Synthesis and characterization of mixed-ligand oxorhenium(V) complexes with new [(PNO/S)(S)] donor atom sets

Article abstract of DOI:10.1039/b101278i

New oxorhenium complexes with 2-(diphenylphosphanyl)-N-(2-thioethyl)benzamide (H₂PNS) and 2-(diphenyl-phosphanyl)-N-(2-hydroxyethyl)benzamide (H₂PNO) and various monodentate thiols as co-ligands are reported. These new complexes, 1-6

Full text of DOI:10.1039/b101278i

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Synthesis and characterization of mixed-ligand oxorhenium(V)
complexes with new [(PNO/S)(S)] donor atom sets
João D. G. Correia,a Ângela Domingos,a Isabel Santosa and Hartmut Spiesb
a Departamento de Química, ITN, Estrada Nacional 10, 2686-953, Sacavém Codex, Portugal.
E-mail: isantos@itn1.itn.pt
b Institute of Bioinorganic & Radiopharmaceutical Chemistry, Forschungszentrum, Rossendorf,
Dresden, D-01314, Germany
Received 8th February 2001, Accepted 22nd May 2001
First published as an Advance Article on the web 12th July 2001
New oxorhenium complexes with 2-(diphenylphosphanyl)-N-(2-thioethyl)benzamide (H2PNS) and 2-(diphenyl-
phosphanyl)-N-(2-hydroxyethyl)benzamide (H2PNO) and various monodentate thiols as co-ligands are reported.
These new complexes, 1–6, have been prepared by reacting [nBu4][Re(O)Cl4] or [Re(O)Cl3(PPh3)2] with the tridentate
H2PNX (X = O, S) ligands and different monothiols. The characterization of the complexes involved IR, 1H and 31
P
NMR spectroscopy and X-ray crystallographic analysis in the case of 1 and 2. Complexes [Re(O)(κ3-PNO)(SPh)] (1),
and [Re(O)(κ3-PNS)(SPh)] (2), adopt a distorted square pyramidal geometry (δ = 3.0Њ, 1 and δ = 1.3Њ for 2), with the
oxo group in the axial position and the equatorial plane being defined by the phosphorus, nitrogen and oxygen (1) or
sulfur (2) atoms of the tridentate chelate and by the sulfur atom of the monothiol.
Introduction
Nowadays, one of the driving forces for the advances in
nuclear medicine, namely for imaging the brain in vivo with the
γ-emitter 99mTc, is the development of new coordination com-
plexes which must be able to cross the blood/brain barrier
(BBB), and bind with high affinity and selectivity to specific
receptors.1 Thus, the radiolabelling of central nervous system
Scheme 1 Structures of the ligands H2PNO and HPN2.
(CNS) receptor ligands with the most important nuclide for
diagnostic purposes, 99mTc, is quite challenging and extensive
efforts have been made in the past few years to achieve this goal.
Tropane derivatives, acting as dopamine transporter ligands,
can be labeled with 99mTc, and the new synthon [99mTc(CO)3]ϩ
was also used to label a derivative of an arylpiperazine (specific
for a sub-class of serotonergic receptors) and a derivatised
tropane, without considerable loss of specificity.2–5 A common
feature to both approaches is the fact that the 99mTc complexes
attached to CNS receptor ligands are neutral in charge and
lipophilic.
of 3 ϩ 1 type compounds, stabilized by the chelates H2PNO
and H2PNS and by several monothiols, including one bearing a
5HT1A receptor ligand: [Re(O)(κ3-PNX)(SPh)] [X = O, (1);
X = S, (2)], [Re(O)(κ3-PNS)(SR)] [R = p-NH2C6H4 (3); R =
CH2CH2COOH (4); R = κ1-HPNS, (5); R = (CH2)2C(O)NH-
(CH2)3N(CH2)2N(m-OMeC6H4)CH2CH2 (6)].
Results and discussion
The novel heterofunctionalized phosphine ligand H2PNS was
synthesized by reacting N-[2-(diphenylphosphanyl)benzoyloxy]-
succinimide with S-(triphenylmethyl)-2-aminoethanethiol in
CH2Cl2, as previously described for H2PNO (Scheme 2).18 An
The mixed-ligand complexes of rhenium and technetium of
the so called [3 ϩ 1] type, which have been thoroughly investi-
gated in the past few years, are also neutral and lipophilic, and
some were proposed as agents for labelling CNS receptor
ligands.6,7 Different series of mixed-ligand complexes of this
type, which are based on a tridentate ligand and a monothiol
co-ligand have been described: [S,S,S]/[S]8,9 [S,O,S]/[S],8,10
[O,N,S]/[S],11,12 [S,N(R),S]/[S]13,14 and [S,N,N]/[S].15,16 One of the
drawbacks of using these complexes in radiopharmacy is the
fact that they present low stability against nucleophiles. In fact,
brain retention exhibited by many members of the 99mTcO-
(SNS/S) series is mediated by the nucleophilic substitution of
the monothiolate co-ligand by gluthathione (GSH) with form-
ation of the hydrophilic complex 99mTcO(SNS/SG).17 This type
of ligand-exchange reaction is reversible and its kinetics
depends not only on the nature of the tridentate and mono-
dentate ligands but also on their concentration. We have been
studying the new (bi)tridentate phosphines H2PNO and HPN2
(Scheme 1), which are quite versatile in terms of denticity and
charge.18,19
We report herein the synthesis and characterization of a
ligand of the same type, H2PNS. We also describe a new series
Scheme
2
Synthesis of the H2PNS ligand; R = N-succinimido;
(i) dichloromethane, r.t., 24 h; (ii) CF3COOH, Et3SiH.
DOI: 10.1039/b101278i
J. Chem. Soc., Dalton Trans., 2001, 2245–2250
2245
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important point in the synthesis of H2PNS is the deprotection
of the thiol group, which has to be carried out with triethyl-
silane in trifluoroacetic acid, to avoid the oxidation of the
phosphorus atom.
Using the new ligands H2PNO and H2PNS, the neutral
mixed-ligand complexes 1 and 2 have been prepared, in
relatively high yield (60–70%), using the synthetic process
indicated in Scheme 3.
Scheme 3 Synthesis of the complexes 1 and 2.
Scheme
4
Synthesis of the monothiol N-[4-(3-aminopropyl)-1-
Taking into account our interest in potential medical appli-
cations, we prepared these model complexes with Tc at the
n.c.a. (non carrier added) level and studied their stability
in vitro, in phosphate buffer and in exchange reactions with
glutathione. In both cases, no exchange is observed with
glutathione and [99mTc(O)(κ3-PNS)(SPh)](2a) remains stable in
solution for a long period.20 These results prompted us to
explore the chemistry of H2PNS with other bifunctional
monodentate co-ligands, such as p-NH2C6H4SH and HSCH2-
CH2COOH, bearing functional groups suitable for binding to
biomolecules. Using these monothiolates and H2PNS we
isolated and characterized the new complexes [Re(O)(κ3-PNS)-
(SC6H4-p-NH2)] (3) and [Re(O)(κ3-PNS)(SCH2CH2COOH)]
(4), following the synthetic procedure indicated in Scheme 3.
These compounds were obtained analytically pure in 60% yield,
after appropriate work-up. An important point in the synthesis
of 3 and 4 is the [Re(O)Cl4]Ϫ : H2PNS : SR molar ratio. This
ratio has to be maintained at 1 : 1 : 1 to avoid the formation of
another complex that was identified as [Re(O)(κ3-PNS)-
(κ1-HPNS)] (5). This compound can be obtained in 58% yield
by reacting [Re(O)Cl4]Ϫ with an excess of H2PNS in the pres-
ence of NEt3. The formation of 5 is due to the coordinative
versatility of H2PNS. In fact, this chelate can coordinate to the
metal either in a κ3 or a κ1 -fashion. This result contrasts with
what has been observed for the ligands of the same family,
H2PNO and HPN2, which, so far, have only shown an κ3 or
κ2-coordination mode.18,19 The different coordinative capability
of this family of PNX ligands is related to the nature of the
X atom, and to their tendency for stabilizing a [ReO]3ϩ core.
The identification of 5 is important for studies at the n.c.a.
level, and suggests a careful optimisation of the ligand concen-
tration in the preparations with 99mTc. Another monothiolate
co-ligand that we tried was a piperazine derivative, bearing
the receptor-binding 1-(2-methoxyphenyl)piperazine moiety:
N-[4-(3-aminopropyl)-1-(2-methoxyphenyl)piperazine]-N-[(3-
thio)propiamide] (HSPipOMe). This ligand was prepared as
described in Scheme 4.
(2-methoxyphenyl)piperazine]-N-[(3-thio)propiamide] (HSPipOMe);
R = N-succinimido; (i) dichloromethane, r.t., 20 h; (ii) CF3COOH,
Et3SiH.
Scheme 5 Synthesis of the complex 6; (i) NaOAc/MeOH, reflux.
band at 1620 cmϪ1 due to the ν(SH) and ν(C᎐O) stretching
᎐
vibrations, respectively. In the 1H NMR spectrum, all the
resonances appear in the expected range, namely broad triplets
at δ = 6.58 and 1.36, which were assigned to the NH and SH
protons, respectively. The 31P NMR spectrum show only one
resonance at δ = Ϫ9.3, comparable to that found for the
H2PNO (Ϫ9.9 ppm).18 For the piperazine derivative, the IR
spectrum presents a strong band at 1640 cmϪ1 due to the
carbonyl stretching vibration, and the 1H NMR spectrum
shows all the expected resonances, including broad triplets at
δ 7.43 and 1.59, assigned to the protons of the amide and thiol
groups, respectively.
The IR spectra of 1–6 exhibit strong bands in the 970–980
cmϪ1 range assigned to the ν(Re᎐O) stretching vibrations. The
᎐
values found compare well with the frequencies found for the
same stretching vibration in other compounds of the 3 ϩ 1 type
(930–980 cmϪ1).8–17 In all the spectra, there are also two strong
absorption bands, typical of the phenylphosphine moiety,
The neutral oxorhenium() complex [Re(O)(κ3-PNS)-
(κ1-HSPipOMe)] (6), with the receptor-binding 1-(2-methoxy-
phenyl)piperazine moiety, specific for the 5-HT1A serotonergic
receptors, was prepared as indicated in Scheme 5. Com-
plexes 1–6 are air and moisture stable, soluble in chlorinated
solvents and alcohols but insoluble in water and hydro-
carbons.
which appear at 750 and 690 cm .
Ϫ1 21 Another common feature
of all IR spectra is the presence of very strong bands in the
range 1590–1610 cmϪ1, which are due to the carbonyl stretching
vibrations. Relative to the corresponding free ligands, the values
The ligands H2PNS and HSPipOMe and the complexes 1–6
found for ν(C᎐O) in 1–6 are lower in energy (by ca. 10–30 cmϪ1),
᎐
1
were fully characterized by elemental analysis, IR, H and 31P
confirming the coordination of the tridentate dianionic chelate.
NMR spectroscopy, and by X-ray diffraction analysis in the
case of 1 and 2.
The IR and NMR spectra of H2PNS compare well with
those of the analogous H2PNO and HPN2, previously
reported.18 The most important features in the IR spectrum of
H2PNS are a weak stretching band at 2540 cmϪ1 and a strong
The lowering in energy compares well with the values found
for the complexes [Re(O)(κ3-PNO)(κ2-PNO)]Cl (1580 cmϪ1
)
and [Re(O)(κ3-PNO)(κ2-DPPBA)] [1580 cmϪ1
; DPPBA =
2-(diphenylphosphanyl)benzoic acid], which present hetero-
functionalized phosphane ligands of the same type.19 For com-
plexes 4, 5 and 6 the IR spectra also present very strong bands
2246
J. Chem. Soc., Dalton Trans., 2001, 2245–2250

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Table 1 Selected bond lengths (Å) and angles (Њ) for [Re(O)(κ3-PNO)-
(SPh)] (1), and [Re(O)(κ3-PNS)(SPh)] (2) (X = O, 1; S, 2)
1
2
Re–O(1)
Re–X(2)
Re–N
Re–S(1)
Re–P
1.638(12)
1.940(12)
2.051(14)
2.296(4)
2.387(4)
1.639(11)
2.273(5)
2.070(12)
2.305(4)
2.410(4)
O(1)–Re–X(2)
O(1)–Re–N
O(1)–Re–S(1)
O(1)–Re–P
N–Re–X(2)
S(1)–Re–X(2)
P–Re–X(2)
N–Re–S(1)
N–Re–P
112.0(6)
113.2(6)
105.4(5)
104.0(5)
81.1(6)
110.7(4)
110.8(5)
107.6(4)
106.7(4)
83.2(4)
88.1(4)
89.5(2)
143.9(4)
141.2(4)
82.3(4)
142.5(2)
141.0(4)
81.5(4)
S(1)–Re–P
85.1(4)
81.5(2)
Fig. 1 ORTEP drawing of complex 1 with atom numbering scheme.
The thermal ellipsoids are drawn at the 30% probability level. Hydrogen
atoms are omitted for clarity.
Re–S(1)–C(4)
112.1(6)
113.4(6)
at 1700, 1650 and 1640 cmϪ1 due to the carbonyl function of the
monodentate thiolates.
The 31P NMR spectra of compounds 1–6 all show one
singlet, which appears in the range 15.9–20.3 ppm. These
resonances are due to the tridentate H2PNX ligands and are
low-field shifted relative to the value found for the correspond-
ing free ligands.
This indicates clearly that the phosphorus is deshielded, and
confirms the strongly acidic character of the [ReO]3ϩ moiety.
For compound 5, the resonance of the phosphorus atom of the
chelate ligand appears specifically at 19.7 ppm, but a second
resonance is observed in this 31P NMR spectrum at Ϫ8.4 ppm,
which is due to the phosphorus atom of the heterofunctional-
ized κ1-coordinated phosphine. The small low field shift of this
resonance, relative to the free ligand (∆ = 0.9 ppm) confirms
that the P atom of this monodentate ligand is not involved in
the coordination of the metal.
In the 1H NMR spectra of 1–6 several sets of multiplet
appear, attributed to the protons of the aromatic rings, most of
them low-field shifted relative to the resonances of the free
ligand. The only important feature of note is that the methyl-
enic protons of the chelate ligands become diastereotopic
because of the asymmetry introduced in the molecule by the
oxo group (exo and endo positions) and by some steric con-
straints, which place these protons in different magnetic
environments.
Crystals suitable for X-ray structural analysis were obtained
for complexes 1 and 2. ORTEP drawings are shown in Fig. 1 and
2. Selected bond distances and angles for both complexes are
presented in Table 1
In both compounds, the coordination geometry is best
described as distorted square pyramidal (C4v), with the axial
Re–O(1) bond distance significantly shorter than the Re–L
(basal) distances. The O(1)–Re–L(basal) angles average 109(1)Њ
for both compounds, compared with the value of 102Њ for the
regular C4v. From the pattern of these angles, it can be seen that
those involving the atoms in the chelate ligand are greater than
the other two angles, which may be due to the presence of the
chelate ligand which introduces significant distortion from the
idealized polyhedron. The Re atom lies 0.69 and 0.74 Å out of
the basal plane in 1 and 2, respectively. The values of the main
shape parameters for the normalized polyhedron,22 namely the
dihedral angles of the diagonals of the basal face [S(1)–N(1),
δe3 = 3.0Њ for 1 and 1.3Њ for 2], and the dihedral angles referred
to the edges O(1)–N(1) and O(1)–S(1) (δe1, δe2 = 72.8, 99.0Њ and
75.5, 80.0Њ for 1 and 2, respectively) compared with the values
(0 and 75.7, 75.7Њ) for the “idealized” dihedral angles for C4v,
show a clear distortion for both compounds, being greater for
Fig. 2 ORTEP drawing of complex 2 with atom numbering scheme.
The thermal ellipsoids are drawn at the 30% probability level. Hydrogen
atoms are omitted for clarity.
compound 1. In terms of trigonality index, τ,23 the values are
0.045 and 0.025 for 1 and 2, respectively (τ = 0 for a regular
square pyramid, τ = 1 for a regular trigonal bipyramid).
The five-membered ring in 1, formed by the atoms Re, O(2),
C(2), C(1) and N are in the twisted form, with C(2) and C(1)
0.51 and Ϫ0.12 Å above and below the plane defined by the
atoms Re, O(2) and N. The five-membered ring in 2, formed by
the atoms Re, N(1), C(2), C(1) and S(2) adopt the envelope
conformation, where C(1) lies 0.63 Å out of the plane defined
by the remaining four atoms. The six-membered rings are, as
usual, non-planar in both compounds. The disparity between
the traditional chair or boat conformation with the irregular
conformations found here is very great and so no description
for the conformations will be attempted.
The Re᎐O(1) bond lengths in 1 [1.638(12) Å] and 2 [1.639(11)
᎐
Å] are comparable but are slightly shorter than the values nor-
mally found in this type of 3 ϩ 1 compound, which normally
are in the range 1.67–1.70 Å.8–17 This difference is certainly
related to the different donor atoms sets of our chelate, namely,
the presence of the phosphorus atom. The Re–S(1) bond dis-
tances in 1 [2.296(4) Å] and 2 [2.305(4) Å] are comparable and
typical of a monothiolate. The Re–S(2) bond distance in 2
compares with the values found for the same type of bond in
complexes of the 3 ϩ 1 type, stabilized by SSS or SNS chelates.
The Re–P bond distances in 1 [2.387(4) Å] and 2 [2.410(4) Å]
are comparable to the value of 2.397(2) Å found in a complex
of the same family [ReO(κ3-PN2)(OMe)Cl].19 The Re–N bond
J. Chem. Soc., Dalton Trans., 2001, 2245–2250
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distances in 1 [2.051(14) Å] and 2 [2.070(12) Å] are within the
expected range when amide groups are involved.
piperazine (0.34 g, 1.36 mmol) in dichloromethane (8 mL),
succinimido 3-[(triphenylmethyl)thio]propionate (0.61 g, 1.36
mmol) dissolved in the same solvent (5 mL) was added at room
temperature under an inert atmosphere. After 20 h, a dilute
solution of HCl was added to the reaction and the aqueous
phase was extracted three times with dichloromethane. The
organic phases were collected, washed with water, dried over
MgSO4, filtered, and the solvent evaporated. A highly viscous
oil, which gave a white solid on standing under vacuum was
obtained (0.72 g, 91%). This product, N-[4-(3-aminopropyl)-1-
(2-methoxyphenyl)piperazine]-N-{[3-(triphenylmethyl)thio]-
Concluding remarks
The complexes of general formula [Re(O)(κ3-PNX)(SR)]
(X = O, S) (1–6) are the first examples of 3 ϩ 1 compounds
stabilized by chelates with PNO and PNS donor atom sets. The
X-ray structural analysis for two examples of this series con-
firms a coordination number of 5 for the metal and indicates a
distorted square pyramidal coordination geometry. The syn-
thesis and characterization of [Re(O)(κ3-PNS)(κ1-HPNS)] (5)
shows two different coordination modes for the H2PNS chelate,
which are different from what has been previously observed for
the H2PNO chelate (κ3/κ2-coordination mode). Studies involv-
ing these neutral and liphophilic compounds at the n.c.a. level
are in progress.
propiamide}, was used in the next step without further purifi-
1
cation. IR (cmϪ1, KBr): 1640 (C᎐O), 1490, 1240, 740, 700. H
᎐
NMR (δ, CDCl3): 7.39–7.14 (15H, arom.), 7.01–6.83 (m,
4 ϩ 1H, arom. ϩ NH), 3.84 (s, 3H, OCH3), 3.30 (q, 2H, CH2),
3.07 (br s, 4H, CH2), 2.67 (br s, 4H, CH2), 2.55 (m, 2H, CH2),
2.48 (t, 2H, CH2), 2.06 (t, 2H, CH2), 1.70 (m, 2H, CH2).
Deprotection of the thiol group was carried out as described
in the literature.25 A colorless viscous oil, which gave a white
solid on standing was obtained (0.33 g, 79%). The product was
used in the preparation of 6 without further purification. IR
Experimental
General
(cmϪ1, KBr) 1640 (C᎐O), 1490, 1240, 750, 700. 1H NMR
᎐
All chemicals were of reagent grade and used without further
purification. 2-(Diphenylphosphanyl)-N-(2-hydroxyethyl)benz-
amide (H2PNO), N-[2-(diphenylphosphanyl)benzoyloxy]-
(δ, CDCl3): 7.43 (br t, 1H, NH), 7.04–6.84 (m, 4H, arom.), 3.85
(s, 3H, OCH3), 3.39 (q, 2H, CH2), 3.16 (br s, 4H, CH2), 2.79 (m,
6H, CH2), 2.64 (t, 2H, CH2), 2.45 (t, 2H, CH2), 1.78 (t, 2H,
CH2), 1.59 (t 1H, SH).
succinimide,
4-(3-aminopropyl)-1-(2-methoxyphenyl)piper-
azine, S-(triphenylmethyl)-2-aminoethanethiol and succin-
imido-3-[(triphenylmethyl)thio]propionate
were
prepared
General procedure for the preparation of complexes 1–4
according to literature methods.5,18,24,25 [nBu4N][Re(O)Cl4] and
[Re(O)Cl3(PPh3)] were prepared as reported in the literature.26,27
Reactions were carried out in air, unless otherwise indicated.
1H and 31P NMR spectra were recorded on a Varian Unity 300
A solution of H2PNX (X = O, S), triethylamine and the corre-
sponding monothiol in dichloromethane was added dropwise,
at room temperature, to a stirred solution of [nBu4N][Re(O)Cl4]
in dichloromethane. The mixture was allowed to react at room
temperature under a nitrogen atmosphere (1, 3 h; 2, 6 h; 3, 18 h,
4, 18 h), and the solvent evaporated.
1
MHz spectrometer; H chemical shifts were referenced relative
to tetramethylsilane and the 31P chemical shifts to external 85%
H3PO4 solution. Chemical shifts are given in ppm. The NMR
samples were prepared in CDCl3. Infrared spectra were
recorded in the range 4000–200 cmϪ1 on a Perkin-Elmer 577
spectrometer from KBr pellets. Elemental analyses were
performed on a Perkin-Elmer automatic analyser.
[Re(O)(κ3-PNO)(κ1-SPh)] 1
Using 0.117 g (0.20 mmol) of [nBu4N][Re(O)Cl4], 0.070 g (0.20
mmol) of H2PNO, 0.110 mL (0.80 mmol) of triethylamine and
0.021 mL (0.20 mmol) of thiophenol in 10 mL of dichloro-
methane, a dark brown residue was obtained. This residue
was chromatographed on a silica gel column with 20% ethyl
acetate–dichloromethane to afford a brown solid that was
formulated as 1 (0.090 g, 70% yield). Brown–yellow crystals of
1, suitable for X-ray diffraction analysis, were obtained by
slow diffusion of hexane into a solution of the complex in
dichloromethane. IR (cmϪ1, KBr): 1590 (C᎐O), 980 (Re᎐O),
2-(Diphenylphosphanyl)-N-(2-thioethyl)benzamide (H2PNS)
N-[2-(diphenylphosphanyl)benzoyloxy]succinimide (1.00 g,
2.48 mmol) dissolved in dichloromethane (10 mL) was added
dropwise to a solution of S-(triphenylmethyl)-2-aminoethane-
thiol (1.66 g, 5.19 mmol) in the same solvent (10 mL). After 24
h at room temperature, under stirring, the solution was evapor-
ated to dryness. The resulting viscous oil was chromatographed
on a silica gel column with 15–30% ethyl acetate–dichloro-
methane (gradient) to afford a white solid (1.21 g, 80%), N-2-[S-
(triphenylmethyl)thioethyl]-2-(diphenylphosphanyl)benzamide.
This product was used in the next step without further purifi-
᎐
᎐
750, 690. 1H NMR (δ, CDCl3): 8.25 (m, 1H, arom.), 7.73–6.99
(m, 17H, arom), 6.78 (m, 1H, arom.), 4.51 (m, 1H, CH, tri-
dentate ligand), 4.20 (m, 1H, CH of tridentate ligand) 4.02 (m,
1H, CH of tridentate ligand), 2.65 (m, 1H, CH of tridentate
ligand); 31P NMR (δ, CDCl3): 15.9. Anal. calc for C27H23NO3-
PSReؒH2O: C, 47.85; H, 3.72; N, 2.07; S 4.72; found: C, 47.77;
H, 3.81; N, 1.97; S, 4.27%.
cation. IR (cmϪ1, KBr): 1630 (C᎐O), 740, 700. 1H NMR
᎐
(δ, CDCl3): 7.85 (m, 1H, arom.), 7.60–7.17 (m, 28H, arom.),
7.08 (b t, 1H, NH), 3.06 (q, 2H, CH2), 2.39 (t, 2H, CH2); 31P
NMR (δ, CDCl3) Ϫ8.4.
[Re(O)(κ3-PNS)(κ1-SPh)] 2
Deprotection of the thiol group was carried out as described
in the literature.25 A colorless viscous oil was obtained, yielding
a white solid after washing with hexane (0.63 g, 86%). The
product was used without further purification. IR (cmϪ1, KBr):
2540, 1620 (C᎐O), 1540, 740, 690. 1H NMR (δ, CDCl ) 7.66 (m,
Using H2PNS (0.062 g, 0.17 mmol), triethylamine (0.094 mL,
0.68 mmol) and thiophenol (0.018 mL, 0.17 mmol) in dry
dichloromethane (4 mL) and a solution of [nBu4N][Re(O)Cl4]
(0.100 g, 0.17 mmol) in dichloromethane (5 mL), a dark brown
oily residue was obtained, after evaporation of the solvent.
After column chromatography (silica gel, 5% ethyl acetate–
dichloromethane) a deep brown solid was obtained and formu-
lated as 2 (0.070 g, 59%). Brown–orange crystals of 2 were
obtained by layering a solution of the complex in dichloro-
methane with hexane. IR (cmϪ1, KBr): 1600 (C᎐O), 980 (Re᎐O),
᎐
3
1H, arom.), 7.42–7.25 (m, 12H, arom.), 6.97 (m, 1H, arom.)
6.58 (b t, 1H, NH), 3.44 (m, 2H, CH2), 2.52 (m, 2H, CH2), 1.36
(m, 1H, SH); 31P NMR (δ, CDCl3) Ϫ9.4. Anal. calc for
C21H20NOPS: C, 69.02; H, 5.52; N, 3.83; S, 8.77; found: C,
68.56; H, 4.84; N, 3.76; S, 8.73%.
᎐
᎐
N-[4-(3-Aminopropyl)-1-(2-methoxyphenyl)]piperazine]-N-
[(3-thio)propiamide] (HSPipOMe)
740, 700. 1H NMR (δ, CDCl3): 8.14 (m, 1H, arom.), 7.73–7.08
(m, 17H, arom), 6.83 (m, 1H, arom.), 5.07 (m, 1H, CH tri-
dentate ligand), 2.79 (m, 1H, CH of tridentate ligand) 2.65 (m,
To a stirred solution of 4-(3-aminopropyl)-1-(methoxy-phenyl)-
2248
J. Chem. Soc., Dalton Trans., 2001, 2245–2250

View Online
Table 2 Crystallographic data for complexes 1 and 2
1
2
Formula
MW
C27H23NO3PSRe
658.69
C27H23NO2PS2Reؒ0.5C6H14
717.84
Crystal system
Space group
Monoclinic
P21/n
Monoclinic
P21/n
a/Å
b/Å
c/Å
9.2050(8)
11.9708(10)
24.627(3)
94.989(10)
2703.4(5)
4
9.4660(9)
11.9835(10)
24.510(3)
97.612(9)
2755.8(5)
4
β/Њ
V/Å3
Z
dcalc/g cmϪ3
1.618
4.658
1.730
4.648
µ/mmϪ1
Measured reflections
Independent reflections [R(int)]
Observed reflections [I > 2σ(I )]
6225
5857(0.1185)
2987
0.0798
0.1547
6392
6026(0.0686)
3258
0.0844
0.1402
a
R1
a
wR2
a The values were calculated for data with [I > 2σ(I )].
1H, CH of tridentate ligand), 2.22 (m, 1H, CH of tridentate
ligand); 31P NMR (δ, CDCl3): 19.6. Anal. calc for C27H23NO2-
PS2ReؒH2O: C, 46.75; H, 3.64; N, 2.02; S 9.23; found: C, 46.11;
H, 3.57; N, 1.96; S, 9.53%.
phere, after which the solution was dark brown. The solvent
was evaporated and the residue obtained was purified by
chromatograpy, using a silica gel column and a mixture of
5–10% ethyl acetate–dichloromethane (gradient). The light
brown oil, yielded solid 5, after washing with hexane (0.92 g,
59%). IR (cmϪ1, KBr): 1650 (C᎐O), 1590 (C᎐O), 980 (Re᎐O),
[Re(O)(κ3-PNS)(κ1-SPhNH2)] 3
᎐
᎐
᎐
740, 690. 1H NMR (δ, CDCl3): 8.13 (m, 1H, arom.), 7.70–7.19
(m, 26H, arom), 7.05 (br t, 1H, NH), 6.79 (m, 1H, arom.), 5.09
(m, 1H, CH tridentate ligand), 4.06 (m, 1H, CH), 3.81 (m, 1H,
CH), 3.70 (m, 2H, CH2), 2.96 (m, 1H, CH), 2.69 (m, 1H, CH)
2.20 (m, 1H, CH); 31P NMR (δ, CDCl3): 19.5 and Ϫ8.5. Anal.
calc for C42H37N2O3P2S2Reؒ2H2O: C, 52.22; H, 4.28; N, 2.90; S,
6.64; found: C, 52.40; H, 4.21; N, 2.84; S, 7.29%.
A solution of H2PNS (0.062 g, 0.17 mmol), triethylamine
(0.094 mL, 0.68 mmol) and p-aminothiophenol (0.021 g, 0.17
mmol) in dry dichloromethane (4 mL) was added dropwise to
a stirred solution of [nBu4N][Re(O)Cl4] (0.100 g, 0.17 mmol).
After reaction, the solvent was evaporated yielding a brown–
orange oily residue. After chromatography (silica gel column,
20% ethyl acetate–dichloromethane) an orange–brown solid (3)
was obtained (0.065 g, 55%). IR (cmϪ1, KBr): 1590 (C᎐O), 980
᎐
[Re(O)(κ3-PNS)(κ1-SPipOMe)] 6
1
(Re᎐O), 750, 690. H NMR (δ, CDCl ): 8.13 (m, 1H, arom.),
᎐
3
7.72–7.21 (12H, arom), 6.81 (m, 1H, arom.), 6.71 (m, 2H) 6.57
(m, 2H, arom), 5.06 (m, 1H, CH tridentate ligand), 2.80 (m, 1H,
CH of tridentate ligand) 2.64 (m, 1H, CH of tridentate ligand),
2.22 (m, 1H, CH of tridentate ligand); 31P NMR (δ, CDCl3):
20.3. Anal. calc for C27H24N2O2PS2Re: C, 47.01; H, 3.51; N,
4.06; S, 9.30; found: C, 46.78; H, 3.77; N, 4.02; S, 9.94%.
To a stirred suspension of [Re(O)Cl3(PPh3)2] (0.42 g, 0.50
mmol) in a 0.15 M methanolic solution of sodium acetate
(9 mL), a mixture of H2PNS (0.18 g, 0.50 mmol) and
HSPipOMe (0.17 g, 0.50 mmol) in the same solution (5 mL)
was added. The suspension was stirred and refluxed for 60 min,
after which, a dark brown solution was obtained. After cooling
to room temperature, the reaction mixture was diluted with
dichloromethane and a 0.01 M HCl solution. The aqueous
phase was then extracted three times with dichloromethane and
the organic phases collected. After drying over magnesium
sulfate, the solution was filtered and the solvent evaporated.
The dark brown residue obtained was washed three times with
diethyl ether and chromatographed on a silica gel column with
5% methanol–chloroform to afford a brown solid 6 (0.116 g,
26%). IR (cmϪ1, KBr): 1640 (C᎐O), 1590 (C᎐O), 970 (Re᎐O),
750, 690. 1H NMR (δ, CDCl3): 8.13 (m, 1H, arom.), 7.69–7.18
(m, 12H, arom), 7.02–6.73 (m, 4H, arom. ϩ NH), 6.77 (m, 1H,
arom.), 5.05 (m, 1H, CH of tridentate ligand) 4.07 (m, 2H,
SCH2), 3.83 (s, 3H, OCH3), 3.35 (m, 2H, CH2 of propyl), 3.16
(br s, 4H, CH2 of piperazine), 4.38 (m, 1H, CH of tridentate
ligand), 2.81–2.58 (m, 9H, SCH2CH2CO of ethyl, CH2 of
piperazine, CH of tridentate ligand), 2.16 (m, 1H, CH of tri-
dentate ligand); 31P NMR (δ, CDCl3): 19.9. Anal. calc for
C38H44N4O4PS2Re: C, 50.60; H, 4.92; N, 6.21; S, 7.11; found: C,
50.16; H, 4.92; N, 5.25; S, 7.63%.
[Re(O)(κ3-PNS)(κ1-SCH2CH2COOH)] 4
A solution of H2PNS (0.031 g, 0.085 mmol), triethylamine
(0.012 mL, 0.085 mmol) and 3-mercaptopropionic acid (0.08
ml, 0.085 mmol) in dry dichloromethane (2 mL) reacted with
[nBu4N][Re(O)Cl4] (0.050 g, 0.085 mmol) in dichloromethane
(3 mL). After evaporation of the solvent, a brown oily residue
was obtained. Addition of methanol to this residue allowed
the precipitation of a solid which was further washed with
methanol. After drying under vacuum a pale brown solid (4)
᎐
᎐
᎐
was obtained (0.034 g, 60%). IR (cmϪ1, KBr): 1700 (C᎐O), 1610
᎐
(C᎐O), 970 (Re᎐O), 750, 690. 1H NMR (δ, CDCl ): 8.13 (m, 1H,
᎐
᎐
3
arom.), 7.68–7.20 (m, 12H, arom), 6.77 (m, 1H, arom.), 5.08
(m, 1H, CH tridentate ligand), 4.04 (m, 1H, CH of tridentate
ligand) 3.98 (m, 1H, CH of tridentate ligand), 2.95 (m, 2H,
CH2), 2.76 (m, 2H, CH2), 2.21 (m, 1H, CH of tridentate
ligand); 31P NMR (δ, CDCl3): 19.8. Anal. calc for C24H23NO4-
PS2Re: C, 42.92; H, 3.45; N, 2.09; S, 9.53; found: C, 43.59; H,
3.34; N, 2.16; S, 10.10%.
[Re(O)(κ3-PNS)(κ1-HPNS)] 5
X-Ray crystallographic analysis
To a stirred solution of [nBu4N][Re(O)Cl4] (0.10 g, 0.17 mmol)
in dry dichloromethane (5 mL), was added a solution of the
same solvent (3 mL) containing H2PNS (0.12 g, 0.33 mmol) and
triethylamine (0.19 mL, 1.36 mmol). The mixture was allowed
to react for 6 h at room temperature under a nitrogen atmos-
A brown–yellow crystal of 1 and a brown–orange crystal of
2 were fixed inside thin-walled glass capillaries. Data were
collected at room temperature on an Enraf-Nonius CAD4
diffractometer with graphite-monochromatized Mo-Kα radi-
ation, using a ω–2θ scan mode. Unit cell dimensions were
J. Chem. Soc., Dalton Trans., 2001, 2245–2250
2249

View Online
7 S. Meegalla, K. Plossl, M. P. Kung, D. A. Stevenson, L. M.
Liable-Sands, A. L. Rheingold and H. F. Kung, J. Am. Chem. Soc.,
1995, 117, 11037.
8 H. Spies, T. Fietz, H. J. Pietsch, B. Johannsen, P. Leibnitz, G. Reck,
D. Scheller and K. Klostermann, J. Chem. Soc., Dalton Trans., 1995,
2277.
9 K. P. Maresca, F. J. Femia, G. H. Bonavia, J. W. Babich and
J. Zubieta, Inorg. Chim. Acta, 2000, 297, 98.
10 K. P. Maresca, F. J. Femia, G. H. Bonavia, J. W. Babich and
J. Zubieta, Inorg. Chem. Commun., 1998, 1, 209.
11 X. Chen, F. J. Fermia, J. W. Babich and J. Zubieta, Inorg. Chim.
Acta, 2000, 306, 113.
12 F. Tisato, F. Refosco, U. Mazzi, G. Bandoli and M. Nicolini,
J. Chem. Soc., Dalton Trans., 1987, 1693.
13 M. Friebe, H. Spies, W. Seichter, P. Leibnitz and B. Johannsen,
J. Chem Soc., Dalton Trans., 2000, 2471.
14 M. Pelecanou, I. C. Pirmettis, M. S. Papadopoulos, C. P.
Raptopoulou, A. Terzis, E. Chiotellis and C. I. Stassinopoulou,
Inorg. Chim. Acta, 1999, 287, 142.
15 M. S. Papadopoulos, M. Pelecanou, I. C. Pirmettis, D. M.
Spyriounis, C. P. Raptopoulou, A. Terzis, C. I. Stassinopoulou and
E. Chiotellis, Inorg. Chem., 1996, 35, 4478.
16 A. Rey, I. Pirmettis, M. Pelecanou, M. Papadopoulos, C. P.
Raptopoulou, L. Mallo, C. I. Stassinopoulou, A. Terzis, E.
Chiotellis and A. Léon, Inorg. Chem., 2000, 39, 4211.
17 (a) R. Syhre, S. Seifert, H. Spies, A. Gupta and B. Johannsen,
Eur. J. Nucl. Med., 1998, 25, 793; (b) B. Nock, T. Maina, A. Tsortos,
M. Pelecanou, C. P. Raptopoulou, M. Papadopoulos, H. J. Pietzsch,
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obtained by least-squares refinement of the setting angles of 25
reflections with 15.5 < 2θ < 27.9Њ for 1 and 14.7 < 2θ < 24.0Њ for
2. For 1 and 2, a summary of the crystallographic data is given
in Table 2. Data were corrected for Lorentz and polarization
effects and for absorption by empirical corrections based on Ψ-
scans.28 The heavy atom positions were located by Patterson
methods using SHELXS-86.29 The remaining atoms were
located by sucessive difference Fourier maps and refined by
least-squares refinements on F 2 using SHELXL-93.30 In the
residual electron density map of 1, a set of three peaks were
located which were assumed to be a disordered solvent mol-
ecule, but to which no chemical identity could be assigned.
They were introduced into the refinement as full occupancy
carbon atoms. The lattice solvent was then excluded from the
formula, from the molecular weight and from the calculation
of the density in Table 2. A disordered half-hexane molecule of
crystallization was also located in the Fourier difference map of
2. All the non-hydrogen atoms (except the solvent atoms in 2)
were refined with anisotropic thermal motion parameters
and the contributions of the hydrogen atoms were included in
calculated positions (except those of the solvent). Atomic
scattering factors and anomalous disperson terms were taken
from ref. 28. The drawings were made with ORTEPII31 and all
the calculations were performed on a DEC α 3000 computer.
CCDC reference numbers 158068 and 158069.
See http://www.rsc.org/suppdata/dt/b1/b101278i/ for crystal-
lographic data in CIF or other electronic format.
18 J. D. G. Correia, Â. Domingos and I. Santos, Eur. J. Inorg. Chem.,
2000, 1523.
19 J. D. G. Correia, Â. Domingos, A. Paulo and I. Santos, J. Chem.
Soc., Dalton Trans., 2000, 2477.
20 C. Fernandes, S. Seifert, H. Spies J. D. G. Correia and I. Santos,
manuscript in preparation.
Acknowledgements
21 K. Nakamoto, Infrared Spectra of Inorganic and Coordination
Compounds, 2nd edn., Wiley-Interscience, New York, 1970, Ch. 3–9.
22 E. L Muetterties and L. J. Guggenberger, J. Am. Chem. Soc., 1974,
96, 1748.
J. D. G. C. thanks the FCT for a PRAXIS XXI postdoctoral
fellowship. This work is being supported by SAPIENS/QUI/
35423/99 and by COST Action B12.
23 A. W. Addison and T. N. Rao, J. Chem. Soc., Dalton Trans., 1984,
1349.
24 J. P. O’ Neil, S. R. Wilson and J. A. Katzenellenbogen, Inorg. Chem.,
1994, 33, 319.
25 D. Brenner, A. Davison, J. Lister-James and A. G. Jones, Inorg.
Chem., 1984, 23, 3793.
26 R. Alberto, R. Schibli, A. Egli, P. August Schubiger, W. A.
Herrmann, G. Artus, U. Abram and T. A. Kaden, J. Organomet.
Chem., 1995, 493, 119.
27 M. S. Ram and J. T. Hupp, Inorg. Chem., 1991, 30, 130.
28 C. K. Fair, MOLEN, Enraf-Nonius, Delft, The Netherlands, 1990.
29 G. M. Sheldrick, SHELXS-86, Program for the Solution of Crystal
Structures, University of Göttingen, Germany, 1986.
30 G. M. Sheldrick, SHELXL-93, Program for the Refinement of
Crystal Structures, University of Göttingen, Germany, 1993.
31 C. K. Johnson, ORTEPII, Report ORNL-5138, Oak Ridge
National Laboratory, Oak Ridge, TN, 1976.
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