Yes / Literature solubilities and NMR and IR studies have been used to obtain properties or descriptors of edaravone. These show that edaravone has a significant hydrogen bond acidity so that it must exist in solution partly as the OH and NH forms, as found by Freyer et al. Descriptors have been assigned to the keto form which has a low hydrogen bond acidity, and which is the dominant form in nonpolar solvents. Physicochemical properties of the keto form can be been calculated such as solubilities in nonpolar solvents, partition coefficients from water to nonpolar solvents, and partition coefficients from air to biological phases.

Neste estudo foi caracterizado o processo de solubilização de solutos neutros em sistemas micelares compostos de surfactantes não iônicos da família de alcoóis secundários etoxilados com o mesmo grupo hidrofóbico e graus diferentes de etoxilação, variando de 5 a 30 subunidades de oxido de etileno. Para isso, foram utilizadas as Relações Lineares de Energias Livres de Solvatação (LSER) como modelo preditivo para a eficiência de incorporação de solutos. As análises de regressão múltipla e as validações apresentadas tiveram por base a constante de incorporação micelar KS como variável dependente e os descritores de soluto de Abraham como as variáveis independentes. A metodologia utilizada para a determinação de KS baseou-se em técnicas fotofísicas (supressão de fluorescência), medidas de solubilização (solubilização em saturação via espectrofotometria de UV-VIS) e técnicas de cromatografia líquida (Cromatografia Micelar) e gasosa (Cromatografia por Análise de Fase Vapor ou Headspace). A determinação realizada forneceu as seguintes LSERs: 15-S-5: Log KS = 0,054 - 0,227A - 1,197B - 0,600S + 0,938E + 1,854V 15-S-7: Log KS = + 0,267 + 0,435A - 1,475B - 0,831S + 1,045E + 1,805V 15-S-15: Log KS = -0,047 + 0,314A - 1,265B - 0,487S + 0,823E + 2,107V 15-S-30: Log KS = - 0,345 + 0,366A - 1,114B - 0,430S + 0,858E + 2,310V Como é típico para sistemas micelares, constatou-se que a partição dos solutos entre os agregados micelares e a fase aquosa é dominada pelas propriedades de volume molar (V) e capacidade receptora de pontes de hidrogênio ou basicidade (B) do soluto, com contribuições secundárias de dipolaridade (S) e refração molar em excesso (E) do soluto. O aumento do tamanho da cabeça hidrofílica de oligômeros de oxietileno (OE) torna a micela menos coesa, facilitando a acomodação de solutos e favorecendo também a penetração de moléculas de água de hidratação que formam pontes de hidrogênio com as unidades de OE. Isto é indicado pelas variações observadas nos coeficientes de B e V. As variações dos coeficientes de S respondem também ao tamanho da cadeia e ao grau de hidratação, o que foi verificado pelos espectros de bandas vibrônicas de fluorescência de pireno e por alterações de deslocamentos químicos de RMN-1H. Anomalias observadas para surfactante 15-S-5 provavelmente deveram-se à presença de isopropanol utilizado como aditivo para solubilizá-lo em meio aquoso. O conjunto de dados obtidos demonstra que o tamanho da cadeia de OE e da micela responde melhor ao modo do que à extensão de solubilização dos solutos analisados, uma vez que a variável KS não responde de maneira linear ao grau de etoxilação para o conjunto de detergentes estudados. / This study has characterized the solubilization of neutral solutes in micellar systems composed of nonionic surfactants belonging to the family of ethoxylated secondary alcohols with the same hydrophobic group and different degrees of ethoxylation ranging from 5 to 30 ethylene oxide units. Linear Solvation Energy Relationships (LSER) was used as a predictive model for the efficiency of incorporation of solutes. The multiple regression analysis and the validations presented were based on the micellar incorporation constant KS as the dependent variable and Abraham solute descriptors as the independent variables. The methodologies utilized to determine the KS values included photophysical techniques (fluorescence quenching), measurements of solubility at saturation (via UV-VIs spectrophotometry), micellar liquid chromatography and gas chromatography (Headspace analysis of the vapor phase above micellar solutions). This study provided the following LSERs: 15-S-5: Log KS = - 0,054 - 0,227A - 1,197B - 0,600S + 0,938E + 1,854V 15-S-7: Log KS = + 0,267 + 0,435A - 1,475B - 0,831S + 1,045E + 1,805V 15-S-15: Log KS = - 0,047 + 0,314A - 1,265B - 0,487S + 0,823E + 2,107V 15-S-30: Log KS = - 0,345 + 0,366A - 1,114B - 0,430S + 0,858E + 2,310V As typically observed for micellar systems, the partitioning of solutes between micellar aggregates and the aqueous phase is dominated by the properties of molar volume (V) and hydrogen bond basicity (B) of the solute, with secondary contributions from the dipolarity (S) and excess molar refraction (E) of the solute. The increase in the size of the hydrophilic oxyethylene (OE) headgroup decreases the cohesion of the micelle, facilitating the accommodation of solutes and also favoring the penetration of waters of hydration that hydrogen bond with the OE units. This is indicated by the changes observed in the coefficients of B and V. The changes observed for S also respond to the size of the OE chain, as reflected in the vibronic bands of the fluorescence spectra of pyrene and changes of proton chemical shifts in 1H-NMR spectra. Anomalies for the surfactant 15-S-5 were probably due to the necessity to include isopropanol as an additive to solubilize it in water. The data show that the OE chain and micelle sizes respond better to the mode than to the extent of solubilization for the solutes analyzed, since the predictor variable KS does not respond consistently to the degree of ethoxylation for the micellar systems studied.

Neste estudo foi caracterizado o processo de solubilização de solutos neutros em sistemas micelares compostos de surfactantes não iônicos da família de alcoóis secundários etoxilados com o mesmo grupo hidrofóbico e graus diferentes de etoxilação, variando de 5 a 30 subunidades de oxido de etileno. Para isso, foram utilizadas as Relações Lineares de Energias Livres de Solvatação (LSER) como modelo preditivo para a eficiência de incorporação de solutos. As análises de regressão múltipla e as validações apresentadas tiveram por base a constante de incorporação micelar KS como variável dependente e os descritores de soluto de Abraham como as variáveis independentes. A metodologia utilizada para a determinação de KS baseou-se em técnicas fotofísicas (supressão de fluorescência), medidas de solubilização (solubilização em saturação via espectrofotometria de UV-VIS) e técnicas de cromatografia líquida (Cromatografia Micelar) e gasosa (Cromatografia por Análise de Fase Vapor ou Headspace). A determinação realizada forneceu as seguintes LSERs: 15-S-5: Log KS = 0,054 - 0,227A - 1,197B - 0,600S + 0,938E + 1,854V 15-S-7: Log KS = + 0,267 + 0,435A - 1,475B - 0,831S + 1,045E + 1,805V 15-S-15: Log KS = -0,047 + 0,314A - 1,265B - 0,487S + 0,823E + 2,107V 15-S-30: Log KS = - 0,345 + 0,366A - 1,114B - 0,430S + 0,858E + 2,310V Como é típico para sistemas micelares, constatou-se que a partição dos solutos entre os agregados micelares e a fase aquosa é dominada pelas propriedades de volume molar (V) e capacidade receptora de pontes de hidrogênio ou basicidade (B) do soluto, com contribuições secundárias de dipolaridade (S) e refração molar em excesso (E) do soluto. O aumento do tamanho da cabeça hidrofílica de oligômeros de oxietileno (OE) torna a micela menos coesa, facilitando a acomodação de solutos e favorecendo também a penetração de moléculas de água de hidratação que formam pontes de hidrogênio com as unidades de OE. Isto é indicado pelas variações observadas nos coeficientes de B e V. As variações dos coeficientes de S respondem também ao tamanho da cadeia e ao grau de hidratação, o que foi verificado pelos espectros de bandas vibrônicas de fluorescência de pireno e por alterações de deslocamentos químicos de RMN-1H. Anomalias observadas para surfactante 15-S-5 provavelmente deveram-se à presença de isopropanol utilizado como aditivo para solubilizá-lo em meio aquoso. O conjunto de dados obtidos demonstra que o tamanho da cadeia de OE e da micela responde melhor ao modo do que à extensão de solubilização dos solutos analisados, uma vez que a variável KS não responde de maneira linear ao grau de etoxilação para o conjunto de detergentes estudados. / This study has characterized the solubilization of neutral solutes in micellar systems composed of nonionic surfactants belonging to the family of ethoxylated secondary alcohols with the same hydrophobic group and different degrees of ethoxylation ranging from 5 to 30 ethylene oxide units. Linear Solvation Energy Relationships (LSER) was used as a predictive model for the efficiency of incorporation of solutes. The multiple regression analysis and the validations presented were based on the micellar incorporation constant KS as the dependent variable and Abraham solute descriptors as the independent variables. The methodologies utilized to determine the KS values included photophysical techniques (fluorescence quenching), measurements of solubility at saturation (via UV-VIs spectrophotometry), micellar liquid chromatography and gas chromatography (Headspace analysis of the vapor phase above micellar solutions). This study provided the following LSERs: 15-S-5: Log KS = - 0,054 - 0,227A - 1,197B - 0,600S + 0,938E + 1,854V 15-S-7: Log KS = + 0,267 + 0,435A - 1,475B - 0,831S + 1,045E + 1,805V 15-S-15: Log KS = - 0,047 + 0,314A - 1,265B - 0,487S + 0,823E + 2,107V 15-S-30: Log KS = - 0,345 + 0,366A - 1,114B - 0,430S + 0,858E + 2,310V As typically observed for micellar systems, the partitioning of solutes between micellar aggregates and the aqueous phase is dominated by the properties of molar volume (V) and hydrogen bond basicity (B) of the solute, with secondary contributions from the dipolarity (S) and excess molar refraction (E) of the solute. The increase in the size of the hydrophilic oxyethylene (OE) headgroup decreases the cohesion of the micelle, facilitating the accommodation of solutes and also favoring the penetration of waters of hydration that hydrogen bond with the OE units. This is indicated by the changes observed in the coefficients of B and V. The changes observed for S also respond to the size of the OE chain, as reflected in the vibronic bands of the fluorescence spectra of pyrene and changes of proton chemical shifts in 1H-NMR spectra. Anomalies for the surfactant 15-S-5 were probably due to the necessity to include isopropanol as an additive to solubilize it in water. The data show that the OE chain and micelle sizes respond better to the mode than to the extent of solubilization for the solutes analyzed, since the predictor variable KS does not respond consistently to the degree of ethoxylation for the micellar systems studied.

Yes / A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions.

Yes / BACKGROUND: There is considerable interest in the blood–tissue distribution of agrochemicals, and a number of researchershave developed experimental methods for in vitro distribution. These methods involve the determination of saline–blood andsaline–tissue partitions; not only are they indirect, but they do not yield the required in vivo distribution.RESULTS: The authors set out equations for gas–tissue and blood–tissue distribution, for partition from water into skin andfor permeation from water through human skin. Together with Abraham descriptors for the agrochemicals, these equationscan be used to predict values for all of these processes. The present predictions compare favourably with experimental in vivoblood–tissue distribution where available. The predictions require no more than simple arithmetic.CONCLUSIONS: The present method represents a much easier and much more economic way of estimating blood–tissuepartitions than the method that uses saline–blood and saline–tissue partitions. It has the added advantages of yielding therequired in vivo partitions and being easily extended to the prediction of partition of agrochemicals from water into skin andpermeation from water through skin.

No / The aim of the present work is to evaluate the similarity between PDMS membranes and human skin in vitro in permeation study by linear free energy relationship (LFER) analyses. The values of the permeability coefficient log Kp (cm/s) under reliable experimental conditions were collected from the literature for a set of 94 compounds including both neutral and ionic species, which cover a broad range of structural diversity. The values of log Kp (cm/s) have been correlated with Abraham descriptors to yield an equation with R2 = 0.952 and SD = 0.38 log units. The established LFER model for log Kp (cm/s) across PDMS membranes showed no close analogy with that through human skin in vitro. A further critical analysis of the coefficients of the LFER models confirmed that the PDMS permeation system is a very poor model for human skin permeation.

Yes / We have used literature values for the solubility of vitamin K3 in organic solvents to obtain Abraham descriptorsfor vitamin K3. Although these descriptors themselves are not exceptional in any way, when combined withequations that we have already set out, they lead to the prediction of important properties of vitamin K3.These include the vapor pressure and heat of sublimation (necessary for the analysis of data on the concentrationof vitamin K3 in ambient air), and the partitions air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane, water-skin, as well as permeation from water through skin. Values of the partitions into biologicalphases are all quite large by comparison to those for organic compounds in general.