Oxo-rhenium(V) mixed-ligand complexes with bidentate functionalized phosphines and tridentate Schiff base ligands

Article abstract of DOI:10.1016/S0020-1693(01)00357-7

A series of monooxo-rhenium(V) mixed-ligand complexes containing bidentate functionalized phosphines and tridentate Schiff base (SB) ligands have been synthesized via ligand-exchange reactions starting from labile Re(V) precursors. A convenient route of synthesis is provided by the isolation of intermediate species such as [Re(O)(Lⁿ)Cl₃]^- (1-3), (Lⁿ = bidentate phosphino-phenolato or phosphino-carboxylato ligands). Subsequent addition of the relevant SB affords neutral mixed-ligand complexes of general formula [Re(O)(Lⁿ)(SB^m)] (1-3m). By reversing the addition of the two ligands, i.e. SB first followed by functionalized phosphine, the resulting mixed-ligand species do not change formulation. Conventional spectroscopic techniques and the single-crystal X-ray structure determination of the two representative compounds ([Re(O)(L¹)(SB^a)] (1a) and [Re(O)(L¹)(SB^b)] (1b)) reveal a distorted octahedral geometry around the rhenium center, with the phosphino-phenolato oxygen located trans to the oxo group and the equatorial sites filled by the SB donors and the phosphine phosphorus. It is worth noting that technetium chemistry works quite differently under the same reaction conditions. In fact, no intermediate species of the type [Tc(O)(Lⁿ)Cl₃]^- can be isolated with [Tc(O)Cl(L¹)₂] and reduced [Tc(Lⁿ)₃] being the major compounds.

Full text of DOI:10.1016/S0020-1693(01)00357-7

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Inorganica Chimica Acta 315 (2001) 205–212
Oxo-rhenium(V) mixed-ligand complexes with bidentate
functionalized phosphines and tridentate Schiff base ligands
Cristina Bolzati a, Marina Porchia a, Giuliano Bandoli b,*, Alessandra Boschi c,
c
Erica Malago` , Licia Uccelli c
a Istituto di Chimica e Tecnologie Inorganiche e dei Materiali A6anzati, Consiglio Nazionale delle Ricerche, Corso Stati Uniti 4,
35127 Pado6a, Italy
b Dipartimento di Scienze Farmaceutiche, Uni6ersita` di Pado6a, Via Marzolo, 5, 35131 Pado6a, Italy
c Laboratorio di Medicina Nucleare, Dipartimento di Medicina Clinica e Sperimentale, Uni6ersita` di Ferrara, Via Borsari, 46,
44100 Ferrara, Italy
Received 10 November 2000; accepted 29 January 2001
Abstract
A series of monooxo-rhenium(V) mixed-ligand complexes containing bidentate functionalized phosphines and tridentate Schiff
base (SB) ligands have been synthesized via ligand-exchange reactions starting from labile Re(V) precursors. A convenient route
of synthesis is provided by the isolation of intermediate species such as [Re(O)(Ln)Cl3]− (1–3), (Ln=bidentate phosphino-pheno-
lato or phosphino-carboxylato ligands). Subsequent addition of the relevant SB affords neutral mixed-ligand complexes of general
formula [Re(O)(Ln)(SBm)] (1–3m). By reversing the addition of the two ligands, i.e. SB first followed by functionalized phosphine,
the resulting mixed-ligand species do not change formulation. Conventional spectroscopic techniques and the single-crystal X-ray
structure determination of the two representative compounds ([Re(O)(L1)(SBa)] (1a) and [Re(O)(L1)(SBb)] (1b)) reveal a distorted
octahedral geometry around the rhenium center, with the phosphino-phenolato oxygen located trans to the oxo group and the
equatorial sites filled by the SB donors and the phosphine phosphorus. It is worth noting that technetium chemistry works quite
differently under the same reaction conditions. In fact, no intermediate species of the type [Tc(O)(Ln)Cl3]− can be isolated with
[Tc(O)Cl(L1)2] and reduced [Tc(Ln)3] being the major compounds. © 2001 Elsevier Science B.V. All rights reserved.
Keywords: Rhenium complexes; Oxo complexes; Crystal structures; Bidentate phosphine complexes; Schiff base complexes
ceutical field. In addition, the recent advent of the two
b-emitters 186Re and 188Re in the therapeutic field [2]
makes even more obvious the use of the third-row
congener itself, in order to elucidate the molecular
structure of ‘hot’ rhenium agents relevant to nuclear
medicine.
Very recently a new concept has emerged in the
design of substitution-inert technetium and rhenium
agents. In this connection, it is necessary to generate a
robust ‘metal-fragment’, to which small bifunctional
ligands bearing specific pharmacophores can be eventu-
ally coordinated. The metal-fragment contains the ion
stabilized in an appropriate oxidation state by means of
a suitable ligand framework, which only partially fills
the coordination sphere. Examples of application of
this concept include the recently developed low valent
Tc-tricarbonyl [TcI(CO)3]+ [3] and the high valent
1. Introduction
Rhenium is often used as a technetium surrogate to
study the macroscopic chemistry of potentially useful
agents in nuclear medicine because of the chemical
similarities of these Group 7 elements. Although re-
markable differences have been observed in terms of
redox behavior and kinetics of substitution [1], the
advantage of operating with ‘cold’ materials (the natu-
ral isotopic mixture of 185Re and 187Re), instead of
using a radioactive nuclide (the soft b-emitter 99gTc),
makes rhenium chemistry, at macroscopic level, very
attractive for researchers involved in the radiopharma-
* Corresponding author. Tel.: +39-49-8275344; fax: +39-49-
8275345.
E-mail address: bandoli@dsfarm.unipd.it (G. Bandoli).
0020-1693/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0020-1693(01)00357-7

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C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
‘super-nitrido’ [TcV(N)(PNP)]2+ [4] (PNP=tridentate
aminediphosphine ligand) fragments. On the opposite
side of the molecule these substitution-inert moieties
accommodate labile ligands, i.e. water molecules and/or
related hydroxyl functions or halide groups. These
monodentate ligands can be readily replaced by incom-
ing small chelate ligands, either bidentate or tridentate
as in the examples detailed above, which may balance
the positive charge of the moiety and fill completely the
final octahedral coordination sphere. In this connec-
tion, technetium and rhenium systems, named ‘3+1’
[5], can also join the metal-fragment concept if we
consider the [MV(O)(SNS)]+ group (SNS=tridentate
aminedithiolate ligand) a substitution-inert moiety to
which a monodentate thiolate group can be attached.
However, the [MV(O)(SNS)]+ moiety and related neu-
tral and lipophilic ‘3+1’-[MV(O)(SNS)(SR)] com-
pounds do not appear to be stable enough both in vivo
and in vitro, given that hydrophilic adducts are gener-
ated during incubation of these agents with physiologi-
cally relevant molecules such as cysteine or glutathione
[6].
this direction have generated a class of monooxo-rhe-
nium mixed-ligand complexes of general formulation
[ReV(O)(L1)(‘T’)], where ‘T’ is a tridentate aminedithio-
late or diaminethiolate ligand (see Refs. [21–23]).
Reactions of the [ReV(O)(Ln)]2+ metal-fragments
with the Schiff base (SB) ligands N-(2-hydroxy-
phenyl)salycilideneimine (H2SBa), N-(2-hydroxy-3-
metoxhyphenyl)salycilideneimine (H2SBb) and N-(2-
mercaptophenyl)salycilideneimine (H2SBc) afford stable
oxorhenium‘3+2’ mixed-ligand complexes [ReV(O)-
(Ln)(SBm)], as outlined in Scheme 1.
Despite the general assumption that rhenium and
technetium exhibit similar synthetic chemistries, we re-
port here on the remarkable different reactivity of
bidentate functionalized phosphines toward oxo-rhe-
nium compounds compared to oxo-technetium analogs.
The strategy adopted for the synthesis of these rhenium
mixed-ligand heterocomplexes appears to be not suit-
able for radiodiagnostic technetium at ‘no carrier
added’ conditions (vide infra). On the contrary, by
using specific phosphines, such strategy might be useful
for rhenium also at ‘no carrier added’ level. Until now
only oxo-rhenium agents including tetradentate frame-
works such as N2S2-diaminodithiols and N3S-MAG3-
type ligands [7] have been tested for radiotherapeutic
application. Our proposed [Re(O)(Ln)] moiety consti-
tutes a novel substitution-inert metal-fragment which
may eventually conjugate bioactive molecules on the
coordination vacant sites.
Looking for additional stable metal-fragments in-
cluding the monooxo core, we have studied the suitabil-
ity of the [ReV(O)(Ln)]2+ framework as a new potential
building-block for producing mixed-ligand heterocom-
plexes (HLn is a bidentate functionalized phosphine, in
detail
diphenylphosphino
HL1=o-diphenylphosphinophenol,
acetic acid and
HL2=
HL3=o-
diphenylphosphino benzoic acid). Previous efforts in
Scheme 1.

C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
207
Table 1
Selected spectral parameters of the rhenium complexes prepared in this work
Complex
w(ReꢀO) (cm−1
)
31P (ppm)
1Himine
1Haromatic 1H, others
[n-bu4N][ReOCl3(L1)] (1)
[n-bu4N][ReOCl3(L2)] (2)
[n-bu4N][ReOCl3(L3)] (3)
[ReO(L1)(SBa)] (1a)
963
985
983
964
959
949
989
978
−8.6 (s)
−14.2 (s)
−22.8 (s)
10.3 (s)
8.1 (s)
8.0 (s)
−1.5 (s)
−8.3 (s)
7.9–6.4
8.2–7.0
8.2–7.0
8.1–6.4
8.1–6.4
8.4–6.2
8.1–6.6
8.4–6.7
0.90, 1.31, 1.53, 3.19 [butyl-H]
0.90, 1.31, 1.65, 3.29 [butyl-H]
0.92, 1.33, 1.65, 3.29 [butyl-H]
8.89 (d), JHP=17 Hz
8.91 (d), JHP=17 Hz
9.02 (d), JHP=19 Hz
8.90 (d), JHP=16 Hz
8.91 (d), JHP=17 Hz
[ReO(L1)(SBb)] (1b)
[ReO(L1)(SBc)] (1c)
3.61 (s), OMe
3.65 (s), OMe
3.80 (s), OMe, 3.91 (dd, CH2)
3.68 (s), OMe
[ReO(L2)(SBb)] (2b)
[ReO(L3)(SBb)] (3b)
2. Experimental
to obtain a pure compound. Yield: 75 mg, 55%. Anal.
Found: C, 45.45; H, 6.01; N, 1.67. Calc. for
C30H48NO3PReCl3: C, 45.36; H, 6.09; N, 1.76%. IR
(KBr, w, cm−1): 2962, 2874, 1639 (s, w[COO]), 1483,
1314, 1285, 1097, 985 (s, w[ReꢀO]), 853, 755, 693, 504.
1H NMR (200 MHz, CDCl3, l ppm): 0.90 (t, 12H);
1.31 (m, 8H); 1.65 (m, 8H); 3.29 (m, 8H) [n-Bu4N]; 3.82
2.1. General
All chemicals were of reagent grade and used as such
without prior purification. The synthesis of
o-diphenylphosphinophenol (HL1) [8], diphenylphos-
phino acetic acid (HL2) [9] and o-diphenylphosphino
benzoic acid (HL3) [10] were performed according to
published protocols. Tridentate SB ligands N-(2-hy-
droxyphenyl)salycilideneimine (H2SBa), N-(2-hydroxy-
3-metoxhyphenyl)salicylideneimine (H2SBb) and N-(2-
mercaptophenyl)salicylideneimine (H2SBc) were synthe-
sized as reported previously [11]. Rhenium was pur-
chased from Aldrich as KReO4 and was converted first
to the labile precursor [(n-C4H9)4N][ReOCl4] according
to published methods [12]. IR spectra were recorded on
KBr pellets on a Mattson 3030 Fourier-transform spec-
2
(d, 2H, JHP=11.0 Hz, PꢁCH2ꢁCOO); 7.0–8.2 (10H,
Ar-H). 13C NMR (200 MHz, CDCl3, l ppm): 13.70,
19.72, 24.05, 58.68 [n-bu4N]; 37.68 (d, PꢁCH2ꢁCOO);
128.70, 130.71, 131.52, 133.26 (Ar-C); 172.62
(PꢁCH2ꢁCOO); 31P NMR (200 MHz, CDCl3, ppm):
−22.8 (s). The product is soluble in chlorinated sol-
vents, sparingly soluble in alcohols and insoluble in
Et2O.
2.3. Synthesis of mixed-ligand oxo-Re(V) complexes
[ReO(Ln)(SBm)]
trophotometer in the region 400–4000 cm−1. H and
1
31P NMR spectra were recorded on a Bruker AC-200
The three mixed-ligand compounds containing the
phosphinophenolato fragment (L1) were prepared using
the same procedure, detailed below for 1a.
1
instrument, using SiMe4 as internal reference (for H)
and 85% aqueous H3PO4 as external reference (for 31P).
Samples were dissolved in deuterated chloroform at a
concentration of approximately 1–2%. Elemental
analyses for C, H, N and S were conducted on a Fisons
EA1108 elemental analyzer.
2.3.1. [ReO(L1)(SBa)] (1a)
The emerald [n-bu4N][ReOCl3(L1)] intermediate com-
plex 1 (120 mg, 0.145 mmol) is suspended in EtOH (15
ml). An equimolar amount of solid N-(2-hydrox-
yphenyl)salicylideneimine H2SBa (31 mg, 0.145 mmol)
is added under stirring at r.t. The darkened mixture was
refluxed for 30 min. On cooling a dark-red precipitate
appeared. The solid was filtered off and washed with a
few drops of EtOH and Et2O (3×10 ml). Recrystalliza-
tion from CH2Cl2–EtOH mixtures gave 81 mg of pure
1a. Yield 81%. Anal. Found: C, 53.06; H, 3.64; N, 1.87.
Calc. for C31H23NO4PRe: C, 53.88; H, 3.35; N, 2.02%.
IR (KBr, w, cm−1): 1604, 1582, 1454, 1432, 1380, 1297,
2.2. Synthesis of intermediate [ReO(Ln)Cl3]−
complexes
2.2.1. [ReO(L1)Cl3]− (1) and [ReO(L3)Cl3]− (3)
Complexes 1 and 3 were prepared as reported previ-
ously [13,14]. For these two complexes selected spectral
parameters are reported in Table 1.
2.2.2. [ReO(L2)Cl3]− (2)
1
A solution of [n-bu4n][ReOCl4] (100.6 mg, 0.171
mmol) in EtOH (10 ml) was treated with a slight excess
of HL2 (50 mg, 0.204 mmol) under stirring at room
temperature (r.t.). The solution became suddenly blue
and deposited within a few minutes a turquoise solid,
which was filtered off and washed with EtOH (3 ml)
and Et2O (3×5 ml). No recrystallization was necessary
1248, 1126, 964 (s, w[ReꢀO]), 855, 840, 755. H NMR
(200 MHz, CDCl3, l ppm): 6.4–8.1 (22H, Ar-H), 8.89
(s, 1H; ꢁCHꢀNꢁ). 31P NMR (200 MHz, CDCl3, l
ppm): 10.3 (s). The product is soluble in chlorinated
solvents, insoluble in alcohols and in Et2O. Crystals
suitable for X-ray diffraction analysis were grown from
CH2Cl2–MeOH mixtures.

208
C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
2.3.2. [ReO(L1)(SBb)] (1b)
Yield 76%. Anal. Found: C, 50.12; H, 3.51; N, 1.82.
Calc. for C33H27NO5PCl2Re: C, 49.18; H, 3.38; N, 1.74.
IR (KBr, w, cm−1): 1585, 1543, 1456, 1426, 1381, 1253,
2.3.4. [ReO(L2)(SBb)] (2b)
The turquoise [n-bu4N][ReOCl3(L2)] intermediate
complex 2 (90 mg, 0.118 mmol) is suspended in EtOH
(15 ml). An equimolar amount of solid N-(2-hydroxy-3-
metoxhyphenyl)salycilideneimine H2SBb (29 mg, 0.119
mmol) is added under stirring at r.t. The mixture
quickly darkened and was refluxed for 30 min. On
cooling a bright-red precipitate appeared, which was
filtered off and washed with a few drops of EtOH and
Et2O (3×10 ml). Recrystallization from CH2Cl2–
EtOH mixtures gave 63 mg of pure 2b. Yield 69%.
Anal. Found: C, 49.12; H, 3.47; N, 1.92. Calc. for
C28H23NO6PRe: C, 48.96; H, 3.37; N, 2.04%. IR (KBr,
w, cm−1): 1663, 1595, 1546, 1480, 1435, 1389, 1256, 989
1
1242, 959 (s, w[ReꢀO]), 855, 832, 740, 511. H NMR
(200 MHz, CDCl3, l ppm): 3.61 (s, 3H; ꢁOCH3);
6.4–8.1 (21H, Ar-H); 8.91 (s, 1H; ꢁCHꢀNꢁ). 31P NMR
(200 MHz, CDCl3, l ppm): 8.1 (s). The product is
soluble in chlorinated solvents, sparingly soluble in
alcohols and insoluble in Et2O. Crystals suitable for
X-ray diffraction analysis were grown from CH2Cl2
solutions layered with MeOH.
2.3.3. [ReO(L1)(SBc)] (1c)
1
Yield 85%. Anal. Found: C, 51.97; H, 3.25; N, 1.89;
S, 4.43. Calc. for C31H23NO3SPRe: C, 52.66; H, 3.28;
N, 1.98; S, 4.53%. IR (KBr, w, cm−1): 1606, 1583, 1541,
1426, 1386, 1253, 1219, 1177, 949 (s, w[ReꢀO]), 853,
(s, w[ReꢀO]), 742, 518. H NMR (200 MHz, CDCl3, l
ppm): 3.80 (s, 3H; ꢁOCH3); 3.91 (dd, 2H; PꢁCH2ꢁ, AB
system); 6.6–8.1 (17H, Ar-H); 8.90 (s, 1H; ꢁCHꢀNꢁ).
31P NMR (200 MHz, CDCl3, l ppm): −1.5 (s). The
product is soluble in chlorinated solvents, insoluble in
alcohols and in Et2O.
1
746, 511. H NMR (200 MHz, CDCl3, l ppm): 3.65 (s,
3H; ꢁOCH3); 6.2–8.4 (21H, Ar-H); 9.02 (s, 1H;
ꢁCHꢀNꢁ). 31P NMR (200 MHz, CDCl3, l ppm): 8.0
(s). The product is soluble in chlorinated solvents,
insoluble in alcohols and in Et2O.
2.3.5. [ReO(L3)(SBb)] (3b)
The turquoise [n-bu4N][ReOCl3(L2)] intermediate
complex 3 (135 mg, 0.157 mmol) is suspended in EtOH
(15 ml). An equimolar amount of solid N-(2-mercap-
tophenyl)salycilideneimine (H2SBc) (36 mg, 0.157
mmol) is added under stirring at r.t. The mixture
becomes dark within a few minutes. It is then refluxed
for 30 min. On cooling a bright-red precipitate ap-
peared, which is filtered off and washed with a few
drops of EtOH and Et2O (3×10 ml). Recrystallization
from CH2Cl2–EtOH mixtures gave 109 mg of pure 3b.
Yield 92%. Anal. Found: C, 52.86; H, 3.53; N, 1.80.
Calc. for C33H25NO6PRe: C, 52.92; H, 3.36; N, 1.87%.
IR (KBr, w, cm−1): 1652, 1595, 1546, 1480, 1434, 1385,
1303, 1283, 1253, 1098, 978 (s, w[ReꢀO]), 837, 747, 694,
Table 2
Structure determination summary of complexes 1a and 1b
Complex 1a
Complex 1b
Empirical formula
Formula weight
Crystal system
C31H23NO4PRe C33H27Cl2NO5PRe
690.67
monoclinic
P21/c
805.63
triclinic
(
Space group
P1
1
Unit cell dimensions
534, 506. H NMR (200 MHz, CDCl3, l ppm): 3.68 (s,
,
a (A)
9.890(4)
15.792(5)
16.949(6)
90.00
99.34
90.00
10.204(5)
11.586(7)
13.832(6)
71.95(4)
75.12(4)
71.99(4)
1455(1)
2
3H; ꢁOCH3), 6.7–8.4 (21H, Ar-H); 8.91 (s, 1H;
ꢁCHꢀNꢁ). 31P NMR (200 MHz, CDCl3, l ppm): ꢁ8.3
(s). The product is soluble in chlorinated solvents,
insoluble in alcohols and in Et2O.
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
Volume (A )
Z
3
,
2612(2)
4
2.4. X-ray diffraction data and crystal structure
determination and refinement for 1a and 1b
Temperature (K)
293(2)
1.756
293(2)
1.839
zcalcd (g cm−3
)
Absorption coefficient
(mm−1
F(000)
Independent reflections
Observed reflections
[I]2|(I)]
4.75
4.46
The experimental X-ray data for 1a and 1b are
summarized in Table 2, while some selected bond
lengths and angles are given in Table 3. Data for both
complexes were collected at r.t. (293 K) on a Siemens
Nicolet R3m/V diffractometer with Mo Ka radiation
)
1352
2812
2016
792
3824
3163
full matrix least-squares on F2
(u=0.71073 A) in the restricted range 2.15[522.5°.
,
Refinement method
Final R indices [I]2|(I)] R1 a=0.045
R1 a=0.046
wR2 b=0.057
1.061
In fact, much of the higher angle data collected were
weak and bore negative intensity. The final cell parame-
ters were determined from 50 reflections at [\10°.
Data were corrected for Lorentz polarization and ab-
sorption effects. Both structures were solved by heavy-
wR2 b=0.068
0.925
Goodness-of-fit
a R1=ꢀꢁꢁFoꢁ−ꢁFcꢁꢁ/ꢀꢁFoꢁ.
b wR2={ꢀ[w(Fo 2−Fc 2)2]/ꢀ[w(Fo 2)2]}1/2
.

C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
209
rhenium heterocomplexes [ReV(O)(Ln)(SBm)] (1–3m)
can be prepared in alcoholic solutions using two alter-
native routes by changing the sequential addition of the
ligands. In both cases intermediate compounds of the
type [ReV(O)(Ln)Cl3]− (1–3) or [ReV(O)(SBm)Cl2]− are
isolated; they further react with the other ligand to give
the heterocomplexes in high yields.
Table 3
Selected bond length (A) and angles (°) for complexes 1a and 1b
,
Complex 1a
Complex 1b
ReꢁP(1)
ReꢁO(1)
ReꢁO(2)
ReꢁO(3)
ReꢁO(4)
ReꢁN(1)
2.425(4)
1.69(1)
2.01(1)
2.03(1)
2.035(9)
2.12(1)
2.432(3)
1.651(9)
2.008(8)
2.047(8)
2.039(8)
2.08(1)
Simultaneous addition of the two different ligands,
HLn and H2SBm, to [ReOCl4]− solutions (1:1:1
metal:HLn:H2SBm ratio) still affords the heterocom-
plexes (in lower yield than above) contaminated by
small amounts of the intermediate species. When an
excess of the two ligands is utilized (1:2:2
metal:HLn:H2SBm ratio), different results are obtained
depending on the functionalized phosphine employed.
While reaction mixtures containing the phosphino-car-
boxylic ligands HL2 or HL3 and the relevant SB yield
the heterocomplexes, the phosphino-phenol ligand HL1
produces the bis-substituted compound [ReV(O)(L1)2Cl]
as the major product, contaminated by several impuri-
ties including the intermediate SB complex
[ReV(O)(SBm)Cl2]−. This challenge reaction indicates
that the phosphino-phenol is by far the kinetic donor,
and that [ReV(O)(L1)2Cl)] is thermodynamically favored
over the heterocomplex. In fact, prolonged reflux does
not induce significant change in the final products. The
reactivity of rhenium with HL1 parallels the chemistry
exhibited by technetium with phosphino-phenol lig-
ands, where the phosphine-rich [TcV(O)(L1)2Cl] [17] and
eventually the reduced tris-substituted mer-[TcIII(L1)3]
[18] complexes are the predominant species under the
synthetic conditions utilized above for rhenium.
O(1)ꢁReꢁP(1)
O(1)ꢁReꢁO(2)
O(1)ꢁReꢁN(1)
O(1)ꢁReꢁO(3)
O(1)ꢁReꢁO(4)
O(2)ꢁReꢁN(1)
N(1)ꢁReꢁO(3)
P(1)ꢁReꢁO(4)
88.6(3)
98.3(4)
110.0(5)
97.8(4)
166.2(4)
78.2(5)
91.8(5)
77.7(3)
90.4(3)
99.3(4)
108.6(5)
93.6(4)
167.9(4)
80.2(5)
91.1(5)
77.8(2)
atom methods and refined using the SHELXTL/PC [15]
and SHELXL-93 [16] suite of programs. To ensure a
good observation/parameters ratio, anisotropy was not
applied to carbon atoms of phenyl rings in 1a, while in
1b all the non-hydrogen atoms, apart the carbon atom
of the disordered CH2Cl2 solvent molecule, were refined
anisotropically. The hydrogen atoms were included in
the calculated positions and refined as riding atoms
using the SHELXL-93 default parameters. The final
Fourier difference maps did not show any significant
features, showing some electron density residuals (up to
1 e A−3) in the vicinity of Re.
,
On the contrary, when phosphino-carboxylic ligands
are employed, a remarkably different reactivity toward
the two metals is observed. While reduced mer-
[TcIII(L2)3] and mer-[TcIII(L3)3] are collected [9], confir-
ming the tendency toward the stabilization of lower
3. Results and discussion
3.1. Synthesis and general considerations
As sketched in Scheme 2, stable mixed-ligand oxo-
Scheme 2.

210
C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
Fig. 1. ORTEP view of complex 1a showing the atom labeling scheme. The thermal ellipsoids are drawn at 40% probability.
oxidation states for technetium, only the mono-substi-
phosphino-carboxylate seems to work as p-acceptor in
intermediate complexes 2 and 3, the 31P singlet signal
falling at −14.2 and −22.8 ppm, respectively, com-
pared to the signals observed for uncoordinated HL2
and HL3 (−17.4 and −4.0 ppm). Again a predomi-
nant downfield shift trend is observed in mixed-ligand
species (see Table 1). The unusual 31P upfield signals
exhibited by complex 3 may be ascribed to the steric
constrains introduced by the six-membered ring of the
L3 ligand bite compared to the five-membered rings of
the L1 and L2 ligands. The presence of the distinctive
tuted
complexes
[ReV(O)(L2)Cl3]−
(2)
and
[ReV(O)(L3)Cl3]− (3) are recovered with rhenium, even
in the presence of a large excess of phosphine, a condi-
tion usually met during the reconstitution of any
radiopharmaceutical.
In this view and according to the results detailed
above, the mono-substituted species [Re(O)(Ln)Cl3]−
(n=2, 3) containing the phosphino-carboxylato groups
appear to be promising candidates for application in
therapy. Studies to explore this possibility are in
progress.
1
n-Butyl protons in the H NMR spectra allow to easily
distinguish intermediate species, while mixed-ligand
compounds exhibit an additional imine proton signal in
the narrow range of 8.89–9.02 ppm indicating coordi-
nation of the SB.
3.2. Characterization
Elemental analyses, as reported in Section 2, are in
good agreement with the proposed formulation. IR
spectra of all synthesized rhenium complexes show the
characteristic ReꢀO stretching vibration in the range
949–989 cm−1, values in accordance with those exhib-
ited by six-coordinated monooxo-rhenium compounds
[12,19]. Additional absorptions typical of coordinated
arylphosphines are shown in the range 900–580 cm−1
[13], while complexes containing the phosphino-car-
boxylato groups exhibit an intense vibration in the
1663–1639 cm−1 region, bathocromic shifted by ap-
proximately 40 cm−1 with respect to those observed in
uncoordinated HL2 and HL3. Negative charged inter-
mediate complexes 1–3 show the presence of the tetra-
butylammonium counterion (strong absorption just
below 3000 cm−1).
3.2.1. Description of the crystal structures
The molecular structure of complexes 1 and 3 have
been elucidated recently and reported in separate con-
tributions [13,14]. The distorted octahedral arrange-
ment (see Scheme 2) resulting from the analyses of the
spectroscopic data for the series of mixed-ligand com-
plexes is confirmed by single-crystal X-ray investiga-
tions of two representative compounds. Both structures
1a and 1b contain discrete monomeric octahedral
monooxo-rhenium(V) complex units (Figs. 1 and 2,
respectively), in which the ONO donor atoms from the
tridentate dinegative ligand, along with the phosphorus
of the chelating moiety, occupy the equatorial plane.
The phenolate oxygen atom of the bidentate ligand,
trans to the oxo atom, completes the octahedral coordi-
nation sphere. The ReꢁOoxo axis is inclined at 80.1 and
81.5° in 1a and 1b, respectively, with respect to the
mean equatorial plane. Distortion from an ideal Re-
The 31P NMR signal of uncoordinated phos-
phinophenol (HL1, −20.8 ppm) moves significantly
downfield in the intermediate complex 1 and in the final
mixed-ligand compounds 1m, according to the strong
acid character of the [ReO]3+ moiety. Conversely, the

C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
211
centered octahedron mainly results in a non-linear
O(4)ꢁReꢁO(1) angle of 166.2 and 167.9° in 1a and 1b,
respectively, accomplished by P(1)ꢁReꢁN(1) and
O(2)ꢁReꢁO(3) angles of 161.3 and 163.2° in 1a and
160.6 and 166.2° for 1b, respectively. In both complexes
the five-membered ReꢁP(1)ꢁC(14)ꢁC(19)ꢁO(4) ring (in
a somewhat envelope form) is virtually normal to the
equatorial plane (dihedral angle of 92.9 and 87.8° in 1a
and 1b, respectively), while the atomic displacements
from the mean plane determined by the (5+6 member)
rings of the tridentate ligand range from +0.20 (for
Re) to −0.18 (for O(3)) in 1a and from +0.13 (for
Re) to −0.09 (for O(3)) in 1b. As expected, the coordi-
nation spheres in both structures are practically super-
imposable (Fig. 3), the weighted root-mean-squares
Bond lengths and angles, which are cumulated in
Table 2, show no unusual features being within the
range expected from the comparison of about 50 other
six-coordinate monooxo-Re(V) complexes retrieved
from the Cambridge Structural Database [20], although
the ReꢁO (trans to Ooxo) deserves a comment. In fact,
,
the ReꢁO distances (2.035(9) and 2.039(8) A in 1a and
1b, respectively) are somewhat shorter than the values
reported for other seven ‘3+2’ oxorhenium complexes
[20–24] incorporating the [ReO(L1)] fragment (from
1
+
,
2.048(3) A in [ReO(L )(N{CH2CH2NH2}2)] [22] to
1
,
2.117(6) A in [ReO(L )(EtN{CH2CH2S}2)] [23]. The
,
ReꢁP(1) distances (2.425(4) and 2.432(3) A in 1a and
1b, respectively) are within the normal range (2.400–
,
2.470 A) found in this type of complexes and closely
1
,
,
deviation being only 0.065 A, when the fitting is per-
parallel the value of 2.428(1) A found in [ReO(L ){(o-
formed using the octahedron atoms.
C6H4)2PPh}] [24], where the oxygen phenolate atom is
Fig. 2. ORTEP view of complex 1b showing the atom labeling scheme. Dashed lines indicate the second equipopulated orientation of the CH2Cl2
molecule.
Fig. 3. Superimposition of complexes 1a (—) and 1b (- - -).

212
C. Bolzati et al. / Inorganica Chimica Acta 315 (2001) 205–212
org. Chem. 34 (1995) 1077. (c) M. Papadopoulos, I. Pirmettis,
M. Pelecanou, C.P. Raptopoulou, A. Terzis, C.I. Stassinopou-
lou, E. Chiotellis, Inorg. Chem. 35 (1996) 7377. (d) I. Pirmettis,
M.S. Papadopoulos, S.G. Mastrostamatis, C.P. Raptopoulou, A.
Terzis, E. Chiotellis, Inorg. Chem. 35 (1996) 1685.
trans to the phosphorus of the OPO tridentate dinega-
tive ligand.
4. Supplementary material
[6] B. Nock, S. Maina, D. Yannoukakos, I. Pirmettis, M. Papado-
poulos, E. Chiotellis, J. Med. Chem. 42 (1999) 1066.
[7] P. Blower, S. Prakash, The Chemistry of Rhenium in Nuclear
Medicine, in: R.W. Hay, J.R. Dilworth, K.B. Nolan (Eds.),
Perspectives on Bioinorganic Chemistry, vol. 4, JAI Press, Stam-
ford, CT, 1999 (and references therein).
[8] (a) T.B. Rauchfuss, Inorg. Chem. 16 (1977) 2966. (b) J. Yardley,
H. Fletcher III, Synthesis (1975) 244.
[9] T. Jarolim, J. Podlahova, J. Inorg. Nucl. Chem. 38 (1976) 125.
[10] F. Refosco, F. Tisato, G. Bandoli, E. Deutsch, J. Chem. Soc.,
Dalton Trans. (1993) 2901.
Crystallographic data (excluding structure factors)
for the structural analysis have been deposited with the
Cambridge Crystallographic Data Centre, CCDC No.
157026 for compound 1a and No. 157027 for com-
pound 1b. Copies of this information may be obtained
free of charge from The Director, CCDC, 12 Union
Road, Cambridge, CB2 1EZ, UK (fax: +44-1223-
336033; e-mail: deposit@ccdc.cam.ac.uk or http://
www.ccdc.cam.ac.uk).
[11] F. Tisato, F. Refosco, U. Mazzi, G. Bandoli, M. Nicolini, J.
Chem. Soc., Dalton Trans. (1987) 1693.
[12] G. Rouschias, Chem. Rev. 74 (1974) 531.
[13] C. Bolzati, F. Tisato, F. Refosco, G. Bandoli, A. Dolmella,
Inorg. Chem. 35 (1996) 6221.
[14] J. Correia, A. Domingos, I. Santos, C. Bolzati, F. Refosco, F.
Tisato, Inorg. Chim. Acta, 2000, submitted for publication.
[15] G.M. Sheldrick, SHELXTL/PC ver. 5.03, Siemens Analytical
X-ray Instruments, Madison, WI, 1994.
[16] G.M. Sheldrick, SHELXL-93, Program for the Refinement of
Crystal Structures, University of Go¨ttigen, Germany, 1993.
[17] C. Bolzati, F. Tisato, F. Refosco, G. Bandoli, Inorg. Chim. Acta
247 (1996) 125.
Acknowledgements
The authors wish to thank Anna Moresco for ele-
mental analyses and skilled technical assistance.
References
[18] C. Bolzati, F. Refosco, F. Tisato, G. Bandoli, A. Dolmella,
Inorg. Chim. Acta 201 (1992) 7.
[1] E.A. Deutsch, K. Libson, J.-L. Vanderheyden, in: M. Nicolini,
G. Bandoli, U. Mazzi (Eds.), Technetium and Rhenium in
Chemistry and Nuclear Medicine, vol. 3, Raven Press, New
York, 1990, p. 13.
[2] (a) S. Jurisson, D. Berning, J. Wei, M. Dangshe, Chem. Rev. 93
(1993) 1137. (b) S. Liu, D.S. Edwards, Chem. Rev. 99 (1999)
2235. (c) J.C. Reubi, J. Nucl. Med. 36 (1995) 1825.
[3] R. Alberto, R. Schibli, A.P. Schubiger, U. Abram, J. Am. Chem.
Soc. 121 (1999) 6076.
[19] F. Refosco, F. Tisato, G. Bandoli, C. Bolzati, A. Dolmella, A.
Moresco, M. Nicolini, J. Chem. Soc., Dalton Trans. (1993) 605.
[20] (a) CSD Database, Release 5.19, 2000. (b) F.H. Allen, J.E.
Davies, J.J. Galloy, O. Johnson, O. Kennard, C.F. Macrae,
E.M. Mitchell, J.M. Smith, D.G. Watson, J. Chem. Inf. Compt.
Sci. 31 (1991) 187.
[21] B. Nock, T. Maina, F. Tisato, C.P. Raptopoulou, A. Terzis, E.
Chiotellis, Inorg. Chem. 39 (2000) 5197.
[4] C. Bolzati, A. Boschi, A. Duatti, S. Prakash, L. Uccelli, F.
Refosco, F. Tisato, G. Bandoli, J. Am. Chem. Soc. 122 (2000)
4510.
[5] (a) H.-J. Pietzsch, H. Spies, S. Hoffmann, J. Stach, Inorg. Chim.
Acta 161 (1989) 15. (b) D.M. Spyriounis, M. Pelecanou, C.I.
Stassinopoulou, C.P. Raptopoulou, A. Terzis, E. Chiotellis, In-
[22] B. Nock, T. Maina, F. Tisato, M. Papadopoulos, C.P. Rapto-
poulou, A. Terzis, E. Chiotellis, Inorg. Chem. 39 (2000) 2178.
[23] B. Nock, T. Maina, F. Tisato, M. Papadopoulos, C.P. Rapto-
poulou, A. Terzis, E. Chiotellis, Inorg. Chem. 38 (1999) 4197.
[24] H. Luo, I. Setyawati, S.J. Rettig, C. Orvig, Inorg. Chem. 34
(1995) 2287.
.