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Updated: Jun 18, 2026
10:28
Probing the Structure and Dynamics of Interfacial Water with Scanning Tunneling Microscopy and Spectroscopy
Published on: May 27, 2018
The unstirrable water layer is unstirrable because it does not exist
1BIOpKa, 3416 Ebba Street, White Bear Lake, Minnesota 55110, USA. rascherrer@biopka.com
Chemistry & Biodiversity
|November 26, 2009
Summary
The unstirred water layer (UWL) model for membrane permeation is challenged. A new hypothesis explains apparent pKa shifts without UWL, proposing a transition state for absorption within the membrane.
Area of Science:
- Membrane transport phenomena
- Physicochemical hydrodynamics
- Drug delivery systems
Background:
- Unstirred water layers (UWL) are often invoked in membrane permeation models, particularly in PAMPA assays.
- Apparent shifts in pKa (pKa(flux)) are observed for lipophilic acids and bases, attributed to UWL acting as a diffusion barrier.
- Existing models struggle to explain these pKa shifts under conditions favoring unionized species.
Purpose of the Study:
- To propose an alternative explanation for the observed pKa(flux) phenomenon that does not rely on the unstirred water layer (UWL).
- To introduce the concept of a transition state for absorption within the membrane to explain pKa shifts.
- To provide a testable hypothesis for the pKa(flux) term in membrane permeation.
Main Methods:
- Theoretical modeling of ionizable compound behavior during membrane passage.
- Analysis of free energy changes during absorption into the membrane.
- Conceptual framework development based on transition state theory.
Main Results:
- The pKa(flux) can be explained by a change in the compound's pKa as it enters the membrane.
- A transition state for absorption is proposed, occurring at maximum free energy within the membrane.
- This transition state pKa directly corresponds to the observed pKa(flux), eliminating the need for UWL.
Conclusions:
- The unstirred water layer (UWL) is not required to explain apparent pKa shifts in membrane permeation.
- The pKa of an ionizable compound changes during membrane transit, with the transition state pKa defining the pKa(flux).
- This new model offers a testable alternative for understanding absorption and permeation rate limitations.
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