Synthesis and structural characterization of a novel Re[P][NN][S][SO] mixed ligand rhenium(III) complex

Article abstract of DOI:10.1016/S0020-1693(02)01377-4

A novel mixed ligand hexacoordinated rhenium(III) complex of the general formula Re^III[P][NN][S][SO] has been synthesized by reacting Re^VOCl₃(PPh₃)₂ with 2,2′-bipyridine (NN), p-thiocresol (S) and N-acetyl-L-cysteine (SO) in a 1:1:1:1 ratio in methanol. During the reaction, the central rhenium atom undergoes reduction from Re(V) to Re(III). The complex was isolated as red crystals and characterized by elemental analysis, IR and NMR spectroscopies. X-ray crystallographic studies showed that the coordination geometry around rhenium is distorted octahedral. The equatorial plane is defined by the two nitrogen atoms of 2,2′-bipyridine, the sulfur of N-acetyl-L-cysteine and the sulfur of the aromatic thiol, while the phosphorous and the carboxylate oxygen of N-acetyl-L-cysteine occupy the apical positions.

Full text of DOI:10.1016/S0020-1693(02)01377-4

Inorganica Chimica Acta 346 (2002) 270ꢁ274
/
www.elsevier.com/locate/ica
Note
Synthesis and structural characterization of a novel Re[P][NN][S][SO]
mixed ligand rhenium(III) complex
D. Papagiannopoulou a, I.C. Pirmettis a, M. Pelecanou b, Ch. Tsoukalas a,
C.P. Raptopoulou c, A. Terzis c, E. Chiotellis d, M. Papadopoulos a,*
a Institute of Radioisotopes-Radiodiagnostic Products, National Centre for Scientific Research ‘Demokritos’, Ag. Paraskevi, 15310 Athens, Greece
b Institute of Biology, National Centre for Scientific Research ‘Demokritos’, 15310 Athens, Greece
c Institute of Materials Science, National Centre for Scientific Research ‘Demokritos’, 15310 Athens, Greece
d School of Pharmacy, Aristotelian University of Thessaloniki, 54006 Thessaloniki, Greece
Received 5 August 2002; accepted 2 October 2002
Abstract
A novel mixed ligand hexacoordinated rhenium(III) complex of the general formula ReIII[P][NN][S][SO] has been synthesized by
reacting ReVOCl3(PPh3)2 with 2,2?-bipyridine (NN), p-thiocresol (S) and N-acetyl-
L-cysteine (SO) in a 1:1:1:1 ratio in methanol.
During the reaction, the central rhenium atom undergoes reduction from Re(V) to Re(III). The complex was isolated as red crystals
and characterized by elemental analysis, IR and NMR spectroscopies. X-ray crystallographic studies showed that the coordination
geometry around rhenium is distorted octahedral. The equatorial plane is defined by the two nitrogen atoms of 2,2?-bipyridine, the
sulfur of N-acetyl-L-cysteine and the sulfur of the aromatic thiol, while the phosphorous and the carboxylate oxygen of N-acetyl-L-
cysteine occupy the apical positions.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Crystal structures; Rhenium complexes; Mixed ligand complexes
1. Introduction
ing on labeling small peptide receptor ligands that will
specifically direct the radiopharmaceutical on a target
tissue.
Extensive research efforts on the inorganic chemistry
of technetium have resulted in the preparation of a great
number of novel Tc-99m compounds and has produced
many useful radiopharmaceuticals with a tremendous
impact on the development of diagnostic nuclear
medicine [1]. Rhenium, a congener of technetium,
exhibits many of the chemical properties of technetium
and investigations of rhenium coordination chemistry
are often performed in conjunction to technetium,
providing thus a non-radioactive alternative to working
with technetium radioisotopes [2]. Furthermore, the b-
emitting radionuclides of rhenium, 186Re and 188Re, are
of great interest to nuclear medicine, as they possess
physical and nuclear properties favorable for use in
systemic radiotherapy [2]. Current efforts [1] are focus-
This work is part of our continuing investigations into
mixed ligand bipyridyl-thiolato complexes of techne-
tium and rhenium [3,4] with the aim to develop a new
class of potentially useful diagnostic and therapeutic
radiopharmaceuticals, respectively. In a previous work
[3], we have synthesized hexacoordinated complexes of
the formula ReVO[NN][S][SO], where NN is 2,2?-bipyr-
idine, S is an aromatic monothiol and SO is thiosalicylic
acid. In an effort to develop bifunctional chelating
agents [2b], we replaced thiosalicylic acid with N-
acetyl-
ligand. N-Acetyl-
L
-cysteine which can also act as an aliphatic SO
L-cysteine can serve as a model for the
incorporation of a peptide in the coordination sphere of
rhenium since the acetyl group may, in principle, be
replaced by a small peptide. However, instead of the
expected oxorhenium(V) complex, a novel mixed ligand
rhenium(III) complex, ReIII[PPh3][NN][p-CH3C6H4S]-
[SCH2CH(NHCOCH3)COO] (1), where NN is 2,2?-
* Corresponding author. Tel.: ꢀ
480.
E-mail address: mspap@rrp.demokritos.gr (M. Papadopoulos).
/
30-1-6503 909; fax: ꢀ30-1-6524
/
0020-1693/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 0 - 1 6 9 3 ( 0 2 ) 0 1 3 7 7 - 4

D. Papagiannopoulou et al. / Inorganica Chimica Acta 346 (2002) 270ꢁ
/
274
271
bipyridine, was isolated and characterized by IR, NMR,
elemental analysis and X-ray crystallography. In this
complex, as originally planned, N-acetyl-L-cysteine is
P21 Nicolet diffractometer upgraded by Crystal Logic
using graphite monochromated Cu Ka radiation. Unit
cell dimensions were determined by using the angular
settings of 25 automatically centered reflections in the
incorporated in the coordination sphere of rhenium.
range 22B
Intensity data were recorded using a u ꢁ
/
2u B
/
548 and they appear in Table 1.
2u scan. Three
/
2. Experimental
standard reflections monitored every 97 reflections
showed less than 3% variation and no decay. Lorentz,
polarization and psi-scan absorption corrections were
applied using CRYSTAL LOGIC software. The structure
was solved by direct methods using SHELXS-86 [6] and
refined by full-matrix least-squares techniques on F2
using SHELXL-93 [7]. Further crystallographic details for
2.1. Materials and methods
IR spectra were recorded as KBr pellets in the range
500 cmꢂ1 on a Perkinꢁ
Elmer 1600 FT-IR spec-
4000ꢁ
/
/
trophotometer and were referenced to polystyrene. The
NMR spectra were recorded in deuteriochloroform on a
Bruker 500 MHz Avance DRX spectrometer using TMS
as reference. Elemental analyses were performed on a
1: 2umax
2.9ꢀa1a2 separation, reflections collected/unique/used
8545/8202 [Rint
[Dr]max/[Dr]min
0.010, R1/wR2 (for all data)ꢃ
ꢃ
118.38, scan speed 1.58 minꢂ1, scan range
/
/
ꢃ
ꢃ
/
0.0206]/8202, 931 parameters refined,
ꢂ3
˚
Perkinꢁ
All laboratory chemicals were of reagent grade. N-
Acetyl- -cysteine, 2,2?-bipyridine and p-thiocresol were
/Elmer 2400/II automated analyzer.
/
2.116/ꢂ
/
0.913
e
A
,
[D/s]max
ꢃ
/
/0.0492/0.1350. All hydro-
L
gen atoms were introduced at calculated positions as
riding on bonded atoms, all non-H atoms were refined
anisotropically (except of the solvent water molecules
which were refined isotropically). The second water
molecule was refined with the occupation factor fixed to
10.50.
purchased from Fluka and ReOCl3(PPh3)2 was prepared
according to the literature [5].
2.2. Synthesis of Re[NN][PPh3][p-
CH3C6H4S][SCH2CH(NHCOCH3)COO] (1)
To a stirred suspension of trichlorobis(triphenylphos-
phine)rhenium(V) oxide (334 mg, 0.4 mmol) in MeOH
(10 ml) CH3COONa in MeOH (2 ml, 0.4 mmol) was
added. A mixture of 2,2?-bipyridine (63 mg, 0.4 mmol),
3. Results and discussion
Refluxing of trichlorobis(triphenylphosphine)rhe-
nium(V) oxide in the presence of 2,2?-bipyridine (NN),
p-thiocresol (50 mg, 0.4 mmol) and N-acetyl-L-cysteine
(66 mg, 0.4 mmol) in MeOH (15 ml) was added under
stirring. The mixture was refluxed for approximately 1
h. During heating the originally green reaction mixture
p-thiocresol and N-acetyl-
nolic solution for 1 h (Fig. 1) yielded a redꢁ
solution which was diluted with CH2Cl2 and then
washed with water. TLC analysis (silica gel, CH2Cl2ꢁ
MeOH, 9:1) of the dichloromethane layer showed the
existence of two complexes, one with Rfꢀ0.8 and a
L
-cysteine in a neutral metha-
/
brown
became redꢁbrown in color. After cooling to room
/
/
temperature, CH2Cl2 was added in the mixture. The
organic layer was washed with H2O, collected and dried
over MgSO4. The volume of the solution was reduced to
/
5 ml and then 5 ml of MeOH was added. The yellowꢁ
/
Table 1
Summary of crystal, intensity collection and refinement data
orange crystals formed were isolated and were shown by
NMR to be the well characterized ReO(NN)(p-
CH3C6H4S)3 complex [3] (yield: 17%, 49 mg). Upon
standing and slow evaporation of the filtrate, red
crystals of complex 1 were formed. Crystals suitable
for X-ray crystallography were obtained by recrystalli-
1×0.75H2O
/
Empirical formula
Formula weight
Temperature (K)
C40H38.5N3O3.75ReS2
902.53
298
˚
Wavelength (A)
Cu Ka 0.710730
P21
zation from MeOHꢁ
/
CH2Cl2.
Space group
˚
Yield: 95 mg (27%), Rfꢃ
/
0.5 (silica gel, CH2Cl2ꢁ
/
a (A)
˚
12.539(1)
20.274(2)
15.846(1)
106.405(4)
3864.3(6)
4
MeOH, 9:1), IR (cmꢂ1, KBr): 1607, 1089, 806, 764,
697. Anal. Calc. for C40H37N3O3PReS2: C, 54.04; H,
4.19; N, 4.73; S, 7.21. Found: C, 53.68; H, 4.32; N, 4.68,
S, 6.95%.
b (A)
˚
c (A)
b (8)
3
V (A )
˚
Z
Dcalcd/Dmeas (Mg mꢂ3
)
1.551/1.53
7.898
1806
Absorption coefficient m (mmꢂ1
F(000)
R indices
)
2.3. X-ray crystallography
a
R1ꢃ
/
0.0492 a, wR2ꢃ
1350
/
A red crystal of 1 (0.06ꢄ
/
0.18ꢄ0.40 mm) suitable for
/
Goodness-of-fit on F2
1.050
X-ray analysis was mounted in air and covered with
epoxy glue. Diffraction measurements were made on a
a
For 8202 reflections with I ꢁ2s(I).
/

272
D. Papagiannopoulou et al. / Inorganica Chimica Acta 346 (2002) 270ꢁ274
/
Table 2
1H and 13C NMR chemical shifts (ppm) for complex 1 in CDCl3 at
25 8C
H-1
H-2
4.33, 2.87 C-1
63.58
55.20
3.92
1.84
8.24
6.86
7.29
8.08
7.99
7.21
6.80
7.82
C-2
C-3
H-5
H-6
178.98
168.42
23.59
C-4
C-5
H-7
H-8
C-6
C-7
153.39
123.51
139.03
120.26
152.75
153.46
119.92
139.08
123.30
152.15
H-9
H-12
C-8
C-9
H-13
H-14
H-15
Fig. 1. Reaction scheme of the formation of the rhenium complexes.
C-10
C-11
H-17 (H-21)
H-23 (H-27)
H-29 (H-33)
H-18 (H-20)
H-24 (H-26)
7.49ꢁ
/
7.41 C-12
C-13
C-14
second with Rfꢀ0.5. The first product precipitated
/
from the reaction mixture as yellow-orange crystals
and proved to be the ReO[NN][p-CH3C6H4S]3 complex
[3]. The second product precipitated subsequently from
the filtrate as red crystals and turned out to be the
ReIII[PPh3][NN][p-
7.26ꢁ
/
7.22 C-15
C-16, C-22, C-28 148.55
(1JCP
133.49
ꢃ
/
47.7 Hz)
9.5 Hz)
H-30 (H-32)
C-17 (C-21)
(2JCP
ꢃ/
CH3C6H4S][SCH2CH(NHCOCH3)COO] complex 1.
The isolation of complex 1 indicates that Re(V) is
partially reduced to Re(III) under the reaction condi-
tions, a fact that has been reported in previous studies
[8]. Complex 1 is soluble in CHCl3 and CH2Cl2, slightly
soluble in MeOH, EtOH and insoluble in ether, pentane
and water. It is stable in the solid state and in solution as
indicated by the NMR studies.
The infrared spectrum of complex 1 is free of any IR
band in the n(ReO) region in agreement with the
absence of the ReO core. The PPh3 group shows a P-
sensitive absorption at 1089 cmꢂ1 and a strong band at
697 cmꢂ1. Furthermore, the peaks found at 806, 764
and 1607 cmꢂ1 are indicative of the existence of the
H-19, H-25, H-31 7.21ꢁ
/
7.18 C-23 (C-27)
C-29 (C-33)
H-35 (H-39)
7.38
C-18 (C-20)
127.94
(3JCP
ꢃ/
9.2 Hz)
H-36 (H-38)
H-40
NH
7.20
2.29
6.83
C-24 (C-26)
C-32 (C-30)
C-19, C-25, C-31 128.89
C-34
132.09
129.85
130.07
135.33
21.09
C-35 (C-39)
C-36 (C-38)
C-37
C-40
Numbering of the atoms is according to the ORTEP diagram of Fig.
3.
aromatic thiol, 2,2?-bipyridine and N-acetyl-
respectively.
L-cysteine,
dron is almost parallel to the planar five membered ring
defined by the NÃCÃCÃN chelating atoms of the
bipyridine and the metal ion (5.1 and 5.88 for mol 1
and mol 2, respectively). The NÃCÃCÃN dihedral angle
of 2,2?-bipyridine is very small (2.18 for mol 1 and 3.98
for mol 2). The six membered ring in the coordination
sphere adopts the rarely occurring unstable half chair
conformation with the acentric carbon atom being out
of the best mean plane of the remaining five atoms (0.85
The NMR spectra of complex 1 consisted of sharp
peaks typical of a diamagnetic complex. 1H and 13C
spectra as well as integration of 1H peaks were in
agreement with the assigned structure. 1H and 13C
NMR chemical shifts for 1 in CDCl3 at 25 8C are given
in Table 2. Assignments were based on a series of 1D
/
/
/
/
/
/
and 2D homonuclear and heteronuclear experiments.
Fig. 2 shows part of the Hꢁ1
(COSY) of complex 1.
1
/
H correlation spectrum
˚
˚
A for C2 in mol 1 and 0.74 A for C42 in mol 2). The
angles around the metal within the tetragonal plane of
the octahedron range from 72.5(3) to 104.1(1)8 for mol 1
and from 72.7(4) to 105.0(1)8 for mol 2, whereas those
involving the apical atoms range from 82.2(3) to 95.7(2)8
for mol 1 and from 80.1(3) to 98.7(3)8 for mol 2. As
An ORTEP diagram of 1 is given in Fig. 3 and selected
bond distances and angles are listed in Table 3.
Compound 1 crystallizes in the monoclinic space group
P21 with two independent molecules in the asymmetric
unit, thereafter referred as mol 1 and mol 2. The
coordination geometry around rhenium is distorted
octahedral. The equatorial plane of the octahedron is
defined by the two nitrogen atoms of 2,2?-bipyridine, the
expected, the bite angle of 2,2?-bipyridine (NÃ
the smallest one in the coordination sphere. The ReÃ
ReÃS and ReÃP bond distances are in the ranges
observed for analogous complexes [3,9].
/
ReÃ
/
N) is
/N,
/
/
sulfur of N-acetyl-
aromatic thiol, while the phosphorous and the carbox-
ylate oxygen of N-acetyl- -cysteine occupy the apical
positions. The equatorial plane of the distorted octahe-
L-cysteine and the sulfur of the
In conclusion, reaction of trichlorobis(triphenylphos-
phine)rhenium(V) oxide with 2,2?-bipyridine, p-thiocre-
sol and N-acetyl-L-cysteine in methanol resulted in the
L

D. Papagiannopoulou et al. / Inorganica Chimica Acta 346 (2002) 270ꢁ
/
274
273
Table 3
Selected bond distances (A) and angles (8) for 1
˚
Mol 1
Mol 2
Bond distances
Re(1)Ã
Re(1)Ã
Re(1)Ã
Re(1)Ã
Re(1)Ã
Re(1)Ã
/
O(1)
N(1)
N(2)
S(2)
S(1)
P(1)
2.151(6)
2.189(9)
2.211(9)
2.258(3)
2.266(3)
2.324(3)
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
/
O(4)
N(4)
N(5)
S(4)
S(3)
P(2)
2.154(8)
2.187(9)
2.20(1)
/
/
/
/
/
/
2.262(4)
2.250(3)
2.326(3)
/
/
/
/
Bond angles
O(1)ÃRe(1)Ã
O(1)ÃRe(1)Ã
N(1)ÃRe(1)Ã
O(1)ÃRe(1)Ã
N(1)ÃRe(1)Ã
N(2)ÃRe(1)Ã
O(1)ÃRe(1)Ã
N(1)ÃRe(1)Ã
N(2)ÃRe(1)Ã
S(2)ÃRe(1)Ã
O(1)ÃRe(1)Ã
N(1)ÃRe(1)Ã
N(2)ÃRe(1)Ã
S(2)ÃRe(1)Ã
S(1)ÃRe(1)Ã
/
/
N(1)
83.3(3)
82.2(3)
72.5(3)
95.7(2)
92.2(3)
164.7(3)
89.8(3)
162.8(3)
91.1(2)
104.1(1)(1)
174.7(2)
94.6(3)
92.5(3)
89.3(1)
90.8(1)
O(4)Ã
O(4)Ã
N(4)Ã
O(4)Ã
N(4)Ã
N(5)Ã
O(4)Ã
N(4)Ã
N(5)Ã
S(3)ÃRe(2)Ã
O(4)ÃRe(2)Ã
N(4)ÃRe(2)Ã
N(5)ÃRe(2)Ã
S(4)ÃRe(2)Ã
S(3)ÃRe(2)Ã
/
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
Re(2)Ã
/
N(4)
84.2(3)
80.1(3)
72.7(4)
93.6(2)
91.6(3)
163.5(3)
92.0(2)
163.2(3)
90.5(3)
105.0(1)
177.8(2)
93.8(2)
98.7(3)
87.1(1)
89.8(1)
/
/N(2)
/
/N(5)
/
/
N(2)
/
/
N(5)
/
/S(2)
/
/S(4)
/
/
S(2)
/
/
S(4)
S(4)
/
/
S(2)
/
/
/
/S(1)
/
/S(3)
/
/
S(1)
/
/
S(3)
S(3)
/
/
S(1)
/
/
/
/
S(1)
/
/
S(4)
/
/P(1)
/
/P(2)
/
/
P(1)
/
/
P(2)
P(2)
/
/
P(1)
/
/
/
/
P(1)
/
/
P(2)
P(2)
/
/
P(1)
/
/
the coordination sphere of the metal. This
[P][NN][S][SO] system is a versatile system because of
the coordination of different ligands, able to bear
functional groups, at the metal center and may prove
useful in the development of rhenium(III) and techne-
tium(III) radiopharmaceuticals.
Fig. 2. Part (8.34ꢁ
spectrum of complex 1 in CDCl3 at 25 8C. The numbering of the
protons that appear as separate peaks is noted.
/
6.73 ppm) of the 1Hꢁ1
H correlation NMR
/
4. Supplementary material
Crystallographic data (excluding structure factors)
have been deposited with the Cambridge Crystallo-
graphic Data Centre, CCDC no. 189967 for complex
1. Copies of the data may be obtained free of charge on
application to The Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: ꢀ44-1223-336-033;
/
e-mail: deposit@ccdc.cam.ac.uk or www: http://
www.ccdc.cam.ac.uk).
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a
novel neutral ReIII[PPh3][NN][p-
complex,
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¨
¨