Synthesis and characterization of five-coordinate rhenium(V) and technetium(V) mixed ligand bifunctional complexes carrying the SNS/S or the SNN/S donor atom set.

Article abstract of DOI:10.1016/s0020-1693(98)00330-2

Two parallel series of bifunctional mixed ligand oxorhenium and oxotechnetium complexes containing the SNS/S or the SNN/S donor atom set are synthesized and characterized in this study. The amine bifunctional anchor is positioned on the common monothiolate p-H₂N-Ph-SH coligand, which by reacting in equimolar amounts with a tridentate aminethiolate ligand LH₂ [LH₂:CH₃CH₂N(CH₂CH ₂SH)₂, (CH₃CH₂)₂NCH₂-CH ₂N(CH₂CH₂SH)₂, (CH₂)₄NCH₂CH₂NHCH₂CH ₂SH and (CH₃CH₂)₂NCH₂CH ₂NH-CH₂CH₂SH] and the corresponding oxometal precursor, leads to the generation of these series. Two representative members ReO{[(C₂H₅)₂NCH₂CH ₂N(CH₂CH₂S)₂](p-H₂N-PhS)} and ReO{[(CH₂)₄NCH₂CH₂NCH ₂CH₂S](p-H₂N-PhS)} are further characterized by crystallographic analysis. The SNS/S analogs adopt a distorted trigonal bipyramidal geometry, while the SNN/S ones prefer a distorted square pyramidal geometry around the metal. Extrapolation of structure at tracer level is investigated by chromatographic methods and is established only for the SNS/S, but not for the SNN/S compounds. Thus, by this initial evaluation, the applicability of the bifunctional SNS/S (but not the SNN/S) system for tagging biomolecules with ^99mTc is demonstrated.

Full text of DOI:10.1016/s0020-1693(98)00330-2

Inorganica Chimica Acta 285 (1999) 97±106
Synthesis and characterization of ®ve-coordinate rhenium(V) and
technetium(V) mixed ligand bifunctional complexes carrying the
SNS/S or the SNN/S donor atom set. Crystal structure of
ReO{[(C2H5)2NCH2CH2N(CH2CH2S)2](p-H2N±PhS)} and
ReO{[(CH2)4NCH2CH2NCH2CH2S](p-H2N±PhS)}
Minas Papadopoulosa, Charalabos Tsoukalasa, Ioannis Pirmettisa, Berthold Nocka, Theodosia
Mainaa, Zainul Abedina, Catherine P. Raptopouloub, Aris Terzisb, Efstratios Chiotellisa,
Ã
a Institute of Radioisotopes-Radiodiagnostic Products, NCSR `Demokritos', P.O. Box 60228, 15310 Aghia Paraskevi, Athens, Greece
b Institute of Materials Science, NCSR `Demokritos', P.O. Box 60228, 15310 Aghia Paraskevi, Athens, Greece
Received 13 February 1998; received in revised form 22 April 1998; accepted 5 June 1998
Abstract
Two parallel series of bifunctional mixed ligand oxorhenium and oxotechnetium complexes containing the SNS/S or the SNN/S donor
atom set are synthesized and characterized in this study. The amine bifunctional anchor is positioned on the common monothiolate p-H2N±
Ph±SH coligand, which by reacting in equimolar amounts with a tridentate aminethiolate ligand LH2 [LH2:CH3CH2N(CH2CH2SH)2,
(CH3CH2)2NCH2±CH2N(CH2CH2SH)2, (CH2)4NCH2CH2NHCH2CH2SH and (CH3CH2)2NCH2CH2NH±CH2CH2SH] and the correspond-
ing oxometal precursor, leads to the generation of these series. Two representative members ReO{[(C2H5)2NCH2CH2N(CH2CH2S)2](p-
H2N±PhS)} and ReO{[(CH2)4NCH2CH2NCH2CH2S](p-H2N±PhS)} are further characterized by crystallographic analysis. The SNS/S
analogs adopt a distorted trigonal bipyramidal geometry, while the SNN/S ones prefer a distorted square pyramidal geometry around the
metal. Extrapolation of structure at tracer level is investigated by chromatographic methods and is established only for the SNS/S, but not
for the SNN/S compounds. Thus, by this initial evaluation, the applicability of the bifunctional SNS/S (but not the SNN/S) system for
tagging biomolecules with 99mTc is demonstrated. # 1999 Elsevier Science S.A. All rights reserved.
Keywords: Crystal structures; Rhenium complexes; Technetium complexes; Mixed ligand complexes; Bifunctional complexes
1. Introduction
and/or highly effective radiotherapy can be theoretically
achieved [1±13].
Recent advances in Nuclear Medicine involve the devel-
opment of new sophisticated molecular probes effectively
used as speci®c tools for the diagnosis and therapy of
disease. According to this new challenging approach, recep-
tor mediated imaging and/or therapy can be achieved by use
of speci®c site-directed molecules ± such as monoclonal
antibodies (MoAbs), receptor seeking peptides and bioactive
drugs ± that labeled with the appropriate radionuclide carry
the radioactivity speci®cally onto target tissues. Due to the
high speci®city of the new radiotracers high quality images
Given that 99mTc still remains the gold standard in
Nuclear Medicine Diagnosis as a consequence of its phy-
sical characteristics (t1/2 ˆ 6 h, monoenergetic gamma
photons 140 keV), widespread availability and cost effec-
tiveness (due to a commercial 99Mo/99mTc generator), the
development of appropriate bifunctional chelating systems
for 99mTc takes a new interest. Thus, several different types
of bifunctional ligands for tagging biomolecules of interest
with 99mTc (and/or accordingly 186=188Re) have been emer-
ging over the past few years [14±24]. Two major approaches
are currently dominating the ®eld. In both cases a bifunc-
tional anchor, often an amine or a carboxylate group, is
positioned on the ligand backbone and is eventually cova-
lently bound to the biomolecule of interest, either after
*Corresponding author. Tel.: +30-1-6513-793; fax: +30-1-6543-526;
e-mail: mainathe@cyclades.nrcps.ariadne-t.gr
0020-1693/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved.
PII: S0020-1693(98)00330-2

98
M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
(preformed chelate approach) or prior to (post-conjugation
approach) complex formation [23].
is puri®ed prior to its use by overnight treatment with
H2O2 and NH4OH in MeOH. Evaporation of the solvent
affords [999Tc]NH4TcO4 as a white powder. The [999Tc]TcV-
gluconate ([999Tc]TcV-Gl) precursor is generated in situ by
following a reported protocol [37]. Technetium-99m is used
as a [99mTc]NaTcO4 solution in physiological saline either
as an in-house preparation (Techne/Demoscan, NCSR
`Demokritos') or as a commercial 99Mo/99mTc generator
eluate (Cis International). The [99mTc]TcV-glucoheptonate
([99mTc]TcV-GH) intermediate is produced by using com-
mercial glucoheptonate kits (Gluco/Demoscan, NCSR
`Demokritos') containing a lyophilized mixture of SnCl2
(0.2 mg, 1.05 mmol) and C14H26CaO16 (200 mg,
0.408 mmol). Solvents for high performance liquid chro-
matography (HPLC) are of HPLC grade; they are ®ltered
through membrane ®lters (0.22 m, Millipore, Milford/USA)
and degased by helium ¯ux before use.
Selection of the proper chelating agent is of vital impor-
tance for the success of the resulting radioagent, since the
chelate moiety greatly in¯uences important overall mole-
cule characteristics, such as in vitro and in vivo stability,
lipophilicity, charge and structure. Extensive recent research
has provided several tetradentate chelating systems suitable
for oxotechnetium(V) and/or oxorhenium(V) [14±24].
However, one of the major inherent handicaps of this
strategy is the time consuming and tedious synthetic routes
involved.
As an alternative strategy, we propose herein the
application of bifunctional mixed ligand systems of the
`3 ‡ 1' type, in order to overcome this handicap and
facilitate overall synthesis. Monofunctional mixed ligand
`3 ‡ 1' systems based on the SNS/S and SNN/S donor
atom sets and suitable for either oxorhenium(V) or oxo-
technetium(V) have been the primary focus of our recent
work [25±29]. As a result, several new radioagents
with potential medical application have been recently
developed [29±31].
The aim of the present work is to evaluate in a ®rst
approach the applicability of these systems as bifunctional
agents for tagging biomolecules of interest with 99mTc. For
this purpose, a common monothiolate coligand containing
an amine bifunctional anchor (p-NH2±Ph±SH) is combined
with four different tridentate aminethiolate ligands, LH2
[LH2:CH3CH2N(CH2CH2SH)2, (CH3CH2)2NCH2±CH2N-
(CH2CH2SH)2, (CH2)4NCH2CH2±NHCH2CH2SH and
(CH3CH2)2NCH2CH2NHCH2CH2SH], thereby generating
two parallel series of bifunctional TcVO and ReVO com-
plexes. Characterization of the above compounds at carrier
level (Re and 99gTc) is followed by an investigation of their
formation at tracer level (99mTc). In this way, a ®rst estima-
tion of their usefulness as bifunctional radioagents for
effectively tagging biologically active molecules can be
derived.
IR spectra are recorded on KBr pellets on a Perkin-Elmer
1
1600Ft-IR spectrophotometer in the region 500±4000 cm
and using polystyrene as reference. Proton NMR spectra are
registered at 250 MHz on a 250AF FT-NMR spectrometer
(Bruker) using CDCl3 sample solutions and Me4Si as an
internal standard; chemical shifts are given in ꢀH. Elemental
analyses for C, H, N and S are conducted on a Perkin-Elmer
2400/II automatic elemental analyzer.
HPLC analysis is performed on a Waters chromatograph
ef®cient with a 600E solvent delivery system and coupled to
both a Waters 991 photodiode array detector (for the
photometric detection of free ligands, Re and [99Tc]-com-
plexes) and to a Beckman 171 radiometric detector (for the
gamma detection of [99mTc] compounds) using a NP Porasil
(10 m, 3.9 mm  300 mm) column isocratically eluted with
CH2Cl2/MeOH (System A). Additionally, a Waters 600
Millenium chromatography system is applied coupled to
both a Waters 486 tunable absorbance detector set at 254 nm
(UV trace) and to a Raytest Stef® gamma detector con-
nected to a LDC Milton Roy computer (gamma trace). In
this system,
a RP-C18 m-Bondapak Waters (10 m,
3.9 mm  150 mm) column is eluted with 2% triethylam-
monium phosphate (TEAP) buffer pH 7.4/EtOH gradient
system (System B): 0±70% EtOH in 20 min at 1 ml min
¯ow rate.
1
2. Experimental
2.1. General
2.2. Safety note
All chemicals are reagent grade and used as such without
further puri®cation. p-Aminothiophenol is purchased from
Fluka. Synthesis and puri®cation of CH3CH2N(CH2-
CH2SH)2 [32,33], (CH3CH2)2NCH2CH2N(CH2CH2SH)2
[34], (CH2)4NCH2±CH2NHCH2CH2SH [35] and (CH3-
CH2)2NCH2CH2NHCH2CH2SH [35] ligands are performed
according to reported protocols. Rhenium is purchased from
Aldrich as KReO4 and is converted to the ReVOCl3(PPh3)2
precursor according to a described method [36]. Techne-
tium-99 is purchased as [999Tc]NH4TcO4 from Oak Ridge
National Laboratories. The partially reduced black solid
Technetium-99g is a weak b-emitter (0.292 MeV) with a
half life of 2.12 Â 105 years. All manipulations of solutions
and solids containing this radionuclide are carried out in a
special laboratory dedicated to the handling of low energy
particle emitting radionuclides. Regular radiation safety
protocols are carefully followed in order to prevent con-
tamination. Technetium-99m is a gamma emitter (141 keV)
with a half life of 6 h. Handling of solutions containing
this radionuclide always proceeds behind suf®cient lead
shielding.

M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
99
2.3. Synthesis of ReVO±L1L2 complexes
2.3.3. (p-Aminophenylthiolato-S){2-[2-(N-pyrrolidinyl)-
ethyleneamino-N,N0]ethylenethiolato-S}-
oxorhenium(V) (3)
2.3.1. (p-Aminophenylthiolato-S)[N-ethyl-N,N-bis-
(ethylene-2-thiolato-S)amino-N]oxorhenium (V) (1)
To a 1 M AcONa solution in MeOH (4 ml) ReVOCl3-
(PPh3)2 (166.6 mg, 0.2 mmol) is placed. To the resulting
In a similar manner 3 is produced by reacting 2-[2-(N-
pyrrolidinyl)ethyleneamino]ethylenethiol (34.86 mg, 0.2
mmol) and p-aminothiophenol (25 mg, 0.2 mmol) on the
ReVOCl3(PPh3)2 precursor (166.6 mg, 0.2 mmol) in MeOH.
Red±brown crystals are collected after slow evaporation
from MeOH/CH2Cl2 (63.8 mg, 64%). The product is solu-
ble in hot CH2Cl2, hot CHCl3, slightly soluble in MeOH,
EtOH and insoluble in Et2O, pentane and H2O.
suspension
a solution of N-ethyl-N,N-bis(ethylene-2-
thiol)amine (33 mg, 0.2 mmol) and p-aminothiophenol
(25 mg, 0.2 mmol) in MeOH (1.0 ml) is added drop-
wise under stirring. The mixture is re¯uxed until a clear
solution results. After addition of H2O (10 ml) the mixture
is extracted in CH2Cl2 and dried over MgSO4. The
organic phase is concentrated under vacuum and an
equal volume of MeOH is added. Green crystals are iso-
lated by slow evaporation from MeOH/CH2Cl2 (73.4 mg,
75%). The complex is soluble in CH2Cl2, CHCl3, slightly
soluble in MeOH, EtOH and insoluble in Et2O, pentane
and H2O.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.7; m.p. (from MeOH/CH2Cl2): 225±2278C (decomp.);
Anal. Calc. for C12H19N2OReS3: C, 29.43; H, 3.91; N,
5.72; S, 19.64. Found: C, 29.79; H, 4.39; N, 5.65; S,
19.22%. UV±Vis (ꢁmax (nm), CH2Cl2): 208, 259, 442; IR
(KBr, ꢂmax (cm 1)): 3460, 3355, 2960, 2925, 1608, 1290,
944 (Re=O str.), 821; 1H NMR ꢀH (250 MHz, CDCl3,
Me4Si): 1.30 (3H, t, CH3CH2N), 2.50±2.90 (4H, m, exo
NCH2CH2S), 3.10±3.55 (4H, m, endo NCH2CH2S), 3.67
(2H, b, NH2), 3.88 (2H, q, CH3CH2N±Re), 6.65 (2H, dd, o-
Ph±H), 7.37 (2H, dd, m-Ph±H).
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.7; m.p. (from MeOH/CH2Cl2): 220±2228C (decomp.);
Anal. Calc. for C14H22N3OReS2: C, 33.72; H, 4.45; N,
8.43; S, 12.86. Found: C, 33.66; H, 4.53; N, 7.94; S,
13.24%. UV±Vis (ꢁmax (nm), CH2Cl2): 245, 310, 385; IR
(KBr, ꢂmax (cm 1)): 3441, 3332, 2963, 2918, 2875, 2833,
1
1626, 1272, 941 (Re=O str.), 828; H NMR ꢀH (250 MHz,
CDCl3, Me4Si): 2.0±2.3 (4H, m, pyrrolidino ±CH2±CH2±),
2.6, 2.9 [2H, m, pyrrolidino CH2±N (away from the ReO
core)], 3.2 (1H, m, exo ±SCH2), 3.3 [1H, m, exo Re±N
(pyrrolidino)±CH2CH2N±], 3.4 [1H, m, exo Re±N±
CH2CH2±N (pyrrolidino)], 3.6±3.9 [6H, m, endo ±SCH2±,
exo ±SCH2CH2N±, endo Re±NCH2±CH2N (pyrrolidino),
pyrrolidino ±CH2±N (toward the ReO core), Re±SPhNH2],
3.8 [1H, m, endo Re±N±CH2CH2±N (pyrrolidino)], 4.1 (1H,
q, endo ±SCH2CH2N±), 4.5 [1H, m, pyrrolidino ±CH2±N
(toward the ReO core)], 6.6 (2H, dd, o-Ph±H), 7.4 (2H, dd,
m-Ph±H ).
2.3.4. (p-Aminophenylthiolato-S){2-[(N,N-diethylamino)-
ethyleneamino-N,N0]-ethylenethiolato-S}-
oxorhenium(V) (4)
2.3.2. (p-Aminophenylthiolato-S){N-[(N0,N0-diethyl)-2-
aminoethylene]-N,N-bis(ethylene-2-thiolato-
S)amino-N}oxorhenium(V) (2)
By following the same procedure as for the preparation of
3 and using 2-[2-(N,N-diethylamino)ethyleneamino]ethyl-
enethiol (35.26 mg, 0.2 mmol) as tridentate ligand complex
4 is produced. Red±brown crystals separate by slow eva-
poration from MeOH/CH2Cl2 (72.1 mg, 72%). This com-
pound is soluble in hot CH2Cl2, hot CHCl3, slightly soluble
in MeOH, EtOH and insoluble in Et2O, pentane and H2O.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.7; m.p. (from MeOH/CH2Cl2): 220±2228C; Anal. Calc.
for C14H24N3OReS2: C, 33.58; H, 4.83; N, 8.39; S, 12.81.
Found: C, 33.51; H, 5.17; N, 8.14; S, 13.12%. UV±Vis (ꢁmax
(nm), CH2Cl2): 241, 305, 380; IR (KBr, ꢂmax (cm 1)):3466,
3354, 2918, 2814, 1615, 1277, 945 (Re=O), 828; 1H NMR
ꢀH (250 MHz, CDCl3, Me4Si): 1.1 [3H, t, ±NCH2CH3
(toward the ReO core)], 1.6 [3H, t, NCH2CH3 (away from
the ReO core)], 1.7, 2.9 [2H, m, ±NCH2CH3 (away from the
ReO core)], 3.1, 3.2 [2H, m, exo ±SCH2CH2N±, exo Re±
N(Et2)±CH2CH2N±], 3.4±3.7 (7H, m, endo ±SCH2CH2N±,
exo ±SCH2CH2N±Re, exo Re±N±CH2CH2±NEt2, Re±
NCH2CH3 (toward the ReO core), Re±S±PhNH2], 3.8
(1H, m, endo Re±N±CH2CH2±NEt2), 3.9 [1H, m endo
Re±N(Et2)±CH2CH2N±], 4.1 (1H, m, endo ±SCH2CH2N±
Re), 6.7 (2H, dd, o-Ph±H), 7.4 (2H, dd, m-Ph±H).
This complex is prepared by reacting equimolar amounts
of [N-(N0,N0-diethyl)-2-aminoethylene]-N,N-bis(ethylene-
2-thiol)amine (47 mg, 0.2 mmol) and p-aminothiophenol
(25 mg, 0.2 mmol) on the ReVOCl3(PPh3)2 (166.6 mg,
0.2 mmol) precursor in a similar manner as for 1. Green
crystals of 2 precipitate by slow evaporation from MeOH/
CH2Cl2 (78.5 mg, 70%). This compound is soluble in
CH2Cl2, CHCl3, slightly soluble in MeOH, EtOH and
insoluble in Et2O, pentane and H2O.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.3; m.p. (from MeOH/CH2Cl2): 203±2048C; Anal. Calc.
for C16H28N3OReS3: C, 34.27; H, 5.03; N, 7.49; S, 17.15.
Found: C, 34.11; H, 5.25; N, 7.37; S, 17.59%. UV±Vis (ꢁmax
(nm), CH2Cl2): 205, 259, 448; IR (KBr, ꢂmax (cm 1)): 3456,
1
3336, 2966, 2922, 1612, 1289, 939 (Re=O str.), 819; H
NMR ꢀH (250 MHz, CDCl3, Me4Si): 1.05 (6H, t,
CH3CH2N), 2.60 (4H, q, CH3CH2N), 2.86 (2H, t,
CH2CH2N±Re), 2.70±3.00 (4H, m, exo NCH2CH2S), 3.45
(2H, m, endo NCH2CH2S), 3.60 (2H, m, endo NCH2CH2S),
3.72 (2H, b, NH2), 3.93 (2H, t, CH2CH2N-Re), 6.70 (2H, dd,
o-Ph±H), 7.45 (2H, dd, m-Ph±H).

100
M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
2.4. Synthesis of TcVO±L1L2 complexes
separate by slow evaporation from MeOH/CH2Cl2
(53.4 mg, 65%). The compound is soluble in CHCl3 and
CH2Cl2, slightly soluble in EtOH and MeOH and insoluble
in Et2O and H2O.
2.4.1. (p-Aminophenylthiolato-S)[N-ethyl-N,N-bis-
(ethylene-2-thiolato-S)amino-N]oxotechnetium(V)-
99g (5)
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.8; m.p. (from CH2Cl2/MeOH): 230±2338C; Anal. Calc.
for C14H22N3OS2TcÁH2O: C, 39.34; H, 5.66; N, 9.84; S
14.97. Found: C, 38.77; H, 5.61; N, 9.50; S, 14.21%. UV±
Vis (ꢁmax (nm), CH2Cl2): 242, 250, 289, 376, 460; IR (KBr,
To a solution of NH499TcO4 (36.2 mg, 0.2 mmol) and
sodium gluconate (200 mg, 0.917 mmol) a solution of SnCl2
(45 mg, 0.237 mmol) in 1N HCl (1.0 ml) is added dropwise
and the pH is adjusted to 7.5. To this mixture a solution of N-
ethyl-N,N-bis(ethylene-2-thiol)amine (33 mg, 0.2 mmol)
and p-aminothiophenol (25 mg, 0.2 mmol) in MeOH
(1.0 ml) is added dropwise under stirring. The reaction
mixture is stirred for 30 min and is then extracted in CH2Cl2.
Red±brown crystals of 5 are collected by slow evaporation
from CH2Cl2/MeOH (48.18 mg, 60%). This complex is
soluble in CH2Cl2 and CHCl3, slightly soluble in MeOH
and EtOH and insoluble in H2O, Et2O and pentane.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.7; m.p. (from CH2Cl2/MeOH): 237±2408C (decomp.);
Anal. Calc. for C12H19N2OS3Tc: C, 35.90; H, 4.77; N,
6.98; S, 23.96. Found: C, 35.70; H, 4.95; N, 7.03; S,
23.80%. UV±Vis (ꢁmax (nm), CH2Cl2): 205, 259, 532; IR
(KBr, ꢂmax (cm 1)): 3428, 3345, 2960, 2925, 1608, 1290,
909 (Tc=O str.), 823; 1H NMR ꢀH (250 MHz, CDCl3,
Me4Si): 1.4 (3H, t, CH3CH2N), 2.5±3.0 (4H, m, exo
±NCH2CH2S±), 3.2±3.6 (4H, m, endo ±NCH2CH2S±), 3.7
(2H, b, S-PhNH2), 4.0 (2H, q, CH3CH2N±Tc), 6.7 (2H, dd,
o-Ph±H), 7.4 (2H, dd, m-Ph±H).
ꢂ
max (cm 1)): 3440, 3333 (±NH2), 2960, 2916, 2866, 2827,
1
1618, 1291, 912 (Tc=O str.), 827; H NMR ꢀH (250 MHz,
CDCl3, Me4Si): 1.9±2.3 (4H, m, ±NCH2±CH2CH2±CH2N±,
pyrrolidinyl), 2.5, 3.1 [1H, m, pyrrolidinyl Tc±NCH2±
(away from the TcO core)], 3.2 (1H, m, exo Tc±S±
CH2CH2N±), 3.3 [1H, m, exo Tc±NCH2CH2N (pyrrolidi-
nyl)], 3.5 [1H, m, exo Tc±NCH2CH2N (pyrrolidinyl)], 3.6±
3.9 [7H, m, endo Tc±S±CH2CH2N±, exo Tc±S±CH2CH2N,
endo Tc±NCH2CH2N (pyrrolidinyl), endo Tc±NCH2CH2N
(pyrrolidinyl), pyrrolidinyl Tc±NCH2CH2± (toward the TcO
core), SPhNH2], 4.2 (1H, q, endo Tc±S±CH2CH2N±), 4.6
[1H, m, pyrrolidino NCH2CH2± (toward the TcO core)], 6.6
(2H, dd, o-Ph±H), 7.4 (2H, dd, m-Ph±H).
2.4.4. (p-Aminophenylthiolato-S){2-[N,N-diethylamino)-
ethyleneamino-N,N0]ethylene-thiolato-S}-
oxotechnetium(V)-99g (8)
This compound is produced by following the same meth-
odology as before and using 2-[2-(N,N-diethylamino)ethy-
leneamino]ethylenethiol (35.26 mg, 0.2 mmol) as tridentate
ligand. Product 8 is obtained in red±brown crystalline form
by slow evaporation from MeOH/CH2Cl2 (53.6 mg, 65%).
The complex is soluble in CH2Cl2 and CHCl3, slightly
soluble in EtOH, MeOH and insoluble in Et2O and H2O.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.7; m.p. (from CH2Cl2/MeOH): 227±2308C; Anal. Calc.
for C14H24N3OS2Tc: C, 40.87; H, 5.88; N, 10.22; S 15.56.
Found: C, 40.35; H, 5.70; N, 9.75; S, 14.96%. UV±Vis (ꢁmax
(nm), CH2Cl2): 248, 295, 384, 450; IR (KBr, ꢂmax (cm 1)):
3439, 3356 (±NH2), 2963, 2930, 2910, 2872, 2828, 1612,
2.4.2. (p-Aminophenylthiolato-S){N-[(N0,N0-diethyl)-2-
aminoethylene]-N,N-bis(ethylene-2-thiolato-S)-
amino-N}oxotechnetium(V)-99g (6)
Red±brown crystals of 6 are obtained by reacting [N-(N0,-
N0-diethyl)-2-aminoethylene]-N,N-bis(ethylene-2-thiol)-
amine (47 mg, 0.2 mmol) with p-aminothiophenol (25 mg,
0.2 mmol) in a similar manner as for 5 (56.71 mg, 60%).
The complex is soluble in CHCl3, CH2Cl2, slightly soluble
in EtOH, MeOH and insoluble in Et2O and H2O.
Rf (SiO2; MeCN:MeOH:CH2Cl2:Et2NH 75:3.5:15:6.5):
0.3; m.p. (from CH2Cl2/MeOH): 214±2178C; Anal. Calc.
for C16H28N3OS3Tc: C, 40.66; H, 5.97; N, 8.89; S 20.35.
Found: C, 40.71; H, 5.55; N, 8.37; S, 20.59%. UV±Vis (ꢁmax
(nm), CH2Cl2): 199, 250, 547; IR (KBr, ꢂmax (cm 1)): 3427,
1
1282, 911 (Tc=O str.), 818 (p-substituent); H NMR ꢀH
(250 MHz, CDCl3, Me4Si): 1.1 [3H, t, ±NCH2CH3 (toward
the TcO core)], 1.6 [3H, t, ±NCH2CH3 (away from the TcO
core)], 1.7, 2.9 [2H, ±NCH2CH3 (away from the TcO core)],
3.1±3.2 [2H, exo Tc±SCH2CH2N±, exo ±NCH2CH2N (pyr-
rolidinyl)], 3.4±3.7 [7H, endo Tc±SCH2CH2±, exo SCH2-
CH2N±, exo Tc±NCH2CH2N (pyrrolidinyl), ±CH2CH3
(toward the TcO core), ±SPh±NH2], 3.8±3.9 (2H, m, endo
Tc±NCH2CH2N (pyrrolidinyl), endo Tc±NCH2CH2±N
(pyrrolidinyl)], 4.1 (1H, m, endo ±SCH2CH2N±Tc), 6.6
(2H, dd, o-Ph±H), 7.4 (2H, dd, m-Ph±H).
1
3340, 2960, 2915, 1619, 1287, 909 (Tc=O str.), 822; H
NMR ꢀH (250 MHz, CDCl3, Me4Si): 1.0 [6H, t, (CH3CH2)2-
N±],2.6[4H,q,(CH3CH2)2N±],2.8(2H,t,±NCH2CH2N±Tc),
2.7±3.0 (4H, m, exo ±NCH2CH2S±), 3.4±3.6 (4H, m, endo
±NCH2CH2S±), 3.7 (2H, b, ±SPhNH2), 3.9 (2H, t, ±NCH2-
CH2N±Tc), 6.7 (2H, dd, o-Ph±H), 7.4 (2H, dd, m-Ph±H).
2.4.3. (p-Aminophenylthiolato-S){2-[2-(N-pyrrolidinyl)-
ethyleneamino-N,N0]ethylenethiolato-S}-
oxotechnetium(V)-99g (7)
Complex 7 is prepared in a similar manner by using 2-[2-
(N-pyrrolidinyl)ethyleneamino]ethylenethiol (34.86 mg,
0.2 mmol) as the tridentate ligand. Red±brown crystals
2.5. Preparation of [99mTc]TcVO±L1L2 complexes
The analogous complexes: [99mTc]-5 ((p-aminophenyl-
thiolato-S)[N-ethyl-N,N-bis(ethylene-2-thiolato-S)amino-N]
oxotechnetium(V)-99m), [99mTc]-6 ((p-aminophenylthio-

M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
101
lato-S){N-[(N0,N0-diethyl)-2-aminoethylene]-N,N-bis-
(ethylene-2-thiolato-S)amino-N}oxotechnetium(V)-99m),
99mTc]-7((p-aminophenylthiolato-S){2-[2-(N-pyrrolidinyl)-
2.7. X-ray crystallography
red prismatic crystal of
[
A
2
with dimensions
ethyleneamino-N,N0]ethylenethiolato-S}oxotechnetium(V)-
99m) and [99mTc]-8 ((p-aminophenylthiolato-S){2-[N,N-
diethylamino)ethyleneamino-N,N0]-ethylenethiolato-S}-
oxotechnetium(V)-99m) are prepared at the tracer level as
described for [99mTc]-5 below. To a centrifuge tube N-ethyl-
N,N-bis(ethylene-2-thiol)amine (3.3 mg, 0.02 mmol) and
p-aminothiophenol (2.5 mg, 0.02 mmol) are placed and a
solution of [99mTc]-GH (1.0 ml, 3±10 mCi) is added. The
mixture is stirred vigorously by a vortex mixer and is then
extracted in CH2Cl2 (3 Â 1.5 ml). The combined organic
extracts are dried over MgSO4, that is ®ltered off. The
radioactivity content of both the aqueous and organic phase
is measured separately [Yield (as determined by organic
extraction): >85%].
0.10 mm  0.45 mm  0.55 mm and a red crystal of 3 with
dimensions 0.10 mm  0.30 mm  0.60 mm were mounted
in air. Diffraction measurements were made on a Crystal
Logic Dual Goniometer diffractometer using graphite
monochromated Mo Ka radiation. Unit cell dimensions
were determined by using the angular settings of 25 auto-
matically centered re¯ections in the range 11 < 2ꢃ < 23 and
are collected in Table 1 along with other crystallographic
data. Intensity measurements were made using ꢃ±2ꢃ scan.
For 2: scan speed 3.08 min 1, scan range 2.3 ‡ a1a2 separa-
tion, 2ꢃmax ˆ 508. For 3: scan speed 3.08 min 1, scan range
2.4 ‡ a1a2 separation, 2ꢃmax ˆ 508. Three standard re¯ec-
tions measured every 97 re¯ections showed less than 3%
intensity ¯uctuation and no decay. Lorentz, polarization and
-scan absorption corrections were applied using Crystal
Logic software.
2.6. High performance liquid chromatographic analysis
For complex 2, 3699 re¯ections were collected and after
averaging the symmetry equivalent data (Rint ˆ 0.0087)
3532 independent re¯ections were obtained. Symmetry
equivalent data for 3 (Rint ˆ 0.0238) were averaged to give
2954 independent re¯ections from a total of 3048 collected.
The structures were solved by direct methods using
SHELXS-86 [38] and re®ned by full-matrix least-squares tech-
niques on F2 with SHELXL-93 [39]. For 2: hydrogen atoms of
C(9) were introduced at calculated positions as riding on
bonded atoms, while those of the methyl C(10) were not
included in the re®nement. All the rest hydrogen atoms were
located by difference maps and re®ned isotropically. All
non-hydrogen atoms were re®ned anisotropically. The ®nal
Samples of complex solutions (20 ml) are injected either
on a RP C18 or on a normal phase column, using the
chromatography systems A or B, as described above at a
1
1 ml min ¯ow rate. L1H2 and L2H free ligands, ReVO±
L1L2 and TcVO±L1L2 complexes are followed photometri-
cally by a UV±Vis detector, whereas [99mTc]TcVO±L1L2
complexes and radiochemical impurities are detected by the
gamma detector. After co-injection of analogous ReVO±
L1L2 or TcVO±L1L2 complexes with the [99mTc]TcVO±L1L2
ones forming at the tracer level and comparison of the UV±
Vis with the gamma chromatographic trace, corroboration
of structure is investigated.
Table 1
Summary of crystal, intensity collection and refinement data for 2 and 3
2
3
Empirical formula
Formula weight
Temperature (K)
Wavelength
C
16H28N3OS3Re
C14H22N3OReS2
498.67
560.79
298
298
Mo Ka 0.71073
P21/c
Mo Ka 0.71073
P21/a
Space group
Ê
a (A)
Ê
b (A)
21.05(1)
7.552(5)
12.949(8)
102.55(2)
2009(2)
4
9.504(3)
8.890(3)
19.829(8)
91.92(1)
1674.4(1)
4
Ê
c (A)
ꢄ (8)
V (A )
Ê 3
Z
Dcalc.
1.854
1.978
1
Absorption coefficient (ꢅ) (mm
F(000)
)
6.368
7.508
1104
a ˆ 0.0000, b ˆ 1.3959
968
a ˆ 0.0411, b ˆ 0.3965
1.039
wa
Goodness-of-fit on F2
R indicesb
1.033
R1 ˆ 0.0234, wR2 ˆ0.0591c
R1 ˆ 0.0296, wR2 ˆ 0.0629
d
R1 ˆ 0.0317, wR2 ˆ 0.0816
R1 ˆ 0.0398, wR2 ˆ 0.0872
R indicesb (all data)
a w ˆ 1/[ꢆ2(Fo2) ‡ (aP)2 ‡ bP] and P ˆ (Max (Fo2, 0) ‡ 2Fc2)/3.
b R1 based on F values, wR2 based on F2.
c For 3110 reflections with I > 2ꢆ(I).
d For 2528 reflections with I > 2ꢆ(I).

102
M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
values for R1, wR2 and GOF for all data are 0.0296, 0.0629
and 1.033. The largest shift/esd in the ®nal cycle was 0.003.
The maximum and minimum residual peaks in the ®nal
difference map were 0.971 and 0.671 e A 3. For 3: all
Ê
non-hydrogen atoms were re®ned anisotropically but all
hydrogen atoms were introduced at calculated positions as
riding on bonded atoms and re®ned isotropically. The ®nal
values for R1, wR2 and GOF for all data are 0.0398, 0.0872
and 1.039. The largest shift/esd in the ®nal cycle was 0.001.
The largest residual peaks in the difference Fourier map
3
Ê
were 0.742 and 0.646 e A
.
3. Results and discussion
Two parallel series of ®ve-coordinate oxorhenium and
oxotechnetium `3 ‡ 1' mixed ligand complexes containing
either the SNS/S or the SNN/S donor atom set are synthe-
sized and characterized in this study. The monothiolate
coligand, common in all derivatives, carries an amine
bifunctional anchor in the para position to the phenylthio-
late group. Thus, by combining the bifunctional p-NH2-Ph-
SH coligand with four different tridentate aminethiolate
ligands, LH2 [LH2: CH3CH2N(CH2CH2SH)2, (CH3CH2)2-
NCH2CH2N(CH2CH2SH)2, (CH2)4NCH2CH2NHCH2CH2-
SH and (CH3CH2)2NCH2CH2NHCH2CH2SH], two parallel
series of bifunctional technetium(V) or rhenium(V) com-
plexes are produced at carrier level, whose chemical proper-
ties and structure are studied and compared (Scheme 1).
Reproduction of the analogous technetium complexes at
tracer level (99mTc) is undertaken and corroboration of struc-
ture with their chemically characterized analogs at carrier
level is investigated by chromatographic methods [40].
The oxorhenium complexes 1, 2, 3 and 4 (Scheme 1) are
generated by reaction of equimolar quantities of tridentate
and p-NH2±Ph±SH ligands with the ReVOCl3(PPh3)2 pre-
cursor according to Eq. (1):
Scheme 1. Bifunctional rhenium and technetium (carrier and tracer)
mixed ligand complexes containing the SNS/S or SNN/S donor atom sets.
1
IR, UV±Vis and H NMR spectroscopies and chromato-
graphic methods (both TLC and HPLC).
The IR spectra of the rhenium and technetium complexes
in the SNS/S series demonstrate, in addition to the bands
originating from coordinating ligands, a characteristic band
1
at 944/939 and 909 cm assigned to the respective Re=O
and Tc=O stretching vibrations, in good agreement with
reported values for similar MVO mixed ligand complexes
[25±31]. The UV±Vis spectra show maxima at 442, 448 nm
for the rhenium and 532, 547 nm for the technetium analogs,
characteristic of ReVO±S or TcVO±S charge-transfer
band(s), respectively, as reported for analogous MVO-thio-
lato complexes [25±31]. The 1H NMR spectra reveal that the
complexes are diamagnetic, consistent for both ReVand TcV
with a d2 electronic con®guration in a distorted trigonal
LH2 ‡ p-NH2 Ph SH ‡ ReVOCl3ꢀPPh3†
2
! ReVO‰ꢀL†ꢀp-NH2 Ph S†Š
(1)
1
bipyramidal ®eld [25±31]. The H NMR spectra demon-
The corresponding 99gTcVO complexes 5, 6, 7 and 8
(Scheme 1) are produced in a similar manner, but using
the technetium(V) gluconate precursor instead, according to
Eq. (2). This precursor forms in situ from a mixture of
NH499gTcO4, sodium gluconate and SnCl2 in 1N HCl after
the pH is adjusted to 7.5. The desired products are then
puri®ed by organic extraction in CH2Cl2:
strate the parent ligand peaks in the ®nal metal complexes
with the exception of the three thiolate protons. The
deshielding effect of either the ReO3‡ or TcO3‡ core (Lewis
acid) to the vicinal protons is apparent and causes a down-
®eld shift of the corresponding proton peaks (compare for
example the CH3CH2N±Tc values of 4.0 ppm in 5 with
those of 2.5 ppm in the free LH2 ligand). On the other hand,
formation of closed ring systems upon metal complexation
introduces considerable rigidity in the resulting complexes,
thereby rendering the attribution of certain proton systems
more complicated. Moreover, the amine substituent of the
SNS ligand may be locked in either a syn or an anti position
in respect to the oxometal core upon coordination and
accordingly formation of two isomers is theoretically pos-
sible. However, correlation of the 1H NMR data to those of
LH2 ‡ p-NH2 Ph SH ‡ 99gTcVO-gluconate
!
99gTcVO‰ꢀL†ꢀp-NH2 Ph S†Š
(2)
Given that the tridentate LH2 ligand and the p-NH2±Ph±
SH coligand are deprotonated upon coordination to the
MO3‡ core, neutral complexes are generated in both the
oxorhenium and the oxotechnetium series. The compounds
newly synthesized are characterized by elemental analysis,

M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
103
exist in the anti con®guration. One may suggest that the
anti isomer might be stabilized by O(1) interactions with the
C(2) and C(3) hydrogen atoms. This, however, is not the
case as can be judged by comparing the O(1)Á Á ÁC(5) dis-
Ê
tance of 2.93 A in the present syn structure with the
O(1)Á Á ÁC(2) and O(1)Á Á ÁC(3) distances of 3.61 and
Ê
3.56 A in the anti isomer of ReO[(C2H5)2NCH2CH2N-
(CH2CH2S)2][SC6H4OCH3] [28]. The coordination geome-
try around the metal is distorted trigonal bipyramidal with
the sulfur atoms of the SNS ligand and the oxo group
de®ning the basal plane and the apices occupied by the
nitrogen atom of the SNS ligand and the sulfur atom of the
monothiol. The angles between the atoms in the basal plane
are close to the ideal 1208 (Table 2), but a value of 159.6(1)8
observed for the S(3)±Re±N(1) angle indicates a distortion
of the trigonal bipyramid, re¯ected also in the value of the
trigonality index [41], ꢇ ˆ 0.64. This type of distortion has
been also observed in the syn isomers of analogous Tc and
Re complexes [26,28]. The bond distances in the coordina-
tion environment of the metal are characteristic for this type
Fig. 1. An ORTEP diagram of ReVO{[(C2H5)2NCH2CH2N(CH2CH2S)2]-
(p-H2N±PhS)} (2) showing also the hydrogen atoms of the amine group,
with 50% probability thermal ellipsoids.
Ê
of complexation. The Re=O double bond of 1.693(3) A is in
the range observed for other ReO3‡ complexes [28,42±53],
Ê
reported SNS/S rhenium and technetium analogs is easily
achieved and is consistent with the formation of only the syn
isomers in a distorted trigonal bipyramidal geometry around
the metal [25±31].
and the Re±N bond length [Re±N(1) ˆ 2.209(4) A] is typi-
cal for the Re±Namine single bond, where the nitrogen atom
exhibits a sp3 hybridization [28,42±53]. As for the metal to
sulfur bond lengths, those in the basal plane are similar [Re±
Ê
Ê
This conclusion is further supported by X-ray data of
complex 2. An ORTEP diagram of 2 is presented in Fig. 1.
Crystal, intensity collection and re®nement data are sum-
S(1) ˆ 2.272(2) A, Re±S(2) ˆ 2.278(2) A], while an
Ê
expected lengthening is observed [Re±S(3) ˆ 2.310(2) A]
Ê
for the Re±S apical bond [28,42±53]. The metal is 0.09 A
Ê
marized in Table 1 and selected bond lengths (A) and angles
displaced out of the basal plane of the trigonal bipyramid
towards the monothiol. The ®ve membered rings de®ned by
the atoms Re, S(1), C(1), C(2), N(1) and Re, S(2), C(4),
C(3), N(1) exist in the envelope form with C(2) and C(3)
(8) are presented in Table 2. The complex is the syn isomer
where the substituent to N(1) is pointing in the same
direction as the oxo group. In a series of analogous
Tc(V) and Re(V) complexes this con®guration is the most
favored as a consequence of interactions between O(1) and
Ê
displaced by 0.59 and 0.64 A, respectively, out of the mean
plane of the remaining four atoms. The dihedral angles of
the chelating agent are 47.2 and 52.78 for S(1)±C(1)±C(2)±
N(1) and S(2)±C(4)±C(3)±N(1), respectively.
Ê
the methylenic hydrogens (O(1)Á Á ÁH(5A) ˆ 2.652 A,
Ê
O(1)Á Á ÁH(5B) ˆ 2.766 A). These interactions no longer
Characterization of the bifunctional SNN/S oxorhenium
and oxotechnetium complexes proceeds in a similar manner.
In particular, the IR spectra demonstrate characteristic
Table 2
Ê
Selected bond lengths (A) and angles (8) for 2 and 3
1
bands at 941/945 cm for the rhenium and at 912/911
cm 1 for the technetium analogs, assigned to M=O strech-
ing vibrations, as reported for similar MVO complexes
[27,28]. The UV±Vis spectra, on the other hand, show
maxima at 385/380 nm for the rhenium and 460/450 nm
for the technetium compounds, originating from the corre-
sponding ReVO±S and TcVO±S charge-transfer band(s), as
reported for similar MVO-thiolato complexes [27,28]. The
1H NMR data suggest that the complexes are diamagnetic
and consistent with a d2 electronic con®guration in a square
pyramidal ®eld for both metals [27,28]. All parent ligand
protons can be detected shifted down®eld after complexa-
tion except for the two thiolate and secondary amine protons
[27,28].
2
3
Re±O(1)
Re±N(1)
Re±S(2)
Re±S(1)
Re±S(3)
1.693(3)
2.209(4)
2.278(2)
2.272(2)
2.310(2)
Re±O
1.706(5)
1.944(5)
2.209(5)
2.284(2)
2.322(2)
Re±N(1)
Re±N(2)
Re±S(1)
Re±S(2)
O(1)±Re±N(1)
O(1)±Re±S(2)
N(1)±Re±S(2)
O(1)±Re±S(1)
N(1)±Re±S(1)
S(2)±Re±S(1)
O(1)±Re±S(3)
N(1)±Re±S(3)
S(2)±Re±S(3)
S(1)±Re±S(3)
95.3(2)
117.8(1)
83.7(1)
O±Re±N(1)
114.7(2)
100.4(2)
78.5(2)
O±Re±N(2)
N(1)±Re±N(2)
O±Re±S(1)
120.4(1)
83.5(1)
108.7(2)
82.2(2)
N(1)±Re±S(1)
N(2)±Re±S(1)
O±Re±S(2)
121.2(1)
105.0(1)
159.6(1)
85.7(1)
149.9(2)
110.8(2)
134.0(2)
87.3(2)
N(1)±Re±S(2)
N(2)±Re±S(2)
S(1)±Re±S(2)
The structure of representative rhenium analog 3 is fully
elucidated by X-ray crystallographic analysis. An ORTEP
87.2(1)
89.7(1)

104
M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
Ê
The value of 1.944(5) A found for the Re±N(1) bond is
carrying a double bond character when the typical values for
Re±N singlet [42±53,56±61] and triplet [62] bond lengths
Ê
are taken into account (2.15 and 1.69 A, respectively). This
value is consistent with those found in other oxorhenium(V)
complexes containing Re±Namide bonds [42,63±66]. The
three bond angles around the deprotonated N(1) atom are
close to 1208 [114.1(6)±124.9(5)8], as expected for the sp2
hybridization of this atom. Moreover, the Re, N(1) and the
carbon atoms adjacent to the nitrogen are nearly coplanar.
Ê
On the other hand, the Re±N(2) bond length of 2.209(5) A is
in the range observed for other ReO3‡ complexes contain-
ing Re±Namine bonds [26,28,42±53], while the angles about
N(2) are close to 1098, as expected for the sp3 hybridization
of this atom. The Re±S bond distances [Re±S(1) ˆ 2.284(2)
Ê
and Re±S(2) ˆ 2.322(2) A] are consistent with those
reported for analogous complexes [26,28,42±53]. The rhe-
Ê
nium atom is 0.70 A out of the basal plane towards the apex.
The ®ve membered rings of the chelating agent exist in the
Ê
envelope form, where C(1) and C(4) are 0.65 and 0.54 A out
of the plane de®ned by Re, S(1), C(2), N(1) and Re, N(2),
C(3), N(1), respectively. The pyrrolidine ring also exists in
Fig. 2. An ORTEP diagram of ReVO{[(CH2)4NCH2CH2NCH2CH2S](p-
H2N±PhS)} (3) with 50% probability thermal ellipsoids. Atom O0 belongs
to a centrosymmetric molecule and is H-bonded to the amine group of the
thiol resulting in the formation of dimers.
Ê
the envelope form with N(2) being the `¯ap' atom (0.59 A
diagram of 3 is shown in Fig. 2. Crystal, intensity, collection
and re®nement data are summarized in Table 1 and selected
bond distances and angles are listed in Table 2, showing that
the complex adopts a distorted square pyramidal geometry
around the metal. The aminethiolate ligand acts as a tri-
dentate chelating agent through the SNN atoms occupying
the basal plane of the distorted square pyramid. The coor-
dination sphere is completed by the monodentate thiol in the
basal plane and the oxo group positioned on the apex of the
pyramid. Examining the S(1)±Re±N(2) and S(2)±Re±N(1)
angles in the basal plane (149.9(2) and 134.0(2)8, respec-
tively), a value of 0.26 for the trigonality index [41] can be
calculated (ꢇ ˆ 0 for a perfect sp and ꢇ ˆ 1 for a perfect
tbp). This intermediate value has also been reported for
analogous Tc(V) complexes presenting the same type of
complexation [27]. The bond distances in the coordination
sphere of rhenium deserve some attention. Thus, the Re=O
displacement). The torsion angles S(1), C(1), C(2), N(1) and
N(1), C(3), C(4), N(2) are 42.0(9) and 43.2(9)8, respec-
tively.
A factor in the stabilization of square pyramidal geometry
in the case of SNN/S species is the sp2 hybridization of N(1),
which forces C(2), C(3), N(1), Re to form a plane with
Ê
largest deviation of 0.06 A for N(1), while in the case of
SNS/S species the same four atoms do not de®ne a plane
Ê
since the largest deviation now is 0.39 A for N(1).
Correlation of structure between rhenium and technetium
complexes at carrier level and those of technetium forming
at tracer level is followed by HPLC adopting both photo-
metric (for Re and 99gTc) and radiometric (for 99mTc)
detection modes. Recovery of radioactivities injected onto
the column is practically quantitative. Comparative chro-
matographic data are summarized in Table 3 and represen-
tative chromatograms for 2, 6 and [99mTc]-6 are shown in
Fig. 3. It is evident that in the SNS/S series a good correla-
tion is achieved between Re, 99gTc and 99mTc complexes
(compare tR for 1, 2 to those of 5, 6 and [99mTc]-5, [99mTc]-
6 complexes in Table 3; Fig. 3). However, in the SNN/S
series, despite the good agreement of chromatographic data
between the Re and the 99gTc compounds at carrier level,
Ê
double bond (1.706(5) A) is longer than usual [42±55] and
can be attributed to the H-bond formed between the oxo
group and the NH2 moiety of a symmetry related molecule,
Ê
resulting in the formation of dimers (N3±HN3A ˆ 0.860 A,
0
0
0
Ê
O Á Á ÁHN3A ˆ 2.347 A, N3-HN3AÁ Á ÁO ˆ 159.18, N3Á Á Á
0
Ê
O ˆ 3.165 A, symmetry operation for O
x, y, z).
Table 3
Cumulative chromatographic data of SNS/S and SNN/S oxometal mixed ligand complexes (M: Re, 99gTc and 99mTc) on a RP C18 column, TEAP buffer/
1
EtOH gradient system from 0 to 70% EtOH in 20 min at a 1 ml min flow rate
Re complex
tR (min)
99gTc complex
tR (min)
99mTc complex
tR (min)
1
2
3
4
20.8
20.7
21.4
21.7
5
6
7
8
20.9
20.8
21.6
21.8
[
[
[
[
99mTc]-5
99mTc]-6
99mTc]-7
99mTc]-8
20.9
20.8
23, 25, 28 (mixture)
24, 27 (mixture)

M. Papadopoulos et al. / Inorganica Chimica Acta 285 (1999) 97±106
105
4. Supplementry material
Atomic co-ordinates, thermal parameters and bond
lengths and angles have been deposited at the Cambridge
Crystallographic Data Centre (CCDC). Any request to the
CCDC for this material should quote the full literature
citation and the reference number.
Acknowledgements
The authors are grateful to the Greek Secretariat of
Athletics (O.P.A.P.) and Mrs. A. Athanasiou for partial
®nancial support (A.T.).
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