display cytotoxic and ichthytoxic activity and have not yet been reported in P. parvum toxicity or in the toxicity of harmful algal species.
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the contribution of Fatty Acid Amides to prymnesium parvum carter toxicity
Harmful Algae, 2012Co-Authors: Matthew J. Bertin, Kevin R. Beauchesne, Kevin M. Huncik, Peter D.r. Moeller, Paul V ZimbaAbstract:Abstract It is well known that toxic blooms of Prymnesium parvum result in widespread fish mortalities. An assemblage of Fatty Acid Amides (FAAs) has been shown to be toxic metabolites of P. parvum. Several compounds and compound classes have been implicated in P. parvum toxicity, but unlike FAAs, thus far none have been shown to accumulate to lethal levels at ichthyotoxic bloom events. The purpose of this study is to characterize the hemolytic activity, cytotoxicity, and ichthyotoxicity of the Fatty Acid Amides identified from P. parvum using mammalian red blood cells, mouse neuroblastoma cells, and rainbow trout gill cells. We also investigate the effect of abiotic factors (divalent cations and pH) on Fatty Acid amide toxicity. Samples from P. parvum bloom events with fish kills were analyzed in order to demonstrate that Fatty Acid Amides are found in lethal levels at fish kills. Hemolytic and cytoxicity assays were completed with the introduction of abiotic factors to assess Fatty Acid Amides toxicity. Our results show that Fatty Acid Amides are detected in toxicologically significant quantities in samples from at least one fish kill event. We also show that the toxicity of oleamide and linoleamide in cell culture is increased in the presence of divalent cations and increasing pH, demonstrating that multiple abiotic factors affect the toxicity of Fatty Acid Amides. Fatty Acid Amides possess the hemolytic and cytotoxic properties previously attributed to P. parvum toxins throughout history. After Fatty Acid Amides have been released into the environment, multiple abiotic factors can increase their toxicity.
Thomas Groth - One of the best experts on this subject based on the ideXlab platform.
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tris 2 aminoethyl amine based α branched Fatty Acid Amides synthesis of lipids and comparative study of transfection efficiency of their lipid formulations
European Journal of Pharmaceutics and Biopharmaceutics, 2015Co-Authors: Nicole Erdmann, Christian Wolk, Ingo Schulze, Christopher Janich, Manuela Folz, Simon Drescher, Matthias Dittrich, Annette Meister, Jurgen Vogel, Thomas GrothAbstract:The synthesis of a new class of cationic lipids, tris(2-aminoethyl)amine-based α-branched Fatty Acid Amides, is described resulting in a series of lipids with specific variations in the lipophilic as well as the hydrophilic part of the lipids. In-vitro structure/transfection relationships were established by application of complexes of these lipids with plasmid DNA (pDNA) to different cell lines. The α-branched Fatty Acid amide bearing two tetradecyl chains and two lysine molecules (T14diLys) in mixture with the co-lipid 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DOPE) (1/2, n/n) exhibits effective pDNA transfer in three different cell lines, namely Hep-G2, A549, and COS-7. The presence of 10% serum during lipoplex incubation of the cells did not affect the transfection efficiency. Based on that, detailed investigations of the complexation of pDNA with the lipid formulation T14diLys/DOPE 1/2 (n/n) were carried out with respect to particle size and charge using dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Additionally, the lipoplex uptake was investigated by confocal laser scanning microscopy (CLSM). Overall, lipoplexes prepared from T14diLys/DOPE 1/2 (n/n) offer large potential as lipid-based polynucleotide carriers and further justify advanced examinations.
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Tris(2-aminoethyl)amine-based α-branched Fatty Acid Amides – Synthesis of lipids and comparative study of transfection efficiency of their lipid formulations
European Journal of Pharmaceutics and Biopharmaceutics, 2015Co-Authors: Nicole Erdmann, Christian Wolk, Ingo Schulze, Christopher Janich, Manuela Folz, Simon Drescher, Matthias Dittrich, Annette Meister, Jurgen Vogel, Thomas GrothAbstract:The synthesis of a new class of cationic lipids, tris(2-aminoethyl)amine-based α-branched Fatty Acid Amides, is described resulting in a series of lipids with specific variations in the lipophilic as well as the hydrophilic part of the lipids. In-vitro structure/transfection relationships were established by application of complexes of these lipids with plasmid DNA (pDNA) to different cell lines. The α-branched Fatty Acid amide bearing two tetradecyl chains and two lysine molecules (T14diLys) in mixture with the co-lipid 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DOPE) (1/2, n/n) exhibits effective pDNA transfer in three different cell lines, namely Hep-G2, A549, and COS-7. The presence of 10% serum during lipoplex incubation of the cells did not affect the transfection efficiency. Based on that, detailed investigations of the complexation of pDNA with the lipid formulation T14diLys/DOPE 1/2 (n/n) were carried out with respect to particle size and charge using dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Additionally, the lipoplex uptake was investigated by confocal laser scanning microscopy (CLSM). Overall, lipoplexes prepared from T14diLys/DOPE 1/2 (n/n) offer large potential as lipid-based polynucleotide carriers and further justify advanced examinations.
Vladimir Dohnal - One of the best experts on this subject based on the ideXlab platform.
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Temperature Dependence of Air−Water Partitioning of N-Methylated (C1 and C2) Fatty Acid Amides
Journal of Chemical & Engineering Data, 2008Co-Authors: Milan Bernauer, Vladimir DohnalAbstract:Air−water partitioning of lower N-methylated Fatty Acid Amides (N-methylformamide, N-methylacetamide, N,N-dimethylformamide, and N,N-dimethylacetamide) was examined at several temperatures in the range from (333 to 373) K employing comparative ebulliometry, differential distillation, and the method of circulation still as suitable experimental techniques. Results are reported in the form of limiting (infinite dilution) relative volatility, limiting activity coefficient, Henry’s law constant, and air−water partition coefficient. For each amide, the present air−water partitioning data and some other relevant VLE measurements from the literature were combined with existing calorimetric data on respective derivative thermal properties and correlated simultaneously by a suitable model equation. In the entire treatment, precautions were taken to minimize the effect of uncertain vapor pressures of pure Amides at lower temperatures. Recommended thermodynamically consistent temperature dependences of the air−water...
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temperature dependence of air water partitioning of n methylated c1 and c2 Fatty Acid Amides
Journal of Chemical & Engineering Data, 2008Co-Authors: Milan Bernauer, Vladimir DohnalAbstract:Air−water partitioning of lower N-methylated Fatty Acid Amides (N-methylformamide, N-methylacetamide, N,N-dimethylformamide, and N,N-dimethylacetamide) was examined at several temperatures in the range from (333 to 373) K employing comparative ebulliometry, differential distillation, and the method of circulation still as suitable experimental techniques. Results are reported in the form of limiting (infinite dilution) relative volatility, limiting activity coefficient, Henry’s law constant, and air−water partition coefficient. For each amide, the present air−water partitioning data and some other relevant VLE measurements from the literature were combined with existing calorimetric data on respective derivative thermal properties and correlated simultaneously by a suitable model equation. In the entire treatment, precautions were taken to minimize the effect of uncertain vapor pressures of pure Amides at lower temperatures. Recommended thermodynamically consistent temperature dependences of the air−water...
