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Literature solubilities have been used to obtain properties or descriptors of melatonin. These indicate the chemical nature of melatonin: it is dipolar and has moderate hydrogen bond acidity and hydrogen bond basicity. The descriptors can be combined with equations that we have previously constructed to estimate water–solvent partition coefficients and solubilities in a huge number of organic solvents. In the same way, a range of biological properties can be estimated. These include blood–tissue partitions, water–skin partition and permeability through skin. [ABSTRACT FROM AUTHOR]

We have used a variety of physicochemical systems, including water‐solvent partitions, solubility in non‐aqueous solvents, and HPLC and gas chromatographic retentions to obtain descriptors for nitro compounds and high energy compounds. These descriptors can then be used to predict a wide range of other physicochemical properties as well as thermodynamic and environmental properties. We illustrate the latter by predictions of the vapor pressure of sublimation, the enthalpy of sublimation and the heat capacity of sublimation at 298.15 K, and predictions of human skin permeability from water. With respect to the obtained descriptors, the most startling finding is that cyclic high energy compounds, with no 'active' hydrogen atom, have a substantial 'hydrogen bond' acidity. We suggest that this is due to electron‐deficient ring systems that act as Lewis acids. [ABSTRACT FROM AUTHOR]

[Display omitted] • Blood-to-tissue partition coefficients predicted for important pharmaceutical compounds. • Solute descriptors calculated for important pharmaceutical compounds. • Skin permeabilities predicted for important pharmaceutical compounds. Abraham model solute descriptors have been determined for nisoldipine, nizatidine, loratadine, zonisamide, oxaprozin, rebamipide, domperidone, temozolomide, 'florfenicol', florfenicol A, dapsone, chrysin, benorilate, β-lapachone, and Ipriflavone based on published partition coefficients, molar solubilities and gas chromatographic retention indices. The calculated solute descriptors, combined with our previously published Abraham model correlations, are used to predict several important physicochemical and biological properties, such as air–water, air-blood, air-lung, air-fat, air-skin, water–lipid, water-membrane and water-skin partition coefficients, as well as permeation from water through skin. [ABSTRACT FROM AUTHOR]

Experimental values of permeability coefficients, as log K p , of chemical compounds across human skin were collected by carefully screening the literature, and adjusted to 37 °C for the effect of temperature. The values of log K p for partially ionized acids and bases were separated into those for their neutral and ionic species, forming a total data set of 247 compounds and species (including 35 ionic species). The obtained log K p values have been regressed against Abraham solute descriptors to yield a correlation equation with R 2 = 0.866 and SD = 0.432 log units. The equation can provide valid predictions for log K p of neutral molecules, ions and ionic species, with predictive R 2 = 0.858 and predictive SD = 0.445 log units calculated by the leave-one-out statistics. The predicted log K p values for Na + and Et 4 N + are in good agreement with the observed values. We calculated the values of log K p of ketoprofen as a function of the pH of the donor solution, and found that log K p markedly varies only when ketoprofen is largely ionized. This explains why models that neglect ionization of permeants still yield reasonable statistical results. The effect of skin thickness on log K p was investigated by inclusion of two indicator variables, one for intermediate thickness skin and one for full thickness skin, into the above equation. The newly obtained equations were found to be statistically very close to the above equation. Therefore, the thickness of human skin used makes little difference to the experimental values of log K p . [ABSTRACT FROM AUTHOR]

Literature data on solubilities of adamantane in organic solvents have been used to obtain properties, or descriptors, of adamantane. There is much less data on substituted adamantanes but we have been able to obtain descriptors for some 40 substituted adamantanes. These descriptors can then be used to estimate a wide range of physicochemical, environmental and other properties of the adamantanes. For the first time, the water-solvent partition coefficient and the gas-solvent partition coefficient into a large range of solvents, can be estimated, the latter being equivalent to Henry's Law constants. A variety of other important properties can also be estimated. These include vapor pressures, enthalpies of vaporization and sublimation, partitions from air and from blood into biological tissues, and skin permeability from water. The descriptors themselves are not exceptional. Adamantane itself has a rather low dipolarity, zero hydrogen bond acidity and a very low hydrogen bond basicity, in common with other multicyclic aliphatic compounds. These lead to adamantane being a very hydrophobic compound, as is evident from our estimated water-octanol partition coefficient. Unlabelled Image • Descriptors determined for 40 substituted adamantanes. • Used to predict solubilities and partition coefficients. • Used to predict thermodynamic quantities. • Descriptors not unusual for multi-cyclic compounds. [ABSTRACT FROM AUTHOR]

The permeability, Kp, of some ionized solutes (including nine acids and nine bases) through human epidermis membrane was measured in this work. Combined with the experimental Kp data set for neutral species created by Abraham and Martins and reliable Kp data for ionic species from the literature, a linear free-energy relationship (LFER) analysis was conducted. The values of log Kp for 118 compounds have been correlated with solute descriptors to yield an LFER equation that incorporates neutral species and ionic species, with R2 = 0.861 and SD = 0.462 log units. The equation can be used to predict Kp for neutral species and ionic species, as well as partly ionized solutes. Predicted values for the passive permeation of the sodium ion and the tetraethylammonium ion are in good accord with the experimental values. It was observed that neutral acids and bases are more permeable than their ionized forms, and that the ratio depends on the actual structure. The correlation between human skin permeation and water-organic solvent/artificial membrane partitions was investigated by comparison of the coefficients in the LFER equations. Partition into cerasome is a reasonable model for partition into skin, and using cerasome as a surrogate for the partitioning process, we separate permeation into partition and diffusion processes. We show that the poor permeability of ionic species is largely due to slow diffusion through the stratum corneum. This is especially marked for a number of protonated base cations. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2034-2044, 2012 [ABSTRACT FROM AUTHOR]

The retention factors of neutral, positively charged, and negatively charged solutes were determined in a liposome electrokinetic chromatography (EKC) system, where cerasome was used as the investigated liposome. The Abraham linear free energy relationship (LFER) for neutral and ionized solutes gave a good account of the retention factors ( N = 71, R = 0.814, and SD = 0.29 log units). It was shown that the calculated retention factors for 16 neutral acids were about four times higher than those of the corresponding anions, whereas the calculated retention factors for neutral bases were less than those for the corresponding cations by a factor of 0.36. The LFER equation for neutral species, anions, and cations was compared with those for partition from water into a number of solvents and for n-octanol-water distribution coefficients. It was shown that the cerasome EKC system is substantially different to the other systems and consequently it could be a very useful additional model system, possibly for predicting skin permeation. It was further shown that there are considerable advantages in the use of Abraham LFERs that can encompass not only neutral molecules but also ionic species. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3105-3113, 2011 [ABSTRACT FROM AUTHOR]