Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines

Article abstract of DOI:10.1016/j.poly.2012.04.008

N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt₄)₂[M(CO)₃X₃] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)₃L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR¹R² moiety. The complexes [⁹⁹Tc(CO)₃(L^PyMor)] and [Re(CO) ₃(L)] (L = L^PyMor, L^PyEt) were characterized by X-ray diffraction. Reactions of [^99mTc(CO)₃(H ₂O)₃]⁺ with the N′- thiocarbamoylpicolylbenzamidines give the corresponding ^99mTc complexes. The ester group in HL^PyCOOEt allows linkage between biomolecules and the metal core.

Full text of DOI:10.1016/j.poly.2012.04.008

Polyhedron 40 (2012) 153–158
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Polyhedron
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Tricarbonyltechnetium(I) and -rhenium(I) complexes with
N0-thiocarbamoylpicolylbenzamidines
Elisabeth Oehlke a, Hung Huy Nguyen b, Nils Kahlcke a, Victor M. Deflon c, Ulrich Abram a,
⇑
a Freie Universität Berlin, Institute of Chemistry and Biochemistry, Fabeckstr. 34-36, D-14195 Berlin, Germany
b Department of Chemistry, Hanoi University of Science, 19 Le Thanh Tong, Hanoi, Viet Nam
c Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
N,N-Dialkylamino(thiocarbonyl)-N0-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br;
M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS
ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The com-
plexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction.
Reactions of [99mTc(CO)3(H2O)3]+ with the N0-thiocarbamoylpicolylbenzamidines give the corresponding
99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core.
Ó 2012 Elsevier Ltd. All rights reserved.
Article history:
Received 9 February 2012
Accepted 11 April 2012
Available online 24 April 2012
Keywords:
Technetium
Rhenium
Carbonyl complexes
Tridentate ligands
Structure analysis
1. Introduction
compounds shown in Scheme 1, have been reported. They are pre-
pared by reactions of benzimidoyl chlorides with functionalized
The radionuclides of technetium and rhenium play an impor-
tant role in the field of nuclear medicine [1–3]. 99mTc (pure
-emit-
amines [6], and can readily be varied in their periphery which
helps to tune their properties or couple them to biomolecules
[7]. The coordination chemistry of such ligands with techne-
tium(V) and rhenium(V) cores has been extensively studied [6–
8]. Similar complexes with the [M(CO)3]+ core are only known with
bidentate N-[(dialkylamino)(thiocarbonyl)]benzamidines up to
now [9].
c
ter, E = 140 keV, t1/2 = 6 h) is the most used isotope for diagnostic
c
radiopharmaceuticals [2]. The b-emitting rhenium isotopes 186Re
and 188Re are under consideration as therapeutic agents for various
forms of cancer or arthritis [3]. One focus of recent research in this
field is the radiolabelling of biomolecules or pharmacophores,
which rapidly and efficiently transport the radionuclide to the tar-
get site. The most common way to incorporate the radiometals is
the use of a strong chelator which coordinates the metal and serves
at the same time as linker to the biomolecule [4]. The tricarbonyl
complexes [M(CO)3(H2O)3]+ (M = 99mTc, 99Tc, Re) are excellent
starting materials for this purpose. A low-pressure synthesis of
[M(CO)3(H2O)3]+ (M = 99mTc, 99Tc, Re) has been developed which
can be performed in aqueous media [5]. The three aqua ligands
can easily be replaced by chelating ligands while the facial binding
carbonyl ligands are largely inert against ligand exchange. Suitable
ligand systems for the [M(CO)3]+ core should preferably be mono-
anionic, tridentate and facial coordinating in order to form neutral
complexes, which are thermodynamically stable and kinetically
inert.
2. Results and discussion
Reactions of (NEt4)2[Re(CO)3Br3] with 1 eq. HLPyMor or HLPyEt
give [Re(CO)3(L)] (L = LPyMor, LPyEt) complexes in almost quantitative
yields. The ESI+ mass spectra of the products show intense signals
corresponding to the expected [M+H]+ ions. The spectrum of [Re
(CO)3(LPyMor)] displays an extra peak for the [M+Na]+ ion. Infrared
spectra of both complexes show the typical pattern for a facial
arrangement of CO ligands (m
C„O: 2206, 1906 and 1865 cmꢀ1 for
[Re(CO)3(LPyMor)]; 2009, 1899 and 1884 cmꢀ1 for [Re(CO)3(LPyEt)].
The mC@N stretches are bathochromically shifted with respect to
those of the non-coordinated benzamidines from 1620 to
1607 cmꢀ1 for [Re(CO)3(LPyMor)] and 1605 cmꢀ1 for [Re(CO)3(LPyEt)].
These shifts are relatively small compared to those, which were ob-
served for rhenium(V) and technetium(V) complexes (up to
Recently, the synthesis of a number of tridentate derivatives of
N,N-[(dialkylamino)-N0-(thiocarbonyl)]benzamidines, such as the
120 cmꢀ1) [6]. Apparently, the large degree of
p-electron delocal-
⇑
ization within the chelate rings, which results in large bathochro-
mic shifts in the IR spectra and an almost perfect C–N
Corresponding author. Tel.: +49 30 838 54002; fax: +49 30 838 52676.
E-mail address: ulrich.abram@fu-berlin.de (U. Abram).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.04.008

154
E. Oehlke et al. / Polyhedron 40 (2012) 153–158
Scheme 1. Ligands used throughout this paper.
bond-length equalization in the rhenium(V) and technetium(V)
complexes does not apply to [Re(CO)3(L)] (L = LPyMor, LPyEt) due to
the facial coordination of the tridentate ligands. The 13C NMR spec-
trum of [Re(CO)3(LPyMor)] shows three signals for the carbon atoms
of the carbonyl ligands at 198.8, 196.4 and 193.3 ppm, reflecting
some influence of the trans-bonded donor atoms. For the other
compounds, unfortunately, 13C NMR of satisfactory quality could
not be obtained due to their lower solubility.
The technetium complex [99Tc(CO)3(LPyMor)] was synthesized
from (NEt4)2[99Tc(CO)3Cl3] and HLPyMor in methanol. Its infrared
spectrum shows the mC@N stretch at 1609 cmꢀ1 and the bands of
the CO ligands at 2017, 1921 and 1886 cmꢀ1. The absence of
absorptions in the regions around 3350 and 3400 cmꢀ1 (in which
the mNH stretch is detected in the spectrum of the uncoordinated
HLPyMor) indicates the expected deprotonation of the ligand during
complex formation. The 99Tc NMR spectrum shows a signal at
ꢀ1220 ppm with a half-width of 596 Hz ((NEt4)2[99Tc(CO)3Cl3]:
d = ꢀ870 ppm,
Dm1/2 = 29 Hz in H2O).
Fig. 2. Ellipsoid representation [16] of the molecular structure of [Re(CO)3(LPyEt)].
Thermal ellipsoids represent 50% probability. H atoms have been omitted for clarity.
Single crystals of [Re(CO)3(LPyMor)], [Re(CO)3(LPyEt)] and
99Tc(CO)3(LPyMor)] were obtained either directly from the reaction
[
solutions or by recrystallization of the initially formed pale-yellow
powders from acetone. Fig. 1 illustrates the molecular structure of
[
ally identical, no extra figure is presented for the rhenium com-
pound. The structure of [Re(CO)3(LPyEt)] is shown in Fig. 2.
Selected bond lengths and angles of all three complexes are pre-
sented in Table 1. The metal atoms show distorted octahedral coor-
Table 1
99Tc(CO)3(LPyMor)]. Since the structure of [Re(CO)3(LPyMor)] is virtu-
Selected bond lengths (Å) and angles (°) in [99Tc(CO)3(LPyMor)], [Re(CO)3(LPyMor)] and
[Re(CO)3(LPyEt)].
[
99Tc(CO)3(LPyMor)]
[Re(CO)3(LPyMor)]
[Re(CO)3(LPyEt)]
M–C11
M–C12
M–C13
M–S1
M–N5
M–N52
S1–C2
C2–N3
C2–N6
N3–C4
C4–N5
N5–C6
1.933(3)
1.911(2)
1.909(3)
2.4895(7)
2.141(2)
2.177(2)
1.750(2)
1.324(3)
1.378(4)
1.360(3)
1.298(3)
1.474(3)
1.938(4)
1.909(4)
1.923(4)
2.491(2)
2.143(3)
2.176(3)
1.754(4)
1.322(5)
1.384(7)
1.351(5)
1.307(5)
1.469(5)
1.934(7)
1.932(8)
1.932(8)
2.500(2)
2.136(6)
2.180(6)
1.755(8)
1.32(1)
1.35(1)
1.36(1)
1.32(1)
1.46(1)
C11–M–N5
C11–M–C12
S1–M–N5
N5–M–N52
M–S1–C2
S1–C2–N3
C2–N3–C4
N3–C4–N5
C4–N5–C6
M–N5–C4
172.00(9)
88.4(1)
171.2(2)
88.7(2)
81.0(1)
74.3(1)
97.5(1)
127.8(3)
124.3(3)
125.4(3)
122.4(3)
127.4(3)
170.5(3)
89.4(3)
81.3(2)
74.5(2)
96.9(3)
126.6(6)
124.1(7)
125.2(7)
121.2(6)
127.7(5)
81.34(5)
74.99(7)
97.77(8)
127.9(2)
124.1(2)
125.4(2)
122.6(2)
127.5(2)
dination spheres with facially bonded carbonyl ligands. The
remaining three coordination positions are occupied by the singly
deprotonated organic ligands. The chelate rings are strongly
Fig. 1. Ellipsoid representation [16] of the molecular structure of
[
99Tc(CO)3
(LPyMor)]. Thermal ellipsoids represent 50% probability. H atoms have been omitted
for clarity.

E. Oehlke et al. / Polyhedron 40 (2012) 153–158
155
only the crude product could be characterized by IR spectroscopy
and mass spectrometry. The IR spectrum shows two bands for
the CO ligands at 2017 and 1894 cmꢀ1, which equals a mean hyp-
sochromic shift of 25 cmꢀ1 compared to the Re starting complex.
The mC@N stretch can be found at 1609 cmꢀ1. Coordination and
deprotonation of the ligand is indicated by the absence of an
absorption for the mNH stretch (m
(N–H): 3371 cmꢀ1 for HLPyCOOEt).
Additionally, a band at 1705 cmꢀ1 can be assigned to the ester
group of the ligand. The ESI+ mass spectrum shows an intense peak
corresponding to the expected [M+H]+ ion. This confirms the pres-
ence of the [Re(CO)3(LPyCOOEt)] in the oily product, which has only
been taken for comparison purposes in the HPLC studies on the
99mTc compounds.
The reaction of (NEt4)2[99Tc(CO)3Cl3] with one equivalent of
HLPyCOOEt in a mixture of methanol and water gives the colorless
complex [99Tc(CO)3(LPyCOOEt)]. It precipitates together with one
equivalent of (NEt4)Cl directly from the reaction mixture and was
analysed as co-precipitate. The IR spectrum exhibits the carbonyl
bands at 2017, 1909 and 1894 cmꢀ1 and the mC@N stretch at
1605 cmꢀ1. The band at 1717 cmꢀ1 can be assigned to the ester
group of the ligand. The 1H NMR spectrum of the complex shows
the expected signals. The resonances of the methyl and methylene
protons of the ethyl ester appear as triplet at 1.32 ppm and as mul-
tiplet between 4.28 and 4.38 ppm. The 99Tc NMR spectrum con-
tains one signal at ꢀ1216 ppm with a half-width of 815 Hz. A
small amount of single crystals of pure [99Tc(CO)3(LPyCOOEt)] was
obtained directly from the pre-concentrated reaction solution.
They were analysed by 1H NMR and X-ray diffraction (monoclinic
space group P21/n, unit cell dimensions: a = 15.315 Å;
b = 16.398 Å; c = 21.404 Å; b = 90.45°). Unfortunately, the crystals
were of low quality and the best data set acquired converged at
an R-value of 13.6%. Thus, a detailed discussion of bond lengths
and angles, which approximately follow the trends described for
the other [M(CO)3(L]) complexes of this communication, will not
be included here. All main structural features of the compound,
however, can certainly be derived from the calculations. A struc-
tural sketch of the complex is shown in Fig. 3. It is obvious, that
the ester substituted ligand also coordinates facially as monoan-
ionic, tridentate ligand to the [99Tc(CO)3]+ core.
Fig. 3. Molecular structure [16] of [99Tc(CO)3(LPyCOOEt)]. H atoms have been omitted
for clarity.
Table 2
HPLC data.
Compound
Retention time (min)
Yield (%)
ꢀ
MO4 (M = Tc, Re)
3.1
6.2
6.7
6.7
–
–
–
–
[Re(CO)3Br3]2ꢀ
[
[
99Tc(CO)3Cl3]2ꢀ
99mTc(CO)3(H2O)3]+
HLPyMor
19.2
24.0
25.2
23.3
–
–
–
97
[Re(CO)3(LPyMor)]
[
[
99Tc(CO)3(LPyMor)]
99mTc(CO)3(LPyMor)]
HLPyEt
21.0
24.0
24.5
–
–
[Re(CO)3(LPyEt)]
[
99mTc(CO)3(LPyEt)]
max. 94
HLPyCOOEt
23.7
25.8
25.5
24.4
–
–
–
[Re(CO)3(LPyCOOEt)]
[
[
99Tc(CO)3(LPyCOOEt)]
99mTc(CO)3(LPyCOOEt)]
max. 96
distorted, with main deviations from planarity of 0.503–0.533 Å for
S1 in the six-membered rings and 0.301–0.307 Å for N5 in the five-
membered rings. Bond lengths within the chelate rings indicate
only partial double bond character of the C@N bonds. The C4–N5
bond lengths between 1.298(3) and 1.32(1) Å best resemble bond
lengths expected for C@N double bonds.
A yellow oil was obtained from the reaction of (NEt4)2[Re
(CO)3Br3] with HLPyCOOEt. All our efforts to purify the product and
to obtain a pure solid sample of [Re(CO)3(LPyCOOEt)] failed. Thus,
The synthesis of the 99mTc complexes [99mTc(CO)3(L)] (L =
LPyMor, LPyEt, LPyCOOEt) was carried out by adding 1 mM ligand solu-
tions in methanol to equal volumes of aqueous [99mTc(CO)3
(H2O)3]+ solutions. The reactions were optimized by variation of
temperature and reaction time. Characterization of the 99mTc com-
pounds was performed by radio-HPLC and comparison with the
Fig. 4. HPLC data for the reactions of [99mTc(CO)3(H2O)3]+ with HLPyEt
.

156
E. Oehlke et al. / Polyhedron 40 (2012) 153–158
Fig. 5. HPLC data for the reactions of [99mTc(CO)3(H2O)3]+ with HLPyCOOEt
.
HPLC traces (radio- and UV-detector) of the corresponding Re and
99Tc compounds. Retention times of all analysed compounds are
shown in Table 2.
with the retention times of the Re and 99Tc complexes suggests
that the main product is the desired complex
[
99mTc(CO)3
(LPyCOOEt)] (tR = 24.4 min). The formation of the side-product can
readily be explained by a partial cleavage of the ester due to the
relatively drastic conditions. This conclusion is supported by the
fact that the reaction is accelerated by the presence of trifluoroace-
tic acid.
The reaction of [99mTc(CO)3(H2O)3]+ with HLPyEt leads to one
product with a retention time of 24.5 min, which well resembles
that of the corresponding rhenium complex [Re(CO)3(LPyEt)]. The
reaction is not completed within a time of 30 min at room temper-
ature, but gives almost quantitative yields at 75 °C (Fig. 4). The
reaction of [99mTc(CO)3(H2O)3]+ with HLPyMor was only carried out
at 75 °C for 30 min. It was straight forward and gave the desired
product [99mTc(CO)3(LPyMor)] (tR = 23.3 min) in a yield of 97%.
Milder reaction conditions are recommended for the synthesis
of [99mTc(CO)3(LPyCOOEt)] in order to avoid (partial) saponification
of the contained ester. Heating of reaction mixtures containing
Suitable reaction conditions, which give [99mTc(CO)3(LPyCOOEt)]
in nearly quantitative yields (96%) have been found with a pro-
longed reaction time (60 min) at room temperature. The observed
reactivity under such conditions is also a promising indicator for
the suitability for the intended application, the labeling of biomol-
ecules, which require mild conditions anyway.
[
99mTc(CO)3(H2O)3]+ and HLPyCOOEt results in the formation of side
3. Conclusions
products as is shown in Fig. 5. The chromatogram of such a reac-
tion mixture at 75 °C for 30 min shows two products with reten-
tion times of 23.0 min (19%) and 24.4 min (77%). A comparison
N,N-Dialkylamino(thiocarbonyl)-N0-picolylbenzamidines
are
excellent ligands for the stabilization of the [M(CO)3]+ core. The
characterization of the Re and 99Tc complexes [M(CO)3(L)]
(M = Re, 99Tc; L = LPyMor, LPyEt, LPyCOOEt) confirm the formation of
stable complexes with a facial coordination of the chelating li-
gands. The corresponding 99mTc complexes can readily be synthe-
sized from [99mTc(CO)3(H2O)3]+ and characterized by comparative
HPLC. Especially the 99mTc complex [99mTc(CO)3(LPyCOOEt)] has
promising properties for further studies since the ester group of
the ligand allows linkage between biomolecules and metal core.
The observed partial cleavage of the ester bond during the complex
formation recommends mild conditions when pre-labelled biocon-
jugates are used for the synthesis of the technetium complexes.
Table 3
X-ray structure data collection and refinement parameters.
[Tc(CO)3(LPyMor)] [Re(CO)3(LPyMor)] [Re(CO)3(LPyEt)]
Formula
C
21H19N4O4TcS
C21H19N4O4ReS
609.66
triclinic
6.606(5)
8.386(5)
20.405(5)
88.82(1)
83.29(1)
74.00(1)
1656.6(3)
C21H21N4O3ReS
595.68
monoclinic
6.718(1)
31.404(2)
10.373(1)
90
103.55(1)
90
2127.3(3)
P21/c
Molecular weight
Crystal system
a (Å)
b (Å)
c (Å)
521.46
triclinic
6.608(1)
8.422(1)
20.450(2)
88.84(1)
83.49(1)
74.20(1)
1088.0(2)
a
(°)
b (°)
4. Experimental
c
(°)
V (Å3)
ꢀ
ꢀ
Space group
P1
P1
4.1. Materials
Z
2
2
4
Dcalc. (g cmꢀ3
)
1.592
0.793
11071
1.080(1)
5.763
11651
1.860
5.841
12672
All reagents used in this study were reagent grade and used
without further purification. Na99mTcO4 was obtained from a
commercially available 99Mo/99mTc generator (DRN 4329 Ultra-
Technekow FM, Mallinckrodt Medical BV). HLPyEt was synthesized
as described in a previous paper [6]. HLPyCOOEt and HLPyMor were
synthesized following the same procedure. The syntheses of corre-
sponding N,N-dialkylamino-N0-(thiocarbonyl)benzimidoyl chlo-
rides followed the standard procedures [10]. (NEt4)2[Re(CO)3Br3]
[11], (NEt4)2[Tc(CO)3Cl3] [12] and [99mTc(CO)3(H2O)3]+ [5a] were
prepared by published methods.
l
(mmꢀ1
)
Number of
reflections
Number of
independent
Number of
parameters
R1/wR2
Goodness-of-fit
(GOF) on F2
CCDC
5759
269
5749
269
5719
271
0.0296/0.0725
1.109
0.0297/0.0723
1.177
0.0553/0.1302
1.029
864853
864854
864855

E. Oehlke et al. / Polyhedron 40 (2012) 153–158
157
4.2. Radiation precautions
1337 (s), 1287 (m), 1264 (m), 1226 (m), 1207 (m), 1189 (m),
1174 (w), 1154 (w), 1110 (m), 1061 (m), 1025 (m), 984 (w),
965 (w), 929 (w), 892 (m), 847 (w), 788 (w), 734 (w), 710 (m),
690 (w), 675 (w). 1H NMR (CDCl3; d, ppm): 3.61–3.87 (m, 6H, Mor-
pholine), 4.27–4.30 (m, 1H, OCH2), 4.56–4.59 (m, 1H, OCH2), 4.88
(d, J = 15.5 Hz, 1H, PyCH2), 5.20 (d, J = 15.7 Hz, 1H, PyCH2), 7.11
(d, J = 7 Hz, 1H, Py), 7.20 (m, 1H, Ph), 7.31–7.39 (m, 5H, Py + Ph),
7.70 (t, J = 6 Hz, 1H, Py), 8.74 (d, J = 5 Hz, 1H, Py). 13C NMR (CDCl3;
d, ppm): 197.9 (CCarbonyl), 196.4 (CCarbonyl), 193.3 (CCarbonyl). ESI-
99Tc is a weak bꢀ-emitter and 99mTc a
c-emitter. All manipula-
tions with these isotopes were performed in a laboratory approved
for the handling of radioactive materials. Normal glassware pro-
vides adequate protection against the low-energy beta emission
of the 99Tc compounds. Secondary X-rays (bremsstrahlung) play
an important role only when larger amounts of 99Tc are used. For
the 99mTc compounds adequate lead shielding was used.
TOF-MS
(m/z):
611.08
[Re(CO)3(LPyMor)+H]+,
633.06
4.3. Physical measurements
[Re(CO)3(LPyMor)+Na]+. High resolution MS of molecular ion
[M+H]+ Calc.: 611.07627, Found: 611.07635. HPLC (TFA/MeOH,
C18rp, min) 24.0.
Infrared spectra were measured from KBr pellets on a Shimadzu
FTIR-spectrometer between 400 and 4000 cmꢀ1. Positive ESI mass
spectra were measured with an Agilent 6210 ESI-TOF (Agilent
Technologies). All MS results are given in the form: m/z, assign-
ment. Elemental analysis of carbon, hydrogen, nitrogen, and sul-
4.4.3. [Re(CO)3(LPyEt)]
HLEt (33 mg, 0.1 mmol) dissolved in 5 mL MeOH was added to a
solution of (NEt4)2[ReBr3(CO)3] (77 mg, 0.1 mmol) in 5 mL MeOH.
The color of the solution immediately turned yellow and a yellow
precipitate deposited within an hour. The yellow powder was fil-
tered off and the product was extracted with acetone. X-ray quality
single crystals were obtained by slow evaporation of the acetone
solution or of the original reaction solution.Yield: 85% (51 mg).
Anal. Calc. for ReSC21H21N4O3: C, 42.34; H 3.55; N, 9.41; S, 5.38.
phur were determined using
a Heraeus Vario EL elemental
analyzer. The elemental analyses of the rhenium compounds
showed systematically too low values for hydrogen and sometimes
carbon (in some cases in a significant extent). This might be caused
by an incomplete combustion of the metal compounds and/or hy-
dride formation, and does not refer to impure samples. Similar
findings have been observed for analogous oxorhenium(V) com-
plexes with the same type of ligands before [13]. We left these val-
ues uncorrected. Additional proof for the identity of the products is
given by high-resolution mass spectra for selected representatives.
The 99Tc values were determined by standard liquid scintillation
counting. NMR-spectra were taken with a JEOL 400 MHz multinu-
clear spectrometer. HPLC analyses were performed on a Merck-
Hitachi L6200 system coupled to a Merck Hitachi (l-4250) UV
detector (set on 250 nm) and a Beckmann radioactivity detector
(171 radioisotope detector). Separations were achieved on a re-
versed-phase column (Nucleosil 100-5 C18, Knauer) using a gradi-
ent of 0.1% CF3COOH in H2O (A) and methanol (B) as eluents and
flow rates of 0.5 mL/min. Method: 0–3 min 100% A; 3.1–9 min
75% A and 25% B; 9.1–20 min 66% A and 34% B; 20–25 min 100%
B; 25–40 min 100% A.
Found: C, 41.69; H, 4.68; N, 8.31; S, 4.42%. IR (m
in cmꢀ1): 2981
(w), 2942 (w), 2009 (s), 1899 (s), 1884 (s), 1654 (m), 1605 (w),
1555 (w), 1526 (w), 1482 (s), 1417 (m), 1396 (m), 1341 (m),
1255 (w), 1174 (m), 1066 (w), 1002 (m), 787 (s), 764 (s), 718 (s),
641 (s), 614 (m), 531 (m). 1H NMR (CDCl3; d, ppm): 1.15 (m, 3H,
CH3), 1.29 (t, J = 6 Hz, 3H, CH3), 3.75 (m, 2H, CH2), 4.15 (q,
J = 7 Hz, 2H, CH2), 4.96 (m, 1H, PyCH2), 5.26 (d, J = 14.3 Hz, 1H,
PyCH2), 7.15–7.28 (m, 2H, Py + Ph), 7.40–7.55 (m, 5H, Py + Ph),
7.67–7.75 (m, 1H, Py), 8.76 (d, J = 5 Hz, 1H, Py). ESI-TOF-MS (m/
z): 597.10 [Re(CO)3(LPyEt)+H]+. High resolution MS of molecular
ion [M+H]+ Calc.: 597.0970, Found: 597.0975. HPLC (TFA/MeOH,
C18rp, min) 24.0.
4.4.4. [99Tc(CO)3(LPyMor)]
HLPyMor (34 mg, 0.1 mmol) dissolved in 5 mL MeOH was added
to a solution of (NEt4)2[TcCl3(CO)3] (55 mg, 0.1 mmol) in 5 mL
MeOH. The color of the solution immediately turned yellow and
a yellow precipitate deposited within an hour. The yellow powder
was filtered off and the product was extracted with acetone. X-ray
quality single crystals were obtained by slow evaporation of the
acetone solution. Yield: 86% (45 mg). Anal. Calc. for TcC21H19N4O4S:
4.4. Syntheses
4.4.1. HLPyMor and HLPyCOOEt
A
solution of the morpholine- or ({4-ethylcarboxylyphe-
nyl}methylamine-substituted benzimidoylchloride [10] (1 mmol)
in 2 mL of dry acetone was added dropwise to a mixture of 2-meth-
ylaminopyridine (109 mg, 1 mmol) and triethylamine (152 mg,
1.5 mmol) in 5 mL of dry acetone over a period of 5 min. The mix-
ture was stirred for 2 h and then cooled to 0 °C. The formed precip-
itate of (HNEt3)Cl was filtered off, and the solvent was removed
under vacuum. The remaining solid was recrystallized from an ace-
tone/methanol mixture. Yields: 280 mg (82%) for HLPyMor and
240 mg (55%). The identity of the ligands was confirmed by IR,
1H NMR spectroscopy and elemental analysis.
Tc, 18.8. Found: Tc, 18.3%. IR (m
in cmꢀ1): 3001 (w), 2970 (w), 2843
(m), 2017 (s), 1921 (s), 1886 (s), 1609 (m), 1539 (m), 1466 (s), 1408
(s), 1335 (s), 1285 (m), 1261 (m), 1207 (m), 1111 (m), 1057 (m),
1022 (m), 964 (w), 930 (w), 891 (m), 791 (w), 764 (m), 706 (m),
648 (m), 610 (m), 520 (m), 455 (w), 428 (w). 1H NMR (CDCl3; d,
ppm): 3.61–3.68 (m, 5H, Morpholine), 3.91 (m, 1H, OCH2), 4.18
(m, 1H, OCH2), 4.55 (m, 1H, OCH2), 4.94 (s, 2H, PyCH2), 7.05 (d,
J = 7.9 Hz, 1H, Py), 7.19 (t, J = 6.2 Hz, 1H, Ph), 7.28–7.35 (m, 5H,
Py + Ph), 7.65 (t, J = 7.7 Hz, 1H, Py), 8.64 (d, J = 5 Hz, 1H, Py). 99Tc
NMR (THF; d, ppm): -1220 (Dm1/2 = 596 Hz). HPLC (TFA/MeOH,
C18rp, min) 25.2.
4.4.2. [Re(CO)3(LPyMor)]
HLPyMor (34 mg, 0.1 mmol) dissolved in 5 mL MeOH was added
to a solution of (NEt4)2[ReBr3(CO)3] (77 mg, 0.1 mmol) in 5 mL
MeOH. The colour of the solution immediately turned yellow and
a yellow precipitate deposited within 1 h. The yellow powder
was filtered off and the product was extracted with acetone. X-
ray quality single crystals were obtained by slow evaporation of
the acetone solution. Yield: 97% (59 mg). Anal. Calc. for Re-
4.4.5. [99Tc(CO)3(LPyCOOEt)]
HLPyCOOEt (43 mg, 0.1 mmol) dissolved in 2 mL MeOH was added
to a solution of (NEt4)2[TcCl3(CO)3] (55 mg, 0.1 mmol) in 5 mL
MeOH and 5 mL H2O. A colorless precipitate of [Tc(CO)3(LPyCOOEt)]
deposited within an hour. This material consists of [Tc(CO)3(LPy-
COOEt)] ꢁ (NEt4)Cl. Yield: 58% (46 mg). Anal. Calc. for
C
21H19N4O4S: C, 41.37; H 3.14; N, 9.19; S, 5.26. Found: C, 41.22;
TcC27H24N4O5S+(NEt4)Cl: Tc, 12.7. Found: Tc, 12.8%. IR (m in
H, 1.68; N, 8.98; S, 4.88%. IR (
m
in cmꢀ1): 2997 (w), 2968 (w),
cmꢀ1): 3067 (w), 2966 (w), 2017 (s), 1909 (s), 1894 (s), 1717
(m), 1605 (w), 1512 (w), 1474 (m), 1373 (w), 1273 (m), 1173
(w), 1103 (m), 1061 (w), 1022 (m), 799 (w), 706 (w), 621 (w).1H
2953 (w), 2841 (w), 2006 (s), 1906 (s), 1865 (s), 1606 (m),
1535 (m), 1468 (s), 1431 (s), 1410 (s), 1387 (m), 1351 (m),

158
E. Oehlke et al. / Polyhedron 40 (2012) 153–158
NMR (CDCl3; d, ppm): 1.23 (t, J = 6.5 Hz, 12H, NCH2CH3), 1.34 (t,
J = 7.1 Hz, 3H, OCH2CH3), 3.43 (q, J = 6.5 Hz, 8H, NCH2CH3), 3.50
(s, 3H, NCH3), 4.28–4.39 (m, 2H, OCH2CH3), 7.04 (d, J = 8 Hz, 1H,
Py), 7.13 (t, J = 6.9 Hz, 1H, Ph), 7.32–7.49 (m, 7H, Ph + Py), 7.64 (t,
J = 7.6 Hz, 1H, Py), 8.01 (d, H = 8.3 Hz, 2H, Ph), 8.52 (d, J = 4.8 Hz,
[Re(CO)3(LPyEt)], respectively. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336 033; or e-mail:
deposit@ccdc.cam.ac.uk.
1H, Py).99Tc NMR (THF; d, ppm): ꢀ1216 (
Dm1/2 = 815 Hz).
An additional small amount of single crystals were obtained by
slow evaporation of the reaction solution. They do not contain co-
crystallized (NEt4)Cl and were used for the crystallographic and 1H
NMR studies. 1H NMR (CDCl3; d, ppm): 1.32 (t, J = 7.1 Hz, 3H,
OCH2CH3), 3.48 (s, 3H, NCH3), 4.28–4.38 (m, 2H, OCH2CH3), 7.04
(d, J = 8 Hz, 1H, Py), 7.13 (t, J = 6.9 Hz, 1H, Ph), 7.31–7.48 (m, 7H,
Ph + Py), 7.63 (t, J = 7.6 Hz, 1H, Py), 8.01 (d, H = 8.3 Hz, 2H, Ph),
8.52 (d, J = 4.8 Hz, 1H, Py). HPLC (TFA/MeOH, C18rp, min) 25.5.
References
[1] (a) S. Bhattacharyya, M. Dixit, Dalton Trans. 40 (2011) 6112;
(b) U. Abram, R. Alberto, J. Braz. Chem. Soc. 17 (2006) 1486.
[2] R. Alberto, U. Abram, in: A. Vértes, S. Nagy, Z. Klencsár, R.G. Lovas, F. Rösch
(Eds.), Handbook of Nuclear Chemistry, vol. 4, Springer, US, 2011, pp. 2073–
2120.
[3] P.J. Blower, S. Prakash, in: R.W. Hay, H.R. Dilworth, K.B. Nolan (Eds.),
Perspectives on Bioinorganic Chemistry, vol. 4, JAI Press Inc., 1999, pp. 91–143.
[4] (a) S.S. Jurisson, J.D. Lydon, Chem. Rev. 99 (1999) 2205;
(b) S. Liu, Chem. Soc. Rev. 33 (2004) 445;
(c) M.D. Bartholomä, A.S. Louie, J.F. Valliant, J. Zubieta, Chem. Rev. 110 (2010)
2903.
[5] (a) R. Alberto, R. Schibli, A. Egli, P.A. Schubiger, W.A. Herrmann, G. Artus, U.
Abram, T.A. Kaden, J. Organomet. Chem. 493 (1995) 119;
(b) R. Alberto, R. Schibli, A. Egli, A.P. Schubiger, U. Abram, T.A. Kaden, J. Am.
Chem. Soc. 120 (1998) 7987.
[6] H.H. Nguyen, J. Grewe, J. Schroer, B. Kuhn, U. Abram, Inorg Chem. 47 (2008)
5136.
[7] (a) H.H. Nguyen, U. Abram, Polyhedron 28 (2009) 3945;
(b) J. Schroer, U. Abram, Polyhedron 28 (2009) 2277.
[8] (a) H.H. Nguyen, K. Hazin, U. Abram, Eur. J. Inorg. Chem. (2011) 78;
(b) H.H. Nguyen, V.M. Deflon, U. Abram, Eur. J. Inorg. Chem. (2009) 3179;
(c) H.H. Nguyen, T.N. Trieu, U. Abram, Z. Anorg, Allg. Chem. 637 (2011) 1330.
[9] (a) U. Abram, S. Abram, R. Alberto, R. Schibli, Inorg. Chim. Acta 248 (1996) 193;
(b) H. Braband, U. Abram, J. Organomet. Chem. 689 (2004) 2066.
[10] L. Beyer, R. Widera, Tetrahedron Lett. 23 (1982) 1881.
[11] R. Alberto, A. Egli, U. Abram, K. Hegetschweiler, V. Gramlich, P.A. Schubiger, J.
Chem. Soc., Dalton Trans. (1994) 2815.
[12] R. Alberto, K. Ortner, N. Wheatley, R. Schibli, A.P. Schubiger, J. Am. Chem. Soc.
123 (2001) 3135.
[13] H.H. Nguyen, J.J. Jegathesh, P.I.S. Maia, V.M. Deflon, R. Gust, S. Bergemann, U.
Abram, Inorg. Chem. 43 (2009) 9356.
4.4.6. [99mTc(CO)3(L)] (L = LPyMor, LPyEt, LPyCOOEt
)
One milliliter of a 10ꢀ3 M solution of the N0-picolylbenzamidine
(HLPyMor, HLPyEt or HLPyCOOEt) in H2O was added to 1 mL of a solu-
tion of [99mTc(CO)3(H2O)3]+ in H2O. The reactions were optimized
by changing temperature and reaction time.
HPLC (TFA/MeOH, C18rp, min) yields with the following li-
gands: HLPyMor 23.3 (75 °C, 30 min, 97%). HLPyEt 24.5 (22 °C,
30 min, 76%; 75 °C, 30 min, 94%). HLPyCOOEt24.4 (75 °C, 30 min,
77%; 22 °C, 30 min, 70%; 22 °C, 60 min, 96%).
4.5. X-ray crystallography
The intensities for the X-ray determinations were collected on a
STOE IPDS 2T instrument with Mo K
a radiation (k = 0.71073 Å).
Standard procedures were applied for data reduction and absorp-
tion correction. Structure solution and refinement were performed
with SIR 97 [14]. Hydrogen atom positions were calculated for ide-
alized positions and treated with the ‘riding model’ option of SHELXL
[15].
More details on data collections and structure calculations are
contained in Table 3. Additional information on the structure
determinations has been deposited with the Cambridge Crystallo-
graphic Data Centre.
[14] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, A. Molterni, M. Burla,
G. Polidori, M. Carnalli, R. Spagna, SIR 97 program for the solution of crystal
structures, Campus Universitario, 1997.
[15] G.M. Sheldrick, SHELXL-97, program for the refinement of crystal structures,
University of Göttingen, Göttingen, Germany, 1997.
[16] K. Brandenburg, H. Putz, DIAMOND – a program for the representation of
crystal structures, vers. 3.2, Crystal Impact, Bonn, Germany 2011.
Appendix A. Supplementary data
CCDC 864853, 864854 and 864855 contains the supplementary
crystallographic data for [Tc(CO)3(LPyMor)], [Re(CO)3(LPyMor)] and