Chiral and achiral platinum(n) complexes for potential use as chemotherapeutic agents: Crystal and molecular structures of cis-[Pt(V)2] and [PtflL^CKMPSO] [HL1 = JV,yV-diethyWV-benzoylthiourea]

Article abstract of DOI:10.1039/a908985c

The synthesis and characterisation of platinum(n) complexes, with the general formula [Pt(acylthioureato)Cl(RR'SO)], is reported. These complexes are readily formed by the reaction of [PtO₂(RR'SO)J with the acylthiourea ligands, A,A-di(2-hydroxyethyl)-./V'-benzoylthiourea (HL), Ar,Ar-diethyl-Ar'-benzoylthiourea (HL1) and Ar,Ar-adipoylbis(W,Ar'-diethylthiourea) (H2L2) in the presence of sodium acetate. Variation of the sulfoxide ligand (RR'SO) enables preparation of achiral complexes when RR'SO is dimethylsulfoxide (DMSO) or methylphenylsulfoxide (MPSO), and chiral complexes when use is made of the chiral sulfoxides, such as (R)-methyl(p-tolyl)sulfoxide and (S)-methyl(/7-tolyl)sulfoxide. The reaction also yields, as a minor product, the corresponding fA and the Pt-S bond Irans to O 2.192(3) A in length. The Pt-O and Pt-Cl bonds are 2.016(9) and 2.334(3) A, respectively, and are within the expected ranges. Similarly, the bond lengths and bond angles around the coordination plane of m-[Pt(L')2] compare well with related complexes. The Royal Society of Chemistry 2000.

Full text of DOI:10.1039/a908985c

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Chiral and achiral platinum(II) complexes for potential use as
chemotherapeutic agents: crystal and molecular structures of
cis-[Pt(L1)2] and [Pt(L1)Cl(MPSO)] [HL1 ؍ N,N-diethyl-NЈ-
benzoylthiourea]
Cheryl Sacht,*a Michael S. Datt,a Stefanus Ottob and Andreas Roodt*b
a Department of Chemistry, Rhodes University, PO Box 94, Grahamstown, 6140, South Africa
b Department of Chemistry, University of the Free State, Bloemfontein, 9300, South Africa.
E-mail: C.Sacht@ru.ac.za
Received 12th November 1999, Accepted 17th January 2000
The synthesis and characterisation of platinum() complexes, with the general formula
[Pt(acylthioureato)Cl(RRЈSO)], is reported. These complexes are readily formed by the reaction of [PtCl2(RRЈSO)2]
with the acylthiourea ligands, N,N-di(2-hydroxyethyl)-NЈ-benzoylthiourea (HL), N,N-diethyl-NЈ-benzoylthiourea
(HL1) and N,N-adipoylbis(NЈ,NЈ-diethylthiourea) (H2L2) in the presence of sodium acetate. Variation of the
sulfoxide ligand (RRЈSO) enables preparation of achiral complexes when RRЈSO is dimethylsulfoxide (DMSO)
or methylphenylsulfoxide (MPSO), and chiral complexes when use is made of the chiral sulfoxides, such as
(R)-methyl(p-tolyl)sulfoxide and (S)-methyl(p-tolyl)sulfoxide. The reaction also yields, as a minor product,
the corresponding cis-bis(acylthioureato)platinum() complexes, which can be removed by chromatography.
The molecular structures of the two products, [Pt(L1)Cl(MPSO)] and cis-[Pt(L1)2], were determined by X-ray
crystallography. The sulfoxide of [Pt(L1)Cl(MPSO)] is sulfur bound, as expected, and cis to the sulfur atom of the
acylthioureato ligand. All bond lengths and bond angles around the square planar platinum are normal, with the
Pt–S bond trans to Cl being 2.257(4) Å and the Pt–S bond trans to O 2.192(3) Å in length. The Pt–O and Pt–Cl
bonds are 2.016(9) and 2.334(3) Å, respectively, and are within the expected ranges. Similarly, the bond lengths
and bond angles around the coordination plane of cis-[Pt(L1)2] compare well with related complexes.
and the stereochemical requirements of the sulfur ligand. These
complexes are also of particular interest because unsymmet-
Introduction
It is well known that cisplatin is a leading antitumour drug used
worldwide for the successful treatment of genitourinary and
head and neck cancers. While this drug has conferred signifi-
cant therapeutic benefit to a large number of cancer sufferers, it
has shown only minor or insufficient activity against a number
of malignancies with high social incidence, such as colon and
breast cancers. In addition to a limited spectrum of activity, the
efficacy of cisplatin is further limited by its severe side-effects
and the drug resistance of some tumours. Due to cisplatin’s
inherent activity but unfortunate drawbacks, a major avenue of
research has been the search for new derivatives with greater
activity and/or decreased toxicity. Of the many thousands of
analogues reported, only one “second generation” complex,
carboplatin, is widely registered for use. Carboplatin is essen-
tially devoid of the major side-effects of cisplatin, its dose-
limiting toxicity being myelosuppression, but the spectrum of
activity for the two drugs is very similar and hence, carboplatin
has provided only limited advances in the search for improved
platinum()-containing anticancer drugs. In an attempt to sup-
plement the narrow spectrum of indication, reduce toxicity and
circumvent resistance, recent efforts have been directed towards
the synthesis and evaluation of platinum complexes that are
structurally different to the classical cisplatin analogues.1,2
One approach has been to expand the range of leaving
groups by using dimethylsulfoxide (DMSO) and unsymmetric-
ally substituted sulfoxides (RRЈSO), to give cationic complexes
of the type [PtCl(diamine)(RRЈSO)]ϩ. These cationic com-
plexes, introduced by Farrell et al.,3 have shown enhanced
cytotoxicity in cisplatin-resistant cell lines and this has been
attributed to a change in reactivity and cellular uptake, which
may be related to the hydrolytic behaviour of the Pt–S bond
rical sulfoxides are in fact chiral and a clear effect of chirality
on biological activity has been noted where RRЈSO = methyl-
(p-tolyl)sulfoxide. This example represents the first demon-
stration of the effect of the leaving group chirality on biological
activity, as well as the first use of a sulfur-containing leaving
group.3
Of the many ‘non-classical’ complexes that are currently
being studied, a few of these are presently undergoing Phase I
clinical trials, such as ZD0473 [cis-amminedichloro(2-methyl-
pyridine)platinum()]4 and BBR3464, a trinuclear 4ϩ-charged
platinum() complex, introduced by Farrell et al., the structure
of which is best described as two trans-[PtCl(NH3)2]ϩ units
bridged by a noncovalent tetra-amine trans-[Pt(NH3)2{NH2-
(CH2)6NH2}2]2ϩ unit.5
In view of the continued need for the synthesis and develop-
ment of new ‘non-classical’ platinum()-based chemothera-
peutic agents to overcome the above-mentioned limitations,
we have combined the use of sulfoxide and acylthiourea,
RC(O)NHC(S)NRЈ2, ligand systems to prepare a novel set
of platinum() complexes having the general formula [Pt(acyl-
thioureato)Cl(RRЈSO)], with potential utility as chemothera-
peutic agents. Our interest in the acylthiourea ligand system
stems from the fact that they are extremely versatile, as the acyl
(R) groups and alkyl (RЈ) groups can be changed easily, giving
rise to a wide variety of ligand systems with different physical
and chemical properties. Hence, systematic variation of the
ligand system could, perhaps, alter the biological activity of the
resultant complexes and thus be used to fine-tune the anti-
tumour behaviour of this series of compounds. Herein we report
the synthesis and characterisation of a series of new platinum()
complexes of the type [Pt(acylthioureato)Cl(RRЈSO)], with the
DOI: 10.1039/a908985c
J. Chem. Soc., Dalton Trans., 2000, 727–733
This journal is © The Royal Society of Chemistry 2000
727

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acylthiourea
ligands
N,N-di(2-hydroxyethyl)-NЈ-benzoyl-
CH2), 1.32 (6H, s, 2CH3). TLC [silica gel, CHCl3–EtOH (2%)]:
Rf 0.66.
thiourea (HL), N,N-diethyl-NЈ-benzoylthiourea (HL1) and
N,N-adipoylbis(NЈ,NЈ-diethylthiourea) (H2L2) and the sulf-
oxides dimethylsulfoxide (DMSO), methylphenylsulfoxide
(MPSO), R-methyl(p-tolyl)sulfoxide (R-MTSO) and S-methyl-
(p-tolyl)sulfoxide (S-MTSO). To the best of our knowledge,
the synthesis and complete characterisation of these [Pt-
(acylthioureato)Cl(RRЈSO)] complexes is being reported for
the first time.
N,N-Adipoylbis(NЈ,NЈ-diethylthiourea) (H2L2). Yield (1.45 g,
19%), mp 97–99 ЊC (Found: C, 51.3; H, 8.3; N, 15.1; S, 17.4.
Calc. for C16H30N4S2O2: C, 51.3; H, 8.1; N, 15.0; S, 17.1%). IR
(KBr pellet, cmϪ1): 3250 (s, sh), 2982 (w–m), 2970 (w), 2930 (w),
1670 (s), 1665 (s, sh), 1655 (w, sh), 1515 (s), 1423 (m–s), 1380
(w), 1350 (w–m), 1330 (m), 1305 (w–m), 1265 (m), 1230 (s), 1155
(w), 1140 (w–m), 1120 (m), 1100 (w), 1079 (m), 1070 (w–m,
shld), 930 (m), 897 (m), 845 (m), 783 (w–m), 768 (w), 705 (w–
m), 680 (w–m), 645 (w), 600 (w), 585 (w), 400 (w), 350 (w), 320
(w), 300 (w), 279 (w). δH (400 MHz, CDCl3): 8.32 (2H, s, NH),
3.93 (4H, br s, 2CH2), 3.52 (4H, br s, 2CH2), 2.38 (4H, t, 2CH2),
1.71 (4H, t, 2CH2), 1.27 (12H, s, 4CH3). TLC [silica gel, CHCl3–
EtOH (2%)]: Rf 0.40.
Experimental
Materials and physical methods
The sulfoxides and potassium tetrachloroplatinate (Aldrich,
Johnson Matthey), DMSO (Merck), adipoyl chloride (Fluka)
and benzoyl chloride (SaArchem) were used as supplied, while
diethylamine and acetone were distilled before use. All other
solvents were commercial grade and were used as received. The
known complexes cis-[PtCl2(DMSO)2], cis-[PtCl2(MPSO)2], cis-
[PtCl2(R-MTSO)2] and cis-[PtCl2(S-MTSO)2] were prepared by
literature procedures.6 The cis-[PtCl2(R-MTSO)2] and cis-[PtCl2-
(S-MTSO)2] complexes were prepared using the optically pure
sulfoxides. The sign and handedness of the optically active free
sulfoxides changes upon complexation to platinum() and the
R and S assignments used throughout this paper refer to the
sign of the sulfoxide when co-ordinated to platinum(). The IR
spectra were obtained as KBr disks between 4000 and 250 cmϪ1
on a Perkin-Elmer 180 spectrophotometer. The 1H NMR
spectra were recorded at 400.13 MHz on a Bruker 400AMX
spectrometer at 30 1 ЊC. All samples were prepared using
deuterated solvents purchased from Aldrich Chemical Com-
pany and 5 mm NMR tubes were used throughout. Chemical
shifts are reported in parts per million (ppm) relative to the
central line of the solvent proton resonance of known shifts
relative to TMS and coupling constants are reported in hertz
(Hz). 195Pt NMR spectra were recorded at 86.02 MHz on a
Bruker 400AMX spectrometer at 30 1 ЊC using 70–100 KHz
spectral widths and 13 µs pulses with 3 s pulse delay. Spectra
were obtained by collecting between 2048 and 16 000 transients
using a line broadening factor of 10 Hz. All 195Pt shifts are
reported relative to external H2PtCl6 [500 mg in 1 ml 30% (v/v)
D2O–HCl (1 M)]. Melting points were determined using a
Reichert hot-stage microscope and are uncorrected. Elemental
analyses were carried out at the microanalytical unit of the
University of Cape Town, South Africa. Thin-layer chromato-
graphy was performed on silica sheets 60F254 (Merck, Darm-
stadt). Reverse phase TLC was performed on glass backed
RP-C18F254S plates (Merck, Darmstadt). Flash chromato-
graphy was performed on silica gel 60. Molecular exclusion
chromatography was performed using Lipophilic Sephadex
LH-20 (Sigma). The optical rotation of chiral complexes was
determined on a Perkin-Elmer 141 Polarimeter in dry acetone
as solvent.
Preparation of complexes
[Pt(L)Cl(DMSO)]. A solution of N,N-di(2-hydroxyethyl)-
NЈ-benzoylthiourea (0.45 mmol) in 10 ml acetonitrile was added
to a stirred solution of cis-[PtCl2(DMSO)2] (0.45 mmol) in 4 ml
acetonitrile–dimethylsulfoxide (1:1, v/v). Sodium acetate (0.6
mmol) in 1 ml water was added and the bright yellow solution
was stirred for 25 h at room temperature. A large excess of
water (130 ml) was added whereupon a yellow precipitate
formed. The solution was refrigerated (4 ЊC) for 70 h. The
yellow precipitate was collected by filtration, recrystallized
from ethanol and dried in an oven (64 ЊC) (yield 196 mg, 75%),
mp 139–139.8 ЊC (Found: C, 29.5; H, 3.7; N, 5.0; S, 11.1.
C14H21N2S2O4ClPt requires C, 29.2; H, 3.7; N, 4.9; S, 11.1%). IR
(KBr pellet, cmϪ1): 3500 (w–m), 3392 (w–m), 2360 (w), 2336
(w), 1516 (m), 1490 (s), 1446 (m), 1404 (m), 1360 (m), 1204
(m), 1142 (m), 982 (w), 980 (w), 932 (w), 716 (w), 446 (m).
δH (400 MHz, DMSO-d6): 8.06 (2H, d, C6H5), 7.59 (1H, t,
C6H5), 7.47 (2H, t, C6H5), 5.05 (1H, t, OH), 4.94 (1H, t, OH),
4.00 (2H, t, CH2), 3.91 (2H, t, CH2), 3.76 (2H, q, CH2), 3.68
(2H, q, CH2). TLC (RP-18F254S, 5.5 ml MeOH–4.5 ml H2O):
Rf 0.18.
[Pt(L1)Cl(MPSO)] (1).
A solution of N,N-diethyl-NЈ-
benzoylthiourea (0.11 g, 0.47 mmol) in 10 ml acetonitrile was
added dropwise to a stirred solution of cis-[PtCl2(MPSO)2]
(0.26 g, 0.47 mmol) in 10 ml acetonitrile–dichloromethane (1:1,
v/v), followed by 1.5 equivalents of sodium acetate in water (1.5
ml). The reaction mixture was stirred for 66 h at room temper-
ature. The resultant orange solution was added to water (100
ml), whereupon the aqueous and organic phases separated. The
aqueous phase was extracted with CH2Cl2 (10 ml) and the
organic phases were combined and dried over anhydrous
MgSO4. The pure product was obtained by chromatography
using Lipophilic Sephadex LH-20 (eluant: CH2Cl2) (yield 28.2
mg, 10%), mp 64–67 ЊC (Found: C, 37.85; H, 3.9; N, 4.6;
S, 10.6. C19H23N2S2O2ClPt requires C, 37.65; H, 3.8; N, 4.6; S,
10.6%). Slow recrystallization from EtOH–CHCl3 yielded crys-
tals suitable for X-ray structure analysis. IR (KBr pellet, cmϪ1):
3070 (m–s), 2985 (m, sh), 2940 (m), 2921 (m), 2875 (w–m), 1570
(m), 1501 (s sh), 1450 (m), 1418 (s), 1356 (m), 1300 (w), 1255
(w), 1206 (w), 1141 (m, sh), 1075 (w–m), 1025 (w), 1000 (w), 946
(w–m), 876 (w), 810 (w), 705 (m–s, sh), 695 (m), 680 (m), 520
(m), 315 (vw), 205 (vw). δH (400 MHz, CDCl3): 8.19 (4H, d,
C6H5), 7.58 (3H, m, C6H5), 7.47 (1H, t, C6H5), 7.37 (2H, t,
C6H5), 3.76 (3H, s, CH3), 3.79 (4H, m, 2CH2), 1.28 (6H, m,
2CH3). TLC [silica gel, CHCl3–EtOH (2%)]: Rf 0.65.
Preparation of ligands
The ligands were prepared using the method of Douglass and
Dains.7 The synthesis and characterisation of the ligand, N,N-
di(2-hydroxyethyl)-NЈ-benzoylthiourea (HL), has recently been
reported.8
N,N-Diethyl-NЈ-benzoylthiourea (HL1). Yield (6.48 g, 55%),
mp 97–98 ЊC (Found: C, 61.0; H, 6.95; N, 11.9; S, 12.9. Calc.
for C12H16OSN2: C, 61.0; H, 6.8; N, 11.9; S, 13.6%). IR (KBr
pellet, cmϪ1): 2970 (m, sh), 2928 (w), 1690 (s, sh), 1575 (w), 1597
(w), 1532 (s), 1452 (s), 1430 (m–s), 1413 (s), 1282 (m–s), 1230
(s), 1167 (m), 1130 (m), 1100 (w–m), 1062 (w–m), 907 (w–m),
845 (w–m), 780 (w–m), 705 (m–s), 653 (w), 635 (m–s). δH (400
MHz, CDCl3) 8.24 (1H, s, NH), 7.82 (2H, d, C6H5), 7.56 (1H, t,
C6H5), 7.46 (2H, t, C6H5), 4.02 (2H, br s, CH2), 3.61 (2H, br s,
[Pt(L1)Cl(DMSO)]. A solution of N,N-diethyl-NЈ-benzoyl-
thiourea (0.130 g, 0.55 mmol) in 20 ml acetonitrile was added
dropwise to a stirred solution of cis-[PtCl2(DMSO)2] (0.234 g,
0.55 mmol) in 6 ml acetonitrile–dimethylsulfoxide (1:1, v/v).
1.5 equivalents of sodium acetate in water (1.5 ml) was then
728
J. Chem. Soc., Dalton Trans., 2000, 727–733

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Table 1 Crystal dataa and refinement detail for compounds 1 and 2
added. The reaction mixture was stirred for 48 h at room tem-
perature. The yellow solution was then added to water (100 ml),
whereupon a precipitate formed. This mixture was placed in a
refrigerator (4 ЊC) overnight. The precipitate was extracted into
chloroform (50 ml) and the organic extract was dried over
anhydrous MgSO4. Analysis of the organic extract showed that
it consisted of [Pt(L1)Cl(DMSO)] and cis-[Pt(L1)2] (2). The
desired complex was obtained after purification by flash
chromatography [eluant: CHCl3–EtOAc (3:1, v/v)] (yield 184
mg, 62%), mp 144–148 ЊC (Found: C, 31.3; H, 4.5; N, 5.1;
S, 11.5. C14H21N2S2O2ClPt requires C, 30.9; H, 3.9; N, 5.15; S,
11.8%). IR (KBr pellet, cmϪ1): 2980 (w), 2930 (w), 1520 (m),
1500 (s, sh), 1140 (m), 1410 (s, sh), 1375 (w–m), 1352 (m), 1305
and 1295 (w–m, br), 1248 (m), 1200 (m, sh), 1139 (m–s), 1095
(w), 1084 (w), 1069 (w), 1025 (m), 880 (w–m), 810 (w–m), 702
(m), 680 (m), 445 (m). δH (400 MHz, CDCl3): 8.16 (2H, d,
C6H5), 7.47 (1H, t, C6H5), 7.36 (2H, t, C6H5), 3.84 (2H, q, CH2),
3.80 (2H, q, CH2), 3.58 (6H, s, 3J(PtH) 23 Hz, CH3), 1.34 (3H, t,
CH3), 1.28 (3H, t, CH3). TLC [silica gel, CHCl3–EtOAc (3:1,
v/v)]: Rf 0.41.
Identification code
Empirical formula
Formula weight
Crystal system
1
2
C19H23ClN2O2PtS2
606.05
C24H30N4O2PtS2
665.73
Monoclinic
P21/n
Triclinic
P1
¯
Space group
a/Å
b/Å
c/Å
α/Њ
8.612(2)
11.776(2)
13.374(3)
115.11(2)
86.44(2)
66.25(2)
1078.8(4)
2
9.926(2)
12.265(3)
21.168(5)
90
91.00(2)
90
2576.7(10)
4
5.636
β/Њ
γ/Њ
V/Å3
Z
µ/mmϪ1
6.837
Temperature/K
Reflections collected
Independent reflections
Rint
293(2)
3450
2918
0.0327
293(2)
3803
3454
0.0215
Final R indices [I > 2σ(I)]
Rb
0.0613
0.1535
0.0355
0.0918
c
RW
a For both compounds, a Nicolet P3 diffractometer (Mo-Kα, λ =
cis-[Pt(L1)2] (2). This complex was isolated from the above-
mentioned reaction by flash chromatography (yield 14 mg, 5%),
mp 170–172 ЊC. Crystals suitable for X-ray crystallography
were obtained by slow evaporation of a chloroform solution
of the complex. (Found: C, 42.7; H, 4.5; N, 8.2; S, 9.4. Calc. for
C24H30N4O2S2Pt: C, 43.3; H, 4.5; N, 8.4; S, 9.6%). IR (KBr
pellet, cmϪ1): 3062 (w), 2960 (w), 2930 (m), 2850 (w), 1585
(m–s), 1525 (s), 1505 (s), 1410 (s), 1370 (w), 1349 (m–s), 1296
(w–m), 1250 (m, s), 1205 (w–m), 1170 (w–m), 1136 (m), 1100
(m), 1027 (w–m), 1036 (w–m), 1020 (w), 1005 (w), 974 (w), 881
(w–m), 810 (w–m), 781 (w), 769 (w), 708 (m), 680 (w–m, sh),
690 (w–m, sh), 665 (w–m, sh), 465 (w), 351 (w), 325 (w), 302
(w), 245 (w–m). δH (400 MHz, CDCl3): 8.25 (4H, d, C6H5), 7.50
(2H, t, C6H5), 7.41 (4H, t, C6H5), 3.84 (4H, q, 2CH2), 3.77 (4H,
q, 2CH2), 1.33 (6H, t, 2CH3), 1.28 (6H, t, 2CH3). TLC [silica
gel, CHCl3–EtOAc (3:1, v/v)]: Rf 0.78.
0.70173 Å) was used. b R = [(Σ|∆F|)/(ΣFo)]. c RW = [Σ[w(∆F2)2]/
2
Σ[w(Fo )2]]0.5
.
515 (m), 315 (w), 280 (w). δH (400 MHz, CDCl3): 8.20 (2H, d,
C6H5), 8.08 (2H, d, C6H5), 7.48 (1H, t, C6H5), 7.37 (4H, m,
C6H5), 3.81 (4H, m, 2CH2), 3.73 (3H, s, CH3), 2.44 (3H, s, CH3),
1.28 (6H, m, 2CH3). TLC [silica gel, CHCl3–EtOH (2%)]: Rf
0.64.
[{Pt(Cl)(DMSO)}2L2]. A solution of N,N-adipoylbis(NЈ,NЈ-
diethylthiourea) (0.134 g, 0.36 mmol) in 10 ml acetonitrile was
added to a solution of cis-[PtCl2(DMSO)2] (0.30 g, 0.71 mmol)
in 6 ml acetonitrile–dimethylsulfoxide (1:1, v/v). Sodium acet-
ate (0.105 g, 1.28 mmol) in water (2 ml) was added and the
solution was stirred at room temperature for 2 d, then placed
in a refrigerator (4 ЊC) for 10 d. The yellow precipitate was
collected by centrifugation and dried in an oven (64 ЊC) (yield
254 mg, 93%), mp >230 ЊC (Found: C, 24.5; H, 4.1; N, 5.7;
S, 12.7. C18H40O4S4N4Pt2Cl2 requires C, 22.4; H, 4.2; N, 5.8; S,
13.3%). IR (KBr pellet, cmϪ1): 2980 (w), 2930 (w), 1525 (m,
shld), 1509 (s, sh), 1500 (s), 1420 (s), 1377 (w), 1350 (m), 1290
(m), 1236 (w–m), 1195 (w), 1130 (m–s), 1095 (w), 1075 (w), 1018
(m), 1000 (w–m), 950 (w), 900 (w), 820 (w), 715 (w), 680 (w),
660 (w), 637 (w), 445 (w–m), 377 (w), 325 (w), 302 (w), 290 (vw),
280 (w), 250 (w). δH (400 MHz, CDCl3): 3.71 (8H, m, 4CH2),
[Pt(L1)Cl(S-MTSO)]. This complex was prepared using the
same procedure as described for [Pt(L1)Cl(DMSO)] above, with
the exception of the following: a solution of N,N-diethyl-NЈ-
benzoylthiourea in 10 ml acetonitrile was added dropwise to a
stirred solution of cis-[PtCl2(S-MTSO)2] in 6 ml acetonitrile.
The pure complex was obtained by flash chromatography
[eluant: CHCl3, followed by CHCl3–EtOH (2%)] (yield 35 mg,
14%), mp 70–74 ЊC. [α]D25 = Ϫ61.7Њ (c 0.180, acetone) (Found:
C, 39.0; H, 4.1; N, 4.6; S, 10.3. C20H25N2S2O2ClPt requires C,
38.7; H, 4.1; N, 4.5; S, 10.3%). IR (KBr pellet, cmϪ1): 2985
(w–m), 2940 (w–m), 1579 (w, sh), 1540 (s, sh), 1501 (vs, sh),
1450 (s), 1430 (s), 1415 (vs), 1380 (m), 1356 (s), 1310 (w–m),
1255 (m), 1210 (m), 1175 (w), 1145 (s, sh), 1125 (w), 1120
(w–m), 1081 (m–s), 1100 (w), 1075 (w), 944 (m), 880 (w–m), 810
(w–m), 795 (w–m), 705 (s), 698 (m, sh), 679 (m), 628 (w–m),
619 (w–m), 515 (m), 315 (w), 280 (w). δH (400 MHz, CDCl3):
8.20 (2H, d, C6H5), 8.07 (2H, d, C6H5), 7.48 (1H, t, C6H5), 7.37
(4H, m, C6H5), 3.81 (4H, m, 2CH2), 3.73 (3, s, CH3), 2.44 (3H,
s, CH3), 1.28 (6H, m, 2CH3). TLC [silica gel, CHCl3–EtOH
(2%)]: Rf 0.64.
3
3.54 (12H, s, J(PtH) 24 Hz, 4CH3), 2.40 (4H, t, 2CH2), 1.67
(4H, m, 2CH2), 1.30 (6H, t, 2CH3), 1.18 (6H, t, CH3). TLC
[silica gel, CHCl3–EtOAc (3:1, v/v)]: Rf 0.23.
Crystal structure determinations
The three dimensional intensity data (Mo-Kα radiation,
λ = 0.71073 Å) were collected on a Nicolet P3 Diffractometer.
All reflections were corrected for Lorentz and polarization
effects. The structures were solved by Patterson9 and succes-
sive Fourier syntheses (SHELXL97).10 The crystals of the
[Pt(L1)Cl(MPSO)] complex (1) were excessively twinned and
showed signs of decomposition. These were therefore covered
with a thin layer of Canada Balsam, thus no absorption correc-
tions were applied. This resulted in residual electron density
peaks corresponding to ca. 3 e ÅϪ3. All the relevant structural
details and refinement parameters are given in Table 1. The
hydrogen atom positions were calculated riding on the adjacent
carbon atom (phenyl C–H = 0.92 Å and methyl C–H = 0.98
Å),10 and were refined with an overall isotropic thermal par-
ameter. The molecular graphics were produced using ORTEP.11
CCDC reference number 186/1811.
[Pt(L1)Cl(R-MTSO)]. This complex was prepared using the
same procedure described for [Pt(L1)Cl(S-MTSO)] above,
except that the solution was stirred for 66 h. (Yield 89 mg, 39%),
mp 72–74 ЊC, [α]D25 = ϩ61.3Њ (c 0.200, acetone) (Found: C,
39.2; H, 4.1; N, 4.6; S, 10.3. C20H25N2S2O2ClPt requires C, 38.7;
H, 4.1; N, 4.5; S, 10.3%). IR (KBr pellet, cmϪ1): 2985 (w–m),
2940 (w–m), 1579 (w, sh), 1540 (s, sh), 1501 (vs, sh), 1450 (s),
1430 (s), 1415 (vs), 1380 (m), 1356 (s), 1310 (w–m), 1255 (m),
1210 (m), 1175 (w), 1145 (s, sh), 1125 (w), 1120 (w–m), 1100
(w), 1081 (m–s), 1075 (w), 944 (m), 880 (w–m), 810 (w–m), 795
(w–m), 705 (s), 698 (m, sh), 679 (m), 628 (w–m), 619 (w–m),
See http://www.rsc.org/suppdata/dt/a9/a908985c/ for crystal-
lographic files in .cif format.
J. Chem. Soc., Dalton Trans., 2000, 727–733
729

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Selected relevant spectroscopic data for PtII sulfoxide
Table
2
Results and discussion
complexes
Synthesis of complexes
NMR (CDCl3, 303 K)
The structures and abbreviations of the complexes are shown in
Scheme 1. The DMSO complexes were prepared using all three
IR
ν(SO)/
1H,
3J(195Pt–
Complex
cmϪ1
δ(SCH3)
1H)/Hz
195Pt, δ
a
a
[Pt(L)Cl(DMSO)]
[Pt(L1)Cl(DMSO)]
[{PtCl(DMSO)}2L2]
[Pt(L1)Cl(MPSO)]
[Pt(L1)Cl(S-MTSO)]
[Pt(L1)Cl(R-MTSO)]
1142
1139
1130
1141
1145
1145
Ϫ3229a
Ϫ3256
Ϫ3256
Ϫ3277
Ϫ3273
Ϫ3273
3.58
3.54
3.76
3.73
3.73
23
24
b
b
b
a Spectrum recorded in DMSO-d6. b Overlapping peaks.
frequency. The ν(SO) peak is shifted to higher frequency upon
complexation and this is indicative of a sulfoxide bonded
through the sulfur atom.6,12 The assignments of the proton
spectra were straightforward and the chemical shift positions
for the methyl protons of the sulfoxides, which are shifted ca.
1 ppm downfield relative to the free sulfoxides, are typical for
S-bonded RRЈSO.6,12 The elucidation of the structures of some
of the complexes was further facilitated by the presence of the
coupling associated with isotopically abundant 195Pt (33.7%,
I = 1/2). The signal due to the methyl protons of the sulfoxides,
in cases where there were no overlapping peaks, showed a 195Pt
3
satellite doublet with J(PtH) of about 23 Hz, which is of the
same order of magnitude as is found for sulfur-bonded sulf-
oxide complexes.6 The 195Pt NMR chemical shift for cis-
[Pt(L1)2] (2) of Ϫ2723 ppm is identical to that reported in the
literature.13 All the [Pt(L1)Cl(RRЈSO)] complexes show 195Pt
chemical shifts in the Ϫ3200 to Ϫ3300 ppm region, which
corresponds to the chemical shift range for S-bonded sulfoxides
and is in agreement with the expected 195Pt chemical shift posi-
tions for a [PtSOSCl] coordination sphere.3,14 For the [Pt-
(L1)Cl(RRЈSO)] complexes, the 195Pt chemical shift positions
for [Pt(L1)Cl(MPSO)] (Ϫ3277 ppm), [Pt(L1)Cl(R-MTSO)]
(Ϫ3273 ppm) and [Pt(L1)Cl(S-MTSO)] (Ϫ3273 ppm) are
upfield relative to the [Pt(L1)Cl(DMSO)] complex (Ϫ3256
ppm). A similar trend has also been observed for the mono-
anionic K[PtCl3(RЈRЉSO)] series and has been attributed to the
phenyl substituent conferring better donor ability on the sulf-
oxide.15 This is best understood by considering the canonical
forms of sulfoxide, which are generally represented as:
Scheme 1 Structural formulae of the complexes.
acylthiourea ligands, while the complexes containing the
unsymmetrical sulfoxides were prepared using N,N-diethyl-NЈ-
benzoylthiourea (HL1) only. The complexes were prepared
according to the general method described by eqns. 1 and 2,
where HL represents an acylthiourea ligand:
K2PtCl4 ϩ 3RRЈSO → cis-[PtCl2(RRЈSO)2] (1)
NaOAc
cis-[PtCl2(RRЈSO)2] ϩ HL
[Pt(L)Cl(RRЈSO)] ϩ cis-[PtL2] (2)
As indicated in eqn. 2, it was found, in most instances, that
in addition to the formation of the desired complex, [Pt(L)-
Cl(RRЈSO)], the neutral cis-[PtL2] complex was also formed.
This was evident from both the 1H NMR spectra and thin layer
chromatography. Integration of the proton resonances indi-
cated that the cis-[PtL2] complex was usually present as the
minor product (ca. 5–15%). The cis-[PtL2] complexes have a
higher mobility on silica gel (Rf ca. 0.8) compared to the [Pt(L)-
Cl(RRЈSO)] complexes (Rf 0.5–0.6) and consequently can be
separated easily using flash column chromatography. Conclu-
sive evidence that the second product was, in fact, cis-[PtL2] was
provided by X-ray crystallography; the structure of cis-[Pt(L1)2]
(2) is described below.
Both forms I and II are considered to contribute to metal
binding. The replacement of alkyl by aryl substituents results in
a decrease in the net positive charge on the free sulfoxide. This
decrease in positive charge favours form II over form I in metal–
sulfoxide binding and thus strengthens the S-bonding through
form II, which is reflected in a more shielded environment for
the Pt nucleus.12
To further confirm the structures of these complexes, single-
crystal structure determinations were performed on [Pt(L1)-
Cl(MPSO)] (1) and cis-[Pt(L1)2] (2).
Structure of [Pt(L1)Cl(MPSO)] (1)
In spite of the fact that the crystals were not of good quality
and no absorption corrections could therefore be applied due to
the use of Canada Balsam, the co-ordination mode and basic
structure is well defined and is of acceptable accuracy. A per-
spective view of a single [Pt(L1)Cl(MPSO)] molecule is given
in Fig. 1, showing the atom numbering scheme for all non-
hydrogen atoms, while the relevant bond lengths and angles are
Characterisation of complexes
All the complexes were characterised by elemental analyses, IR,
1H and 195Pt NMR spectroscopy. A collection of selected spec-
troscopic data is reported in Table 2. The strong IR band in the
region of 1130–1145 cmϪ1 is assigned to the ν(SO) stretching
730
J. Chem. Soc., Dalton Trans., 2000, 727–733

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Table 3 Selected bond lengths (Å) and angles (Њ) for 1 and 2 with
e.s.d.s in parentheses
2
1
Ligand A
Ligand B
Pt–O(1)
Pt–S(1)
Pt–S(2)
Pt–Cl(1)
2.016(9)
2.257(4)
2.192(3)
2.334(3)
1.736(14)
1.462(11)
1.77(2)
1.77(2)
1.26(2)
1.28(2)
1.35(2)
1.34(2)
1.48(2)
1.75(5)
1.51(2)
1.55(3)
1.11(4)
2.018(5)
2.231(2)
2.023(6)
2.233(2)
S(1)–C(1)
S(2)–O(2)
S(2)–C(21)
S(2)–C(7)
O(1)–C(2)
N(1)–C(2)
N(1)–C(1)
N(2)–C(1)
N(2)–C(3)
N(2)–C(5)
C(2)–C(11)
C(3)–C(4)
C(5)–C(6)
1.731(7)
1.723(7)
1.271(8)
1.313(9)
1.341(9)
1.350(9)
1.467(9)
1.471(9)
1.491(10)
1.491(12)
1.487(11)
1.262(8)
1.319(9)
1.350(9)
1.336(9)
1.479(9)
1.475(10)
1.498(11)
1.499(11)
1.503(13)
Fig. 1 The molecular structure of chloro(N,N-diethyl-NЈ-benzoyl-
thioureato)(methylphenylsulfoxide)platinum() (1), showing the atom
numbering scheme adopted. The hydrogen atoms have been omitted for
clarity. The ellipsoids denote 30% probability.
O(1)–Pt–S(2)
O(1)–Pt–S(1)
177.2(3)
93.3(3)
94.8(2)
82.7(2)
177.1(2)
177.5(2)
88.10(7)
94.4(2)
O(1A)–Pt(1)–O(1B)
O(1A)–Pt(1)–S(1B)
O(1B)–Pt(1)–S(1A)
S(1A)–Pt(1)–S(1B)
S(2)–Pt–S(1)
O(1)–Pt–Cl(1)
S(2)–Pt–Cl(1)
S(1)–Pt–Cl(1)
C(1)–S(1)–Pt
O(2)–S(2)–Pt
C(21)–S(2)–Pt
C(7)–S(2)–Pt
89.09(13)
84.1(3)
93.48(13)
177.24(13)
107.2(6)
117.4(4)
111.7(4)
110.7(6)
129.9(9)
107.6(6)
107.4(8)
100.7(8)
126.8(13)
122(2)
107.9(3)
128.7(5)
108.1(3)
128.2(5)
C(2)–O(1)–Pt
O(2)–S(2)–C(21)
O(2)–S(2)–C(7)
C(21)–S(2)–C(7)
C(2)–N(1)–C(1)
C(1)–N(2)–C(3)
C(1)–N(2)–C(5)
C(3)–N(2)–C(5)
N(2)–C(1)–N(1)
N(2)–C(1)–S(1)
N(1)–C(1)–S(1)
O(1)–C(2)–N(1)
O(1)–C(2)–C(11)
N(1)–C(2)–C(11)
N(2)–C(3)–C(4)
C(2)–C(5)–N(2)
127.4(6)
120.9(6)
123.3(6)
115.8(6)
114.8(6)
116.3(5)
128.8(6)
130.7(7)
115.3(6)
113.9(6)
111.9(6)
112.8(7)
125.5(6)
122.4(7)
123.3(7)
114.3(6)
114.2(6)
116.6(6)
129.2(5)
131.9(7)
112.7(7)
115.3(6)
111.7(7)
111.8(8)
124(2)
113(2)
Fig. 2 The molecular structure of cis-bis(N,N-diethyl-NЈ-benzoyl-
thioureato)platinum() (2), showing the atom numbering scheme
adopted. The hydrogen atoms have been omitted for clarity. The
ellipsoids denote 30% probability.
113.0(13)
117.5(13)
129.5(12)
131.6(14)
111.8(13)
116.6(12)
110(2)
given in Table 3. The complex displays the expected square-
planar configuration around the platinum atom and the struc-
ture determination confirms that the sulfoxide is S-bonded to
PtII and co-ordinated in a cis fashion relative to the S atom of
the acylthiourea ligand. Since the synthesis and characteris-
ation of these [Pt(acylthioureato)Cl(RRЈSO)] complexes is
being reported for the first time, this crystal and molecular
structure thus provides the first structural details for PtII
complexes with this specific co-ordination sphere.
100(4)
compared to bond distances in related compounds in the liter-
ature (vide supra) and are also discussed below with respect to
the trans influence of the different donor atoms.
Structure of cis-[Pt(L1)2] (2)
The structure shows discrete [Pt(L1)Cl(MPSO)] molecules
with R and S configurations at the chiral sulfur atom, crystallis-
The molecular structure of cis-[Pt(L1)2], showing the atom
numbering scheme, is given in Fig. 2 and the relevant bond
lengths and angles are summarised in Table 3. The overall
structure is consistent with that of cis-bis(N,N-di(n-butyl)-NЈ-
benzoylthioureato)platinum() and related complexes in that
the ligands are coordinated to the platinum in a cis configur-
ation.8,17 The bond lengths and angles in the acylthiourea
ligand also compare well with those reported for cis-bis(N,N-
di(n-butyl)-NЈ-benzoylthioureato)platinum().17 Similarly to
the [PtCl(L1)(MPSO)] complex above, the bond lengths of the
thiocarbonyl [C(1A)–S(1A) 1.731(7); C(1B)–S(1B) = 1.723(7)
Å] and carbonyl [C(2A)–O(1A) 1.271(8); C(2B)–O(1B) =
¯
ing as a racemic mixture in the triclinic space group P1. The
dimensions of the sulfoxide ligand compare well with previ-
ously reported structural results.16 The phenyl ring of the
sulfoxide ligand lies almost perpendicular (111Њ) to the PtII
co-ordination plane. The bond lengths and angles in the acyl-
thiourea ligand compare well with those reported for cis-
bis(N,N-di(n-butyl)-NЈ-benzoylthioureato)platinum().17 The
bond lengths of the thiocarbonyl [C(1)–S(1) 1.736(14) Å] and
carbonyl [C(2)–O(1) 1.26(2) Å] bonds are longer than the aver-
age C᎐S and C᎐O bond lengths of 1.71 and 1.23 Å, respectively,
᎐
᎐
while the C–N bond lengths in the chelate ring are all shorter
than the average C–N single bond length of 1.479 Å, and indi-
cate extensive delocalization in the chelate ring.
1.262(8) Å] bonds are longer than average for C᎐S and C᎐O
᎐
᎐
bond, while the C–N bonds in the chelate ring are all shorter
than the average for C–N single bonds. The latter indicates, as
The bond distances within the PtII co-ordination sphere are
J. Chem. Soc., Dalton Trans., 2000, 727–733
731

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Table 4 Correlation of interatomic Pt–X bond distances in analogous PtII complexes (X = S, O, Cl)
Summary of bond data
This study
Bond
Donor atom
Trans atom
Bond range/Å
Ref.
Bond/Å
Complex
Pt–S
sulfoxide-S
sulfoxide-S
thioether-S
N,N-dimethyl-O-
ethylthiocarbamate-S
N-propyl-NЈ-benzoyl-
thiourea-S
sulfoxide-O
chloride
chloride
2.174(2)–2.217(2)
2.188(4)–2.244(3)
2.243(1)–2.292(6)
2.285(4)–2.291(4)
19–22
16, 23
24–27
28
2.192(3)
1
—
—
—
—
—
—
chloride
chloride
2.278(6)
29
—
—
acylthioureato-S
N,N-butyl-NЈ-benzoyl-
thioureato-S
N,N-butyl-NЈ-naphtholyl-
thioureato-S
—
—
—
—
chloride
acylthioureato-O
—
—
17
2.257(4)
2.232(2)
1
2
2.230(2)–2.233(2)
acylthioureato-S
2.250(4)
30
—
—
Pt–Cl
Pt–O
sulfoxide-S
thioether-S
2.289(3)–2.337(5)
2.298(7)–2.327(2)
—
16
24–27
—
—
—
2.334(3)
—
—
—
1
acylthioureato-S
N-propyl-NЈ-benzoyl-
thiourea-S
N,N-dimethyl-O-
ethylthiocarbamate-S
sulfoxide-S
2.307(4)–2.324(5)
29
—
—
2.320(4)–2.321(4)
28
—
—
N–O and O–O chelate ligands
N,N-butyl-NЈ-benzoyl-
thioureato-S
1.994(7)–2.033(7)
2.017(5)–2.026(4)
19–22
17
2.016(9)
2.021(6)
1
2
acylthioureato-O
N,N-butyl-NЈ-naphtholyl-
thioureato-S
acylthioureato-S
1.98(1)
30
—
—
for complex 1, extensive delocalization of electrons within the
chelate ring of the cis-[Pt(L1)2] complex. All other bond lengths
fall within the expected range. It is evident from the packing
diagram that there are no significant intermolecular contacts
between the discrete molecules in the crystal.
The Pt–S and Pt–O bond distances are discussed below in
conjunction with a range of literature examples, as well as the
trans influence of the sulfur and oxygen atoms in the chelated
acylthioureato backbone.
cis-[Pt(L1)2] complex [2.232(2) Å] and cis-bis(N,N-di(n-butyl)-
NЈ-benzoylthioureato)platinum() [2.230(2)–2.233(2) Å],17
presumably because this bond is trans to Cl, whereas in cis-
[Pt(L1)2] and cis-bis(N,N-di(n-butyl)-NЈ-benzoylthioureato)-
platinum()17 the Pt–S bonds are trans to oxygen atoms.
The Pt–Cl bond distance of 2.334(3) Å found in complex 1
lies at the longer side of the range, spanning 2.289(3)–2.337(5)
Å, for PtII complexes containing Pt–Cl bonds trans to sulfoxide
ligands and is longer than all the other Pt–Cl bond distances
given in Table 4. It is therefore interesting to note that the sulfur
donor atom of the bidentate acylthiourea ligand displays a
larger trans influence than the sulfur donor atoms of the
thioether, N,N-dimethyl-O-ethylthiocarbamate, N-benzoyl-NЈ-
propylthiourea and most sulfoxide ligands listed in Table 4,
which is indicative of significant σ-bonding. This is also in
agreement with the observed trend that S-bonded sulfoxides
display a fairly weak trans influence on Cl, N and O ligands.16
The Pt–O(acylthioureato) bond length in complex 1 (2.016(9)
Å) is not significantly different from those found in complex 2
and falls within the range 1.994(7)–2.033(7) Å found for PtII
sulfoxide complexes where Pt–O bonds are trans to the sulf-
oxide S donor atom. It seems that the tendency of elongation,
as observed on the Pt–Cl bond mentioned above, is not reflected
in the Pt–O bonds, which again follows the observed trend that
S-bonded sulfoxides display a fairly weak trans influence on O
ligands.16
Correlation of the Pt–X bond distances in complexes 1 and 2
A summary of relevant Pt–S, Pt–Cl and Pt–O bond distance
ranges for complexes analogous to 1 and 2 is given in Table 4,
and these are divided in terms of the type of sulfur donor
ligand in the coordination sphere.
For complex 1, the Pt–S(sulfoxide) bond distance of 2.192(3)
Å falls within the range of 2.168(2) to 2.257(8) Å found for
complexes having only one S-bonded sulfoxide.16 Studies have
shown that the length of this Pt–S bond depends not only on
the trans but also on the cis ligands.16 The effect of the trans
ligand is shown in Table 4, where the Pt–S(sulfoxide) bond
distances trans to O range from 2.174(2)–2.217(2) Å and for
bis sulfoxide complexes the Pt–S(sulfoxide) bonds with trans
Cl range from 2.188(4) Ϫ 2.244(3) Å. The longest bonds in
this latter range are found in complexes containing sulfoxides
bulkier than DMSO or with π-accepting ligands in the cis pos-
ition.16 In the present study, the Pt–S(sulfoxide) bond distance is
significantly shorter than those found in the cis-[PtCl2(MPSO)2]
complex [2.241(1), 2.245(1) Å],15,18 presumably because the Pt–
S bond in the latter complex is trans to Cl whereas in the present
structure the Pt–S bond is trans to the acylthioureato-O donor
atom.
Similarly, the Pt–S(acylthioureato) bond distance of 2.257(4)
Å in complex 1 is found on the lower side of the range [span-
ning 2.243(1)–2.292(6) Å] for PtII complexes containing bis
thioether ligands as given in Table 4, and is also shorter than the
Pt–S bond distances reported for cis-dichlorobis(N,N-dimethyl-
O-ethylthiocarbamate)platinum()28 as well as cis-bis(N-benz-
oyl-NЈ-propylthiourea)dichloroplatinum(),29 which range
from 2.278(2)–2.291(4) Å. The Pt–S(1) bond length in 1,
however, is longer compared to the Pt–S bond lengths in the
Conclusions
The spectroscopic data for the platinum() sulfoxide complexes
and the X-ray structural data for the [PtCl(L1)(MPSO)] (1)
complex have shown that the sulfoxides are S-bonded to the
platinum() ion and that the sulfoxides are cis to the S atom of
the acylthiourea ligand. The bis(acylthiourea) complex (2, cis-
[Pt(L1)2]) exhibits the expected cis geometry.
Preliminary in vitro cytotoxicity studies of [Pt(L1)-
Cl(DMSO)], [Pt(L)Cl(DMSO)], [{Pt(Cl)(DMSO)}2L2] and
related complexes, which contain either electron-withdrawing
or electron-releasing substituents on the phenyl moiety, as well
as different amine functionalities attached to the thiocarbonyl
group, have recently been carried out against a HeLa cancer cell
line. The [Pt(L1)Cl(DMSO)], [Pt(L)Cl(DMSO)] and [{Pt(Cl)-
732
J. Chem. Soc., Dalton Trans., 2000, 727–733

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9 G. M. Sheldrick, SHELXS-86, Program for Crystal Structure
Determination, University of Göttingen, Germany, 1986.
10 G. M. Sheldrick, SHELXL-97, Program for Crystal Structure
Refinement, University of Göttingen, Germany, 1997.
11 C. K. Johnson, ORTEP II, Report ORNL-5138, Oak Ridge
National Laboratory, TN, USA, 1976.
12 J. A. Davies, Adv. Inorg. Chem. Radiochem., 1981, 24, 115.
13 K. R. Koch and M. C. Matoetoe, Magn. Reson. Chem., 1991, 29,
1158.
14 P. S. Pregosin, Coord. Chem. Rev., 1982, 44, 247.
15 S. G. de Almeida, J. L. Hubbard and N. Farrell, Inorg. Chim. Acta,
1992, 193, 149.
16 M. Calligaris and O. Carugo, Coord. Chem. Rev., 1996, 153, 83 and
references therein.
17 A. Irving, K. R. Koch and M. Matoetoe, Inorg. Chim. Acta, 1993,
206, 193.
18 L. Antolini, U. Folli, D. Iarossi, L. Schenetti and F. Taddei, J. Chem.
Soc., Perkin Trans. 2, 1991, 2, 955.
(DMSO)}2L2] complexes did not exhibit any cytotoxic
behaviour, whereas a notable concentration-dependent anti-
proliferative effect was observed for the HeLa cell line treated
with the [Pt(acylthioureato)Cl(DMSO)] complexes containing
the N,N-diethyl-NЈ-(m-nitrobenzoyl)thiourea, N-morpholino-
NЈ-(m-nitrobenzoyl)thiourea or N-morpholino-NЈ-(m-meth-
oxybenzoyl)thiourea ligands. These preliminary results are
most encouraging in that they support our hypothesis that the
acylthiourea ligand could play an important role in the bio-
logical activity of this series of complexes and can thus be used
to fine-tune their antitumour behaviour.31 Detailed studies are
currently underway to investigate the biological activity of this
series of complexes and to try and establish a structure–activity
relationship.
19 G. Annibale, L. Cattalini, L. Canovese, B. Pitteri, A. Tiripicchio,
M. Tiripicchio Camellini and M. L. Tobe, J. Chem. Soc., Dalton
Trans., 1986, 1101.
20 P. B. Viossat, A. Michelet, P. Khodadad and N. Rodier, Acta
Crystallogr., Sect. C, 1990, 46, 1733.
21 L. E. Erickson, G. S. Jones, J. L. Blanchard and K. J. Ahmed, Inorg.
Chem., 1991, 30, 3147.
22 F. D. Rochon, P. C. Kong and R. Melanson, Inorg. Chem., 1990, 29,
2708.
Acknowledgements
We wish to gratefully acknowledge financial assistance from
Rhodes University, the University of the Free State and the
South African National Research Foundation. We are also
grateful to Johnson Matthey for the generous loan of K2PtCl4.
This manuscript was written in part whilst on sabbatical leave
at Edinburgh University and C. S. would like to thank the RSC
for a Journals Grant for International Authors towards this
sabbatical.
23 K. Lövqvist, Ph.D. Dissertation, Lund University, Sweden, 1996.
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