Crystal structure and conformation study of 4-N,N-dimethylamine benzaldehyde thiosemicarbazone derivative

Article abstract of DOI:10.1080/15421400903568138

Thiosemicarbazones are N-N-S donor ligands having the ability to bind metal ions and inhibit ribonucleoside reductase, an enzyme important for DNA synthesis of all the mammalian cells. One of the important phenyl thiosemicarbazones, the title compound, ha

Full text of DOI:10.1080/15421400903568138

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Crystal Structure and Conformation
Study of 4-N,N-Dimethylamine
Benzaldehyde Thiosemicarbazone
Derivative
a b
a
b
N. Sampath
, Rita Mathews , M. N. Ponnuswamy & Lin-Woo
a
Kang
a
Department of Advanced Technology Fusion , Konkuk University ,
Gwangjin-gu, Seoul, Korea
b
Department of Crystallography and Biophysics , University of
Madras, Guindy Campus , Chennai, India
Published online: 18 Mar 2010.
To cite this article: N. Sampath , Rita Mathews , M. N. Ponnuswamy & Lin-Woo Kang (2010) Crystal
Structure and Conformation Study of 4-N,N-Dimethylamine Benzaldehyde Thiosemicarbazone
Derivative, Molecular Crystals and Liquid Crystals, 518:1, 151-159, DOI: 10.1080/15421400903568138
To link to this article: http://dx.doi.org/10.1080/15421400903568138
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Mol. Cryst. Liq. Cryst., Vol. 518: pp. 151–159, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400903568138
Crystal Structure and Conformation Study
of 4-N,N-Dimethylamine Benzaldehyde
Thiosemicarbazone Derivative
1
N. SAMPATH, RITA MATHEWS,
,2
1
2
M. N. PONNUSWAMY, AND LIN-WOO KANG
1
1
Department of Advanced Technology Fusion, Konkuk University,
Gwangjin-gu, Seoul, Korea
2
Department of Crystallography and Biophysics, University of Madras,
Guindy Campus, Chennai, India
Thiosemicarbazones are N-N-S donor ligands having the ability to bind metal ions and
inhibit ribonucleoside reductase, an enzyme important for DNA synthesis of all the
mammalian cells. One of the important phenyl thiosemicarbazones, the title compound,
has been synthesized and its stereo projection was analyzed by crystallographic methods.
The X-ray data of DABT are C H N S; M.W ¼ 222.31, monoclinic, space group
1
0
14 4
˚
˚
3
˚
ꢀ
P2
1
1
=n, a ¼ 5.677(7)A, b ¼ 8.951(2)A, c ¼ 22.773(4)A, b ¼ 93.51(5) ; V¼
˚ ˚
a 1 2
3
155.1(1)A , Z¼ 4, Dcal ¼ 1.278 Mg=m , k (Cu K
) ¼ 1.54184 A, final R
and wR
are 0.0563 and 0.1407, respectively. The molecular packing can be viewed as a dimer
held together by two N-H ꢁ ꢁ ꢁ S type intermolecular hydrogen bonds. In addition to
van der Waals forces, C-H ꢁ ꢁ ꢁ N, N-Hꢁ ꢁ ꢁ S, C-H ꢁ ꢁ ꢁ S, and N-H ꢁ ꢁ ꢁ N types of inter-
and intramolecular hydrogen bonds facilitate the molecules in crystal packing.
Keywords Conformation; heterocyclic; hydrogen bond; space group; thiosemi-
carbazone
Introduction
The relationship between the metal ions and cancer are interesting and controversial.
French and Freedlander [1] suggested that some antitumor agents possess the ability
to function as chelating agents. So, French and Blanz [2] prepared many thiosemicar-
bazone (TSC) derivatives and found that all the tumor inhibitors potentially act as
N-N-S type donor ligands. The biological activities of TSCs depend on the parent
aldehydes or ketones [3]. Pyridine-2-carbaldehyde thiosemicarbazone was the first
heterocyclic compound (HFoTsc) reported to have carcinostatic properties [4].
The mechanism of action of HFoTsc is due to its ability to inhibit the biosynthesis
of DNA, possibly by blocking the enzyme ribonucleoside reductase (RNR) or block-
ing base replication; creation of lesions in DNA strands by oxidative rupture [4,5].
Address correspondence to N. Sampath, Department of Advanced Technology Fusion,
Konkuk University, Hwayang dong 1, Gwangjin-gu, Seoul 143-701, Korea. E-mail: sampath@
konkuk.ac.kr or M. N. Ponnuswamy, Department of Crystallography and Biophysics, Univer-
sity of Madras, Guindy Campus, Chennai, India. E-mail: mnpsy@hotmail.com
151

1
52
N. Sampath et al.
Scheme 1. Chemical diagram of DABT molecule.
Thiosemicarbazone is a versatile tridentant ligand, which combines with aldehydes
or ketones to generate the TSC derivatives. These types of derivatives have a wide range
of biological activities such as antitumor [6], antimalarial [7], antileukemic [8], antiviral
[
9], antibacterial [10], and antifertility [11] properties because of their reduction
capabilities. The TSC moiety is planar and adopts an extended (E) conformation
due to the extensive p-electron delocalization throughout the moiety. In general, the
N, S donor ligands of TSCs are attributed to their ability to form metal chelates [12]
and non linear optical properties [13] due to their reductive capacities [14].
The electrons are smearing on the sulfur and hydrazinic N atoms due to electron
delocalization, which helps in complexation with positively charged metal ions. Both
these S and N atoms chelate to metal ions of the biological molecule and are believed
to possess the pharmaceutical activity of this molecule. In addition to the biological
properties, the TSCs possess second-order nonlinear optical (NLO) properties,
which have broad applications in opto-electronics, such as optical frequency conver-
sion [15,16] and optical parameter oscillator (OPO).
As a part of the ongoing study on thiosemicarbazone derivatives, four different
para- substituted phenyl thiosemicarbazone derivatives have been synthesized and
their antimicrobial activity has been tested against 10 different bacterial species and
2
Candida fungi (unpublished results). Among these, the compound 4-N,N-
dimethylaminebenzaldehyde thiosemicarbazone (DABT) reduces the bacterial and fun-
gal growth significantly. In order to analyze the stereochemistry and molecular
geometry of DABT, it was synthesized and characterized by X-ray crystallography
method. The chemical diagram of compound DABT is shown in Scheme 1.
Experiments
Synthesis of Phenyl Thiosemicarbazones
The respective benzaldehyde (1) (0.1 M) was taken in the medium of 100% ethanol along
with a little higher quantity (0.12 M) of thiosemicarbazide (2) in the presence of a few
drops of conc. HCl. This reaction mixture was allowed to react on a water bath for
4 h and the respective thiosemicarbazone (3) derivative was separated out as colorless
solids and dried. The dried samples were crystallized using suitable organic solvents.

X-Ray Structure of a Phenyl Thiosemicarbazone Derivative
X-Ray Data Collection and Reduction
153
A single crystal of DABT was mounted on a glass fiber and used for data collection.
Cell constants and an orientation matrix for data collection were obtained by
least-squares refinement of the diffraction data from 25 reflections in an ENRAF–
NONIUS CAD4 automatic diffractometer [17]. Data were collected at 293(2) K
˚
using CuKa radiation (k ¼ 1.54184 A) (University of Madras, Chennai, India) and
the data reduction was carried out by XCAD4 [18] program. Out of 3614 reflections
collected, 3304 reflections with I ꢂ 2r(I) were used for structure solution and refine-
ment. The intensity data were corrected for Lorentz and polarization effects.
Structure Solution and Refinement
The structure was solved by direct methods using the program SHELXS97 [19],
2
which revealed the position of all non-hydrogen atoms, and refined on F by a
full-matrix least squares procedure using SHELXL97 [19]. The non-hydrogen atoms
were refined anisotropically and the positions of hydrogen atoms were derived
from the difference Fourier map. The final cycle of refinement converged to
R ¼ 0.0563 and wR ¼ 0.1407 for the observed reflections. The maximum and mini-
1
2
mum heights in the final difference Fourier map were found to be 0.440 and ꢃ0.261
ꢃ3
˚
e ꢁ A , respectively. Least-squares planes and asymmetry calculations were done
using the program PARST97 [20]. The thermal ellipsoid plot and packing were done
respectively using ORTEP [21] and PLATON [22]. Non-bonded interaction graphics
were created using the program PLATON [22]. The crystallographic data and meth-
ods of data collection, solution, and refinement are shown in Table 1 and the atomic
coordinates of the non-hydrogen atoms with their equivalent thermal displacement
parameters are presented in Table 2. All other information about DABT structure
is included in the deposited material (CCDC 744645).
Result and Discussion
The synthesized phenyl thiosemicarbazone derivatives, namely DABT crystallized in
monoclinic space group P2 =n. The perspective view of DABT ORTEP diagram is
1
shown in Fig. 1. The S atom and the hydrazinic N8 atom are trans with respect to
C10-N9 bond. A similar type of trans configuration is noted in many structures of
thiosemicarbazide [23], N-methyl-2,6-diphenyl-3-isopropyl piperidin-4-one thiosemi-
carbazone [24] and 3,4,5-trimethoxy benzaldehyde thiosemicarbazone monohydrate
[
25]. The torsion angles and mean plane calculations confirm that the whole TSC
moiety adopts an extended conformation and almost lies in the same plane of the
benzene ring. The corresponding torsion angles of TSC are as follows:
ꢀ
Angle ( )
DABT
Conformational bonds
C7-N8-N9-C10
N8-N9-C10-N11
N8-N9-C10-S1
175.8 (2)
5.7 (3)
174.1 (1)
˚
The bond length variation in C4-C7 of molecule DABT [1.441(3)A] indicates the
˚
influence of conjugation between the phenyl ring and C7-N8 [1.277(2)A for DABT]

1
54
N. Sampath et al.
Table 1. Crystal data and other relevant details for DABT
Parameters
DABT
CCDC 744645
CCDC
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system, space group
Unit cell dimensions
C H N S
10 14 4
222.31
293(2) K
˚
0.71073 A (Mo K )
Monoclinic, P2 =n
1
a
˚
˚
a ¼ 5.677(7)A
b ¼ 8.951(2)A
˚
c ¼ 22.773(4)A
ꢀ
b ¼ 93.51(5)
3
˚
Volume A
1155.1(1)
4, 1.278 Mg=m
3
Z, Calculated density
Absorption coefficient
F(000)
Theta range for data collection
Limiting indices
ꢃ1
0.254 mm
472
ꢀ
1.79 to 30.00
0 ꢄ h ꢄ 7
0
ꢄ k ꢄ 12
ꢃ31 ꢄ l ꢄ 31
Reflections collected=unique
Refinement method
Data=restraints=parameters
3614=3304 [R ¼ 0.021]
int
2
Full-matrix least-squares on F
3304=0=192
1.095
2
Goodness-of-fit on F
Final R-indices [I > 2r(I)]
R-indices (all data)
Largest diff. peak and hole
R ¼ 0.0563, wR ¼ 0.1407
1
2
R ¼ 0.0887, wR ¼ 0.1618
1
2
ꢃ3
˚
0.440 and ꢃ0.261 e ꢁ A
imine double bonds. A similar effect is also noted in some other structures, 2,3-dihy-
0
droxybenzaldehyde thiosemicarbazone [26] and salicylaldehyde-4,4 -(hexane-1,6-diyl)
thiosemicarbazone [27]. The bond lengths (Fig. 2a) in the thiosemicarbazone moiety
show electron delocalization effect (Scheme 2) and this is extended even up to the imine
nitrogen group. The TSC moiety and phenyl ring almost lie in the same plane, which is
ꢀ
confirmed by the orientation angle of 15.5(1) .
The bond angle of C2-C1-C6 [117.0(2) ] in DABT is comparatively much
ꢀ
ꢀ
shorter than other reported structures having bond angle ranges from 120 to 121
[
26,27]. This may be due to the effect of H ꢁ ꢁ ꢁ H short contacts between the atoms
˚ ˚
H14B ꢁ ꢁ ꢁ H6 ¼ 2.02(4)A and H2 ꢁ ꢁ ꢁ H13B ¼ 2.22(3)A. These short contacts create
electron–electron repulsion between the hydrogens, pushing the atoms C2 and C6
in opposite directions. The bond lengths of C1-C2, C1-C6, C3-C4, and C4-C5 in
˚
DABT molecule are 1.419(3), 1.399(3), 1.395(3), and 1.393(2)A, respectively. These
˚
lengths are considerably higher than the normal value of 1.37 A. These bond length
variations are attributed to the resonance character of the dimethyl amine, phenyl
ring and also that of imine nitrogen (Scheme 3).
In DABT, the whole molecule lies almost in the same plane. This happens due to
the presence of hetero p-electron delocalization in the entire molecule (Scheme 3).

X-Ray Structure of a Phenyl Thiosemicarbazone Derivative
155
4
Table 2. Atomic coordinates (ꢅ10 ) and their equivalent isotropic displacement
2
3
˚
parameters (A ꢅ 10 ) for the non-hydrogen atoms of DABT
ꢆ
Ueq
Atoms
x
y
z
S1
C1
C2
C3
C4
C5
C6
C7
N8
N9
C10
N11
N12
C13
C14
7026(1)
ꢃ2779(3)
ꢃ2787(3)
ꢃ1175(3)
557(3)
3445(1)
3653(2)
4491(2)
4225(2)
3130(2)
2301(2)
2541(2)
2861(2)
3534(2)
3189(2)
3751(2)
4532(2)
3909(2)
5142(3)
3147(4)
574(1)
3518(1)
2989(1)
2581(1)
2669(1)
3187(1)
3599(1)
2269(1)
1776(1)
1459(1)
921(1)
70(1)
50(1)
54(1)
51(1)
48(1)
57(1)
58(1)
52(1)
50(1)
55(1)
48(1)
58(1)
63(1)
67(1)
90(1)
558(4)
ꢃ1059(4)
2381(4)
2455(3)
4365(3)
4559(3)
2765(3)
690(1)
ꢃ4373(3)
ꢃ6017(4)
ꢃ4166(7)
3925(1)
3859(1)
4483(1)
P P
ꢆ
ꢆ
ꢆ
U
eq ¼ (1=3)
i
j
U
ij
a
i
j i
a a
ꢁ a
j
.
ꢀ
The corresponding torsion angles [C2-C1-N12-C13¼] ꢃ 5.6(3) , [C6-C1-N12-C13¼]
ꢀ
ꢀ
ꢀ
1
this fact. The sum of the bond angles around the atom N12 is 358.7 , thus confirm-
74.8(2) , [C2-C1-N12-C14¼] ꢃ 173.6(2) , and [C6-C1-N12-C14¼] 6.9(3) support
ꢀ
2
ing that the atom N12 is in sp hybridized state. The N,N-dimethyl group is oriented
ꢀ
at an angle of 10.4(2) to the phenyl ring. This deviation in planarity is attributed by
the short contacts between the H13B ꢁ ꢁ ꢁ H2 and H14B ꢁ ꢁ ꢁ H6.
Packing Features
The packing molecule of DABT viewed down the b-axis is shown in Fig. 3. The
molecules are stabilized by N-H ꢁ ꢁ ꢁ N, N-H ꢁ ꢁ ꢁ S, C-H ꢁ ꢁ ꢁ S, and C-H ꢁ ꢁ ꢁ N types of
Figure 1. ORTEP diagram of the molecule DABT showing the thermal ellipsoids at 30%
probability level.

1
56
N. Sampath et al.
˚
Figure 2. Geometrical diagram of the molecules of DABT (a) Bond lengths (A); (b) bond
ꢀ
ꢀ
angles ( ); (c) selected torsion angles ( ). Hydrogen atoms are removed for clarity.
intra- and intermolecular hydrogen bonds (Table 3). The N-H ꢁ ꢁ ꢁ N type intra
molecular hydrogen bond forms a five-membered ring and this facilitates TSC moi-
ety to form an extended conformation [28,29]. A pair of N11-H11 ꢁ ꢁ ꢁ S hydrogen
bonds across the centers of inversion result in a dimer between the symmetry related
molecules of DABT. Such dimerization has also been observed in similar structures
Scheme 2. Resonance structures of thiosemicarbazone (TSC) moiety.

X-Ray Structure of a Phenyl Thiosemicarbazone Derivative
157
Scheme 3. Resonance character of the DABT structure.
Figure 3. Packing of the molecules DABT viewed down the b-axis. Dashed lines represent
hydrogen bonds.
Table 3. Hydrogen bondings and the possible non-bonded interactions
ꢀ
˚
for DABT ( , A)
D-H ꢁ ꢁ ꢁ A
d(D-H)
d(D ꢁ ꢁ ꢁ A)
d(H ꢁ ꢁ ꢁ A)
<D-H ꢁ ꢁ ꢁ A
N11-H11A ꢁ ꢁ ꢁ N8
0.87(3)
0.94(2)
0.95(3)
0.87(3)
0.90(2)
0.950
2.645(2)
3.555(3)
3.896(3)
3.395(4)
3.409(2)
3.644
2.30(3)
2.72(2)
3.00(3)
2.75(3)
2.52(2)
2.960
105.9(2)
151.5(1)
160.2(3)
135.0(5)
174.6(1)
130.6
i
C5-H5 ꢁ ꢁ ꢁ N8
ii
C13-H13A ꢁ ꢁ ꢁ S1
iii
N11-H11A ꢁ ꢁ ꢁ S1
iv
N11-H11B ꢁ ꢁ ꢁ S1
iii
C13-H13B ꢁ ꢁ ꢁ Cg
Equivalent positions:
i. ꢃx þ 1=2, y ꢃ 1=2, ꢃz þ 1=2
ii. ꢃx þ 1=2, y þ 1=2, ꢃz þ 1=2
iii. x ꢃ 1, y, z
iv. ꢃx þ 1, ꢃy þ 1, ꢃz
Cg is the centroid of the benzene ring [Cg ¼ C1 through C6].

1
58
N. Sampath et al.
like piperidine thiosemicarbazone derivatives [29] and it is found to be a common
feature of these moieties. This dimer interaction extends along the a-axis and makes
a catenation to help the crystal pack tightly. In addition to van der Waals forces,
another weak C-H ꢁ ꢁ ꢁ p [Cg ¼ C1 through C6] interaction [30] helps the molecules
for crystal packing.
Supplementary Material
Crystallographic data (excluding structure factors) for the structure reported in this
article have been deposited with the Cambridge Crystallographic Database Centre
as supplementary publication no. CCDC 744645. Copies of available material can
be obtained free of charge at http://www.ccdc.cam.ac.uk/conts/retrieving.html
(
1
or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: þ44
223336033; e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgement
NS is grateful to the Council of Scientific and Industrial Research (CSIR), India,
for a Senior Research Fellowship (SRF). The author is also grateful to Konkuk
University for its support.
References
[1] French, F. A., & Freedlander, B. L. (1958). Canc. Res., 18, 1290.
[2] French, F. A., & Blanz, E. J., Jr. (1966). J. Med. Chem., 9, 585.
[3] Scovill, J. P., Klayman, D. L., & Franchino, C. F. (1982). J. Med. Chem., 25, 1261.
[4] Agrawal, K. C., & Sartorelli, A. C. (1978). Prog. Med. Chem., 15, 321.
[5] Miller, M. C., Stineman, C. N., Vance, J. R., West, D. X., & Hall, I. H. (1998). Anticanc.
Res., 18, 4131.
[
[
6] Klayman, D. L., Scovill, J. P., Bartosevich, J. F., & Mason, C. J. (1979). J. Med. Chem.,
22, 1367.
7] Nagarajan, K., Talwalker, P. K., Kulkarni, C. L., Venkateswaralu, A., Prabhu, S. S., &
Nayak, G. V. (1984). Indian J. Chem., 23B, 1243.
[
[
8] Cymerman, J. C., Willis, D., Rubbo, S. D., & Edgar, J. (1955). Nature (London), 176, 34.
9] Tian, Y.-P., Duan, C.-Y., Lu, Z.-L., You, X.-Z., Fun, H.-K., & Kandasamy, S. (1996).
Polyhedron, 15, 2263.
[
[
[
10] Palenik, G. J., Rendle, D. F., & Carter, W. S. (1974). Acta Crsyt., B30, 2390.
11] Buland, D. M. (1994). Chem. Rev., 94, 1.
12] Chemla, D. S., & Zyss, J. (1987). Nonlinear Optical Properties of Organic Molecules and
Crystals, v. 1=2. Academic Press: New York, 1.
[13] French, F. A., & Freedlander, B. L. (1958). Canc. Res., 18, 1290.
[14] Scovill, J. P., Klayman, D. L., & Franchino, C. F. (1982). J. Med. Chem., 25, 1261.
[15] Agrawal, K. C., & Sartorelli, A. C. (1978). Prog. Med. Chem., 15, 321.
[16] Miller, M. C., Stineman, C. N., Vance, J. R., West, D. X., & Hall, I. H. (1998). Anticanc.
Res., 18, 4131.
[17] Enraf-Nonius. (1994). CAD-4 EXPRESS Software. Enraf-Nonius, Delft: The
Netherlands.
[
[
18] Harms, K. (1996). XCAD4, University of Marburg: Germany.
19] Sheldrick, G. M. (1997). SHELXS97: Program for the Crystal Structure Solution and
Refinement, University of Gottingen: Germany.
[20] Nardelli, M. (1995). J. Appl. Cryst., 28, 659.

X-Ray Structure of a Phenyl Thiosemicarbazone Derivative
159
[
[
[
[
21] Vickovic, I. (1994). ORTEP 92. J. Appl. Cryst., 27, 473.
22] Spek, A. L. (2003). PLATON Molecular Graphics Program. J. Appl. Cryst., 36, 7.
23] Hansen, F., & Hazell, R. (1969). Acta. Chem. Scand., 23, 1359.
24] Sampath, N., Malathy Sony, S. M., Nethaji, M., & Ponnuswamy, M. N. (2003). Acta
Cryst., C59, o346.
[25] Kokila, M. K., Puttaraja, K. M. V., & Sarala, T. (1995). Acta Cryst., C51, 330.
[26] Latheef, L., Manoj, E., & Kurup, M. R. P. (2006). Acta Cryst., C62, o16.
[27] Swesi, A. T., Farina, Y., Kassim, M., & Ng, S. W. (2006). Acta Cryst., E62, o5457.
[28] Sampath, N., Ponnuswamy, M. N., & Nethaji, M. (2006). Cryst. Res. Tech., 41, 192.
[29] Sampath, N., Ponnuswamy, M. N., & Nethaji, M. (2006). Mol. Cryst. Liq. Cryst., 452, 93.
[30] Desiraju, G. R. (1989). Crystal engineering—The design of organic solids. In: Material
Science Monographs, No. 54. Desiraju, G. R. (Ed.), Elsevier Science: New York,
85–113.