Transport in Quantitative Structure-activity Relationships VI: Relationship Between Transport Rate Constants and Partition Coefficients

Waterbeemd, H. Van De; Bakel, Paul Van; Jansen, A. C. A.

doi:10.1002/jps.2600700930

Cited by 31 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it is rather difficult to relate these trends to specific interactions. Interphase transport rates may limit antioxidant activity as po- larity decreases (34). Castle and Perkins (35) suggested that this effect determines the low activity of the lipophilic α-tocopherol in SDS-linoleic acid mixed micelles.…”

Section: Resultsmentioning

confidence: 99%

The influence of various emulsifiers on the partitioning and antioxidant activity of hydroxybenzoic acids and their derivatives in oil‐in‐water emulsions

Stöckmann

Schwarz

Huynh-Ba

2000

J Americ Oil Chem Soc

109

108

View full text Add to dashboard Cite

The partitioning behavior of a series of hydroxybenzoic acids and their derivatives was determined in biphasic water-oil systems, emulsifier solutions, and oil-in-water (O/W) emulsions. The effect of gradually decreasing polarity on partitioning behavior and antioxidant efficiency in O/W emulsions was investigated by using gallic acid and its esters as antioxidants. Sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), polyoxyethylene 20 cetyl ether (Brij 58), and partially hydrolyzed soybean lecithin (PHLC, Emultop ® ) were used to investigate the influence of different classes of emulsifiers on the partitioning behavior. The antioxidant activity of gallic acid and its methyl, ethyl, propyl, butyl, and octyl esters showed markedly different trends in O/W emulsions depending on the emulsifier used. The results are discussed with respect to the properties of the emulsifiers, such as hydrogen bond basicity, hydrophobic interactions, and structural properties.

show abstract

Section: Resultsmentioning

confidence: 99%

The influence of various emulsifiers on the partitioning and antioxidant activity of hydroxybenzoic acids and their derivatives in oil‐in‐water emulsions

Stöckmann

Schwarz

Huynh-Ba

2000

J Americ Oil Chem Soc

109

108

View full text Add to dashboard Cite

show abstract

“…The fits to experimental data are usually excellent, explaining more than 95% of the variance in the data. 70 They hold for compounds of different structures, for ionizable molecules and ion pairs, 71 and even when measured at different pH values if the distribution coefficients are used. 63 For these reasons, eqs 4 are frequently used in simulations of drug transport in a series of aqueous and nonpolar phases.…”

Section: Resultsmentioning

confidence: 99%

Structural Determinants of Drug Partitioning in n-Hexadecane/Water System

Natesan

Wang

Lukáčová

et al. 2013

J. Chem. Inf. Model.

View full text Add to dashboard Cite

Surrogate phases have been widely used as correlates for modeling transport and partitioning of drugs in biological systems, taking advantage of chemical similarity between the surrogate and the phospholipid bilayer as the elementary unit of biological phases, which is responsible for most of transport and partitioning. Solvation in strata of the phospholipid bilayer is an important drug characteristics because it affects the rates of absorption and distribution, as well as the interactions with the membrane proteins having the binding sites located inside the bilayer. The bilayer core can be emulated by n-hexadecane (C16), and the headgroup stratum is often considered a hydrophilic phase because of the high water content. Therefore, we tested the hypothesis that the C16/water partition coefficients (P) can predict the bilayer locations of drugs and other small molecules better than other surrogate systems. Altogether 514 PC16/W values for nonionizable (458) and completely ionized (56) compounds were collected from the literature or measured, when necessary. With the intent to create a fragment-based prediction system, the PC16/W values were factorized into the fragment solvation parameters (f) and correction factors based on the ClogP fragmentation scheme. A script for the PC16/W prediction using the ClogP output is provided. To further expand the prediction system and reveal solvation differences, the fC16/W values were correlated with their more widely available counterparts for the 1-octanol/water system (O/W) using solvatochromic parameters. The analysis for 50 compounds with known bilayer location shows that the available and predicted PC16/W and PO/W values alone or the PC16/O values representing their ratio do not satisfactorily predict the preference for drug accumulation in bilayer strata. These observations indicate that the headgroups stratum, albeit well hydrated, does not have solvation characteristics similar to water and is also poorly described by the O/W partition characteristics.

show abstract

“…[13] In order to calculate the concentration of free benzoic acid in the aqueous phase, Eqs. [2], [3], and [9] need to be solved simultaneously to give…”

Section: Partitioning Of Benzoic Acid Between the Oil And Aqueous Phasesmentioning

confidence: 99%

“…Brossard et al (11) reported also the importance of the viscosity of the phases on the volatility of aroma compounds. A fundamental study of the interfacial transport requires that such measurements be made in stirred macroscopic two-phase systems in order to be able to extract from the kinetic data the rate of transport across the interface as well as that through the interfacial layer (12)(13)(14)(15). Such results enable determination of the rate-limiting step of the transfer.…”

Section: Introductionmentioning

confidence: 99%