Supramolecular structures from lysine peptides and carbon dioxide

Article abstract of DOI:10.1021/jo061144k

The design, synthesis, and characterization of novel linear and cross-linked supramolecular polymers that are easily available from biologically friendly lysine peptides and carbon dioxide (CO₂) are reported here. Polymeric structures 5, 6, and

Full text of DOI:10.1021/jo061144k

Supramolecular Structures from Lysine Peptides and Carbon
Dioxide
Vaclav Stastny, Anjenique Anderson, and Dmitry M. Rudkevich*
Department of Chemistry & Biochemistry, The UniVersity of Texas at Arlington,
Arlington, Texas 76019-0065
rudkeVich@uta.edu
ReceiVed June 5, 2006
The design, synthesis, and characterization of novel linear and cross-linked supramolecular polymers
that are easily available from biologically friendly lysine peptides and carbon dioxide (CO2) are reported
here. Polymeric structures 5, 6, and 19 readily form from peptides 2, 3, and 15, respectively, at ambient
temperatures by simply bubbling CO2 through their solutions in apolar organic solvents (CHCl3, benzene)
and even in the presence of 10% MeOH. The resulting gels can be easily isolated from solution, dried,
and stored refrigerated for several months. At the same time, they may thermally release CO2 and convert
back to the corresponding monomers. As a consequence, their structures and physical properties are
switchable. They may also trap, store, and release foreign molecules. The typical entrapment procedure
was demonstrated for tripeptide 3, CO2, and the commercially available dye coumarin 2.
Introduction
solvents. Being robust and stable, they, however, release CO2
upon gentle heating and transform back to the amines. In this
paper, we report on the design, synthesis, and characterization
of novel supramolecular polymers and cross-linked 3D materials
that are based on peptides. Fabrication of molecular materials
using simple and versatile peptide construction motifs is a
quickly emerging area in bio(nano)technology.3 We show that
short lysine peptides reversibly react with CO2 to form
polymeric assemblies. These are stable under laboratory condi-
tions but may thermally release CO2 and convert back to the
monomers. As a consequence, their structures and physical
properties are switchable. They also may trap, store, and release
foreign molecules under thermal control. Accordingly, our work
opens novel perspectives for the design of switchable supramo-
lecular materials for molecular storage and other applications.
Supramolecular polymers represent a novel class of macro-
molecules, in which monomeric units are held together by
reversible forces.1 Supramolecular polymers thus combine
features of conventional polymers with properties resulting from
the bonding reversibility. The degree of polymerization, life-
times, physical properties, and architectures of supramolecular
polymers can be switched “on-off” through the main chain
self-assembly-dissociation processes. We recently proposed to
build supramolecular polymers using dynamic, reversible chem-
istry between carbon dioxide (CO2) and primary amines (Figure
1).2 Carbamate bridges between monomers readily form by
simply bubbling CO2 through solutions of amines in apolar
(1) (a) Supramolecular Polymers, 2nd ed.; Ciferri, A., Ed.; CRC Press:
Boca Raton, FL, 2005. (b) Bosman, A. W.; Brunsveld, L.; Folmer, B. J.
B.; Sijbesma, R. P.; Meijer, E. W. Macromol. Symp. 2003, 201, 143-154.
(c) Lehn, J.-M. Polym. Int. 2002, 51, 825-839. (d) Schubert, U. S.;
Eschbaumer, C. Angew. Chem., Int. Ed. 2002, 41, 2892-2926. (e) ten Cate,
A. T.; Sijbesma, R. P. Macromol. Rapid Commun. 2002, 23, 1094-1112.
(f) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem.
ReV. 2001, 101, 4071-4097. (g) Schmuck, C.; Wienand, W. Angew. Chem.,
Int. Ed. 2001, 40, 4363-4369. (h) Castellano, R. K.; Rudkevich, D. M.;
Rebek, J., Jr. Proc. Natl. Acad. Sci. USA 1997, 94, 7132-7137. (i) Lange,
R. F. M.; van Gurp, M.; Meijer, E. W. J. Polym. Sci., Part A 1999, 37,
3657-3670. (j) Castellano, R. K.; Rebek, J., Jr. J. Am. Chem. Soc. 1998,
120, 3657-3663.
Results and Discussion
Design. CO2 is known to rapidly react with amines at ordinary
temperatures and pressures to form carbamate salts.4 Their
(3) (a) Zhao, X.; Zhang, S. Trends Biotechnol. 2004, 22, 470-476. (b)
Voyer, N.; Lamothe, J. Tetrahedron 1995, 51, 9241-9284.
(4) (a) Dell’Amico, D. B.; Calderazzo, F.; Labella, L.; Marchetti, F.;
Pampaloni, G. Chem. ReV. 2003, 103, 3857-3898. (b) Hampe, E. M.;
Rudkevich, D. M. Tetrahedron 2003, 59, 9619-9625. (c) Masuda, K.; Ito,
Y.; Horiguchi, M.; Fujita, H. Tetrahedron 2005, 61, 213-229.
(2) Review from this laboratory: Rudkevich, D. M.; Xu, H. Chem.
Commun. 2005, 2651-2659.
10.1021/jo061144k CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/12/2006
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J. Org. Chem. 2006, 71, 8696-8705

Supramolecular Structures
ing9 results show that Boc-(L)-Lys-(L)-Lys-OMe dipeptide 2
represents an ideal unit for the construction of the linear
supramolecular polymer 5. As shown in Figure 3A, both of its
free ꢀ-NH2 groups are pointing to opposite directions, thus
allowing the formation of a chainlike carbamate structure.
Similarly, Boc-(L)-Lys-(L)-Lys-(L)-Lys-OMe tripeptide 3,
having three free ꢀ-NH2 groups, enables the construction of
three-dimensional carbamate 6 after reaction with CO2. Figure
3B shows that carbamate 6 possesses a quite developed porous
structure with 20-25 Å pores. Such cross-linked supramolecular
polymers may be suitable for the encapsulation of various guests.
Synthesis (Scheme 1). Boc-(L)-Lys-NHPr (1) was synthe-
sized from commercially available Boc-(L)-Lys(Cbz)-OH (7)
and n-propylamine in the presence of EDCI‚HCl and HOBt in
CH2Cl2, followed by the cleavage of the Cbz protecting group
by Pd/C and H2 in MeOH, in overall ∼85% yield. Similarly,
lysine dipeptide 10 was prepared from commercially available
Boc-(L)-Lys(Cbz)-OH (7) and (L)-Lys(Cbz)-OMe‚HCl (9),
using EDCI‚HCl and HOBt as peptide coupling agents, in 85%
yield. Derivative 10 was further used for the synthesis of both
lysine tripeptide 3 and bridged lysine dipeptide 15. First, 10
was treated with in situ-generated HCl (from AcCl in MeOH)
to cleave the Boc protective group, which gave the correspond-
ing ammonium salt 11 in 91% yield. This was then coupled
with Boc-(L)-Lys(Cbz)-OH (7) under the same conditions as
described above to give Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-(L)-
Lys(Cbz)-OMe (12) in 82% yield. Finally, the cleavage of the
Cbz protective group (H2, Pd/C, MeOH) offered Boc-(L)-Lys-
(L)-Lys-(L)-Lys-OMe (3) in a quantitative yield.
To further increase the number of reactive amino groups, we
again employed the above-mentioned lysine dipeptide and
designed a building block bearing two relatively distant pairs
of reactive amino groups. We expected that the presence of a
sufficiently long spacer between both lysine dipeptide subunits
could have a significant influence on the size and shape of the
pores in the interior structure. To obtain bridged dipeptide 15,
Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-OMe (10) was initially hydro-
lyzed under basic conditions (aq NaOH). The resulting car-
boxylic acid 13 was then coupled with 1,12-diaminododecane
to give the protected bridged dipeptide 14 in 90% yield. This
was finally treated with Pd/C under H2 atmosphere to give 15
in a quantitative yield.
FIGURE 1. Design of carbamate-based linear and cross-linked
supramolecular (reversible) polymers from CO2.
formation is thermally reversible. This chemistry has been
utilized in amine-based “CO2 scrubbers”5 and also for the
preparation of organogels.6 While reactions between CO2 and
amino acids have been known for years,7 this has never been
used for the construction of novel materials.8 In this work,
peptide monomers 1-3 were designed, which (a) are readily
available either from commercial sources or via two or three
synthetic steps, utilizing conventional peptide chemistry, (b) are
chiral, (c) are biologically friendly, (d) can be easily function-
alized on the periphery, and (e) possess terminal CO2-philic
primary amino groups and, therefore, can react with CO2 in
apolar solution.
The approach is sketched in Figure 2 and introduces linear
and cross-linked lysine-based supramolecular structures 4-6.
Simple Boc-(L)-Lys-NHPr (1) was selected as a model com-
pound. It served to verify the reactivity of a primary ꢀ-NH2
group with CO2 and also to allow us to obtain characteristic
NMR data for lysine-based carbamates. The molecular model-
Syntheses of Lysine-Based Carbamates and Their NMR
Study. CO2 quantitatively reacts with simple lysine derivative
1 upon bubbling though the DMSO-d6 solution with the
formation of carbamic acid 16 (Scheme 2, Figure 4). The acid
1
is quite stable in solution and was characterized by H, 13C,
1
and H-1H COSY NMR spectroscopy. The appearance of a
(5) (a) Yamaguchi, T.; Koval, C. A.; Nobel, R. D.; Bowman, C. Chem.
Eng. Sci. 1996, 51, 4781-4789. (b) Yamaguchi, T.; Boetje, L. M.; Koval,
C. A.; Noble, R. D.; Bowman, C. N. Ind. Eng. Chem. Res. 1995, 34, 4071-
4077. (c) Kosaraju, P.; Kovvali, A. S.; Korikov, A.; Sirkar, K. K. Ind. Eng.
Chem. Res. 2005, 44, 1250-1258 and references therein. (d) Bates, E. D.;
Mayton, R. D.; Ntai, I.; Davis, J. H., Jr. J. Am. Chem. Soc. 2002, 124,
926-927.
new triplet at 6.65 ppm, belonging to the -NHC(O)OH protons,
and a significant shift of the corresponding R-CH2 methylene
protons to the lower field of 2.88 ppm in the 1H NMR spectrum,
together with a new carbonyl signal at 158 ppm in the 13C NMR
spectrum, represent clear evidence for carbamic acid formation.
It is noteworthy that free carbamic acids are still very rare and
can be seen only in polar aprotic solvents, when larger quantities
of CO2 are used.4,10
(6) (a) George, M.; Weiss, R. G. J. Am. Chem. Soc. 2001, 123, 10393-
10394. (b) George, M.; Weiss, R. G. Langmuir 2002, 18, 7124-7135. (c)
George, M.; Weiss, R. G. Langmuir 2003, 19, 1017-1025. (d) George,
M.; Weiss, R. G. Langmuir 2003, 19, 8168-8176. (e) Carretti, E.; Dei, L.;
Baglioni, P.; Weiss, R. G. J. Am. Chem. Soc. 2003, 125, 5121-5129.
(7) (a) Davis, A. S.; O’Brien, P.; Nunn, P. B. Bioorg. Chem. 1993, 21,
309-318. (b) Chen, J.-G.; Sandberg, M.; Weber, S. G. J. Am. Chem. Soc.
1993, 115, 7343-7350. (c) McGhee, W.; Riley, D.; Christ, K.; Pan, Y.;
Parnas, B. J. Org. Chem. 1995, 60, 2820-2830.
On the contrary, the use of an apolar aprotic solvent, such as
CHCl3, directly leads to the formation of the corresponding
(9) MacroModel 7.1; MM2 and Amber* Force Field. See: Mohamadi,
F.; Richards, N. G.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.;
Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440-
467.
(8) For the preliminary results from this laboratory, see: (a) Xu, H.;
Rudkevich, D. M. Chem.sEur. J. 2004, 10, 5432-5442. (b) Rudkevich,
D. M.; Woldemariam, G. A.; Xu, H. Polym. Prepr. 2005, 6, 1162-1163.
J. Org. Chem, Vol. 71, No. 23, 2006 8697

Stastny et al.
FIGURE 2. Design of (L)-lysine-based supramolecular polymers using CO2 as a linking agent.
ammonium carbamate salt 4 (Figure 2). Upon bubbling CO2
directly into the solution of 1 in CDCl3 ([1] ) 1 M), lysine-
based carbamate 4 was obtained in a quantitative yield (1H
NMR, Figure 5). Compound 4 was also prepared by the
bubbling of CO2 in nondeuterated CHCl3, followed by removal
of the solvent under reduced pressure at room temperature
(Figure 4). Finally, the solution of 1 in benzene-MeOH (10:1)
also reacted with CO2.11 The solvent was subsequently removed
under reduced pressure at room temperature, affording the same
compound 4.
2.55 and 2.83 ppm, which were assigned as two different
R-CH2N methylene groups (Figure 4C). A broad signal at ∼5.3
+
ppm, which most probably belongs to the ammonium NH3
protons, was found to be concentration dependent. Upon
increasing the concentration, it shifts downfield. At 0.05 M,
this signal was observed at 4.1 ppm, at 0.2 M, it was shifted to
5.34 ppm, and finally, at 0.5 M, it was present at 6.00 ppm. On
the other hand, the broad carbamate-C(O)NH signal showed
only a slight concentration dependence and moved in an opposite
manner from 6.56 (0.05 M) to 6.19 (0.5 M) with increasing
concentration. Both the ammonium and carbamate amide
signals, along with other amide NH protons in the molecule,
disappeared upon addition of several drops of D2O.
To further prove the carbamate salt formation, 13C-labeled
CO2 (13CO2) was bubbled through the solution of 1 in benzene-
MeOH (10:1) after which carbamate 4, labeled with the 13C-
carbonyl group, was isolated.12 Its structure was confirmed by
1D and 2D NMR measurements, 13C NMR spectroscopy, and
also 1H-13C HMBC (heteronuclear multibond correlation)
spectra (Figure 6). Clear evidence for the N-C covalent bond
formation between the amine nitrogen and the 13CO2 carbon
was obtained. For example, a strong signal for the 13C-labeled
carbamate carbonyl group appeared, as expected, at 160.3 ppm
and showed a cross-peak with the R-CH2 methylene protons at
2.83 ppm in the HMBC spectrum.
The 1H NMR spectrum of carbamate 4, prepared from 1 and
CO2 in CDCl3, clearly shows two 1:1 signals at 2.74 and 2.94
ppm, which correspond to two different R-CH2N methylene
groups from the carbamate and ammonium ends (Figure 5B).
The spectrum also shows two pairs of signals corresponding to
the amide and BOC-carbamate NH protons. This feature was
not seen in DMSO-d6, where the carbamate salt is solvated and
dissociated.
1
When measured in DMSO-d6, the H NMR spectrum of
carbamate 4 shows the nonequal intensities of the signals at
(10) (a) Hampe, E. M.; Rudkevich, D. M. Chem. Commun. 2002, 1450-
1451. (b) Aresta, M.; Ballivet-Tkatchenko, D.; Dell’Amico, D. B.; Bonnet,
M. C.; Boschi, D.; Calderazzo, F.; Faure, R.; Labella, L.; Marchetti, F.
Chem. Commun. 2000, 1099-1100 and references therein. (c) Wittmann,
K.; Wisniewski, W.; Mynott, R.; Leitner, W.; Kranemann, C. L.; Rische,
T.; Eilbracht, P.; Kluwer, S.; Ernsting, J. M.; Elsevier, C. J. Chem.sEur.
J. 2001, 7, 4584-4589. (d) Fu¨rstner, A.; Ackermann, L.; Beck, K.; Hori,
H.; Koch, D.; Langemann, K.; Liebl, M.; Six, C.; Leitner, W. J. Am. Chem.
Soc. 2001, 123, 9000-9006.
(11) No significant amounts of alkylammonium bicarbonates were found
in cases when benzene-MeOH (10:1) was used. This was concluded from
the analysis of the corresponding 1H NMR, 13C NMR, and 1H-13C HMBC
spectra. The compounds obtained in benzene-MeOH (10:1) were identical
to those obtained using CHCl3 (CDCl3) solutions. For the discussion, see:
Ito, Y.; Ushitora, H. Tetrahedron 2006, 62, 226-235.
Carbamate 4 was found to be quite stable when stored in
CDCl3 and refrigerated for 4 months. The reversibility of
carbamate formation was proven by simple heating of an NMR
(12) When regular CO2 was used in such experiments, a much weaker
13C carbamate signal was detected, which may be due to partial dissociation
of carbamate derivatives to free amine and CO2 in DMSO solution. For
the detailed discussion, see ref 4c.
8698 J. Org. Chem., Vol. 71, No. 23, 2006

Supramolecular Structures
FIGURE 3. (A) Molecular model of the Boc-(L)-Lys-(L)-Lys-OMe-based carbamate linear polymer 5. Seven monomer units are shown. (B)
Molecular model of the Boc-(L)-Lys-(L)-Lys-(L)-Lys-OMe-based carbamate cross-linked polymer 6. Fourteen monomeric units are depicted.
MacroModel 7.1; Amber* Force Field.9
tube containing carbamate 4 in DMSO-d6 to ∼100 °C and
simultaneous bubbling of N2 through this solution for 1 min.
The 1H NMR spectrum obtained after the reversal of carbamate
formation was identical to that of the starting “free” amine 1.
Likewise, lysine dipeptide 2 readily reacts with CO2 in
DMSO-d6 with the quantitative formation of carbamic acid 17
(Scheme 2). The appearance of a multiplet at 6.66 ppm,
belonging to both -NHC(O)OH protons, and the pronounced
shift of R-CH2 methylene protons to a lower field of 2.88 ppm,
together with a new carbonyl signal at 158 ppm, represent
unambiguous evidence of carbamic acid formation (see Figure
7B). Dipeptide 2 was found to be well soluble (up to 1.2 M) in
CHCl3, but when CO2 was bubbled through the solution of 2
in CHCl3 (0.15-1.2 M concentration range), the corresponding
carbamate 5 formed as a colorless gel. After removal from the
solution, gel 5 quickly turned into a white powder.
Product 5 is insoluble in most apolar aprotic solvents, and
NMR measurements were performed in DMSO-d6, where
carbamate 5 exists in equilibrium with the corresponding
carbamic acid 17 and “free” amine 2.4c In contrast to the starting
lysine dipeptide 2, carbamate 5 showed two different signals at
a 1:1 ratio for the R-CH2 methylene protons (Figure 7C). The
appearance of new broad signals at ∼6 ppm, corresponding to
the carbamate NH and ammonium NH3+ protons, respectively,
represents additional structural evidence for 5. The position of
the broad NH3+ signal was found to be concentration dependent.
It moves downfield upon increasing the concentration.
The carbamate formation was also evident from the 13C NMR
and HMBC experiments, where 13C-labeled CO2 was used.12
As shown in Figure 8B,C, a very intene signal for the 13C-
labeled carbamate carbonyl group appeared, as expected, at
160.9 ppm and gave a strong cross-peak with the R-CH2
methylene protons at 2.85 ppm in the HMBC spectrum. This
proves the N-C bond formation between the amine nitrogen
in 5 and the 13CO2 carbon. Solid carbamate 5 was found to be
stable when stored refrigerated for at least 4 months. The
carbamate bonds can, however, be broken by heating to ∼100
°C and simultaneous bubbling of N2 through the solution. The
1H NMR spectrum obtained after such treatment was identical
to that of starting amine 2.
The presence of three reactive ꢀ-NH2 groups in lysine
tripeptide 3 allowed for the preparation of cross-linked su-
pramolecular polymer 6. Bubbling CO2 directly into the DMSO-
d6 solution of 3 resulted in the corresponding carbamic acid 18
(Scheme 2), which was characterized by NMR spectroscopy
(see Figure 9B). At the same time, it was not possible to dissolve
J. Org. Chem, Vol. 71, No. 23, 2006 8699

Stastny et al.
SCHEME 1. Syntheses of Short (L)-Lysine Peptidesa
1
FIGURE 4. Portions of the H NMR spectra (500 MHz, 295 ( 1 K,
DMSO-d6) of: (A) Boc-(L)-Lys-NHPr (1); (B) carbamic acid (16),
prepared from 1 and CO2; (C) carbamate 4. Here and further in the
paper, the residual solvent signals are marked as “•”and all spectral
assignments were done by using 1D (1H, 13C, 13C-DEPT 135) and 2D
a Conditions: (a) n-PrNH2, EDCI‚HCl, HOBt, N-methylmorpholine,
CH2Cl2, 85%. (b) H2, 10% Pd/C, MeOH, >95%. (c) 7, EDCI‚HCl, HOBt,
N-methylmorpholine, CH2Cl2, 85%. (d) H2, 10% Pd/C, MeOH, >95%. (e)
AcCl, MeOH, 0 °C, 91%. (f) 7, EDCI‚HCl, HOBt, N-methylmorpholine,
CH2Cl2, 82%. (g) H2, 10% Pd/C, MeOH, >95%. (h) MeOH, 1 M aq NaOH,
then 1 M aq HCl, 88%. (i) NH2-(CH2)12-NH2, EDCI‚HCl, HOBt, N-
methylmorpholine, CH2Cl2, 90%. (j) H2, 10% Pd/C, MeOH, >95%.
1
(1H-1H COSY, 13C-1H HETCOR, H-13C HMBC) NMR measure-
ments in combination.
SCHEME 2. Synthesis of (L)-Lysine-Based Carbamic Acids
16-18a
1
FIGURE 5. Portions of the H NMR spectra (500 MHz, 295 ( 1 K,
CDCl3) of: (A) Boc-(L)-Lys-NHPr (1); (B) carbamate 4, prepared from
1 and CO2 in CDCl3 4.
concentrations (0.02 M). The introduction of a longer alkyl chain
into the structure of 3 also did not help. On the other hand,
compound 3 was found to be well soluble in MeOH and also
in its mixtures with CHCl3 and benzene. Bubbling CO2 through
the clear solution of tripeptide 3 in benzene-MeOH (10:1) at
g0.16 M concentrations successfully resulted in the formation
of cross-linked polymer 6 as a colorless gel, which turned to a
white powder when exposed to the air. Two new broad signals
belonging to the carbamate NH and ammonium NH3+ protons
appeared at 6.11 and 5.51 ppm, respectively (Figure 9C). The
+
NH3 signal showed significant concentration dependence. It
was observed at 5.51 ppm for 0.16 M and appeared at 6.49
ppm when the concentration was increased to 0.64 M. On the
other hand, the corresponding carbamate NH signal moved only
slightly upfield from 6.11 to 5.94 ppm in the same concentration
range. Characteristic broad peaks of R-CH2 methylene protons
were found at 2.85 and 2.57 ppm and did not show any
concentration dependence (Figure 9C). Finally, the experiment
a Conditions: (a) CO2, DMSO.
tripeptide 3 in CHCl3 or any other aprotic solvents (hexane,
benzene, toluene, MeCN, EtOAc, and THF), even at low
8700 J. Org. Chem., Vol. 71, No. 23, 2006

Supramolecular Structures
1
FIGURE 7. Portions of the H NMR spectra (300 MHz, 295 ( 1 K,
DMSO-d6) of: (A) Boc-(L)-Lys-(L)-Lys-OMe (2); (B) carbamic acid
17; (C) polymeric carbamate 5, prepared from 1 and CO2 in CHCl3,
followed by evaporation.
tions, these voids are of 20-25 Å dimensions, which makes
them suitable for the entrapment of various organic substrates.
We found that when CO2 cross-links tripeptide 3 in the presence
of an organic guest of 1-1.5 nm size, gel 6 instantly entraps it.
In the preliminary experiment, we used gel 6 to trap a commer-
cial fluorescent dye, such as coumarin 2, and employed con-
ventional UV-vis spectrophotometry to monitor this process.
In a typical experiment, tripeptide 3 was dissolved in a small
volume of benzene-MeOH (10:1) and then coumarin 2 was
added in at a 2.5:1 molar ratio. CO2 was bubbled through the
solution for 10 min, and the decrease in the absorption of
coumarin 2 in the supernatant solution was systematically
recorded at λmax ) 358 nm (Figure 12). In this process, gel 6
was formed, which trapped the dye. As a consequence, the
concentration of coumarin 2, and therefore its absorption, in
solution decreased. From the absorbance measurements, up to
∼65 ( 3% of coumarin 2 was entrapped.14 We feel that the
same rules apply for other guests of comparable dimensions.
FIGURE 6. (A) Downfield portion of the 13C NMR spectrum of
compound 1 (75 MHz, 295 ( 1 K, CDCl3). (B) Downfield portion of
the 13C NMR spectrum of carbamate 4 prepared with 13CO2 (75 MHz,
1
295 ( 1 K, DMSO-d6). (C) H-13C HMBC spectrum of carbamate 4
prepared from 1 in benzene-MeOH (10:1) by using 13CO2 (75 MHz,
295 ( 1 K, DMSO-d6).
with 13C-labeled CO2 gave evidence of the carbamate car-
bonyl group. A strong signal was found at 161.7 ppm, which
is very similar to the chemical shifts for carbamates 4 and 5
(Figure 10).
Similarly, bubbling CO2 through the clear solution of bridged
lysine dipeptide 15 in benzene-MeOH (10:1) led to the
formation of a colorless gel 19 (Figure 11). This cross-linked
supramolecular polymer 19 was characterized by NMR tech-
niques (see Supporting Information). Both carbamate materials
6 and 19 are stable when stored refrigerated as solids for at
least several days. The reversibility of carbamate bonds in both
compounds was proven by heating the samples in DMSO-d6 in
an NMR tube to ∼100 °C with simultaneous flashing with N2
Conclusions
1
for several minutes. The H NMR spectra obtained after this
An approach has been proposed and demonstrated to construct
supramolecular 2D and 3D polymeric structures from amino
acids and short peptides upon their reaction with CO2 gas. Short
lysine-based peptides reversibly react with CO2 to form
polymeric gels. These are stable under laboratory conditions
but release CO2 at elevated temperatures and dissociate back
to monomers. Accordingly, their architecture and properties are
thermally switchable. These gels may also trap, store, and release
treatment were identical with those of starting amines 3 and
15, respectively.
Preliminary Guest Entrapment Experiments. A number
of cross-linked supramolecular polymers are known;1 however,
to our knowledge, they have not been used for guest storage
and release purposes.13 Cross-linked structures 6 and 19 possess
multiple voids, which are generated between the peptide chains
and the lysine-carbamate bridges. According to our calcula-
(14) In the control experiment, CO2 was bubbled through the solution
of neat coumarin 2 and the absorption at λmax ) 358 nm was recorded. No
visible changes were observed after 10 min.
(13) For the preliminary results from this laboratory, see: Xu, H.;
Rudkevich, D. M. Org. Lett. 2005, 7, 3223-3226.
J. Org. Chem, Vol. 71, No. 23, 2006 8701

Stastny et al.
1
FIGURE 9. Portions of the H NMR spectra (300 MHz, 295 ( 1 K,
DMSO-d6) of: (A) Boc-(L)-Lys-(L)-Lys-(L)-Lys-OMe (3); (B) carbamic
acid 18; (C) polymeric carbamate 6, prepared from 3 and CO2 in
benzene-MeOH (10:1).
FIGURE 8. (A) Downfield portion of the 13C NMR spectrum of
compound 2 (75 MHz, 295 ( 1 K, DMSO-d6). (B) Downfield portion
of the 13C NMR spectrum of carbamate 5 prepared with 13CO2 (75
MHz, 295 ( 1 K, DMSO-d6). (C) 1H-13C HMBC spectrum of
carbamate 5 prepared from 2 in CHCl3 by using 13CO2 followed by
evaporation (300 MHz, 295 ( 1 K, DMSO-d6).
foreign molecules of industrial or biological interest. Such
encapsulation studies are currently in progress. It would also
be interesting to functionalize the monomeric peptides with
molecular recognition sites, catalytic units, polymerizable
groups, etc. and compose functional materials upon introduction
of CO2. This work has been started. Another important
achievement is that CO2 gas can be used as a building block.
Considering the huge significance of CO2 in the environment,
our results offer means for creating environmentally-responsive
materials.15
FIGURE 10. Downfield portion of the 13C NMR spectra (75 MHz,
295 ( 1 K, DMSO-d6) of: (A) tripeptide 3; (B) carbamate 6 prepared
from 3 and 13CO2 in benzene-MeOH (10:1).
sensitive compounds were run under a dried N2 atmosphere. For
column chromatography, silica gel ((60 Å, 200-425 mesh) was
used. Dipeptide 2 was obtained according to the known protocol.16
Boc-Lys(Cbz)-OH (7) and (L)-Lys(Cbz)-OMe‚HCl (9) were pur-
chased from a commercial supplier. 13C-labeled CO2, containing
99 atom % 13C and 3 atom % 18O, was purchased commercially.
Molecular modeling was performed using commercially available
MacroModel 7.1.9
Boc-(L)-Lys(Cbz)-NH-n-Pr (8). Boc-Lys(Cbz)-OH (7; 500 mg,
1.31 mmol) was dissolved in CH2Cl2 (5 mL), and the solution was
cooled in an ice bath to 0 °C. HOBt (209 mg, 1.31 mmol), EDCI‚
HCl (277 mg, 1.45 mmol), and N-methylmorpholine (0.304 mL,
2.76 mmol) were then added. The mixture was stirred for 15 min,
after which n-propylamine (0.108 mL, 1.31 mmol) was added. The
reaction mixture was stirred at 0 °C for 1 h and then at rt for the
Experimental Section
General. Melting points were determined on a Mel-Temp
apparatus and are uncorrected. 1H and 13C NMR spectra were
recorded at 295 ( 1 °C on JEOL 300 and 500 MHz spectrometers.
1H NMR spectra were recorded at 300 and 500 MHz. 13C NMR
spectra were recorded at 75 and 125 MHz. Chemical shifts were
measured relative to residual nondeuterated solvent resonances.
FTIR spectra were recorded using KBr pellets. Electrospray
ionization (ESI) time-of-flight (TOF) reflectron experiments were
performed at the Scripps Center for Mass Spectrometry. Samples
were electrosprayed into the TOF reflectron analyzer at an ESI
voltage of 4000 V and a flow rate of 200 µL/min. When applicable,
the presence of solvent in analytical samples was confirmed by
NMR spectroscopy. All experiments with moisture- and/or air-
(16) Xu, H.; Kinsel, G. R.; Zhang, J.; Li, M.; Rudkevich, D. M.
Tetrahedron 2003, 59, 5837-5848.
(15) Xiaoding, X.; Moulijn, J. A. Energy Fuels 1996, 10, 305-325.
8702 J. Org. Chem., Vol. 71, No. 23, 2006

Supramolecular Structures
1174. Anal. Calcd for C22H35N3O5: C, 62.69; H, 8.37; N, 9.97.
Found: C, 62.40; H, 8.42; N, 10.13.
Boc-(L)-Lys-NHPr (1). Compound 8 (408 mg, 0.97 mmol) was
dissolved in MeOH (5 mL) and added to the flask with Pd/C (10%,
30 mg) under N2. The mixture was stirred under H2 atmosphere
for 16 h. The reaction mixture was then filtered through diatoma-
ceous earth and evaporated under reduced pressure. The residue
was then dried under high vacuum at rt to give derivative 1 as a
colorless viscous oil that was used without further purification:
yield 288 mg (>95%). 1H NMR (DMSO-d6) δ 7.74 (br, 1 H), 6.74
(d, J ) 8.3 Hz, 1 H), 3.85-3.75 (m, 1 H), 3.05-2.95 (m, 2 H),
1.55-1.50, 1.50-1.45, 1.25-1.20 (3 × m, 8 H), 1.32 (s, 9 H),
0.82 (t, J ) 7.8 Hz, 3 H). 13C NMR (DMSO-d6) δ 172.6, 155.9,
73.4, 54.3, 41.0, 40.8, 32.4, 31.4, 28.2, 22.7, 22.5, 11.2. Calcd for
C14H29N3O3‚0.4MeOH: C, 57.61; H, 10.27; N, 14.00. Found: C,
57.40; H, 10.00; N, 14.18.
Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-OMe (10). This compound was
prepared by a modification of the known procedure.8 (L)-Lys(Cbz)-
OMe‚HCl (9; 500 mg, 1.51 mmol) and Boc-(L)-Lys(Cbz)-OH (7;
575 mg, 1.51 mmol) were dissolved in CH2Cl2 (30 mL), after which
N-methylmorpholine (0.2 mL, 3.32 mmol) was added. The mixture
was cooled to 0 °C in an ice bath, and then HOBt (224.5 mg, 1.661
mmol) was added. EDCI‚HCl (318.4 mg, 1.661 mmol) and
N-methylmorpholine (0.2 mL, 3.32 mmol) in CH2Cl2 (30 mL) were
then added, and the reaction mixture was stirred for 1 h at 0 °C
and then at rt overnight. The reaction mixture was then washed
successively with H2O (100 mL), 10% (w/w) aqueous solution of
NaHCO3 (100 mL), 10% (w/w) aqueous solution of citric acid (100
mL), and again with H2O (100 mL). The organic layer was dried
over MgSO4 and then evaporated under reduced pressure to give
10 as a colorless viscous compound. The spectral and analytical
data were in agreement with the previously published data.8
(L)-Lys(Cbz)-(L)-Lys(Cbz)-OMe‚HCl (11). Acetyl chloride
(0.22 mL, 3.12 mmol) was added into MeOH (5 mL), and the
mixture was stirred at 0 °C in an ice bath for 30 min. Boc-(L)-
Lys(Cbz)-(L)-Lys(Cbz)-OMe (10; 196 mg, 0.132 mmol) in MeOH
(5 mL) was then added, and the reaction mixture was stirred at rt
overnight. After 16 h, no starting material was present in the reaction
mixture according to TLC (SiO2, CH2Cl2-MeOH, 96:4). The
solvent was evaporated under reduced pressure, and then the residue
was dissolved in MeOH (1 mL), after which diethyl ether (20 mL)
was added. Product 11 was obtained as a white precipitate that
was removed by filtration and dried under high vacuum: yield 168
mg (91%); mp 122-124 °C. 1H NMR (DMSO-d6) δ 8.80 (d, J )
6.9 Hz, 1 H), 8.16 (br, 3 H), 7.36-7.32 (m, 10 H), 7.28 (t, J ) 6.4
Hz, 1 H), 7.22 (t, J ) 5.5 Hz, 1 H), 5.00 (s, 4 H), 4.27-4.25 (m,
1 H), 3.80-3.78 (m, 1 H), 3.62 (s, 3 H), 3.00-2.98 (m, 4 H), 1.72-
1.71 (m, 2 H), 1.64-1.59 (m, 2 H), 1.42-1.32 (m, 8 H). 13C NMR
(DMSO-d6) δ 172.5, 169.4, 156.7, 156.7, 137.8, 137.8, 128.9, 128.3,
128.3, 65.7, 52.7, 52.5, 31.3, 29.6, 29.5, 23.2, 21.8. IR (cm-1, KBr)
ν 3336, 2934, 1734, 1689, 1657, 1543, 1282, 1258. ESI-MS TOF
m/z: 591.2576 ([M - H]- calcd for C29H40N4O7Cl, 591.2591).
Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-(L)-Lys(Cbz)-OMe (12). (L)-
Lys(Cbz)-(L)-Lys(Cbz)-OMe‚HCl (11; 154 mg, 0.26 mmol) and
Boc-Lys(Cbz)-OH (7; 99 mg, 0.26 mmol) were dissolved in
CH2Cl2 (10 mL), after which N-methylmorpholine (0.03 mL, 0.29
mmol) was added. The mixture was cooled to 0 °C in an ice bath,
and then HOBt (39 mg, 0.29 mmol) was added, followed by the
solution of EDCI‚HCl (55 mg, 0.29 mmol) and N-methylmorpholine
(0.03 mL, 0.29 mmol) in CH2Cl2 (10 mL). The mixture was stirred
for 1 h at 0 °C and then overnight at rt. The reaction mixture was
then washed successively with H2O (50 mL), 10% (w/w) aqueous
solution of NaHCO3 (50 mL), 1 M aqueous solution of citric acid
(50 mL), and again with H2O (50 mL). The organic layer was dried
over MgSO4 and then evaporated under reduced pressure to give
12 as a white crystalline compound: yield 196 mg (82%); mp 102-
104 °C. 1H NMR (DMSO-d6) δ 8.23 (d, J ) 6.5 Hz, 1 H), 7.68 (d,
J ) 8.3 Hz, 1 H), 7.40-7.30 (m, 15 H), 7.18 (t, J ) 6.2 Hz, 3 H),
6.84 (d, J ) 7.9 Hz, 1 H), 4.96 (s, 6 H), 4.30-4.25 (m, 1 H),
FIGURE 11. Cross-linked polymer 19 prepared from peptide-based
tetramine 15 and CO2.
FIGURE 12. Guest entrapment experiment with tripeptide 3, CO2,
and coumarin 2 in benzene-MeOH (10:1).
next 20 h. It was then diluted with CH2Cl2 (30 mL), and the organic
layer was washed with H2O (100 mL), 1 M aqueous solution of
citric acid (100 mL), 10% (w/w) aqueous solution of NaHCO3 (100
mL), and again with H2O (100 mL). The organic layer was dried
over MgSO4 and evaporated under reduced pressure. Product 8 was
obtained as a slightly yellow crystalline compound: yield 471 mg
(85%); mp 91-92 °C. 1H NMR (DMSO-d6) δ 7.71 (t, J ) 6.2 Hz,
1 H), 7.31 (m, 5 H), 7.20 (t, J ) 5.5 Hz, 1 H), 6.70 (d, J ) 8.3 Hz,
1 H), 4.97 (s, 2 H), 3.80-3.75 (m, 1 H), 3.05-2.85 (m, 4 H), 1.50-
1.40, 1.40-1.35, and 1.25-1.15 (3 × m, 8 H), 1.34 (s, 9 H), 0.80
(t, J ) 8.6 Hz, 3 H). 13C NMR (DMSO-d6) δ 172.5, 156.7, 155.8,
137.9, 128.9, 128.3, 78.4, 65.7, 54.9, 32.4, 29.7, 28.7, 23.4, 22.9,
11.8. IR (cm-1, KBr) ν 3326, 2937, 2864, 1689, 1655, 1542, 1271,
J. Org. Chem, Vol. 71, No. 23, 2006 8703

Stastny et al.
4.20-4.10 (m, 1 H), 3.90-3.80 (m, 1 H), 3.56 (s, 3 H), 3.00-
2.90 (m, 6 H), 1.70-1.55, 1.50-1.40, and 1.30-1.20 (3 × m, 18
H), 1.33 (s, 9 H). 13C NMR (DMSO-d6) δ 172.9, 172.5, 172.3,
156.6, 155.9, 137.9, 128.9, 128.3, 78.7, 65.7, 55.0, 52.5, 52.3, 31.0,
29.7, 29.7, 29.5, 28.7, 23.3, 23.2. IR (cm-1, KBr) ν 3325, 2939,
1693, 1640, 1539, 1255. ESI-MS TOF m/z: 919.4810 ([M + H]+
calcd for C48H67N6O12, 919.4811). Anal. Calcd for C48H66N6O12:
C, 62.73; H, 7.24; N, 9.14. Found: C, 62.28; H, 7.29; N, 9.35.
Boc-(L)-Lys-(L)-Lys-(L)-Lys-OMe (3). Pd/C (10%) (50 mg)
was placed into a flask under N2, after which Boc-(L)-Lys(Cbz)-
(L)-Lys(Cbz)-(L)-Lys(Cbz)-OMe (12; 490 mg, 0.53 mmol) in
MeOH (10 mL) was added. The mixture was stirred under H2
atmosphere for 3 h, filtered through diatomaceous earth, and
evaporated under reduced pressure. The residue was dried under
high vacuum at rt to yield tripeptide 3 as a white crystalline
compound: yield 265 mg (>95%); mp 226-228 °C (decomp). 1H
NMR (DMSO-d6) δ 8.28 (br, 2 H), 7.73 (br, 2 H), 6.91 (br, 1 H),
4.30 (br, 1 H), 4.19 (br, 1 H), 3.90 (br, 1 H), 3.60 (s, 3 H), 1.65-
(Cbz)-(L)-Lys(Cbz)-(L)-Lys(Cbz)-NH(CH2)6-]2 (14; 283 mg, 0.195
mmol) in MeOH (10 mL) was added. The mixture was stirred under
H2 atmosphere overnight, filtered through diatomaceous earth, and
evaporated under reduced pressure. The residue was then dried
under high vacuum at rt to give tetraamine 15 as a colorless
1
crystalline compound: yield 178 mg (>95%); mp 62-64 °C. H
NMR (DMSO-d6) δ 7.92 and 7.82 (2 × br, 4 H), 7.02 (br, 2 H),
4.18 (br, 2 H), 3.85 (br, 2 H), 3.04, 2.98, and 2.87 (3 × br, 4 H),
2.55 (br, 8 H), 1.57, 1.49, and 1.37 (3 × br, 44 H), 1.22 (s, 18 H).
13C NMR (DMSO-d6) δ 172.4, 171.8, 156.2, 155.9, 78.7, 78.6, 55.1,
52.9, 39.8, 38.9, 32.6, 32.0, 31.5, 29.5, 29.2, 28.7, 26.8, 23.2, 22.9.
ESI-MS TOF m/z: 913.7165 ([M + H]+ calcd for C46H93N10O8,
913.7172), 935.6986 ([M + Na]+ calcd for C46H92N10O8Na,
935.6991).
General Procedure for the Preparation of Carbamic Acids
(16-18). Dry CO2 was bubbled through the solution of Boc-(L)-
Lys-NHPr (1; 0.5 mmol) in DMSO-d6 (0.5 mL) in the NMR tube
for 10 min, after which the NMR spectra were recorded. The
solution remained clear during this time. 16: 1H NMR (DMSO-d6)
δ 7.72 (t, J ) 5.5 Hz, 1 H), 6.73 (d, J ) 9.6 Hz, 1 H), 6.65 (t, J
) 5.5 Hz, 1 H), 3.85-3.80 (m, 1 H), 3.05-2.90 (m, 2 H), 2.90-
2.85 (m, 2 H), 1.55-1.50, 1.50-1.40, and 1.25-1.15 (3 × m, 8
H), 1.34 (s, 9 H), 0.82 (t, J ) 7.8, 3 H). 13C NMR (DMSO-d6) δ
172.5, 157.5, 155.6, 78.3, 54.8, 32.3, 29.9, 28.6, 23.5, 22.8, 11.9.
Dry CO2 gas was bubbled through the solution of Boc-(L)-Lys-
(L)-Lys-OMe (2; 39 mg, 0.1 mmol) in DMSO-d6 (0.5 mL) in the
1.50, 1.50-1.40, and 1.30-1.20 (3 × m, 18 H), 1.38 (s, 9 H). 13
C
NMR (DMSO-d6) δ 172.9, 172.5, 172.4, 155.9, 78.6, 54.8, 52.5,
52.4, 32.3, 31.9, 30.8, 29.5, 28.7, 23.0. ESI-MS TOF m/z: 517.3703
([M + H]+ calcd for C24H49N6O6, 517.3708).
Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-OH (13). Boc-(L)-Lys(Cbz)-
(L)-Lys(Cbz)-OMe (10; 690 mg, 1.05 mmol) was dissolved in
MeOH (10 mL), and 1 M aqueous NaOH solution (1.6 mL) was
then added. The mixture was stirred at rt for 2 h, the solvent was
removed under reduced pressure, the residue was dissolved in H2O
(15 mL), and the pH was adjusted to 2-3 by slow addition of 1 M
aqueous HCl. The resulting suspension was then extracted with
CH2Cl2 (3 × 20 mL). The combined organic layers were dried over
MgSO4 and evaporated under reduced pressure to give product
13 as a colorless crystalline compound: yield 595 mg (88%); mp
50-55 °C. 1H NMR (DMSO-d6) δ 7.89 (d, J ) 8.3 Hz, 1 H), 7.40-
7.35 (m, 10 H), 7.19 (t, J ) 5.9 Hz, 2 H), 6.78 (d, J ) 8.9 Hz, 1
H), 4.97 (s, 4 H), 4.15-4.10 (m, 1 H), 3.90-3.80 (m, 1 H), 2.95-
2.90 (m, 4 H), 1.70-1.65, 1.60-1.50, and 1.30-1.25 (3 × m, 12
H), 1.33 (s, 9 H). 13C NMR (DMSO-d6) δ 174.1, 172.8, 156.6,
155.8, 137.8, 128.9, 128.2, 78.5, 65.7, 54.5, 52.1, 32.2, 31.2, 29.7,
29.5, 28.7, 23.3, 23.1. IR (cm-1, KBr) ν 3327, 2939, 1702, 1533,
1252. Anal. Calcd for C33H46N4O9: C, 61.67; H, 7.21; N, 8.72.
Found: C, 61.25; H, 7.03; N, 8.66.
[Boc-(L)-Lys(Cbz)-(L)-Lys(Cbz)-NH(CH2)6-]2 (14). Boc-(L)-
Lys(Cbz)-(L)-Lys(Cbz)-OH (13; 400 mg, 0.622 mmol) and 1,12-
diaminododecane (62 mg, 0.311 mmol) were dissolved in CH2Cl2
(10 mL), the mixture was cooled to 0 °C in an ice bath, and then
HOBt (92 mg, 0.684 mmol) was added. A solution containing
EDCI‚HCl (131 mg, 0.684 mmol) and N-methylmorpholine (0.1
mL, 0.809 mmol) in CH2Cl2 (10 mL) was subsequently added, and
the mixture was stirred at 0 °C for 1 h and at rt overnight. The
reaction mixture was washed successively with H2O (100 mL), 10%
(w/w) aqueous solution of NaHCO3 (100 mL), 1 M aqueous solution
of citric acid (110 mL), and again with H2O (100 mL). The organic
layer was dried over MgSO4 and then evaporated under reduced
pressure to give 14 as a colorless crystalline compound: yield 405
mg (90%); mp 138-140 °C. 1H NMR (DMSO-d6) δ 7.97 and 7.66
(2 × d, J ) 8.3 and 7.6 Hz, 2 H), 7.81 (t, J ) 4.8 Hz, 2 H), 7.35-
7.25 (m, 20 H), 7.20-7.15 (m, 4 H), 6.99 and 6.89 (2 × d, J ) 6.5
and 8.3 Hz, 2 H), 4.96 (s, 8 H), 4.20-4.05 (m, 2 H), 3.85-3.75
(m, 2 H), 3.05-2.90 (m, 12 H), 1.55-1.40 (m, 20 H), 1.34 (br, 24
H), 1.18 (s, 18 H). 13C NMR (DMSO-d6) δ 172.4, 171.7, 156.6,
156.0, 137.9, 128.9, 128.3, 78.8, 78.7, 65.7, 55.1, 52.9, 39.0, 32.6,
31.9, 29.6, 29.3, 28.7, 26.9, 23.3, 23.0. IR (cm-1, KBr) ν 3319,
2931, 1693, 1643, 1540, 1259. ESI-MS TOF m/z: 1449.8636 ([M
+ H]+ calcd for C78H117N10O16, 1449.8643), 1471.8463 ([M + Na]+
calcd for C78H116N10O16Na, 1471.8443). Anal. Calcd for
C78H116N10O16‚1.5H2O: C, 63.43; H, 8.12; N, 9.48. Found: C,
63.17; H, 7.81; N, 9.33.
1
NMR tube for 10 min. 17: H NMR (DMSO-d6) δ 8.09 (d, J )
7.3 Hz, 1 H), 6.78 (d, J ) 8.3, 1 H), 6.70-6.65 (m, 2 H), 4.20-
4.15 (m, 1 H), 3.90-3.85 (m, 1 H), 3.61 (s, 3 H), 2.90-2.85 (m,
4 H), 1.65-1.55, 1.55-1.40, and 1.30-1.15 (3 × m, 12 H), 1.36
(s, 9 H). 13C NMR (DMSO-d6) δ 173.0, 157.6, 155.8, 78.6, 54.6,
52.3, 32.1, 31.2, 29.9, 29.8, 28.7, 23.1, 22.8. 18: 1H NMR (DMSO-
d6) δ 8.25 (d, J ) 6.9 Hz, 1 H), 7.68 (d, J ) 7.9 Hz, 1 H), 6.87 (d,
J ) 7.9 Hz, 1 H), 6.70-6.60 (m, 3 H), 4.30-4.20 and 4.20-4.10
(2 × m, 2 H), 3.85-3.80 (m, 1 H), 3.58 (s, 3 H), 2.90-2.80 (m,
6 H), 1.65-1.40 and 1.30-1.15 (2 × m, 18 H), 1.34 (s, 9 H). 13
C
NMR (DMSO-d6) δ 173.0, 172.5, 172.3, 157.6, 155.9, 78.6, 55.4,
54.9, 52.5, 52.3, 32.6, 32.1, 31.0, 29.9, 29.8, 29.7, 28.7, 23.4, 23.1,
22.8. Carbamic acid from 15: 1H NMR (DMSO-d6) δ 8.02, 7.83,
and 7.69 (3 × br, 4 H), 7.03 and 6.94 (2 × br, 2 H), 6.67 (br, 3 H),
4.20-4.15 and 4.10-4.05 (2 × m, 2 H), 3.83 (br, 2 H), 3.05-
3.00 (m, 4 H), 2.88 (br, 6 H), 1.60-1.45 and 1.40-1.30 (2 × m,
44 H), 1.22 (s, 18 H). 13C NMR (DMSO-d6) δ 172.5, 171.7, 157.7,
156.0, 78.7, 55.1, 52.8, 39.0, 32.7, 32.0, 29.9, 29.5, 29.3, 28.6, 26.8,
23.4, 23.0.
Carbamate (4). Method A. Dry CO2 was bubbled through the
solution of Boc-(L)-Lys-NHPr (1; 140 mg, 0.49 mmol) in CDCl3
(0.5 mL) in the NMR tube for 5 min, after which the spectra were
1
recorded. The solution remained clear during this time. H NMR
(CDCl3) δ 8.05 (br, 3 H), 7.32 and 7.21 (2 × br, 2 H), 6.00 (br, 1
H), 5.73 (br, 1 H), 5.27 (br, 1 H), 4.10-3.95 (m, 2 H), 3.20-3.00
(m, 4 H), 2.94 (br, 2 H), 2.74 (br, 2 H), 1.70-1.60, 1.55-1.50,
and 1.50-1.40 (3 × m, 16 H), 1.34 (s, 18 H), 0.82 (t, J ) 6.9 Hz,
6 H). 13C NMR (CDCl3) δ 172.6, 172.4, 163.2, 156.1, 79.6, 54.5,
54.3, 41.4, 41.1, 39.2, 32.8, 32.2, 32.1, 28.4, 23.1, 22.8, 22.6, 11.4.
Method B. Dry CO2 was bubbled through the solution of 1 (140
mg, 0.49 mmol) in CHCl3 (1 mL) for 10 min. The solution remained
clear during this time. The solvent was evaporated under reduced
pressure at rt, and the viscous residue was dried at rt under high
vacuum for 5 h to give material 4 as a white crystalline powder.
Calcd for C29H58N6O3‚2CHCl3: C, 43.42; H, 7.05; N, 9.80.
Found: C, 43.67; H, 7.30; N, 9.61. Method C. Dry CO2 was
bubbled through the solution of 1 (158 mg, 0.57 mmol) in a mixture
of benzene (1 mL) and MeOH (0.1 mL) for 40 min. The solution
remained clear during this time. The residual solvent was evaporated
under reduced pressure at rt, and the colorless viscous residue was
dried at rt under high vacuum for 5 h to give carbamate 4 as a
1
[Boc-(L)-Lys-(L)-Lys-NH(CH2)6-]2 (15). Pd/C (10%) (50 mg)
was placed into a flask flushed with N2, and then [Boc-(L)-Lys-
white crystalline powder. H NMR (DMSO-d6) δ 7.79 (br, 2 H),
6.76 (d, J ) 8.9 Hz, 2 H), 6.35 (br, 1 H), 5.33 (br, 4 H), 3.85-
8704 J. Org. Chem., Vol. 71, No. 23, 2006

Supramolecular Structures
3.75 (m, 2 H), 3.05-2.85 (m, 5 H), 2.55 (br t, 2 H), 1.6-1.1 (br
m, 16 H), 1.32 (s, 18 H), 0.78 (t, J ) 8.9 Hz, 6 H). 13C NMR
(DMSO-d6) δ 172.5, 158.2, 155.8, 78.4, 54.9, 32.3, 32.4, 29.9, 28.7,
23.3, 22.9, 11.8.
was removed and washed quickly with benzene (1 mL). The gel
turned to a white solid powder when exposed to the air. It was
dried under high vacuum at rt for 1 h to give material 19. 1H NMR
(DMSO-d6) δ 7.95 and 7.79 (2 × br, 4 H), 7.06 (br, 2 H), 6.3-5.3
(br, 11 H), 4.17 and 4.07 (2 × br, 2 H), 3.86 (br, 2 H), 3.05-2.98
(br m, 8 H), 2.61 (br, 4 H), 1.35-1.2 (br m, 44 H), 1.21 (s, 18 H).
13C NMR (DMSO-d6) δ 172.5, 171.8, 160.5, 156.0, 78.6, 55.2, 52.9,
39.0, 32.5, 31.9, 30.3, 29.5, 29.3, 28.7, 26.8, 23.1.
Entrapment Experiments. In a typical procedure, CO2 was
gently bubbled through the solution of tripeptide 3 (50 mg, 0.1
mmol) and coumarin 2 (8.4 mg, 0.04 mmol) in benzene-MeOH
(10:1) (0.5 mL) over a period of 10 min. Aliquots of the supernatant
solution (0.0025 mL) were taken before CO2 bubbling and after 2,
5, 7, and 10 min of CO2 bubbling and diluted to 1 mL with the
same solvent. UV-vis spectra were recorded; the decrease in
coumarin 2 absorption at λmax ) 358 nm was followed. A colorless
gel was formed within 1-2 min of CO2 bubbling. The experiments
were performed at least in triplicate, giving a good reproducibility.
Carbamate (5). Dry CO2 was bubbled through the solution of
Boc-(L)-Lys-(L)-Lys-OMe (2; 200 mg, 0.515 mmol) in CHCl3 (1
mL) for 10 min. During this period, material 5 was formed as a
colorless gel. This was removed, washed quickly with CHCl3 (2
1
mL), and dried under high vacuum at rt for 20 min. H NMR
(DMSO-d6) δ 8.25-8.15 (m, 1 H), 6.85 (d, J ) 7.2 Hz, 1 H), 6.23
(br, 1 H), 5.11 (br, 6 H), 4.17 (br, 1 H), 3.89 (br, 1 H), 3.57 (s, 3
H), 2.86 (br, 2 H), 2.56 (br, 2 H), 1.65-1.50 (m, 12 H), 1.34 (s, 9
H). 13C NMR (DMSO-d6) δ 173.0, 160.3, 155.8, 78.5, 54.5, 52.3,
51.8, 40.6, 40.4, 32.1, 31.7, 31.0, 30.2, 28.7, 22.9. Calcd for
C19H36N4O7‚0.4CHCl3: C, 48.52; H, 7.64; N, 11.67. Found: C,
48.51; H, 7.68; N, 12.08.
Carbamate (6). Dry CO2 was bubbled through the solution of
Boc-(L)-Lys-(L)-Lys-(L)-Lys-OMe (3; 41 mg, 0.079 mmol) in a
mixture of benzene (0.5 mL) and MeOH (0.05 mL) for 5 min. The
solution turned turbid, and a colorless gel was formed. This was
removed and washed quickly with benzene (1 mL). The gel quickly
turned to a white solid when exposed to the air. It was dried under
Acknowledgment. We are grateful to Getachew A. Wolde-
mariam and Dr. Heng Xu for preliminary experiments. The
American Chemical Society Petroleum Research Fund (42334-
AC4) and the Alfred P. Sloan Foundation generously provided
financial support. We also thank the NSF for funding the
purchase of the 300 MHz NMR spectrometer (CHE-0234811).
A.A. was a 2005 McNair Summer Scholar at UT-Arlington.
1
high vacuum at rt for 1 h to yield polymeric material 6. H NMR
(DMSO-d6) δ 8.40 (br, 1 H), 8.04 (br, 1 H), 6.94 (br, 1 H), 6.11
(br, 1 H), 5.51 (br, 6 H), 4.25 (br, 1 H), 4.15 (br, 1 H), 3.87 (br, 1
H), 3.57 (s, 3 H), 2.85 (br, 2 H), 2.57 (br, 2 H), 1.65-150 and
1.40-1.25 (2 × m, 18 H), 1.33 (s, 9 H). 13C NMR (DMSO-d6) δ
173.0, 172.6, 172.4, 161.7, 155.8, 78.4, 54.9, 52.6, 52.3, 32.3, 32.1,
30.8, 30.2, 28.7, 23.0.
Carbamate (19). Dry CO2 was bubbled through the solution of
[Boc-(L)-Lys-(L)-Lys-NH(CH2)6-]2 (15; 60 mg, 0.066 mmol) in a
mixture of benzene (0.5 mL) and MeOH (0.05 mL) for 10 min.
The solution turned turbid, and a colorless gel was formed. This
Supporting Information Available: High-field 1H and 13C
NMR spectra for compounds 1-19. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO061144K
J. Org. Chem, Vol. 71, No. 23, 2006 8705