Technetium and rhenium in five-coordinate symmetrical and dissymmetrical nitrido complexes with alkyl phosphino-thiol ligands. Synthesis and structural characterization

Article abstract of DOI:10.1021/ic801436d

The reactivity of bulky alkylphosphino-thiol ligands (PSH) toward nitride-M(V, VI) (M = Tc/Re) precursors was investigated. Neutral five-coordinate monosubstituted complexes of the type [M(N)(PS)CI(PPh ₃)] (Tc1-4, Re1-2) were prepared in moderate to high yields. It was found that these [M(N)(PS)Cl(PPh₃)] species underwent ligand-exchange reactions under mild conditions when reacted with bidentate mononegative ligands having soft donor atoms such as dithiocarbamates (NaLⁿ) to afford stable dissymmetrical mixed-substituted complexes of the type [M(N)(PS)(Lⁿ)] (Tc5,8-10, Re5-9) containing two different bidentate chelating ligands bound to the [M≡N]²⁺ moiety. In these reactions, the dithiocarbamate replaced the two labile monodentate ligands (Cl and PPh₃) leaving the [M(N)(PS)]⁺ building block intact. In the above reactions, technetium and rhenium were found to behave in a similar way. Instead, under more drastic conditions, reactions of PSH with [M(N)Cl ₂(PPh₃)₂] gave a mixture of monosubstituted [M(N)(PS)Cl(PPh₃)] and bis-substituted species [M(N)(PS)₂] (Tc11-14) in the case of technetium, whereas only monosubstituted [M(N)(PS)Cl(PPh₃)] complexes were recovered for rhenium. All isolated products were characterized by elemental analysis, IR and multinuclear ( ¹H, ¹³C, and ³¹P) NMR spectroscopies, ESI MS spectrometry, and X-ray crystal structure determination of the representative monosubstituted [Tc(N)(PStbu)Cl(PPh₃)] (Tc4) and mixed-substituted [Re(N)(PScy)(L³)] (Re7) and [Re(N)(PSiso)(L⁴)] (Re9) complexes. The latter rhenium complexes represent the first example of a square-pyramidal nitrido Re species with the basal plane defined by a PS ₃ donor set. Monosubstituted [M(N)(PS)Cl(PPh₃)] species bearing the substitution-inert [M(N)(PS)]⁺ moieties act as suitable building blocks proposed for the construction of new classes of dissymmetrical nitrido compounds with potential application in the development of essential and target specific ^99mTc and ¹⁸⁸Re radiopharmaceuticals for imaging and therapy, respectively.

Full text of DOI:10.1021/ic801436d

Inorg. Chem. 2008, 47, 11972-11983
Technetium and Rhenium in Five-Coordinate Symmetrical and
Dissymmetrical Nitrido Complexes with Alkyl Phosphino-thiol Ligands.
Synthesis and Structural Characterization
Cristina Bolzati,*,† Mario Cavazza-Ceccato,‡ Stefania Agostini,‡ Francesco Tisato,†
and Giuliano Bandoli‡
ICIS - CNR, Corso Stati Uniti, 4, 35127 PadoVa, Italy, and Department of Pharmaceutical
Sciences, UniVersity of Padua, Via Marzolo, 5, 35131 PadoVa, Italy
Received July 31, 2008
The reactivity of bulky alkylphosphino-thiol ligands (PSH) toward nitride-M(V, VI) (M ) Tc/Re) precursors was
investigated. Neutral five-coordinate monosubstituted complexes of the type [M(N)(PS)Cl(PPh3)] (Tc1-4, Re1-2)
were prepared in moderate to high yields. It was found that these [M(N)(PS)Cl(PPh3)] species underwent ligand-
exchange reactions under mild conditions when reacted with bidentate mononegative ligands having soft donor
atoms such as dithiocarbamates (NaLn) to afford stable dissymmetrical mixed-substituted complexes of the type
[M(N)(PS)(Ln)] (Tc5,8-10, Re5-9) containing two different bidentate chelating ligands bound to the [Mt N]2+
moiety. In these reactions, the dithiocarbamate replaced the two labile monodentate ligands (Cl and PPh3) leaving
the [M(N)(PS)]+ building block intact. In the above reactions, technetium and rhenium were found to behave in a
similar way. Instead, under more drastic conditions, reactions of PSH with [M(N)Cl2(PPh3)2] gave a mixture of
monosubstituted [M(N)(PS)Cl(PPh3)] and bis-substituted species [M(N)(PS)2] (Tc11-14) in the case of technetium,
whereas only monosubstituted [M(N)(PS)Cl(PPh3)] complexes were recovered for rhenium. All isolated products
were characterized by elemental analysis, IR and multinuclear (1H, 13C, and 31P) NMR spectroscopies, ESI MS
spectrometry, and X-ray crystal structure determination of the representative monosubstituted [Tc(N)(PStbu)Cl(PPh3)]
(Tc4) and mixed-substituted [Re(N)(PScy)(L3)] (Re7) and [Re(N)(PSiso)(L4)] (Re9) complexes. The latter rhenium
complexes represent the first example of a square-pyramidal nitrido Re species with the basal plane defined by a
PS3 donor set. Monosubstituted [M(N)(PS)Cl(PPh3)] species bearing the substitution-inert [M(N)(PS)]+ moieties act
as suitable building blocks proposed for the construction of new classes of dissymmetrical nitrido compounds with
potential application in the development of essential and target specific 99mTc and 188Re radiopharmaceuticals for
imaging and therapy, respectively.
Introduction
modalities, in particular of positron emission tomography
(PET) techniques.1 Positron-emitting radionuclides currently
have an advantage over single-photon-emitting radionuclides
in the resolution of the human image, but in the small-animal
imaging field, single-photon emission computed tomography
(SPECT) is becoming increasingly competitive with PET by
exhibiting higher resolution and comparable sensitivity.2-4
Despite the introduction of efficient new technologies
based on Tc chemistry (Tc-HYNIC, [Tc(CO)3]+, and [Tc-
(N)(PNP)]2+), there is an apparent stagnation in introducing
novel 99mTc radiopharmaceuticals due to scientific and
economic factors, such as the difficulties in designing Tc-
labeled biologically active compounds, the high cost of
development, the limited return on the investment, and the
increasing performance and competition of other imaging
(1) Eckelman, W. C.; Erba, P. A.; Schwaiger, M.; Wagner, H. N. J.;
Alberto, R.; Mazzi, U. J. Nucl. Med. Biol. 2007, 34, 1–4.
(2) Levin, C. S. Eur. J. Nucl. Med. Mol. Imaging 2005, 32, S325–S345.
(3) Mahmood, A.; Limpa-Amara, N.; MacKenzie, J. D.; Zimmerman,
R. E.; El Fakhri, G.; Moore, S. C.; Jones, A. G. In Proceedings of the
SeVenth International Symposium on Technetium in Chemistry and
Nuclear Medicine. Mazzi U, Ed.; 7 Servizi Grafici Editoriali snc:
Padova, Italy, 2006; 465-470.
* To whom correspondence should be addressed. Phone: +39 049
8275352. Fax: +39 049 8275366. E-mail: bolzati@icis.cnr.it.
†
ICIS - CNR.
University of Padua.
‡
11972 Inorganic Chemistry, Vol. 47, No. 24, 2008
10.1021/ic801436d CCC: $40.75  2008 American Chemical Society
Published on Web 11/13/2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
In addition, the ability to monitor two emission energies and,
therefore, two radiopharmaceuticals simultaneously give
SPECT another advantage. It appears that, for human studies,
SPECT will be following this trend in instrumentation as
well, and thus, 99mTc should be competitive in all situations
as long as the biological half-life of the targeted molecule is
consistent with the physical half-life of 99mTc.
An analysis of the recent literature shows that the number
of papers focusing on in vivo evaluation by using small-
animal SPECT of new 99mTc-based compounds has increased
reflecting a renewed interest in the research of SPECT
compounds.5
Considering the 99mTc radiopharmaceuticals scenario, at
present it appears that the commercially available 99mTc
tracers, used in routine clinical practice as myocardial or
brain perfusion imaging agents, are far from ideal, while the
introduction in the clinical field of receptor-specific radiop-
harmaceuticals still remains in infancy. Hence, efforts
addressed to devise new strategies useful to find more
efficient 99mTc perfusion and new receptor imaging agents
continue.
In past years, the chemistry of potential 99mTc radiophar-
maceuticals has been expanded due to the introduction of
an efficient method for the production, at tracer level, of
99mTc species containing the terminal Tct N multiple bond,
in sterile and pyrogen-free conditions. It was found that the
resulting [Tct N]2+ core could be viewed as a true inorganic
functional group exhibiting very high stability under a wide
range of experimental conditions.6 Based on these consid-
erations, extensive studies have been carried out on the
synthesis and biological evaluation of different classes of
symmetrical and dissymmetrical five-coordinate nitrido tech-
profiles in rats of some of these different compounds
displayed promising biological properties.9 In particular, the
monocationic [99mTc(N)(DBODC)(PNP5)]+ complex [DBODC
) bis-(N-ethoxyethyl)dithiocarbamato; PNP5 ) bis-N,N-
(dimethoxypropylphosphinoethyl)ethoxyethylamine] showed
high and persistent myocardial uptake with favorable target-
to-not-target ratios, and it is currently under investigation
as potential myocardial imaging agent.10
Over the past few years, we reported an extensive study
on the reactivity of different bidentate mixed phosphino-
thiol (R2PSH) ligands (R ) phenyl, tolyl, cyclohexyl) toward
both pertechnetate and prereduced technetium compounds
such as oxo-Tc(V) and nitride-Tc(V/VI) precursors.7,11 Reaction
of [Tc(N)Cl2(PPh3)2] with the bulky 2-(dicyclohexylphos-
phino)-ethanethiol (PScyH) ligand afforded a rare example
of monosubstituted species [Tc(N)(PScy)Cl(PPh3)].12 This
complex was produced at tracer level with the metastabile
isotope 99mTc.
99mTc studies aimed to evaluate the role of the PPh3 in
the formation of monosubstituted complexes, with respect
to the use of other tertiary phosphines [TPPS ) tris(3-
sulfonatophenyl)phosphine; PCN ) tris(2-cyanoethyl)phos-
phine; P(CH2OH)3 ) tris(hydroxymethyl)phophine], which
were selected according to their electronic and steric proper-
ties, showed the key role of the PPh3 unit in controlling the
formation and stabilization of reactive monosubstituted entity
characterized by the [99mTc(N)(PS)]+ building block.13
Furthermore, it was found that [99mTc(N)(PS)Cl(PPh3)]
reacted almost quantitatively with mononegative bidentate
ligands, such as dithiocarbamates (NaLn), to provide another
class of neutral species, assigned as mixed-substituted
[
99mTc(N)(PS)(Ln)] compounds. Preliminary biodistribution
netium complexes of the type
[
[
99mTc(N)(L)2],
studies of representative [99mTc(N)(PS)(Ln)] tracers revealed
an initial brain uptake followed by a rapid washout, indicating
their ability to cross in and out of the blood-brain barrier
(BBB).13
99mTc(N)(Ar2PS)2] (where L is a dithiocarbamate and Ar2PS
an arylphosphino-thiolate ligand), and
[
99mTc(N)
(YZ)(PNP)]+/0 (where YZ is a π-donor bidentate ligand and
PNP a polydentate aminodiphosphine).7,8 Biodistribution
The purpose of this investigation was to elucidate the
chemical structure of these mixed-substituted 99mTc agents.
This was achieved through the comparison of their chemical
and physical properties with those of the corresponding
compounds prepared at macroscopic level with the long-lived
isotope Tc and with the naturally occurring mixture of cold
Re isotopes and characterized by standard analytical and
spectroscopic methods.
(4) Madsen, M. T. J. Nucl. Med. 2007, 48, 661–673.
(5) Wagner, H. N., Jr. J. Nucl. Med. 2006, 47, 13N–39N.
(6) Duatti, A.; Marchi, A.; Pasqualini, R. J. Chem. Soc., Dalton Trans.
1990, 3729–3733.
(7) Bolzati, C.; Boschi, A.; Uccelli, L.; Malago`, E.; Bandoli, G.; Tisato,
F.; Refosco, F.; Pasqualini, R.; Duatti, A. Inorg. Chem. 1999, 38, 4473–
4479.
(8) (a) Bolzati, C.; Boschi, A.; Duatti, A.; Prakash, S.; Uccelli, L.; Refosco,
F.; Tisato, F.; Bandoli, G. J. Am. Chem. Soc. 2000, 122, 4510–4511.
(b) Boschi, A.; Bolzati, C.; Benini, E.; Malago`, E.; Uccelli, L.; Duatti,
A.; Piffanelli, A.; Refosco, F.; Tisato, F. Bioconjugate Chem. 2001,
12, 1035–1042. (c) Bolzati, C.; Boschi, A.; Uccelli, L.; Tisato, F.;
Refosco, F.; Cagnolini, A.; Duatti, A.; Prakash, S.; Bandoli, G.;
Vittadini, A. J. Am. Chem. Soc. 2002, 124, 11468–11479.
(9) (a) Pasqualini, R.; Duatti, A.; Bellande, E.; Comazzi, V.; Brucato,
V.; Hoffschir, D.; Fagret, D.; Comet, M. J. Nucl. Med. 1994, 35, 334–
341. (b) Pasqualini, R.; Bellande, E.; Comazzi, V.; Laine´, J.; Le´cayon,
M.; Hoffschir, D.; Duatti, A. J. Nucl. Med. 1993, 34,18 P. No 63
abstract. (c) Zhang, J; Wang, X.; Li, C. Y. J. Nucl. Med. Biol. 2002,
29, 665–669. (d) Bolzati, C.; Uccelli, L.; Boschi, A.; Malago`, E.;
Duatti, A.; Tisato, F.; Refosco, F.; Pasqualini, R.; Piffanelli, A. J. Nucl.
Med. Biol. 2000, 27, 369–374. (e) Boschi, A.; Bolzati, C.; Uccelli,
L.; Duatti, A.; Benini, E.; Refosco, F.; Tisato, F.; Piffanelli, A. Nucl.
Med. Commun. 2002, 23, 689–693. (f) Boschi, A.; Uccelli, L.; Bolzati,
C.; Duatti, A.; Sabba, N.; Moretti, E.; Di Domenico, G.; Zavattini,
G.; Refosco, F.; Giganti, M. J. Nucl. Med. 2003, 44, 806–814. (g)
Liu, S.; He, Z.; Hsieh, W. Y.; Kim, Y. Nucl. Med. Biol. 2006, 33,
419–432.
The elucidation of the molecular structure of this new class
of complexes could be essential to (i) clarify the chemical
behavior and the reactivity of this new class of complexes,
(10) (a) Hatada, K.; Riou, L. M.; Ruiz, M.; Yamamichi, Y.; Duatti, A.;
Lima, R. L.; Goode, A. R.; Watson, D. D.; Gorge, A.; Beller, G. A.;
Glover, D. K. J. Nucl. Med. 2004, 45, 2095–2101. (b) Hatada, K.;
Ruiz, M.; Riou, L. M.; Lima, R. L.; Goode, A. R.; Watson, D. D.;
Beller, G. A.; Glover, D. K. J. Nucl. Cardiol. 2006, 6, 779–790.
(11) (a) Bolzati, C.; Refosco, F.; Tisato, F.; Bandoli, G.; Dolmella, A. Inorg.
Chim. Acta 1992, 201, 7–10. (b) Tisato, F.; Refosco, F.; Bandoli, G.;
Bolzati, C.; Moresco, A. J. Chem. Soc., Dalton Trans. 1994, 1453–
1461.
(12) Bolzati, C.; Malago`, E.; Boschi, A.; Cagnolini, A.; Porchia, M.;
Bandoli, G. New J. Chem. 1999, 23, 807–809.
(13) Bolzati, C.; Benini, E.; Cavazza-Ceccato, M.; Cazzola, E.; Malago`,
E.; Agostini, S.; Tisato, F.; Refosco, F.; Bandoli, G. Bioconjugate
Chem. 2006, 17, 419–428.
Inorganic Chemistry, Vol. 47, No. 24, 2008 11973

Bolzati et al.
Physical Measurements. Elemental analyses (C, H, N, S) were
performed on a Carlo Erba 1106 elemental analyzer. FT IR spectra
were recorded on a Nicolet 510P Fourier transform spectrometer
in the range 4000-200 cm-1 and in KBr mixture using a Spectra-
Tec diffuse-reflectance collector accessory. 1H, 13C, and 31P NMR
spectra were acquired at room temperature in CDCl3 on a Brucker
300 instrument, using SiMe4 as internal reference (1H and 13C) and
85% aqueous H3PO4 as external reference (31P).
Mass spectrometric measurements (ESI MS) were performed
with a LCQ DECA (Thermo Finnigan, San Jose, CA) ion trap
instrument operating in the positive ion mode.
Chromatographic separations were accomplished on a SiO2
column (30 cm × 2 cm, 70-230 mesh, Aldrich). TLC analyses
were carried out using C18 F254S or SiO2 F254S plates (Merck) eluted
with a mixture of CH3CN/H2O (90/10) or EtOH/CHCl3/C6H6 (0.1/
2/1.5), respectively. Tc radioactivity on TLC plates was detected
and measured using a Cyclone Instrument equipped with a
phosphorus imaging screen and OptiQuant image analysis software
(Packard, Meridian, CT).
Figure 1. Phosphino-thiol and dithiocarbamate ligands.
(ii) understand the mechanism responsible of their biodis-
tribution profile, and (iii) provide an important design strategy
aimed at improving the biological properties of these
molecules through rational modification of their chemical
structure.
Synthesis of Monosubstituted Complexes. [Tc(N)(PScy)Cl(PPh3)]
(Tc1) was prepared as previously reported.12
[Tc(N)(PS)Cl(PPh3)] (PS ) PSiso, PSibu, PStbu) (Tc2-4). To
0.092 mmol of [Tc(N)Cl2(PPh3)2] suspended in CH2Cl2 (5 mL) was
added 0.140 mmol of the selected PSH ligand dissolved in EtOH
(5 mL). The mixture was stirred at reflux for 30 min during which
the solution became clear and the color changed to yellow. The
solvents were removed, and the residue was treated with EtOH. A
yellow precipitate was collected by filtration and washed with EtOH
followed by n-hexane. The solid was dissolved in CHCl3, loaded
onto a silica column previously conditioned, and eluted with CHCl3.
A yellow band was separated and collected. The eluate was
evaporated, and the residue was treated with Et2O to yield the pure
[Tc(N)(PS)Cl(PPh3)] compound (yields 80-85%).
Hence, this study describes the synthesis and the solution-
and solid-state determination of the molecular structure of
three series of Tc and Re compounds: monosubstituted
[M(N)(PS)Cl(PPh3)] (Tc1-4, Re1-2), dissymmetric mixed-
substituted [M(N)(PS)(Ln)] (Tc5,8-10, Re5-9), and sym-
metric bis-substituted [Tc(N)(PS)2] (Tc11-14), where PS
and Ln indicate the deprotonated form of alkyl phosphino-
thiolate and of dithiocarbamate ligands, respectively.
Bidentate phosphino-thiol (PSH) and dithiocarbamate
(NaLn) ligands utilized in our experiments are depicted in
Figure 1.
[Tc(N)(PSiso)Cl(PPh3)] (Tc2): Yield 80%. Anal. Calcd for
C26H33NP2SClTc (MW 588.06): C 53.10, H 5.65, N 2.39, S 5.45.
Found: C 53.24, H 5.69, N 2.32, S 5.22.
Experimental Section
Caution! Tc is a weak ꢀ-emitter (Eꢀ ) 0.292 MeV, t1/2 ) 1.12
× 105 years). All manipulations were carried out in laboratories
approVed for low-leVel radioactiVity use. Handling milligram
amounts of Tc does not present a serious health hazard, since
common laboratory glassware proVides adequate shielding and all
work is performed in approVed and monitored hoods and gloVe-
boxes. Bremsstrahlung is not a significant problem due to the low
energy of the ꢀ-particles; howeVer, proper radiation safety
procedures must be followed at all times, and particular care should
be taken when handling solid samples.
Materials. All chemicals and reagents were purchased from
Aldrich Chemicals. The solvents were reagent grade and were used
without further purification. Due to the tendency of the phosphine
thiol ligands to oxidize, all the solvents used in reactions with PSH
were previously degassed to remove dissolved trace dioxygen.
Commercially available [(NH4)TcO4] (Oak Ridge National
Laboratories) was purified from a black contaminant (TcO2 ·nH2O)
by addition of H2O2 and NH4OH solutions followed by recrystal-
lization as [(NH4)TcO4] from hot water.
FT-IR (KBr, cm-1): [1065 (ν Tct N)], [3054 ν(H-Ar)],
[2955-2870 ν(H-alkyl)], [746-693 ν(H-Ar)].
31P NMR (CDCl3 ppm): δ 96.9 (bs), 40.7 (bs). 1H NMR (CDCl3
ppm): δ 7.95-7.28 (m, 15H, C6H5P), 2.96 and 2.75 (m, 1H + 1H,
SCH2CH2P), 2.72 and 2.41 (m, 1H + 1H, PCH(CH3)2), 2.39 and
1.79 (m, 1H + 1H, SCH2CH2P), 1.48, 1.24, and 0.70 (dd, 3H +
6H + 3H, PCH(CH3)2).
[Tc(N)(PSibu)Cl(PPh3)] (Tc3): Yield 82%. Anal. Calcd for
C28H37NP2SClTc (MW 616.06): C 54.59, H 6.05, N 2.27, S 5.20.
Found: C 54.84, H 6.44, N 2.09, S 5.22.
FT-IR (KBr, cm-1): [1052 (ν Tct N)], [3055 ν(H-Ar)],
[2956-2867 ν(H-alkyl)], [749-695 ν(H-Ar)]. 31P NMR (CDCl3
ppm): δ 65.3 (bs), 38.4 (bs). 1H NMR (CDCl3 ppm): δ 7.80-7.36
(m, 15H, C6H5P), 3.08-1.75 (2H + 2H + 2H + 2H + 1H + 1H,
(SCH2CH2P), PCH2CH(CH3)2, (SCH2CH2P), and PCH2CH(CH3)2),
1.18-0.81 (12H, PCH2CH(CH3)2).
ESI MS (m/z): 580.2 [M - Cl]+.
[Tc(N)(PStbu)Cl(PPh3)] (Tc4): Yield 85%. Yellow crystals of
Tc4 suitable for X-ray studies were obtained by slow diffusion of
n-hexane into a CH2Cl2 solution of the compound.
[(AsPh4)Tc(N)Cl4] and [Tc(N)Cl2(PPh3)2] were prepared as
previously described.14 The phosphine thiol ligands were purchased
from Argus Chemicals (Prato, Italy). Dithiocarbamates NaL1 and
NaL2 were purchased from Sigma Aldrich. The remaining dithio-
carbamates were synthesized according to literature methods.6,9
Anal. Calcd for C28H37NP2SClTc (MW 616.06): C 54.59, H 6.05,
N 2.27, S 5.20. Found C 54.62, H 6.09, N 2.22, S 5.25.
FT-IR (KBr, cm-1): [1066 (ν Tct N)], [3049 ν(H-Ar)],
[2957-2868 ν(H-alkyl)], [749-692 ν(H-Ar)]. 31P NMR
(14) (a) Baldas, J.; Boas, J. F.; Bonnymann, J.; Williams, G. A. J. Chem.
Soc., Dalton Trans. 1984, 2394. (b) Abram, U.; Lorenz, B.; Kaden,
L.; Scheller, D. Polyhedron 1988, 7, 285–289.
1
(CDCl3 ppm): δ 102.6 (bs), 40.4 (bs). H NMR (CDCl3 ppm):
δ 7.83-7.33 (m, 15H, C6H5-P), 3.13 [m, 1H, SCH2CH2P], 2.48
11974 Inorganic Chemistry, Vol. 47, No. 24, 2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
[m, 1H + 1H, SCH2CH2P and SCH2CH2P], 1.86 [m, 1H,
SCH2CH2P], 1.58 [d, 3JHP ) 13 Hz, 9H, C(CH3)3], 1.17 [d, 3JHP
) 13 Hz, 9H, C(CH3)3].
[Re(N)(PS)Cl(PPh3)] (PS ) PScy, PSiso) (Re1,2). The reactions
were carried out as indicated for the Tc complexes. Column
chromatography was not necessary to obtain pure Re products. After
cooling, the solvents were completely removed by gentle dinitrogen
stream, and the residue was treated with EtOH. A yellow precipitate
was collected by filtration and washed with EtOH followed by Et2O
and n-hexane.
[Re(N)(PScy)Cl(PPh3)] (Re1): Yield 90%. Anal. Calcd for
C32H41NP2SClRe (MW 755.33): C 50.88, H 5.47, N 1.85, S 4.24.
Found: C 50.84, H 5.44, N 1.81, S 4.32.
FT-IR(KBr,cm-1):[1075ν(Ret N)],[3055ν(H-Ar)],[2926-2851
ν(H-Cy)], [746-694 ν(H-Ar)].
CHCl3. Evaporation by a dinitrogen stream of the eluate led to the
isolation of a pure yellow solid. A different eluant was utilized for
the purification of Tc9 (CHCl3/MeOH 98/2).
[Tc(N)(PSiso)(L2)] (Tc8): Yield 81%. Anal. Calcd for
C13H26N2PS3Tc (MW 436.51): C 35.77, H 6.00, N 6.41, S 22.03.
Found: C 35.79, H 6.04, N 6.40, S 22.23.
FT IR (cm-1): [1062 ν(Tct N)], [2956-2870 ν(H-alkyl)], [1510
ν(S2CN<)].
31P NMR (CDCl3 ppm): δ 102.7 (bs). 1H NMR (CDCl3 ppm): δ
3.83 [m, 4H, NCH2CH2], 2.92 [m, 2H, SCH2CH2P], 2.32 [m, 1H
+ 1H, PCH(CH3)2], 2.06 [m, 4H, NCH2-CH2], 2.06 and 2.00 [m,
1H + 1H, SCH2CH2P], 1.22 [m, 9H, PCH(CH3)2], 0.93 [dd, 3H,
PCH(CH3)2]. 13 C NMR (CDCl3 ppm): δ 211.05 (CS2), 50.28 and
2
50.06 (s + s, NCH2CH2), 31.16 [d, JPC ) 7.5 Hz, SCH2CH2P],
26.09 [d, 1JPC ) 30.1 Hz, SCH2CH2P], 24.95-24.64 [NCH2CH2],
23.82 and 23.55 [s + s, PCH(CH3)2], 19.42, 18.88, 17.42 and 17.21
[4s, PCH(CH3)2].
31P NMR (CDCl3 ppm): δ 82.7 (d, 2JPP ) 170 Hz, PCH2CH2S),
35.9 (d, 2JPP ) 170 Hz, PPh3). 1H NMR (CDCl3 ppm): δ 7.86-7.29
(m, 15H, C6H5P), 2.91 and 2.63 (m + m, 1H + 1H, SCH2CH2P),
2.02-1.03 (22H, CyP), 1.93 and 1.46 (m + m, 1H + 1H,
(SCH2CH2P)).
[Re(N)(PSiso)Cl(PPh3)] (Re2): Yield 85%. Anal. Calcd for
C26H33NP2SClRe (MW 675.26): C 46.24, H 4.92, N 2.07, S 4.75.
Found: C 46.29, H 4.93, N 2.10, S 4.80.
ESI-MS(+) (m/z): 459 [M + Na]+ (54%), 437 [M + H]+ (36%),
367 [M + H - pyr]+ (100%).
[Tc(N)(PSiso)(L4)] (Tc9): Yield 75%. Anal. Calcd for
C15H31N3PS3Tc (MW 479.58): C 37.56, H 6.51, N 8.76, S 20.05.
Found: C 37.62, H 6.53, N 8.71, S 20.22.
FT-IR (KBr, cm-1): [1062 ν(Tct N)], [2959-2821 ν(H-alkyl)],
[1517 ν(S2CN<)].
FT-IR(KBr,cm-1):[1075ν(Ret N)],[3052ν(H-Ar)],[2957-2870
ν(H-alkyl)], [747-694 ν(H-Ar)].
31P NMR (CDCl3 ppm): δ 102.3 (bs). 1H NMR (CDCl3 ppm): δ
4.15 and 3.92 [m + m, 2H + 2H, NCH2CH2NCH2CH3], 2.93 [m,
2H, SCH2CH2P], 2.57 [m, 4H, NCH2CH2NCH2CH3], 2.47 [q, 2H,
NCH2CH3], 2.31 and 2.25 [m + m, 1H + 1H, PCH(CH3)2], 2.08
and 1.93 [m + m, 1H + 1H, SCH2CH2P], 1.36-0.94 [4 dd, 12H,
PCH(CH3)2], 1.11 [t, 3H, NCH2CH3]. 13C NMR (CDCl3 ppm): δ
210.5 (s, CS2), 51.9 [s, NCH2CH2NCH2CH3], 51.71 (s, NCH2CH3),
31P NMR (CDCl3 ppm): δ 92.0 (d, 2JPP ) 170 Hz, PCH2CH2S),
35.2 (d, 2JPP ) 170 Hz, PPh3). 1H NMR (CDCl3 ppm): δ 7.90-7.28
(m, 15H, C6H5P), 2.95 and 2.63 (m + m, 1H + 1H, SCH2CH2P),
2.75 and 2.42 (m + m, 1H + 1H, PCH(CH3)2), 1.96 and 1.44 (m
+ m, 1H + 1H, SCH2CH2P), 1.51, 1.25, and 0.62 (dd, 3H + 6H
+ 3H, PCH(CH3)2).
2
47.7 and 47.1 (s + s, NCH2CH2NCH2CH3], 31.08 [d, JPC ) 7.3
Hz, SCH2CH2P], 26.12 [d, 1JPC ) 29.6 Hz, 1C, SCH2CH2P], 24.82
Monosubstituted [M(N)(PS)Cl(PPh3)] compounds are soluble in
chlorinated solvents, benzene, and toluene and insoluble in alcohols,
MeCN, Et2O, and n-hexane.
1
1
[d, JPC ) 24.3 MHz, PCH(CH3)2], 23.66 [d, JPC ) 23.6 Hz,
PCH(CH3)2], 19.42, 18.86, 17.41, and 17.24 [4s, PCH(CH3)2], 11.90
(s, NCH2CH3).
Synthesis of Mixed-Substituted Dissymmetrical Complexes.
[M(N)(PS)(Ln)] (M ) Tc5,8-10, Re5-9). To 0.051 mmol of the
selected intermediate complex (M1-4) dissolved in 5 mL of
[Tc(N)(PStbu)(L3)] (Tc10): Yield 84%. Anal. Calcd for
C16H32N2PS3Tc (MW 478.60): C 40.15, H 6.74, N 5.85, S 20.09.
Found: C 40.22, H 6.51, N 5.71, S 21.05.
CH2Cl2, 0.06 mmol of the appropriate dithiocarbamate ligand (L1-4
)
FT-IR (KBr, cm-1): [1063 (ν Tct N)], [2957-2868 ν(H-alkyl)],
[1512 ν(S2CN<)].
was added. The reaction mixture was stirred at room temperature
for 30 min. Rapidly the solution became clear, and the color
changed to yellow-green.
The reaction mixture was concentrated by gentle dinitrogen
stream and a white powder was removed by filtration. The solvent
was completely evaporated and the yellow-green residue was treated
with n-hexane to remove the PPh3.
31P NMR (CDCl3 ppm): δ 115.9 (bs). 1H NMR (CDCl3 ppm): δ
4.14 and 3.88 [m, 2H + 2H, NCH2CH2CH2], 2.96 [m, 2H,
SCH2CH2P], 2.12 [m, 2H, SCH2CH2P], 1.75 [bs, 4H + 2H,
3
NCH2CH2CH2 and NCH2CH2CH2], 1.45 and 1.19 [d, JHP ) 13
Hz, 9H + 9H, PC(CH3)3].
[Re(N)(PScy)(L1)] (Re5): Yield 60%. Anal. Calcd for
C19H36N2PS3Re (MW 606.13): C 37.65, H 5.98, N 4,62, S 15.86.
Found: C 37.22, H 6.01, N 4.65, S 16.98.
[Tc(N)(PScy)(L1)] (Tc5): The final product was isolated as pure
yellow powder upon treatment of the residue with Et2O. Yield 85%.
Anal. Calcd for C19H36N2PS3Tc (MW ) 516.06): C 44.22, H 7.03,
N 5.42, S 12.42. Found: C 43.65, H 7.12, N 5.56, S 13.20.
FT IR (cm-1): [1059 ν(Tct N)], [2928-2851 ν(H-Cy)].
FT-IR (KBr, cm-1): [1072 ν(Ret N)] [2940-2850 ν(H-Cy)],
[1522 ν(S2CN<)].
1
31P NMR (CDCl3 ppm): δ 84.6 (s). H NMR (CDCl3 ppm): δ
1
31P NMR (CDCl3 ppm): δ 92.5 (bs). H NMR (CDCl3 ppm): δ
4.05-3.53 (4H, NCH2CH3), 2.81 (m, 2H, SCH2CH2P), 2.15-1.12
(22H + 2H + 6H, CyP, SCH2CH2P and NCH2CH3).
[Re(N)(PScy)(L2)] (Re6): Yield 70%. Anal. Calcd for
C19H34N2PS3Re (MW 604.11): C 37.77, H 5.67, N 4,63, S 15.92.
Found: C 36.48, H 5.37, N 4.51, S 16.24.
4.02-3.67 (4H, NCH2CH3), 2.89 (m, 2H, SCH2CH2P), 2.16-1.16
(22H + 2H + 6H, CyP, SCH2CH2P and NCH2CH3).
ESI-MS(+) (m/z): 1058 [2 M + Na]+ (60%), 541 [M + Na]+
(26%), 519 [M + H]+ (100%).
[M(N)(PS)(Ln)] (M6-10). Column chromatography was neces-
sary to separate pure species from the corresponding bis-substituted
[Tc(N)(Ln)2] and other unidentified side products. The residue was
dissolved in CHCl3 (1 mL) and loaded onto a silica column
previously conditioned with CHCl3. The column was eluted with
FT-IR (KBr, cm-1): [1072 ν(Ret N)], [2924-2850 ν(H-Cy)],
[1508 ν(S2CN<)].
31P NMR (CDCl3 ppm): δ 84.3 (s). 1H NMR (CDCl3 ppm): δ 3.82
(m, 4H, N[CH2CH2]2), 2.81 (m, 2H, SCH2CH2P), 2.18-1.12 (22H +
13
2H + 4H, CyP, SCH2CH2P and N[CH2CH2]2). C NMR (CDCl3
Inorganic Chemistry, Vol. 47, No. 24, 2008 11975

Bolzati et al.
ppm): δ 218.77 (CS2), 50.26 and 49.88 (s + s, NCH2CH2), 35.95 [d,
2JPC ) 6.8 Hz, SCH2CH2P], 34.76, 34.36, 33.95, 33.59 29.68, 29.21,
27.99, 27.48, 27.05, 26.92, 26.52, 26.00, 25.73, 24.86, 24.72.
[Re(N)(PScy)(L3)] (Re7): Yellow crystals of Re7·1/2H2O suit-
able for X-ray studies were obtained by slow diffusion of n-hexane
into a CH2Cl2 solution of the compound. Yield 73%. Anal. Calcd
for C20H36N2PS3Re (MW 618.13): C 38.86, H 5.87, N 4,55, S 15.56.
Found: C 38.67, H 6.01, N 4.60, S 15.85.
product was identified as the pure [Tc(N)(PS)2] compound (yield
≈ 80%) and the second yellow complex as the oxidized derivative
(yield < 10%).
For method b, to 0.092 mmol of [Tc(N)Cl2(PPh3)2] suspended
in CH2Cl2 (5 mL) was added 0.928 mmol of the selected PSH ligand
dissolved in EtOH (5 mL). The reaction mixture was stirred at reflux
under dinitrogen atmosphere overnight. After cooling, the solvents
were removed by gentle dinitrogen stream, and the residue was
treated with n-hexane. A yellow precipitate was collected by
filtration. The solid was dissolved in CHCl3 and loaded onto a silica
column previously conditioned with CHCl3. The column was eluted
with CHCl3, and two yellow bands were separated and collected.
The eluate was evaporated, and the residues were treated with Et2O
to yield the complexes. The first yellow product was identified as
[Tc(N)(PS)Cl(PPh3)] (vide infra) and the second yellow complex
as [Tc(N)(PS)2] (yields 60-80%).
FT-IR (KBr, cm-1): [1073 ν(Ret N)], [2913-2849 ν(H-Cy)],
[1522 ν(S2CN<)].
1
31P NMR (CDCl3 ppm): δ 84.6 (s). H NMR (CDCl3 ppm): δ
4.08 and 3.76 (m + m, 2H + 2H, N[CH2CH2]2CH2), 2.91 (m, 2H,
SCH2CH2P), 2.21-1.04 (22H + 2H + + 2H + 4H, CyP,
13
SCH2CH2P and N[CH2CH2]2CH2).
C NMR (CDCl3 ppm): δ
2
224.08 (CS2), 49.07 and 48.24 (s + s, NCH2CH2), 35.80 [d, JPC
) 6.8 Hz, SCH2CH2P], 34.72, 34.31, 33.88, 33.53 29.26, 29.21,
27.88, 27.44, 27.03, 26.92, 26.56, 26.00, 25.73, 25.66, 24.48, 23.91.
[Re(N)(PSiso)(L2)] (Re8): Yield 65%. Anal. Calcd for
C13H26N2PS3Re (MW 524.05): C 29.79, H 5.00, N 5,34, S 18.35.
Found: C 29.07, H 5.07, N 5.40, S 18.80.
[Tc(N)(PSme)2] (Tc11): Yield 60%. Anal. Calcd for
C8H20P2S2NTc (M.W 354.95): C 27.07, H 5.67, N 3.94, S 9.03.
Found: C 27.92, H 5.40, N 3.51, S 9.50. FT-IR (KBr, cm-1): [1066
(ν Tct N)], [2950-2867 ν(H-alkyl)].
FT-IR (KBr, cm-1): [1072 ν(Ret N)], [2952-2868 ν(H-alkyl)],
[1508 ν(S2CN<)].
31P NMR (CDCl3 ppm): δ 48.9 (bs). H NMR (CDCl3 ppm): δ
1
1.57 [m, 12H P(CH3)2], 2.08 and 2.01 [m, 2H + 2H, SCH2CH2P],
2.89 [m, 4H, SCH2CH2P].
13C NMR (CDCl3 ppm):
δ 35.90 [SCH2CH2P], 28.79
31P NMR (CDCl3 ppm): δ 94.0(s). H NMR (CDCl3 ppm): δ
1
3.83 (m, 4H, N[CH2CH2]2), 2.85 (m, 2H, SCH2CH2P), 2.30 (m,
1H + 1H, PCH(CH3)2), 2.08 (m, 4H, N[CH2CH2]2), 1.91 and 1.52
(m+m,1H+1H,SCH2CH2P),1.30-0.91(6H+6H,PCH(CH3)2).ESI-
MS(+) (m/z): 547 [M + Na]+ (100%), 525 [M + H]+ (20%).
[Re(N)(PSiso)(L4)] (Re9): Yellow crystals of Re9 suitable for
X-ray studies were obtained by slow diffusion of n-hexane into a
CH2Cl2 solution of the compound. Anal. Calcd for C15H31N3PS3Re
(MW 567.09): C 31.77, H 5.51, N 7,41, S 16.96. Found: C 31.27,
H 5.50, N 7.49, S 17.32.
[SCH2CH2P], 17.15 and 11.11 [P(CH3)2].
[Tc(N)(PSiso)2] (Tc12): Yield 81%. Anal. Calcd for
C16H36NP2S2Tc (MW 467.59): C 41.10, H 7.76, N 3.01, S 13.71.
Found C 40.84, H 7.44, N 2.81, S 13.92.
FT-IR (KBr, cm-1): [1065 (ν Tct N)], [2928-2869 ν(H-alkyl)].
1
31P NMR (CDCl3 ppm): 98.8 (bs). H NMR (CDCl3 ppm): δ
0.82 [m, 6H, PCH(CH3)2], 1.25 [m, 12H, PCH(CH3)2], 1.44 [m,
6H, PCH(CH3)2], 1.89 and 2.10 (2H + 2H, PCH(CH3)2], 2.47 (m,
4H, (SCH2CH2P)], 2.94 [m, 4H, SCH2CH2P].
[Tc(N)(PSibu)2] (Tc13): Yield 76%. Anal. Calcd for
C20H44NP2S2Tc (MW 523.70): C 45.87, H 8.68, N 2.68, S 12.24.
Found C 46.97, H 8.98, N 2.56, S 13.24.
FT-IR (KBr, cm-1): [1048 (ν Tct N)], [2954-2867 ν(H-alkyl)].
31P (CDCl3 ppm): 66.7 (bs). 1H NMR (CDCl3 ppm): δ 2.99 and
2.67 [m, 2H + 2H, (SCH2CH2P)], 2.32 and 2.05 [m, 2H + 2H,
PCH2CH(CH3)2], 2.25 and 2.01 [m, 2H + 2H, SCH2CH2P], 1.95
and 1.55 [m, 4H + 4H, PCH2CH(CH3)2], 1.15, 1.08, 1.05 and 0.96
[4d, 6H + 6H + 6H + 6H, (CH3)2CHCH2P]. 13C NMR (CDCl3
ppm): δ 35.56 and 32.54 [SCH2CH2P], 33.15 [PCH2CH(CH3)2],
28.37 [SCH2CH2P], 26.58 and 25.04 [PCH2CH(CH3)2], 25.61- 24.54
[PCH2CH(CH3)]. ESI-MS(+) (m/z): 1069 [2M + Na]+ (52%), [(2M
+ H) - PSibu]+ (72%), 524 [M + H]+ (100%).
FT-IR (KBr, cm-1):[1072 ν(Ret N)], [2958-2810 ν(H-alkyl)],
[1524 ν(S2CN<)].
1
31P NMR (CDCl3 ppm): δ 94.1 (s). H NMR (CCl3 ppm): δ
4.11 and 3.84 (m + m, 2H + 2H, N[CH2CH2]2NCH2CH3), 2.85
(m, 2H, SCH2CH2P), 2.58 (m, 4H, N[CH2CH2]2NCH2CH3), 2.48
(q, 2H, N[CH2CH2]2NCH2CH3), 2.32 (m, 1H + 1H, PCH(CH3)2),
1.92 and 1.53 (m + m, 1H + 1H, SCH2CH2P), 1.39-0.89 (6H +
6H + 3H, PCH(CH3)2 and N[CH2CH2]2NCH2CH3).
13C NMR (CDCl3 ppm): δ 228.26 (CS2), 51.86, 51.79, 51.62,
2
47.77, 46.92, 36.26 [d, JPC ) 6.6 Hz, SCH2CH2P], 27.55, 27.11,
25.73, 25.33, 24.36, 23.99, 19.33, 17.56, 11.93.
ESI-MS(+) (m/z): 590 [M + Na]+ (26%), 568 [M + H]+ (52%),
547 [M + Na - CH(CH3)2]+ (100%).
Mixed-substituted complexes are soluble in chlorinated solvents,
MeCN, and alcohols and insoluble in n-hexane, Et2O, and water.
Synthesis of Bis-substituted Complexes. [Tc(N)(PS)2]
[Tc(N)(PSibu)(OPSibu)] (Tc13a): Yield < 10%. Anal. Calcd
for C20H44NP2S2Tc (MW 668.203): C 57.52, H 6.18, N 2.1, S 5.22.
Found C 53.84, H 6.44, N2.81, S 5.22.
(Tc11-14) (PS
)
PSme, PSiso, PSibu, PStbu) and
[Tc(N)(PSibu)(OPSibu)] (Tc13a). For method a, to 0.194 mmol
of the selected PSH ligand dissolved in degassed EtOH (5 mL)
were added ten drops of TFA (10% v/v) followed by 0.05 mmol
of [(AsPh4)Tc(N)Cl4] dissolved in CH2Cl2 (2 mL). The reaction
mixture was stirred at reflux under dinitrogen atmosphere for 2 h
during which the solution became yellow-brown. The solvents were
removed by gentle dinitrogen stream, and the crude product was
treated with Et2O. Column chromatography was necessary to
separate pure species. The residue was dissolved in CHCl3 and
loaded onto a silica column previously conditioned with CHCl3.
The column was eluted with CHCl3 and two yellow bands were
separated and collected. The eluate was evaporated, and the residues
were treated with Et2O to yield the complexes. The first yellow
FT-IR (KBr, cm-1): [1053 (ν Tct N)], [2957-2869 ν(H-alkyl)].
2
31P NMR (CDCl3 ppm): δ 65.5 (bs), 46.3 (d, JPP ) 134 Hz).
1H NMR (CDCl3 ppm): δ 3.62 (m, 1H), 2.96 (m, 1H), 2.75 (m,
1H + 1H), 2.32-1.70 [8H], 2.20 (m, 2H + 1H), 2.13 (m, 1H),
1.93 (m, 1H), 1.77 (m, 1H + 1H), 1.41 (dt, 1H), 1.10 (m, 18H),
1.00 (dd, 6H).
[Tc(N)(PStbu)2] (Tc14): Yield 80%. Anal. Calcd for
C20H44NP2S2Tc (MW 523.70): C 45.87, H 8.68, N 2.68, S 12.24.
Found: C 45.97, H 8.83, N 2.60, S 13.11.
FT-IR (KBr, cm-1): [1062 (ν Tct N)], [2967-2863 ν(H-alkyl)].
31P NMR (CDCl3 ppm): δ 109.0 (bs). 1H NMR (CDCl3 ppm): δ
3.12-2.87 [4H, (SCH2CH2P)], 2.26-2.02 [4H, (SCH2CH2P)], 1.51
and 1.22 [m, 18H, PC(CH3)3]. 13C NMR (CDCl3 ppm): δ 34.96
11976 Inorganic Chemistry, Vol. 47, No. 24, 2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
Scheme 1
[PC(CH3)3], 32.45 [SCH2CH2P], 29.58 and 29.37 [PC(CH3)3], 27.19
[SCH2CH2P].
collection of monosubstituted [Tc(N)(PS)Cl(PPh3)] species
in high yield. In contrast, less restricted reaction conditions
were required to obtain the analogous monosubstituted Re
compounds in high yield. In this case, even the use of a large
excess of ligand, conditions generally met in radiopharma-
ceuticals preparations, produced only the monosubstituted
Re complexes, while the corresponding bis-substituted Re
compounds were never observed.
As exceptions of this general behavior, in Tc synthesis
the use of the less sterically hindered PSmeH ligand led to
the formation of the bis-substituted compound [Tc(N)(PS-
me)2], and when the bulkiest PStbuH ligand was used, the
monosubstituted [Re(N)(PS)Cl(PPh3)] was never formed
under a wide range of reaction conditions.
X-ray Crystallography. The measurements were collected at
room temperature on a Philips PW1100 diffractometer with
graphite-monochromated Mo KR radiation. The structures of Tc4,
Re7 · 1/2H2O, and Re9 were solved by heavy-atom methods
expanded using Fourier techniques and refined by full-matrix least-
squares method on F2.15 The non-hydrogen atoms (excluding the
water oxygens in Re7 · 1/2H2O) were refined anisotropically; the
hydrogen atoms were placed in idealized positions and allowed to
ride with the parent atoms to which each were bonded. The final
difference maps were featureless. Supplementary crystallographic
data files for complexes Tc4, Re7·1/2H2O and Re9 have been
deposited at Cambridge Crystallographic Data Centre (www.ccd-
c.cam.ac.uk), numbers CCDC 689602, 689603, and 689604,
respectively.
The reactivity of [M(N)(PS)Cl(PPh3)] complexes toward
different mononegative bidentate ligands, such as PSH and
NaLn was investigated. In particular, [Tc(N)(PS)Cl(PPh3)]
was treated in refluxing CH2Cl2/EtOH with 2-10-fold excess
of the selected alkylphosphino-thiol ligand, eq 2. TLC
analysis showed that, when the reactions were carried out
with 5-fold molar excess of PSH at reflux for 8 h, a 6:4
mixture of symmetric bis-substituted [Tc(N)(PS)2] and
monosubstituted [Tc(N)(PS)Cl(PPh3)] was recovered. When
the amount of the PS-ligand (10-fold molar excess) was
increased and the bis-substituted/monosubstituted mixture
was refluxed overnight, the ratio was enriched in the bis-
Results
Synthesis, Characterization and Reactivity of
Monosubstituted [M(N)(PS)Cl(PPh3)] Complexes (M )
Tc1-4, Re1,2). According to the synthetic pathway outlined in
Scheme 1, monosubstituted nitrido M(V) complexes of the type
[M(N)(PS)Cl(PPh3)] were prepared by reaction of the
[M(N)Cl2(PPh3)2] precursors with the appropriate bulky alkylphos-
phinothiol ligand in refluxing CH2Cl2/EtOH mixtures, eq 1.
In the case of Tc, accurate control of the metal/ligand
stoichiometric ratio and heating time (30 min) allowed the
(15) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–122.
Inorganic Chemistry, Vol. 47, No. 24, 2008 11977

Bolzati et al.
Table 1. 31P NMR (CDCl3) Spectral Data of Five-Coordinate Phosphino Thiolato Complexes
compounds
δ
31P (ppm)
∆ (δcomplex - δfree
)
compounds
δ
31P (ppm)
∆ (δcomplex - δfree)
PScyH
5.1
PSisoH/P(O)SisoH
PsibuH/P(O)SibuH
PStbuH/P(O)StbuH
+3.6/+46.0
-38.6/+46.0
+26.2/+77.3
2
2
[Tc(N)(PScy)Cl(PPh3)] Tc1* 86.3 (d, cy2P, JPP 162 Hz), 39.3
91.9
93.3
[Re(N)(PScy)Cl(PPh3)] Re1 82.7 (d,cy2P, JPP 170 Hz), 35.9
88.5
89.1
(d, Ph3P,2JPP 162 Hz)
(d, Ph3P, JPP 170 Hz)
2
2
[Tc(N)(PSiso)Cl(PPh3)] Tc2 96.9 (d b, iso2P)), 40.7 (d b, Ph3P)
[Re(N)(PSiso)Cl(PPh3)] Re2 92.7 (d,iso22P, JPP 170 Hz), 35.9
(d, Ph3P, JPP 170 Hz)
[Tc(N)(PSibu)Cl(PPh3)] Tc3 65.3 (d b, ibu2P), 38.4 (d b, Ph3P)
[Tc(N)(PStbu)Cl(PPh3)] Tc4 102.6 (d b,tbu2P), 40.5 (d, Ph3P)
103.9
76.4
97.6
[Tc(N)(PScy)(L1)] Tc5
92.5 (s)
[Re(N)(PScy)(L1)] Re5
[Re(N)(PScy)(L2)] Re6
[Re(N)(PScy)(L3)] Re7
[Re(N)(PSiso)(L2)]Re8
[Re(N)(PSiso)(L4)] Re9
84.34
84.61
94.01
94.11
79.24
79.61
90.41
90.51
[Tc(N)(PSiso)(L2)] Tc8
[Tc(N)(PSiso)(L4)] Tc9
[Tc(N)(PStbu)(L3)] Tc10
[Tc(N)(PScy)2]*
102.7 (s)
102.3 (s)
115.96 (s)
85.9 (s)
99.1
98.7
89.7
91
[Tc(N)(PSme)2] Tc11
[Tc(N)(PSiso)2] Tc12
[Tc(N)(PSibu)2] Tc13
98.8 (s)
66.7 (s)
95.2
105.3
[Tc(N)(PSibu)(OPSibu)]Tc13a 65.55 (s), 46.81-45.70 (d)
[Tc(N)(PStbu)2] Tc14 109.08 (s) (273 K)
82.9
substituted species (8:2) without reaching quantitative con-
version. This behavior indicates that steric and electronic
effects due to the presence of two different P donors provided
an efficient stabilization of the [Tc(N)(PS)Cl(PPh3)] arrange-
ment making difficult the substitution of the second mono-
dentate ligand by an additional bulky alkylphosphinothiolate
ligand. Under similar reaction conditions monosubstituted
[Re(N)(PS)Cl(PPh3)] did not convert into bis-substituted
complexes at all.
In contrast, chloride and PPh3 were promptly replaced by
dithiocarbamate ligand at room temperature allowing the
preparation of a new class of neutral, dissymmetrical mixed-
substituted complexes, eq 3 (Vide infra).
Elemental analyses of complexes M1-4 were in agree-
ment with the proposed formulation. FT-IR spectra exhibited
a medium to intense vibration in the range 1075-1052 cm-1
typical of the ν(Mt N) stretching, along with vibrations
characteristics of both the aliphatic groups of the PS ligand
(2957-2851 cm-1) and coordinated triphenylphosphine
(3055-3049 cm-1; 749-692 cm-1).
significantly downfield shifted (see Table 1) compared with
the corresponding ones in uncoordinated ligands by ca. 100
and 45 ppm for phosphinothiolate and triphenylphosphine,
respectively, indicating the better donor properties of PSH
compared with PPh3. The magnitude of the coordination
chemical shifts (∆) value for phosphinothiolate P (see Table
1) is a function of the phosphine Tolman cone angle. Small
cone angles determine larger shifts as for [Tc(N)(PSibu-
)Cl(PPh3)], and larger cone angles determine smaller shifts
as for [Tc(N)(PStbu)Cl(PPh3)].16
This behavior was also observed in mixed-substituted
[Tc(N)(PS)(Ln)] and bis-substituted [TcV(N)(PS)2] compounds.
1H NMR spectra of [M(N)(PS)Cl(PPh3)] showed signals
in the 7.9-7.3 ppm range due to aromatic PPh3 protons and
a series of signals in the aliphatic region corresponding to
the alkyl substituents and ethylene bridging chain of the PS
ligand. As an example, the two-dimensional 1H-1H COSY
map of the [Tc(N)(PSiso)Cl(PPh3)] complex (Tc2) in the
aliphatic region is sketched in Figure S2 (Supporting
Information). The analysis provides evidence that geminal
protons of the ethylene bridging chain are diastereotopic (four
different proton signals) and that the two isopropyl substit-
uents at P are magnetically nonequivalent (dotted lines in
the map).
ESI(+) mass spectra of the representative Tc3 compound
did not show the molecular ion peak but the only attributable
signal at m/z 580.2 corresponding to the [M(N)(PS)(PPh3)]+
fragment ion. Monosubstituted complexes were characterized
in the solution state by means of 31P NMR spectroscopy.
The presence of two magnetically nonequivalent P donors
resulted in two sharp doublet signals in the case of rhenium
derivatives (Re1,2) (see Table 1 and in Supporting Informa-
The description of the structure of the monosubstituted
[Tc(PStbu)Cl(PPh3)] complex (Tc4) is reported below.
Synthesis and Characterization of Dissymmetrical
Mixed-Substituted [M(N)(PS)(Ln)] Complexes. As outlined
in Scheme 1, dissymmetrical nitrido M(V) complexes
[M(N)(PS)(Ln)] (M5-10) were prepared via ligand exchange
reaction treating monosubstituted [M(N)(PS)Cl(PPh3)] de-
rivatives with a dithiocarbamate ligand in CH2Cl2/MeOH
solutions at room temperature, eq 3. In these reactions, the
monosubstituted species selectively and instantaneously
reacted with the mononegative ligand irrespective of the
nature of the PS coligand to afford novel five-coordinate
mixed-substituted compounds, characterized by the presence
of two different bidentate ligands around the [Mt N] group,
in nearly quantitative yields.
2
tion, Figure S1a). The JPP coupling constant of 170 Hz is
consistent with a reciprocal trans orientation of triphe-
nylphosphine and phosphinothiolate P donors. In Tc1-4
derivatives, such signals appeared as two broad singlets at
room temperature (Figure S1c, Supporting Information),
which narrowed on lowering the temperature to 250 K. The
downfield signal (in the range 102.6-65.3 ppm) was
assigned to the phosphinothiolate P atom by comparison with
the signals of the bis-substituted and mixed-substituted
species (Vide infra). The other signal (in the range 40.7-35.9
ppm) corresponded to coordinated PPh3. Both signals are
11978 Inorganic Chemistry, Vol. 47, No. 24, 2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
Scheme 2
Identical mixed-substituted compounds were obtained
by reacting the corresponding symmetrical bis-substituted
[Tc(N)(Ln)2] species with a large excess of the selected
phosphinothiol ligand. In this case, the reaction yield
decreased considerably (<30%) (Scheme 1, eq 4). TLC
studies showed the presence of three spots of comparable
intensity, attributable to the following products: the
dissymmetrical mixed-substituted [Tc(N)(PS)(Ln)] com-
pound and two bis-substituted species identified as [Tc-
(N)(PS)2] and [Tc(N)(Ln)2] compounds. In contrast, no
formation of [Tc(N)(PS)(Ln)] was observed when the
reaction was carried out using [Tc(N)(PS)2] as starting
material. This behavior underlines the superior coordina-
tion ability of bidentate phosphino-thiolate with respect
to dithiocarbamate toward the [Tct N]2+ core and the
remarkable kinetic inertness and stability of the sym-
metrical [Tc(N)(PS)2] complexes.
Physical and chemical characterization of the isolated
mixed-substituted compounds indicated that all contain the
[M(N)(PS)]+ fragment. In detail, elemental analyses were
in agreement with the proposed formulations. FT-IR spectra
exhibited the characteristic ν(Tct N) stretching vibration in
the range 1073-1059 cm-1, along with typical absorption
of coordinated alkyl phosphine in the region 2959-2810
cm-1.
technetium species compared with the corresponding signal
in rhenium analogs.
Both 1H and 13C NMR spectra showed complicated
patterns consistent with coordination of the phosphinothiolate
and the dithiocarbamate ligands. For illustrative purposes,
1
1
the H-1H COSY and H-13C HMQC maps of [Tc(N)(P-
Siso)(L4)] (Tc9) are reported in Figure S3 (Supporting
Information).
Synthesis and Characterization of Symmetric
Bis-Substituted [Tc(N)(PS)2] Complexes. As previously
reported,7 symmetric bis-substituted nitrido Tc(V) complexes
[Tc(N)(PS)2] (Tc11-14) were easily prepared in high yield (ca.
80%) by reacting the prereduced precursor Tc(VI)
[(AsPh4)Tc(N)Cl4] in acidic media with a 3-fold molar excess
of the appropriate PSH. In these reduction-substitution reac-
tions, PSH acts both as reducing and as coordinating agent,
giving neutral five-coordinate bis-substituted Tc(V) complexes.
When the reactions were carried out without the addition
of a proton source, the yield of [Tc(N)(PS)2] was lowered
to <50% because of the formation of several byproducts,
among which Tc13a, containing an oxophosphine-thiolate
ligand, was characterized by multinuclear NMR spectroscopy
(Scheme 2, eq 5).
Bis-substituted [Tc(N)(PS)2] compounds can be also
obtained via ligand exchange reaction of PSH onto the Tc(V)
precursor [Tc(N)Cl2(PPh3)2] using 10-fold molar excess of
PSH at reflux overnight (Scheme 2, eq 6). In these reactions,
the yield of [Tc(N)(PS)2] was significantly lowered because
of the competitive formation of the corresponding mono-
substituted [Tc(N)(PS)Cl(PPh3)] compounds.
ESI(+) mass spectra of mixed-substituted compounds
showed the protonated ([M + H]+) and the cationized [M
+ Na]+ molecular ion peaks. Under collision experiments,
[M + H]+ exhibited fragmentation processes mainly related
to the dithiocarbamate moiety.17
The appearance of a singlet in the 31P NMR spectra,
(Figure S1b,d, Supporting Information) was diagnostic for
the formation of mixed-substituted complexes. As observed
in monosubstituted complexes, the 31P signal was signifi-
cantly broadened as well as slightly downfield shifted for
Complexes Tc11-14 were characterized by elemental
analysis, IR and NMR spectroscopies, and ESI-MS. FT-IR
spectra exhibited the characteristic ν (Tct N) stretching
vibration in the range 1065-1048 cm-1, along with absorp-
tion of coordinated alkyl phosphine in the region 2967-2863
Inorganic Chemistry, Vol. 47, No. 24, 2008 11979

Bolzati et al.
Table 2. Crystallographic Data for Tc4, Re7·1/2H2O, and Re9
Tc4
Re7 ·1/2H2O
Re9
empirical formula
fw
crystal system
space group
a (Å)
C28H37ClNP2STc
615.04
C20H36N2PS3Re·1/2H2O
626.86
C15H31N5PS3Re
566.78
monoclinic
P21/c (No. 14)
13.177(3)
12.032(2)
14.207(3)
90
107.91(3)
90
2143.3(7)
4, 1.756
6.04
21
ω - 2θ
4180
3656
208
0.052
0.112
triclinic
monoclinic
P21/c (No. 14)
20.912(4)
13.921(4)
17.927(4)
90
100.03(3)
90
5139(2)
8, 1.620
5.05
21
ω - 2θ
7974
7701
495
0.044
0.103
j
P1 (No. 2)
9.479(2)
15.477(3)
22.763(5)
107.17(3)
90.54(3)
96.27(3)
3169(1)
4, 1.289
7.21
b (Å)
c (Å)
R (deg)
ꢀ (deg)
γ (deg)
V (Å3)
Z, Dcalcd (g cm-3
)
µ(Mo KR), cm-1
T, °C
21
scan type
ω - 2θ
13690
5616
613
0.047
measured reflns
obsd reflns [I > 2σ(I)]
refined params
R1a
wR2b
0.106
0.795
GOFc
1.219
1.364
a R1 ) ∑(|F0|/|Fc|)/∑(|F0|). b wR2 ) {∑[w(F0 - Fc )2]/∑[w(F0)2]}1/2
.
c GOF ) {∑[w(F0 - Fc )2]/(n - p)}1/2 (n ) reflections; p ) parameters).
2
2
2
2
Table 3. Selected Bond Lengths (Å) and Angles (deg) for Tc4, Re7·1/2H2O, and Re9
Tc4
Re7 ·1/2H2O
Re9
Tc-N
Tc-Cl
Tc-S
Tc-P(1)
Tc-P(2)
1.610(5)
2.406(2)
2.339(2)
2.457(2)
2.457(2)
Re-N(1)
Re-S(1)
Re-S(2)
Re-S(3)
Re-P(1)
1.64(1)
Re-N(1)
Re-S(1)
Re-S(2)
Re-S(3)
Re-P(1)
1.66(1)
2.336(3)
2.389(3)
2.422(3)
2.376(3)
2.333(3)
2.396(3)
2.432(3)
2.383(2)
N-Tc-Cl
112.0(2)
108.7(2)
99.6(2)
96.2(2)
83.5(1)
102.7(2)
109.6(2)
S(1)-Re-P(1)
S(2)-Re-S(3)
N(1)-Re-P(1)
N(1)-Re-S(1)
N(1)-Re-S(2)
N(1)-Re-S(3)
S(1)-Re-S(2)
S(3)-Re-P(1)
83.0(1)
73.0(1)
S(1)-Re-P(1)
S(2)-Re-S(3)
N(1)-Re-P(1)
N(1)-Re-S(1)
N(1)-Re-S(2)
N(1)-Re-S(3)
S(1)-Re-S(2)
S(3)-Re-P(1)
83.6(1)
72.3(1)
N-Tc-S
N-Tc-P(1)
N-Tc-P(2)
S-Tc-P(1)
Tc-P(1)-C(1)
Tc-S-C(2)
100.6(4)
110.3(4)
107.0(4)
108.5(4)
142.1(1)
150.8(1)
100.4(3)
109.8(4)
107.1(3)
107.1(3)
142.0(1)
152.6(1)
cm-1.The ESI mass spectra of selected representative com-
pounds showed the main peaks corresponding to the proto-
nated [M + H]+ molecules.16
confirmed in the 31P spectrum by the appearance of two signals:
a broad singlet at 65.5 ppm, value typical for metal-coordinated
PSibu, and a doublet at 46.2 ppm (2JPP ) 135 Hz) corresponding
to metal-coordinated OPSibu. The chemical structure of the
hypothesized compound is sketched in Scheme 2 with the metal
binding bidentate PSibu and OPSibu through the P,S and O,S
bites, respectively. Coordination of oxidized phosphinethiolate
ligands have previously been observed with various transition
metal complexes.18
The singlet in the 31P NMR spectra of bis-substituted
technetium complexes indicated magnetic equivalence of the
two phosphine-thiolate P. Such a signal was remarkably
downfield shifted (see Table 1) compared with the corre-
sponding signal typical of uncoordinated PSH. As already
pointed out in monosubstituted and mixed-substituted com-
1
plexes, H and 13C spectra confirmed the magnetic non-
Description of the structures Tc4, Re7 ·1/2H2O, and
Re9. Crystals suitable for X-ray studies were obtained by slow
diffusion of n-hexane into a CH2Cl2 solution for Tc4 and by slow
diffusion of MeCN into a CHCl3 solution for Re7·1/2H2O and Re9.
Data collection parameters and crystal data are reported in Table
2. Selected bond lengths and angles are listed in Table 3.
In complexes Tc4 and Re7 ·1/2H2O, as illustrated in Figures
2 and 3, the unique portion of the unit cell comprises two
neutral molecules (A and B) and since A and B are virtually
superimposable (a part of the tert-Bu groups in Tc4 and the
conformation of the five-membered ReS(1)C(1)C(2)P(1) ring
in Re7 ·1/2H2O), the mean values for bond lengths and angles
are reported in Table 3. In the crystal building of Re7 ·
equivalence of the phosphorus substituents and the diaste-
reotopic nature of the bridging methylene groups. For
illustrative purposes, the 1H-1H COSY and 1H-13C HMQC
maps of [Tc(N)(PSibu)2] (Tc13) are reported in Figure S4
(Supporting Information).
As an example of the byproduct generated in substitution
reduction reactions in nonprotic media, the NMR characteriza-
tion of the bis-substituted mixed oxo-phosphinothiolate complex
[Tc(N)(PSibu)(OPSibu)] (Tc13a) is reported. The complicated
patterns shown in 1H and 13C spectra indicated the presence of
two nonequivalent phosphinothiolate ligands. This feature was
(16) Tolmann, C. A. Chem. ReV. 1977, 77, 313–348.
11980 Inorganic Chemistry, Vol. 47, No. 24, 2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
Figure 2. ORTEP view (33.3% probability) of the complex Tc4.
1/2H2O, a water molecule, without any relevant interaction,
goes with each A-B couple.
In Tc4, the coordination geometry around the Tc center
can be described as intermediate between square pyramidal
(spy) and trigonal bipyramidal (tbpy). In fact, the τ index19
(τ ) 0 for ideal spy and τ )1 for ideal tbpy) is 0.33 and
0.48 for A and B, respectively. In the tbpy description, the
nitrido-group, the chloride, and the thiolato sulfur atoms
occupy the equatorial sites (Tc out of 0.02 Å) with the two
phosphine phosphorus atoms at the apexes of the bipyramid.
The twist-envelope five-membered chelate ring is practically
orthogonal to the N-Cl-S basal plane (88.8° and 86.6° in
A and B, respectively); the overall environment closely
parallels that of the parent complex [Tc(N)Cl(PScy)(PPh3)]
(Tc1),12 and the metrical parameters are in good agreement
with the literature data.20
Figure 3. ORTEP view (33.3% probability) of the complex Re7·1/2H2O.
The water molecule is omitted for simplicity.
The coordination geometry of Re7 ·1/2H2O can be better
regarded as spy (τ ) 0.14 and 0.18 for A and B, respec-
tively); the Re atom deviates markedly (by 0.67 Å) from
the PS3 donor set plane toward the nitrido apex, and the basal
donors are displaced by (0.07 Å.
Inspection of the Cambridge Crystallographic Database
(CCD; version 5.28 of November 2006 and two updates)21
reveals that (i) the number of spy nitrido-Re(V) mono-
nuclear complexes containing in the basal plane P or S as
donor atoms is twenty, (ii) in eight complexes the set is
P2X2 (X ) Cl, Br), (iii) the copresence of P and S donors
is restricted to three compounds with donor set PS2Cl,22
PS2N,23 and P2S2.7
(17) Tubaro, M.; Traldi, P.; Bolzati, C.; Tisato, F.; Refosco, F.; Benini,
E.; Cavazza-Ceccato, M. Rapid Commun. Mass Spectrom. 2005, 19,
1874–1880.
(18) (a) Freiberg, E.; Davis, W. M.; Nicholson, T.; Davison, A.; Jones,
A.; G Inorg. Chem. 2002, 41, 5667–5674. (b) Pe´rez-Lourido, P.;
Romero, J.; Garc`ıa-Va´zquez, J. A.; Sousa, A.; Maresca, K. P.; Zubieta,
J. Inorg. Chem. 1999, 38, 1511–1519. (c) Pe´rez-Lourido, P.; Romero,
J.; Garcy´a´-Va´zquez, J. A.; Sousa, A.; Maresca, K. P.; Zubieta, J. Inorg.
Chem. 1999, 38, 1293–1298. (d) Pe´rez-Lourido, P.; Romero, J.; Garc´ıa-
Va´zquez, J. A.; Sousa, A.; Maresca, K. P.; Zubieta, J. Inorg. Chem.
1999, 38, 3709–3715. (e) Pe`z-Lourido, P.; Romero, J.; Garc`ıa-Va´zquez,
J. A.; Sousa, A.; Maresca, K. P.; Rose, D. J.; Zubieta, J. Inorg. Chem.
1998, 37, 3331–3336. (f) Rose, D. J.; Maresca, K. P.; Kettler, P. B.;
Da Chang, Y.; Soghomomian, V.; Chen, Q.; Abrams, M. J.; Larsen,
S. K. Zubieta J. Inorg. Chem. 1996, 35, 3548–3558.
The Re-S(2) and Re-S(3) bond lengths (2.393 (3) and
2.427(3) Å) match those in the two nitrido-Re(V)
complexes containing the monoanionic form of the dithio-
carbamate ligand,24 while the Tc-S(1) distance (2.335(3)
Å) represents the shortest one, although in accordance with
the values found in the two complexes of reference 22.
(21) (a) Allen, F. H. Acta Crystallogr. 2002, B58, 380–388. (b) Macrae,
C. F.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Shields, G. P.;
Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Crystallogr. 2006,
39, 453–457.
(19) Addison, A. W.; Rao, T. N.; Reedijk, J.; Van Riˆjn, J.; Verschoor,
G. C. J. Chem. Soc., Dalton Trans. 1984, 1349–1356.
(20) (a) Bandoli, G.; Tisato, F.; Dolmella, A.; Agostini, S. Coord. Chem.
Rew. 2006, 250, 561–573. (b) Bandoli, G.; Dolmella, A.; Porchia, M.;
Refosco, F.; Tisato, F. Coord. Chem. Rew. 2001, 214, 43–90.
(22) Rossi, R.; Marchi, A.; Martelli, L.; Magon, L.; Peruzzini, M.; Casellato,
U.; Graziani, R. J. Chem. Soc., Dalton Trans. 1993, 723–729.
(23) Abram, U.; Ritter, S. Inorg. Chim. Acta 1994, 216, 31–36.
Inorganic Chemistry, Vol. 47, No. 24, 2008 11981

Bolzati et al.
as bidentate ligands, while the third one acts as monodentate
only via the sulfur donor. Expansion of the coordination sphere
to a six-coordinate octahedron occurs only in the case of tris-
aryl-PSH ligands, in which extensive π-delocalization through
the benzene ring of the P,S-bite grants chelation of the third
ligand.11
Introduction of the terminal nitrido group into the metal
coordination sphere (giving the [Tc(N)]+2 moiety) allows for
the synthesis of neutral, five-coordinate bis-substituted
[TcV(N)(PS)2] complexes, whose geometry is described as being
intermediate between spy and tbpy.7 The choice for the
arrangement is primarily determined by the length of the alkyl
chain of the P,S-ligand. The ethylene bridging chain favors spy
geometry and the propylene chain favors tbpy geometry.
In all reported Tc- and Re-phosphinothiolate complexes,
the substituents at P were invariably aromatic groups, either
phenyl or substituted phenyl.17,25
Figure 4. ORTEP view (33.3% probability) of the complex Re9.
The Re-P(1) (2.379 (3) Å) and Re-N(1) (1.65 (1) Å)
distance are within the range of values observed in the twenty
comparable complexes.
The structural difference between A and B resides in the
five-membered ring conformation (Figure 3). In both mol-
ecules, the twist-envelope C2 conformation is assumed, but
in A the P(1) and C(2) atoms are +0.38 and -0.26 Å out of
the Re-S(1)-C(1) plane, respectively, whereas in B, S(1)
and C(1)′ are +0.17 and -0.45 Å out of the Re′-P(1)′-C(2)′
plane. As a consequence, the greatest torsion angles are 39.2°
about the P(1)-C(2) bond and 41.1° about S(1)′-C(1)′ in
A and B, respectively.
The Re9 complex closely confirms the metrical data
exhibited by Re7 · 1/2H2O in its form B (Figure 4). In
particular, the twist-enveloped ReS(1)C(1)C(2)P(1) ring
shows S(1) and C(1) atoms out of the Re-P(1)-C(2) ring
by +0.33 and -0.36 Å, respectively, with the greatest torsion
angle (44.1°) about S(1)-C(1) bond.
It is interesting to note that variation of the carbon chain
joining the P and S donor drives the coordination geometry
around the metal center, even if the five-coordinate geometry
is generally favored.7 In all these five- or six-coordinated
complexes, the metal coordination sphere is completely
saturated by the phosphinothiolate ligand, while the corre-
sponding monosubstituted compounds were never achieved.
Biodistribution studies of a series of bis-substituted
[
99mTcV(N)(PS)2] complexes displayed interesting biological
properties.9d In particular, a tracer of this series, incorporating
the 2-dimethylphosphino-propanethiolate ligand, showed the
ability to penetrate the intact BBB making these neutral and
lipophilic compounds attractive to devise a new class of
potential brain perfusion imaging agents. Hence, other
phosphinothiols containing linear or branched alkyl substit-
uents (see Figure 1) have been designed for preparing novel,
lipophilic bis-substituted nitrido Tc(V) species. However, the
diminished π-back properties of alkyl-PS ligands compared
with aryl-PS ones and the peculiar steric constraints of the
phosphine substituents allowed the isolation of rare mono-
substituted compounds, [M(N)(PS)Cl(PPh3)], in which only
one alkylphosphinothiolate was coordinated to the [M(N)]2+
group and the coordination sphere was completed by
monodentate Cl and PPh3. The X-ray molecular structure of
the representative monosubstituted Tc4 complex shows that
the two different P donors are trans coordinated in the solid
state. This feature was confirmed in solution by the occur-
rence of two doublets (with a 2JPP coupling constant of 170
Hz characteristic of a trans-P arrangement) in the 31P NMR
spectra of Re1 and Re2. The trans-P arrangement was crucial
for the stabilization of monosubstituted derivatives because
it allowed delocalization of the high electronic density of
the [M(N)(PS)]+ moiety onto π-accepting PPh3.
Discussion
Phosphinothiols (PSH) represent a class of efficient
chelate ligands whose reactivity toward several metal ions
is well documented, especially for bisaryl-alkyl-phosphi-
nothiols.25 The combination of π-acceptor P with π-donor
S atoms confers peculiar coordination properties to the
P,S-chelate allowing the stabilization of metals in different
oxidation states. Illustrative examples are the chemistries
exhibited by group 7 metals Tc and Re. Starting from
[TcO4]- precursor, the reducing properties of both P and
S donors usually permit the formation of neutral tris-
substituted Tc(III) complexes adopting either tbpy or
octahedral environments and preventing the isolation of
mono-oxo containing Tc(V) compounds.26 The five-
coordinate tbpy geometry, in which two π-acceptor
phosphorus atoms are located at the apexes of the
bipyramid and three π-donor sulfurs at the trigonal base,
is the preferred arrangement exhibited by M(III) com-
plexes.27 In these derivatives, two phosphinothiolates act
Although monosubstituted complexes were accessible for
both metals, their further reactivity with phosphinothiols was
remarkably different. In fact, the use of an excess of PSH
gave rise to bis-substituted [Tc(N)(PS)2] complexes, whereas
the corresponding bis-substituted [Re(N)(PS)2] compounds
did not form at all under similar or more drastic reaction
conditions. Moreover, the different reactivity between the
second and third row congeners was evidenced when
(24) (a) Bolzati, C.; Refosco, F.; Cagnolini, A.; Tisato, F.; Boschi, A.;
Duatti, A.; Uccelli, L.; Dolmella, A.; Marotta, E.; Tubaro, M. Eur.
J. Inorg. Chem. 2004, 1902–1913. (b) Fletcher, S. R.; Skapski, A. C.
J. Chem. Soc., Dalton Trans. 1972, 1079–1082.
(25) Blower, P. J.; Dilworth, J. R. Coord. Chem. ReV. 1987, 76, 121–185.
(26) Dilworth, J. R.; Hutson, A. J.; Morton, S.; Harman, M.; Hursthouse,
M. B.; Zubieta, J.; Archer, C. M.; Kelly, J. D. Polyhedron 1992, 11,
2151–2155.
(27) Maina, T.; Pecorale, A.; Dolmella, A.; Bandoli, G.; Mazzi, U. J. Chem.
Soc., Dalton Trans. 1994, 2437–2443.
11982 Inorganic Chemistry, Vol. 47, No. 24, 2008

Mixed-Substituted Phosphino-thiol Tc/Re-Complexes
particularly encumbering substituents at P were used. For
example, PStbuH straightforwardly afforded monosubstituted
[Tc(N)(PStbu)Cl(PPh3)], while the corresponding rhenium
analog did not form. In any case, the choice of phosphine
substituents played a determining role in the control of the
formation of the monosubstituted compound, as illustrated
by the behavior of the less sterically hindered PSmeH ligand,
which produced only bis-substituted [Tc(N)(PSme)2] without
formation of the monosubstituted [Tc(N)(PSme)Cl(PPh3)].
Monosubstituted [M(N)(PS)Cl(PPh3)] complexes reacted with
dithiocarbamate ligands that selectively replaced monodentate
ClandPPh3groupsgivingneutralmixed-substituted[M(N)(PS)(Ln)].
As established by the X-ray molecular structures of Re7 ·1/
2H2O and Re9 (outlined in Figures 3 and 4), these complexes
are shown to adopt a spy geometry characterized by the
presence of the unprecedented PS3 coordination set on the
basal plane and of the terminal nitrido group at the apex of
the pyramid. The monoanionic dithiocarbamate ligand bonds
the metal through the two sulfur donors producing a neutral
species and making possible extensive π-delocalization
through the four membered S-C-S-Re ring, as confirmed
by the equivalence of the involved M-S bond distance
(Table 3). The accurate combination of phosphinothiolate/
dithiocarbamate donor/acceptor groups is responsible for the
high stability and kinetic inertness of the resulting mixed-
substituted complexes.12 It is worth noting that upon going
from monosubstituted to mixed-substituted compounds the
[M(N)(PS)]+ moieties remain intact. This behavior indicates
that [M(N)(PS)]+ can be considered as a substitution-inert
building block useful for the preparation of new classes of
mixed-ligand 99mTc/188Re compounds.
Carrier-free [99mTc(N)(PS)2] and [99mTc(N)(PS)(Ln)] spe-
cies, whose chemical nature has been proven to be identical
to those of long-lived [Tc(N)(PS)2] and [M(N)(PS)(Ln)] by
chromatographic techniques coupled with radiometric and
UV-vis detections, have already been prepared in high
radiochemical yield.13 Interesting biological profiles for some
of these compounds have been revealed by in ViVo studies,
indicating their ability to cross in and out of the intact BBB.
Hence they are currently under investigation as prototypes
to design new potential brain imaging agents.
The full chemical characterization of these bis-substituted
and mixed-substituted Tc(N)-compounds, combined with
previously reported data give the basis for an initial
structure-activity relationship study.7,9a,12,13 Thus, while the
variation of the carbon chain linking P and S donor in bis-
substituted [Tc(N)(PS)2] seems to have an effect in driving
the coordination geometry from spy to tby, the brain uptake
of two analogue [Tc(N)(PS)2] complexes (where PS is
alternatively a 2-dimethylphosphino propanethiolate or a
2-dimethylphosphino ethanethiolate ligand) are almost the
same suggesting that probably the geometry is not crucial
for the brain uptake. As the cone angle and the sterical
hindrance of the substituents on the P atom increase, the
percentage of cerebral uptake generally decreases. In mixed-
substituted Tc(N) compounds, the replacement of linear
dithiocarbamate (L1) with the corresponding alicyclic ligand
(L2) affects primarily lipophilicity and molecular volume,
as well as diminishing the conformational changes. These
changes are also responsible for the increase in the percent
of injected dose per gram (%ID/g) in the brain.
These results indicated that for these agents the initial
brain uptake was mainly driven by the physical properties
of the complex (i.e., lipophilicity, dimension, shape) and
that the absence on their chemical structures of functional
groups (which through enzymatic or chemical conversion
or receptor interaction are involved in the cerebral trapping
mechanism) is responsible for their rapid tissue washout.
These findings would suggest that future studies should
be focused on more compact molecules and on changes of
the easily modifiable dithiocarbamate coligand with the
appropriate group designed as a trapping mechanism in order
to increase the brain retention for longer time intervals.
Conclusion
In this paper, we have continued to explore the coordina-
tion chemistry of the group 7 metals Tc and Re with
phosphinothiol (PSH) ligands. Alkyl-PSH ligands reacted as
mononegative chelates toward labile nitride-M(V) precur-
sors to afford rare examples of monosubstituted compounds
of the type [M(N)(PS)Cl(PPh3)]. The accessibility of mono-
substituted [M(N)(PS)Cl(PPh3)] species was a function of
the metal used and of the substituents at the phosphinothiolate
P atom. In these complexes, the [M(N)(PS)]+ moieties were
substitution-inert, whereas monodentate chloride and PPh3
were substitution-labile. Hence, [M(N)(PS)Cl(PPh3)] species
were employed as starting materials for the preparation of
additional neutral, symmetrical bis-substituted [Tc(N)(PS)2]
and dissymmetrical mixed-substituted [M(N)(PS)(Ln)] com-
plexes (Ln ) monoanionic dithiocarbamate). All isolated
compounds were completely characterized in solution and
solid states. Crystal structures of mixed-substituted Re7 and
Re9 complexes revealed a square-pyramidal geometry with
the unprecedented PS3 coordination set on the basal plane.
This study confirms that the monosubstituted [M(N)(P-
S)Cl(PPh3)] compounds play an important role in the
development of a new class of dissymmetrical nitrido
compounds containing two different bidentate ligands bound
to the [Tct N]2+ core.
The flexibility of this system, owing to the possibility to
change the substituents at the P atoms, the bidentate ligand,
or both, can be exploited to design a wide range of Mt N
mixed compounds useful in diagnosis or therapy.
Acknowledgment. The authors are grateful to Prof.
Alessandro Dolmella for fruitful discussion and to Anna Rosa
Moresco for elemental analysis.
Supporting Information Available: NMR data of representative
monosubstituted, mixed-substituted and bis-substituted compounds
are reported in Figures S1, S2, S3 and S4. This material is available
free of charge via the Internet at http://pubs.acs.org.
IC801436D
Inorganic Chemistry, Vol. 47, No. 24, 2008 11983