Synthesis, solution-state and solid-state structural characterization of monocationic nitrido heterocomplexes [M(N)(DTC)(PNP)]+ (M = 99Tc, Re; DTC = dithiocarbamate; PNP = heterodiphosphane)

Article abstract of DOI:10.1002/ejic.200300666

Mono-cationic nitrido heterocomplexes of general formula [M(N)(DTC)(PNP)]⁺ (where M is ⁹⁹Tc or Re, DTC is the monoanionic form of a dithiocarbamate ligand, and PNP is a diphosphane ligand with a tertiary amine-containing five-membered spacer) were prepared by ligand-exchange reactions with the labile precursors [M(N)Cl ₂(PPh₃)₂] in dichloromethane/alcohol mixtures. The molecular structure of the representative rhenium complex [Re(N)(dedc)(pnp2)][PF₆] (1) displays a distorted, square-pyramidal geometry with the dithiocarbamate sulfur and the diphosphane phosphorus atoms spanning the four coordination positions on the equatorial plane. If the additional interactions between the nitrido nitrogen and the weakly bonded trans N-diphosphane heteroatom, the molecular geometry can be viewed as pseudooctahedral. The structure in solution, as established by multinuclear NMR spectroscopy and ESI spectrometry, is monomeric, and identical to that shown in the solid state. Replacement of the phenyl groups on the phosphorous atoms in complexes 1, 2, 5, and 6 with alkyl groups modified neither the course of the reaction nor the composition of the resulting complexes. These results, together with the observation that no symmetrical complexes containing two identical bidentate ligands were produced in these reactions, strongly supports the conclusion that a mixed coordination sphere, composed by a combination of π-donor and π-acceptor atoms around the [M≡N]²⁺ group, constitutes a highly stable system. Compounds containing dangling alkyl-substituted groups in the outer sphere (3, 4, 7, and 8) were fully characterized by multinuclear NMR spectroscopy and ESI mass spectrometry. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300666

FULL PAPER
Synthesis, Solution-State and Solid-State Structural Characterization of
99
Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]؉ (M ؍ Tc, Re;
DTC ؍ Dithiocarbamate; PNP ؍ Heterodiphosphane)
Cristina Bolzati,[a] Fiorenzo Refosco,[a] Aldo Cagnolini,[a] Francesco Tisato,*[a]
Alessandra Boschi,[b] Adriano Duatti,[b] Licia Uccelli,[b] Alessandro Dolmella,[c]
Ester Marotta,[d] and Michela Tubaro[d]
Keywords: Technetium / Rhenium / Radiopharmaceuticals / NMR spectroscopy / P ligands
Mono-cationic nitrido heterocomplexes of general formula
[M(N)(DTC)(PNP)]+ (where M is 99Tc or Re, DTC is the mono-
anionic form of a dithiocarbamate ligand, and PNP is a di-
phosphane ligand with a tertiary amine-containing five-
meric, and identical to that shown in the solid state. Replace-
ment of the phenyl groups on the phosphorous atoms in com-
plexes 1, 2, 5, and 6 with alkyl groups modified neither the
course of the reaction nor the composition of the resulting
membered spacer) were prepared by ligand-exchange reac- complexes. These results, together with the observation that
tions with the labile precursors [M(N)Cl2(PPh3)2] in dichloro- no symmetrical complexes containing two identical bidentate
methane/alcohol mixtures. The molecular structure of the
representative rhenium complex [Re(N)(dedc)(pnp2)][PF6]
(1) displays a distorted, square-pyramidal geometry with the
ligands were produced in these reactions, strongly supports
the conclusion that a mixed coordination sphere, composed
by a combination of π-donor and π-acceptor atoms around
dithiocarbamate sulfur and the diphosphane phosphorus the [MϵN]2+ group, constitutes a highly stable system. Com-
atoms spanning the four coordination positions on the equa-
pounds containing dangling alkyl-substituted groups in the
torial plane. If the additional interactions between the nitrido outer sphere (3, 4, 7, and 8) were fully characterized by mul-
nitrogen and the weakly bonded trans N-diphosphane het-
eroatom, the molecular geometry can be viewed as pseudo-
octahedral. The structure in solution, as established by multi-
tinuclear NMR spectroscopy and ESI mass spectrometry.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
nuclear NMR spectroscopy and ESI spectrometry, is mono- Germany, 2004)
Introduction
the development of effective diagnostic or therapeutic ag-
ents. Ultimately, this requires the design of radiopharma-
ceuticals possessing specific molecular features. Metal com-
plexes of technetium and rhenium characterized by a selec-
tive reactivity toward a selected set of coordinating atoms
are currently attracting much interest as suitable precursors
Radioactive isotopes of the two elements technetium and
rhenium play an important role in nuclear medicine for di-
agnostic and therapeutic applications. In particular, the γ-
emitting radionuclide 99mTc has almost ideal properties
(Eγ ϭ 142 keV, t1/2 ϭ 6.06 h) for the imaging of internal
organs. Similarly, the β-emitting radionuclide 188Re is cur-
rently considered to be an important candidate for the de-
velopment of therapeutic agents for the treatment of de-
generative diseases. Selective uptake into the target organ is
one of the key issues that should be always considered in
for
the
design
and
preparation
of
new
radiopharmaceuticals.[1Ϫ3] These complexes can be viewed
as being composed of a robust metal-containing fragment
with
a few substitution-labile coordination positions,
spanned by some weakly bound ancillary ligands. It turns
out that these ancillary substituents can be easily replaced
by ligands which only carry a specific set of coordinating
atoms. The metal unit, therefore, manifests a selective reac-
tivity towards a specific class of ligands, and is almost com-
pletely inert towards other types of reagents. Examples of
this specific class include the low-valent aqua-carbonyl
[TcI(CO)3(OH2)3]ϩ complex[4,5] and high-valent, nitrido-di-
phosphane [Tc(N)(PNP)Cl2] complexes.[6,7] In these com-
plexes, the [Tc(CO)3]ϩ and [Tc(N)(PNP)]2ϩ fragments are
the stable molecular units. In contrast, the water and halide
[a]
Istituto di Chimica Inorganica e delle Superfici Ϫ C.N.R.,
Area della Ricerca, Corso Stati Uniti, 4, 35127 Padua, Italy
Fax: (internat.) ϩ39-049-8702911
E-mail: tisato@icis.cnr.it
[b]
Laboratory of Nuclear Medicine, Department of Clinical &
Experimental Medicine, University of Ferrara,
Via L. Borsari, 46, 44100 Ferrara, Italy
[c]
Department of Pharmaceutical Sciences, University of Padua,
Via Marzolo, 5, 35131 Padua, Italy
[d]
ISTM Ϫ C.N.R.,
Area della Ricerca, Corso Stati Uniti, 4, 35127 Padua, Italy
1902
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejic.200300666
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Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
ligands can be efficiently substituted by a series of bi-func- concentrations), yielded mono-cationic nitrido hetero-
tional tridentate σ-donor ligands (L) and bidentate π-donor complexes, thought to be of general formula
ligands (LЈ), respectively, to yield mixed heterocomplexes of
[
99mTc(N)(DTC)(PNP)]ϩ. Biological evaluation of these
new products demonstrated that they selectively accumulate
the type [Tc(CO)3(L)]ϩ [8,9] and [Tc(N)(PNP)(LЈ)].[10,11]
In the last few years, we have investigated the design of in the myocardium of rats. For some derivatives, retention
nitrido-containing species by exploiting the strong electro- in this region was accompanied by a very fast blood, lung
philic character exhibited by the [M(N)(PNP)]2ϩ metal and liver clearance, suggesting that these tracers could be
fragment, which selectively reacts with nucleophilic biden- potentially utilized for obtaining SPECT myocardial images
tate ligands having a π-donor set of coordinating atoms. In of superior quality compared to those obtained using cur-
particular, emphasis was placed on bidentate ligands con- rently available commercial agents.[13,14] The elucidation of
taining both heteroatomic chelating sites (such as cysteine, the molecular structure of these compounds, therefore, ap-
thiocarboxylic acids, and aminothiols) and homoatomic pears to be of utmost importance for the comprehension
sites (such as dithiols and dithiocarbamates). For example, of their peculiar biological properties. For this reason, we
small peptides having a terminal cysteine residue have been synthesized and structurally characterized a series of nitrido
efficiently labeled with the [99mTc(N)(PNP)]2ϩ complex at a heterocomplexes of technetium and rhenium, obtained by
high-specific-activity level.[10] A cysteine-conjugated 2- treating the nitrido precursors [M(N)Cl2(PNP)] (M ϭ Re,
methoxyphenylpiperazine ligand was linked to the same Tc) with the appropriate dithiocarbamate ligand.
metal fragment to investigate the binding affinity of the re-
The present study describes the synthesis, and solid-state
sulting heterocomplex for 5-HT1A receptors in the central and solution-state determination of the molecular struc-
nervous system.[12]
ture of 99Tc and Re mono-cationic compounds
Within the class of homoatomic bidentate ligands, mono- [M(N)(DTC)(PNP)]ϩ, where DTC indicates the derivatives
anionic dithiocarbamates (DTC) were found to possess a diethyldithiocarbamate (dedc) and N,NЈ-bis(ethoxyethyl)di-
strong affinity for the [99mTc(N)(PNP)]2ϩ complex. Reac- thiocarbamate (dbodc), and PNP represents the diphos-
tions with these ligands, carried out at tracer level (µ phane ligands bis[(diphenylphosphanyl)ethyl]methoxyethyl-
Figure 1. PNP and DTC ligands utilized in this study
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F. Tisato et al.
FULL PAPER
amine (pnp2), bis[(diphenylphosphanyl)ethyl]methylamine
(pnp24), bis[(dimethoxypropylphosphanyl)ethyl]methoxy-
ethylamine (pnp3) and bis[(dimethoxypropylphosphanyl)-
ethyl]ethoxyethylamine (pnp5). The dithiocarbamate and
heterodiphosphane ligands utilized here are depicted
in Figure 1, and the molecular structure of the
[M(N)(DTC)(PNP)]ϩ complexes is outlined in Figure 2.
Results and Discussion
Synthesis of Technetium and Rhenium Complexes
Technetium and rhenium nitrido heterocomplexes con-
taining one diphosphane and one dithiocarbamate ligand
bound to the same TcϵN group were prepared by a one-
pot procedure, as shown in Scheme 1. Reaction of equimo-
lar amounts of [M(N)Cl2(PPh3)2] and the relevant diphos-
phane ligand in dichloromethane/ethanol yielded the inter-
mediate precursor [M(N)Cl2(PNP)], which in turn provided
the mixed-ligand complex on treatment with a slight excess
of dithiocarbamate. Formation of the corresponding bis-
substituted complexes with two identical polydentate li-
gands was not observed, even when 3:1 or 1:3 PNP/DTC
ratios were used.
The reaction was faster for the technetium species, and
afforded nearly quantitative yields. The preparation of the
rhenium analogues required more drastic conditions (i.e.
prolonged reflux), and yields dropped sharply, owing to the
concomitant production of unstable side-products.
Characterization of the Complexes
The complexes were characterized by elemental analysis,
spectroscopic methods and, in the case of complex 1, X-ray
diffraction. The IR spectra of both 1 and 2 exhibit bands
of medium intensity at ca. 1060 cmϪ1, attributable to the
νReϵN stretching vibration. Complex 1 displays an ad-
ditional strong vibration at 840 cmϪ1, characteristic of the
hexafluorophosphate counter-anion.
X-ray Crystal Structure of [Re(N)(dedc)(pnp2)][PF6] (1)
Figure 3 shows the molecular structure of complex 1, to-
gether with the essential numbering scheme. Relevant bond
lengths and angles are given in Table 1. Crystallographic
and structure refinement data are summarized in Table 2
(see Exp. Sect.).
Figure
2.
Sketch
of
the
molecular
structure
of
[M(N)(TDC)(PNP)]ϩ complexes
Scheme 1. Reaction pathway for the preparation of mixed nitride-M() heterocomplexes 1؊8
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Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
Figure 4. A close view of complex 1. The phenyl rings have been
replaced by pseudo atoms labelled as Ph. The C(7) atom position
is split in two positions, each with an occupancy factor of 0.5
Figure 3. An ORTEP view of complex 1 with essential atom num-
bering. Hydrogen atoms have been omitted for clarity; displace-
ment ellipsoids have been drawn at the 40% probability level
methyldithiocarbazate monoanion, POP ϭ bis[(diphenyl-
phosphanyl)ethyl]ether).[7] The S(1)ϪReϪS(2) bite angle of
72.5(1)° and the ReϪS(1) and ReϪS(2) bond lengths of
˚
Table 1. Selected Bond lengths (A) and Angles (°) for complex 1
˚
2.425(3) and 2.413(3) A are in agreement with the reported
ReϪS(1)
ReϪP(1)
ReϪN(1)
S(1)ϪC(8)
2.425(3)
2.408(3)
1.660(9)
1.75(1)
ReϪS(2)
ReϪP(2)
Re···N(2)
S(2)ϪC(8)
2.413(3)
2.396(3)
2.73(1)
1.72(1)
data (average ReϪS distance and SϪReϪS angle of 2.433
˚
A and 71.3°, respectively).
The position assumed by the phenyl rings bound to the
phosphorous atoms deserves comment. The two facing phe-
nyl groups (labeled as A and D in Figure 3) adopt the so-
called ‘‘parallel displaced’’ arrangement, characterized by
S(1)ϪReϪS(2)
P(1)ϪReϪP(2)
N(1)ϪReϪS(1)
N(1)ϪReϪS(2)
72.5(1)
101.2(1)
105.4(3)
106.4(4)
N(1)ϪReϪP(1)
N(1)ϪReϪP(2)
N(1)ϪRe···N(2)
S(1)ϪC(8)ϪS(2)
93.3(4)
96.8(3)
164.4(5)
110.9(7)
˚
the X(A) and X(D) centroid distance of 4.11 A, and the
C(1A)ϪX(A)ϪX(D)ϪC(1D) ‘‘twist angle’’ of 24.1°. These
values corroborate the hypothesis of a possible role for π-
bonds in stabilizing the cis-P coordination. On the other
hand, the two rings bound to each phosphorous atom are
roughly orthogonal to each other, with dihedral angles of
83.9° and 103.9° between the mean planes of A and B, and
C and D, respectively. The A, B, C, and D phenyl rings have
dihedral angles with the S2P2 equatorial plane of 93.3,
117.0, 114.7, and 69.3,°respectively. This plane has a di-
hedral angle of 13.6° to the dithiocarbamate plane [sp2 ge-
ometry at N(3)], defined by the six S(1), S(2), C(8), N(3),
C(9), and C(11) atoms. The methylene carbons of the di-
phosphane chain, C(1), C(4), C(2), and C(3), are located,
Crystalline 1 is made up of well-separated mono-cationic
units and PF6 anions, which do not show any interaction
Ϫ
below the sum of the van der Waals radii. The environment
around the Re atom is square pyramidal, or pseudo-octa-
hedral if we consider the additional weak interaction of
N(2) with the metal, with the base plane defined by the
P(1), S(1), S(2) and P(2) atoms (Figure 4).
˚
None of these atoms deviate more than 0.02 A from the
˚
mean plane, whereas Re is located 0.41 A above the plane,
˚
towards N(1). The ReϵN(1) distance of 1.660(9) A is close
˚
V
˚
respectively, at 1.69, 1.81, 2.64 and 2.64 A below the mean
to the average of 1.675 A found for terminal nitride-Re
compounds (29 entries in the Cambridge Structural Datab-
ase[15]). A similar search for the diphenylphosphinorheni-
S2P2 basal plane, whereas N(2) faces this plane at the inter-
˚
mediate distance of 2.29 A. This additional metalϪN(2) in-
˚
teraction provides further thermodynamic stability to the
system and contributes to the kinetic inertness shown by
this class of mixed nitrido heterocomplexes.
um() synthon gave an average value of 2.484 A for the
ReVϪPPh2R bond (25 entries), a distance markedly longer
than those found for 1 [for which ReϪP(1) and ReϪP(2)
˚
are 2.408(3) and 2.396(3) A, respectively). This shortening
ESI Mass Spectrometry
can be ascribed to the cationic nature of the complex, as
previously observed for similar [Re(N)(pnp2)(L)][BF4] and
The ESI mass spectra of the rhenium complexes 1Ϫ4
[Re(N)(pnp2)(POP)][BF4] compounds (L ϭ S-methyl 2- each show a peak corresponding to the molecular ion with
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F. Tisato et al.
FULL PAPER
no additional detectable fragments, indicating the high sta- corresponding to the unexpected loss of phosphorous-con-
bility of the cation in the oxidative/reductive conditions taining residues originating from the pnp5 ligand. As shown
typical of ESI experiments. To gain further information on in Scheme 3, the resulting species at m/z ϭ 727 most likely
the ligand-rhenium bond strengths, a series of collision adopt a five-coordinate structure (the common arrange-
experiments was undertaken. Such collisions (performed ment for nitrido-containing rhenium compounds), in which
with an ion trap) inidicate the presence of decomposition a native bidentate P,N-phosphinoamine ligand shares the
channels with a low critical energy; the eventual products coordination positions around the ReϭN group with the
represent the more energetically favored pathways. For dithiocarbamate unit. It should be noted that this first frag-
complex 4, under these conditions, many fragment ions be- mentation is identical to that exhibited by the isostructural
come detectable (as summarized in Scheme 2). The related technetium complex 8, which was separately investigated in
collision-induced decomposition pathway is illustrated in a previous study.[16]
Scheme 3. Collision of the molecular cation (m/z ϭ 933)
No variation in the first collision-induced fragmentation
produces abundant fragments at m/z ϭ 755 and 727, both profile is observed for any of the complexes investigated,
Scheme 2. MSn data for complex 4 obtained by resonant excitation of the indicated precursor ion and of the main collision-generated
fragment ions; below, A) ESI-MS spectrum of compound 4; B) MS2 spectrum of the molecular ion (m/z ϭ 727); C) MS3 spectrum of
product ion at m/z ϭ 698; D) MS3 spectrum of the product ion at m/z ϭ 681
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Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
Scheme 3. Fragmentation scheme proposed to rationalize the collision-induced decomposition behavior of complex 4
either by decreasing the bulkiness at the dithiocarbamate the steric hindrance at the N-diphosphinoamine function
ligand (bdodc Ǟ dedc, 4 Ǟ 3), replacing dangling methoxy- (pnp2 Ǟ pnp24, 1 Ǟ 2).
ethyl substituents at the diphosphane phosphorous with ri-
Further MSn experiments implied the loss of ethanol fol-
gid phenyl groups (pnp3 Ǟ pnp2, 3 Ǟ 1), or by diminishing lowed by release of other groups originating from the di-
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F. Tisato et al.
FULL PAPER
thiocarbamate and/or the phosphinoamine ligands. In the magnetic equivalence of the two diphosphane phosphorus
latter case, the substituents begin to play a significant role atoms, complexes 1Ϫ8 exhibit a singlet in the 31P NMR
in the decomposition pathways. For example, dedc com- spectrum, the peak profile being narrow (ν1/2 ഠ 25 Hz) in
plexes 1Ϫ3 always retain the dithiocarbamate ligand intact, the case of rhenium and broad (ν1/2 ഠ 350 Hz) in the case
in contrast to the dbodc complex 4, which undergoes cleav- of technetium.
age of the CϪN bond CϪN, with retention of carbon disul-
fide. Moreover, the bidentate P,N-phosphinoamine ligand
in complexes 1 and 2 releases the diarylalkylphosphane arm
and retains the amine group, whereas the reverse is ob-
served for complexes 3 and 4, which carry the more strongly
donating trialkylphosphanes.
One-dimensional proton and carbon spectra are quite
complicated owing to the presence of overlapping methyl
and methylene signals. However, the use of several two-di-
mensional experiments including homonuclear 1H-1H
1
COSY and heteronuclear H-13C HETCOR makes the as-
signment of each signal possible. By way of example, COSY
and HETCOR maps and the corresponding proton and
carbon spectra for the technetium complex 8 are shown in
Figure 5.
Multinuclear NMR Spectroscopy
The remarkable downfield shift of the 31P signal from
negative values typical of uncoordinated diphosphanes to
The assignment was determined as follows. Methyl car-
positive values for these complexes is diagnostic of metal- bons may be distinguished from methylene carbons with the
phosphorus coordination. Consistent with the expected 13C DEPT-135 experiment (as shown in the bottom right
1
Figure 5. NMR spectra and maps of complex 8; 1H-1H COSY spectrum (top left); H-13C HETCOR spectrum (bottom left); 13C-DEPT
135 spectrum (bottom right); atom numbering scheme (top right); example of interpretation: carbon b is connected (solid line) with
methylene protons b (multiplet at ca. 3.5 ppm) through a unique spot in the HETCOR map; protons b are coupled with methyl protons
a (triplet at ca 1.20 ppm) in the COSY map; protons a are in turn connected with carbon a (dotted line) through another spot in the
HETCOR map; the same interpretation strategy is applied for carbon and protons c and d, and for the other networks
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Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
diagram in Figure 5), the former being phased ‘‘down’’ (on in the spacer or diphosphanes carrying a quaternary am-
the left of the spectrum, as shown) and the latter being monium group in the middle of the spacer yielded only mix-
phased ‘‘up’’ (on the right of the spectrum). The downfield- tures from which the isolation of stable compounds was un-
shifted methyl carbons correspond to the terminal methoxy successful, thus supporting the view that contact of the lone
groups of the phosphane substituents (C-n and C-nЈ); the pair of the amine nitrogen with the metal is important.
splitting is determined by the relative syn and anti orien-
The high chemical stability of mono-cationic
tation of each substituent with respect to the TcϵN core. [M(N)(DTC)(PNP)]ϩ heterocomplexes is also partially re-
The upfield-shifted methyl signal in the carbon spectrum sponsible for their interesting biological properties. These
consists of two overlapping signals (split correctly into two complexes showed selective localization into the myocar-
components in the proton spectrum), due to the presence dium of rats and retention in this region for a prolonged
of two chemically inequivalent ethoxy groups (Me-a and time.[13,14] Modification of the outer sphere pendant groups
Me-e). The related methylene protons of the terminal was found to influence both the kinetics of uptake by
ethoxy groups CH2-b and CH2-f, as well as the methylene the heart and clearance from the background organs,
network of the dithiocarbamate (CH2-c and CH2-d) are dis- giving unprecedentedly high heart/liver and heart/lung
tinguished in the COSY spectrum. Analogously, the methyl- uptake
ratios.[14]
Hence,
the
prototype
agent
ene chain of the pendant N-diphosphane ethoxyethyl frag-
[
99mTc(N)(dbodc)(pnp5)]ϩ was proposed as a potential can-
ment (CH2-h and CH2-g) shows cross peaks in the COSY didate for the development of a new myocardial perfusion
spectrum, as well as two distinct peaks in the HETCOR tracer.[17] These findings prompted us to prepare and
spectrum. Regarding the terminal methoxy groups Me-n characterize macroscopic amounts of the corresponding
and Me-nЈ outlined above, the diphosphane methoxypropyl 99Tc and Re complexes with the aim to elucidate their mo-
chains are oriented syn and anti with respect to the TcϵN lecular structure. As outlined in Figure 4, the solid-state ge-
core, giving two distinct proton networks (i, l and m, and ometry exhibited by the representative rhenium complex 1
iЈ, lЈ and mЈ). The peaks due to the bridging diphosphane is distorted square pyramidal [or pseudo-octahedral if we
methylene protons (o and p) are widely separated and show consider the additional ReϪN(2) contact]. However, the
a cross-peak in the COSY spectrum. The diastereotopic na- flexiblity of the methoxypropyl groups made it impossible
ture of the bridging methylene protons is clear from the to grow crystals suitable for X-ray diffraction studies.
HETCOR map, which shows two distinct spots for each Therefore, we were forced to characterize alkyldiphos-
bridging carbon.
phane-containing compounds in the solution state by
means of combined mass spectrometry and multinuclear
NMR investigations. These experiments confirmed that the
Comments
The efficient synthesis of mono-cationic heterocomplexes molecular structure of these complexes (shown in Figures 2
[M(N)(DTC)(PNP)]ϩ (M ϭ Tc, Re) described here provides and 5) is monomeric and, most importantly, identical to
a clear example of reactions able to form complexes con- that shown by the aryldiphosphane-containing species (Fig-
taining two different polydentate ligands coordinated to the ure 4). In particular, the diphosphane phosphorous atoms,
same TcϵN group. As previously noted for the similar com- as well as the pendant arms of the dithiocarbamate unit,
pound [M(N)(L)(POP)]ϩ [L ϭ S-methyl 2-methyldithiocar- were found to be magnetically equivalent, whereas the
bazate mono-anion, POP ϭ bis[(diphenylphosphanyl)ethy-
l]ether],[7] the remarkable stability of this class of complexes
results from a balance of π-acceptor and π-donor properties
provided by the combination of the diphosphane and dithi-
ocarbamate ligands bound to the same [MϵN]2ϩ group.
The exclusive formation of the mixed complexes
[M(N)(DTC)(PNP)]ϩ, without the concomitant production
of the symmetrical species [M(N)(DTC)2], is attributed to
the strong electrophilic character of the metal fragment
[M(N)(PNP)]2ϩ. This electrophilic character results from
removal of electronic density from the two residual posi-
tions of the five-coordinate arrangement determined by the
two π-acceptor atoms. As a consequence, these two bonding
sites are activated only towards soft, π-donor atoms, and
the whole metal fragment [M(N)(PNP)]2ϩ becomes strongly
stabilized upon substitution with an appropriate bidentate
π-donor ligand. The additional contact between the metal
center and the PNP diphosphane nitrogen helps to explain
the remarkable kinetic inertness demonstrated by these
class of heterocomplexes toward transchelation by other
Figure 6. HPLC co-injection profiles for the complexes
chelating agents.[14] In this regard, it should be mentioned
[
99mTc(N)(dbodc)(pnp5)]ϩ and [99Tc(N)(dbodc)(pnp5)]ϩ 8 (solid
that diphosphanes incorporating merely methylene groups line, radiometric trace; dashed line, UV/Vis trace)
Eur. J. Inorg. Chem. 2004, 1902Ϫ1913
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1909

F. Tisato et al.
FULL PAPER
ized to perrhenate and then reduced to suitable ReV compounds
prior to use. Diethyldithiocarbamate sodium salt (dedcNa) was
purchased from Aldrich Chimica and N,NЈ-bis(ethoxyethyl)dithi-
ocarbamate sodium salt (dbodcNa) was prepared according to lit-
erature methods or obtained from Alchemy, Italy.[20] Aryl diphos-
phanes (pnp2 and pnp24) and alkyl diphosphanes (pnp3 and pnp5)
were synthesized as reported previously[21,22] or purchased from
Argus Chemicals, Italy. Aryl diphosphanes are stable both as solids
and in solution, but alkyl diphosphanes are air and moisture sensi-
tive, and should be handled carefully under a nitrogen atmosphere
methoxypropyl substituents on the phosphorous atoms
were magnetically inequivalent, and oriented syn and anti
with respect to the terminal nitrido group.
Strong support for the conclusion that the chemical nat-
ure of the complex [99mTc(N)(dbodc)(pnp5)]ϩ (prepared at
tracer level) is similar to that of the corresponding 99mTc
analogue (isolated in macroscopic amounts) was obtained
by comparison of their chromatographic profiles after
HPLC co-injection. As shown in Figure 6, the two species
co-eluted at 29.38 min (radiometric trace) and at 28.23 min and stored under nitrogen at Ϫ20 °C to avoid oxidation of the
tertiary diphosphane to the corresponding diphosphaneoxide.
Common laboratory solvents and other chemicals were used as re-
ceived.
(UV/Vis trace).
Conclusion
Elemental analyses (C, H, N, S) were performed on a CarloϪErba
1106 elemental analyzer. FT IR spectra were recorded on a Nicolet
510P Fourier-transform spectrometer in the range 4000Ϫ400 cmϪ1
in KBr mixtures using a Spectra-Tech diffuse-reflectance collector
accessory for technetium compounds and on a Mattson 3030 Four-
ier-transform spectrometer in the range 4000Ϫ400 cmϪ1 in KBr
pellets for rhenium compounds. Proton and 31P NMR spectra were
collected on a Bruker AC-300 instrument, using SiMe4 as an in-
ternal reference (for 1H) and 85% aqueous H3PO4 as an external
reference (for 31P). Mass spectrometric measurements were per-
formed with a LCQ DECA instrument (ThermoFinnigan, Palo
Alto, CA, USA) using ca. 5 ϫ 10Ϫ6 M methanol solutions of rhe-
nium complexes 1؊4, which were injected by a syringe pump at a
flow rate of 5 µL/min. MSn experiments were performed by selec-
tion of the ionic species of interest followed by collision with He
inside the ion trap (He pressure 10Ϫ4 Torr) accomplished by res-
onant excitation. The supplementary rf voltage was in the range
0.25Ϫ4.00 V. Thin-layer chromatography (TLC) was performed
using plates from Merck (Silica gel 60 F 254).
A new family of cationic mixed nitrido heterocomplexes
of general formula [M(N)(DTC)(PNP)]ϩ, where M is 99Tc
or Re, DTC is the mono-anionic form of a dithiocarbamate
ligand and PNP is a heterodiphosphane incorporating a ter-
tiary amine group in a five-membered spacer, has been syn-
thesized and completely characterized both in the solid and
in the solution state. The molecular structure of this class
of mixed complexes is best described as pseudo-octahedral,
with the diphosphane ligand facing the dithiocarbamate
unit on the equatorial plane. The terminal nitrido and the
weakly bound heterodiphosphane nitrogen complete the oc-
tahedron in a reciprocal trans-axial arrangement. The pecu-
liar combination of π-acceptor phosphorous and π-donor
sulfur around the MϵN group ensures remarkable thermo-
dynamic stability and associated high kinetic inertness
towards transchelation reactions. One of these complexes
prepared at tracer level, [99mTc(N)(dbodc)(pnp5)]ϩ, has
shown interesting biological properties in animal models.
Ligands
Diphosphanes and Dithiocarbamates: The diphosphane ligands util-
ized in this work were prepared according to published meth-
ods.[21,22] The full NMR characterizations of these diphosphanes
and of the branched dithiocarbamate Nadbodc are detailed below.
Experimental Section
Bis[(diphenylphosphanyl)ethyl]methoxyethylamine (pnp2): 1H NMR
General Remarks: Caution! 99Tc is a weak β-emitter (Eβ ϭ 0.292
MeV, t1/2 ϭ 2.12 ϫ 105 years). All manipulations were carried out
in laboratories approved for low-level radioactivity using moni-
tored hoods and glove-boxes. When handled in milligram amounts,
99Tc does not present a serious health hazard since common labora-
tory glassware provides adequate shielding. Bremsstrahlung radi-
ation is not a significant problem due to the low-energy of the β-
particles. However, normal radiation safety procedures must be
used at all times, especially with solid samples, to prevent contami-
nation and inhalation. Methanolic solutions (concentration ca. 2
ϫ 10Ϫ6 M) were used for mass spectrometric measurements (ESI).
For a 50-minute analysis at a flow-rate of 5 µL/min, the amount
of 99Tc injected into the mass spectrometer led to a radioactivity
level lower than the environmental background.
(300 MHz, Me4Si, CDCl3):
δ ϭ 2.07 [m, 4 H, NϪ(CH2Ϫ
CH2ϪPPh2)2], 2.59 [m, 4 H ϩ 2 H, NϪ(CH2ϪCH2ϪPPh2)2 and
NϪCH2ϪCH2ϪOϪCH3], 3.20 (s, 3 H, NϪCH2ϪCH2ϪOϪCH3),
3.26 (t, 3J ϭ 9 Hz, 2 H; NϪCH2ϪCH2ϪOϪCH3), 7.30Ϫ7.40
(ϪPPh2, 20 H) ppm. 13C NMR (300 MHz, Me4Si, CDCl3): δ ϭ 25.0
1
2
(d, JC,P ϭ 13 Hz; NϪCH2ϪCH2ϪPPh2), 50.1 (d, JC,P ϭ 35 Hz;
NϪCH2ϪCH2ϪPPh2), 52.8 (s, NϪCH2ϪCH2ϪOϪCH3), 58.7 (s,
NϪCH2ϪCH2ϪOCH3), 70.7 (s, NϪCH2ϪCH2ϪOCH3), 128.4 (d,
3JC,P ϭ 8 Hz), 128.5 (s), 132.7 (d, JC,P ϭ 22 Hz), 138.4 (d, JC,P
ϭ
2
1
8 Hz) (aromatic C) ppm. 31P NMR (300 MHz, 85% H3PO4, CDCl3):
δ ϭ Ϫ21.5 (s).
Bis[(diphenylphosphanyl)ethyl]methylamine (pnp24): 1H NMR
(300 MHz, Me4Si, CDCl3):
δ ϭ 2.14 [m, 4 H, NϪ(CH2Ϫ
CH2ϪPPh2)2], 2.24 (s,
3
H, NϪCH3), 2.48 [m,
4
H,
Technetium (as [NH4][99TcO4]) was obtained from Oak Ridge
National Laboratory. Samples were dissolved in water and treated
with excess aqueous ammonia and 30% H2O2 at 80 °C prior to use
to eliminate residual TcO2. Solid samples of purified ammonium
pertechnetate were obtained by slow evaporation of the solvent at
40 °C. Literature methods were applied to prepare the starting
compounds [M(N)Cl2(PPh3)2][18,19] and the intermediate species
NϪ(CH2ϪCH2ϪPPh2)2], 7.30Ϫ7.41 (ϪPPh2, 20 H) ppm. 13C NMR
1
(300 MHz, Me4Si, CDCl3):
NϪCH2ϪCH2ϪPPh2), 39.6 (s, NϪCH3), 52.7 (d, JC,P ϭ 29 Hz,
δ
ϭ
22.1 (d, JC,P
ϭ
18 Hz;
2
3
NϪCH2ϪCH2ϪPPh2), 128.9 (d, JC,P ϭ 7 Hz), 129.5 (s), 132.7 (d,
1JC,P ϭ 20 Hz), 135.6 (d, 2JC,P ϭ 9 Hz) (aromatic C) ppm. 31P NMR
(300 MHz, 85% H3PO4, CDCl3): δ ϭ Ϫ21.5 (d) ppm.
[M(N)Cl2(PNP)].[7] Finely powdered rhenium was obtained as a Bis[(dimethoxypropylphosphanyl)ethyl]methoxyethylamine (pnp3): 1H
gift from H. C. Starck GmbH, Germany. Samples were first oxid- NMR (300 MHz, Me4Si, CDCl3): δ ϭ 1.36Ϫ1.75 (4 H ϩ16 H,
1910
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Inorg. Chem. 2004, 1902Ϫ1913

Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
NϪ(CH2ϪCH2)2Ϫ[PϪ(CH2ϪCH2ϪCH2ϪOϪCH3)2]2), 2.62 [m, 2 H
night to afford pure compounds as a yellow-orange oils (yield
ϩ4 H, CH3ϪOϪCH2ϪCH2ϪNϪ(CH2ϪCH2)2ϪP], 3.30 (s, 3 H ϩ12 Ͼ90%). For all rhenium complexes, column chromatography (de-
H, OϪCH3), 3.38 (t, 3J
CH2ϪCH2ϪOϪCH3), 3.42 (t, 3J
ϭ
9 Hz,
9 Hz,
8
H, PϪCH2Ϫ scribed below) was necessary to separate the pure species. The fil-
2 H, NϪCH2Ϫ trate was evaporated to dryness and then re-dissolved in the mini-
ϭ
CH2ϪOϪCH3) ppm. 13C NMR (300 MHz, Me4Si, CDCl3): δ ϭ 23.4 mum amount of chloroform. The resulting solution was loaded
1
1
(d, JC,P ϭ 12 Hz, PϪCH2ϪCH2ϪCH2ϪOϪCH3), 24.2 [d, JC,P
ϭ
onto a silica column (diameter 2 cm, length 30 cm) previously con-
13 Hz; PϪ(CH2ϪCH2)2ϪN], 26.0 (d, 2JC,P ϭ 13 Hz; PϪCH2ϪCH2Ϫ ditioned with chloroform. Elution was conducted with chloroform
2
CH2ϪOϪCH3), 50.9 [d, JC,P ϭ 21 Hz; PϪ(CH2ϪCH2)2ϪN], 52.5
(s, NϪCH2ϪCH2ϪOϪCH3), 58.5 (s, PϪCH2ϪCH2ϪCH2ϪOCH3),
(100 mL) followed by a mixture of ethanol/chloroform/toluene/0.5
 ammonium acetate (5:3:3:0.5) to provide the pure compounds in
58.9 (s, NϪCH2ϪCH2ϪOCH3), 71.1 (s, NϪCH2ϪCH2ϪOCH3), low-to-moderate yields (25Ϫ40%). The light yellow residue ob-
73.4Ϫ73.6 (PϪCH2ϪCH2ϪCH2ϪOCH3) ppm. 31P NMR (300 MHz,
85% H3PO4, CDCl3): δ ϭ Ϫ 34.4 (s).
tained after chromatography of complex 1 was dissolved in meth-
anol (2 mL) and added to an excess of NH4PF6 in methanol
(3 mL). Trituration with diethyl ether (20 mL) yielded a yellow-
orange powder, which was filtered off, washed with diethyl ether (2
ϫ 5 mL) and dried under vacuum.
Bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine (pnp5): 1H
NMR (300 MHz, Me4Si, CDCl3): δ ϭ 1.19 (t, 3J ϭ 7 Hz, 3 H,
P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 1.45 (m, 8 H, PϪCH2ϪCH2Ϫ
CH2ϪOϪCH3), 1.54 [m, 4 H, (PϪCH2ϪCH2)2NϪ), 1.68 [m, 8 H,
[Re(N)(dedc)(pnp2)][PF6] (1): C36H45F6N3OP3S2Re (993.0): calcd. C
43.54, H 4.57, N 4.23, S 6.45; found C 43.72, H 4.51, N 4.41, S 6.63.
IR (KBr): ν˜ ϭ 1434 cmϪ1 (s), 1100 (s, ReϪP), 1061 [m, Re(N)],
840 (vs, PF6), 693 (s). 1H NMR (CDCl3, ppm): δ ϭ 1.27 [t, 6 H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2],
2.65
[m,
4
H
ϩ
2 H, PϪ(CH2ϪCH2)2ϪNϪCH2ϪCH2ϪOϪCH2ϪCH3], 3.33 [s, 12
H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 3.40 [t, 3J ϭ 6 Hz, 8 H,
S2CN(CH2ϪCH3)2], 2.53 (t,
3.00Ϫ3.51 [8 H, (PϪCH2ϪCH2)2NϪ], 3.27 (s, 3 H,
P2NϪCH2ϪCH2ϪOϪCH3), 3.57 (t, 2 H, P2NϪCH2Ϫ
CH2ϪOϪCH3), 3.70 [m, 4 H, S2CN(CH2ϪCH3)2], 6.95Ϫ7.94 (20 H,
C6H5ϪP) ppm. 13C NMR (CDCl3, ppm):
12.5 [s,
S2CNϪ(CH2ϪCH3)2], 25.1 [d, JC,P ϭ 14 Hz; PϪ(CH2ϪCH2)2NϪ],
45.0 (s, S2CN(CH2ϪCH3)2], 49.5 [s, P(CH2ϪCH2)2NϪ], 50.9 (s,
P2NϪCH2ϪCH2ϪOϪCH3), 58.9 (s, P2NϪCH2ϪCH2ϪOϪCH3),
67.2 (s, P2NϪCH2ϪCH2ϪOϪCH3), 128.8Ϫ134.0 (C6H5ϪP), 215.8
[s, S2CNϪ(CH2ϪCH3)2] ppm. 31P NMR (CDCl3, ppm): δ ϭ 18.3
(s), Ϫ144.0 (septet, PF6). ESI MS (m/z): 848 [M]ϩ. Yield 35%.
2 H, P2NϪCH2ϪCH2ϪOϪCH3),
PϪ(CH2ϪCH2ϪCH2ϪOϪCH3)2], 3.49 (m,
2
H
ϩ
2
H,
ϾNϪCH2ϪCH2ϪOϪCH2ϪCH3) ppm. 13C NMR (CDCl3, ppm):
1
δ ϭ 15.1 (s, ϾNϪCH2ϪCH2ϪOϪCH2ϪCH3), 23.4 (d, JC,P
12 Hz; PϪCH2ϪCH2ϪCH2ϪOϪCH3), 24.3 [d, JC,P ϭ 12 Hz;
ϭ
1
2
δ
ϭ
PϪ(CH2ϪCH2)2ϪN], 26.0 (d, JC,P
ϭ 14 Hz; PϪCH2ϪCH2Ϫ
1
CH2ϪOϪCH3), 51.0 [d, JC,P ϭ 21 Hz; PϪ(CH2ϪCH2)2ϪN], 52.5
(s, ϾNϪCH2ϪCH2ϪOϪCH2ϪCH3), 58.5 (s, PϪCH2ϪCH2ϪCH2Ϫ
OϪCH3), 66.5 (s, ϾNϪCH2ϪCH2ϪOϪCH2ϪCH3), 69.0 (s, ϾNϪ
CH2ϪCH2ϪOϪCH2ϪCH3), 73.4 and 73.6 (PϪCH2ϪCH2Ϫ
CH2ϪOϪCH3) ppm. 31P NMR (300 MHz, 85% H3PO4, CDCl3): δ ϭ
Ϫ 31.7 (s).
N,NЈ-Bis(ethoxyethyl)dithiocarbamate Sodium Salt (Nadbodc): 1H
NMR (300 MHz, D2O): δ ϭ 1.20 [t, 6 H, S2CN(CH2ϪCH2ϪOϪ
CH2ϪCH3)2], 3.62 [q, 4 H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 3.85
[Re(N)(dedc)(pnp24)][Cl] (2): C34H41ClN3P2ReS2 (839.4): calcd. C
48.64, H 4.92, N 5.00, S 7.64; found C 48.78, H 5.01, N 5.21, S 7.88.
1H NMR (CDCl3, ppm): δ ϭ 1.28 [t, 6 H, S2CN(CH2ϪCH3)2], 2.09
(s, 3 H, NϪCH3), 2.86Ϫ3.56 [8 H, (PϪCH2ϪCH2)2NϪ], 3.70 [m, 4
H, S2CN(CH2ϪCH3)2], 6.96Ϫ7.95 (20 H, C6H5ϪP) ppm. 13C NMR
(CDCl3, ppm): 12.5 [s, S2CNϪ(CH2ϪCH3)2], 24.2 [d, ϪPϪ(CH2Ϫ
CH2)2NϪ], 44.6 (s, NϪCH3), 45.2 [s, S2CN(CH2ϪCH3)2], 50.3 [s,
[t,
4 H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 4.29 [t, 4 H,
S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2] ppm. 13C NMR (300 MHz,
D2O ppm): δ ϭ 17.1 [s, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 57.2 [s,
S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 69.6 and 69.9 [s, S2CN(CH2Ϫ
CH2ϪOϪCH2ϪCH3)2], 213.9 [s, S2CN(CH2ϪCH2ϪOϪCH2Ϫ
CH3)2].
P(CH2ϪCH2)2NϪ],
128.9Ϫ132.4
(C6H5ϪP),
212.5
[s,
S2CNϪ(CH2ϪCH3)2] ppm. 31P NMR (CDCl3, ppm): δ ϭ 18.8 (s).
ESI MS (m/z): 804 [M]ϩ. Yield 25%.
Synthesis of Technetium and Rhenium Complexes: A general one-
pot procedure was adopted for the preparation of both technetium
and rhenium complexes.
[Re(N)(dedc)(pnp3)][Cl] (3): C28H61ClN3O5P2ReS2 (867.5): calcd. C
38.76, H 7.09, N 4.84, S 7.39; found C 39.01, H 7.16, N 4.98, S 7.59.
1H NMR (CDCl3, ppm): δ ϭ 1.37 [t, 6 H, S2CN(CH2ϪCH3)2], 1.73
[M(N)(DTC)(PNP)][Cl] (M ؍ 99Tc, Re) (1؊8): A solution of the
appropriate diphosphane (0.05 mmol) in ethanol (10 mL) was ad-
ded under a nitrogen atmosphere to a three-neck round-bottomed
flask containing a suspension of [M(N)Cl2(PPh3)2] (0.05 mmol) in
dichloromethane (10 mL). The mixture was stirred for 60 min at
[m,
4
H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 1.85 [m,
4
H,
H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 2.04 [m,
2
H
ϩ 2
(PϪCH2ϪCH2)2NϪendo and P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.31
[m, H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.42 (t, H,
P2NϪCH2ϪCH2ϪOϪCH3), 2.66 [m, 2 H, (PϪCH2ϪCH2)2NϪendo],
4
2
room temperature (or at reflux for rhenium complexes) to give a 2.70 [m, 2 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.93 [m, 2 H,
clear bright yellow solution. A solution of DTC sodium salt (PϪCH2ϪCH2)2NϪexo], 3.20 (s, 3 H, P2NϪCH2ϪCH2ϪOϪCH3),
(0.055 mmol) in ethanol (5 mL) was added, and, after reflux for 3.22 [m, H, (PϪCH2ϪCH2)2NϪexo], 3.35 [s, H,
2
6
an additional 60 min (overnight reflux is necessary for rhenium
complexes), the yellow solution was cooled and the solvent re-
moved by a gentle stream of nitrogen. The residue was treated with
dichloromethane (5 mL) and a white precipitate was separated by
filtration. The filtrate was again evaporated to dryness to give a
pale yellow solid residue (for compounds containing aryl diphos-
phanes), or a yellow oil (for compounds containing alkyl diphos-
P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 3.37 [s, 6 H, P(CH2ϪCH2Ϫ
CH2ϪOϪCH3)2exo], 3.38 (m, 2 H, P2NϪCH2ϪCH2ϪOϪCH3),
3.50 [m,
H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 3.82 [m,
S2CN(CH2ϪCH3)2] ppm. 13C NMR (CDCl3, ppm): δ ϭ 12.6
(s, S2CNϪ(CH2ϪCH3)2], 22.9Ϫ26.1 [2 and d,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo/exo (PϪCH2ϪCH2)2NϪ and
4
H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 3.59 [m,
4
4
H,
s
3
,
phanes). Technetium complexes 5 and 6 were purified by treating P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 45.3 [s, S2CN(CH2ϪCH3)2], 48.7 [s,
the residue with ethanol (3 mL). A yellow precipitate was collected
by filtration, washed with diethyl ether (4 ϫ 5 mL) and dried under
vacuum. The oily products 7 and 8 were placed under vacuum over-
P(CH2ϪCH2)2NϪ], 50.3 (s, P2NϪCH2ϪCH2ϪOϪCH3), 58.5 and
58.7 [2 s, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 58.8 (s,
P2NϪCH2ϪCH2ϪOϪCH3), 66.9 (s, P2NϪCH2ϪCH2ϪOϪCH3),
Eur. J. Inorg. Chem. 2004, 1902Ϫ1913
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1911

F. Tisato et al.
FULL PAPER
72.3Ϫ72.5 [m, P(CH2ϪCH2ϪCH2ϪOϪCH3)2] ppm. 31P NMR CH2ϪOϪCH3), 2.54 [m, 2 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2],
(CDCl3, ppm): δ ϭ 13.4 (s). ESI MS (m/z): 832 [M]ϩ. Yield 30%.
2.56 [m,
(PϪCH2ϪCH2)2NϪexo], 3.03 [m, 2 H, (PϪCH2ϪCH2)2NϪexo],
3.14 (s, H, P2NϪCH2ϪCH2ϪOϪCH3), 3.29 (t, H,
P2NϪCH2ϪCH2ϪOϪCH3), 3.31 [s, 6 H, P(CH2ϪCH2ϪCH2Ϫ
OϪCH3)2endo], 3.33 [s, 6 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo],
3.40 (m, 2 H, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 3.45 [q ϩ m, 4 H
2
H, (PϪCH2ϪCH2)2NϪendo], 2.76 [m,
2
H,
[Re(N)(dbodc)(pnp5)][Cl] (4): C33H71ClN3O7P2ReS2 (969.7): calcd. C
40.90, H 7.38, N 4.33, S 6.61; found C 41.08, H 7.46, N 4.28, S 6.86.
1H NMR (CDCl3, ppm): δ ϭ 1.09 (t, 3 H, P2NϪCH2ϪCH2Ϫ
OϪCH2ϪCH3), 1.19 [t, 6 H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2],
1.78 [m, 4 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 1.87 [m, 4 H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 2.04 [m, 2 H, (PϪCH2ϪCH2)2
NϪendo], 2.06 and 2.31 [m, 2 H ϩ 4 H, P(CH2ϪCH2ϪCH2Ϫ
OϪCH3)2], 2.45 (t, 2 H, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 2.67 [m,
2 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.70 [m, 2 H, (PϪCH2Ϫ
CH2)2NϪendo], 2.90 [m, 2 H, (PϪCH2ϪCH2)2NϪexo], 3.23 [m, 2 H,
3
2
ϩ4 H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2
ϩ P(CH2ϪCH2Ϫ
CH2ϪOϪCH3)2endo], 3.55 [m,
OϪCH3)2exo], 3.69 [m,
4
H, P(CH2ϪCH2ϪCH2Ϫ
4
H, S2CN(CH2ϪCH2ϪOϪ
CH2ϪCH3)2], 4.14 [m, 4 H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2]
ppm. NMR (CDCl3, ppm): 15.0 [s,
13C
S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2], 22.0Ϫ24.4 [2 s and 3 d,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo/exo (PϪCH2ϪCH2)2NϪ],
δ
ϭ
(PϪCH2ϪCH2)2NϪexo], 3.32 (q,
CH2ϪCH3), 3.35 [s, 6 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 3.37
[s, H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 3.39 (m, H,
P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 3.50 [q ϩ m, 4 H ϩ 4 H,
S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2 P(CH2ϪCH2ϪCH2ϪOϪ
CH3)2endo], 3.59 [m, 4 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 3.76 [m,
H, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 4.10 [m, H,
S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2] ppm. 13C NMR (CDCl3, ppm):
2 H, P2NϪCH2ϪCH2ϪOϪ
,
ϩ
47.4 [s, P(CH2ϪCH2)2NϪ], 50.2 (s, P2NϪCH2ϪCH2ϪOϪCH3),
51.9 [s, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 58.6 and 58.7 [2 s,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 66.8 (s, P2NϪCH2ϪCH2Ϫ
OϪCH3), 67.0 [s, S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2], 67.8 [s,
S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2], 72.3Ϫ72.5 [m, P(CH2Ϫ
CH2ϪCH2ϪOϪCH3)2], 213.8 [s, S2CNϪ(CH2ϪCH2ϪOϪ
CH2ϪCH3)2].31P NMR (CDCl3, ppm): δ ϭ 29.9 (bs). Yield 85%.
6
2
ϩ
4
4
δ
ϭ
15.1
[s,
S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2
and
ϩ
P2NϪCH2ϪCH2ϪOϪCH2ϪCH3], 23.9Ϫ26.1 [2
s
3
d,
[Tc(N)(dbodc)(pnp5)][Cl] (8): C33H71ClN3O7P2S2Tc (882.4): calcd.
C 44.91, H 8.11, N 4.76, S 7.27; found C 45.32, H 8.33, N 4.67, S
7.44. 1H NMR (CDCl3, ppm): δ ϭ 1.07 (t, 3 H, P2NϪCH2Ϫ
P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo/exo, (PϪCH2ϪCH2)2NϪ)], 48.7
[s, P(CH2ϪCH2)2NϪ], 50.4 (s, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3),
51.9 [s, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 58.5 and 58.7 [2 s,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 64.7 (s, P2NϪCH2ϪCH2ϪOϪ
CH2ϪCH3), 66.5 (s, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 66.9 [s,
S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2], 67.8 [s, S2CNϪ(CH2ϪCH2Ϫ
OϪCH2ϪCH3)2], 72.3Ϫ72.5 [m, P(CH2ϪCH2ϪCH2ϪOϪCH3)2],
220.2 [s, S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2] ppm. 31P NMR
(CDCl3, ppm): δ ϭ 13.4 (s). ESI MS (m/z): 933 [M]ϩ. Yield 30%.
CH2ϪOϪCH2ϪCH3), 1.18 [t,
6 H, S2CN(CH2ϪCH2ϪOϪ
CH2ϪCH3)2], 1.84 [m, 4 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo],
1.90 [m, 4 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 2.10 [m, 2 H,
(PϪCH2ϪCH2)2NϪendo], 2.14 and 2.24 [m,
2 H ϩ 4 H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.38 (t, 2 H, P2NϪCH2ϪCH2Ϫ
OϪCH2ϪCH3), 2.53 [m, 2 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2],
2.56 [m,
2
H, (PϪCH2ϪCH2)2NϪendo], 2.77 [m,
2
H,
(PϪCH2ϪCH2)2NϪexo], 3.04 [m, 2 H, (PϪCH2ϪCH2)2NϪexo],
3.32 (q, 2 H, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 3.34 [s, 6 H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo], 3.36 [s, 6 H, P(CH2ϪCH2Ϫ
[Tc(N)(dedc)(pnp2)][Cl] (5): C36H45ClN3P2S2Tc (780.2): calcd. C
54.30, H 5.69, N 5.28, S 8.05; found C 54.62, H 5.59, N 5.33, S
8.32. 1H NMR (CDCl3, ppm):
δ
ϭ
1.22 (t,
S2CN(CH2ϪCH3)2], 2.45 (t, 2 H, P2NϪCH2ϪCH2ϪOϪCH3),
2.96Ϫ3.46 [8 H, (PϪCH2ϪCH2)2NϪ], 3.22 (s, H,
P2NϪCH2ϪCH2ϪOϪCH3), 3.50 (t, H, P2NϪCH2Ϫ
6
H,
CH2ϪOϪCH3)2exo], 3.40 (m,
2
H, P2NϪCH2ϪCH2ϪOϪ
CH2ϪCH3), 3.50 [q ϩ m, 4 H ϩ 4 H, S2CN(CH2ϪCH2ϪOϪ
CH2ϪCH3)2] ϩ P(CH2ϪCH2ϪCH2ϪOϪCH3)2endo, 3.59 [m, 4 H,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], 3.72 [m, 4 H, S2CN(CH2Ϫ
3
2
CH2ϪOϪCH3), 3.75 [m, 4 H, S2CN(CH2ϪCH3)2], 6.96Ϫ7.89 (20
H, C6H5ϪP) ppm. 13C NMR (CDCl3, ppm): δ ϭ 12.5 [s,
S2CNϪ(CH2ϪCH3)2], 24.0 [d, JC,P ϭ 14 Hz; PϪ(CH2ϪCH2)2NϪ],
44.8 [s, S2CN(CH2ϪCH3)2], 48.5 [s, P(CH2ϪCH2)2NϪ], 50.9 (s,
P2NϪCH2ϪCH2ϪOϪCH3), 58.9 (s, P2NϪCH2ϪCH2ϪOϪCH3),
67.4 (s, P2NϪCH2ϪCH2ϪOϪCH3), S2CN(CH2ϪCH3)2] ppm. 13C
NMR NMR (CDCl3, ppm): δ ϭ 29.9 (bs). Yield 80%.
CH2ϪOϪCH2ϪCH3)2],
4.17
[m,
4
H,
S2CN(CH2Ϫ
CH2ϪOϪCH2ϪCH3)2] ppm. 13C NMR (CDCl3, ppm): δ ϭ 15.1
[s, S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2
OϪCH2ϪCH3], 22.0Ϫ24.4 [2 and
CH2ϪOϪCH3)2endo/exo
ϩ
P2NϪCH2ϪCH2Ϫ
d, P(CH2ϪCH2Ϫ
s
3
,
ϩ
(PϪCH2ϪCH2)2NϪ], 47.4 [s,
P(CH2ϪCH2)2NϪ], 50.3 (s, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3),
51.9 [s, S2CN(CH2ϪCH2ϪOϪCH2ϪCH3)2], 58.6 and 58.7 [2 s,
P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 64.7 (s, P2NϪCH2ϪCH2ϪOϪ
CH2ϪCH3), 66.5 (s, P2NϪCH2ϪCH2ϪOϪCH2ϪCH3), 66.7 [s,
S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2], 67.8 [s, S2CNϪ(CH2Ϫ
CH2ϪOϪCH2ϪCH3)2], 72.3Ϫ72.6 [m, P(CH2ϪCH2ϪCH2Ϫ
OϪCH3)2], 214.0 [s, S2CNϪ(CH2ϪCH2ϪOϪCH2ϪCH3)2] ppm.
31P NMR (CDCl3, ppm): δ ϭ 30.2 (bs). ESI MS (m/z): 847 [M]ϩ.
Yield 89%.
[Tc(N)(dedc)(pnp24)][Cl] (6): C34H41ClN3OP2S2Tc (768.1): calcd. C
54.28, H 5.49, N 5.58, S 8.52; found C 54.63, H 5.71, N 5.39, S
1
8.23. H NMR (CDCl3, ppm): 1.23 (t, 6 H, NϪCH2ϪCH3), 1.98
(s, 3 H, NϪCH3), 2.23Ϫ3.35 [8 H, (PϪCH2ϪCH2)2ϪNϪ], 3.72 (m,
4 H, NϪCH2ϪCH3), 6.97Ϫ7.89 (20 H, Harom) ppm. 13C NMR
(CDCl3, ppm):
ϪPϪ(CH2ϪCH2)2NϪ],
δ
ϭ
12.5 [s, S2CNϪ(CH2ϪCH3)2], 23.5 [d,
43.5 (s, NϪCH3), 44.9 [s,
S2CN(CH2ϪCH3)2], 49.8 [s, P(CH2ϪCH2)2NϪ], 128.9Ϫ132.3
(C6H5ϪP), 210.5 [s, S2CNϪ(CH2ϪCH3)2] ppm. 31P NMR (CDCl3,
ppm): δ ϭ 34.4 (bs). Yield 78%.
X-ray Crystallographic Study: Single crystals of complex 1 were
grown by slow evaporation from DMSO solutions as light yellow
blocks. Pertinent crystallographic data and structure refinement
data are summarized in Table 2. The data set was collected at room
temperature on a Nicolet Siemens R3m /V diffractometer with
[Tc(N)(dbodc)(pnp3)][Cl] (7): C32H69ClN3O7P2S2Tc (868.3): calcd.
C 44.25, H 8.01, N 4.84, S 7.38; found C 44.22, H 8.22, N 4.77, S
7.55. 1H NMR (CDCl3, ppm): δ ϭ 1.15 [t, 6 H, S2CN(CH2ϪCH2Ϫ graphite-monochromatized Mo-Kα radiation. Cell parameters were
OϪCH2ϪCH3)2], 1.84 [m,
OϪCH3)2endo], 1.90 [m, 4 H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2exo], polarization and absorption corrections (Ψ-scans method), the
2.10 [m, 2 H, (PϪCH2ϪCH2)2NϪendo], 2.14 and 2.24 [m, 2 H ϩ 4 structure was solved using the SHELXTL NT computer pro-
H, P(CH2ϪCH2ϪCH2ϪOϪCH3)2], 2.35 (t, 2 H, P2NϪCH2Ϫ gram[23] and refined with SHELXL-97[24] by the full-matrix least-
4
H, P(CH2ϪCH2ϪCH2Ϫ
obtained by fitting a set of 50 high-angle reflections. After Lorentz,
1912
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2004, 1902Ϫ1913

Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]ϩ
FULL PAPER
R. Alberto, R. Schibli, R. Waibel, U. Abram, A. P. Schubiger,
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4510Ϫ4511.
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Schaffland, R. Waibel, D. Tourwe, L. Jeannin, K. Iterbeke, A.
[5]
[6]
Table 2. Crystallographic data for complex 1
Formula
C36H45F6N3OP3ReS2
993.0
Formula mass
Cryst. syst.
Space group
monoclinic
P21/c (No. 14)
11.730(2)
30.234(6)
11.732(2)
93.44(3)
4153(1)
4; 1.588
32.0
23
0.71073
24
4809
0.053
[7]
[8]
˚
a, A
˚
b, A
˚
c, A
`
β, °
P. Schubiger, J. Nucl. Med. 1999, 40, 1913Ϫ1917.
3
˚
V, A
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R. Waibel, R. Alberto, J. Willuda, R. Finnern, R. Schibli, A.
Stichelberger, A. Egli, U. Abram, J.-P. Mach, A. Pluckthun, A.
P. Schubiger, Nat. Biotechnol. 1999, 17, 897Ϫ901.
Z, Dcalcd., g cmϪ3
µ (Mo-Kα), (cmϪ1
T (°C)
)
[10]
`
A. Boschi, C. Bolzati, E. Benini, E. Malago, L. Uccelli, A.
˚
λ (Mo-Kα), A
Duatti, A. Piffanelli, F. Refosco, F. Tisato, Bioconjugate Chem.
2001, 12, 1035Ϫ1042.
Θmax, °
Obsd. reflections [I Ͼ 2σ(I)]
[11]
[12]
F. Refosco, C. Bolzati, A. Duatti, F. Tisato, L. Uccelli, Recent
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wR2[b]
GOF[c]
0.121
1.045
`
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[a]
[b]
2
2 2
R1 ϭ Σ|Fo| Ϫ |Fc|/Σ|Fo|.
wR2 ϭ {Σ[w (Fo Ϫ Fc ) ]/
[13]
[14]
[15]
Σ[w(Fo ) ]}1/2 [c] GOF ϭ {Σ[w (Fo Ϫ Fc ) ]/(n Ϫ p)}1/2 (n ϭ reflec-
.
2 2
2
2 2
tions; p ϭ parameters).
squares technique based on F2. Figures were drawn with the OR-
TEP II program.[25] The final difference map was featureless, apart
from a relevant residue in the vicinity of C(7) atom, indicating a
possible second position [C(7Ј)]. This model was refined satisfac-
torily with occupancies of ca. 0.5. Anisotropy was applied only to
nonϪcarbon atoms to assure a good reflections/parameters ratio.
CCDC-220372 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223-336-033; E-mail:
deposit@ccdc.cam.ac.uk].
[16]
[17]
[18]
[19]
[20]
Acknowledgments
The authors are grateful to Nihon Medi-Physics, Tokio, Japan, for
financial support of this work, and to A. Moresco for elemental
analyses.
[21]
[22]
[23]
[24]
[25]
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Received September 25, 2003
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Early View Article
Published Online March 31, 2004
Eur. J. Inorg. Chem. 2004, 1902Ϫ1913
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1913