Hydrophilic Carotenoids: Carotenoid Aggregates - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 43

However, it is obvious that bolaamphiphiles (molecules that have hydrophilic groups at both ends of
a hydrophobic hydrocarbon chain) such as crocin, 3.7 , Cardax, 3.19 , or the lysine compound, 3.20 ,
cannot form micelles; self-association of these molecules builds other edii ces. The morphology of
an aggregate can easily be predicted by determining the critical packing parameter ( cpp ), a number
obtained by dividing the volume of the hydrophobic part v L by the product of the length of the hydro-
phobic part l L and the molecular area a m , cpp ν L /l L a m (Israelachvilli et al. 1976). According to the

calculated value, spherical, cylindrical, and bilayer structure aggregates are probable. Whereas a m
is derived from experimental values, v L and l L have to be calculated from molecular models. It is,
however, difi cult to estimate l L , since a considerable part of the carotenoid chain is dragged into
water due to the weak hydrophilicity of double bonds. The lysophospholipid, 3.15 , with its C17:8
chain (ring and methyl groups exert no signii cant inl uence on

=

) corresponds to a lysophospholipid
with a C10:0 or C11:0 saturated chain (Foss et al. 2005a). The ccp concept was originally developed
for saturated carbon chains. (The hydrophobicity of unsaturation has no signii cance for the effec-
tive chain lengths of bolaamphiphiles (Foss et al. 2005c).)
The size of carotenoid aggregates have been determined by dynamic light scattering (DLS),
a noninvasive method (Santos and Castanho 1996). DLS also allows distinguishing between spheri-
cal or cylindrical aggregates. The hydrodynamic radii r H of hydrophilic carotenoids in water are
given in Table 3.1. Size and molecular structure of the bolaamphiphiles crocin, 3.7 , and Cardax,
3.19 , indicate nonspherical aggregates. The aggregates of the dianionic Cardax, 3.19 —in water
r H

γ

m—slightly decreased when dispersed in physiologically relevant sodium chloride (NaCl)
solutions, and then increased to r H

= 1.3 μ

= 3 μ m in 0.5 M NaCl, and to r H = 10 μ m in 2.0 M NaCl, Figure 3.5

(Foss et al. 2005c). The DLS-determined aggregate size of r H 110 nm for the lysine derivative,

3.20 , in pure water was coni rmed by transmission electron microscopy (TEM) examinations, but
the aggregates appeared sometimes globular, Figure 3.6, and sometimes rod-shaped. In contrast
to anionic Cardax, 3.19 , the aggregates of cationic lysine derivative 3.20 did not grow or shrink in
NaCl solutions (Nalum Naess et al. 2007).
The cholinester, 3.35 , formed aggregates in pure water with r H

=

250 nm; after adding NaCl solu-
tions of differing concentrations, the aggregates increased in size up to r H

=

= 900 nm. After stand-

ing 48 h, the aggregates had returned to their initial size r H = 250 nm. When a saturated aqueous

10

d

8

6

4

c

2

a

b

0

0.0 0.5 1.0 1.5 2.0

NaCl (M)

FIGURE 3.5 Cardax 3.19 forms nonspherical aggregates with an equivalent hydrodynamic radius
(a) r H = 1.3 mm (water), (b) r H = 1.2 mm (0.155 M NaCl) (believed to be due to osmotic shrinkage), (c) r H = 3 mm
(0.5 M NaCl), and (d) r H = 10 mm (2.0 M NaCl). (Reprinted from Foss, B.J. et al., Chem. Phys. Lipids ., 135,
157, 2005c. With permission.)