Amphiphilic and cation-complexing compounds based on peptidoamines

Article abstract of DOI:10.1039/b006739n

The synthesis of different types of amphiphilic compounds containing peptidoamine groups leads to surfactants with original properties such as the ability to coordinate metal ions. Water soluble acylcarcinine and alkylamidocarnosine surfactants are compared and the preparation of a silyloxyalkylamidocarnosine is described. The latter can be copolymerised with tetraalkoxysilanes to yield amphipathic organo-mineral solids that are also good ligands for metal cations.

Full text of DOI:10.1039/b006739n

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Amphiphilic and cation-complexing compounds based on
peptidoamines
Faouzia Hamdoune,a Chaouki El Moujahid,a Ludwig Rodehuser,c Christine Gerardin,c
Bernard Henry,c Marie Jose Stebe,c Jacques Amos,c Mohamed Marraha,b
Abderrahman Asskalia and Claude Selve*c
a Departement de Genie Chimique, Faculte des Sciences et T echniques, Universite Abdelmalek
Assaadi, BP 416, T anger, Morocco
b Departement de Chimie, Faculte des Sciences, Universite Abdelmalek Assaadi, BP 2121,
T etouan, Morocco
c L aboratoire de Chimie Physique Organique et Collo•dale (CNRS UMR 7565), Faculte des
Sciences, Universite Henri Poincare-Nancy I, BP 239, 54506 V andoeuvre les Nancy
cedex, France. E-mail: claude.selve=lesoc.uhp-nancy.fr; Fax: ]33 3 83 91 25 32;
T el: ]33 3 83 91 23 60
Received (in Strasbourg, France) 1st August 2000, Accepted 22nd September 2000
First published as an Advance Article on the web 20th November 2000
The synthesis of di†erent types of amphiphilic compounds containing peptidoamine groups leads to surfactants
with original properties such as the ability to coordinate metal ions. Water soluble acylcarcinine and
alkylamidocarnosine surfactants are compared and the preparation of a silyloxyalkylamidocarnosine is described.
The latter can be copolymerised with tetraalkoxysilanes to yield amphipathic organo-mineral solids that are also
good ligands for metal cations.
We have been interested for some time in peptidoamines, a
generic term describing pseudo-oligopeptides. Amongst these,
Results and discussion
compounds comprising an imidazole group stemming from
histidine or histamine,1,2 such as carcinine3 and carnosine,4
are of special interest. When they are connected to a hydro-
phobic moiety the resulting compounds generally show
surfactant properties. We have indeed found that lipo-
oligopeptide-like structures are surface active;5 in the same
manner, a peptidoamine group may represent the hydrophilic
part in this type of molecule. Moreover, amphiphilic mol-
ecules of this type containing a pseudopeptide are likely
to complex metal cations6 and to have anti-oxidative
properties.7 These features are due to the presence of
Synthesis of acyl and perÑuoroacyl carcinines
Carcinine and its analogues 1È4 (Scheme 1) have been pre-
pared following classical methods that were modiÐed in order
to optimise the yields of the desired pseudopeptide derivatives.
The Ðrst synthesis of carcinine was described by Arnould and
Frentz.10 By using a methodology from the procedure indi-
cated in this article, we have been able to improve consider-
ably the yields of the preparation. Starting from Boc-b-alanine
and histamine, the coupling reaction is achieved by activation
with BOP [benzotriazol-1-yloxytris(dimethylamino)phospho-
nium hexaÑuorophosphate] in chloroform solution. The Boc
protecting group is then hydrolysed in situ by treatment with
hydrochloric acid in ether, leading to the solid product with
an overall yield of 85%. The same procedure has been used to
synthesise other pseudopeptide derivatives; in all these cases
yields are excellent.11 The coupling reaction with the hydro-
phobic moiety is carried out directly with the pseudopeptide
a
pseudopeptide moiety containing an imidazole ring.8
We have therefore synthesised surfactants incorporating
peptidoamines as polar headgroups as well as a hydrophobic
part.9
Depending on the properties of the products initially pro-
duced, we have modiÐed the structures in order to improve
their complexing and surfactant characteristics. Following this
procedure, two series of molecular surfactants, containing
either a perhydrogenated or a perÑuorinated alkyl chain as
the hydrophobic portion, have been prepared with the aim of
Ðnding the most appropriate structures for grafting onto a
solid support. The grafted silica, bearing a peptidoamine as
the hydrophilic group, constitutes a second type of amphi-
philic material.
For the preparation of the molecular surfactants, the alkyl
chains are introduced in the form of fatty acids or amines,
linked to the rest of the molecule by an amide bond. The silica
compounds have been prepared starting from 3-(triethoxysilyl)
propylamine (TESPA) to which carnosine is linked by amidiÐ-
cation via the carboxyl group of its histidine moiety.
Scheme 1
DOI: 10.1039/b006739n
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1037
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2000

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Scheme 3
obtained. The fatty acids, both perhydrogenated and per-
Ñuorinated, are activated with BOP as the coupling agent
(Scheme 2).
The results of complexation studies on compounds 1, 2, and
3 (Table 1) with the Cu2` cation reveal a very low capacity of
these molecules to complex the divalent copper ion. It seems
as if these structures are less appropriate for the complexation
of metal cations as compared with free carcinine and its deriv-
atives, which have been proven to be good ligands for ions
Scheme 2
Table 1 Amphipathic compounds: acyl carcinines, alkylamido carnosines and silyloxyalkylamido carnosines
A
B
Yield (%)
CMC/104 mol L~1
1
2
3
4
5
6
7
8
9
C F CF2CHÈC(O)
H
H
H
H
61
74
65
73
84
80
81
67
68
79
56
7.5
77
6.8
È
95
È
72
9.2
È
5 11
C F CF2CHÈC(O)
7 15
H(CH ) ÈC(O)
2 9
H(CH ) ÈC(O)
2 11
H
C(O)ÈNHÈ(CH ) H
C(O)ÈNHÈ(CH )
2 8
H
H
H
H
H
H
H
2 10
C(O)ÈNHÈ(CH )
2 14
C(O)ÈNHÈC H C F
6 13
2 4
C(O)ÈNHÈC H C F
2
4
8 17
10
C(O)ÈNHÈ(CH ) SiOEt
2 3
3
Scheme 4
1038
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such as Zn2` or Cu2` in the studies of Henry et al.8 It has
been shown by these authors that the terminal amino group is
strongly implicated in the formation of the metal complexes.
Our Ðrst synthetic approach using the amino group to
create a link with the hydrophobic part via a peptide bond
thus leads to surfactants in which the electron-donor capacity
of the corresponding nitrogen atom is largely diminished due
to the carboxyl moiety in the vicinity. In order to preserve
their complexing ability it seems necessary therefore to keep a
free terminal amino group in the structure of the surface-
active molecules.
using ethanol as co-solvent and ammonia in a catalytic
amount.13 The ethanol, water, and ammonia are added simul-
taneously to the TEOSÈmonomer mixture to avoid any
premature reaction.
The copolymer precipitates several hours after mixing. The
solvents are slowly evaporated; after 5 days, a dry white solid
is obtained, which is washed thoroughly with dichloro-
methane and methanol. The product was analysed by 13C and
29Si solid state NMR.
The Boc protecting groups are removed from the polymeric
material by treatment with gaseous HCl. Removal from the
monomer implies the risk of premature uncontrolled polym-
erisation. The removal of the Boc groups is veriÐed by the
Synthesis of alkyl and perÑuoroalkylamido carnosines
disappearance of its characteristic absorption (l \ 1680
These considerations have led us to substitute carcinine for
carnosine in the molecular structure, thereby allowing us to
link the hydrophobic side-chain in the form of an alkyl amine
to a carboxyl group, thus leaving the terminal amino group
free for the complexation of cations. Hence the peptide part of
the molecule should have similar coordinating properties to a
pseudocarcinine (Scheme 1) and show comparable surfactant
characteristics.
CO
cm~1) in the IR spectrum of the product.
Coordination to copper(II) ions
In order to verify the ability of the amphiphilic compounds
described above to complex divalent metal cations, we have
added dilute (10~4 M) copper nitrate in 0.01 molar KNO to
3
solutions or, in the case of substituted silica, to suspensions of
The synthetic pathway to these derivatives starts from car-
nosine protected by a Boc moiety on the terminal amino
group; the coupling with the hydrophobic alkylamine is
achieved by activation with BOP (Scheme 3).
the amphiphiles and monitored the concentration of free
copper by means of an ion-selective electrode (ISE) at con-
stant pH. As shown in Fig. 1(a), in the presence of silica-
grafted carnosine, the electrode potential remains stable at a
The linkage of the hydrophobic chain via an amide bond in
the alkylamido carnosines should enhance the hydrophilic
character of these surfactants as compared to acyl carcinines
and increase their solubility in water without a†ecting their
coordinating ability. The experimental results conÐrm this
hypothesis. Indeed, the critical micellar concentrations (CMC)
of acyl carcinine with a comparable hydrophobic part (e.g.
compounds 1 or 2) are lower than those of the corresponding
alkylamido carnosines 8 or 9, respectively (Table 1).
As for the coordinating properties, measurements with the
copper(II) ion give evidence for the excellent ligand character-
istics of these molecules, which are comparable to those of
unsubstituted carcinine.
Synthesis of silyloxyalkylamido carnosine
These observations have led us to prepare an amphiphilic and
coordinating material based on the alkylamido carnosine
structure. By introducing a silyloxy group into the structure,
we were able to synthesise in a further step a supported
amphipathic coordinating material by solÈgel copolymer-
isation (Scheme 4).
The synthesis of the silyloxyalkylamido carnosines starts
with the preparation of
a monomer containing a tri-
alkoxysilane group. The monomer is obtained by amide
coupling between the amino group of 3-aminopropyl-
triethoxysilane (TESPA) and the carboxyl group of carnosine.
The amino groups of the latter (terminal and imidazole NH )
2
have to be protected by Boc substituents. In order to avoid
solvolysis of the triethoxysilane moiety during the synthesis,
which would lead to uncontrolled polymerisation, it is neces-
sary to preclude the introduction of water or alcohols, even in
trace amounts. We have therefore chosen isopropenyl chloro-
formiate as the coupling agent, yielding easily removable by-
products such as carbon dioxide and acetone during the
reaction. An excess of the agent itself can easily be evaporated
under reduced pressure. Hydrochloric acid generated during
the synthesis is trapped with N-methylmorpholine; the hydro-
chloride formed is removed by treatment with diethyl ether
(Scheme 4).
The monomers are obtained in good yields. They are subse-
quently polymerised following the so-called solÈgel pro-
Fig. 1 Ion-selective electrode measurements of copper(II) ion activity
in the presence of silica-bound carnosine (a), decanoylcarcinine 3 (b)
and decylamidocarnosine 6 (c) as a function of total copper concentra-
tion. T \ 25 ¡C, pH \ 6.
cedure,12 which consists of
a copolymerisation under
controlled conditions at ambient temperature in the presence
of a tetraalkoxysilane, in this case tetraethoxysilane (TEOS),
New J. Chem., 2000, 24, 1037È1042
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low value up to a total copper concentration of 20 lM. This
means that all added copper in this region is strongly bound
to the ligand until all coordination sites at the surface of the
silica are saturated with metal ions. Above this value, the
activity of free Cu2` ions increases with the total copper con-
centration.
The situation is quite di†erent in the presence of decylcar-
cinine [Fig. 1(b)]. The concentration of free Cu2` rises imme-
diately as the copper concentration is increased, giving
evidence for the very low coordinating capacity of this com-
pound in which the terminal amino group is engaged in an
amide bond. When this group is present, however, as in decyl
carnosine [Fig. 1(c)] the copper ions are bound in a similar
way as above.
recovered in the form of a white paste. The removal of the Boc
protecting group on the terminal amino group is achieved by
slowly adding 20 mL of a 1 N HCl solution in diethyl ether to
the crude product. The mixture is stirred at room temperature
for 2 h. The product obtained is washed with four 50 mL
portions of diethyl ether. The crude compound is extracted
with boiling ethyl acetate to yield a white powder after Ðl-
tration. It is recrystallised from methanolÈethyl acetate. Yield:
71% (white crystals). IR: l 3400È3250, l 1717, l
NH
CO
imidazole
1620 cm~1. NMR 1H (D O): d 2.67 (CH a, t, J \ 7), 2.97
2
2
(CH , t, J \ 6.65), 3.25 (CH b, t, J \ 7) 3.53 (NCH , t,
2im
2
2
J \ 6.65 Hz), 7.3 and 8.61 (2CH ).
im
Preparation of acyl carcinines 1È4. The appropriate alkyl
fatty acid (2.4 mmol) and 1 equiv. of BOP are added to a
solution of carcinine É 2HCl (0.6 g) in acetonitrile (25 mL) and
1 g of diisopropylethylamine or triethylamine. The mixture is
stirred at room temperature for 12 h. The precipitate is Ðltered
o† and washed with 10 mL of hot chloroform (3 times) and
with 5 mL of cold distilled water. The product is a white
Conclusion
A simple and efficient method for the synthesis of perhydroge-
nated or perÑuorinated lipo-peptidoamines, like carcinine or
carnosine, is reported. It gives access to two kinds of original
products: amphiphilic molecular compounds and an amphi-
philic material constituted of grafted silica, obtained by
copolymerisation of new carnosine silane derivatives. We are
presently examining whether this approach can be applied to
other oligopeptides.
powder, obtained in 61 to 74% yield (see Table 1). IR: l
NH
3400È3200, l 1720 l
1620 cm~1.
CO
imidazole
It has been shown that the capacity of amphiphilic com-
pounds based on peptidoamines to complex divalent tran-
sition metal ions and in particular copper(II) depends to a
large extent on the presence of free amino groups in their
structure. By choosing the appropriate peptidoamine (e.g. car-
nosine instead of carcinine) as the starting material for the
syntheses the coordinating capacity of the products could be
signiÐcantly enhanced. The immobilisation, in a second step,
of the ligands in a silica-like structure by controlled polym-
erisation of appropriate amphiphilic monomers has yielded
original organo-mineral compounds in which the affinity of
the peptidoamine groups for divalent cations is preserved.
Further studies on the coordination of these products to
copper and other cations are under way and will be published
later.
PerÑuorinated surfactants.14 1: (Z)-PerÑuoro-2H-oct-2-
enecarboxycarcinine É HCl, yield 0.8 g (61%) and 2: (Z)-
perÑuoro-2H-dec-2-enecarboxycarcinine É HCl, yield 1.17
g
(74%). IR: m 1660 cm~1; 1H NMR (CD OD): d 2.65
C/C
(CH a, t, J \ 7, 2.95 (CH , t, J \ 7, 3.30 (CH , t, J \ 7),
2im 2b
3.59 (NCH , t, J \ 7, 6.00 (CF2CH, d, J \ 31 Hz), 7.31
HvF
and 8.60 (2 CH ), 19F NMR (CD OD): d [82 (CF ,
im
d, J \ 10 Hz), [119 (CF C, m), [108 (CF, m), [127
FvF
to [123 [(CF) , m]. Elemental analysis for
3
2
2
3
3
2
2
n
(C N O Cl, MW \ 658) calc. (found):
18 15 16
(32.34); H 2.30 (2.19); N 8.50 (8.34); F 46.14 (45.98%).
H
F
C 32.82
4
2
Hydrogenated surfactants. 3: Decylcarboxycarcinine É HCl,
yield 0.6 g (65%) and 4: dodecylcarboxycarcinine É HCl, yield
0.7 g (73%). 1H NMR (CD OD): d 0.95 (CH , t, J \ 6.5), 1.17
3
3
[(CH ) , m)], 1.47 (CH , m), 2.17 [CH C(O), t, J \ 7.5], 2.67
2 n
(CH a, t, J \ 7), 2.97 (CH , t, J \ 7), 3.30 (CH , t, J \ 7),
2im 2b
2
2
Experimental
2
3.59 (NCH , t, J \ 7 Hz), 7.31 and 8.60 (2 CH ). Elemental
2
im
analysis for 3 (C
H
N O Cl, MW \ 372) calc. (found): C
Experimental protocols
18 33
4 2
57.97 (57.84); H 8.92 (8.59); N 15.02 (14.84%).
All solvents were reagent grade and used without further puri-
Ðcation. The progress of reactions and the purity of products
were evaluated on thin layer silica gel chromatographic (TLC)
Preparation of alkylamido carnosines 5–9. Preparation of
aminoalkyl histidines. One equivalent of the fatty amine
plates (Merck, Kieselgel 60 F ) with ethyl acetateÈhexane or
254
chloroformÈmethanol mixtures as eluents.
RNH , 1 equiv. of BOP, and 2 equiv. of triethylamine are
2
PuriÐcation was carried out by Ñash silica gel column chro-
matography with the same eluents. Melting points were deter-
mined with an electronic apparatus (Electrothermal) and have
not been corrected. The proton (1H) and Ñuorine (19F) NMR
spectra were recorded on Bruker AM 400 or AC 250 spectro-
meters. The chemical shifts, d, are reported downÐeld from
added to a solution of 3 mmol of Boc-His in acetonitrile (200
mL). The mixture is stirred at room temperature for 15 h. The
precipitate is Ðltered o† and washed three times with 10 mL of
acetonitrile. The crude product is dissolved in ethyl acetate
(120 mL), washed twice with 20 mL of a solution of 2 N HCl,
20 mL of brine and twice with 30 mL of a saturated solution
of sodium bicarbonate. The organic phase is dried over mag-
nesium sulfate and the solvent evaporated under reduced pres-
sure. The products are white powders with melting points:
internal tetramethylsilane (TMS) and CFCl , respectively.
3
The IR spectra were recorded on PerkinÈElmer 580D or 1600
FTIR spectrometers. The elemental analyses were carried out
at the Centre de Microanalyses du CNRS (Vernaison, France).
They agree with the proposed structures and illustrative
results are reported for some compounds.
Boc-His-NHC H
:
146 ¡C; Boc-His-NHC
H
; 151 ¡C;
8
17
10 21
Boc-His-NHC
H
:
158 ¡C;
Boc-His-NHC H C F
:
14 29
2 4 6 13
166 ¡C; Boc-His-NHC H C F : 171 ¡C.
2
4 8 17
Syntheses
Preparation of carcinine (b-alanyl-histamine). Boc-b-alanine
(10 mmol) is dissolved in chloroform (50 mL) and 3 equiv. of
diisopropylethylamine or triethylamine, 1 equiv. of histamine
(Ham) and 1 equiv. of BOP are added to the solution. The
mixture is stirred at room temperature for 12 h. The solvent is
evaporated under reduced pressure. The crude residue is
Boc removal. The mixture of Boc-His-NHR (2.5 mmol) in
THF (30 mL) is stirred at room temperature for 12 h with a
saturated solution of HCl in anhydrous ether (40 mL). The
solvents are evaporated under reduced pressure. The product
1040
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obtained is the dihydrochloride of His-NHR; it is used as such
for the coupling step with Boc-b-Ala.
s], 1.60 (CH , m), 1.65 [CH (BOC), s], 2.50 (CH a, m), 2.95
2b
3
2
(CH , dd, J \ 8 and 16), 3.15 (CH , dd, J \ 4.5 and 16),
2im 2im
Preparation of BOC-b-Ala-His-NHR. One equivalent of the
corresponding His-NH-R prepared above, 1 equiv. of BOP,
and 4 equiv. of triethylamine are added to a solution of 2
mmol of Boc-b-Ala in acetonitrile (150 mL). The mixture is
stirred at room temperature for 24 h. The precipitate is Ðltered
o† and washed three times with 10 mL of acetonitrile. The
crude product is dissolved in ethyl acetate (120 mL), washed
twice with 20 mL of a solution of 2 N HCl, 20 mL of brine
and twice with 30 mL of a saturated solution of sodium bicar-
bonate. The organic phase is dried over magnesium sulfate
and the solvent is evaporated under reduced pressure. The
products are white powders; they are used directly for the
synthesis of the corresponding aminoalkylamidocarnosine É
2HCl. The protecting groups are removed with a saturated
solution of HCl in a similar way as described above for Boc-
His-NHR. The aminoalkylamido carnosine dihydrochlorides
are obtained as white powders. General spectroscopic charac-
3.25 (CH b, m), 3.45 (CH , m), 3.85 (CH , q, J \ 9 Hz), 4.65
2
2c
2
(CH, m), 5.60 (NH, m), 7.10 (NH, m), 7.30 (CH , s), 8.05
im
(CH , s).
im
Polymerisation. A mixture of 4.29 g of water, 22.47 g of
ethanol and 0.22 g of NH is introduced into a solution of
3
4.23 g of monomer diBoc-10 in 6.82 g of tetraethoxysilane.
The mixture is left at room temperature for 5 days, allowing
the evaporation of the solvents. The solid is then washed with
methanol and dichloromethane. IR: l 3200È3400 l 1655
NH
CO
l
1680 cm~1. 13C (solid) NMR: d 10; 20; 30; 40; 120È140;
CO
160; 175. 29Si (solid) NMR: d [110.
Removal of the Boc protecting group. HCl gas is introduced
teristics: IR: l 3420È3270, l 1644, l
1543 cm~1.
NH
CO
imidazole
in a suspension of the polymer in Et O. The mixture is stirred
Hydrogenated surfactants. 5: octylaminocarnosine É 2HCl,
yield 0.76 g (84%); 6: decylaminocarnosine É 2HCl, yield 0.7 g
(80%); 7: tetradecylaminocarnosine É 2HCl, yield 0.8 g (81%).
1H NMR (CD OD): d 0.90 (CH , t, J \ 7), 1.30 [(CH ) , m]),
2
for 12 h at room temperature. The solid is Ðltered and washed
with Et O. 13C (solid) NMR: d 10; 20; 40; 120È140; 175. 29Si
2
(solid) NMR: d [110.
3
3
2 n
1.50 (CH , m), 2.72 (CH a, m), 3.15 (CH , 1H, dd, J \ 6
2im
and 12), 3.20 (CH b and NCH , t, J \ 4.5), 3.25 (CH , 1H,
2im
2
2
2
2
Surface activity
dd, J \ 4.5 and 12 Hz), 4.75 (CH, m), 7.40 and 8.80 (2 CH
,
im
s). Elemental analysis for 5 (C
H
N O Cl, MW \ 409) calc.
The surface tension measurements were made either with a
DognonÈAbribat or a Kruss K10T tensiometer using the Wil-
helmy plate method in order to assess the critical micellar
concentrations of the compounds from surface tension vs. con-
centration plots.
Aqueous solutions of the surfactants were prepared starting
from stock solutions of known concentration by successive
dilutions with distilled water. Their surface tension c was mea-
sured at 25 ¡C after complete equilibration of the system. Each
value is a mean of three successive measurements. The esti-
mated error of the surface tension measurements is ^1 mN
m~1.
17 33
5 2
(found): C 49.75 (49.64); H 8.11 (7.95); N 17.07 (17.64%).
PerÑuorinated surfactants. 8: 2H,2H,3H,3H-perÑuoro-
octylaminocarnosine É 2HCl, yield 0.87 g (67%); 9: 2H,2H,3H,
3H-perÑuorodecylaminocarnosine É 2HCl, yield 1.01 g (68%).
1H NMR (CD OD): d 2.65 (CH a, t, J \ 7), 2.95 (CH , t,
3
2
2im
J \ 7), 3.30 (CH , t, J \ 7), 3.59 (NCH , t, J \ 7), 6.00
2b
(CF2CH, d, J \ 31 Hz), 7.31 and 8.60 (2 CH ); 19F NMR
HvF im
2
(CD OD): d \ [82 (CF , d, J \ 10 Hz), [119 (CF C, m),
3
3
FvF
2
[108 (CF, m), [127 to [123 [(CF ) , m]. Elemental
2 n
analysis for 9 (C
H F N O Cl , MW \ 743) calc. (found):
19 20 17
5 2 2
C 30.66 (30.45); H 2.71 (2.89); N 9.41(9.23); F 43.39 (42.59%).
Potentiometry
Preparation of grafted silica. Preparation of diBoc-carnosine.
Di-tert-butyl dicarbonate (0.04 mol, 2.2 equiv.) is added at
0 ¡C to a solution of 0.017 mol of carnosine in a mixture of 10
mL of water, 20 ml of dioxane and 10 ml of 1 N aqueous
NaOH. After stirring for 30 min at room temperature, the
solution is concentrated under reduced pressure to 50% of its
initial volume and then 30 mL of ethyl acetate is added. The
mixture is acidiÐed with 1 N HCl at 5 ¡C to pH 2. The
aqueous phase is extracted with ethyl acetate. The organic
The coordination equilibria were investigated by poten-
tiometric titrations in aqueous solution at a constant ionic
strength of 0.01 mol L~1 (KNO ) and T \ 298 ^ 1 K by
using a titration apparatus including a Radiometer PHM 240
precision digital ion-meter and a copper(II) ion-selective elec-
trode. The pH was monitored permanently during the titra-
tion and adjusted if necessary by addition of base.
3
phase is dried over MgSO and the solvent evaporated under
4
reduced pressure. The residue is thoroughly washed with
Acknowledgements
Et O. IR: l 3200È3400, l 1655, l 1680 cm~1. 1H NMR
2
NH
CO
CO
We are grateful to Dr P. Tekely for recording the silicium and
carbon solid state NMR spectra and for many helpful dis-
cussions. We thank S. Moreau and G. Enderlin for their tech-
nical assistance during the synthesis of some of the products
and E. Eppiger for her valuable technical assistance with high
resolution NMR measurements.
(CDCl ): d 1.40 and 1.60 [CH (Boc), s], 2.40 (CH a, d, J \ 7),
3
3
2
2im
3.10 (CH , 1H, dd, J \ 8 and 16), 3.25 (CH , 1H, dd,
2im
J \ 4.5 and 16), 3.45 (CH b, m), 4.65 (CH, m), 5.25 (NH, m),
2
6.75 (NH, d, J \ 7), 7.25 (CH , s), 8.15 (CH , s, 1H).
im
im
Preparation of the (triethoxysilyl)alkylamidocarnosine
monomer. 10: N-Methylmorpholine (0.01 mol) is added under
argon to a solution of 0.01 mol of di-Boc-carnosine in 50 mL
of tetrahydrofuran. After cooling the solution to [15 ¡C a
mixture of 0.01 mol of isopropenyl chloroformiate and 0.01
mol of 3-aminopropyltriethoxysilane in 10 ml of THF is intro-
duced into the reaction vessel. The solution is allowed to
warm up to room temperature; after Ðltration of the precipi-
tate the solution is evaporated under reduced pressure and the
residue is washed with Et O to yield a white solid. IR: l
References
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NH
3200È3400, l 1655, l 1680 cm ~1. 1H NMR (CD OD): d
CO CO
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