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1-octanol/water Distribution Coefficients (water + distribution_coefficient)
Selected AbstractsApplication of ALOGPS to predict 1-octanol/water distribution coefficients, logP, and logD, of AstraZeneca in-house databaseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2004Igor V. Tetko Abstract The ALOGPS 2.1 was developed to predict 1-octanol/water partition coefficients, logP, and aqueous solubility of neutral compounds. An exclusive feature of this program is its ability to incorporate new user-provided data by means of self-learning properties of Associative Neural Networks. Using this feature, it calculated a similar performance, RMSE,=,0.7 and mean average error 0.5, for 2569 neutral logP, and 8122 pH-dependent logD7.4, distribution coefficients from the AstraZeneca "in-house" database. The high performance of the program for the logD7.4 prediction looks surprising, because this property also depends on ionization constants pKa. Therefore, logD7.4 is considered to be more difficult to predict than its neutral analog. We explain and illustrate this result and, moreover, discuss a possible application of the approach to calculate other pharmacokinetic and biological activities of chemicals important for drug development. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:3103,3110, 2004 [source] Rapidly profiling blood,brain barrier penetration with liposome EKCELECTROPHORESIS, Issue 14 2007Yongjun Wang Abstract This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood,brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steady-state concentrations ratio of compounds in the brain and in the blood expressed as log,BB, log,kLEKC, log,kVEKC, and other lipophilic descriptors including octanol/water partition coefficient (Clog,P), octanol/water distribution coefficients (log,D7.4), and polar surface area (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log,BB were correlated with the above five lipophilic descriptors, and the results showed that log,kLEKC gave the better correlation coefficient (r2,=,0.811, p <0.0001) than those of log,D7.4, Clog,P, PSA, and log,kVEKC (r2,=,0.730, 0.672, 0.627, and 0.620, p <0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB. [source] Influence of soil pH on the sorption of ionizable chemicals: Modeling advancesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009Antonio Franco Abstract The soil,water distribution coefficient of ionizable chemicals (Kd) depends on the soil acidity, mainly because the pH governs speciation. Using pH-specific Kd values normalized to organic carbon (KOC) from the literature, a method was developed to estimate the KOC of monovalent organic acids and bases. The regression considers pH-dependent speciation and species-specific partition coefficients, calculated from the dissociation constant (pKa) and the octanol,water partition coefficient of the neutral molecule (log Pn). Probably because of the lower pH near the organic colloid,water interface, the optimal pH to model dissociation was lower than the bulk soil pH. The knowledge of the soil pH allows calculation of the fractions of neutral and ionic molecules in the system, thus improving the existing regression for acids. The same approach was not successful with bases, for which the impact of pH on the total sorption is contrasting. In fact, the shortcomings of the model assumptions affect the predictive power for acids and for bases differently. We evaluated accuracy and limitations of the regressions for their use in the environmental fate assessment of ionizable chemicals. [source] A thermodynamics-based estimation model for adsorption of organic compounds by carbonaceous materials in environmental sorbentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2003Paul C. M. van Noort Abstract A model was developed to estimate Langmuir affinities for adsorption of low-polarity organic compounds from either water or air by carbonaceous sorbents. Sorption enthalpies and entropies provided the basic information for the description of sorption affinities in terms of the entropy of melting and either solubility in water or vapor pressure. For m -xylene, polycyclic aromatic hydrocarbons (PAHs) and chlorobenzenes on 10 different sorbents, 80% of the measured sorption affinities fall within a factor of four of the model estimates. Equations for the limiting distribution coefficients in terms of either octanol,air (KOA) or octanol,water partition (Kow) coefficients were derived from regressions of calculated affinities combined with an estimated relation between experimental Langmuir sorption capacities and Kow. Estimated soot,water distribution coefficients were within a factor of three of measured data for polychlorobiphenyls (PCBs) and lower molecular weight PAHs on automotive soot samples and captured the dependence of PCB distribution coefficients on the extent of ortho substitution. For higher molecular weight PAHs, sorption was underestimated. For soot in sediment,water distribution coefficients of PAHs and PCBs, estimated values captured both the trend of measured data with Kow and the dependence on sorbate planarity. Tentative application to aerosol,air distribution explained the observed independence of distribution coefficient,KOA relations for PCBs on the extent of ortho substitution and suggested nonequilibrium conditions for PAHs in comparison with recent measurements. [source] | ||||||||||