helices are reported in the literature.5,6 In this report, we
present the formation of supramolecular double helical
structures in crystals from a series of water-soluble synthetic
dipeptides (1-3), each containing an N-terminally positioned
â-alanine (â-Ala) residue while the C-terminus is occupied
by a bulky hydrophobic Xaa residue (Xaa ) Val/Ile/Phe).
Gorbitz has made a seminal contribution in structures of
hydrophobic dipeptides6 that are based exclusively on
R-amino acids. The left-handed dipeptide double helices of
Val-Ala class structures are formed through hydrogen bonds,
and these hydrophobic dipeptides are self-assembled to form
microporous organic materials.6a Though Gorbitz’s dipeptides
and our reported dipeptides (1-3) form supramolecular
double helices through hydrogen bonds, our reported dipep-
tides are somewhat different from Gorbitz’s dipeptides
chemically and structurally, and they can be termed as the
â-Ala-Xaa class.
A series of water-soluble dipeptides, where â-alanine is
used as a constituent, â-Ala-L-Val (1), â-Ala-L-Ile (2), â-Ala-
L-Phe (3), and its retro analogue L-Phe-â-Ala (4), have been
synthesized by conventional solution-phase methodology,7
purified, characterized, and studied. Colorless monoclinic
crystals of peptides 1, 3, and 4 and colorless triclinic crystals
of peptide 2, suitable for X-ray diffraction studies,8 were
obtained from their aqueous solutions by slow evaporation.
Peptides 1 and 3 crystallize with two peptide molecules in
the asymmetric unit, named A and B, and peptide 2
crystallizes with four peptide molecules in the asymmetric
unit, named A, B, C, and D (Figure 1a-c). However, peptide
4 has only one molecule in the asymmetric unit (Figure 1d).
Interestingly, the central (θ) torsion angle around the -C(â)-
(4) (a) Tanaka, Y.; Katagiri, H.; Furusho, Y.; Yashima, E. Angew. Chem.,
Int. Ed. 2005, 44, 3867-3870. (b) Ikeda, M.; Tanaka, Y.; Hasegawa, T.;
Furusho, Y.; Yashima, E. J. Am. Chem. Soc. 2006, 128, 6806-6807. (c)
Furusho, Y.; Tanaka, Y.; Yashima, E. Org. Lett. 2006, 8, 2583-2586.
(5) (a) Benedetti, E.; Di Blasio, B.; Pedone, C.; Lorenzi, G. P.; Tomasic,
L.; Gramlich, V. Nature 1979, 282, 630. (b) Langs, D. A. Science 1988,
241, 188-191. (c) Wittung, P.; Nielsen, P. E.; Buchardt, O.; Egholm, M.;
Norden, B. Nature 1994, 368, 561-563.
(6) (a) Go¨rbitz, C. H. Chem.-Eur. J. 2007, 13, 1022-1031. (b) Go¨rbitz,
C. H. New J. Chem. 2003, 27, 1789-1793. (c) Go¨rbitz, C. H. Curr. Opin.
Solid State Mater. Sci. 2002, 6, 109-116.
(7) Bodanszky, M.; Bodanszky, A. The Practice of Peptide Synthesis;
Springer-Verlag: New York, 1984; pp 1-282.
(8) Crystal data for peptide 1: C8H16N2O3, FW ) 188.23, monoclinic,
space group P21, a ) 11.1153 (15) Å, b ) 5.4908 (8) Å, c ) 16.1643 (17)
Å, â ) 91.345 (10)°, Z ) 4, dcalcd ) 1.268 g cm-3. Crystal data for peptide
2: C9H18N2O3, FW ) 202.25, triclinic, space group P1, a ) 12.5522 (14)
Å, b ) 5.5160 (5) Å, c ) 15.9248 (19) Å, R ) 89.816 (9)°, â ) 87.074
(10)°, γ ) 89.234 (8)°, Z ) 4, dcalcd ) 1.220 g cm-3. The structure is only
slightly distorted from monoclinic P21. Crystal data for peptide 3:
C12H16N2O3, FW ) 236.27, monoclinic, space group P21, a ) 13.9345
(12) Å, b ) 5.5848 (5) Å, c ) 15.4060 (13) Å, â ) 92.408 (7)°, Z ) 4,
dcalcd ) 1.310 g cm-3. Crystal data for peptide 4: C12H16N2O3, FW )
236.27, monoclinic, space group P21, a ) 8.1292 (11) Å, b ) 5.7648 (8)
Figure 1. (a)-(d) ORTEP diagrams with atomic numbering
scheme of peptides 1-4, respectively. Ellipsoids are at 30%
probability. There are, respectively, two, four, two, and one
molecules in the asymmetric units of peptides 1, 2, 3, and 4. All
independent molecules are shown. Intramolecular hydrogen bonds
are shown as dotted lines (g ) gauche and t ) trans).
Å, c ) 12.434 (2) Å, â ) 97.293 (13)°, Z ) 2, dcalcd ) 1.358 g cm-3
.
Diffraction data were measured with Mo KR (λ ) 0.71073 Å) radiation at
150 K using an Oxford Diffraction X-Calibur CCD system. Data analyses
were carried out with the Crysalis program.9 The structures were solved by
direct methods using the SHELXS-9710 program. Refinements were carried
out with a full matrix least squares method against F2 using SHELXL-
97.11 The non-hydrogen atoms were refined with anisotropic thermal
parameters. The hydrogen atoms were included in geometric positions and
given thermal parameters equivalent to 1.2 times those of the atom to which
they were attached. The final R values were R1 ) 0.0683, 0.1028, 0.0317,
0.0733 and wR2 ) 0.1548, 0.2926, 0.0876, 0.1255 for 1297, 7405, 3691,
1183 data with I > 2σ(I) for peptides 1-4, respectively. Crystallographic
data have been deposited at the Cambridge Crystallographic Data Centre
with reference numbers CCDC 634356-634359.
C(R)- bond of the conformationally flexible â-Ala residue
appears to play a critical role in dictating the overall distinct
structural features. For peptides 1 and 3, one of the
conformers present in the asymmetric unit adopts a folded
gauche conformation (θ ∼ 60°) whereas the other conformers
favor an extended trans conformation (θ ∼ 180°) around
the -C(â)-C(R)- bond of the â-Ala residue (Supporting
Information, Table S1). For peptide 2, two of the four
1348
Org. Lett., Vol. 9, No. 7, 2007