Synthesis and characterization of nonconventional surfactants of aromatic amino acid-glycerol ethers: Effect of the amino acid moiety on the orientation and surface properties of these soap-type amphiphiles

Article abstract of DOI:10.1002/chem.200501529

The synthesis, characterization, and surface properties of soaptype amphiphiles comprising alkyl chains of 10-16 carbon atoms linked through an ether group to a glycerolamino acid hydrophilic head group is described. The surface properties of members of this series derived from histidine and tyrosine were compared with those of phenylalanine and tryptophan derivatives described previously and with those of conventional soaps. In all cases, the amino acid derivatives showed superior surface properties, and an interesting differentiation was discovered regarding the orientation of tryptophan derivatives.

Full text of DOI:10.1002/chem.200501529

FULL PAPER
DOI: 10.1002/chem.200501529
Synthesis and Characterization of Nonconventional Surfactants of Aromatic
Amino Acid–Glycerol Ethers: Effect of the Amino Acid Moiety on the
Orientation and Surface Properties of These Soap-Type Amphiphiles
[
a]
[a]
[b]
Evdoxia-Maria A. Varka, Maria G. Heli, Evdoxia Coutouli-Argyropoulou, and
[
a]
Sofia A. Pegiadou*
Abstract: The synthesis, characteriza-
tion, and surface properties of soap-
type amphiphiles comprising alkyl
chains of 10–16 carbon atoms linked
through an ether group to a glycerol–
amino acid hydrophilic head group is
described. The surface properties of
members of this series derived from
histidine and tyrosine were compared
with those of phenylalanine and trypto-
phan derivatives described previously
and with those of conventional soaps.
In all cases, the amino acid derivatives
showed superior surface properties,
and an interesting differentiation was
discovered regarding the orientation of
tryptophan derivatives.
Keywords: amphiphiles · aromatic
amino acids · surface chemistry ·
surfactants · synthesis
Introduction
possess enhanced surface properties and solubility and have,
therefore, been proposed as alternatives to the classic soaps.
As such alternatives, the two nonconventional, homolo-
gous series of carboxylic-acid salts from the aromatic amino
acid tryptophan and phenylalanine conjugated to glycerol
through an amide bond were recently synthesized, charac-
Recently, the nonconventional, ecofriendly surfactants have
become of great importance in applications, such as deter-
gency, emulsification, and wetting, as well as in other per-
[1,2]
sonal care formulations.
The classic soap is still consid-
[9,10a]
ered absolutely ecological as it possesses better biodegrada-
bility and is milder to the skin than the commercial surfac-
terized, and studied.
In these compounds the hydropho-
bic alkyl chain is conjugated to glycerol through an ether
bond, giving an advantage over the hydrolysable ester bond
[2b–f]
tants derived from petrochemicals.
However, the fatty
[11,12]
acid salts, namely soaps, have drawbacks, such as poor sur-
face-active properties, low solubility in neutral cold water,
and formation of insoluble calcium salts in hard water.
of glycerol esters.
Although these surfactants are soap-
type sodium salts, due to the carboxylic group of the amino
acid, they possess very low critical micelle concentrations
(CMC) and low corresponding surface tensions (gcmc), com-
[3]
Nevertheless, the above surfactants are very suitable for the
study of the orientation of amphiphiles at interfaces as well
as for the aggregation and micellar formation in solutions of
[3,9a]
pared to conventional soaps.
They also gave very promis-
ing results upon application as wetting agents in the mercer-
ization of cotton, as cleansing agents, and as emulsifiers in
oil/water emulsions. This encouraged us to continue the syn-
thesis of analogous surfactants with the remaining two aro-
matic amino acids, that is, histidine and tyrosine, thus, com-
pleting the whole family. Moreover, the amino acids are
[
4–7]
different pH ranges.
Moreover, soap-type surfactants in-
[8]
cluding a moiety, such as a peptide linkage or a 1,3-dioxo-
lane ring , in addition to the hydrophilic carboxylic group,
[3]
[
a] E.-M. A. Varka, M. G. Heli, Prof. S. A. Pegiadou
Laboratory of Organic Chemical Technology
Chemistry Department, Aristotle University of Thessaloniki
4 124, Thessaloniki (Greece)
Fax : (+30)231-099-7769
[13]
generally key intermediates in enzymic redox reactions.
The tryptophan itself plays an important role in the study of
2
+
5
structural changes of proteins and as a sensor for Ca
ions.
[13]
Thus, we expect that the aromatic amino acids as
E-mail: sopegiad@chem.auth.gr
moieties of amphipilic molecules could facilitate these stud-
ies in aqueous solutions.
[
b] E. Coutouli-Argyropoulou
Laboratory of Organic Chemistry
Chemistry Department, Aristotle University of Thessaloniki
5
4 124, Thessaloniki (Greece)
Chem. Eur. J. 2006, 12, 8305 –8311
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8305

Results and Discussion
presence of sodium cations in the reaction medium is ex-
pected to affect further the stability of the conformers, be-
cause of the well-documented interaction of aromatic side
chains of amino acids as neutral donor groups for alkali
Synthesis and characterization: The new homologous series,
derivatives of histidine and tyrosine with 10, 12, 14, or 16
carbon atoms in the hydrophobic alkyl chain, namely
HisGE and TyrGE, were synthesized in good yields (63–
2%) according to Scheme 1.
The starting compounds, chlorides 1, synthesized by reac-
[17–21]
metal cations.
In conformation III, cooperation of the
aryl group with the dominant carboxylate-anion donor to
sodium binding is expected to cause a further stabilization.
By combining steric factors and binding-metal interactions,
conformer III is expected to be
7
the most favorable. In this con-
formation, the amino group is
less hindered and is more reac-
tive towards a primary halide,
such as 1, in an S 2-type substi-
N
tution-reaction process.
The IR spectra for all com-
pounds 4-HisGE and 4-TyrGE
show absorptions in the region
ꢀ
1
3
400–3244 cm due to OH and
NH stretching vibration, as in
the series of TrpGE and PhGE
[9,10]
Scheme 1. Synthesis of the aromatic amino acid–glycerol ether surfactants.
derivatives.
Furthermore,
absorption peaks at 1580 and
ꢀ
1
1
610 cm suggest the existence
ꢀ
+
tion of epichlorohydrin with the corresponding fatty alco-
hols, reacted as alkylating agents with the amino acids 2 to
give, after acidification of the initially obtained sodium salts
of carboxylate anion (COO ) and alkylamine ( NH R) as a
2
zwitterion.
1
The H NMR spectra are in accordance with the proposed
3
, the target amphiphiles 4 in satisfactory yields. Direct se-
structures and contain the expected chemical shifts for both
the alkyloxypropanol and amino acid moieties. Due to the
restricted solubility of the compounds, the spectra were re-
corded in alkaline methanol, thus, the labile protons (OH,
NH, COOH) do not appear in the spectrum. The histidine
derivatives (HisGE) exhibit two singlets at d=6.83 and
7.51–7.53 ppm for the imidazole protons, whereas the tyro-
sine derivatives (TyrGE) exhibit two doublets at d=6.54–
6.62 and 6.92–7.01 ppm for the aromatic-ring protons. The
aliphatic-chain protons give the expected peaks in the
region 0.89–1.55 ppm. The protons attached to the heteroa-
toms and the methylene protons next to the aromatic ring
give a series of complex and broad multiplets in the region
2.45–3.85 ppm. Due to the complexity and the broadening
of the multiplets, a complete assignment of these protons
was not possible in most cases. Indicatively for the TyrGE-
10 derivative, a more detailed assignment based on decou-
lective monoalkylation of amino acids and their esters is not
generally applicable and most alkylation methods referred
to in the literature deal mainly with N-methylation reac-
tions. For alkylations other than methylation, procedures via
intermediate-activated nitrophenylsulfonyl derivatives are
[14]
usually employed.
The relative reactivity of 1 towards
amino acids may be ascribed partially to the neighboring-
group assistance of the hydroxyl group. Participation of the
hydroxyl group has been invoked for the ease of quarteniza-
[15,16]
tion of secondary amines with epichlorohydrin.
Howev-
er, attempted alkylation reactions of 1 with a series of
amino acids missing an aromatic moiety, such as alanine,
glutamine, isoleucine, arginine, proline, and valine, failed to
give any product, indicating that structural features of the
amino acid also affect the course of the reaction.
The observed differences in reactivities between aromatic
and nonaromatic amino acids can be explained by examin-
ing the conformations around the bond connecting the
chiral carbon and the methylene carbon. As depicted in
Figure 1, on the basis of stereochemical reasons only, the
less-hindered conformations II and III are expected to be
the most stable. In the case of aromatic amino acids, the
pling experiments carried out on a sample taken in D O/
2
KOH solution was possible. Thus, the methylene protons
next to the nitrogen give a multiplet at d=2.45–2.70 ppm,
the methylene protons next to the aromatic ring give a mul-
tiplet at d=2.75–2.85 ppm, the methine proton next to the
carboxyl gives an almost-triplet at d=3.26 ppm, the methyl-
ene protons next to oxygen give a multiplet at d=3.35–
3
.36 ppm, and the methine proton next to oxygen is the
most deshielded and gives a symmetric multiplet centered at
1
3
d=3.88 ppm. The C NMR spectra are clearer. All the car-
bons give characteristic chemical shifts close to the expected
values, as assigned in the experimental part. Notably, some
of the carbons give two peaks (values separated by slashes
Figure 1. Conformations of aromatic amino acids around the C
a
ꢀC
b
bond.
8306
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Chem. Eur. J. 2006, 12, 8305 –8311

Surfactants of Aromatic Amino Acid–Glycerol Ethers
FULL PAPER
ꢀ
ꢁ
in the experimental part) corresponding to the two possible
diastereoisomeric structures. Because compounds 3 were ob-
tained from the reaction of a racemic chloride with the l-
amino acid, they must be mixtures of two diastereoisomers
1
@g
Gmax ¼ ꢀ
ð1Þ
2:303nRT @logc
2
3
1
0
Amin
¼
NGmax
ð2Þ
(
dl and ll).
in which (@g/@logc) is the maximum slope in each case; T=
absolute temperature; n=1 (in a 1:1 ionic surfactant in the
presence of a 1:1 electrolyte ), R=8.31 Jmol K , and N
Surface-active properties of surfactants 4: All compounds 4
are insoluble in aqueous solution between pH 4–10. Conse-
quently, the surface-active study of these compounds was
undertaken in alkaline solution at pH 12 and it is assumed
that at this pH surfactants 4 behave as carboxylates 3, that
is, as anionic surfactants.
[10b]
ꢀ1 ꢀ1
is Avogadroꢁs number.
The CMC values of compounds 4-HisGE and 4-TyrGE
show a fairly linear decrease as the number of methylene
groups in the alkyl chain is reduced. This is expected from
the increase in hydrophobicity, evident in Figure 4, that is
Figures 2 and 3 show plots of the surface tension (g)
versus log of surfactant concentration for all surfactant ho-
Figure 4. Relationship between logCMC (critical micelle concentration)
Figure 2. Surface tension versus logc of compounds 4-HisGEs in aqueous
and the alkyl-chain length of the 4-HisGEs (
) and 4-TyrGEs (^).
&
solutions at pH 12. ^: R = C10
H H25, ”: R = C14H , : R
21, ~: R = C12
&
29
=
16 33
C H .
[
9a,10a]
common to analogous compounds
and that is observed
[10d]
usually in homologous series of conventional
as well as
[10a,d]
nonconventional surfactants.
As in a conventional series of homologues, the efficiency
of absorption, pc , increases as the number of carbon atoms
2
0
increases. The larger the pc20 value, the more efficiently the
surfactant is absorbed at the interface and the more effi-
ciently it reduces surface tension. This increase is fairly
linear, as seen in Figure 5 for surfactants 4-HisGEs and 4-
[9a,10a]
TyrGEs, as it occurs in other carboxyl systems.
Figure 3. Surface tension versus logc of compounds 4-TyrGEs in aqueous
solutions at pH 12. ^: R = C10
: R = C14 29, ”: R
H
21, ~: R = C12
H
25
,
&
H
=
16 33
C H .
mologues 4-HisGE and 4-TyrGE, derivatives of histidine
and tyrosine, respectively. The absence of a minimum in the
curves reflects the high purity of the new compounds. The
surface-active parameters, such as critical micelle concentra-
tion (CMC), surface tension corresponding to this concen-
tration (gCMC), and efficiency of absorption (pc ) were de-
20
termined from the curves of Figures 2 and 3. The values of
surface excess (Gmax) and area per molecule (Amin) were cal-
culated by using the Gibbs adsorption Equations (1) and
[
9a,10a,b]
(
2):
Figure 5. Plots of pc20 versus the number of carbon atoms in surfactants
-HisGEs (
) and 4-TyrGEs (^) (pc20 =log of surfactant concentration
required to reduce the surface tension of the solvent by 20 mNm ).
4
&
ꢀ
1
Chem. Eur. J. 2006, 12, 8305 –8311
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8307

S. A. Pegiadou et al.
All the physicochemical parameters of the new surfactants
HisGE and TyrGE, and for comparison, those of TrpGE
and PhGE synthesized previously, are listed in Table 1.
Area per molecule (Amin) and orientation of surfactants at
the air/water surface: Surprisingly, as evident from Table 1,
TrpGE derivatives have the lowest A values, in a range
min
2
2[3]
5
1–67 Š close to that of sodium laurate (69 Š ), whereas
all the derivatives of the three other amino acids have
higher Amin values in a range 80–118 Š . However, according
Table 1. Surface-active parameters for surfactants 4 of all four homolo-
gous series in aqueous solution at pH 12 and T=258C.
2
to the hydrophobicity of the new surfactants, it could be ex-
pected that the PhGEs should posses the lowest Amin values,
as they are more hydrophobic.
Because the area per molecule is mainly determined from
the cross-sectional area of the hydrophilic group at the inter-
face, these findings suggest that the cross-sectional area is
smaller in tryptophan derivatives. For the PhGE and TyrGE
derivatives, the orientation 1 in Figure 6 is suggested, in
Compound CMC
g
CMC
pc20
A
[Š ]
min
2
T
K
[8C]
5
ꢀ3
ꢀ1
[
”10 moldm
]
[mNm
]
R=C10
TrpGE
TyrGE
H
21
25
29
33
[
a]
36.00
10.00
4.80
33.00
40.00
32.30
42.20
4.70 67.00
5.30 91.90
6.15 97.00
5.20 100.00
50
52
50
54
[
b]
PhGE
HisGE
R=C12
TrpGE
TyrGE
5.80
H
[
a]
3.80
5.80
3.50
4.80
32.00
38.00
30.00
36.90
5.50 51.00
5.70 80.00
6.39 103.00
5.40 100.00
56
52
51
54
[
b]
PhGE
HisGE
R=C14
TrpGE
TyrGE
H
[
a]
2.00
3.80
1.00
4.31
30.50
34.00
28.75
32.50
6.10 64.00
6.20 106.00
7.00 103.00
6.00 104.50
52
53
52
55.5
[
b]
PhGE
HisGE
R=C16
TrpGE
TyrGE
PhGE
HisGE
H
[
a]
1.70
3.10
0.91
3.70
30.00
28.00
28.40
28.10
6.30 66.00
6.50 114.00
7.05 118.00
6.4 106.00
53
54.5
53
[
c]
56
[
a] Values from ref. [9a]. [b] Values from ref. [10a]. [c] Value from
ref. [10a], for the member with R=C15
31
H .
According to the molecular structure, the most hydropho-
bic surfactants were expected to be those of the PhGE
series. This is evident from the data in Table 1, which shows
that for the same alkyl chain, phenylalanine derivatives
have the lowest CMC and gcmc, and the highest pc20 values.
The new surfactants have much lower CMC values than
the typical soaps. Thus, in alkaline solution, the CMC of the
ꢀ
2
[3,9a]
sodium laurate is approximately 2”10 m,
whereas the
ꢀ
5
CMCs of all the compounds studied are of the order 10 m.
These values are also much lower than sodium salts of N-
[8a]
acylamino acids.
This behavior is probably due to the
presence of the aromatic moiety of the amino acids, which
increases significantly the hydrophobicity of the new surfac-
tants and their ability to create micelles in the bulk solution
at very low concentrations. This is very effective in applica-
tions of detergency and wetting. The gcmc of the members
with 12 carbon atoms in the hydrophobic alkyl chain ranges
[3]
Figure 6. Orientation of surfactants PhGE (1) and TrpGE (2) at the air/
water surface.
ꢀ
1
ꢀ1
between 30 and 38 mNm ; the lowest value (30 mNm ) is
that of the most hydrophobic PhGE derivative, and the
which all hydrophilic centers are in contact with the aqueous
layer. In contrast, for TrpGE derivatives, the orientation 2 is
the most probable, in which the indole moiety is in contact
with the aqueous phase. Indole has been proved to be an ef-
fective polar head group for vesicle formation, and trypto-
phan residues are also known to work as membrane anchors
ꢀ1 [3]
value of the sodium laurate is 37.5 mNm . Similarly, the
Krafft point, known as the temperature at which the solubil-
ity is equal to the CMC and can be regarded as the tempera-
ture at which micelles become soluble,
0 and 568C for all members of the four homologous series.
These values are higher than the value 198C for the above-
mentioned soap under the same conditions, in accordance
with the higher hydrophobicity and consequently lower solu-
bility of the studied compounds.
[3,10b]
ranges between
5
[22–25]
in proteins.
[3]
Concerning the HisGE members, orientiations like those
of TrpGE members would be adopted, in which the imida-
zole ring, similarly to indole, is in conduct with water
8308
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Chem. Eur. J. 2006, 12, 8305 –8311

Surfactants of Aromatic Amino Acid–Glycerol Ethers
FULL PAPER
through one of its nitrogen atoms (Figure 6, example 2).
However, Amin values of HisGE are closer to those of PhGE
and TyrGE, indicative of orientations similar to those of
PhGE and TyrGE (Figure 6, example 1) Moreover, to the
best of our knowledge, imidazole derivatives do not exhibit
behavior analogous to that of indole and tryptophan at
water/air interfaces.
many); chloroform and hexane by Merck (Darmstadt, Germany); histi-
dine, tyrosine, glutamic acid, alanine, glutamine, isoleucine, arginine, pro-
line, valine, and glutaminic acid by Panreac PRS (Barcelona, Spain), and
silica gel plates by Riedel de Häen.
Thin layer chromatography was employed to monitor the progress of all
the reactions by using butanol/acetic acid/ethanol/water 4:2:3:3 as eluent.
Compounds 1 were visualized by spraying the TLC plates with a solution
of 20% sulfuric acid in methanol, followed by charring on a hot plate for
a few minutes. For surfactants 4, a ninhydrin solution (3 g ninhydrin dis-
solved in a mixture of 3 mL acetic acid and 97 mL butanol) was applied
until it turned violet.
Conclusion
A Perkin–Elmer 2004 II analyzer was used for all elemental analyses. IR
spectra were recorded by using a Perkin–Elmer FTIR (Spectrum One)
1
The synthesis of glycerol ether–amino acid surfactants con-
taining the aromatic amino acids tryptophan, phenylalanine,
tyrosine, and histidine was completed easily in a two-step
procedure with very good yields. The ability to apply this
simple synthetic procedure for aromatic amino acids, in con-
trast to aliphatic amino acids that failed to give analogous
derivatives, was attributed to the complexation of the amino
acid aromatic moiety with alkali ions, which stabilized favor-
able conformations for substitution reactions.
spectrophotometer. H NMR spectra were recorded at 300 MHz and
1
3
C NMR spectra were recorded at 75.5 MHz, both by using a Bruker 300
AM spectrometer in (CD OD/NaOH) solutions. Chemical shifts are re-
3
ported in parts per million (d, in ppm) downfield from tetramethylsilane.
All melting points were determined by using a hot-stage Koffler appara-
tus and were uncorrected.
Synthetic procedures
General procedure for the synthesis of 3-alkyloxy-1-chloropropan-2-ols 1:
In a round-bottomed flask, aliphatic alcohol (0.01 mmol), epichlorohy-
drin (0.01 mmol), and concentrated sulfuric acid (0.1 mL) were stirred
under reflux in dried toluene for 2 h. The reaction was monitored by
TLC. The reaction mixture was evaporated under vacuum and purified
by performing silica gel column chromatography (Chromagel 60 A CC,
The new amphiphiles could be characterized as environ-
mentally friendly as they possess, on one hand, the glycerol
skeleton and an aromatic amino acid, both existing in natu-
ral products available from renewable sources, and on the
other hand, a biodegradable linear alkyl chain. Given the bi-
ocompatibility of the above surfactants, they are promising
candidates for several food, cosmetic, and pharmaceutical
applications, especially in conditions of extreme pH and
temperature, due to their stable ether bond compared with
the hydrolysable ester bond of glycerol esters. Furthermore,
by incorporating the amino acids in a micellar environment
they could serve as model compounds for theoretical investi-
gations of proteins and peptides in aqueous solutions.
Initial studies of their surface behavior revealed very
good surface properties. Thus, the critical micelle concentra-
tions and surface tensions of all members of the four homol-
ogous series are significantly lower than the corresponding
values of the typical soaps. These findings enhance further
the expected applicabilities of these novel compounds in the
above-mentioned areas. Another very interesting result was
that the values of area per molecule of surfactant for deriva-
tives of tryptophan were significantly lower that those for
derivatives of the amino acids phenylalanine, tyrosine, and
histidine. A suggestion was made that the more condensed
packing of tryptophan derivatives at the water/air surface is
due to a different orientation of these molecules, whereby
the indole functions as a polar head group with the NH di-
rected toward the water face, in agreement with the known
peculiar role of tryptophan residues in stabilizing membrane
proteins.
7
0–230 mesh) using an eluent of hexane/chloroform!chloroform (3:1!
100% CHCl ). Pure compounds 1 were obtained as oily liquids in yields
of 40–45%. Their elemental analyses and H NMR spectra are described
3
1
[
9a,10a]
elsewhere.
General procedure for the synthesis of N-[3-(alkyloxy)-2-hydroxypropyl]
amino acids 4: A solution of absolute methanol containing 1 and amino
acid (ratio, 1:1.5 mmol) and sodium hydroxide (0.5 g, pH 12) was stirred
under reflux for 5–6 h. The reaction was monitored on a TLC plate
sprayed with ninhydrin solution. The solution was then adjusted with
1
0% HCl to pH 3 for tyrosine and pH 4–5 for histidine. These were the
most appropriate conditions so that the final compounds could be pre-
cipitated as white solids without being contaminated by the unreacted
amino acid. The solids were filtered, washed three to four times with dis-
tilled water, solubilized in alkaline methanol, and reprecipitated with
10% HCl at the exact pH. The final products were obtained analytically
pure as white solids.
Under the same conditions, the reactions with the aliphatic amino acids
alanine, glutamine, isoleucine, arginine, proline, and valine failed to give
any products.
N-[3-(Decyloxy)-2-hydroxypropyl]tyrosine (TyrGE-10): M.p. 187–1888C;
1
yield 66%; H NMR (CD
3
OD/KOH): d=0.89 (t, J=7.1 Hz, 3H; CH
3
),
1.29 (m, 14H; (CH ) CH ), 1.52 (m, 2H; CH
2
7
3
2
ACHTREUNG
(CH ) CH ), 2.45–3.84 (m,
2
7
3
10H; CH
2 2 2 2
OCH , CH NH, CHOH, NHCHCOOH, CH Ar), 6.62 (d, J=
1
3
7
.6 Hz, 2H; Ar-H), 7.01 ppm (d, J=7.6 Hz, 2H; Ar-H); C NMR
(
CD
3
OD/KOH): d=14.4 (CH
CH ), 40.3 (CH Ar), 52.3/52.4 (CH
OCH CHOH, NHCHCOOH), 119.7/119.8,
124.8/124.9, 131.0/131.1 and 166.6 (C-Ar), 182.0/182.41 ppm (COOH); IR
3
), 23.7, 27.2, 30.4, 30.5, 30.6, 30.7 and 33.0
(
(CH
2
)
8
3
2
2
NH), 67.4/67.7, 70.4/70.7, 71.9/
7
2.6 and 74.7/74.9 (CH
2
2
,
ꢀ
ꢀ1
(KBr): n˜ max =3400–3244 (HO and NH), 1580 (COO ), 1610 cm (NH);
elemental analysis calcd (%) for C22 ·2H O: C 61.25, H 9.51, N
.25; found: C 61.40, H 9.50, N 3.20.
N-[3-(Dodecyloxy)-2-hydroxypropyl]tyrosine (TyrGE-12): M.p. 185–
H
37NO
5
2
3
1
1
868C; yield 70%; H NMR (CD
CH ), 1.29 (m, 18H; (CH CH ), 1.55 (m, 2H; CH
.75 (m, 10H; CH OCH , CH NH, CHOH, NHCHCOOH, CH
d, J=7.3 Hz, 2H; Ar-H), 6.92 ppm (d, J=7.3 Hz, 2H; Ar-H); C NMR
CD OD/KOH): d=14.4 (CH ), 23.7, 24.4, 27.0, 27.2, 30.4, 30.5, 30.6, 30.7
), 40.3 (CH Ar), 52.3/52.4 (CH NH), 67.4/67.7, 70.4/
70.7, 71.8/72.6 and 74.7/74.9 (CH OCH , CHOH, NHCHCOOH), 119.8/
3
OD/KOH): d=0.89 (t, J=7.1 Hz, 3H;
(CH CH ), 2.56–
Ar), 6.54
3
2
)
9
3
2
A
H
E
N
2
)
9
3
3
(
(
2
2
2
2
1
3
Experimental Section
3
3
and 33.1 ((CH
2
)
10CH
3
2
2
Materials and methods: Pure epichlorohydrin, aliphatic alcohols with 10,
2
2
1
2, 14, or 16 carbon atoms, pure toluene, sulfuric acid, absolute methanol,
119.9, 124.8/124.9, 131.1/131.2 and 166.9 (C-Ar), 182.1/182.5 ppm
(COOH); IR (KBr): n˜ max =3400–3244 (HO and NH), 1580 (COO ),
ꢀ
and butanol (for analysis) were supplied by Riedel de Häen (Salze, Ger-
Chem. Eur. J. 2006, 12, 8305 –8311
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8309

S. A. Pegiadou et al.
ꢀ
1
ꢀ6
1
9
610 cm (NH); elemental analysis calcd (%) for C24
.69, N 3.30; found: C 68.18, H 9.74, N 3.23.
H
41NO
5
: C 68.08, H
(10 m), an aging time of 30 min was used, whereas for the most concen-
ꢀ
3
trated solutions (10 m), the time was 15 min. The surface tension of de-
ionized water at pH 12 was found to be 74 mNm at 258C.
ꢀ1
N-[2-Hydroxy-3-(tetradecyloxy)propyl]tyrosine (TyrGE-14): M.p. 180–
1
1
818C; yield 63%; H NMR (CD
CH ), 1.29 (m, 22H; (CH ), 1.54 (m, 2H; CH
.85 (m, 10H; CH OCH , CH NH, CHOH, NHCHCOOH, CH
d, J=7.9 Hz, 2H; Ar-H), 6.99 ppm (d, J=7.9 Hz, 2H; Ar-H); C NMR
CD OD/KOH): d=14.4 (CH ), 23.7, 27.1, 30.4, 30.5, 30.6, 30.7, 30.8 and
3.0 ((CH ), 40.2 (CH Ar), 52.2/52.4 (CH NH), 67.3/67.7, 70.4/70.6,
2.6 and 74.6/74.8 (CH OCH CHOH, NHCHCOOH), 119.6/119.7,
3
OD/KOH): d=0.89 (t, J=7.1 Hz, 3H;
(CH ), 2.52–
Ar), 6.56
Krafft point measurements: The Krafft point was measured by preparing
1 wt% of each surfactant in alkaline water (pH 12) and observing with
the naked eye the temperature at which the solution became clear.
3
2
)
11CH
3
2
A
H
R
U
G
2
)11CH
3
[
3]
3
(
(
3
7
1
(
1
6
2
2
2
2
1
3
3
3
2
)
12CH
3
2
2
2
2
,
24.9/125.0, 131.0/131.1 and 166.28/166.33 (C-Ar), 182.0/182.3 ppm
ꢀ
COOH); IR (KBr): n˜ max =3400–3244 (HO and NH), 1580 (COO ),
Acknowledgements
ꢀ
1
610 cm (NH); elemental analysis calcd (%) for C26
4.06, H 10.13, N 2.87; found: C 64.14, H 10.08, N 3.00.
5 2
H45NO ·2H O: C
This work was supported by the Ministry of Science and Technology of
Greece (EPEAEK Iraklitos).
N-[3-(Hexadecyloxy)-2-hydroxypropyl]tyrosine (TyrGE-16): M.p. 184–
858C; yield 65%; IR (KBr): n˜ max =3400–3244 (HO and NH), 1580
1
(
C
2
ꢀ
ꢀ1
COO ), 1610 cm
·2H O: C 65.24, H 10.29, N 2.71; found: C 65.50, H 10.31, N
(NH); elemental analysis calcd (%) for
28
H
49NO
5
2
[1] a) M. R. Infante, A. Pinazo, J. Seguer, Colloids Surf. A 1997, 123–
124, 49–70; b) P. Clapes, M. R. Infante, Biocatal. Biotransform.
2002, 20, 215–233; c) M. C. Moran, A. Pinazo, L. Perez, P. Clapes,
M. Angeles, M. T. Garcia, M. P. Vinardell, M. R. Infante, Green
Chem. 2004, 6, 233–240.
[2] a) K. Holmberg, Novel Surfactants, Marcel Dekker, New York,
1998; b) L. Ho Tan Tai, Formulating Detergents and Personal Care
Products: A Complete Guide to Product Development, AOCS Press,
New York, 2000; c) A. T.-J. Goon, C.-L. Goh, Contact Dermatitis
2000, 43, 133–136; d) F. H. W. Jungbauer, P. van der Vleuten, J. W.
Groothoff, P. J. Coenraads, Contact Dermatitis 2004, 50, 245–251;
e) H. R. Smith, D. K. B. Armstrong, D. Holloway, L. Whittam, D. A.
Basketter, J. P. McFadden, Br. J. Dermatol. 2002, 146, 849–852;
f) Anionic Surfactants: Biochemistry, Toxicology, Dermatology
.66.
N-[3-(Decyloxy)-2-hydroxypropyl]histidine (HisGE-10): M.p. 170–1718C;
1
yield 70%; H NMR (CD
3
OD/KOH): d=0.89 (t, J=7.1 Hz, 3H; CH
), 1.52 (m, 2H; CH (CH CH ), 2.59–3.78 (m,
NH, CHOH, NHCHCOOH, CH Im), 6.83 (s, 1H;
), 23.7, 27.2,
Im), 52.4 (CH NH), 65.6,
, CHOH, NHCHCOOH), 121.1, 134.1 and
36.0 (C-Im), 181.5 ppm (COOH); IR (KBr): n˜ max =3400–3244 (HO and
3
),
1
1
.29 (m, 14H; (CH
2
)
7
CH
3
2
A
H
R
U
G
2
)
7
3
0H; CH OCH , CH
2
2
2
2
1
3
Im-H), 7.52 ppm (s, 1H; Im-H); C NMR: d=14.5 (CH
3
3
7
1
0.5, 30.6, 30.8, 31.7 and 33.1 ((CH
2
)
8
CH
3
, CH
2
2
0.7, 72.6 and 74.9 (CH OCH
2
2
ꢀ
ꢀ1
NH), 1580 (COO ), 1610 cm (NH); elemental analysis calcd (%) for
: C 61.79, H 9.49, N 11.38; found: C 61.87, H 9.55, N 11.12.
N-[3-(Dodecyloxy)-2-hydroxypropyl]histidine (HisGE-12): M.p. 173–
19 35 3 4
C H N O
1
1
1
1
748C; yield 68%; H NMR (CD
.28 (m, 18H; (CH CH ), 1.54 (m, 2H; CH
0H; CH OCH , CH NH, CHOH, NHCHCOOH, CH
2
3
OD/KOH): d=0.89 (m, 3H; CH
(CH CH ), 2.58–3.78 (m,
Im), 6.83 (s, 1H;
), 23.7, 27.2,
Im), 52.4 (CH NH),
5.6/65.7, 70.5/70.7, 72.6 and 74.6/74.9 (CH OCH CHOH,
3
),
(
Eds.: C. Gloxhuber, K. Kunstler), Marcel Dekker, New York, 1992.
2
)
9
3
2
A
H
E
N
2
)
9
3
[
[
[
3] D. Ono, A. Masuyama, Y. Nakatsuji, M. Okahara, S. Yamamara, T.
Takeda, J. Am. Oil Chem. Soc. 1993, 70, 29–36.
4] J. R. Kanicky, A. F. Poniatowski, N. R. Mehta, D. O. Shah, Langmuir
2
2
2
1
3
Im-H), 7.51 ppm (s, 1H; Im-H); C NMR: d=14.5 (CH
3
3
6
0.5, 30.6, 30.8, 31.6, 31.7 and 33.1 ((CH
2
)
10CH
3
, CH
2
2
2
000, 16, 172–177.
2
2
,
5] J. R. Kanicky, D. O. Shah, Langmuir 2003, 19, 2034–2038.
NHCHCOOH), 121.0, 134.1 and 136.0 (C-Im), 181.5 ppm (COOH); IR
KBr): n˜ max =3400–3244 (HO and NH), 1580 (COO ), 1610 cm (NH);
elemental analysis calcd (%) for C21
found: C 63.39, H 9.56, N 10.30.
ꢀ
ꢀ1
[6] V. B. Fainerman, D. Vollhardt, R. Johann, Langmuir 2000, 16, 7731–
736.
(
7
39 3 4
H N O : C 63.48, H 9.82, N 10.58;
[
[
7] J. T. Kunjappu, P. Somasundaran, Langmuir 1995, 11, 428–432.
8] a) A. George, N. Jain, A. Desai, P. Bahadur, Tenside Surfactants
Deterg. 1998, 35, 368–374; b) S. Miyagishi, N. Takeuchi, T. Asakawa,
M. Inoh, Colloids Surf. A 2002, 197, 125–132; c) E. L. Soo, A. B.
Salleh, M. Basri, R. N. Z. R. A. Rahman, K. Kamaruddin, J. Biosci.
Bioeng. 2003, 95, 361–367; d) M. R. Infante, L. Perez, A. Pinazo, P.
Clapes, M. C. Moran, M. Angelet, M. T. Garcia, M. P. Vinardell, C.
R. Chim. 2004, 7, 583–832.
N-[2-Hydroxyl-3-(tetradecyloxy)propyl]histidine (HisGE-14): M.p. 169–
1
1
(
1
78C; yield 72%; H NMR (CD
m, 22H; (CH ), 1.54 (m, 2H; CH
NH, CHOH, NHCHCOOH, CH
3
OD/KOH): d=0.89 (m, 3H; CH
(CH ), 2.50–3.79 (m,
Im), 6.83 (s, 1H;
), 23.7, 27.2,
Im), 52.3 (CH NH),
5.5/65.6, 70.4/70.7, 72.6 and 74.6/74.8 (CH OCH CHOH,
3
), 1.28
2
)
11CH
3
2
A
H
R
U
G
2 3
)11CH
0H; CH
2
OCH
2
, CH
2
2
1
3
Im-H), 7.53 ppm (s, 1H; Im-H); C NMR: d=14.5 (CH
3
3
6
0.4, 30.6, 30.7, 31.4, 31.5 and 33.0 ((CH
2
)
12CH
3
, CH
2
2
2
2
,
[
9] a) S. Pegiadou, L. Perez, M. R. Infante, J. Surfactants Deterg. 2000,
NHCHCOOH), 121.1, 133.8/133.9 and 135.7 (C-Im), 181.4/181.6 ppm
3
, 517–524; b) C. Delgado, M. D. Merchan, M. M. Velazquez, S. Pe-
giadou, L. Perez, M. R. Infante, Colloids Surf. A 2004, 233, 137–
44; c) M. M. Velazquez, F. Ortega, F. Monroy, R. G. Rubio, S. Pe-
giadou, L. Perez, M. R. Infante, J. Colloid Interface Sci. 2005, 283,
44–152; d) E. P. Kalogianni, E.-M. Varka, T. D. Karapantsios, S.
Pegiadou, Langmuir 2006, 22, 46–51.
ꢀ
(
1
COOH); IR (KBr): n˜ max =3400–3244 (HO and NH), 1580 (COO ),
ꢀ
1
43 3 4
610 cm (NH); elemental analysis calcd (%) for C23H N O : C 64.94,
1
H 10.12, N 9.88; found: C 65.00, H 10.10, N 9.76.
N-[3-(Hexadecyloxy)-2-hydroxypropyl]histidine (HisGE-16): M.p. 172–
1
1
1
738C; yield 70%; H NMR (CD
CH ), 1.27 (m, 26H; (CH ), 1.54 (m, 2H; CH
.85 (m, 10H; CH OCH , CH NH, CHOH, NHCHCOOH, CH
s, 1H; Im-H), 7.52 ppm (s, 1H; Im-H); C NMR: d=14.5 (CH
3
OD/KOH): d=0.89 (t, J=6.9 Hz, 3H;
(CH ), 2.59–
Im), 6.83
), 23.7,
NH), 65.7/
, CHOH, NHCHCOOH),
20.9, 134.2 and 136.4 (C-Im), 181.8 ppm (COOH); IR (KBr): n˜ max
3
2
)
13CH
3
2
A
H
R
U
G
2 3
)13CH
[
10] a) E. M. Varka, E. Coutouli-Argyropoulou, M. R. Infante, S. Pegia-
dou, J. Surfactants Deterg. 2004, 7, 409–414; b) M. J. Rosen, Surfac-
tants and Interfacial Phenomena, John Wiley, New York, 1978,
p. 58–59; c) D. G. Hall, G. J. T. Tiddy, Anionic Surfactants: Physical
Chemistry of Surfactant Action (Ed.: E. H. Lucassen-Reynders),
Marcel Dekker, New York, 1981, Vol. 11, pp. 55, 61ff.; d) M. R. In-
fante, L. Perez, A. Pinazo, Novel Surfactants (Ed.: K. Holmberg),
Marcel Dekker, New York, 1998, Vol. 74, p. 87.
3
(
2
6
1
3
2
2
2
2
1
3
3
7.2, 30.4, 30.6, 30.8, and 33.1 ((CH
2
)
14CH
3
, CH
2 2
Im), 52.4 (CH
5.8, 70.4/70.7, 72.6 and 74.6/74.8 (CH
2
OCH
2
=
ꢀ
ꢀ1
400–3244 (HO and NH), 1580 (COO ), 1610 cm (NH); elemental
: C 66.23, H 10.38, N 9.27; found: C
analysis calcd (%) for C25
6.33, H 10.53, N 9.50.
47 3 4
H N O
6
[
11] I. Blute, B. Kronberg, M. Svensson, R. Unelius, Tenside Surfactants
Deterg. 1998, 35, 207–212.
Surface tension measurements: Surface tension measurements at equili-
brium (g) were determined by using a KSV Sigma 70 (Helsinki, Finland)
tensiometer fitted with a Wilhelmy plate. All the solutions containing dif-
ferent concentrations of compounds 4 were prepared at pH 12 by using
deionized water and 1n sodium hydroxide and were stored in closed
glass bottles for 24 h before measurement. For the very dilute solutions
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b) K. Fukuda, O. Soderman, B. Lindman, K. Shinoda, Langmuir
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Sci. 1999, 220, 57–62; d) K. Urata, N. Takaishi, J. Surfactants Deterg.
1999, 2, 91–103.
8310
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 8305 –8311

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8311