Synthesis and crystal structure of thiazole orange derivative

Article abstract of DOI:10.1007/s10870-011-0080-0

The title compound of Thiazole Orange derivative was synthesized by the reaction of benzothiazolium and 4-methyl quinoline salts, which was determined by 1HNMR and MS. A crystalline hydrate of thiazole orange derivative was obtained when the crystal formed and characterized by single-crystal X-ray diffraction. The crystal belongs to the Triclinic system, and the cell parameters of space group P-1 were a = 10.162(2) A, b = 10.501(2) A, c = 11.040(2) A, α = 92.17(3)^o, β = 117.10(3) ^o, γ = 92.28(3)^o, V = 1045.9(4) A³, Z = 2, Dc = 1.380 mg/m^-3, μ = 0.2 mm^-1, F(000) = 460, and the final R = 0.0625 and wR = 0.1862 for 3658 observed reflections (I > 2σ(I)). The two aromatic rings linked by the methylene bridged chain are a coplanar structure.

Full text of DOI:10.1007/s10870-011-0080-0

J Chem Crystallogr (2011) 41:1232–1236
DOI 10.1007/s10870-011-0080-0
ORIGINAL PAPER
Synthesis and Crystal Structure of Thiazole Orange Derivative
•
Xuening Fei Yingchun Gu Yunquan Lan
•
•
•
Bin Shi Baolian Zhang
Received: 20 November 2009 / Accepted: 15 April 2011 / Published online: 2 May 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compound of Thiazole Orange deriv-
ative was synthesized by the reaction of benzothiazolium
and 4-methyl quinoline salts, which was determined by
1HNMR and MS. A crystalline hydrate of thiazole orange
derivative was obtained when the crystal formed and
characterized by single-crystal X-ray diffraction. The
crystal belongs to the Triclinic system, and the cell param-
basic groups in DNA, identify the status of amino group
and the active site of proteins, detect protein at the
picomolar scale, distinguish nucleic acids with different
conformations and the chemically reactive activities of
related drugs [1–3].
Thiazole orange (TO), a benzothiazole ring covalently
linked to a quinoline ring through a monomethine bridge,
has been widely used as the embedded cyanine dye for
labeling nucleic acids. The probe inserting into DNA
structures by affinity is remarkable, which is due to their
significant fluorescence enhancements when bound to cel-
lular nucleic acids or to a specific surface-expressed protein
partner [4] in sharp contrast to their low quantum yield in
solution [5]. Design and modification fluorescent dyes can
improve their application properties in the development of
biological markers. So the transformation and modification
of fluorescent dyes are much concerned [6] shown as
below:
˚
eters of space group P-1 were a = 10.162(2) A, b =
o
o
˚
˚
10.501(2) A, c = 11.040(2) A, a = 92.17(3) , b = 117.10(3) ,
o
3
-3
˚
c = 92.28(3) , V = 1045.9(4) A , Z = 2, Dc = 1.380 mg/m ,
l = 0.2 mm-1, F(000) = 460, and the final R = 0.0625
and wR = 0.1862 for 3658 observed reflections (I [ 2r(I)).
The two aromatic rings linked by the methylene bridged
chain are a coplanar structure.
Keywords Thiazole orange derivative Á Single crystals Á
Characterization Á Coplanar structure
(1) Design, synthesis and modification of fluorescent
probe molecules [7],
Introduction
(2) Synthesis methods of cyanine dyes [8, 9],
(3) Targeting labeling between fluorescent probe and
cancer cells [10, 11],
Fluorescent dyes probes have attracted much attention
because of their specialities with fast detection speeds,
good repeatability, low dosage, and non-radiation advan-
tage. The cyanine dye based probe is used to detect the
structures of RNA and DNA, study the remedy of damaged
(4) Improvements of strength and sensitivity fluorescent
dyes [12–14].
In recent years, researchers intensively investigated the
modification of TO on the ring of benzothiazole or the side-
chain binding with nitrogen on lepidine to improve their
fluorescence intensities [15–24]. The substituent group on
N of lepidine greatly affected the fluorescent properties of
biomacromolecule labeled by probe. Changing the alkyl
group on N of molecules can adjust the solubility and affect
the aggregation behavior of dye. For example, long-chain
alkyl group on N of cyanine dye can decrease or eliminate
X. Fei Á Y. Gu
School of Chemical Engineering and Technology,
Tianjin University, Tianjin 300072, China
X. Fei (&) Á Y. Gu Á Y. Lan Á B. Shi Á B. Zhang
Department of Material Science and Engineering, Tianjin
Institute of Urban Construction, No. 26 Jinjing Road,
Xiqing District, Tianjin 300384, China
e-mail: xueningfei@126.com
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J Chem Crystallogr (2011) 41:1232–1236
1233
the crystallization caused by aggregation. Introducing
proper hydrophilic substituent group onto N of lepidine can
extended the application field in labeling protein.
Carboxyl group play a key role in the formation of
protein and it can combine with the hydrophilic group such
as amino, hydroxyl, mercapto group to form hydrogen
bond, which can make the dye insert into the structure of
protein. There will be a torsion in the molecular structure
of dye because it may be affected by the constrain from the
skelet of the protein, so the fluorescence of dye will be
enhanced [25].
solubility. A saturated solution of TO-COOH in methanol
at 25 °C was filtered thrice to remove suspended particles.
The solution was then transferred into a beaker and allowed
for slow evaporation at ambient temperature and the
crystalline hydrate of TO-COOH was obtained. The
resulting crystals are stable and non-hygroscopic at room
temperature. 1H NMR (300 MHz, DMSO-d6): d 2.74
(t, J = 6.45 Hz, 2H), 3.99 (s, 3H, CH3), 4.74 (t, J =
6.10 Hz, 2H,), 6.88 (s, 1H), 7.32 (d, J = 6.9 0 Hz, 1H),
7.40 (t, J = 7.65 Hz, 1H), 7.60 (t, J = 7.80 Hz, 1H),
7.75–7.78 (m, 2H), 7.96(t, J = 7.8 Hz, 1H), 8.00(d, J =
The fluorescent properties and the application of TO and
its derivatives with carboxyl groups in biochemistry pro-
voked us to study the crystal structure of TO derivative
with carboxylic acid groups (TO-COOH).
Table 1 Crystal structure data for the title compound
Formula
C21H26N2O6S
434.50
In this article, we present our results on the synthesis
and crystal growth of TO-COOH. The structure is shown in
Fig. 1. The crystal of the title compound belongs to the P-1
space group in triclinic crystal system.
Formula weight
CCDC deposit no
Temperature (K)
Wavelength
CCDC-739300
113(2)
0.71073 A
Triclinic
P-1
Crystal system
Space group
Experimental
˚
a (A)
10.162(2)
10.501(2)
11.040(2)
92.17(3)
117.10(3)
92.28(3)
0.2
1HNMR spectra were recorded on a Bruker AC-P300
(300 MHz) spectrometer. Chemical shifts are reported in
parts per million (ppm) downfield from TMS (tetrameth-
ylsilane), using DMSO-d6 as a solvent. Mass spectral
analyses were obtained using an electrospray ionization
(ESI) mass spectrometer.
˚
b (A)
˚
c (A)
a (o)
b (°)
c (°)
l (mm-1
)
3
Volume (A )
The dye was synthesized by a slightly modified proce-
dure described previously [25]. The benzothiazolium was
prepared via nitrogen quaternization by reacting 2-ben-
zylmercaptobenzothiazole with methyl p-methyltoluene-
sulfonate at 110 °C for 24 h and 4-methyl quinoline salts
of was synthesized from 4-methylquinoline reacting with
3-bromopropionic acid in refluxing acetone for 8 h. The
dye was obtained in 97% yield by condensation of the
corresponding benzothiazolium with 4-methyl quinoline
salts and triethylamine (Et3N) in ethanol at room temper-
ature for 1 h.
˚
1045.9(4)
2
Z
Calculated density (g/cm3)
Absorption coefficient (mm-1
F(000)
1.380
)
0.196
460
Crystal size (mm)
0.20 9 0.16 9 0.12
1.94–25.02
h Range for data collection (°)
Index ranges
-12 B h B 12,
-12 B k B 12,
-13 B l B 13
Reflections
collected/unique [R(int)]
8366/3658 [0.0358]
To grow the crystal, the solubility of the compound was
evaluated in numerous solvents such as acetone, methanol,
DMF and DMSO. Its solubility in DMSO and DMF is
higher compared to that in methanol and acetone. We used
methanol as the solvent to grow crystal due to its moderate
Completeness (%)
Refinement method
99.1 (to 25.02)
Full-matrix least-squares
procedure on F2
1/[r2(F2o) ? (0.1362P)2
? 0.0230P], where
P = (F2o ? 2F2c)/3),
Weight, w
O
Data/restrains/parameters
Goodness-of-fit on F2
3658/27/308
S
1.089
C
N
OH
Final R indices [I [ 2sigma(I)]
R indices (all data)
R1 = 0.0625, wR2 = 0.1862
R1 = 0.0787, wR2 = 0.2079
0.9769 and 0.9619
0.752 and -0.433
N
H
OTs
Max. and min. transmission
-3
)
˚
Largest diff. peak and hole (e A
Fig. 1 Main structure of the title compound
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J Chem Crystallogr (2011) 41:1232–1236
7.8 Hz, 1H), 8.12 (d, J = 9.00 Hz, 1H), 8.69 (d, J =
9.00 Hz, 1H), 8.77 (d, J = 9.00 Hz, 1H). ESI–MS: m/e
363.25 (M?), 364.25 (M?? 1).
Results and Discussion
The selected bond lengths and bond angles are listed in
Table 2, and the selected torsion angles for non-hydrogen
atoms are given in Table 3. The molecular structure of the
title compound is shown in Fig. 2. The crystal belongs to a
crystalline hydrate with 6 crystal water. The packing dia-
gram of the title compound in a unit cell is shown in Fig. 3.
The O–HÁÁÁO hydrogen bonds among the crystalloid water
exist in the crystal.
Structure Determination and Refinement
A red crystal of the title compound having approximate
dimensions of 0.20 9 0.16 9 0.12 cm3 was mounted on
the top of a glass fiber. X-ray diffraction data were col-
lected on a Bruker Smart-1000 CCD diffractometer
equipped with a graphite-monochromatized MoKa radia-
The bond length of C9–C10 and C9–C8 on the bridged
˚
chain are 1.403(4) and 1.389(4) A respectively, between
˚
tion (0.7170 A) by using an x/u scan mode in the range
the length of C–C and C=C suggesting that the delocal-
of 1.94 B h B 25.02° (-12 B h B 12, -12 B k B 12,
-13 B l B 13) at 113(2) K. A total of 8366 reflections were
collected with 3658 unique ones (Rint = 0.0359), of which
2901 with I [ 2r(I) were observed. The structure was solved
by direct methods and refined on F2 by full-matrix least-
squares procedure with SHELXS-97 and SHELXL-97 [26].
The crystal data and other structure refinement parameters of
the title compound are listed in Table 1.
ization of p electrons exists. The length of C9–H9
˚
(0.9300 A) is similar to that of aromatic hydrogen and
shorter than the typical C–H. The angle of C11–C10–C9–
C8 (-0.7 (5)°)indicates that C11, C10, C9, C8 are in a
plane. In the meanwhile we find that the angles of C18–
C10–C9–C8 and C9–C10–C18–C13 are 179.3 (3)° and
-179.3 (3)° respectively, which indicate that C18, C13,
C10, C9, C8 are in a plane. So, quinoline ring is planar with
˚
Table 2 Selected bond lengths (A) and bond angles (°)
Bond
Dist.
Bond
Dist.
Bond
Dist.
S(1)–C(1)
S(1)–C(8)
O(1)–C(21)
N(1)–C(8)
N(1)–C(6)
N(1)–C(7)
O(2)–C(21)
1.731(3)
1.740(3)
1.237(4)
1.368(4)
1.393(4)
1.461(4)
1.261(4)
C(10)–C(11)
C(10)–C(9)
C(10)–(18)
C(9)–C(8)
1.399(4)
1.403(4)
1.462(4)
1.389(4)
0.9300
N(2)–C(19)
C(21)–(20)
C(17)–C(16)
C(20)–C(19)
C(13)–C(14)
C(11)–(12)
C(16)–C(15)
1.499(4)
1.537(4)
1.352(5)
1.499(5)
1.396(5)
1.377(4)
1.407(5)
C(9)–H(9)
N(2)–C(12)
N(2)–C(13)
1.336(4)
1.392(4)
Angle
(°)
Angle
(°)
Angle
(°)
C(8)–N(1)–C(6)
C(8)–N(1)–C(7)
C(6)–N(1)–C(7)
N(1)–C(8)–C(9)
N(1)–C(8)–S(1)
C(9)–C(8)–S(1)
115.0(2)
122.1(2)
122.9(2)
122.1(3)
110.2(2)
127.6(2)
C(11)–C(10)–C(9)
C(11)–C(10)–C(18)
C(9)–C(10)–C(18)
C(12)–N(2)–C(13)
C(12)–N(2)–C(19)
C(13)–N(2)–C(19)
124.7(3)
114.7(3)
120.6(3)
120.0(3)
118.0(3)
121.9(3)
C(8)–C(9)–C(10)
C(8)–C(9)–H(9)
128.7(3)
115.6
C(10)–C(9)–H(9)
C(13)–C(18)–C(17)
C(13)–C(18)–C(10)
C(17)–C(18)–C(10)
115.6
116.5(3)
121.0(3)
122.6(3)
Table 3 Selected torsion angles (°)
Angle
(°)
-0.7(5)
Angle
(°)
Angle
(°)
C11–C10–C9–C8
C18–C10–C9–C8
C9–C10–C18–C13
C9–C10–C18–C17
O1–C21–C20–C19
O2–C21–C20–C19
C6–N1–C8–C9
179.8(3)
C7–N1–C8–S1
C10–C9–C8–N1
C10–C9–C8–S1
C1–S1–C8–C9
178.3(2)
179.6(3)
-0.6(5)
179.6(3)
179.3(3)
-179.3(3)
1.5(4)
-0.7(4)
179.8(3)
-1.8(5)
C7–N1–C8–C9
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J Chem Crystallogr (2011) 41:1232–1236
1235
Fig. 2 X-ray crystal structure
of the title compound
The Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: ?44(0)1223-336033.
Acknowledgments The authors are grateful for financial support
from the National Natural Science Foundation of China (No. 20772090,
21072147), Key Project of Science and Technology Committee of
Tianjin, China (No.08JCZDJC18200, 10JCYBJC10500).
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CCDC 739300 contains the supplementary crystallographic
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