The crystal structure of DL-lomenfloxacin hydrate

Article abstract of DOI:10.1007/s10870-009-9531-2

The DL-lomenfloxacin hydrate is an innersalt, which crystallizes in space group C2/c with cell parameters a = 22.897(10), b = 8.682(1), c = 18.365(2) A, β = 93.6 33(9)°, V = 3,705(3) A³ and Z = 8. The piperazinyl ring adopts a chair conformation, and the quinolone ring is essentially planar. The plane defined by C atoms of the piperazinyl ring is not coplanar with the quinolone ring. The carboxylate group shows two disorder parts, and is not coplanar with the quinolone ring, the dihedral angle between them is 113.8°. The disorder carboxylate group is split into two parts, the planes of which are skewed at the dihedral angles of 24.5 and 21.6° with the plane of the quinolone ring, respectively. The IR of the title compound is measured and studied. Springer Science+Business Media, LLC 2008.

Full text of DOI:10.1007/s10870-009-9531-2

J Chem Crystallogr (2009) 39:384–388
DOI 10.1007/s10870-009-9531-2
COMMUNICATION
The Crystal Structure of DL-Lomenfloxacin Hydrate
Zhan Shu Æ Hai Yan Li Æ Lin Lin Ma Æ
Wei Liang Chen Æ Zhi Min Jin
Received: 3 September 2008 / Accepted: 17 February 2009 / Published online: 10 March 2009
Ó Springer Science+Business Media, LLC 2009
Abstract The DL-lomenfloxacin hydrate is an innersalt,
which crystallizes in space group C2/c with cell parameters
by inhibiting the reproduction and repair of their DNA [3].
Previously, the structures of norfloxacin and sparfloxacin,
which are similar with that of DL-lomenfloxacin, have been
reported [4, 5]. There are several specifications of lomen-
floxacin including hydrochloride salt and different optical
forms in industry and market. The IR of the lomenfloxacin
with unknown specification has been reported previously
by Wang et al. [6]. This spectrum is exactly the same with
that of lomenfloxacin HCl reported by Xu and Zun [7], but
shows great difference with that of DL-lomenfloxacin in this
study. This arises confusions which is needed to study
carefully.
˚
a = 22.897(10), b = 8.682(1), c = 18.365(2) A, b = 93.6
3
˚
3
3(9)°, V = 3,705(3) A and Z = 8. The piperazinyl ring
adopts a chair conformation, and the quinolone ring is
essentially planar. The plane defined by C atoms of the
piperazinyl ring is not coplanar with the quinolone ring.
The carboxylate group shows two disorder parts, and is not
coplanar with the quinolone ring, the dihedral angle
between them is 113.8°. The disorder carboxylate group is
split into two parts, the planes of which are skewed at the
dihedral angles of 24.5 and 21.6° with the plane of the
quinolone ring, respectively. The IR of the title compound
is measured and studied.
Experimental
Keywords DL-Lomenfloxacin ꢀ Crystal structure ꢀ
IR
The DL-lomenfloxacin HCl and triethylamine in 1:1 molar
ratio were dissolved in water by heating to a temperature
where a clear solution was resulted, and colorless crystals
were obtained by standing the solution for several days at
room temperature.
Introduction
In recent years, a number of highly potent broad-spectrum
antibacterial agents have been synthesized, and several
have been introduced into clinical use. The lomefloxacin is
one of the antimicrobial drugs, which has excellent activity
against the Gram-positive and Gram-negative bacterial
pathogens [1, 2]. This drug stops multiplication of bacteria
The IR spectrum shows bands: 3,415, 3,083, 1,612,
1,587, 1,519, 1,468, 1,402, 1,369, 1,347, 1,325, 1,274,
1,247, 1,141, 1,115, 1,068, 1,051, 1,019, 1,001, 914, 822,
-
1
800, 733, 654, and 513 cm
.
A single crystal of the title compound was mounted on a
Bruker diffractometer with graphite monochromated MoKa
radiation. The structure was solved by direct methods and
expanded using Fourier techniques. The H atoms involved
in hydrogen bonding were deduced from a difference
Fourier map, while others were placed in calculated posi-
tions. Non-H atoms were refined anisotropically using the
SHELX-93 program package [8], while all H atoms were
fixed in the refinement. For the disorder water molecules in
the crystal, no hydrogen bonds could be localized. The
Z. Shu ꢀ H. Y. Li ꢀ L. L. Ma ꢀ W. L. Chen ꢀ Z. M. Jin (&)
College of Pharmaceutical Sciences, Zhejiang University of
Technology, 310032 Hangzhou, China
e-mail: apharm@sina.com
1
23

J Chem Crystallogr (2009) 39:384–388
385
˚
Table 1 Crystal data and structure refinement
Table 2 Selected bond lengths [A] and angles [°]
Compound
C
16
H
18
F
2
N
3
COOHꢀ4.78H
2
O
Atoms
Lengths
Atoms
Lengths
CCDC deposit no.
Color/shape
700791
Colorless/prism
F(1)–C(9)
F(2)–C(7)
O(1)–C(1)
O(2)–C(1)
O(3)–C(3)
N(1)–C(6)
N(1)–C(5)
N(1)–C(16)
N(2)–C(8)
N(2)–C(11)
N(2)–C(14)
N(3)–C(13)
N(3)–C(12)
1.349(4)
1.349(4)
1.265(12)
1.258(9)
1.246(4)
1.345(4)
1.393(4)
1.486(4)
1.411(4)
1.448(5)
1.460(4)
1.489(4)
1.499(5)
C(1)–C(2)
C(2)–C(6)
C(2)–C(3)
C(3)–C(4)
C(4)–C(10)
C(4)–C(5)
C(5)–C(7)
C(7)–C(8)
C(8)–C(9)
C(9)–C(10)
C(11)–C(12)
C(12)–C(15)
C(13)–C(14)
C(16)–C(17)
1.499(8)
1.370(5)
1.428(4)
1.477(4)
1.390(4)
1.408(4)
1.414(4)
1.381(5)
1.402(5)
1.357(4)
1.496(5)
1.498(5)
1.509(4)
1.497(7)
Chemical formula
Cell weight
17 19 2 3 4.78
C H F N O
3,845.74
273(2)K
Temperature
Crystal system
Space group
Monoclinic
C2/c
Cell dimensions
a = 22.897(3), b = 14.147(4),
c = 11.460(3) and
b = 93.63(1)°
3
˚
3,705(3) A
Volume
Z
8
3
Density (calculated)
Absorption coefficient
Diffractometer/scan
h Range for data collection (°)
Reflections measured
Independent/observed
Data/restraints/parameters
1.724 g/cm
-
0.194 mm
1
Bruker Smart
1.69–26.87
Atoms
Angles
Atoms
Angles
3,266
O(2)–C(1)–O(1)
O(2)–C(1)–C(2)
O(1)–C(1)–C(2)
C(6)–N(1)–C(5)
C(6)–N(1)–C(16)
C(5)–N(1)–C(16)
C(8)–N(2)–C(11)
C(8)–N(2)–C(14)
C(11)–N(2)–C(14)
C(13)–N(3)–C(12)
C(6)–C(2)–C(3)
C(6)–C(2)–C(1)
C(3)–C(2)–C(1)
C(7)–C(8)–C(9)
C(7)–C(8)–N(2)
C(9)–C(8)–N(2)
F(1)–C(9)–C(10)
F(1)–C(9)–C(8)
C(10)–C(9)–C(8)
C(9)–C(10)–C(4)
121.9(13)
118.7(16)
117(2)
O(3)–C(3)–C(2)
O(3)–C(3)–C(4)
C(2)–C(3)–C(4)
C(10)–C(4)–C(5)
C(10)–C(4)–C(3)
C(5)–C(4)–C(3)
N(1)–C(5)–C(4)
N(1)–C(5)–C(7)
C(4)–C(5)–C(7)
N(1)–C(6)–C(2)
F(2)–C(7)–C(8)
F(2)–C(7)–C(5)
C(8)–C(7)–C(5)
N(2)–C(11)–C(12)
C(11)–C(12)–C(15)
C(11)–C(12)–N(3)
C(15)–C(12)–N(3)
N(3)–C(13)–C(14)
N(2)–C(14)–C(13)
N(1)–C(16)–C(17)
125.7(3)
119.2(3)
115.1(3)
120.1(3)
117.8(3)
122.1(3)
118.8(3)
124.2(3)
116.9(3)
127.0(3)
116.4(3)
120.0(3)
123.6(3)
110.9(3)
114.3(4)
111.1(3)
110.3(3)
111.0(3)
107.8(3)
112.5(4)
10,915/3,975 [R(int) = 0.0323]
3,975/5/286
1.057
2
Goodness of fit on F
118.4(3)
116.5(3)
125.1(3)
116.0(3)
119.7(3)
112.7(3)
112.0(3)
118.4(3)
117.3(10)
124.2(9)
116.2(3)
124.9(3)
118.8(3)
120.1(3)
117.4(3)
122.6(3)
120.6(3)
Final R indices [I [ 2r(I)]
R indices (all data)
R
R
1
= 0.0966, wR
= 0.1141, wR
2
2
= 0.2685
= 0.2845
1
-
3
˚
0.857 and -0.355 e A
Largest diff. peak and hole
carboxylate group was in disorder states, and was split
into two parts with occupation of 46.3 and 53.7 in refine-
ment, respectively. Scattering factors used were taken
from international tables for X-ray crystallography [9].
Crystal data and refinement parameters were summarized
in Table 1, and the selected bonds and angles were listed
in Table 2, and hydrogen bonds detail was presented in
Table 3.
Results and Discussion
As illustrated in Fig. 1, the DL-lomenfloxacin is an inner-
salt, where the H atom of the carboxyl group is removed
from the parent to the atom N(3) of the piperazinyl ring.
Quinolone group itself is planar, except for the piperazinyl
moiety and the ethyl group attached to the N(1) atom. The
piperazinyl moiety is in a chair form. The dihedral angle
between the quinolone and the plane that is consisted with
the C atoms of the piperazinyl ring is 113.8°, and the plane
of two parts of the disorder carboxylate group make the
dihedral angles of 24.5 and 21.6° with the plane of the
quinolinyl ring, respectively.
˚
different from those [1.356(3) and 1.360(3) A] in the
quinolone ring of the sparfloxacin reported [4]. The six
bond lengths of the benzene ring in the quinolone group,
˚
falling in range from 1.357(4) to 1.414(4) A, are abnor-
mal, which indicates that the C–C bond lengths are not
equal to the normal bond lengths of the benzene ring
˚
[1.390 A]. These bond distances are reported to be in the
˚
range [1.389(3)–1.430(2) A] in case of a quinolone group
The two C–F bonds in quinolone ring, C(7)–F(2) and
˚
C(9)–F(1), have the same distance of 1.349(4) A, which is
[4], hence deviation from the normal benzene ring
geometry.
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J Chem Crystallogr (2009) 39:384–388
Symmetry code
˚
Table 3 Hydrogen bonds (distance, A; angle, °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
N3–H3AꢀꢀꢀO2
N3–H3AꢀꢀꢀO2
N3–H3BꢀꢀꢀO2
N3–H3BꢀꢀꢀO3
C6–H6ꢀꢀꢀO6
0.863
0.863
0.916
0.916
0.93
1.974
1.921
2.191
2.057
2.49
2.832
2.778
2.844
2.860
3.404
3.271
3.072
3.380
3.243
3.354
3.157
172.63
172.08
127.63
145.55
168.02
128.05
127.84
164.19
133.31
147.74
127.48
x ? 1/2, -y ? 1/2, ?z - 1/2
x ? 1/2, -y ? 1/2, ?z - 1/2
-x ? 1/2, ?y ? 1/2, -z ? 1/2
-x ? 1/2, ?y ? 1/2, -z ? 1/2
0
C12–H12ꢀꢀꢀO1
C12–H12ꢀꢀꢀO1
0.98
2.57
x ? 1/2, -y ? 1/2, ?z - 1/2
x ? 1/2, -y ? 1/2, ?z - 1/2
-x ? 1/2, ?y ? 1/2, -z ? 1/2
-x ? 1/2, ?y ? 1/2, -z ? 1/2
0
0.98
2.37
C14–H14AꢀꢀꢀO3
C14–H14BꢀꢀꢀO3
C16–H16AꢀꢀꢀO6
C16–H16BꢀꢀꢀF1
0.97
2.44
0.97
2.50
0.97
2.49
0.97
2.47
-x ? 1/2, ?y ? 1/2, -z ? 1/2
Fig. 1 Molecular structure of
DL-lomenfloxcin showing 40%
probability displacement
ellipsoids
In the molecule of the DL-lomenfloxacin, the eight C–N
bonds can be divided into three groups. Five bond lengths,
˚
falling in the range from 1.448(5) to 1.499(5) A, are char-
Figure 2 shows the crystal packing of the DL-lomen-
floxacin viewed along the b axis. The protonated N(3) atom
of the piperazinyl group is involved in hydrogen bonding
with the quinolone carbonyl O(3) and the O(2) atom of the
carboxylate group, and the structure exhibits intermolecu-
lar hydrogen bonds of the type C–HꢀꢀꢀO, the stability of the
crystal structure can be accounted by these hydrogen
bonds, and the intermolecular H-bonds link the neighbor-
ing molecules to form helical chains.
acterized of normal C–N single bonds. Two short C–N
˚
bonds, C(5)–N(1) [1.393(4) A] and C(6)–N(1) [1.345(4) A],
˚
˚
and the other short C–N bond, C(8)–N(2) [1.411(4) A],
arises from the conjugation of the lone pair of electron on and
N1 and N2 with the quinolone group, respectively. The bond
angles around N1 and N2 are different.
In DL-lemenfloxacin, the bond lengths of C(1)–O(2) and
˚
C(1)–O(1) [1.258(9) and 1.265(12) A] in the disorder
Figure 3 shows the IR spectrum of the title compound.
-
The broad band from 3,300 to 3,500 cm centering at
1
-
1
3,415 cm is due O–H stretching of the disorder water
carboxylate group are little longer than the C(3)–O(3) bond
˚
length [1.246(4) A] which is the shortest length, and are in
-
1
molecules, and the strong peak at 3,083 cm
may be
good agreement with the mean value observed for C–O
˚
bonds in carboxylate ions [1.268(4) and 1.253(4) A,
attributed to N–H stretching of the protonated piperazinyl
group. It is interesting to note that there exist broad band
-
ranging from 2,759 to 2,458 cm for the lomenfloxacin
1
respectively] reported [5].
1
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J Chem Crystallogr (2009) 39:384–388
387
Fig. 2 Crystal packing viewed along the b axis. H-bonding for water molecules are omitted for clarity, and others are shown as dashed lines
-
1
[
6], which is characteristic of mas(NH) stretching vibra-
tion; and that there is no such band for the DL-
from 1,725 to 1,700 cm
and the later ranging from
-
1
-1
1,550 to 1,630 cm . The peak at 1,725 cm is consistent
with lomenfloxacin HCl where the carboxyl group may
remain its carboxylic form. But, it is contradicted to lo-
menfloxacin, where, as it is revealed in this study, the
lomenfloxacin in this study. There strong peak of the title
-
1
compound at 1,612 cm may be attributed to C=O of the
quinolone ring stretching, which as is conjugating with the
benzene ring and carboxylate. There is also a moderate
carboxyl group turns to be a carboxylate. The CH
-1
deformation vibration appears at 1,468 cm . Besides, DL-
2
-
1
peak at 1,587 cm which may be attributed to C=O of
the carboxylate. There are two different C=O in the lo-
menfloxacin molecule, and there must have two different
C=O peaks in the IR spectrum of lomenfloxacin. But,
lomenfloxacin has a moderate broad band in the region of
-
1
1,001–1,141 cm which can be assigned to benzene and
pyridine ring breathing. The bands between 654 and
-1
-
1
there is only one C=O peak at 1,725 cm for lomen-
floxacin in Wang’s study [6]. In infrared spectra, the
carboxylic group always show up at much higher wave
number than the carboxylate does, the former ranging
822 cm which is due to C–N and C–F stretching, are
-
1
moderate. There is a moderate peak at 513 cm , which
attributes to ring deformation. In a sum, the title com-
pound is different from Wang’s and Xu’s sample.
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J Chem Crystallogr (2009) 39:384–388
4
000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Fig. 3 IR spectrum of DL-lomefloxacin hydrate
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