Electrochemical synthesis of a 6-coordinate cadmium(II) complex with N-methylisatin N(4)-cyclohexylthiosemicarbazone

Article abstract of DOI:10.1515/znb-2000-0205

Cadmium metal was oxidized in the presence of N-methylisatin N(4)-cyclohexyl-thiosemicarbazone (HMeIs4Chex) in an acetonitrile solution, which produced a complex of the formula [Cd(MeIs4Chex)₂]. The two MeIs4Chex ligands are at an angle close to 90° from each other, and there is hydrogen bonding to two adjacent molecules by the anionic ligands remaining NH groups. The complex crystallizes in the monoclinic space group P2₁/c with a = 11.820(4), b = 11.491(4), c = 27.834(4) A, β = 106.82(2)°, V = 3618.7(17) A°³ and Z = 4.

Full text of DOI:10.1515/znb-2000-0205

Electrochemical Synthesis of a 6-Coordinate Cadmium(II) Complex with
N-Methylisatin N(4)-cyclohexylthiosemicarbazone
Elena Labisbal3, Antonio Sousaa, Alfonso Castiñeiras3, Jose A. García-Vázquez3,
Jaime Romero3, Gordon A. Bainb, and Douglas X. Westb
3Departamento de Quimica Inorganica, Universidad de Santiago de Compostela,
E-15706 Santiago de Compostela, Spain
bDepartment of Chemistry, Illinois State University, Normal, IL 61790-4160
Reprint requests to Prof. Dr. A. Castineiras. FAX +34-81-547163. E-mail:qiac01 @usc.es
Z. Naturforsch. 55 b, 162-166 (2000); received October 18, 1999
Cadmium, N-Methylisatin N(4)-Cyclohexylthiosemicarbazone, Electrochemical Synthesis,
X-Ray Data
Cadmium metal was oxidized in the presence of N-methylisatin N(4)-cyclohexyl-
thiosemicarbazone (HMeIs4Chex) in an acetonitrile solution, which produced a complex of
the formula [Cd(MeIs4Chex)2]. The two MeIs4Chex ligands are at an angle close to 90° from
each other, and there is hydrogen bonding to two adjacent molecules by the anionic ligands
remaining NH groups. The complex crystallizes in the monoclinic space group P2]/c with a =
1
1.820(4), b = 11.491(4), c = 27.834(4) A, ß = 106.82(2)°, V = 3618.7(17) Ä* and Z = 4.
Introduction
only one of a 6-coordinate bis(thiosemicarbazone)
complex of cadmium reported to date,
a
Interest in compounds related to 1-methylisatin
CdN4S2 species [8]. We report here the struc-
thiosemicarbazone, methisazone, is based on its ture of a Cd02N 2S2 complex of N-methylisatin
antiviral activity [1-3]. It has been suggested that N(4)-cyclohexylthiosemicarbazone, HMeIs4Chex,
thiosemicarbazone drugs inhibit virus growth by
which is the first complex with a metal center for
binding to copper ions which are constituents of this ligand.
the virus [4]. Along with other molecular modifica-
tions, replacement of hydrogen atoms at the N(4)-
position of the thiosemicarbazone moiety, Fig. 1,
has been explored [5], A single phenyl or methyl
group attached to N(4) results in a total loss of anti-
smallpox activity, and a propenyl group reduced
activity to 4% of that of the unsubstituted thiosemi-
carbazone, while substitution of two alkyl groups at
N(4) yielded compounds with activity against ec-
tromelia and type 2 polio [6]. However, in other
I
Fig. 1. Depiction of HMeIs4Chex showing intramolec-
ular hydrogen bonding between the thiosemicarbazone
series of thiosemicarbazones possessing biological
activity, no predictable structure/activity relation- moiety and the isatin amide oxygen atom, as well as
ship for the N(4) substituent has been found to the N4-H---N1 hydrogen bonding common to N(4)-
alkylthiosemicarbazones.
date [7], Therefore, structural studies of a variety
of thiosemicarbazones coordinated to various dif-
ferent metal centers continues to be of consider-
Experimental
Reagents, materials and syntheses
able interest. Although there have been a number of
structure determinations of 5-coordinate cadmium
complexes with one tridentate thiosemicarbazone
HMeIs4Chex was prepared by condensation of 1-
methylisatin (0.05 mols, 8.05 g, Aldrich) with a 2:1 molar
ligand and two halogen ligands in the coordina- excess of hydrazine monohydrate (Aldrich) in EtOH un-
tion sphere [8-11], to our knowledge there has been
der reflux, and then reacting 0.005 mol (0.875 g) of the
0
932-0776/00/0200-0162 $ 06.00 (c) 2000 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
K
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/22/15 4:06 PM

E. Labisbai et al. ■Electrochemical Synthesis of a 6 -Coordinate Cadmium(II) Complex
163
Table 1. Crystal data and structure refinement for metal Table 2. Selected bond distances (A) and angles (°) for
complexes of N-methylisatin N(4)-cyclohexylthiosemi-
carbazone.
[Cd(MeIs4Chex)2].
Cd-N12
Cd-Sl
Cd-Ol
2.301(9)
2.569(4)
2.514(8)
Cd-N22
Cd-S2
Cd-02
2.300(9)
2.569(4)
2.515(9)
1.711(13)
1.292(13)
1.345(11)
1.343(13)
1.344(13)
1.209(14)
Empirical formula
Color, habit
Formula weight
Temperature, K
Crystal system
Space group
C32H38CdN802S2
yellow, plate
743.22
S1-C9
1.705(13) S2-C29
1.305(11) N22-C28
1.351(12) N22-N23
1.357(14) N23-C29
1.339(13) N24-C29
293(2)
N12-C8
N12-N13
N13-C9
N14-C9
Ol-Cl
monoclinic
P2,/c (#14)
11.820(4)
11.491(4)
27.834(4)
90(0)
«
[A]
MA]
c [A]
Q[°]
02-C21
1.229(13)
N12-Cd-N22 157.3(3)
S2-Cd-Sl
107.14(12)
118.0(2)
74.7(3)
70.3(3)
92.5(3)
145.0(2)
98.9(2)
N12-Cd-S2
N12-Cd-Sl
N12-Cd-01
N12-Cd-02
SI-Cd-Ol
121.6(2)
74.6(3)
70.4(3)
91.6(3)
143.8(2)
91.2(2)
80.8(3)
97.0(5)
109.1(9)
117.3(9)
N22-Cd-Sl
N22-Cd-S2
N22-Cd-02
N22-Cd-01
S2-Cd-02
S2-Cd-01
1
06.82(2)
ßl°]
9
0(0)
7
[°]
o
Volume [Ä ]
3618.7(17)
4
1.364
Z
Density [Mg/m3]
Absorption coefficient [mm-1]
Crystal size [mm]
Sl-Cd-02
0.758
0
1-Cd-02
0.25 x 0.15 x 0.15
2.34 - 24.40
-13 < h < 13
C9-Sl-Cd
C l-Ol-Cd
C8-N12-Cd
C29-S2-Cd
C21-02-Cd
C28-N22-Cd
N23-N22-Cd
96.4(5)
109.0(10)
118.6(9)
126.1(8)
9
Range for data collection [°]
Index ranges
-
-
13 < k < 0
32 < / < 13
N13-N12-Cd 125.1(7)
C8-N12-N13 117.5(11) C28-N22-N23 115.1(11)
N12-N13-C9 112.2( 11) N22-N23-C29 111.1(11)
N13-C9-N14 112.5(14) N23-C29-N24 113.1(12)
N13-C9-S1
N14-C9-S1
Ol-Cl-Nl 1
Reflections collected
Unique reflections
Absorption correction
Max. / min. transmission
Data / parameters
Goodness-of-Fit on F2
Final R indices [I > 2a(l)]
5939
5805
•//-scan
129.6(11) N23-C29-S2
117.9(11) N24-C29-S2
127.7(13) 02-C21-N21
124.4(14) 02-C21-C28
131.5(10)
115.3(11)
129.1(15)
125.8(15)
0.963/0.910
5805 / 408
0.904
R\ = 0.0676
wR2 = 0.0931
/?, =0.3926
wR2 = 0.1468
0.601 and-1.033
0
1-C1-C8
R indices (all data)
Largest diff. peak/hole [eA-3]
resulting hydrazone with an equimolar amount (0.706
g) of cyclohexyl isothiocyanate (Aldrich) in EtOH with
warming. The resulting yellow product (yield = 72%)
was washed with isopropanol followed by diethyl ether
and stored in a vacuum desiccator over calcium sulfate.
[
Cd(MeIs4Chex)2] was prepared by electrochemical ox-
idation of cadmium in a solution of HMeIs4Chex (0.19
mmol, 59 mg) in CH3CN (40 ml) containing 10 mg of
tetramethylammonium perchlorate for 1h at 5 mA. A loss
of 10.5 mg of the anode resulted.
Fig. 2. Perspective drawing of [Cd(MeIs4Chex)2] at 50%
probability.
X-ray data collection and processing
11.286°. Data were collected at 293(2) K using MoKa
radiation (A = 0.71073 A) and the omega-scan technique,
A yellow plate crystal of [Cd(MeIs4Chex)2] was and corrected for Lorentz and polarization effects [12].
mounted on a glass fibber and used for data collection
with a Nonius MACH3 automatic diffractometer. The cell
constants and an orientation matrix for data collection
A semi-empirical absorption correction, <^-scan, was car-
ried out [13]. The structure was solved by direct meth-
ods [14] and subsequent difference Fourier maps, and
were obtained by least-squares refinement of the diffrac- refined on F2by a full-matrix least-squares procedure us-
tion data from 25 reflections in the range of 7.491 < 9 < ing anisotropic displacement factors [15]. All hydrogen
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/22/15 4:06 PM

1
64
E. Labisbai et al. ■Electrochemical Synthesis of a 6 -Coordinate Cadmium(II) Complex
Table 3. Hydrogen bonding, root mean square plane deviations and angles between planes for [Cd(MeIs4Chex)2].
Donor
N14
N24
Acceptor3
S2#1
S l#2
D-H
0.86
0.86
H -A
2.76
3.00
D -A
3.578(10)
3.626(10)
ZD-H-A
159.3
131.4
Plane
Rms dev.
L with previous plane
C 1-C2-C3-C4-C5-C6-C7-C8-N11
C8-N12-N13-C9-N14-S1
C28-N22-N23-C29-N24-S2
0.0262
0.0539
0.0585
0.0096
18.23(0.41)
82.30(0.21)
4.69(0.42)
C21-C22-C23-C24-C25-C26-C27-C28-N21
aSymmetry transformation used to generate equivalent atoms: #l -x + 1, y + 1/2, -z + 1/2; #2 -x + 1, y - 1/2, -z + 1/2.
Table 4. A comparison of thiosemicarbazone moiety bond distances for isatin thiosemicarbazones, isatin thiosemicar-
bazone complexes and bis(thiosemicarbazone)cadmium(II) complexes.
Compound
C8-N12
N12-N13
N13-C9
C9-S1
C9-N14
Ref.
HIs4Ea
HIs4pTb
HIsheximc
1.285(5)
1.288(4)
1.305(5)
1.306(4)
1.304(6)
1.298(12)
1.29(1)
1.348(5)
1.346(4)
1.362(6)
1.337(4)
1.342(6)
1.348(12)
1.36(1)
1.383(5)
1.383(4)
1.375(4)
1.364(5)
1.357(7)
1.350(14)
1.33(1)
1.676(5)
1.662(4)
1.672(4)
1.711(4)
1.726(6)
1.708(13)
1.72(1)
1.321(6)
1.333(5)
1.339(6)
1.345(5)
1.342(7)
1.341(13)
1.36(2)
21
21
21
20
20
e
[
[
[
[
Zn(Ishexim)2]
Pb(Ishexim)2]
Cd(MeIs4Chex)2]
Cd(Fo4DH)2]d
8
a isatin N(4)-ethylthiosemicarbazone; b isatin N(4)-/?-tolylthiosemicarbazone; c isatin 3-hexamethyleneiminylthio-
semicarbazone;d bis(2-formylpyridine N(4)-methylthiosemi-carbazonato)cadmium(II);e this work.
atoms were located in their calculated positions (C-H 0.93
imine nitrogen atoms in [Cd(MeIs4Chex)2J form
-
0.97 A) and refined using a riding model. Atom scat- shorter bonds, Cd-N, 2.301(9) vs. 2.352(8) A. This
tering factors were taken from the International Table for difference probably results from the difference be-
X-ray Crystallography [16] and molecular graphics are tween the amide oxygen of MeIs4Chex and the
from PLATON99 [17].
pyridyl nitrogen of Fe4DH, even though both are
involved in 5-membered, conjugated chelate rings
with their imine nitrogen atoms.
Results and Discussion
The coordination polyhedron for [Cd(MeIs4-
Table 2 lists selected bond distances and an- Chex)2] may be regarded as derived from an oc-
gles for[Cd(M eIs4Chex)2]. The cadmium atom is tahedron in which the two ligands are bonded in a
6
-coordinate with each ligand bonding via its meridional arrangement. The deviation from octa-
thiolato sulfur [Cd-S, 2.569(4) A], imine nitro- hedral symmetry is due to the short bite of the lig-
gen [Cd-N, 2.301(9), 2.300(9) A] and the isatin
moiety's amide oxygen atom [Cd-O, 2.514(8),
ands; the SI-Cd-O 1 and S2-C d-02 "trans" angles
are 143.8(2) and 145.0(2)°, respectively, which are
similar to 143.2(2)° found for [Cd(Fo4DH)2] [8],
The N-Cd-S bite angles, 74.6(3) and 74.7(3)°, are
larger than the N-Cd-O angles, 70.4(3) and 70.3(3)°.
This difference in the two 5-membered chelate rings
2
.515(9) A]; the bonding of the two ligands
is essentially equivalent. The previously reported
-coordinate bis(thiosemicarbazone)cadmium(II)
complex, [Cd(Fo4DH)2], where Fo4DH is the anion
6
of 2-formylpyridine thiosemicarbazone, has similar can be attributed to the differences in atomic vol-
Cd-donor atom distances [8]. For the two complexes
the average bond distances with the thiolato sulfur
atoms are similar [Cd-S, 2.569(4) vs. 2.577(3) A]
for [Cd(MeIs4Chex)2] and [Cd(Fo4DH)2], but the
ume of sulfur and oxygen. The best planes of the
two thiosemicarbazone moieties. Table 3, approach
orthogonality, 82.30(21)°, but this dihedral angle is
smaller than 92.4(2)° found for [Cd(Fo4DH)2] [8],
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/22/15 4:06 PM

E. Labisbai et al. • Electrochemical Synthesis of a 6 -Coordinate Cadmium(II) Complex
165
The isatin portions of the two ligands have small de- bond on complexation of the anion, and the com-
viations from planarity, 0.0262 and 0.0096 A, and
these planes are at angles of 18.23(41) and 4.69(42)°
to their thiosemicarbazone moieties.
plexes tend to have a shorter bond than the three un-
complexed thiosemicarbazones. Again the change
is greater for transition metal complexes [19].
The present study expands our knowledge of
6-coordinate cadmium(II) complexes by provid-
ing data for a new type of chelating thiosemi-
carbazone with ONS bonding. This structure of a
bis(thiosemicarbazone)cadmium(II) complex is the
first reported for an N-methyl-isatin thiosemicar-
bazone. It should be emphasized that electrochem-
ical synthesis employing a low current density has
provided a diffractable crystal of this new complex,
and this technique is currently being used to pro-
duce additional metal complexes containing only
the desired ligand.
There is intermolecular hydrogen bonding be-
tween the N-H groups (N14-H and N24-H) of
the thiosemicarbazone moiety and a sulfur atoms
on adjacent molecules, Table 3. The non-bonding
N-H S distances, 3.578(10) and 3.626(10) A,
are longer than the 3.348(3)-3.523(4) A range
found for nine substituted thioureas [18], as well
as the 3.357(5) and 3.429(4) A reported for 2-
pyridineformamide N(4)-methylthiosemicarbazone
[
19]. However, [Pb(Ishexim)2], where Ishexim
is the anion of isatin 3-hexamethyleneiminyl-
thiosemicarbazone, has an N-H S non-bonding
distance between the isatin nitrogen and a sulfur
atom of a neighbouring molecule of 3.758(5) A [20].
Unfortunately, we have not been able to grow a
crystal of HMeIs4Chex or any other N-methylisatin
thiosemicarbazone to compare changes in the bond-
ing of the thiosemicarbazone moiety upon coor-
dination. However, structures have been solved
for three isatin thiosemicarbazones [21J, and Ta-
ble 4 is a compilation of bond distances of these
thiosemicarbazones and related complexes includ-
ing [Cd(Fo4DH)2] [8]. The increase in the bond
distance of C9-S1 is in agreement with its change
from a double bond to a single bond on complexa-
tion of the anion; the increase is much greater with
transition metal ions [19]. Among the other bonds
C13-C9 formally changes from a single to a double
Supplem entary M aterial
Crystallographic data for C32H38CdN802S?,
[
Cd(MeIs4Chex)2], CCDC#, 136015 have been de-
posited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC-
1
003/m. Copies of available material can be ob-
tained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: +44
1
223 336033 or e-mail: deposit@ ccdc.cam.ac.uk).
Acknowledgement
We thanks the Universidad de Santiago de Compostela
for financial support to carry out research at Illinois State
University.
[
1] L. Thompson, S. A. Milton, J. E. Officer, G. H. Hitch-
K. G. Rajendran, A. E. Liberta, D. X. West, Anti-
cancer Drugs 4, 241 (1993); I. H. Hall, S. Y. Chen,
K. G. Rajendran, D. X. West, Appl. Organomet.
Chem. 10, 485 (1996); I. H. Hall, M. C. Miller III,
D. X. West, Metal-Based Drugs 4, 89 (1997); M.
C. Miller III, K. F. Bastow, C. N. Stineman, J. R.
Vance, S. C. Song, D. X. West, I. H. Hall, Arch.
Pharm. 331, 121 (1998).M. C. Miller C. N. Stine-
man, J. R. Vance, D. X. West, I. H. Hall, Anticancer
Res. 18,4131 (1998); M. C. Miller, C. N. Stineman,
J. R. Vance, D. X. West, I. H. Hall, Appl. Organomet.
Chem. 13, 9(1999).
ings, J. Immunol. 70, 229 (1953).
[
[
2] D. J. Bauer, Brit. J. Exp. Path. 36, 105 (1956).
3] D. J. Bauer, P. W. Sadler, Brit. J. Pharmacol. 15, 101
1960).
4] C. L. Hoagland, S. M. Ward, L. E. Smadel, T. M.
Rivers, J. Exptl. Med. 74, 69 (1941).
(
[
[5] G. M. Abu El-Reasch, M. A. Khattab, U. I. El-
Ayaan, Synth. React. Inorg. Met-org. Chem. 22, 1417
(
1992).
6] P. W. Sadler, Ann. NY Acad. Sei. 130, 71 (1965).
7] D. X. West, A. E. Liberia, I. H. Hall, K. G. Rajen-
dran, Anticancer Drugs 4, 231 (1993); I. H. Hall,
[
[
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/22/15 4:06 PM

1
66
E. Labisbai et al. ■Electrochemical Synthesis of a 6 -Coordinate Cadmium(II) Complex
[
8] J. S. Casas, M. V. Castano, M. S. Garcia-Tasende,
I. Martmez-Santamarta, J. Sordo, E. E. Castellano,
J. Zukerman-Schpector, J. Chem. Research (S) 324
1992); (M) 2626 (1992).
9] E. Bermejo, A. Castineiras, R. Dominguez, R. Car-
[15] G. M. Sheldrick, 1997, SHELX-97. Program for
the Refinement of Crystal Structures, University of
Göttingen, Germany.
(
[16] International Tables for X-ray Crystallography,
1995, Vol. C, Kluwer Academic Publishers, Dor-
drecht, The Netherlands.
[17] A. L. Spek, PLATON. A Multipurpose Crystallo-
graphic Tool, 1999, Utrecht University, Utrecht, The
Netherlands.
[
ballo, C. Maichle-Mössmer. J. Strähle, D. X. West,
Z. Anorg. Allg. Chem. 625, 961 (1999).
[
10] E. Bermejo, R. Carballo, A. Castineiras, R. Domin-
guez, A. E. Liberta, C. Maichle-Mössmer, M. M.
Salberg, D. X. West, Eur. J. Inorg. Chem. 965
[18] D. X. West, J. K. Swearingen, A. K. Hermetet, L. J.
Ackerman, C. Presto, J. Mol. Struct., in press.
(1999).
[
[
[
11] E. Bermejo, R. Carballo, A. Castineiras, R. Domin- [19] D. X. West, J. K. Swearingen, J. Valdes-Martmez,
guez, A. E. Liberta, C. Maichle-Mössmer, D. X.
West, Z. Naturforsch. 54b, 777 (1999).
12] M. Kretschmar, 1997, GENHKL Program for the
reduction of CAD4 diffractometer data, University
of Tübingen, Germany.
S. Hernändez-Ortega, A. K. El-Sawaf, F. van Meurs,
A. Castineiras, I. Garcia, E. Bermejo, Polyhedron
18,2919(1999).
[20] E. Labisbal, A. Sousa, A. Castineiras, A. Garcia-
Väzquez, J. Romero, D. X. West, unpubl. results.
[21] G. A. Bain, D. X. West, J. Krejci, J. Valdes-
Martmez, S. Hernändez-Ortega, R. A.Toscano,
Polyhedron 16, 855 (1997) and references therein.
13] A. C. T. North, D. C. Phillips, F. S. Mathews, Acta
Crystallogr. A24, 351 (1968).
[
14] G. M. Sheldrick, Acta Crystallogr. A46,467 (1990).
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 7/22/15 4:06 PM