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Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. stefan.balaz@ndsu.edu

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Dimyristoylphosphatidylcholine bilayer/water532,538 versus 1-octanol/water partition coefficients(544)P for (●) nonpolar compounds, (▲) phenols, (△) alcohols, (▼) anilines, and (★) polar compounds with no hydrogen-bond donor group. Lines represent linear fits to the data for (—) nonpolar compounds, (- - -) phenols and alcohols, and (· · ·) polar compounds without hydrogen-bond donor ability. More details are given in the text.
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fig5: Dimyristoylphosphatidylcholine bilayer/water532,538 versus 1-octanol/water partition coefficients(544)P for (●) nonpolar compounds, (▲) phenols, (△) alcohols, (▼) anilines, and (★) polar compounds with no hydrogen-bond donor group. Lines represent linear fits to the data for (—) nonpolar compounds, (- - -) phenols and alcohols, and (· · ·) polar compounds without hydrogen-bond donor ability. More details are given in the text.

Mentions: The correlations of the partition coefficients of chemicals in liposomes and in the 1-octanol/water system become nonlinear for large molecules, presumably because of the energy needed to create a cavity(535) in the structured bilayer subregions 2 and 3 (section ). The correlations displayed separate trends for neutral, negatively charged, and positively charged molecules, with the last category exhibiting the largest scatter.(536) The relationships broke down even for a homologous series exhibiting different preferred bilayer locales for individual members.(537) If more-diverse chemicals were considered, the relationship seemed to hold, with a broader scatter and within certain size and lipophilicity limits,535,538 for neutral molecules(539) but not for charged molecules.342,540 The differences are more significant for acids, as opposed to bases, because the former show more-pronounced pH dependences of the bilayer/water partition coefficients (PB/W) than the latter. This phenomenon is caused by the interactions with the headgroups of neutral and acidic phospholipids, which lead to a rearrangement in the headgroups.541,542 The former profiles are still rather shallow in comparison with those for the 1-octanol/water partition coefficients (PO/W). The differences of the PB/W values for different pH of the aqueous phases are dependent on the ionization character of the chemical: they are comparatively small for bases and can reach a magnitude100-fold larger for acids.(543) The PO/W values of both acids and bases can differ by 3−4 orders of magnitudes in the systems with differing pH values of the aqueous phase. A careful comparison of the data measured above the gel-to-liquid transition temperature with the experimental or calculated PO/W values(544) showed that, even for neutral chemicals, different lines can be discerned for polar compounds with or without hydrogen-bond donor ability(538) and nonpolar compounds,(532) as shown in Figure 5. On the bilogarithmic scale, the lines have the slopes of 0.63 for nonpolar compounds, 0.82 for polar compounds without hydrogen-bond donor groups, and 1.27 for the group consisting of hydrogen-bond donors and acceptors (phenols and alcohols). However, the entire dataset exhibits a reasonable linear relationship with the squared correlation coefficient r2 = 0.950, as noticed previously.(539)


Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

Dimyristoylphosphatidylcholine bilayer/water532,538 versus 1-octanol/water partition coefficients(544)P for (●) nonpolar compounds, (▲) phenols, (△) alcohols, (▼) anilines, and (★) polar compounds with no hydrogen-bond donor group. Lines represent linear fits to the data for (—) nonpolar compounds, (- - -) phenols and alcohols, and (· · ·) polar compounds without hydrogen-bond donor ability. More details are given in the text.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2682929&req=5

fig5: Dimyristoylphosphatidylcholine bilayer/water532,538 versus 1-octanol/water partition coefficients(544)P for (●) nonpolar compounds, (▲) phenols, (△) alcohols, (▼) anilines, and (★) polar compounds with no hydrogen-bond donor group. Lines represent linear fits to the data for (—) nonpolar compounds, (- - -) phenols and alcohols, and (· · ·) polar compounds without hydrogen-bond donor ability. More details are given in the text.
Mentions: The correlations of the partition coefficients of chemicals in liposomes and in the 1-octanol/water system become nonlinear for large molecules, presumably because of the energy needed to create a cavity(535) in the structured bilayer subregions 2 and 3 (section ). The correlations displayed separate trends for neutral, negatively charged, and positively charged molecules, with the last category exhibiting the largest scatter.(536) The relationships broke down even for a homologous series exhibiting different preferred bilayer locales for individual members.(537) If more-diverse chemicals were considered, the relationship seemed to hold, with a broader scatter and within certain size and lipophilicity limits,535,538 for neutral molecules(539) but not for charged molecules.342,540 The differences are more significant for acids, as opposed to bases, because the former show more-pronounced pH dependences of the bilayer/water partition coefficients (PB/W) than the latter. This phenomenon is caused by the interactions with the headgroups of neutral and acidic phospholipids, which lead to a rearrangement in the headgroups.541,542 The former profiles are still rather shallow in comparison with those for the 1-octanol/water partition coefficients (PO/W). The differences of the PB/W values for different pH of the aqueous phases are dependent on the ionization character of the chemical: they are comparatively small for bases and can reach a magnitude100-fold larger for acids.(543) The PO/W values of both acids and bases can differ by 3−4 orders of magnitudes in the systems with differing pH values of the aqueous phase. A careful comparison of the data measured above the gel-to-liquid transition temperature with the experimental or calculated PO/W values(544) showed that, even for neutral chemicals, different lines can be discerned for polar compounds with or without hydrogen-bond donor ability(538) and nonpolar compounds,(532) as shown in Figure 5. On the bilogarithmic scale, the lines have the slopes of 0.63 for nonpolar compounds, 0.82 for polar compounds without hydrogen-bond donor groups, and 1.27 for the group consisting of hydrogen-bond donors and acceptors (phenols and alcohols). However, the entire dataset exhibits a reasonable linear relationship with the squared correlation coefficient r2 = 0.950, as noticed previously.(539)

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. stefan.balaz@ndsu.edu

Show MeSH
Related in: MedlinePlus