N-Methyl-DL-aspartic acid monohydrate

Article abstract of DOI:10.1107/S0108270100008593

The title compound, C₅H₉NO₄·H₂O, has been synthesized and crystallized. It crystallizes in Cc with one molecule in the asymmetric unit. The compound is found in its zwitterionic form. D and L forms of the compou

Full text of DOI:10.1107/S0108270100008593

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
Ê
other aspartic acid structures, with C3ÐC4 [1.5145 (14) A]
(
(
Table 1) signi®cantly shorter than the other CÐC bonds
Dawson, 1977; Derissen et al., 1968; Rao, 1973; Sawka-
ISSN 0108-2701
Dobrowolska et al., 1990; Zvargulis & Hambley, 1994; Flaig et
al., 1998).
N-Methyl-DL-aspartic acid mono-
hydrate
a
b
Dennis Madsen *² and Philip Pattison
a
European Synchrotron Radiation Facility, BP 220, 38043 Grenoble CEDEX, France,
Rao (1973) de®ned three four-atom planes to compare
different conformations of aspartic acid: C1,C2,C3,C4 (A);
O1,O2,C1,C2 (B); and O3,O4,C3,C4 (C). The r.m.s. deviations
of the atoms from the least-squares planes are small: A = 0.082,
b
and Institute of Crystallography, University of Lausanne, BSP, Dorigny, CH-1015
Lausanne, Switzerland
Correspondence e-mail: dennis@xray.bmc.uu.se
Received 28 February 2000
Accepted 19 June 2000
Ê
B = 0.005 and C = 0.009 A.
The dihedral angle between the ꢁ-carboxylic acid group
C4,O3,O4) with respect to the carbon skeleton (A,C)
(
ꢀ
The title compound, C H NO ÁH O, has been synthesized and
[15.70 (18) ] is between that found in DLASP and LASP,
where the dihedral angles found were, respectively, 3.9 and
5
9
4
2
crystallized. It crystallizes in Cc with one molecule in the
asymmetric unit. The compound is found in its zwitterionic
form. d and l forms of the compound are linked in the crystal
via OÐHÁ Á ÁO and NÐHÁ Á ÁO hydrogen bonds, both directly
between the aspartic acid-derivative entities and to the crystal
water molecule. A weak intramolecular NÐHÁ Á ÁO interaction
is found. The carbon skeleton is slightly twisted with CÐCÐ
ꢀ
50.7 . The conformation around C1ÐC2 (corresponding to
the torsion angle denoted in protein crystallography) is
signi®cantly different from that found in LASP, DLASP and
1
NMDASP, with = O1ÐC1ÐC2ÐN1 = 159.02 (12) and
ꢀ
2
=
ꢀ
O2ÐC1ÐC2ÐN1 = � 22.54 (17) . In LASP, DLASP and the
1
two conformers in NMDASP,
ꢀ
= 172.2, 144.8 and 164.1/
ꢀ
ꢀ
2
CÐC = 166.83 (11) . A comparison with other derivatives of
165.0 , and
Similarly, the orientation of the ꢀ-carboxylate group is
somewhat distorted compared with the other structures, with
= � 6.1, � 37.8 and � 17.7/� 17.9 , respectively.
aspartic acid shows only two rotamers ± one with a near planar
carbon skeleton and one with a signi®cantly twisted carbon
skeleton.
ꢀ
ꢀ
A,B = 82.05 (5) in (I), 64.2 in DLASP and 95.6 in LASP,
respectively. The ꢀ-carboxylate group is oriented to facilitate a
weak hydrogen bond, N1ÐH2Á Á ÁO2 (cf. Table 2). A similar
weak NÐHÁ Á ÁO interaction is also found in NMDASP. The
conformation around the C3ÐC4 bond is different from that
found in LASP, with torsion angles C2ÐC3ÐC4ÐO3 =
Comment
Aspartic acid is one of the naturally formed amino acids and
several substituted and unsubstituted structures have been
published: l-aspartic acid (LASP; Derissen et al., 1968), dl-
aspartic acid hydrochloride (Dawson, 1977), dl-aspartic acid
with X-rays (DLASP; Rao, 1973) and with neutrons (Sequeira
et al., 1989), N-methyl-d-aspartic acid monohydrate
ꢀ
ꢀ
�
11.94 (19) and C2ÐC3ÐC4ÐO4 = 167.77 (12) in (I), and
ꢀ
corresponding values of 131.4 and � 51.3 in LASP. In DLASP
and the two conformers in NMDASP, the corresponding
(
NMDASP; Sawka-Dobrowolska et al., 1990) and N-carbamyl-
dl-aspartic acid (Zvargulis & Hambley, 1994). A charge-
density study has recently been carried out on dl-aspartic acid
(
Flaig et al., 1998). The values from the charge-density study
will be used in the following comparison for dl-aspartic acid.
Differences in the conformation of aspartic acid have been
found between the present study of N-methyl-dl-aspartic acid
monohydrate, (I), and the previous studies. The labelling
scheme shown in Fig. 1 follows the standard used in other
0
similar structures. A relabelling with C2 = C and C1 = C
ꢀ
translates the present labelling scheme into that used in
protein structures.
All of the bond distances in the present compound are,
within the standard uncertainty, identical to those found in
Figure 1
A molecular drawing of (I) showing the labelling scheme. The ellipsoids
enclose 50% probability displacement.
² Current address: Department of Cell and Molecular Biology, Uppsala
University, Biomedical Centre, Box 596, S-751 24 Uppsala, Sweden.
Acta Cryst. (2000). C56, 1157±1158
# 2000 International Union of Crystallography ꢁ Printed in Great Britain ± all rights reserved 1157

organic compounds
ꢀ
torsion angles are 2.4 and 7.2/19.1 , and � 176.9 and � 172.5/
Table 1
Selected geometric parameters (A, ).
Ê
ꢀ
ꢀ
�
162.9 , respectively.
In all the derivatives of aspartic acid found in the literature,
C1ÐC2
C2ÐC3
1.535 (2)
1.5268 (19)
C3ÐC4
1.5145 (14)
the hydrogen-bond pattern varies signi®cantly. Aspartic acid
has, furthermore, been crystallized both in the optically active
form with only one handedness of the molecule in the crystal
structure as well as in the optically inactive form with both
hands present in the crystal structure. Most are found in the
zwitterionic form, except N-carbamyl-dl-aspartic acid. The
aspartic acid side chain has, however, only been found in
basically two rotamers ± one with a near planar carbon
skeleton (C1,C2,C3,C4) and one with a carbon skeleton
O1ÐC1ÐC2ÐN1
O2ÐC1ÐC2ÐN1
O1ÐC1ÐC2ÐC3
O2ÐC1ÐC2ÐC3
159.02 (12)
� 22.54 (17)
� 78.94 (15)
99.49 (15)
N1ÐC2ÐC3ÐC4
C1ÐC2ÐC3ÐC4
C2ÐC3ÐC4ÐO3
C2ÐC3ÐC4ÐO4
� 71.80 (14)
166.83 (11)
� 11.94 (19)
167.77 (12)
Table 2
Hydrogen-bonding geometry (A, ).
Ê
ꢀ
ꢀ
twisted about 60 (e.g. as found in N-methyl-d-aspartic acid
monohydrate). The ideal rotamers are slightly distorted to
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
i
OWÐH1WÁ Á ÁO1
OWÐH2WÁ Á ÁO1
0.87 (4)
0.83 (3)
0.82 (4)
0.89 (3)
0.89 (3)
0.84 (3)
1.87 (5)
1.92 (3)
1.77 (4)
2.18 (3)
2.18 (3)
2.00 (2)
2.7337 (15)
2.7472 (17)
2.5761 (18)
2.6658 (18)
2.9596 (18)
2.7931 (17)
169 (4)
175 (3)
171 (3)
114 (2)
146 (2)
158 (2)
ꢀ
facilitate the maximum number of hydrogen bonds [about 13
ꢀ
ii
i
in (I) with C1ÐC2ÐC3ÐC4 = 166.83 (11) ]. The ꢁ-carboxylic
O4ÐH9Á Á ÁO2
N1ÐH2Á Á ÁO2
acid group is, however, rather ¯exible to form the maximum
number of hydrogen bonds, as demonstrated by the high
variation in the angle (A,C) between the previously de®ned
planes.
iii
N1ÐH2Á Á ÁOW
iv
N1ÐH3Á Á ÁOW
1
2
1
2
1
2
Symmetry codes: (i) x;y;1 ‡ z; (ii) x;� y; ‡ z; (iii) x �
;
‡ y;z � 1; (iv)
1
2
1
2
1
x �
;
� y;z �
.
2
The ®ndings show that the rotamers used in protein crys-
tallography structure determination are very persistent even
in the case of substituted amino acids in the zwitterionic form.
The data were collected at the Swiss±Norwegian beamline at the
European Synchrotron Radiation Facility.
Experimental
Data collection: MAR software; cell re®nement: DENZO (Otwi-
nowski & Minor, 1997); data reduction: DENZO and CCP4 (Evans,
The compound was synthesized by dissolving maleic acid in ethanol
and subsequent slow addition of an equimolar amount of methyl-
amine. The solution was heated to about 343 K for 3±4 h. Cooling the
solution slowly to room temperature gave crystals suited for X-ray
diffraction almost immediately. The crystals were very unstable in air.
They were therefore produced immediately before the data collection
to give the best possible crystal quality.
1994); program(s) used to solve structure: SHELXS97 (Sheldrick,
1990); program(s) used to re®ne structure: SHELXL97 (Sheldrick,
1997); molecular graphics: ORTEPII (Johnson, 1976).
The authors wish to thank Mr Henrik Birkedal for
comments on the manuscript.
Crystal data
�
x
D = 1.490 Mg m
3
C
5
H
9
NO
4
ÁH
2
O
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: AV1045). Services for accessing these data are
described at the back of the journal.
M
r
= 165.15
Monoclinic, Cc
Synchrotron radiation
Cell parameters from 6678
re¯ections
Ê
a = 9.282 A
Ê
b = 10.803 A
c = 7.887 A
ꢁ
V = 736.1 A
Z = 4
ꢀ
� 1
ꢂ= 2.97±28.03
ꢃ= 0.134 mm
T = 122 (2) K
Ê
ꢀ
Ê
= 111.45
3
Multi-faceted, colourless
0.2 Â 0.15 Â 0.15 mm
References
Dawson, B. (1977). Acta Cryst. B33, 882±884.
Derissen, J. L., Endeman, H. J. & Peerdeman, A. F. (1968). Acta Cryst. B24,
1349±1354.
Evans, P. R. (1994). Acta Cryst. D50, 760±763.
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2227±2238.
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National
Laboratory, Tennessee, USA.
Otwinowski, Z. & Minor, W. (1997). Methods Enzymol. 276, 307±326.
Rao, S. T. (1973). Acta Cryst. B29, 1718±1720.
Sawka-Dobrowolska, W., Gøowiak, T., Kozøowski, H. & Mastalerz, P. (1990).
Acta Cryst. C46, 1679±1681.
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908.
Sheldrick, G. M. (1990). Acta Cryst. A46, 467±473.
Sheldrick, G. M. (1997). SHELXL97. University of G oÈ ttingen, Germany.
Spek, A. L. (1990). Acta Cryst. A46, C-34.
Data collection
MAR Image Plate diffractometer
scans
Rint = 0.029
ꢀ
'
ꢂ
max = 28.03
6
8
8
678 measured re¯ections
93 independent re¯ections
91 re¯ections with I > 2ꢄ(I)
h = � 12 ! 11
k = � 14 ! 14
l = � 9 ! 9
Re®nement
2
2
2
2
Re®nement on F
2
R[F > 2ꢄ(F )] = 0.030
wR(F ) = 0.074
S = 1.312
o
w = 1/[ꢄ(F ) + (0.0480P)
2
+ 0.1021P]
where P = (F
2
2
2
c
o
+ 2F
)/3
(Á/ꢄ)max = 0.042
Áꢅmax = 0.39 e A
Ê
� 3
Ê
8
1
93 re¯ections
45 parameters
� 3
Áꢅmin = � 0.22 e A
Extinction correction: SHELXL97
Sheldrick, 1997)
Extinction coef®cient: 0.048 (9)
All H-atom parameters re®ned
(
Zvargulis, E. S. & Hambley, T. W. (1994). Acta Cryst. C50, 2058±2060.
1
158 Madsen and Pattison ꢁ
C H
5
NO
ÁH
O
Acta Cryst. (2000). C56, 1157±1158
9
4
2