The exocyclic functionalisation of bis(thiosemicarbazonate) complexes of zinc and copper: The synthesis of monomeric and dimeric species

Article abstract of DOI:10.1039/b705087a

This paper reports the synthesis of bimetallic zinc thiosemicarbazone complexes with rigid aromatic linkers, using either 1,3- or 1,4- benzenediamines or 1,3- or 1,4- benzenedialdehydes as the basis of the linking groups. Non-rigid aliphatic diamines and

Full text of DOI:10.1039/b705087a

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The exocyclic functionalisation of bis(thiosemicarbazonate) complexes of zinc
and copper: the synthesis of monomeric and dimeric species†‡
Martin Christlieb,b Harriet S. R. Struthers,a Paul D. Bonnitcha,a Andrew R. Cowleya and
Jonathan R. Dilworth*a
Received 3rd April 2007, Accepted 26th June 2007
First published as an Advance Article on the web 2nd October 2007
DOI: 10.1039/b705087a
This paper reports the synthesis of bimetallic zinc thiosemicarbazone complexes with rigid aromatic
linkers, using either 1,3- or 1,4- benzenediamines or 1,3- or 1,4- benzenedialdehydes as the basis of the
linking groups. Non-rigid aliphatic diamines and dialdehydes were also used to link the zinc
chelating units. Reaction of a bis(thiosemicarbazone) with a pendant NHNH2 group with
monoaldehydes or ketones gives a range of monomeric complexes with exocylic imine groups bearing a
range of substituents. The zinc complexes can be quantitatively and rapidly transmetallated to the
corresponding copper complexes and this route or direct reaction with the free ligand can be used to
radiolabel the monomeric species with 64Cu. In vivo and in vitro studies of one of the 64Cu imine
complexes shows substantial hypoxic selectivity and high tumour uptake in a murine model.
PET which has resolution on the scale of millimetres. Although
Zn[ATSM] is only weakly fluorescent, it was possible to show
that the complex was taken-up by the cells and localised in the
Introduction
The metal complexes of bis(thiosemicarbazones) 1 (Fig. 1)
have been of interest to chemists and biologists since it
nucleus and as yet unidentified organelles in the cytoplasm of
was discovered that the inherent biological activity of the
IGROV (ovarian), MCF-7 (breast) and PC-3 (prostate) tumour
bis(thiosemicarbazones) was enhanced by formation of their
copper and zinc complexes.1 More recently, the copper complex of
cells. In order to pursue structure–activity relationships for uptake
in cells and in vivo, it became desirable to synthesise new zinc
bis(thiosemicarbazone) complexes, and we wished to explore the
effect on biological activity of using binuclear derivatives. Binding
of thiosemicarbazone complexes to specific receptor sites may
well be important and we wished to see if cellular distribution
was modified in the binuclear species. Recently, we reported the
diacetylbis(N-methylthiosemicarbazone) ATSM-H2 (Fig. 1: M =
Cu, R1 = R2 = Me) has been investigated as a PET (positron
emission tomography) marker for hypoxia.2–7 Recent results show
that Cu[ATSM] is indeed taken up by tumours in vivo and that
there is selective uptake in the hypoxic regions.8 However, the
mechanism of action at the cellular level is still not understood
and problems remain.
In 2005 we showed that the fluorescence of Zn[ATSM] 1
(R1 = R2 = Me) could be used to study the cellular uptake of
a bis(thiosemicarbazone) complex,9 which is not possible with
synthesis of a novel zinc complex Zn[ATSE/A-G] 1a (Fig. 1: M =
Zn) and its transformation into a novel copper complex.10 We have
also reported preliminary details of the synthesis of two dimetallic
complexes which proved to have interesting fluorescent (Zn(II))
and electrochemical properties (Cu(II)).11 In this paper we report
that the synthetic intermediate Zn[ATSR/A] used in the synthesis
of 1a is a versatile synthetic intermediate that can be used as
the starting point for the synthesis of both monometallic and
bimetallic derivatives (Fig. 2).
aChemistry Research Laboratory, University of Oxford, 12 Mansfield Road,
Oxford, UK OX1 3TA. E-mail: jon.dilworth@chem.ox.ac.uk; Fax: +44
(0)1865 272690; Tel: +44 (0)1865 185151
bThe Gray Cancer Institute, University of Oxford, Mount Vernon Hospital,
Northwood, Middlesex, UK HA6 2JR
Various syntheses exist for the preparation of both sym-
metric (R1 = R2, Scheme 1) and dissymmetric (R1 = R2)
ꢀ
† Based on the presentation given at Dalton Discussion No. 10, 3rd–5th
September 2007, University of Durham, Durham, UK.
‡ CCDC reference number 635631. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b705087a
bis(thiosemicarbazones). The starting point for the synthe-
sis is commonly a diketone; addition of two equivalents of
a thiosemicarbazide 3 to a diketone generates a symmetric
Fig. 1 Metal complexes of bis(thiosemicarbazones).
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Fig. 2 General structure of bimetallic complexes.
Fig. 3 Routes to linked thiosemicarbazide ligands.
Scheme
1
General synthetic scheme for the preparation of bis-
(thiosemicarbazones).
Scheme 2 Synthesis of a 4-substituted-3-thiosemicarbazide.
Results and discussion
bis(thiosemicarbazone) 5 (R = Rꢁ).12 Alternatively, reaction of
the diketone with one equivalent of a thiosemicarbazide 3 gives a
mono(thiosemicarbazone) 4, which can be isolated and condensed
with a second thiosemicarbazide to give the desired dissymmetric
Rigid spacers
After numerous unsuccessful attempts to make thiosemicar-
bazides from aromatic diamines, we used commercially available
isothiocyanates 8 and 9 (Fig. 4). The addition of excess hydrazine
to a solution of the diisothiocyanate in ethanol followed by heating
for 30 min gives dithiosemicarbazides 10 and 11 in 75% and 93%
yield respectively.
bis(thiosemicarbazone) 5 (R
ꢀ
= Rꢁ).1,13 These syntheses are far
from trivial, and the reaction conditions need to be controlled
very carefully to avoid the formation of heterocyclic and other
by-products.14
Treatment of bis(thiosemicarbazone) 5 with zinc acetate in
methanol forms the zinc complex 1. Alternatively, the metal
complex 1 may be prepared without the isolation of 5 via a
templated reaction of a mono(thiosemicarbazone) 4 with one
equivalent of a thiosemicarbazide in the presence of zinc acetate.
Our first approach to the synthesis of bimetallic complexes
required the synthesis of a compound containing two linked
thiosemicarbazides 6 (Fig. 3) which could then either be used to
join two mono-keto-(thiosemicarbazone) units 4 (Route a, Fig. 3)
or used in place of 3 and condensed with butanedione (Route b).
The synthetic approach to the formation of linked thiosemi-
carbazides is based on the work of Scovill.15 The synthesis is
usually conducted in a stepwise fashion (Scheme 2), isolating the
intermediates en route, but we have found that a one-pot procedure
is usually effective: an amine 7 is treated sequentially with carbon
disulfide (Scheme 2), sodium chloroacetate and hydrazine hydrate
to give the corresponding 4-substituted thiosemicarbazide 3.
Fig. 4 Structures 8 to 11.
The bimetallic complexes 12–15 (Fig. 5) were prepared by tem-
plated reactions of linked thiosemicarbazides 10 or 11, following
the method outlined in Scheme 2. Zinc acetate, thiosemicarbazides
10 and mono(methylthiosemicarbazone) 4 (R = Me) were heated
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under reflux in methanol for 16 h. After cooling an orange solid
precipitate formed, which was shown to be bimetallic complex
12, in 39% isolated yield. In a similar fashion the analogous
compounds, 13, 14 and 15 (Fig. 5) were prepared. Zn2[ATSM/1,4-
Ph/ATSM] 12 seems to be particularly hygroscopic and even after
◦
24 h drying under vacuum at 70 C, the proton NMR showed a
significant amount of water. The complexes were characterised by
1
NMR, mass spectroscopy and elemental analysis. The H NMR
spectra are consistent with the proposed structures and are distinct
1
from the H NMR spectra of the uncomplexed ligands (see 17
below). Notably, signals corresponding to the N(2) protons are
lost on complexation and the chemical shift of the N(4) protons is
decreased (moved to higher field).
Scheme 3 Synthesis of the linked bis(thiosemicarbazide) 17 from 16.
Non-rigid spacers
The method of Scovill15 was used to prepare ethane-1,2-
di(thiosemicarbazide) 19 from ethylenediamine via diacid 18
(Scheme 4). The reaction proceeded more readily than the reaction
with 1,4-diaminobenzene. A solution of 1,2-diaminoethane in
water was treated, in turn, with carbon disulfide, sodium chloroac-
etate and hydrazine. Although the product precipitates readily
from the final reaction mixture in good purity, the yield is poor;
15%. We were unable to improve this yield despite using a range
of reaction conditions.
Fig. 5 Bimetallic zinc complexes 12 to 15.
After a successful synthesis of the zinc complexes via a
template reaction we investigated the synthesis of the free lig-
ands which would in turn permit the synthesis of complexes
of other metals without using transmetallation. As outlined
above (Scheme 1), dissymmetric bis(thiosemicarbazones) are
generally prepared by heating a mono(thiosemicarbazone) 4
with a dissimilar thiosemicarbazide and acetic acid under reflux
in methanol for 3 h. However, under these conditions there
was no reaction between the linked thiosemicarbazide 11 and
either mono(4-methylthiosemicarbazone) 4 (R = Me) or mono(4-
phenylthiosemicarbazone) 4 (R = Ph). In both cases the thiosemi-
carbazide 11 was recovered unchanged. Suspecting that the lack
of reactivity was a solubility issue, butanedione was added to 11
to give a linked mono(thiosemicarbazone) 16 in 92% yield, which
was then heated under reflux in methanol with an acetic acid
catalyst with 4-methylthiosemicarbazide for 16 h to give the linked
bis(thiosemicarbazide) 17 in 77% yield (Scheme 3). The ligand can
be recrystallised from DMSO–methanol.
Scheme 4 Synthesis of ethylene linked thiosemicarbazide 19.
Repeating the one-step procedure described above using
propane-1,3-diamine as the starting material was problematic
because the thiosemicarbazide formed is water soluble. Removal
of the water gave a complex mixture of products from which it was
not possible to isolate the desired product.
Two novel bimetallic complexes were prepared by zinc-
templated reactions of 19 with mono-keto-(4-methylthiosemicar-
bazone) 4 (R = Me) to give 20 (68% yield) and mono-keto-(4-
phenylthiosemicarbazone) 4 (R = Ph) to give 21 (66% yield, see
Fig. 6).
The reaction of the linked thiosemicarbazide 19 with
butanedione proceeded readily in water following the method of
13
Gummerus (Scheme 1) to give the linked mono(thiosemicar-
Formation of a bis(thiosemicarbazone) (btsc) from the 1,4-
derivative 10 was complicated by the very low solubility of 17
in almost all common solvents except DMF and DMSO, and we
were unable to isolate pure ligand.
bazone) 22 in 56% yield. The reaction of 22 with 4-phenylthiosemi-
carbazide (Scheme 5) was carried out using the standard
conditions for dissymmetric bis(thiosemicarbazones) formation
discussed above. Refluxing in methanol for 16 h allowed isolation
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Fig. 6 Bimetallic zinc complexes 20 and 21.
Scheme 6 Synthesis of zinc complex 27.
was carried out initially between two equivalents of the zinc
complex and one equivalent of terephthalaldehyde, heating under
reflux in methanol with an acetic acid catalyst for 16 h to give a 76%
1
yield of the bimetallic complex 28. The H NMR of the product
=
showed a peak at 8.11 ppm characteristic of the N CHAr protons,
and a singlet at 7.64 ppm (for a symmetric Ar–H) demonstrating
that the terephthalaldehyde had been symmetrically substituted.
The reaction was repeated with isophthalaldehyde (benzene-
1,3-dicarboxaldehyde) which gave the corresponding 1,3-binuclear
complex 29 in 68% yield under similar reaction conditions.
The two aldehyde groups in terephthaldehyde and isophthalde-
hyde are electronically linked and it was anticipated that the reac-
tivity of the remaining aldehyde would be decreased after the first
imine formation. This should allow isolation of structures such
as 30 or 31 (Fig. 7). These could then be combined either with a
second zinc complex, different to the first, or a completely different
structure, maybe a copper complex or biological targeting group.
Reaction of Zn[ATSM/A] with an excess of terephtha-
laldehyde, heating under reflux for 3 h, gave Zn[ATSM/A–
terephthalaldehyde] 30 (Fig. 7) in 82% yield. The mononuclear
complex Zn[ATSM/A–isophthalaldehyde] 31 was also prepared
in 38% yield, although this precipitated less readily out of solution.
The yield of 31 was increased to 73% by maintaining the mixture
at reflux for 24 h. We hoped that the pendant aldehyde groups of
30 and 31 would be points of attachment for biological targeting
vectors. However treatment of 30 with benzylamine and acetic
acid in refluxing methanol over 3 h gave no reaction.
Having successfully found a route to binuclear complexes
attempts were made to vary the distance between the metal centres.
Glyoxal was used to link two complexes to form 32 (Fig. 8) in 79%
yield. It was not possible to isolate the monometallic complex 33;
using one equivalent of glyoxal, a mixture of 33 and the bimetallic
species 32 was obtained.
Crystals of 32 (Fig. 9) suitable for single crystal X-ray crystallog-
raphy were isolated from DMSO. This structure has been described
previously and will not be discussed in detail. The complex is
located on a crystallographic centre of inversion. The link between
the two bis(thiosemicarbazone) units is planar but the best planes
of the N and S atoms coordinated to the Zn atom is slightly inclined
by 12.5◦ with respect to this. As in most bis(thiosemicarbazone)
complexes the metal is coordinated by an additional ligand in the
axial site. The Zn is displaced towards the coordinated DMSO by
Scheme 5 Synthesis of the linked bis(thiosemicarbazones) 23 and 24.
of 23 in 79% yield. The reaction of 22 with 4-methylthiosemi-
carbazide was also successful and gave 24 in 82% yield.
The previous two sections have shown that while preparation
of uncomplexed linked bis(thiosemicarbazones) is possible, the
bimetallic zinc complexes are better prepared, in higher yields
and a greater degree of purity, by template reactions of linked
thiosemicarbazides 6 and mono(thiosemicarbazones) 4 with zinc
acetate. Despite our successes, the chemistry outlined above did
not work in all cases.14 We therefore turned our attention to a third
strategy; we sought to link two preformed bis(thiosemicarbazones)
ligands or their zinc complexes.
Linkages via zinc [ATSM/A]
The synthesis of a new bis(thiosemicarbazone) ligand, bu-
tandione (4-methylthiosemicarbazone) (thiocarbohydrazone) 26
(Scheme 6), has recently been demonstrated.10 Thiocarbo-
hydrazide 25 was treated with mono-keto-(4-methylthiosemi-
carbazone) 4 (R = Me) in ethanol, giving the desired ligand
ATSM/AH2 26 in 77% yield. Importantly, this material could
readily be recyrstallised from DMSO to analytical purity.
The corresponding zinc complex Zn[ATSM/A] 27 was prepared
in 59% yield from the ligand and zinc acetate by refluxing in
methanol.17 The complex showed increased solubility relative to
other zinc bis(thiosemicarbazone) complexes.
The terminal nitrogen of Zn[ATSM/A] 27 is hydrazinic
and stable hydrazone formation should be possible. The reac-
tion of Zn[ATSM/A] 27 with terephthalaldehyde (benzene-1,4-
dicarboxaldehyde) was also investigated (Scheme 7). The reaction
˚
0.40 A from the plane of the coordinated N and S atoms. Both NH
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Scheme 7 Synthesis of the bimetallic complex 28.
Fig. 7 Structures of 30 and 31.
Fig. 8 Structures of 32 and 33.
Fig. 9 ORTEP representation (40% ellipsoids) of the structure of 32.
groups form hydrogen bonds to oxygen atoms of uncoordinated
solvent.
A range of other mononuclear imine complexes were prepared
in fair to good isolated yields using the carbonyl compounds
indicated in Table 1.
The Zn[ATSM/A–2ꢁ-hydroxyacetophenone] complex 50 was
found to give crystals suitable for X-ray analysis after standing in
DMSO. An ORTEP representation is given in Fig. 11 and Table 2
gives selected bond distances.
The reaction between Zn[ATSM/A] 27 and butanedione gives
imine 34, in 65% yield. The isolated product is shown to be clean
by NMR spectroscopy without purification (Scheme 8).
The mononuclear complexes 35–37 were prepared similarly in
65–75% yield (Fig. 10) using an excess of the dicarbonyl.
Fig. 10 Structures of 35, 36 and 37.
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Table 1 Aldehydes and ketones used in condensation reactions with Zn[ATSM/A] with the isolated yields of the imine products
Carbonyl
Compound (yield (%))
Carbonyl
Compound (yield (%))
38 (54)
45 (46)
39 (62)
46 (58)
40 (90)
41 (53)
42 (67)
47 (39)
48 (50)
49 (60)
43 (73)
44 (49)
50 (58)
51 (70)
˚
Table 2 Selected bond lengths (A) for complex 50
Zn(1)–S(1)
Zn(1)–S(2)
Zn(1)–N(2)
Zn(1)–N(3)
Zn(1)–O(2)
N(1)–N(2)
N(1)–C(1)
2.3912(8)
2.3459(9)
2.126(3)
2.134(3)
2.027(2)
1.368(3)
1.320(4)
C(1)–S(1)
C(1)–N(5)
N(3)–N(4)
N(4)–C(4)
C(4)–S(2)
C(4)–N(7)
O(1)–N(6)
1.734(3)
1.371(4)
1.376(4)
1.327(4)
1.756(4)
1.344(4)
2.552(4)
Scheme 8 Condensation of butanedione with Zn[ATSM/A].
(Fig. 11). The complex is pseudo square pyramidal with the
bis(thiosemicarbazone) ligand essentially planar and the zinc ion
raised out of the plane of the bis(thiosemicarbazone) moiety [S1–
Zn1–N3 and N2–N1–S2 angles 150.49(7)◦ and 146.92(7)◦ respec-
tively]. The Zn–S and Zn–N distances are commensurate with
other zinc bis(thiosemicarbazone) structures. The terminal imine
bond adopts the E-configuration, with the methyl group of the ace-
tophenone cis to the N(5) atom. It is likely that this configuration
is sterically favourable and is further stabilised by the hydrogen
bond between the hydroxyl group on the acetophenone and the
˚
N(6) of the bis(thiosemicarbazone) [O(1)–N(6) 2.552(4) A]. The
uncoordinated DMSO molecule contributes to intermolecular
hydrogen bonds with the coordinated water molecule [O(2)–
Fig. 11 ORTEP representation (40% ellipsoids) of the structure of zinc
complex 50.
˚
O(3) 2.606(4) A]. In addition, the packing diagram reveals in-
termolecular hydrogen bonds between adjacent complexes [N(7)–
1
Complex 50 crystallises in orthorhombic space group Pbca with
a water molecule bound to the axial site and a DMSO of solvation
O(1) 2.997(4), O(2)–N(1) 2.724(3)]. H NMR studies on 1 : 1
DMSO–H2O solutions of Zn(ATSM–2ꢁ-hydroxyacetophenone)
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showed no detectable hydrolysis of the terminal imine bond after
24 h. This is comparable with results achieved for other imine
conjugates {Zn[ATSM/A–acetophenone] and Zn[ATSM/A–2-
nitrobenzaldehyde]} which also contain a phenyl group adjacent to
the terminal imine (2-nitrobenzaldehyde studies were performed
in 40% aqueous DMSO solution due to solubility limitations).
While the aliphatic imines, such as propanal, show some hydrolysis
under these conditions, an estimated 80% of the compound is
Thiosemicarbazides
Benzene-1,4-dithiosemicarbazide 10. An aqueous solution of
hydrazine (0.72 mL, 25.00 mmol in 0.5 mL water) was added to
a solution of benzene-1,4-diisothiocyanate (0.24 g, 1.25 mmol) in
ethanol (20 mL). The mixture was stirred for 30 min and then
cooled in an ice bath. The resulting grey precipitate was collected
by filtration, washed well with ethanol and water and dried in
vacuo. The product was isolated as a pale grey powder (0.33 g,
=
intact after 24 h. The N–N and C N bond distances in the ter-
1
75%). (Mass: 279.0468. Calc. for C8H12N6NaS2: 279.0463.) H
minal imine bond of the Zn(ATSM/A–2ꢁ-hydroxyacetophenone)
NMR: d 4.78 (4H, s, NH2); 7.52 (4H, s, ArH); 9.10 (2H, s, PhNH);
9.66 (2H, s, NHNH2). 13C NMR: d 122.98; 135.01; 178.93. MS
ES+: m/z 279.05 (100%, [C8H12N6S2]Na+).
˚
structure [1.362(4) and 1.371(4) A respectively] suggest that there
is significant electron delocalisation which may help explain this
stability of the imine bond to hydrolysis.
1-Methylbenzene-2,4-dithiosemicarbazide 11. As per pro-
cedure for benzene-1,4-dithiosemicarbazide except with 1-
methylbenzene-2,4-diisothiocyanate (0.52 g, 2.52 mmol) and hy-
drazine (1.57 mL, 50 mmol). The product was isolated as a white
powder (1.38 g, 93%). 1H NMR: d 2.15 (3H, s, PhCH3); 4.79 (4H, s,
NH2); 7.11 (1H, d, J 8.28, ArH); 7.43 (1H, m, J 6.54, ArH); 7.81
(1H, m, ArH); 9.09 (2H, s, PhNH); 9.57 (1H, s, NH). 13C NMR: d
180.5; 179.6; 137.9; 137.2; 129.6; 129.5; 122.4; 121.2; 17.7.
Transmetallation and biological studies
Reaction of the monomeric zinc complexes with one equivalent of
copper(II) in aqueous methanol results in rapid and quantitative
formation of the analogous Cu(II) complexes. This procedure,
direct reaction with the free ligand was used for high yield
radiolabelling with copper-64. Extensive biological studies on
complex 49 (cell uptake studies, in vivo biodistributions and
PET imaging in a murine model) have shown high hypoxic
selectivity and tumour uptake with a significant difference in
biodistribution to Cu[ATSM]. This demonstrates that the strategy
of altering the biological behaviour of Cu[ATSM] by modification
of the exocyclic nitrogen is valid, and does not necessarily impair
hypoxic selectivity. A number of other copper imine complexes are
currently under investigation, and full details of these biological
studies and those of the fluorescent zinc complexes will be reported
elsewhere.
Ethane-1,2-dithiosemicarbazide
19. Ethane-1,2-diamine
(1.67 mL, 25.00 mmol) was added to NaOH (2.00 g, 50.00 mmol)
in water (40 mL). CS2 (4.50 mL, 75.00 mmol) was added and the
reaction mixture was stirred for 4 h, after which time the organic
layer had disappeared. The orange solution was treated with
sodium chloroacetate (5.83 g, 50.00 mmol) and left to stir for 16 h.
The cloudy yellow solution was acidified with 2 M HCl (5 mL)
and an excess of NH2NH2 (10.88 mL, 0.35 mol) was added. The
mixture was heated at 90 ◦C for 2 h. The precipitate formed
was collected by filtration, washed well with water and dried in
vacuo. The product was isolated as a white powder (3.32 g, 64%).
1H NMR: d 3.60 (4H, s, CH2); 4.45 (4H, s, NH2); 8.02 (2H, s,
CH2NH); 8.69 (2H, s, NHNH2). 13C NMR: d 42.53; 180.87. MS
ES+: m/z 231.05 (50%, [C4H12N6S2]Na+).
Conclusions
The introduction of a pendant NHNH2 group onto the
bis(thiosemicarbazonate) metal complex core has been shown to
be a flexible high yield route to the synthesis of a range of new
monomeric and dimeric complexes. Significantly the monomeric
Zn complexes can readily be transmetallated with copper(II) and
the 64Cu-labelled complexes show high hypoxic selectivity.
Mono-keto-(thiosemicarbazones)
General procedure: Mono-keto-(4-methylthiosemicarbazone) 5a.
Butanedione (1.07 mL, 12.00 mmol) and conc. HCl (0.5 mL) were
added to 4-methylthiosemicarbazide (1.05 g, 10.00 mmol) in water
(20 mL). The mixture was cooled in an ice bath and stirred for
30 min. A bulky white solid settled out of solution and was filtered
off, washed with cold water and left to dry in air for 24 h. The
Experimental
General procedures
All reagents and solvents were obtained from commercial sources
(Sigma-Aldrich and Lancaster) and, unless otherwise stated, were
used as received. Elemental analyses were performed by the
microanalysis service of the Inorganic Chemistry Laboratory at
the University of Oxford. NMR spectra were recorded on either
a Varian Mercury VX300 spectrometer (1H NMR at 300 MHz
and 13C{1H} NMR at 75.5 MHz) or a Varian Unity 500-MHz
spectrometer (1H NMR at 499.9 MHz and 13C{1H} NMR at
125.7 MHz) using the residual solvent signal as an internal
reference. Mass spectra were recorded on a Micromass LCT
time-of-flight mass spectrometer using positive ion electrospray
(ES+), solid probe electron impact (EI), or field ionization (FI+)
techniques. Where possible, accurate masses are reported to four
decimal places using tetraoctylammonium bromide (466.5352 Da)
as an internal reference.
1
product was isolated as a white solid (1.05 g, 61%). H NMR: d
1.95 (3H, s, CH3); 2.42 (3H, s, CH3); 3.05 (3H, d, J 4.56, NHCH3);
8.63 (1H, d, J 3.94, NHCH3); 10.65 (1H, s, NH). 13C NMR: d
10.00; 24.75; 31.39; 145.42; 178.88; 197.43. MS ES+: m/z 173.97
(100%, [C6H11N3OS]H+).
Mono-keto-(4-phenylthiosemicarbazone) 5b. As per general
procedure except with butanedione (1.22 mL, 13.92 mmol), conc.
HCl (0.5 mL) and 4-phenylthiosemicarbazide (1.57 g, 9.40 mmol).
The product was isolated as a pale orange solid (1.79 g, 81%). 1H
NMR: d 2.03 (3H, s, CH3); 2.48 (3H, s, CH3); 7.25 (1H, t, J 7.37,
ArH); 7.40 (2H, t, J 7.76, ArH); 7.55 (2H, d, J 7.49, ArH); 10.20
(1H, s, NHPh); 10.98 (1H, s, NH). 13C NMR: d 198.0; 178.2; 149.6;
146.7; 139.4; 129.1; 126.2; 25.5; 10.8. MS ES+: m/z 258.07 (100%,
[C11H13N3OS]Na+).
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1
Mono-keto-(1-methylbenzene-2,4-dithiosemicarbazone) 16. As
per general procedure except with butanedione (0.23 mL,
1.19 mmol), conc. HCl (0.5 mL) and 1-methylbenzene-2,4-
dithiosemicarbazide (0.32 g, 2.62 mmol). The product was isolated
as a cream solid (0.44 g, 92%). (Mass: 407.1319. Calc. for
C21H28N12S4Zn2: C, 35.65; H, 4.0; N, 23.75%.) H NMR: d 2.10
(3H, s, CH3); 2.12 (3H, s, CH3); 2.18 (3H, s, CH3); 2.22 (3H, s,
CH3); 2.24 (3H, s, PhCH3); 2.84 (H, s, NHCH3); 7.02 (1H, d,
J 8.48, ArH); 7.31 (1H, s, CH3NH); 7.37 (1H, s, CH3NH);
7.49 (1H, m, J 8.35, 2.05, ArH); 7.93 (1H, d, J 1.84, ArH);
8.60 (1H, s, PhNH); 9.29 (1H, s, PhNH). 13C NMR: d 13.80;
14.16; 14.65; 17.60; 29.18; 116.58; 118.22; 125.68; 129.34; 138.44;
138.89; 146.84; 148.50; 172.35; 174.84. MS ES+: 709.01 (100%,
[Zn2L]H+); 1415.07 (10, [Zn2L]2H+).
1
C17H23N6O2S2: 407.1324.) H NMR: d 2.05 (6H, s, CH3); 2.25
(3H, s, PhCH3); 2.51 (6H, s, CH3); 7.32 (1H, d, J 8.32, ArH);
7.47 (1H, m, J 8.17, 2.05, ArH); 7.67 (1H, d, J 1.87, ArH); 10.15
(1H, s, PhNH); 10.24 (1H, s, PhNH); 10.99 (1H, s, NH); 11.00
(1H, s, NH). 13C NMR: d 198.13; 198.10; 178.6; 178.0, 149.8;
146.8; 137.9; 137.1; 133.1; 130.1; 125.5; 124.6; 25.5; 25.4; 17.8;
10.8. MS ES+: m/z 429.11 (100%, [C17H22N6O2S2]Na+).
1,3-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-phenylthiosemicarbazonate)-3ꢀ-(4ꢀꢀ-N-
thiosemicarbazonate)zinc(II)}-6-methylbenzene
15. As
per
general procedure except with zinc acetate (0.25 g, 1.14 mmol),
1-methylbenzene-2,4-dithiosemicarbazide (0.15 g, 0.56 mmol)
and mono-keto-(4-phenylthiosemicarbazone) (0.26 g, 1.11 mmol).
The product was isolated as a yellow-orange powder (0.31 g,
68%). (Found: C, 43.8; H, 3.85; N, 19.6. Calc. for C31H32N12S4Zn2:
Mono-keto-(ethane-1,2-dithiosemicarbazone). As per general
procedure except with butanedione (0.46 mL, 5.29 mmol),
conc. HCl (0.5 mL) and ethane-1,2-dithiosemicarbazide (0.50 g,
2.40 mmol). The product was isolated as a cream powder (1.34 g,
56%). (Mass: 367.0973. Calc. for C12H20N6NaO2S2: 367.0987.)
1H NMR: d 1.94 (6H, s, CH3); 2.39 (6H, s, CH3); 3.89 (4H, m,
CH2); 8.73 (2H, s, CH2NH); 10.76 (2H, s, NH). 13C NMR: d
197.9; 179.3; 146.5; 44.0; 25.4; 10.7. MS ES+: m/z 367.10 (100%,
[C12H20N6O2S2]Na+).
1
C, 44.8; H, 3.9; N, 20.2%.) H NMR: d 9.45 (1H, s, NH); 9.44
(1H, s, NH); 9.39 (1H, s, NH); 8.82 (1H, s, NH); 7.92 (1H, d, J
2.3, ArH); 7.79 (4H, d, J 8.2, PhH); 7.51 (1H, dd, J 8.2 and 2.1,
ArH); 7.23 (4H, t, J 8.2, PhH); 7.04 (1H, d, J 8.5, ArH); 6.90 (2H,
t, J 8.2, PhH); 2.31 (3H, s, ArCH3); 2.27 (6H, s, CH3); 2.13 (6H, s,
CH3). 13C NMR: d 176.3; 173.7; 173.6; 173.4; 149.2; 149.0; 148.5;
146.7; 141.6; 141.5; 139.2; 138.8; 129.9; 128.8; 126.8; 122.0; 121.9;
120.4; 120.3; 119.2; 117.5; 18.1; 15.2; 15.1; 14.6. MS MALDI:
833.11 (100%, [Zn2L]H+).
Bimetallic zinc complexes using template route
General procedure: 1,4-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-methylthiosemi-
carbazonate)-3ꢀ-(4ꢀꢀ-N-thiosemicarbazonate)zinc(II)}benzene 12.
Zinc acetate (0.29 g, 1.32 mmol) and benzene-1,4-di-thiosemicar-
bazide (0.15 g, 0.59 mmol) were added to a solution of mono-keto-
(4-methylthiosemicarbazone) (0.20 g, 1.18 mmol) in methanol.
The mixture was heated under reflux for 16 h and allowed to
cool slowly to room temperature. The orange solid that formed
was collected by filtration, washed with methanol and diethyl
ether and dried in vacuo. The product was isolated as an orange
powder (0.16 g, 39%). (Found: C, 36.45; H, 4.0; N, 21.5. Calc.
for C20H26N12S4Zn2: C, 34.6; H, 3.8; N, 24.2%.) 1H NMR: d 2.24
(6H, s, CH3); 2.29 (6H, s, CH3); 2.85 (6H, s, CH3NH); 7.37 (2H, s,
CH3NH); 7.66 (4H, s, ArH); 9.27 (2H, s, PhNH). 13C NMR: d
not available due to very low solubility. MS ES+: 692.07 (100%,
[Zn2L]H+), 348.00 (40, [Zn2L]H22+).
1,2-Bis{diacetyl-2ꢀ -(4ꢀꢀ -N -methylthiosemicarbazonate)-3ꢀ -(4ꢀꢀ -
N-thiosemicarbazonate)zinc(II)}ethane 20. As per general pro-
cedure except with zinc acetate (0.30 g, 1.37 mmol), ethane-
1,2-dithiosemicarbazide (0.13 g, 0.63 mmol) and mono-keto-(4-
methylthiosemicarbazone) (0.22 g, 1.27 mmol). The product was
isolated as a yellow powder (0.27 g, 68%). (Found: C, 29.2; H,
4.2; N, 25.4. Calc. for C16H26N12S4Zn2: C, 29.8; H, 4.1; N, 26.0%.)
(Mass: 642.9925. Calc. for C16H27N12S4Zn2: 642.9947.) 1H NMR:
d 2.20 (6H, s, CH3); 2.23 (6H, s, CH3); 2.82 (6H, d, J 4.11, CH3);
3.51 (4H, m, CH2); 7.24 (2H, s, NH); 7.38 (2H, s, NH). MS ES+:
642.99 (100%, [Zn2L]H+). 13C NMR: d 179.0; 146.0; 145.5; 48.6;
29.2; 14.1 13.5.
1,2-Bis{diacetyl-2ꢀ -(4ꢀꢀ -N -phenylthiosemicarbazonate)-3ꢀ -(4ꢀꢀ -
N-thiosemicarbazonate)zinc(II)}ethane 21. As per general pro-
cedure except with zinc acetate (0.26 g, 1.18 mmol), ethane-1,2-
dithiosemicarbazonate (0.11 g, 0.53 mmol) and mono-keto-(4-
phenylthiosemicarbazone) (0.26 g, 1.11 mmol). The product was
isolated as a yellow powder (0.27 g, 66%). (Found: C, 39.5; H, 4.0;
N, 20.75. Calc. for C26H30N12S4Zn2: C, 40.6; H, 3.9; N, 21.8%.)
1H NMR: d 2.29 (6H, s, CH3); 2.31 (6H, s, CH3); 3.55 (4H, m,
CH2); 6.90 (2H, t, J 7.30, ArH); 7.24 (4H, t, J 7.87, ArH); 7.57
(2H, s, NHCH2); 7.81 (4H, d, J 7.99, ArH); 9.38 (2H, s, NHPh).
13C NMR: d 173.2; 149.4; 141.6; 128.8; 121.8; 120.3; 42.6; 15.2;
14.5. MS ES+: m/z 705.11 (100%, [ZnLH2]H+); 769.02 (60%,
[Zn2L]H+).
1,4-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-phenylthiosemicarbazonate)-3ꢀ-(4ꢀꢀ-N-
thiosemicarbazonate)zinc(II)}benzene 13. As per general
procedure except with zinc acetate (0.40 g, 1.82 mmol), benzene-
1,4-di-thiosemicarbazide (0.21 g, 0.82 mmol) and mono-keto-(4-
phenylthiosemicarbazone) (0.39 g, 1.67 mmol). The product was
isolated as an orange powder (0.46 g, 69%). (Found: C, 42.3; H,
3.6; N, 19.4. Calc. for C30H30N12S4Zn2: C, 44.1; H, 3.7; N, 20.6%.)
1H NMR: d 2.34 (6H, s, CH3); 6.93 (2H, t, J 7.32, ArH); 7.26 (4H,
t, J 7.88, ArH); 7.69 (4H, s, ArH); 7.82 (4H, d, J 7.90, ArH); 9.45
(2H, s, PhNH); 9.48 (2H, s, PhNH). 13C NMR: d 173.6; 173.5;
149.0; 148.1; 141.5; 135.9; 128.8; 122.0; 120.7; 120.4; 15.2; 15.1.
MS MALDI: 819.51 (100%, [Zn2L]H+).
1,3-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-methylthiosemicarbazonate)-3ꢀ-(4ꢀꢀ-N-
Linked bis(thiosemicarbazone) ligands
thiosemicarbazonate)zinc(II)}-6-methylbenzene
14. As
per
general procedure except with zinc acetate (0.37 g, 1.69 mmol),
1-methylbenzene-2,4-dithiosemicarbazonate (0.23 g, 0.85 mmol)
1,3-Bis{diacetyl-2ꢀ -(4ꢀꢀ -N-methylthiosemicarbazide)-3ꢀ -(4ꢀꢀ -N-
thiosemicarbazide)}-6-methylbenzene 17. As per general proce-
dure except with 4-methylthiosemicarbazide (0.47 g, 4.48 mmol),
acetic acid (0.5 mL) and mono-keto-(1-methylbenzene-2,4-
dithiosemicarbazone) (0.82 g 2.03 mmol). The product was
and
mono-keto-(4-methylthiosemicarbazonate)
(0.30
g,
1.73 mmol). The product was isolated as a yellow powder
(0.26 g, 48%). (Found: C, 35.3; H, 4.4; N, 23.6. Calc. for
5050 | Dalton Trans., 2007, 5043–5054
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©

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isolated as a yellow powder (0.90 g, 77%). 1H NMR: d 2.25 (3H, s,
CH3); 2.29 (6H, s, CH3); 2.34 (3H, s, PhCH3); 3.03 (6H, d, J 4.40,
NHCH3); 7.24 (1H, d, J 8.23, ArH); 7.45 (1H, m, J 7.32, ArH);
7.68 (1H, d, J 1.95, ArH); 8.42 (2H, q, J 4.50, CH3NH); 9.87
(1H, s, PhNH); 9.96 (1H, s, PhNH); 10.29 (1H, s, NH); 10.34
(1H, s, NH); 10.58 (2H, s, NH). 13C NMR: d 178.9; 178.6; 177.9;
177.0; 149.8; 149.5; 148.2; 146.9; 138.0; 137.1; 133.1; 132.4; 130.1;
125.5; 31.7; 25.4; 17.8; 12.5; 12.3; 12.1; 10.8. MS ES+: m/z 603.17
(10%, [C21H32N12S4]Na+).
4.0; N, 24.9. Calc. for C22H28N14S4Zn2: C, 35.3; H, 3.8; N, 26.2%.)
1H NMR: d 2.24 (6H, s, CH3); 2.28 (6H, s, CH3); 2.85 (6H, s,
NHCH3); 7.36 (2H, m, NHCH3); 7.44 (1H, m, 5-ArH); 7.54
(2H, m, 4-ArH); 8.00 (1H, s, 2-ArH); 8.13 (2H, s, C(N)H); 11.37
(2H, s, NHNR). 13C NMR: d 13.86; 14.26; 127.14; 129.08; 135.57;
140.82; 140.86; 148.41. MS ES+: m/z 749.01 (100%, ZnLH+).
The synthesis and characterisation of 1,2-bis{diacetyl-
2ꢁ -(4ꢁꢁ -N-methylthiosemicarbazonate)-3ꢁ -(4ꢁꢁ -N-aminomethinyl-
thiosemicarbazonate)zinc(II)}ethane 32 has been published
previously.11 We here present the carbon-13 NMR data which
was not available before. 13C NMR: d 176.3 (2 carbons); 148.8;
141.0; 14.3; 13.8. MS ES+: m/z 672.97 (100%, ZnLH+). Crystals
suitable for single crystal X-ray crystallography were isolated from
the NMR sample.
1,2-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-phenylthiosemicarbazide)-3ꢀ-(4ꢀꢀ-N-thio-
semicarbazide)}ethane 23. 4-Phenylthiosemicarbazide (0.15 g,
0.92 mmol) and acetic acid (0.5 mL) were added to a solution of
mono-keto-(ethane-1,2-dithiosemicarbazone) (0.15 g, 0.44 mmol)
in methanol (30 mL). The mixture was heated under reflux for
16 h under an atmosphere of nitrogen and allowed to cool slowly
to room temperature. The resulting white solid was washed with
methanol and diethyl ether and dried in vacuo. The product was
Mononuclear complexes derived from 26 or 27
General procedure: Diacetyl-2-(4-N-methyl-3-thiosemicar-
bazonate)-3-[4-N-(amino-2ꢀ -(3ꢀ -oxobutylidene))-3-thiosemicarba-
zonate]zinc(II) 44. Zn[ATSM/A] (0.20 g, 0.62 mmol) and
butanedione (0.11 mL, 1.23 mmol) were added to methanol
(20 mL). The mixture was heated under reflux for 3 h under
an atmosphere of nitrogen and allowed to cool slowly to room
temperature. A bright orange powder formed which was washed
with methanol and diethyl ether and dried in vacuo. The product
was isolated as a bright orange solid (0.16 g, 65%). (MS ES+
found mass: 392.0311. Calc. mass for C11H18N7OS2Zn: 392.0306.)
(Found: C, 33.8; H, 4.5; N, 23.7; S, 15.9; Zn, 16.7. Calc. for
C11H17N7OS2Zn: C, 33.6; H, 4.4; N, 25.0; S, 16.3; Zn, 16.7%.)
1H NMR: d 1.94 (3H, s, CH3); 2.24 (3H, s, CH3); 2.31 (3H, s,
CH3); 2.34 (3H, s, CH3); 2.86 (3H, s, NHCH3); 7.49 (1H, s,
NHCH3); 10.62 (1H, s, NHNR). 13C NMR: d 9.46; 13.81; 14.33;
23.95; 29.20; 144.30; 151.45; 177.46; 197.24. MS ES+: m/z 392.03
(100%, ZnLH+).
1
isolated as a pale yellow solid (0.22 g, 79%). H NMR: d 2.26
(6H, s, CH3); 2.29 (6H, s, CH3); 3.88 (4H, m, CH2); 7.21 (2H, d, J
7.34, ArH); 7.37 (4H, t, J 7.78, ArH); 7.55 (4H, t, J 7.65, ArH);
8.59 (2H, m, NHCH2); 9.98 (2H, s, NHPh); 10.44 (2H, s, NH);
10.63 (2H, s, NH). MS ES+: m/z 665.19 (10%, [C26H34N12S4]Na+).
1,2-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-methylthiosemicarbazide)-3ꢀ-(4ꢀꢀ-N-thio-
semicarbazide)}ethane 24. As per general procedure except
with 4-methylthiosemicarbazide (0.09 g, 0.86 mmol), acetic
acid (0.5 mL) and mono-keto-(ethane-1,2-dithiosemicarbazone)
(0.16 g, 0.41 mmol). The product was isolated as a cream solid
1
(0.19 g, 82%). H NMR: d 2.20 (6H, s, CH3); 2.21 (6H, s, CH3);
3.01 (6H, d, J 4.49, NHCH3); 3.85 (4H, m, CH2); 8.39 (2H, q, J
4.57, NHCH3); 8.54 (2H, s, NHCH2); 10.26 (2H, s, NH); 10.35
(2H, s, NH). 13C NMR: d 178.8; 178.6; 149.1; 148.3; 44.0; 31.6;
12.3; 12.2.
The synthesis and characterisation of ATSM/AH2 26 and
Zn[ATSM/A] 27 have been described previously.10
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(4ꢀ -carboxaldehyde-benzylidene))-3-thiosemicarbazonate]zinc(II)
30. As per general procedure except with Zn[ATSM/A] (0.34 g,
1.06 mmol) and terephthalaldehyde (0.28 g, 2.12 mmol). The
product was isolated as an orange-red solid (0.39 g, 82%). (Found:
C, 40.0; H, 4.5; N, 21.6. Calc. for C15H17N7OS2Zn: C, 40.9; H,
3.9; N, 22.3%.) (MS ES+ found mass: 440.0288. Calc. mass for
Binuclear complexes derived from 26 and 27
General procedure: 1,4-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-methylthiosemi-
carbazonate)-3ꢀ -(4ꢀꢀ -N -aminomethinyl-thiosemicarbazonate)zinc-
(II)}benzene 28. Zn[ATSM/A] (0.18 g, 0.56 mmol) and tereph-
thalaldehyde (0.04 g, 0.28 mmol) were added to methanol (30 mL).
The mixture was heated under reflux for 16 h under an atmosphere
of nitrogen and allowed to cool slowly to room temperature. An
orange powder formed which was washed with methanol and
diethyl ether and dried in vacuo. The product was isolated as a
yellow-orange solid (0.16 g, 76%). (Found: C, 34.7; H, 4.8; N,
24.9. Calc. for C22H28N14S4Zn2: C, 35.3; H, 3.8; N, 26.2%.) (Mass:
1
C15H17N7OS2Zn: 440.0306.) H NMR: d 2.23 (3H, s, CH3); 2.29
(3H, s, CH3); 2.85 (3H, s, NHCH3); 7.41 (1H, s, NHCH3); 7.82
(2H, d, J 8.19, 3-ArH); 7.93 (2H, d, J 8.13, 2-ArH); 8.17 (1H, s,
C(N)H); 10.00 (1H, s, C(O)H); 11.58 (1H, s, NHNR). 13C NMR:
d 13.52; 13.93; 126.32; 129.68; 135.44; 139.33; 140.68; 148.86;
192.20. MS ES+: m/z 440.10 (100%, ZnLH+).
1
745.0136. Calc. mass for C22H29N14S4Zn: 745.0165.) H NMR: d
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(3ꢀ -carboxaldehyde-benzylidene))-3-thiosemicarbazonate]zinc(II)
31. As per general procedure except with Zn[ATSM/A] (0.16 g,
0.48 mmol) and isophthalaldehyde (0.13 g, 0.97 mmol). The
product was isolated as an orange-red solid (0.08 g, 38%). (MS ES+
found mass: 440.0308. Calc. mass for C15H17N7OS2Zn: 440.0306.)
(Found: C, 40.9; H, 3.9; N, 22.2. Calc. for C15H17N7OS2Zn: C,
40.9; H, 3.9; N, 22.2%.) 1H NMR: d 2.23 (3H, s, CH3); 2.29
(3H, s, CH3); 2.85 (3H, s, NHCH3); 7.38 (1H, s, NHCH3); 7.64
(1H, t, J 7.64, 5-ArH); 7.87 (1H, d, J 7.64, 6-ArH); 7.94 (1H,
d, J 7.71, 4-ArH); 8.13 (1H, s, 2-ArH); 10.06 (1H, s, C(O)H);
2.23 (6H, s, CH3); 2.28 (6H, s, CH3); 2.85 (6H, d, J 1.79, NHCH3);
7.37 (2H, bs, NHCH3); 7.64 (4H, s, ArH); 8.11 (2H, s, C(N)H);
11.37 (2H, s, NHNR). 13C NMR: d 176.1 (2 carbons); 172.0; 148.3;
141.0; 135.6; 126.7; 21.1; 14.2; 13.9. MS ES+: m/z 747.01 (100%,
ZnLH+).
1,3-Bis{diacetyl-2ꢀ-(4ꢀꢀ-N-methylthiosemicarbazonate)-3ꢀ-(4ꢀꢀ-N-
aminomethinylthiosemicarbazonate)zinc(II)}benzene 29. As per
general procedure except with Zn[ATSM/A] (0.17 g, 0.52 mmol)
and isophthalaldehyde (0.03 g, 0.26 mmol). The product was
isolated as a bright orange solid (0.13 g, 68%). (Found: C, 34.9; H,
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The Royal Society of Chemistry 2007
Dalton Trans., 2007, 5043–5054 | 5051
©

View Article Online
11.45 (1H, s, NHNR). 13C NMR: d 13.81; 14.18; 126.83; 129.48;
129.59; 131.80; 136.20; 136.55; 139.95; 148.65; 193.11. MS ES+:
m/z 440.03 (100%, Zn[ATSM/A − isophthalaldehyde mono
condensate]H+).
This reaction was repeated, heating for 24 h which raised the
yield to 73%.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(2-pyridyl)methylidene)-3-thiosemicarbazonate]zinc(II)
40. As
per general procedure except with Zn[ATSM/A] (0.14 g,
0.22 mmol) and 2-pyridinecarboxaldehyde (0.04 mL, 0.43 mmol).
The solvent was removed from the reaction mixture with a rotary
evaporator. The crude product was dissolved in methanol and
precipitated with water. The product was washed with diethyl
ether and dried in vacuo. The product was isolated as a yellow
solid (0.16 g, 91%). (MS ES+ found mass: 413.0323. Calc. mass
for C13H17N8S2Zn: 413.0309.) 1H NMR: d 1.89 (3H, s, CH3); 2.22
(3H, s, CH3); 2.27 (3H, s, CH3); 7.30 (1H, t, J 7.6, PyrH); 7.38
(1H, m, NHCH3); 7.81 (1H, d, J 7.6, PyrH); 7.85 (1H, t, J 7.6,
PyrH); 8.15 (1H, s, C(H)N); 8.52 (1H, d, J 5.6, PyrH); 11.78
(1H, br s, NHNR); 13C NMR: d 178.4; 175.9; 172.1; 154.2; 152.4;
148.6; 141.8; 136.5; 123.3; 119.2; 21.1; 14.2; 13.8. MS ES+: m/z
413.03 (100%, ZnLH+); 829.05 (12%, Zn2L2H+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
1ꢀ-(1-carboxylic acid-ethylidene))-3-thiosemicarbazonate]zinc(II).
As per general procedure except with Zn[ATSM/A] (0.16 g,
0.48 mmol) and pyruvic acid (0.07 mL, 0.96 mmol). The product
1
was isolated as a yellow powder (0.12 g, 65%). H NMR: d 2.18
(3H, s, CH3); 2.22 (3H, s, CH3); 2.26 (3H, s, CH3); 2.83 (3H,
d, J 3.11, NHCH3); 7.35 (1H, s, NHCH3); 8.90 (1H, s, OH);
10.11 (1H, s, NHNR). 13C NMR: d 11.68; 14.38; 29.69; 31.61;
146.64; 149.45; 166.67; 177.93; 178.70. MS ES+: m/z 394.07
(80%, ZnLH+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
2ꢀ-(1ꢀ-oxo-1ꢀ-phenylethylidene))-3-thiosemicarbazonate]zinc(II) Zn-
[ATSM/A–phenylglyoxal]. As per general procedure except
with Zn[ATSM/A] (0.24 g, 0.73 mmol) and phenylglyoxal (0.20 g,
1.47 mmol). The product was isolated as a dark red solid (0.24 g,
75%). (Found: C, 41.0; H, 4.3; N, 22.1. Calc. for C15H17N7OS2Zn:
C, 40.9; H, 3.9; N, 22.3%.) (MS ES+ found mass: 440.0312. Calc.
(4-fluorophenyl)methylidene)-3-thiosemicarbazonate]zinc(II)
41.
As per general procedure except with Zn[ATSM/A] (0.13 g,
0.41 mmol) and 4-fluorobenzaldehyde (0.09 mL, 0.81 mmol). The
product was isolated as a yellow powder (0.09 g, 53%). (MS ES+
found mass: 430.0266. Calc. mass for C14H17FN7S2Zn: 430.0262.)
1H NMR: d 2.23 (3H, s, CH3); 2.27 (3H, s, CH3); 2.85 (3H, m,
NHCH3); 7.25 (2H, t, J 8.85, ArH); 7.36 (1H, s, NHCH3); 7.66
(2H, m, ArH); 8.10 (1H, s, C(N)H). 13C NMR: d 178.5, 176.3,
173.4, 162.4 (JCF 251), 148.3, 140.3, 131.8, 128.3, 115.75 (JCF 25),
21.1, 14.2, 13.8. 19F NMR: d 112.28. MS ES+: m/z 430.07 (100%,
ZnLH+).
1
mass for C15H17N7OS2Zn: 440.0306.) H NMR: d 2.24 (3H, s,
CH3); 2.31 (3H, s, CH3); 2.86 (3H, s, NHCH3); 7.50 (2H, t, J 7.50,
ArH); 7.61 (2H, t, J 7.27, ArH); 7.87 (1H, s, C(N)H); 8.28 (2H,
d, J 7.32, ArH); 12.06 (1H, s, NHNR). 13C NMR: d 13.62; 14.12;
127.94; 130.11; 132.37; 135.60; 136.03; 138.04; 188.50. MS ES+:
m/z 440.04 (100%, ZnLH+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(4-nitrophenyl)methylidene)-3-thiosemicarbazonate]zinc(II)
42.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
benzylidene)-3-thiosemicarbazonate]zinc(II) 38. As per general
procedure except with Zn[ATSM/A] (0.21 g, 0.63 mmol) and
benzaldehyde (0.13 mL, 1.27 mmol). The product was isolated
as a yellow solid (0.27 g, 54%). (MS ES+ found mass: 412.0368.
Calc. mass for C14H18N7S2Zn: 412.0357.) (Found: C, 40.7; H, 4.6;
N, 23.5; S, 15.9. Calc. for C14H17N7S2Zn: C, 40.7; H, 4.15; N, 23.8;
S, 15.5%.) 1H NMR: d 2.23 (3H, s, CH3); 2.27 (3H, s, CH3); 2.85
(3H, d, J 2.74, NHCH3); 7.34 (1H, t, J 7.11, ArH); 7.35 (1H, s,
NHCH3); 7.41 (2H, t, J 7.19, ArH); 7.62 (2H, d, J 7.00, ArH);
8.11 (1H, s, C(N)H); 11.30 (1H, s, NHNR). 13C NMR: d 14.29;
14.62; 126.76; 129.15; 129.34; 135.64; 141.87; 148.66. MS ES+:
m/z 412.04 (100%, ZnLH+).
As per general procedure except with Zn[ATSM/A] (0.34 g,
1.0 mmol) and 4-nitrobenzaldehyde (0.32 g, 2.2 mmol). The
solvent was allowed to cool and the product collected as a
precipitate. The crude product was dissolved in methanol and
precipitated with water. The product was washed with diethyl
ether and dried in vacuo. The product was isolated as a deep
orange solid (0.33 g, 73%). (MS ES+ found mass: 457.0210. Calc.
mass for C14H16N8O2S2Zn: 457.0207.) (Found: C, 36.5; H, 3.4;
N, 24.1. Calc. for C14H16N8O2S2Zn: C, 36.7; H, 3.5; N, 24.5%.)
1H NMR: d 11.67 (H, s, HN-N), 8.24 (2H, d, J 8.4, phenyl),
=
8.16 (H, s, N CH), 7.84 (2H, d, J 8.4, phenyl), 7.40 (1H, s br,
HN-CH3), 2.84 (3H, s, N-CH3), 2.27 (3H, s, CH3), 2.21 (3H, s,
CH3). 13C NMR: d 176.4, 176.3, 149.6, 149.0, 146.9, 141.9, 139.1,
127.0, 124.1, 29.2, 14.2, 13.8.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(2-furyl)methylidene)-3-thiosemicarbazonate]zinc(II) 39. As per
general procedure except with Zn[ATSM/A] (0.36 g, 1.10 mmol)
and 2-furaldehyde (0.18 mL, 2.20 mmol). The product was
isolated as a yellow-orange powder (0.27 g, 62%). (MS ES+
found mass: 402.0145. Calc. mass for C12H16N7OS2Zn: 402.0149.)
(Found: C, 35.8; H, 4.4; N, 23.8; S, 15.8; Zn, 16.2. Calc. for
C12H15N7OS2Zn: C, 35.8; H, 3.8; N, 24.3; S, 15.9; Zn, 16.3%.)
1H NMR: d 2.22 (3H, s, CH3); 2.26 (3H, s, CH3); 2.84 (3H, m,
NHCH3); 6.58 (1H, m, ArH); 6.73 (1H, d, J 3.20, ArH); 7.37
(1H, m, NHCH3); 7.78 (1H, m, ArH); 8.02 (1H, s, C(N)H); 11.21
(1H, s, NHNR). 13C NMR: d 13.82; 14.19; 29.20; 48.57; 111.42;
112.01; 131.97; 144.13; 148.21; 150.06. MS ES+: m/z 402.01
(100%, ZnLH+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(2-nitrophenyl)methylidene)-3-thiosemicarbazonate]zinc(II)
43.
As per general procedure except with Zn[ATSM/A] (0.34 g,
1.0 mmol) and 2-nitrobenzaldehyde (0.32 g, 2.2 mmol). The
solvent was allowed to cool and the product collected as a
precipitate. The product was washed with diethyl ether and
dried in vacuo. The product was isolated as a deep orange solid
(0.31 g, 67%). (MS ES+ found mass: 457.0216. Calc. mass for
C14H16N8O2S2Zn: 457.0207.) (Found: C, 37.0; H, 3.6; N, 24.1.
Calc. for C14H16N8O2S2Zn: C, 36.7; H, 3.5; N, 24.5%.) 1H NMR: d
=
11.65 (H, s, HN-N), 8.52 (H, s, N CH), 8.08 (H, d, J 8.1, phenyl)
7.98 (H, d, J 8.1, phenyl), 7.75 (H, t, J 8.1, phenyl), 7.55 (H, t, J
8.1, phenyl), 7.40 (H, s br, HN-CH3), 2.83 (3H, s, HN CH3), 2.26
5052 | Dalton Trans., 2007, 5043–5054
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(3H, s, CH3), 2.21 (3H, s, CH3). 13C NMR: d 176.3, 176.2, 149.5,
147.5, 144.8, 136.0, 133.4, 129.6, 129.3, 127.3, 124.6, 29.2, 14.2,
13.8.
CH2CH2CH3); 1.54 (4H, m, J 7.21, CH2CH2CH3); 2.22 (3H, s,
CH3); 2.26 (3H, s, CH3); 2.85 (3H, d, J 3.05, NHCH3); 6.65 (2H,
d, J 8.75, ArH); 7.29 (1H, s, NHCH3); 7.40 (2H, d, J 8.65, ArH);
7.96 (1H, s, C(N)H); 10.97 (1H, s, NHNR). 13C NMR: d 11.14;
13.83; 14.03; 19.97; 51.78; 111.10; 121.53; 127.93; 142.7; 148.40.
MS ES+: m/z 511.14 (100%, ZnLH+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(3,5-ditertbutyl-4-hydroxyphenyl)methylidene)-3-thiosemicarbazo-
nate]zinc(II) 44. As per general procedure except with
Zn[ATSM/A] (0.34 g, 1.0 mmol) and 3,5-tert-butyl-4-hydro-
xybenzaldehyde (0.52 g, 2.0 mmol). The solvent was allowed
to cool and the product collected as a precipitate. The crude
product was dissolved in methanol and precipitated with
water. The product was washed with diethyl ether and dried
in vacuo. The product was isolated as a bright orange solid
(0.27 g, 49%). (MS ES+ found mass: 540.1547. Calc. mass for
C22H33N7OS2Zn: 540.1558.) (Found: C, 48.5; H, 6.2; N, 17.9.
Calc. for C22H33N7OS2Zn: C, 48.8; H, 6.2; N, 18.1%.) 1H NMR: d
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
propylidene)-3-thiosemicarbazonate]zinc(II) 48. As per general
procedure except with Zn[ATSM/A] (0.18 g, 0.55 mmol) and
propionaldehyde (0.05 mL, 0.65 mmol). The solvent was allowed
to cool and the product collected as a precipitate. The product
was washed with diethyl ether and dried in vacuo. The product
was isolated as a yellow solid (0.10 g, 50%). (MS ES+ found mass:
1
364.0350. Calc. mass for C10H18N7S2Zn: 364.0357.) H NMR: d
1.01 (3H, t, J 7.51, CH2CH3); 2.21 (3H, s, CH3); 2.83 (2H, m,
CH2CH3); 3.01 (3H, s, NHCH3); 7.29 (1H, s, NHCH3); 7.41 (1H,
t, J 5.34, C(N)H); 11.78 (1H, s, NHNR). MS ES+: m/z 364.04
(100%, ZnLH+).
=
11.14 (H, s, HN-N), 8.03 (H, s, N CH), 7.42 (2H, s, phenyl), 7.35
(H, s br, HN-CH3), 7.28 (H, s, hydroxyl), 2.84 (3H, s, N CH3),
2.24 (3H, s, CH3), 2.21 (3H, s, CH3), 1.38 (18H, s, t-butyl). 13C
NMR: d 176.0, 175.6, 155.2, 147.2, 145.1, 142.9, 139.1, 126.7,
123.8, 34.6, 30.1, 29.0, 14.1, 14.0.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
1-(1-phenylethylidene))-3-thiosemicarbazonate]zinc(II)
49. As
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(2-hydroxyphenyl)methylidene)-3-thiosemicarbazonate]zinc(II) 45.
As per general procedure except with Zn[ATSM/A] (0.16 g,
0.49 mmol) and salicylaldehyde (0.10 mL, 0.98 mmol). The
product was isolated as an orange powder (0.10 g, 46%). (MS ES+
found mass: 428.0301. Calc. mass for C14H18N7OS2Zn: 428.0306.)
(Found: C, 38.6; H, 4.7; N, 21.9; S, 14.9. Calc. for C14H17N7S2Zn:
C, 39.2; H, 4.0; N, 22.9; S, 15.0%.) 1H NMR: d 2.24 (3H, s, CH3);
2.28 (3H, s, CH3); 2.86 (3H, m, NHCH3); 6.86 (1H, m, ArH);
6.89 (1H, m, ArH); 7.23 (1H, t, J 7.13, ArH); 7.32 (1H, d, J 7.63,
ArH); 7.43 (1H, s, NHCH3); 8.22 (1H, s, C(N)H); 11.57 (1H, s,
NHNR); 11.78 (1H, s, OH). 13C NMR: d 13.79; 14.03; 116.34;
118.75; 119.07; 129.75; 130.07; 142.90; 149.28; 157.13. MS ES+:
m/z 428.03 (100%, ZnLH+).
per general procedure except with Zn[ATSM/A] (0.34 g,
1.0 mmol) and acetophenone (0.26 g, 2.2 mmol). The solvent
was allowed to cool and the product collected as a precipitate.
The crude product was dissolved in methanol and precipitated
with water. The product was washed with diethyl ether and
dried in vacuo. The product was isolated as a deep orange solid
(0.26 g, 60%). (MS ES+ found mass: 426.0508. Calc. mass for
C15H19N7S2Zn: 426.0513.) (Found: C, 41.8; H, 4.5; N, 22.8. Calc.
1
for C15H19N7S2Zn: C, 42.2; H, 4.5; N, 23.0%.) H NMR: d 10.05
(H, s, HN-N), 7.80 (2H, d, J 8.1, phenyl), 7.38 (4H total, m, 1H
HN-CH3 and 3H phenyl), 2.84 (3H, s, N-CH3), 2.27 (3H, s, CH3),
2.25 (3H, s, N C–CH3), 2.21 (3H, s, CH3). 13C NMR: d 176.4
=
(2 carbons), 148.2, 146.3, 138.8, 133.2, 128.4, 128.0, 125.8, 29.2,
14.9, 14.1, 13.2.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
1-(2-hydroxynaphthyl)methylidene)-3-thiosemicarbazonate]zinc(II)
46. As per general procedure except with Zn[ATSM/A] (0.18 g,
0.55 mmol) and 2-hydroxynaphthaldehyde (0.19 g, 1.10 mmol).
The product was isolated as a dark yellow powder (0.15 g, 58%).
(MS ES+ found mass: 478.0448. Calc. mass for C18H20N7OS2Zn:
478.0462.) (Found: C, 43.3; H, 4.9; N, 18.9; S, 12.8. Calc. for
C18H21N7O2S2Zn [M + H2O]: C, 43.5; H, 4.3; N, 19.7; S, 12.9%.)
1H NMR: d 2.23 (3H, s, CH3); 2.30 (3H, s, CH3); 2.85 (3H, s,
NHCH3); 7.19 (1H, d, J 8.94, ArH); 7.37 (1H, t, J 7.44, ArH);
7.42 (1H, s, NHCH3); 7.56 (1H, t, J 7.50, ArH); 7.83 (1H, d, J
5.87, ArH); 7.86 (1H, d, J 4.68, ArH); 8.02 (1H, d, J 8.45, ArH);
9.15 (1H, s, C(N)H); 11.55 (1H, s, NHNR); 13.00 (1H, s, OH).
13C NMR: d 13.53; 13.78; 48.29; 109.03; 119.13; 120.17; 123.38;
127.45; 127.78; 128.97; 131.35; 140.34; 157.10. MS ES+: m/z
478.04 (100%, ZnLH+).
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
1-(1-(2ꢀ-hydroxyphenyl)ethylidene))-3-thiosemicarbazonate]zinc(II)
50. As per general procedure except with Zn[ATSM/A] (0.34 g,
1.0 mmol) and 2-hydroxyacetophenone (0.30 g, 2.2 mmol). The
solvent was allowed to cool and the product collected as a
precipitate. The crude product was dissolved in methanol and
precipitated with water. The product was washed with diethyl
ether and dried in vacuo. The product was isolated as a bright
orange solid (0.26, 58%). (MS ES+ found mass: 442.0476. Calc.
mass for C15H19N7OS2Zn: 442.0462.) (Found: C, 40.7; H, 4.7; N,
1
22.3. Calc. for C15H19N7OS2Zn: C, 41.0; H, 4.3; N, 22.1%.) H
NMR: d 13.24 (1H, s, hydroxy), 10.52 (H, s, HN-N), 7.55 (H, d,
J 7.2, phenyl), 7.40 (H, bs, NH), 7.23 (1H, t, J 7.2, phenyl), 6.87
(1H, m, phenyl), 2.84 (3H, s, N CH3), 2.38 (3H, s, CH3), 2.32
(3H, s, CH3), 2.24 (3H, s, CH3). 13C NMR: d 176.3 (2 carbons),
158.2, 150.2, 144.8 (2 carbons), 130.1, 127.8, 120.1, 118.3, 117.1,
29.2, 14.1, 13.8, 13.2.
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
(4-dipropylaminophenyl)methylidene)-3-thiosemicarbazonate]zinc-
(II) 47. As per general procedure except with Zn[ATSM/A]
(0.44 g, 1.36 mmol) and 4-(dipropylamino)benzaldehyde (0.30 g,
1.46 mmol). The product was isolated as a bright red powder
(0.26 g, 39%). (MS ES+ found mass: 511.1416. Calc. mass
Diacetyl-2-(4-N-methyl-3-thiosemicarbazonate)-3-[4-N-(amino-
2ꢀ-propylidene)-3-thiosemicarbazonate]zinc(II) 51. As per general
procedure except with Zn[ATSM/A] (0.34 g, 1.0 mmol) and
acetone (0.12 g, 2.2 mmol). The solvent was allowed to cool and
the product collected as a precipitate. The crude product was
dissolved in methanol and precipitated with water. The product
1
for C20H31N8S2Zn: 511.1405.) H NMR: d 0.89 (6H, t, J 7.29,
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was washed with diethyl ether and dried in vacuo. The product
was isolated as a yellow solid (0.26, 70%). (MS ES+ found mass:
364.0355. Calc. mass for C10H17N7S2Zn: 364.0357.) (Found: C,
32.9; H, 4.7; N, 26.9. Calc. for C10H17N7S2Zn: C, 32.9; H, 4.7; N,
26.9%.) 1H NMR: d 9.40 (H, s, HN-N), 7.32 (H, s br, HN-CH3),
2.84 (3H, s, N-CH3), 2.22 (3H, s, CH3), 2.21 (3H, s, CH3), 1.92
2 J. L. J. Dearling and P. J. Blower, Chem. Commun., 1998, 2531–
2532.
3 P. McQuade, K. E. Martin, T. C. Castle, M. J. Went, P. J. Blower, M. J.
Welch and J. S. Lewis, Nucl. Med. Biol., 2005, 32, 147–156.
4 Y. Arano, A. Yokoyama, Y. Magata, H. Saji, K. Horiuchi and K.
Torizuka, Int. J. Nucl. Med. Biol., 1986, 12, 425–430.
5 Y. Arano, A. Yokoyama, T. Furukawa, K. Horuichi, T. Yahata, H. Saji,
H. Sakahara, T. Nakashima, M. Koizumi, K. Endo and K. Torizulia,
J. Nucl. Med., 1987, 28, 1027–1033.
6 T. Hosotani, A. Yokoyama, Y. Arano, K. Horiuchi, H. Wasaki, H.
Saji and I. J. N. M. B. K. Torizuka, Int. J. Nucl. Med. Biol., 1986, 12,
431–437.
(3H, s, N C–CH3), 1.87 (3H, s, N C–CH3). 13C NMR: d 176.1
=
=
(2 carbons), 151.1, 147.1, 145.9, 29.2, 25.0, 17.4, 14.1, 13.8.
X-Ray crystallography
7 D. W. McPherson, G. Umbricht and J. F. F. Knapp, J. Labelled Compd.
Radiopharm., 1990, 28, 877–899.
Crystallographic data for 50 were collected at 180 K on a Nonius
KappaCCD with graphite monochromated MoKa radiation. The
images were processed with the DENZO and SCALEPACK
programmes.16 The structure was solved using the programme
SIR92.17 The refinement and graphical calculations were per-
formed with the CRYSTALS programme suite.18 Non-hydrogen
atoms were refined with anisotropic displacement parameters.
Hydrogens were located in Fourier maps and their positions
adjusted geometrically after each cycle of refinement with isotropic
thermal parameters. Chebychev weighting schemes and empirical
absorption corrections were applied.19
8 H. Yuan, T. Schroeder, J. E. Bowsher, L. W. Hedlund, T. Wong and
M. W. Dewhirst, J. Nucl. Med., 2006, 47, 989–998.
9 A. R. Cowley, J. Davis, J. R. Dilworth, P. S. Donnelly, R. Dobson, A.
Nightingale, J. M. Peach, B. Shore, D. Kerr and L. Seymour, Chem.
Commun., 2005, 845–847.
10 J. P. Holland, F. I. Aigbirhio, P. Burke, M. Christlieb, G. C. Churchill,
A. R. Cowley, J. R. Dilworth, P. S. Donnelly, J. C. Green, J. M. Peach,
S. R. Vasudevan and J. E. Warren, Inorg. Chem., 2007, 46, 465–485.
11 M. Christlieb, A. R. Cowley, J. R. Dilworth, P. S. Donnelly, B. M.
Paterson, H. S. R. Struthers and J. M. White, Dalton Trans., 2007,
327–331.
12 D. X. West, J. S. Ives, G. A. Bain, A. E. Liberta, J. Valde´s-Mart´ınez,
K. H. Ebert and S. Herna´ndez-Ortega, Polyhedron, 1997, 16, 1895–
1905.
13 G. R. Gummerus, Commentat. Phys.–Math., 1966, 32, 43, (Chem.
Crystal data for 50·DMSO. C17H27N7O3S3Zn, M = 539.02,
Abstr., 1966, 67, 63894).
˚
Z = 8, orthorhombic, space group Pbca, a = 16.7287(2) A, b =
14 M. Christlieb and J. R. Dilworth, Chem.–Eur. J., 2006, 12, 6194–6206.
15 J. P. Scovill, Phosphorus, Sulfur Silicon Relat. Elem., 1991, 60, 15–19.
16 Z. Otwinowski and W. Minor, in Processing of X-ray Diffraction Data
Collected in Oscillation Mode, ed. C. W. Carter and R. M. Sweet, 1997.
17 A. Altomare, G. Cascarano, G. Giacovazzo, A. Guagliardi, M. C.
Burla, G. Polidori and M. Camalli, J. Appl. Crystallogr., 1994, 27,
435.
18 D. J. Watkin, C. K. Prout, J. R. Carruthers, P. W. Betteridge and R. I.
Cooper, in CRYSTALS, University of Oxford, Oxford, 2001.
19 N. Walker and D. Stuart, Acta Crystallogr., Sect. A, 1983, 39, 138.
3
˚
˚
˚
13.7692(2) A, c = 20.6788(3) A, U = 4763.17(11) A , T = 180 K,
38140 reflections collected, 5972 independent. Final R = 0.0406,
wR = 0.0471.
References
1 H. G. Petering, H. H. Buskirk and G. E. Underwood, Cancer Res.,
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5054 | Dalton Trans., 2007, 5043–5054
This journal is
The Royal Society of Chemistry 2007
©