[ReO(N2O2)X] complexes: "4 + 1"?

Article abstract of DOI:10.1021/ic001416g

[ReO(ppme)X] (where ppme(2-) is 2,5-diazo-N,N'-dimethylhexyl-1,6-bis(phenylphosphinate), X = Br0.3Cl0.7) has been synthesized via a substitution reaction and structurally characterized. The coordination geometry is a distorted octahedron and one phosphinate coordinates cis and the other trans to the oxo O atom. This coordination mode is conserved in all [ReOppmeX] complexes synthesized in this study. [ReO(ppme)Cl] has been prepared by a reduction/complexation reaction from [NH4][ReO4]. [ReO(ppme)Cl] reacts with thiocyanate and benzene thiolate forming [ReO(ppme)X] (X = (-)NCS, (-)SC6H5), but the one-pot synthesis of the respective ternary thiolate complexes from perrhenate was not successful. The reduction/complexation reaction of a thiol, H2ppmeCl4, and perrhenate resulted in the formation of [H3ppme][ReO(SR)4], the reaction of which with [ReO(ppme)Cl] does not lead to [ReO(ppme)SR] in high yields.

Full text of DOI:10.1021/ic001416g

Inorg. Chem. 2001, 40, 4623-4626
4623
[ReO(N2O2)X] Complexes: “4 + 1”?
Liang Xu, Mark P. Lowe, Steven J. Rettig, and Chris Orvig*,†
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia,
2036 Main Mall, Vancouver, B.C. V6T 1Z1, Canada
ReceiVed December 18, 2000
[ReO(ppme)X] (where ppme2- is 2,5-diazo-N,N′-dimethylhexyl-1,6-bis(phenylphosphinate), X ) Br0.3Cl0.7) has
been synthesized via a substitution reaction and structurally characterized. The coordination geometry is a distorted
octahedron and one phosphinate coordinates cis and the other trans to the oxo O atom. This coordination mode
is conserved in all [ReOppmeX] complexes synthesized in this study. [ReO(ppme)Cl] has been prepared by a
reduction/complexation reaction from [NH4][ReO4]. [ReO(ppme)Cl] reacts with thiocyanate and benzene thiolate
forming [ReO(ppme)X] (X ) -NCS, -SC6H5), but the one-pot synthesis of the respective ternary thiolate complexes
from perrhenate was not successful. The reduction/complexation reaction of a thiol, H2ppmeCl4, and perrhenate
resulted in the formation of [H3ppme][ReO(SR)4], the reaction of which with [ReO(ppme)Cl] does not lead to
[ReO(ppme)SR] in high yields.
Introduction
instability of Schiff base imine linkages. Also, the O donors in
these ligands are mostly phenolates or enolates, both of which
The resurgence of interest in rhenium chemistry partially
stems from its radiopharmaceutical applications. Rhenium is
similar to technetium, whose radionuclide (99mTc) is the
workhorse of diagnostic nuclear medicine;1-13 also, the radio-
isotopes 186Re and 188Re, which have suitable â-emitting
properties, are being investigated for potential use in therapeutic
nuclear medicine.4,6,8 For example, a 186Re complex with
hydroxyethylidene diphosphonate (HEDP) has been proven to
be beneficial in clinical trials for the palliation of bone pain.4,6,14
Following up on a study of tripodal amine phosphinate ligands
and their complexes with lanthanides and group 13 metals, we
made H4ppmeCl2, an N2O2 donor set amine phosphinate ligand
for ReVdO or TcVdO complexation.15,16 Volumes of data exist
on Re/TcdO complexes with tetradentate N2O2 ligands, but
most studies have been carried out with Schiff base or amine
phenolate/enolate systems.5,17-23 The complexes are usually
hydrolytically sensitive, a factor attributed sometimes to the
bind well under basic conditions. To our knowledge, no N2O2
ligands with carboxylate, phosphonate, or phosphinate O donors,
i.e., those that bind under neutral or acidic conditions, have been
successfully complexed to this MVdO core. Given the hydro-
lytic instability of Tc and ease of oxidation of Re at high pH
(where the phenolates and enolates binds best), the incorporation
of phosphinates should introduce a bias for the ligand to
coordinate in low pH reaction conditions, favorable to both the
reduction of the metal ion and the stability of the complex.
† Tel: 604-822-4449. Fax: 604-822-2847. E-mail: orvig@chem.ubc.ca.
(1) Clarke, M.; Podbielski, L. Coord. Chem. ReV. 1987, 78, 253.
(2) Deutsch, E.; Libson, K.; Jurisson, S.; Lindoy, L. F. Prog. Inorg. Chem.
1983, 30, 75.
We are also interested in ternary complexes. Dianionic N2O2
ligands usually complex MVdO with an additional alcoholate,
halide, or bridging oxo ligand, forming overall neutral
complexes.5,17-23 In light of a series of successful “3 + 1”
complexes, in which a monodentate thiolate, bearing a receptor
moiety, complements a tridentate NS2 or S3 donor set ligand,7,24-27
we discuss here the potential of N2O2 donors to form “4 + 1”
(3) Jurisson, S.; Desilets, C. P.; Jia, W.; Ma, D. Chem. ReV. 1993, 93,
1137.
(4) Dilworth, J. R.; Parrott, S. J. Chem. Soc. ReV. 1998, 27, 43.
(5) Tisato, F.; Refosco, F.; Bandoli, G. Coord. Chem. ReV. 1994, 135,
235.
(6) Volkert, W. A.; Hoffman, T. J. Chem. ReV. 1999, 99, 2269.
(7) Jurisson, S. S.; Lydon, J. D. Chem. ReV. 1999, 99, 2205.
(8) Heeg, M. J.; Jurisson, S. S. Acc. Chem. Res. 1999, 32, 1053.
(9) Liu, S.; Edwards, D. S. Chem. ReV. 1999, 99, 2235.
(10) Lister-James, J.; Moyer, B. R.; Dean, R. T. Q. J. Nucl. Med. 1996,
40, 221.
(17) Middleton, A. R.; Masters, A. F.; Wilkinson, G. J. Chem. Soc., Dalton
Trans. 1979, 542.
(11) Okarvi, S. M. Nucl. Med. Commun. 1999, 20, 1093.
(12) Ercan, M. T.; Kostakoglu, L. Current Pharma. Des. 2000, 6, 1159.
(13) Boerman, O. C.; Oyen, W. J. C.; Corstens, F. H. M. Semin. Nucl.
Med. 2000, 30, 195.
(14) Deklerk, J. M. H.; Vanhetschip, A. D.; Zonnenberg, B. A.; Vandijk,
A.; Quirijnen, J. M. S. P.; Blijham, G. H.; Vanrijk, P. P. J. Nucl.
Med. 1996, 37, 244.
(18) Jurisson, S.; Lindoy, L. F.; Dancey, K. P.; McPartlin, M.; Tasker, P.
A.; Uppal, D. K.; Deutsch, E. Inorg. Chem. 1984, 23, 227.
(19) Bandoli, G.; Nicolini, M.; Mazzi, U.; Refosco, F. J. Chem. Soc., Dalton
Trans. 1984, 2505.
(20) Banbery, H. J.; McQuillan, F.; Hamor, T. A.; Jones, C. J.; McCleverty,
J. A. J. Chem. Soc., Dalton Trans. 1989, 1405.
(21) Luo, H.; Liu, S.; Rettig, S. J.; Orvig, C. Can J. Chem. 1995, 73, 2272.
(22) Herrmann, W. A.; Rauch, M. U.; Artus, R. J. Inorg. Chem. 1996, 35,
1988.
(15) Lowe, M. P.; Rettig, S. J.; Orvig, C. J. Am. Chem. Soc. 1996, 118,
10446.
(16) Lowe, M. P.; Caravan, P.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1998,
37, 1637.
(23) van Bommel, K. J. C.; Verboom, W.; Kooijman, H.; Spek, A. L.;
Reinhoudt, D. N. Inorg. Chem. 1998, 37, 4197.
10.1021/ic001416g CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/26/2001

4624 Inorganic Chemistry, Vol. 40, No. 18, 2001
Xu et al.
84 (two peaks, ∆δ ) 0.3), 38 (two peaks, ∆δ ) 0.5). A microcrystalline
material precipitated when diethyl ether diffused into an ethanolic
solution of the product. Single crystals precipitated from a CD3CN
solution made of the crystalline material.
complexes with monodentate thiolates. A known problem in
the “3 + 1” complexes is that the monodentate thiolate is easily
demetalated by endogenous thiolate ligands (e.g., glutathione)
and a tetradentate co-ligand could potentially make a complex
which has a saturated coordination sphere, therefore slowing
the unwanted substitution reaction.
[ReO(ppme)Cl]‚H2O. To a hot methanolic solution (10 mL) of H4-
ppmeCl2 (142 mg, 0.300 mmol) and [NH4][ReO4] (157 mg, 0.586
mmol) was added triphenylphosphine (90 mg, 0.34 mmol). The mixture
was heated for 20 h at 70 °C to yield a blue solution and a small amount
of precipitate. The solution was decanted, concentrated, and dried under
vacuum. The resultant blue residue was suspended in acetone, and the
suspension was filtered. Diethyl ether was added liberally to the filtrate
to precipitate the blue product, which was filtered out and dried to
yield 180 mg (91.6%). A crystalline material formed on slow evapora-
tion of an acetone/water solution of the product. Anal. Calcd (Found)
for C18H26ClN2O5P2Re: C, 33.26 (33.03); H, 4.03 (3.98); N, 4.31 (4.03).
IR (cm-1, KBr disk): 1206, 1199, 1124, 949, 931. Mass spectrum
(LSIMS): m/z 633 ([ReO(ppme)Cl + H]+), 597 ([ReO(ppme)]+). 31P-
{1H} NMR (acetone-d6): 84, 38. HPLC: peak maximum at 1.2 min.
[ReO(ppme)NCS]‚CH3OH. To a methanolic solution (3 mL) of
[ReO(ppme)Cl]‚H2O (65 mg, 0.10 mmol) was added KSCN (11 mg,
0.11 mmol), resulting in immediate precipitation of a white salt. The
supernatant was decanted and was allowed to stand at room temperature
for 2 days upon which time more white precipitate was formed and
subsequently filtered out. The filtrate was concentrated and dried. The
isolated yield was very low (<10 mg). Anal. Calcd (Found) for
C20H28N3O6P2ReS: C, 34.98 (35.30); H, 4.11 (4.00); N, 6.12 (5.73).
IR (cm-1, KBr disk): 2060, 1206, 1123, 945, 923. Mass spectrum
(LSIMS): m/z 656 ([M + H]+), 597 ([M - NCS]+). 31P{1H} (acetone-
d6) NMR δ: 79, 38. HPLC: peak maximum at 2.0 min.
[ReO(ppme)(SC6H5)]. Method A. [ReO(ppme)Cl]‚H2O (23 mg,
0.035 mmol) was dissolved in 1 mL of acetone-d6, and KSC6H5 (8
mg, 0.05 mmol) was added but was not soluble. The mixture was heated
at 70 °C for 40 h, during which time a white precipitate slowly formed.
The supernatant was decanted and the 31P NMR spectrum recorded.
Method B. ReO(ppme)Cl‚H2O (63 mg, 0.10 mmol) and [H3ppme]-
[ReO(SC6H5)4] (same preparation as [H3ppme][ReO(SC6H5OCH3)4]‚
2H2O, 20 mg, 0.019 mmol) were dissolved in 2 mL of CD3CN with a
few drops of D2O. The mixture was heated at 70 °C for 40 h, upon
which time ReO(ppme)(SC6H5), ReO(ppme)Cl, and [H3ppme][ReO-
(SC6H5)4] were seen in the 31P and 1H NMR spectra. More [H3ppme]-
[ReO(SC6H5)4] (a total of 48 mg, 0.046 mmol) was added in two
portions, each followed by 20 h of heating. More D2O was added,
resulting in the formation of a black oily precipitate which was allowed
to settle. The supernatant was decanted and more D2O was added in
order to precipitate the brown product. The solvent was further reduced
by rotary evaporation and was decanted off. The brown product was
dried under vacuum. The isolated yield was low (<10 mg). Anal. Calcd
(Found) for C24H29N2O5P2ReS: C, 40.85 (40.71); H, 4.14 (4.19); N,
3.97 (4.20). IR (cm-1, KBr disk): 1200 (νPO), 1126(νPO), 952, 930.
Mass spectrum (LSIMS): m/z 1473 ([2M + H]+), 707 ([M + H]+),
597 ([M - C6H5S]+). 31P{1H} NMR (CD3CN) δ: 74, 34. HPLC: peak
maximum at 2.3 min.
Experimental Section
Materials. N,N′-Dimethylethylenediamine, phenylphosphinic acid,
30% formaldehyde, 37% HCl, potassium thiocyanate, benzenethiol,
4-methoxythiophenol, lipophilic Sephadex LH-20, and tetrabutyl-
ammonium bromide were obtained from Aldrich, Alfa, Fisher, or Sigma
and used without further purification. [NH4][ReO4] was received as a
gift from Johnson-Matthey. [(C4H9)4N][ReOBr4]28 and ReO(P(C6H5)3)2-
29
Cl3 were synthesized by literature methods.
Instrumentation. IR (infrared) spectra were recorded as KBr disks
in the range 4000-500 cm-1 on a Mattson Galaxy Series 5000 FTIR
spectrophotometer. Mass spectra (Cs+, LSIMS (liquid secondary ion
mass spectrometry)) were obtained on a Kratos Concept II H32Q with
1
thioglycerol as the matrix. All H NMR spectra were recorded on a
Bruker AC-200E spectrometer at 200 MHz and are reported as δ in
ppm downfield from TMS. All 31P{1H} NMR spectra were recorded
on the same instrument at 81 MHz and are reported as δ in ppm
downfield from external phosphoric acid.
HPLC. Experiments were performed with Waters 501 HPLC pumps,
a Waters U6K injector, and a Waters Lambda-Max model 481 LC
spectrophotometer, all interfaced to a PC. A Hamilton PRP-1 reverse
phase column (15 cm) was used; all runs were isocratic using 50/50
acetonitrile/water as the eluent at a flow rate of 1.0 mL/min. Gradient
experiments were performed but no extra peaks were found. After some
of the experiments, acetonitrile or methanol was used to elute the
column but no extra species were detected in 40 min. The experiments
were performed with the detector set at 350, 475, 600, and 698 nm for
each sample.
H4ppmeCl2. Phenylphosphinic acid (3.5 g, 25 mmol) and N,N′-
dimethylethylenediamine (1.0 g, 11 mmol) were dissolved in 6 M HCl
(40 mL). The solution was heated to reflux, and 37% formaldehyde
(4.9 g, 57 mmol) was added dropwise over 20 min. The solution was
refluxed for 4.5 h and then concentrated to yield a white solid, which
was dissolved in methanol (200 mL), and diethyl ether (100 mL) was
added to precipitate the white product. The yield was quantitative. Anal.
Calcd (Found) for C18H28Cl2N2O4P2: C, 46.07 (46.27); H, 6.01 (6.24);
N, 5.97 (5.86). Mass spectrum (LSIMS): m/z 397 ([H3ppme]+). 31P-
{1H} NMR (D2O) δ: 19 (s). 1H NMR (D2O) δ: 7.8-7.4 (10 H, 2 sets
of multiplets, PC6H5), 3.7 (4 H, s, ethylene), 3.5 (4 H, d, NCH2P), 2.9
(6 H, s, NCH3).
[ReO(ppme)X], X ) Br0.3/Cl0.7. To a stirred ethanolic solution (10
mL) of H4ppmeCl2 (62 mg, 0.13 mmol) was added [N(C4H9)4][ReOBr4]
(100 mg, 0.13 mmol) dissolved in 10 mL of ethanol. A gray precipitate
formed immediately but redissolved when triethylamine (63 mg, 0.63
mmol) was added dropwise. The blue solution was refluxed for 2 h
and was concentrated. The concentrated solution was loaded onto a
Sephadex LH-20 column and eluted with ethanol. The blue fraction
was collected, concentrated, and dried under vacuum to yield 59 mg
(∼ 70%). Mass spectrum (LSIMS): m/z 699 ([ReO(ppme)Br + Na]+),
677 ([ReO(ppme)Br + H]+), 655 ([ReO(ppme)Cl + Na]+), 633 ([ReO-
(ppme)Cl + H]+), 597 ([ReO(ppme)]+). 31P{1H} NMR (CD3CN) δ:
[H3ppme][ReO(SC6H4OCH3)4]‚2H2O. To a solution of H4ppmeCl2
(94 mg, 0.20 mmol) and [NH4][ReO4] (54 mg, 0.20 mmol) in 5 mL of
methanol was added HSC6H4OCH3 (180 mg, 1.29 mmol). The solution
immediately turned dark brown and a red/brown microcrystalline
material precipitated soon afterward. After a few hours, the crystals
were filtered out, washed with methanol, and dried under vacuum to
yield (199 mg, 86%). Anal. Calcd (Found) for C46H59N2O11P2ReS4:
C, 46.34 (46.59); H, 4.99 (4.85); N, 2.35(2.35). IR (cm-1, KBr disk):
1
1589, 1174 (νPO), 959 (νReO). 31P{1H} NMR (DMSO-d6) δ: 25. H
(24) Papadopoulos, M. S.; Pirmettis, I. C.; Pelecanou, M.; Raptopoulou,
C. P.; Terzis, A.; Stassinopoulou, C. I.; Chiotellis, E. Inorg. Chem.
1996, 35, 7377, and references therein.
(25) Nock, B. A.; Maina, T.; Yannoukakos, D.; Pirmettis, I. C.; Papa-
dopoulos, M. S.; Chiotellis, E. J. Med. Chem. 1999, 42, 1066, and
references therein.
(26) Syhre, R.; Seifert, S.; Spies, H.; Gupta, B.; Johannsen, B. Eur. J. Nucl.
Med. 1998, 25, 793.
(27) Meegalla, S.; Plo¨ssl, K.; Kung, M.-P.; Stevenson, D. A.; Liable-Sands,
L. M.; Rheingold, A. I.; Kung, H. F. J. Am. Chem. Soc. 1995, 117,
1137.
NMR (DMSO-d6) δ: 7.9-7.4 (10 H, 2 sets of multiplets, PC6H5), 7.4
and 6.9 (8 H each, 2 sets of doublets, SC6H4O), 3.8 (12 H, s, OCH3),
3.6-3.4 (8 H, overlapped methylene H), 2.7 (6 H, s, NCH3).
[ReO(ppme)(SC6H4OCH3)]. Same as method B for [ReO(ppme)-
(SC6H5)], and [ReO(SC6H4OCH3)4][H3ppme] (a total of 54 mg, 0.046
mmol, in 4 portions) was used. Anal. Calcd (Found) for C25H31N2O6P2-
ReS: C, 40.81 (40.91); H, 4.25 (4.49); N, 3.81(3.50). IR (cm-1, KBr
disk): 1198 (νPO), 1122 (νPO), 950, 930. Mass spectrum (LSIMS): m/z
1473 ([2M + H]+), 737 ([M + H]+), 597 ([M - C7H7OS]+). 31P{1H}
NMR (acetone-d6) δ: 80, 38. HPLC: peak maximum at 2.3 min.
(28) Cotton, F. A.; Lippard, S. J. Inorg. Chem. 1966, 5, 9.
(29) Chatt, J.; Rowe, G. A. J. Chem. Soc. 1962, 4019.

[ReO(N2O2)X] Complexes: “4 + 1”?
Inorganic Chemistry, Vol. 40, No. 18, 2001 4625
Table 1. Selected Crystallographic Data for [ReO(ppme)X] X )
a
Br0.29/Cl0.71
formula
fw
cryst syst
space group
A, Å
C18H24Br0.29Cl0.71N2O5P2Re
644.90
tetragonal
P41
12.898(1)
C, Å
13.456(2)
2238.4(5)
V, Å3
Z
F
4
calc, g/cm3
1.913
1252.88
F(000)
T, °C
21.0
radiation
Mo KR (λ ) 0.710 69 Å)
62.09
0.653-1.000
65.0°
4517
4207
2489
272
µ, cm-1
Figure 1. ORTEP drawing of ReO(ppme)(Br0.3Cl0.7). Thermal el-
lipsoids for the non-hydrogen atoms are drawn at the 33% probability
level.
transmission factors
2θmax
total reflections
unique reflections
reflections with I > 3σ(I)
no. of variables
R; Rw
Table 2. Selected Bond Lengths (Å) and Angles (deg) in
[ReO(ppme)X] X ) Br0.29/Cl0.71
Re-O(5)
Re-N(1)
Re-N(2)
Re-O(3)
Re-O(1)
Re-Br/Cl
1.666(6)
2.187(7)
2.139(6)
1.995(6)
2.031(5)
2.48(1)/2.38(1)
0.032; 0.026
a R ) ∑||Fo| - |Fc||/∑|Fo|, I > 3σ(I); Rw ) (∑w(|Fo| - |Fc|)2/
∑w(Fo ))1/2
.
2
X-ray Crystallographic Analysis. A blue prismatic crystal of [ReO-
(ppme)Br0.29Cl0.71] was mounted on a glass fiber for data collection on
a Rigaku AFC6S diffractometer at 21 °C (Table 1). The data were
collected using the ω-2θ scan technique to a maximum 2θ value of
65° and were corrected for Lorentz and polarization effects. A correction
for secondary extinction was applied (coefficient ) 3.78(10) × 10-7).
The structure was solved by heavy-atom Patterson methods30 and
expanded using Fourier techniques.31 The halide position was occupied
by Cl or Br. The halides were resolved, and the population parameter
of the most abundant (Cl) was refined. The non-hydrogen atoms were
refined anisotropically, and the hydrogen atoms were fixed in calculated
positions with the C-H ) 0.98 Å.
Br/Cl-Re-O(5)
N(1)-Re-O(5)
N(2)-Re-O(5)
O(3)-Re-O(5)
O(1)-Re-O(5)
N(1)-Re-N(2)
N(1)-Re-O(3)
N(1)-Re-O(1)
N(1)-Re-Br/Cl
N(2)-Re-O(1)
N(2)-Re-O(3)
96.0(4)/96.2(4)
88.8(3)
92.1(3)
109.1(3)
166.5(3)
83.3(3)
159.7(2)
78.3(2)
97.2(5)/98.9(4)
82.6(2)
86.6(2)
phine impeded the substitution reaction because ReO(P(C6H5)3)2-
Cl3 was formed and remained intact for days in the reaction
mixture. Similarly, ReO(P(C6H5)3)2Cl3 did not react with ppme
in a simple substitution fashion.
Results and Discussion
Under anhydrous conditions and in the presence of a base,
H4ppmeCl2 reacts with [(C4H9)4N][ReOBr4] to form [ReO-
(ppme)X] (X ) Br/Cl), a blue mixture of halide complexes
which are difficult to separate. In contrast, ammonium perrhe-
nate can be reduced with triphenylphosphine in the presence of
the ligand to form [ReO(ppme)Cl] in a vial and in high yield.
Elemental analysis of the blue crystalline material agrees with
its formulation, LSIMS shows [M + H]+ and [M - Cl]+ peaks,
and the IR spectrum shows prominent PO peaks as well as two
possible νRedO at 931 and 949 cm-1 (identification of the Red
O peak was not attempted). The 31P NMR spectrum exhibits
two resonances at 84 and 38 ppm, indicating a drastic difference
in the coordinating phosphinates: one cis and the other trans
Single crystals of ReO(ppme)X (X ) Br/Cl) precipitated from
a CD3CN solution of the complex mixture, and the X-ray
crystallographic analysis confirmed the structure proposed based
on NMR results (Figure 1 and Table 2). The Re center is
coordinated by the N2O2 ligand and oxo O and halide atoms,
forming a distorted octahedron. The halide atom is coordinated
cis to the oxo atom, and the two N-methyl groups are syn to
the oxo O atom. The cis coordination of the halide atom to the
oxo atom is common, and to our knowledge, it is the only mode
of coordination in ReO(N2O2)Cl complexes.22,23 The distortion,
where the ligand coordinating sites squeeze toward each other
and bend away from the oxo O, is also typical of a ReO(N2O2)X
complex. The RedO bond is 1.666 Å and is at the short end of
the reported values; the Re-N, Re-O, and Re-Cl bond lengths
are within the expected ranges.20,22,23,32,33
Unlike a few other ReO(N2O2) complexes, in which coordi-
nation modes vary and a few diasteromers persist, one ReO-
(ppme)X diastereomer forms preferentially. Also, the halide
position is not labile: simple solvolysis of the halide in CD3-
OD or D2O was not seen (by 31P NMR spectroscopy) even over
a day or two. (The complex, however, decomposes in a heated
CD3OD/D2O mixture over a few weeks.) These features suggest
an excellent opportunity for conjugating the [ReO(ppme)]+ unit
1
to the oxo O atom (vide infra). Correspondingly, the H NMR
spectrum shows that (1) the molecule is asymmetric, (2) the
two sides of the ligand are in markedly different chemical
environments, and (3) the molecule is rigid at room temperature.
The reduction/complexation reaction is interesting. In a 1:1:1
methanolic mixture of [NH4][ReO4], triphenylphosphine, and
H4ppmeCl2, [ReO(ppme)Cl] formed almost exclusively (as
detected by 31P NMR spectroscopy). Triphenylphosphine oxide
and a very small amount of triphenylphosphine-related com-
plexes were also formed. The presence of excess triphenylphos-
(30) PATTY; The DIRDIF program system, Technical Report of the
Crystallography Laboratory, University of Nijmegen, The Netherlands,
1992.
(32) Gilli, G.; Sacerdoti, M.; Bertolasi, V.; Rossi, R. Acta Crystallogr. 1982,
(31) DIRDIF94; The DIRDIF-94 program system, Technical Report of the
Crystallography Laboratory, University of Nijmegen, The Netherlands,
1994.
B38, 100.
(33) Luo, H.; Setyawati, I.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1995, 34,
2287.

4626 Inorganic Chemistry, Vol. 40, No. 18, 2001
Xu et al.
to a monodentate ligand through a halide substitution reaction.
Following the success of the aforementioned series of “3 + 1”
complexes,7,24-27 we probed [ReO(ppme)]+ as a potential “4
+ 1” system.
very stable. Aside from the minor misfortune that ppme2- does
not coordinate to the metal, this material is interesting.
[ReO(SR)4]- complexes have been studied extensively, but to
our knowledge, one-pot syntheses from perrhenate have not been
reported.35,36 Recently, thiols conjugated to a biologically active
molecule (BAM) have been fixed onto solid supports and then
reacted with Tc precursors to form Tc-thiolate-BAM conju-
gates in solution, so that no free BAM was actually present in
solution.37,38 This approach reduced competition of free BAM
binding to the receptor. In light of this development and because
[H3ppme][ReO(SR)4] has little solubility in water or alcohol, it
could be used as a solid thiol source in forming ternary
complexes.
Reactions of ReO(ppme)Cl with [H3ppme][ReO(SR)4], how-
ever, are slow. Biphasic reaction of solid [H3ppme][ReO(SR)4]
and [ReO(ppme)Cl] in methanol produces little [ReO(ppme)-
(SR)] even after 2 days at 70 °C; also, when both starting
materials were dissolved in acetonitrile the formation of [ReO-
(ppme)(SR)] took days of heating. When the reaction was
monitored by 31P NMR, the coexistence of [ReO(SR)4]-, ReO-
(ppme)(SR), and [ReO(ppme)Cl] was evident, and the ratio of
the species changed when more [ReO(SR)4]- was added. Thus,
[ReO(SR)4]- and [ReO(ppme)Cl] species exist in equilibrium
with [ReO(ppme)SR] and some side product, and the equilib-
rium does not lie heavily toward the formation of the ternary
thiolate complexes. This equilibrium precludes the actual use
of “4 + 1” complexes in nuclear medicine.
ReO(ppme)Cl reacts with KSCN or KSC6H5 to form [ReO-
(ppme)(NCS)] or [ReO(ppme)(SC6H5)], respectively. [ReO-
(ppme)(SC6H4OCH3)] was also made but from a different route
(vide infra). The products were characterized by LSIMS and
IR and 31P NMR spectra. Their purities were checked by
elemental analysis and HPLC. The IR spectra of all the [ReO-
(ppme)X] complexes are similar. Diagnostic νPO and νRedO
stretches are evident in every complex, but vary slightly in
frequency. Additional ligand peaks are seen for the respective
coligand. The NCS- is likely to be N-bound in [ReO(ppme)-
NCS] based on analogous νCN values.34 (The CN stretching
frequencies in N-bonded complexes are near 2050 cm-1 and
that in S-bonded complexes are near 2100 cm-1, but CN
stretching alone is not definitive evidence in such determina-
tion.34) The (+)LSIMS spectra of all the ReO(ppme)X com-
plexes invariably exhibit prominent [M + H]+ and [M - X]+
peaks. The 31P NMR spectra show two peaks at ∼80 and ∼35
ppm, and the 1H NMR spectra display similar resonances
resulting from the ppme backbone. These features demonstrate
that the complexes share the same structure with respect to ReO-
(ppme) and only differ in X coordination. These complexes also
have similar solubilities in water and organic or mixed solvents.
Related to this, HPLC experiments show that these complexes
are similarly retained on a reverse phase column.
31P NMR experiments following these reactions suggested
that the substitutions were reasonably simple and that only the
products and the free ligand (ppme) were found in the mixture.
The free ligand formation can be explained by decomposition
of the complex and/or failure of ppme2- to compete with the
thiol. This demetalation of ppme2- is ominous in a one-pot
synthesis of the ternary complexes. In a radiopharmaceutical
“kit” formulation where perrhenate (or pertechnetate) would be
reduced with both of the ligands in excess, formation of ternary
complexes would require the ligands to complement, rather than
to compete with, each other.
Conclusions
[ReO(ppme)Cl] has been synthesized and a [ReO(ppme)X]
(X ) Br0.3Cl0.7) sample has been structurally characterized.
Substitution of X with thiocyanate and aromatic thiolates was
successful, but the one-pot synthesis of the respective ternary
thiolate complexes was not. Reduction/complexation reaction
of thiol, H2ppmeCl4, and perrhenate resulted in the formation
of [H3ppme][ReO(SR)4], the reaction of which with ReO(ppme)-
Cl does not lead to [ReO(ppme)SR] in high yields.
Acknowledgment. The authors gratefully acknowledge
DuPont Pharmaceuticals for its support, the Natural Sciences
and Engineering Research Council for operating grants, and Mr.
Peter Borda for elemental analysis.
An attempted one-pot synthesis of the ternary complex [ReO-
(ppme)SR] resulted in the formation of [H3ppme][ReO(SR)4]
(-SR ) -SC6H4OCH3). [NH4][ReO4] reacts rapidly with excess
HSR in the presence of H4ppmeCl in methanol, and the red
crystalline tetrathiolate complex precipitated in high yields. The
immediate questions raised are whether the formation of the
unwanted product is driven by its insoluble nature and whether
it can be converted to the desired ternary complex. [H3ppme]-
[ReO(SR)4] was dissolved in CD3CN and heated or left in the
open air for a few days, but it did not convert to the “4 + 1”
complex, even after addition of KOH. Thus, this complex is
Supporting Information Available: X-ray crystallographic files
in CIF format for structure [ReO(ppme)X] (X ) Br0.3Cl0.7). This
material is available free of charge via the Internet at http://pubs.acs.org.
IC001416G
(35) McDonell, A. C.; Hambley, T. W.; Snow, M. R.; Wedd, A. G. Aust.
J. Chem. 1983, 36, 253.
(36) Dilworth, J. R.; Hu, J.; Miller, J. R.; Hughes, D. L.; Zubieta, J. A.;
Chen, Q. J. Chem. Soc., Dalton Trans. 1995, 3153.
(37) Pollak, A.; Roe, D. G.; Pollock, C. M.; Lu, L. F. L.; Thornback, J. R.
J. Am. Chem. Soc. 1999, 121, 11593.
(34) Nakamoto, K. Infrared and Raman Spectra of Inorganic Coordination
Compounds; John Wiley & Sons: New York, 1986.
(38) Dunn-Dufault, R.; Pollak, A.; Thornback, J. R.; Ballinger, J. R.
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