Choline carboxylate surfactants: biocompatible and highly soluble in ...

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Choline carboxylate surfactants: biocompatible and highly soluble in water†
Regina Klein, Didier Touraud and Werner Kunz*
Received 29th November 2007, Accepted 7th February 2008
First published as an Advance Article on the web 19th February 2008
DOI: 10.1039/b718466b
With choline as a beneficial counterion of biological origin,
long-chain carboxylates become water soluble at room
temperature.
Introduction
Soaps have been known for over 2000 years. The oldest and most
common surfactants are sodium or potassium carboxylates due
to their simple preparation by neutralization of fatty acids with
the respective hydroxides. 1 Nonetheless, these surfactants are
restricted in their applicability by their limited solubility in water.
The criterion for a surfactant’s solubility is its Krafft point or
Krafft temperature. It is the temperature at which the solubility
of a surfactant equals the critical micellization concentration
(cmc) and subsequently rises sharply. 2 Furthermore, it is commonly
accepted to define the Krafft point of an ionic amphiphile
as the clearing temperature of a 1 wt% surfactant solution, since
the cmc is generally far below 1 wt%. 2
While the Krafft point is still about 25 ◦ C in the case
of sodium laurate (NaC12), it is already about 45 ◦ C for
sodium myristate (NaC14) or even about 60 ◦ C for sodium
palmitate (NaC16). 3–5 In the same manner as the Krafft point
rises systematically with growing length of the hydrophobic
chain, the surface activity of an amphiphile, its washing ability
and its solubilising power increase. 6 In 1972, Shinoda et al.
pointed out that the type of the counterion markedly affects
the Krafft point of a surfactant. 7 Accordingly, Yu et al. found,
in 1990, that a substitution of sodium in alkyl sulfates by
tetrabutylammonium (TBA) considerably reduces the Krafft
point, e.g. from 50 ◦ Ctobelow23 ◦ C in the case of octadecyl
sulfate. 8 Furthermore, Jansson et al. showed that replacing
sodium in NaC12 by tetraalkylammonium (TAA) ions can
lower the Krafft temperature (T Kr)tobelow0 ◦ C. 9 This general
behavior was confirmed by Zana et al. who found, for example,
that TBA stearate (C18) is soluble down to 0 ◦ C, while sodium
stearate (NaC18) has a Krafft point of 71 ◦ C. 5,10
Obviously, substitution of the alkali counterions in soaps by
quaternary ammonium ions results in a significantly increased
solubility. However, this substitution simultaneously renders the
systems toxicologically questionable, since simple TAA ions are
potentially harmful. For instance, TAA cations act as phase
Institute of Physical and Theoretical Chemistry, University of
Regensburg, 93040, Regensburg, Germany.
E-mail: Werner.Kunz@chemie.uni-regensburg.de; Fax: +49 941 943 45
32; Tel: +49 941 943 40 44
† Electronic supplementary information (ESI) available: Information
regarding the synthesis, 1 H- and 13 C-NMR, ES-MS and conductivity
data of ChCm, TMACm and KCm with m = 12–18. See DOI:
10.1039/b718466b
transfer catalysts and as such they can transport ions across
biological membranes. 11,12 Additionally, they can block cellular
ion channels even at very low concentrations (500 lM ofTBA
induces a blocking of the cardiac sodium channel), whereby the
blocking efficiency increases with the length of the alkyl side
chains. 13–16
A way to benefit from the tendency of quaternary ammonium
ions as counterions to reduce the Krafft points of soaps
and to avoid their toxicological influence at the same time
is to use a quaternary ammonium ion of biological origin,
such as choline. Choline chemically refers to the cation (2hydroxyethyl)trimethylammnonium
(see Fig. 1).
Fig. 1 Molecular structure of the choline cation.
Choline, formerly known as vitamin B 4, is present in most
foods. 17,18 In 1998, it was classified as an essential nutrient for
humans. 19 Choline is essential for several biological functions of
the human body. For instance, it serves as a precursor for phospholipids,
the constituents of biological membranes. 17 Furthermore,
it is a precursor for the neurotransmitter acetylcholine. 20
Moreover, its derivative betaine provides a source of methyl
groups for protein synthesis and transmethylation reactions. 21
Apparently, the hydroxy group of choline, in contrast to
the simple TAA ions, ensures the physiological degradability.
For example, it was found that for rat glioma cells, choline
chloride is the least toxic amine, 5.5 times less toxic than
tetramethylammonium (TMA) chloride and more than 500
hundred times less toxic than TBA chloride. 22 Due to the
hydroxy group, choline can, for instance, be esterified to give
acetylcholine and phospatidylcholine. Furthermore, choline can
also be environmentally decomposed by microorganisms. 23
Choline carboxylates have already been described in the literature
as ingredients of certain formulations, comprising, for example,
cosmetic products or cryoprotectant agents for plants. 24,25
However, there is no physicochemical characterization of these
species published to date. In this communication, we report
on the Krafft points and the critical micellar concentrations of
choline salts of fatty acids, ranging from dodecanoic acid (C12)
to octadecanoic acid (C18). Furthermore, we relate these values
to the cmc’s and Krafft points of the corresponding sodium,
potassium and TMA carboxylates. The whole phase diagrams
of these choline surfactants, established by SAXS and SANS
measurements, will be presented in a forthcoming publication.
This journal is © The Royal Society of Chemistry 2008 Green Chem., 2008, 10, 433–435 | 433

Experimental data about synthesis, analysis and characterisation
of choline carboxylates (ChCm), potassium carboxylates
(KCm) and TMA carboxylates (TMACm) with m = 12–18 can
be found in the ESI.†
Results and discussion
Critical micellization concentration (cmc)
In Table 1, the values of the cmc’s for the investigated choline
surfactants are compared with those of the related sodium
and potassium carboxylates. Apparently, the cmc’s of choline
carboxylates are in the same order of magnitude as those of
the alkali soaps. Moreover, the cmc of ChC12 coincides nearly
exactly with that of TMAC12 (cmc = 25 mM), 9 indicating that
the hydroxy group of choline does not influence noticeably the
micelle formation.
Furthermore, the cmc of ChCm decreases linearly by a factor
of 4 per addition of two CH 2 groups. This feature, typical
for ionic amphiphiles, can be illustrated by eqn (1), where the
logarithm of the cmc is a linear function of the alkyl chain length
n C. 28
log cmc = An C + B (1)
For mono-ionic surfactants, the constant A typically adopts
the value 0.3, 29 which is in good agreement with that found for
the investigated surfactants (0.29). The parameter B (1.9) is a
constant for a particular ionic head at a given temperature and
corresponds well to that found in the literature for potassium
carboxylates (1.9). 29
From the values of the cmc’s, it can be deduced that choline
carboxylates at low concentrations generally act in the same
manner as the alkali carboxylates in aqueous solutions. Since,
for instance, the sodium salts are completely dissociated in dilute
solution, 26 thecholinesaltscanalsobeassumedtorevealno
association of the carboxylic headgroup with the counterion
choline. In contrast, the TAA salts of sulfates exhibit a precmc
ion-pairing. 30 Accordingly, the cmc values of TAA sulfates
(e.g. cmc (TMA dodecyl sulfate) = 5.53 mM) are reduced in
comparison to the corresponding alkali sulfates (e.g. cmc (Na
dodecyl sulfate) = 8.32 mM). 30
Nonetheless, the most outstanding property of these choline
salts is the fact that they are capable of forming micelles at
room temperature even with palmitic acid (C16)—in contrast
to the homologous alkali soaps, which are restricted in their
solubility. As a consequence of the potential use of longer-chain
surfactants, a relatively high surface tension reduction down to
about 25 mN m −1 for ChC16 can be obtained. 31
Table 1 Comparison of the cmc’s [mM] of choline, sodium and
potassium carboxylates at 25 ◦ C
Choline Sodium Potassium
C12 25.5 24.4 a 25.5 b
C14 6.4 6.9 a 6.6 b
C16 1.8 — —
a From ref. 26. b From ref. 27.
Krafft point
The Krafft point of a surfactant is the result of the interplay
between two competing thermodynamic forces. One is the
free energy of the solid crystalline state and the other is the
free energy of the micellar solution. A strong head group
interaction and a good packing in a crystal lattice contribute
to the crystal’s stability, which is associated with a low free
energy. Consequently, the Krafft point is elevated. In turn, a
low free energy of the micellar solution, promoted by e.g. the
hydrophilicity of a compound, favours the solubilised state.
However, the energetic state of the micellar solution varies only
slightly when changing the counterion, whereas the free energy
of the crystalline state may change considerably from system to
system. 32 Hence, the latter contribution can be considered as the
main driving force in determining the solubilisation temperature.
In Fig. 2, the Krafft temperatures for ChCm,TMACm,KCm
and NaCm with m = 12–18 are shown. The values, which
we determined for the potassium carboxylates are generally in
good agreement with those found by McBain et al. 33 and are
in all cases 14–15 ◦ C lower than those of the corresponding
sodium salts. Concerning the TMA carboxylates, only one value
of T Kr has been reported so far to our knowledge, namely
for TMAC12 (

ions and can be continued by the implementation of TAA ions. 33
As pointed out above, the micellar state of the ChCm surfactants
does not differ a lot from the NaCm and KCm soaps. Thus, the
reason for the pronounced T Kr reduction of choline carboxylates
with respect to the alkali soaps must be a high free energy of the
crystalline state of ChCm. Taking into account the almost equal
T Kr values of ChCm and TMACm, the alcohol group of choline
seems to have no noticeable influence, as observed similarly for
the micellization process. Very probably, it is mainly the size of
the bulky quaternary ammonium headgroup of choline which
hinders the regular packing in a crystal lattice, rendering the solid
crystalline state energetically less favourable. Consequently, the
Krafft point decreases.
Conclusion
Choline carboxylate surfactants have been found to combine
the characteristics of common alkali carboxylates in the low
concentration regime with a substantially increased solubility.
Accordingly, ChCm surfactants can be used at ambient temperature
up to m = 16. Additionally, the investigated choline salts
are produced by a straightforward synthesis with little or no
heat requirement. Moreover, choline can be decomposed both in
the environment and in the human body. Consequently, choline
soaps, consisting exclusively of biogenic material occurring in the
human body, are physiologically and environmentally harmless,
and as such convenient for e.g. drug delivery systems.
Notes and references
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This journal is © The Royal Society of Chemistry 2008 Green Chem., 2008, 10, 433–435 | 435