Chemistry Reference
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afforded three sets of distinctive CR profiles (Katz et al. 2006). One set of compounds
provided uniformly low CR values, independent of the small molecule concentration.
A second class of compounds afforded high CR values but only at high micromolar
or millimolar concentrations of the small molecule. The last set of molecules also
gave rise to high CR values but at low micromolar concentrations. Fluorescence,
DSC, and SAXS measurements of compound binding to the PDA vesicles was
carried out to determine the mechanism of action for these three compound
classes. The low CR values with the first set of compounds was attributed to the
weak membrane binding of these molecules. Compounds that resulted in high CR
values at high concentrations were molecules that insert into the phospholipid
bilayer but do not induce large structural lipid rearrangement (the trigger for a chro-
matic transition) until higher concentrations. Compounds that bind and aggregate at
the surface of the membrane bilayer induce perturbations in lipid packing at very
low concentrations, triggering the color change of the vesicle. As a result, we can
rapidly categorize a given molecule into one of the three compound classes by
measuring the CR at three different compound concentrations (Fig. 12.5).
The lipid-binding and perturbing activities of small molecules that facilitate drug
delivery through skin and cellular membranes, known as membrane permeation
enhancers, have been studied using PDA liposomes (Evrard et al. 2001; Valenta
et al. 2004). Some enhancers such as oleic acid exert their effects directly and
induce chromatic transitions when added to PDA/phospholipid vesicles. Other
enhancers such as the oligoethylene glycol Transcutol only give rise to a chromatic
transition when added to vesicles in the presence of a drug, suggesting a synergistic
mode of action. Addition of a-cyclodextrin, a cyclic oligosaccharide that forms
inclusion complexes with hydrophobic molecules, to PDA vesicles triggers chromatic
transitions (Kim, Lee, Lee, et al. 2005).
12.2.4. Cation and pH Sensors
Liposomes prepared from diacetylene hydrazide 7 undergo chromatic transitions in
response to pH changes (Jonas et al. 1999). Liposomes of 7, which form only in
Figure 12.5 Patterns generated upon addition of a membrane surface-binding molecule (I),
membrane penetrating compound (II), and a compound that does not interact with membranes
(III). Adapted from Katz et al. (2006). Copyright 2006 Springer. (See color insert.)
