Syntheses and first crystal structures of rhenium complexes derived from ω-functionalized fatty acids as model compounds of technetium tracers for myocardial metabolism imaging

Article abstract of DOI:10.1002/1099-0682(200205)2002:5<1219::AID-EJIC1219>3.0.CO;2-N

In an attempt to develop new technetium-based radiopharmaceuticals for the noninvasive diagnosis of myocardial metabolism, we have synthesized three examples of novel metal-containing fatty acid derivatives according to the "3+1 " mixed-ligand and the Schiff base/tricarbonyl design. The chelates contain the metal core in the oxidation states +5 and +1, respectively, and are attached to the end-position of a fatty acid chain. The complex formation was accomplished by ligand-exchange reactions with three different rhenium precursors, whereas the inactive rhenium metal was utilized as a surrogate of the technetium radionuclide. The molecular structures of the fatty acid complexes 7, 10 and 14 were determined by single-crystal X-ray diffraction analyses and impressively show a general problem in technetium tracer research, namely the significant structural alterations of bioactive molecules by coordination even to small metal chelates. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0682(200205)2002:5<1219::AID-EJIC1219>3.0.CO;2-N

FULL PAPER
Syntheses and First Crystal Structures of Rhenium Complexes Derived from
ω-Functionalized Fatty Acids as Model Compounds of Technetium Tracers for
Myocardial Metabolism Imaging
Christian M. Jung,[a] Werner Kraus,[b] Peter Leibnitz,[b] Hans-Jürgen Pietzsch,[a]
Joachim Kropp,[c] and Hartmut Spies*[a]
Keywords: Rhenium / Technetium / Fatty acids / Drug research / Radiopharmaceuticals
In an attempt to develop new technetium-based radiophar- precursors, whereas the inactive rhenium metal was utilized
maceuticals for the noninvasive diagnosis of myocardial
metabolism, we have synthesized three examples of novel
metal-containing fatty acid derivatives according to the ‘‘3+1’’
mixed-ligand and the Schiff base/tricarbonyl design. The
chelates contain the metal core in the oxidation states +5 and
+1, respectively, and are attached to the end-position of a
fatty acid chain. The complex formation was accomplished
by ligand-exchange reactions with three different rhenium
as a surrogate of the technetium radionuclide. The molecular
structures of the fatty acid complexes 7, 10 and 14 were de-
termined by single-crystal X-ray diffraction analyses and im-
pressively show a general problem in technetium tracer re-
search, namely the significant structural alterations of bioac-
tive molecules by coordination even to small metal chelates.
(
Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
tracers in routine cardiac diagnostics. On the other hand,
Naturally occurring long-chain fatty acids serve as the the low-price availability from the 99Mo/99mTc generator
main energy source of the normoxic myocardium. Regional combined with its optimal radiophysical properties, and the
alterations in the myocardial fatty acid oxidation may indi- commercial distribution of pre-prepared instant kits for
cate ischemic heart diseases and cardiomyophaties at an various clinical examinations have made technetium-99m
early stage and therefore possess a remarkable diagnostic the preferred radiolabel in nuclear medicinal imaging.[2] The
potential in nuclear medicine. Although radio-iodinated progress in 99mTc tracer design to monitor specific endo-
fatty acids such as 15-(p-[123I]iodophenyl)pentadecanoic genic functions is nevertheless severely limited by the effect
acid (IPPA) and its β-methyl-branched derivative BMIPP of the artificial radiometal and its coordination chemistry
have proven their applicability for myocardial metabolism on the in vivo behaviour of labelled bioactive molecules.
imaging in numerous clinical trials, fatty acid scintigraphy
has not yet reached widespread application in nuclear medi-
cine.[1] Compared to the technetium-99m-based perfusion
tracers that are mainly applied at present, radiolabelled
fatty acids allow more convincing scans of viable myocar-
dium. However, logistical disadvantages and disproportion-
ately high costs of the accelerator-produced radionuclide
iodine-123 still conflict with a major acceptance of these
The synthesis of technetium-containing long-chain fatty
acids for accessing regional discrepancies in myocardial en-
ergy production has been a goal of many research groups
since 1975.[3] Although a variety of different chelating moi-
eties were used to attach the radiometal at the fatty acid
skeleton, low myocardial extraction and poor recognition
as a substrate for the β-oxidation in living cells has pre-
vented an application of these 99mTc-labelled agents in nuc-
lear medicine. A characteristic feature of almost all the
[a]
Forschungszentrum Rossendorf e.V., Institut für Bio- technetium-99m fatty acid analogues described so far is the
anorganische und Radiopharmazeutische Chemie,
focus on polar tetradentate N2S2 chelates with a central
Postfach 510119, 01314 Dresden, Germany
oxometal(V) core. In our attempt to create new technetium-
labelled fatty acids with an improved myocardial profile, we
therefore concentrate on alternative coordination moieties
according to the ‘‘nϩ1’’ mixed-ligand approach[4] and the
Schiff base/tricarbonyl design.[5] Since working with radio-
active compounds affords great care and is subjected to
some restrictions, the third-row congener rhenium was used
Fax: (internat.) ϩ 49-(0)351/260-3232
E-mail: H.Spies@fz-rossendorf.de
[b]
[c]
Bundesanstalt für Materialforschung und -prüfung,
Richard-Willstätter-Straße 11, 12489 Berlin, Germany
E-mail: W.Kraus@bam.de
Medizinische Fakultät Carl Gustav Carus an der Technischen
Universität Dresden, Klinik und Poliklinik für Nuklearmedizin,
Fetscherstraße 74, 01307 Dresden, Germany
E-mail: jkmed@rcs.urz.tu-dresden.de
Eur. J. Inorg. Chem. 2002, 1219Ϫ1225
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ1948/02/0505Ϫ1219 $ 20.00ϩ.50/0
1219

C. M. Jung, W. Kraus, P. Leibnitz, H.-J. Pietzsch, J. Kropp, H. Spies
FULL PAPER
in our preliminary studies as a surrogate for the radio- tions; complex 7 was obtained almost quantitatively by
active technetium.
smooth chloride exchange of the thia fatty acid 5 at the
preformed oxorhenium(V) precursor 6 (Scheme 2). The co-
ordination sphere of these mixed-ligand complexes differs
in the central donor atom of the tridentate chelator, being
sulfur in the model compound 7 and nitrogen in complex
10. Accompanied by the alteration of the tridentate ligand
part is a change in colour from reddish-brown (for 7) to
dark green (for 10). The infrared spectra of both complexes
Results and Discussion
In this paper we report the synthesis and crystal structure
of three new classes of rhenium-containing fatty acid ana-
logues. From our point of view, success in the development
of bioactive metal-based fatty acid tracers is primarily de-
pendent on the choice of a suitable chelating moiety, which
allows a strong binding of the bioligand to the metal centre
but preserves the physiological integrity of the fatty acid.
Since the carboxylic group probably plays a fundamental
role in the substrate cognition in vivo we decided to func-
tionalize fatty acid ligands in their ω-position. For the head
structures we used the skeleton of the IPPA tracer,[6] which
has been well tested in clinical trials, and the metabolism-
blocking sulfur-inserted fatty acid analogue 14-(R,S)-
[18F]fluoro-6-thiaheptadecanoic acid (FTHA),[7] as well as
the naturally occurring lauric acid.
show a strong absorption band in the region of 955 cmϪ1
,
which is distinctive of the central ReϭO3ϩ moiety. In the 1H
NMR spectra of compound 7 the protons of the tridentate
chelator give representative coupling patterns at δH ϭ 4.27,
3.90, 3.09 and 1.95; the equivalent signals of the
‘‘SN(Me)S’’ ligand are partly widened and coincided and
are observed between δH ϭ 3.9Ϫ2.6.
Suitable ω-sulfanyl fatty acid ligands required for the
‘‘3ϩ1’’ mixed-ligand concept were synthesized starting
from the corresponding ω-bromo derivatives. Whereas the
pentadecanoic acid starting material was reasonably acces-
sible by acidic ring opening of the corresponding ω-hy-
droxylactone by hydrobromic acid,[8] the thia-inserted hep-
tadecanoic acid analogue 4 was prepared in three steps
starting from the commercially available 5-bromovaleric
acid 1. After nucleophilic substitution of the halide at the
end position by a sulfanyl unit, the fatty acid body was
built up by coupling to 11-bromo-1-undecanol under basic
conditions. Conversion of the hydroxy group into a bromide
was accomplished by an adopted version of the Appel reac-
tion.[9] Sulfonyl groups in the ω-position of the fatty acids
5 and 8 were finally introduced by nucleophilic attack of
sodium thiophosphate and subsequent acidic hydrolysis[10]
(Scheme 1).
Scheme 2. Syntheses of ‘‘3ϩ1’’ mixed-ligand complexes 7 and 10
Both complexes 7 and 10 were obtained as crystalline
solids by slow solvent evaporation at room temperature and
were investigated by X-ray analysis. As characteristic of
‘‘SSS’’-coordinated ‘‘3ϩ1’’ mixed-ligand complexes, 7 pos-
sesses a square-pyramidal coordination sphere around the
central metal core. The distorted basal surface, stretched by
the four sulfur donor atoms, exhibits a twisted orientation
with respect to the planar arrangement of the fatty acid
chain (Figure 1). An alteration of the tridentate to the
‘‘SN(Me)S’’ chelator results in a transition of the coordina-
tion sphere to a distorted trigonal-bipyramidal geometry. In
10 (Figure 2) the axial positions are occupied by the nitro-
gen donor of the tridentate ligand and the sulfur atom of
the monodentate fatty acid derivative, respectively; the cor-
ner sites of the triangular plane, however, are taken up by
Scheme 1. Synthesis of ω-sulfanyl ε-thia fatty acid 5
Coordination of the ω-sulfanyl fatty acid ligands 5 and 8 the oxygen atom of the ReϭO3ϩ unit and the two sulfanyl
to the rhenium precursors 6[11] and 9[12] according the groups of the ‘‘SN(Me)S’’ ligand. In structures 7 and 10,
‘‘3ϩ1’’ approach offers access to the oxorhenium(V) com- bond lengths and angles within the chelate moieties are of
plexes 7 and 10, respectively. Preparation of 10 was accom- the order of magnitude expected for these types of rhenium
plished in moderate yields by a one-pot synthesis of the coordination compounds (Table 1). However, a special or-
tetrachlorooxorhenate 9, the protected ‘‘SN(Me)S’’ tri- der/disorder phenomenon was detected in the crystal pack-
dentate and the ω-sulfanyl fatty acid 8 under basic condi- ing of 10. As frequently observed in this type of complexes
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Eur. J. Inorg. Chem. 2002, 1219Ϫ1225

Rhenium Complexes Derived from ω-Functionalized Fatty Acids
FULL PAPER
Figure 1. Molecular structure of ‘‘SSS’’-coordinated ‘‘3ϩ1‘‘ mixed-
ligand complex 7
˚
Table 1. Selected bond lengths [A] and angles [°] for ‘‘3ϩ1’’ mixed-
ligand complexes 7 and 10
Figure 2. Molecular structure of ‘‘SN(Me)S’’-coordinated ‘‘3ϩ1’’
mixed-ligand complex 10
7
10
ReϪO(1)
ReϪS(1)
ReϪS(2)
ReϪS(3)
1.684(8)
2.303(3)
2.377(3)
2.293(3)
2.301(3)
114.2(3)
100.3(3)
ReϪO(1)
ReϪN
ReϪS(1)
ReϪS(2)
1.671(5)
2.208(7)
2.273(4)
2.265(3)
2.295(3)
95.3(3)
119.0(2)
118.3(2)
105.2(2)
82.72(16)
83.99(17)
159.44(18)
88.54(8)
121.99(11)
84.96(10)
pounds, bidentate aromatic Schiff base ligands are exceed-
ingly suitable for coordinating the tricarbonylmetal(I) moi-
ety. We therefore synthesized an appropriate fatty acid de-
rivative; starting from commercially available ω-amino-
lauric acid (11), the corresponding Schiff base 12 was
obtained by simple condensation of picolinaldehyde with
the amino group of the analogous lauric acid salt. Since the
resulting imines decompose even by neutralisation,[14] the
protonation of the carboxyl function was carried out sub-
sequent to the stabilizing attachment of the tricarbon-
ylrhenium moiety. The two nitrogen donor atoms replace
two bromide ions of the tricarbonylrhenium(I) precursor
13.[15] The third halide substituent, however, is responsible
ReϪS(4)
ReϪS(3)
O(1)ϪReϪS(1)
O(1)ϪReϪS(2)
O(1)ϪReϪS(3)
O(1)ϪReϪS(4)
S(1)ϪReϪS(2)
S(3)ϪReϪS(1)
S(3)ϪReϪS(2)
S(3)ϪReϪS(4)
S(4)ϪReϪS(1)
S(4)ϪReϪS(2)
O(1)ϪReϪN
O(1)ϪReϪS(1)
O(1)ϪReϪS(2)
O(1)ϪReϪS(3)
NϪReϪS(1)
NϪReϪS(2)
NϪReϪS(3)
S(1)ϪReϪS(3)
S(2)ϪReϪS(1)
S(2)ϪReϪS(3)
115.7(3)
106.6(3)
84.22(13)
129.88(14)
83.41(12)
81.05(11)
88.76(11)
152.78(12)
the ‘‘SN(Me)S’’ chelator can change its conformation by a for the compensation of the electrical charge and remains
flip-flop mechanism giving rise to a statistical distribution fixed in the coordination sphere of the metal(I) core
of two equal isomers within the crystal.[13]
(Scheme 3). Complex 14 was obtained as a deep orange
Alberto et al. recently introduced the ‘‘fac-[M(CO)3]ϩ’’ compound and showed the characteristic carbonyl absorp-
fragment as promising synthon for the labelling of biomole- tion bands at 2021 and 1902 cmϪ1 in the infrared spectrum.
cules with technetium.[5] Due to the known tendency of the The imine proton of the fatty acid ligand was detected as a
1
metal(I) core to interact strongly with soft donor com- sharp singlet in the H NMR spectrum at δH ϭ 8.70; the
Eur. J. Inorg. Chem. 2002, 1219Ϫ1225
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C. M. Jung, W. Kraus, P. Leibnitz, H.-J. Pietzsch, J. Kropp, H. Spies
FULL PAPER
13C signals of the three carbonyl substituents were observed
˚
Table 2. Selected bond lengths [A] and angles [°] for tricarbon-
ylrhenium(I) complex 14
at δC ϭ 196.6, 195.8 and 186.1.
14
ReϪC(1)
ReϪC(2)
ReϪC(3)
ReϪN(1)
ReϪN(2)
ReϪBr
O(1)ϪC(1)
O(2)ϪC(2)
O(3)ϪC(3)
N(1)ϪC(8)
N(2)ϪC(9)
C(8)ϪC(9)
1.871(12)
1.883(12)
1.873(13)
2.159(7)
C(1)ϪReϪC(2)
C(1)ϪReϪC(3)
C(3)ϪReϪC(2)
C(1)ϪReϪN(1)
C(1)ϪReϪN(2)
C(2)ϪReϪN(1)
C(2)ϪReϪN(2)
C(3)ϪReϪN(1)
C(3)ϪReϪN(2)
C(1)ϪReϪBr(1)
C(2)ϪReϪBr(1)
C(3)ϪReϪBr(1)
N(1)ϪReϪBr(1)
N(2)ϪReϪBr(1)
N(2)ϪReϪN(1)
89.6(6)
88.6(6)
89.9(5)
97.2(5)
171.5(5)
170.7(4)
98.6(5)
96.5(4)
93.9(5)
92.6(4)
89.2(4)
178.5(4)
84.3(2)
85.0(2)
74.4(3)
2.152(9)
2.6253(13)
1.158(14)
1.168(13)
1.137(14)
1.345(12)
1.272(14)
1.452(15)
Scheme 3. Synthesis of tricarbonylrhenium(I) complex 14
Compound 14 crystallized upon slow concentration of a
saturated solution in acetonitrile. As expected for this type
of complex, the molecular structure shows an octahedral
coordination sphere around the central rhenium(I) core.
The three carbonyl moieties are arranged facial to each
other, and the remaining coordination sites are occupied
by the bidentate Schiff base ligand and a bromine atom
(Figure 3, Table 2).
Particularly conspicuous in the molecular structure of all
three complexes, 7, 10, and 14, are the proportions between
the chelate moieties and the fatty acid ligands. The drastic
structural alteration of the biomolecules, even by coordina-
tion to small-sized metal chelates, is certainly a main reason
for the laborious progress in the development of new tech-
netium-based radiotracers with the objective of assessment
of specific endogenous processes and physiological func-
tions. Nevertheless, structural integrity is only one of sev-
eral parameters, besides others such as lipophilicity and po-
larity, that influence the in vivo behaviour of potential
99mTc radiotracers. Therefore further investigations con-
cerning the biological profile of the technetium-99m ana-
logues of 7, 10 and 14 will be done to estimate the value of
these compounds as potential radiotracers for myocardial
metabolism imaging.
Experimental Section
General Remarks: All chemicals and solvents were of reagent grade
and utilized without further purification, with the exception of pic-
olinaldehyde, which was freshly distilled prior to use. 11-Bromo-1-
undecanol and 12-aminolauric acid were purchased from Fluka.
Sodium
thiophosphate[16]
and N-methyl-3-azapentane-1,5-
dithiolϪoxalic acid[17] were prepared according to the literature.
The syntheses involving air-sensitive compounds were carried out
under argon using the standard Schlenk technique. The standard
workup procedure for product isolation was quenching the reaction
mixture in an aqueous solution, followed by extracting thoroughly
with CHCl3, washing the extracts with saturated saline, drying
owith MgSO4 and evaporating the solvent under reduced pressure.
Column chromatography was performed according to Still[18] by
using Merck silica gel (0.040Ϫ0.063 mm). IR: PerkinϪElmer Spe-
1
cord 2000. NMR: Varian Inova-400. For H NMR CDCl3 (δH
ϭ
7.26) and CD3OD (δH ϭ 3.31) were used as solvents, for 13C NMR
CDCl3 (δC ϭ 77.0). Elemental analyses: LECO CHNS 932.
15-Sulfanylpentadecanoic Acid (8): 1.96 g (10.9 mmol) of sodium
thiophosphate in 20 mL of H2O was added to a solution of 1.75 g
(5.45 mmol) of 15-bromopentadecanoic acid[8] in 50 mL of di-
Figure 3. Molecular structure of tricarbonylrhenium(I) complex 14
1222
Eur. J. Inorg. Chem. 2002, 1219Ϫ1225

Rhenium Complexes Derived from ω-Functionalized Fatty Acids
FULL PAPER
methylformamide. The resulting slurry was stirred for 72 h while
increasing the temperature from 25 to 50 °C. Afterwards, the mix-
7.8,
1
H, CH2SH), 1.49Ϫ1.79 (m,
8
H, CH2CH2SH,
CH2CH2SCH2CH2, CH2CH2COOH), 2.37 (t, 3J ϭ 7.2, 2 H,
ture was quenched with 3.5% HCl (pH ϭ 2) and stirred overnight. CH2COOH), 2.44Ϫ2.55 (m, 6 H, CH2SCH2, CH2SH). C16H32O2S2
Dilution with additional 30 mL of H2O and subsequent standard
workup yielded a light yellow solid, which was purified by column
chromatography (n-hexane/Et2O/HOAc, 70:30:1). Yield: 1.22 g
(320.56): calcd. C 59.95, H 10.06, S 20.01; found C 59.97, H 10.08,
S 20.12.
Oxorhenium(V) Complex 7: 50 mg (128 µmol) of chloro(3-thiapen-
tane-1,5-dithiolato)oxorhenium(V) (6)[11] was dissolved in 6 mL of
hot acetonitrile while stirring. To this mixture 45 mg (140 µmol) of
the fatty acid 5 was added. The mixture was refluxed for 30 min
and then concentrated to dryness. The residue was purified by flash
chromatography (CHCl3/EtOAc/HOAc, 60:40:1). Crystals suitable
for single crystal analysis were obtained by slow evaporation of a
saturated CHCl3/acetonitrile solution of 7 at room temperature.
1
(82%). IR (KBr): ν˜ ϭ 1714 (CϭO) cmϪ1. H NMR (CDCl3): δ ϭ
1.21Ϫ1.41 (m, 20 H, 10 ϫ CH2), 1.33 (t, 3J ϭ 7.7 Hz, 1 H, CH2SH),
1.55Ϫ1.67 (m, 4 H, CH2CH2SH, CH2CH2COOH), 2.34 (t, 3J ϭ
7.5, 2 H, CH2COOH), 2.52 (dt, 3J ϭ 7.4, CH2SH, 2 H). C15H30O2S
(274.47): calcd. C 65.46, H 11.02, S 11.68; found C 65.50, H 10.98,
S 11.72.
5-Sulfanylvaleric Acid (2): A mixture of 5.00 g (27.6 mmol) of 5-
bromovaleric acid (1) and 3.15 g (41.4 mmol) of thiourea in 50 mL
of ethanol was heated under reflux for 16 h. After cooling off to
room temperature, the solvent was evaporated under reduced pres-
sure and the residue heated with 50 mL of 7.5  NaOH for another
6 h. The mixture was carefully acidified with 2.5  H2SO4, the or-
ganic layer separated and the aqueous phase extracted as usual.
Purification of the remaining raw material was accomplished by
distillation under vacuum. Yield: 3.04 g (82%). b.p. 102Ϫ104 °C/
Yield: 81 mg (94%). IR (KBr): ν˜ ϭ 1703 (CϭO), 958 (ReϭO) cmϪ1
1H NMR (CDCl3): δ ϭ 1.23Ϫ1.41 (m, 12 H, 6 ϫ CH2), 1.46Ϫ1.60
.
3
3
(m, 4 H), 1.64 (quint, J ϭ 7.3, 2 H), 1.74 (quint, J ϭ 7.4, 2 H,
CH2CH2SCH2CH2, CH2CH2COOH, CH2CH2CH2SRe), 1.88
3
(quint, J ϭ 7.6, 2 H, CH2CH2SReO‘‘SSS’’), 1.95 (ddd, J1 ϭ 4.9,
J2 ϭ 9.9, J3 ϭ 14.6, 2 H, A-part ABCD system ‘‘SSS’’), 2.38 (t,
3
3
3J ϭ 7.3, 2 H, CH2COOH), 2.49 (t, J ϭ 7.3, 2 H), 2.52 (t, J ϭ
7.1, 2 H, CH2SCH2CH2CH2), 3.09 (dt, J1 ϭ 4.0, J2 ϭ 13.8, 2 H,
B-part ABCD system ‘‘SSS’’), 3.83 (t, 3J
ϭ 7.5, 2 H,
1
3
0.7 Torr. H NMR (CDCl3): δ ϭ 1.35 (t, J ϭ 7.9, 1 H, CH2SH),
1.59Ϫ1.80 (m, 4 H, CH2CH2CH2SH), 2.37 (t, 3J ϭ 7.1, 2 H,
CH2COOH), 2.54 (dt, 3J ϭ 7.2, 2 H, CH2SH), 10.2Ϫ11.3 (br, 1 H,
COOH). 13C NMR: δ ϭ 23.3, 24.1 (CH2S, CH2CH2COOH), 33.2,
33.4 (CH2CH2S, CH2COOH), 179.8 (COOH). C5H10O2S (134.20):
calcd. C 44.75, H 7.51, S 23.89; found C 44.43, H 7.74, S 23.50.
CH2SReO‘‘SSS’’), 3.90 (dd, J1 ϭ 3.8, J2 ϭ 10.2, 2 H, C-part ABCD
system ‘‘SSS’’), 4.27 (dd, J1 ϭ 4.7, J2 ϭ 13.1, 2 H, D-part ABCD
system ‘‘SSS’’). C20H39O3ReS4 (674.06): calcd. C 35.64, H 5.83, S
23.79; found C 35.46, H 5.81, 23.86.
Oxorhenium(V) Complex 10: A mixture of 140 mg (510 µmol) of
8, 109 mg (452 µmol) of N-methyl-3-azapentane-1,5-dithiolϪoxalic
acid, 265 mg (452 µmol) of tetrachlorooxorhenate 9[12] and 4 mL
of 1  methanolic NaOAc in 25 mL of MeOH was stirred at 40 °C
for 24 h. The solvent was removed under reduced pressure and the
remaining brown solid partitioned between 25 mL of H2O and
CHCl3. After standard workup, the pure complex was isolated by
column chromatography (CHCl3/EtOAc/HOAc, 50:50:1) and sub-
sequent crystallisation from ethanol. Yield: 191 mg (68%). IR
17-Hydroxy-6-thiaheptadecanoic Acid (3): To a solution of 2.50 g
(43.7 mmol) of KOH in 85 mL of ethanol was added, whilst stir-
ring, 2.9 g (21.6 mmol) of 2 and subsequently 5.40 g (21.5 mmol)
of 11-bromo-1-undecanol. After heating under reflux for 12 h, the
mixture was acidified with 2.5  H2SO4 and the solvent evaporated
under reduced pressure. The residue was partitioned between 75
mL of H2O and CHCl3 and worked up by standard procedures.
Crystallisation from MeOH at Ϫ15 °C yielded the pure fatty acid
3 as a colourless solid. Yield: 5.66 g (86%). IR (KBr): ν˜ ϭ 1690
(KBr): ν˜ ϭ 1705 (CϭO), 950 (ReϭO) cmϪ1 1H NMR (CDCl3):
.
δ ϭ 1.20Ϫ1.38 (m, 18 H, 9 ϫ CH2), 1.47 (quint, 3J ϭ 7.4, 2 H,
CH2CH2CH2SRe), 1.63 (quint, 3J ϭ 7.4, 2 H, CH2CH2COOH),
1.85 (quint, 3J ϭ 7.4, 2 H, CH2CH2SRe‘‘SNS’’), 2.35 (t, 3J ϭ 7.6, 2
H, CH2COOH), 2.63 (m, 2 H, ‘‘SNS’’), 3.16Ϫ3.22 (m, 4 H, ‘‘SNS’’,
CH2SReO‘‘SNS’’), 3.35 (s, 3 H, NCH3), 3.54 (m, 2 H, ‘‘SNS’’),
3.5Ϫ3.9 (br, 2 H, ‘‘SNS’’). C20H40NO3ReS3 (624.95): calcd. C
38.44, H 6.45, N 2.24, S 15.39; found C 38.52, H 6.65, N 2.21,
S 15.47.
(CϭO) cmϪ1 1H NMR (CDCl3): δ ϭ 1.19Ϫ1.39 (m, 14 H, 7 ϫ
.
CH2), 1.47Ϫ1.76 (m, 8 H, CH2CH2OH, CH2CH2SCH2CH2,
CH2CH2COOH), 2.33 (t, 3J ϭ 7.2, 2 H, CH2COOH), 2.46 (t, 3J ϭ
3
7.4, 2 H), 2.48 (t, 3J ϭ 7.2, 2 H, CH2SCH2), 3.59 (t, J ϭ 6.7, 2
H, CH2OH), 6.77 (br, 2 H, CH2OH, COOH). C16H32O3S (304.49):
calcd. C 63.11, H 10.59, S 10.53; found C 63.04, H 10.50, S 10.47.
17-Bromo-6-thiaheptadecanoic Acid (4): 646 mg (2.46 mmol) of
PPh3 was added, whilst stirring, to
a solution of 817 mg
Sodium
12-{[(Pyridin-2-yl)methylene]amino}undecanoate
(12):
(2.46 mmol) of CBr4 and 250 mg (821 µmol) of 3 in 25 mL of ace-
tonitrile at 0 °C. The mixture was allowed to reach ambient temper-
ature and was stirred overnight. The solvent was evaporated under
reduced pressure and the residue partitioned between 50 mL of
H2O and CHCl3 followed by standard workup and column chro-
matography (n-hexane/Et2O/HOAc, 75:25:1). Yield: 238 mg (79%).
IR (KBr): ν˜ ϭ 1693 (CϭO), 647 (CϪBr) cmϪ1. 1H NMR (CDCl3):
δ ϭ 1.22Ϫ1.48 (m, 14 H, 7 ϫ CH2), 1.50Ϫ1.80 (m, 6 H,
200 mg (777 µmol) of amino fatty acid 11 was dissolved in 5 mL
of MeOH, containing 31 mg (775 µmol) of NaOH. The solution
was filtered and then concentrated to dryness. The residue was re-
dissolved in 5 mL of MeOH and 125 mg (1.15 mmol) of freshly
distilled picolinaldehyde was added whilst stirring at 0 °C. The mix-
ture was stirred for additional 12 h at room temperature before
removing the solvent and washing the residue carefully with several
portions of acetone and Et2O. Schiff base sodium salt 12 was ob-
tained as a light brown powder without any further purification
steps. Yield: 248 mg (87%). IR (KBr): ν˜ ϭ 1648 (CHϭN), 1561
3
CH2CH2SCH2CH2, CH2CH2COOH), 1.85 (quint, J ϭ 7.1, 2 H,
3
3
CH2CH2Br), 2.38 (t, J ϭ 7.2, 2 H, CH2COOH), 2.49 (t, J ϭ 7.5,
2 H,), 2.52 (t, 3J ϭ 7.4, 2 H, CH2SCH2), 3.40 (t, 3J ϭ 6.9, 2 H,
CH2Br). C16H31BrO2S (267.39): calcd. C 52.31, H 8.50, S 8.73;
found C 52.28, H 8.38, S 8.53.
(CϭO) cmϪ1. H NMR (CD3OD): δ ϭ 1.23Ϫ1.42 (m, 14 H, 7 ϫ
1
CH2), 1.59 (m, 2 H), 1.73 (m, 2 H CH2CH2N, CH2CH2COONa),
2.14 (t, 3J ϭ 7.6, CH2COONa, 2 H), 3.68 (t, 3J ϭ 7.0, 2 H, CH2N),
7.48 (m, 1 H, H5-Ar), 7.91 (m, 1 H, H4-Ar), 7.99 (m, 1 H, H3-Ar),
8.37 (s, 1 H, CHϭN), 8.61 (m, 1 H, H6-Ar). C18H27N2NaO2
17-Sulfanyl-6-thiaheptadecanoic Acid (5): ω-Sulfanyl ligand 5 was
prepared from 200 mg (544 µmol) of 4 by the procedure described
for 8. Yield: 122 mg (70%). IR (KBr): ν˜ ϭ 1694 (CϭO) cmϪ1. H (326.41): calcd. C 66.23, H 8.34, N 8.58; found C 65.94, H 8.53,
1
3
NMR (CDCl3): δ ϭ 1.20Ϫ1.41 (m, 14 H, 7 ϫ CH2), 1.32 (t, J ϭ N 8.87.
Eur. J. Inorg. Chem. 2002, 1219Ϫ1225
1223

C. M. Jung, W. Kraus, P. Leibnitz, H.-J. Pietzsch, J. Kropp, H. Spies
Table 3. Crystallographic data and structure refinement for complexes 7, 10 and 14
FULL PAPER
7
10
14
Empirical formula
Formula mass
Crystal system
Space group
C20H39O3ReS5
674.01
orthorhombic
Pbca
9.0585(3)
13.1617(4)
45.3602(15)
C20H40NO3ReS3
624.91
monoclinic
P21/c
16.17(2)
11.082(16)
14.18(2)
C21H28BrN2O5Re
654.56
triclinic
¯
P1
˚
a [A]
6.6516(14)
8.1605(16)
23.325(5)
˚
b [A]
˚
c [A]
α [°]
β [°]
γ [°]
90
90
90
5408.1(3)
90
92.15(3)
90
2538(6)
89.678(4)
86.915(4)
74.811(4)
1220.0(4)
3
˚
V [A ]
Z
8
4
2
Dcalcd. [g cmϪ3
]
1.656
4.898
1.635
5.054
1.782
6.649
Absorption coefficient [mmϪ1
]
F(000)
2704
1256
636
Crystal size [mmϪ1
θ range [°]
]
0.450 ϫ 0.360 ϫ 0.054
1.80Ϫ29.03
Ϫ11 Յ h Յ 12
Ϫ17 Յ k Յ 17
Ϫ61 Յ l Յ 48
30609
0.21 ϫ 0.11 ϫ 0.05
2.23Ϫ23.43
Ϫ17 Յ h Յ 17
Ϫ12 Յ k Յ 10
Ϫ15 Յ l Յ 15
10503
0.4 ϫ 0.28 ϫ 0.1
0.87Ϫ20.00
Ϫ6 Յ h Յ 6
Ϫ6 Յ k Յ 7
Ϫ20 Յ l Յ 22
3785
Index ranges
Reflections collected
Independent reflections
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I Ͼ 2σ(I)]
R indices (all data)
6759 [Rint ϭ 0.0704]
Ψ scan
3639 [Rint ϭ 0.0608]
Ψ scan
0.31671, 0.20085
full-matrix least squares on F2
3639/14/280
2282 [Rint ϭ 0.0705]
Ψ scan
0.409, 0.253
full-matrix least squares on F2
2282/11/271
0.866
R1 ϭ 0.0416, wR2 ϭ 0.1147
R1 ϭ 0.0454, wR2 ϭ 0.1238
0.898, Ϫ1.825
0.350, 0.173
full-matrix least squares on F2
6654/0/263
1.161
0.666
R1 ϭ 0.0841, wR2 ϭ 0.2088
R1 ϭ 0.0928, wR2 ϭ 0.2136
2.170, Ϫ2.066
R1 ϭ 0.0345, wR2 ϭ 0.0910
R1 ϭ 0.0454, wR2 ϭ 0.0983
0.948, Ϫ1.670
Ϫ3
˚
Largest diff. peak and hole [eA
]
(Tricarbonyl)rhenium(I) Complex 14: 45 mg (130 µmol) of fatty acid of hydrogen atoms were calculated corresponding to their geomet-
ligand 12 was dissolved in 2 mL of MeOH and added to a solution
rical conditions and refined using the riding model. Atomic num-
of 100 mg (130 µmol) of tricarbonylrhenium(I) precursor 13[15] in bering schemes are shown in Figure 1 (for 7), Figure 2 (for 10) and
1 mL of MeOH. The mixture immediately turned to a deep orange Figure 3 (for 14). Selected bond lengths and angles are listed in
colour and became cloudy within 15 min. After stirring overnight Tables 1 and 2. For complex 7 only crystals of poor quality were
at room temperature, the solvent was removed in a nitrogen stream.
Then 1 mL of CHCl3 and 1 mL of 4  aqueous HBr were added
and the mixture was vigorously stirred for another 24 h. After-
available, reflected in a relatively high R value for this compound.
CCDC-156312 (7), -172606 (10) and -172605 (14) contain the sup-
plementary crystallographic data for this paper. These data can be
wards, the organic layer was separated and the aqueous phase thor- obtained free of charge at www.ccdc.cam.ac.uk/conts/retriev-
oughly extracted in the usual manner. Purification of the obtained ing.html or from the Cambridge Crystallographic Data Centre, 12,
residue was accomplished by column chromatography (CHCl3/ Union Road, Cambridge CB2 1EZ, UK [Fax: (internat.) ϩ 44-
EtOAc/HOAc, 100:25:4). Crystals of complex 14 suitable for single-
crystal X-ray analysis were obtained by slow crystallization of 14
from an acetonitrile solution at room temperature. Yield: (74%).
1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
IR (KBr): ν˜ ϭ 2021, 1902 (CϵO), 1713 (CϭO) cmϪ1 1H NMR
.
Acknowledgments
This work was funded by grants from the Deutsche Forschungs-
gemeinschaft and Fonds der Chemischen Industrie.
(CDCl3): δ ϭ 1.22Ϫ1.43 (m, 14 H, 7 ϫ CH2), 1.62 (quint, 3J ϭ
7.2, 2 H, CH2CH2COOH), 1.94Ϫ2.35 (m, 2 H, CH2CH2N), 2.34
(t, 3J ϭ 7.4, 2 H, CH2COOH), 4.03 (m, 1 H), 4.26 (m, 1 H, CH2N),
7.56 (m, 1 H, H5-Ar), 7.90 (m, 1 H, H4-Ar), 8.05 (m, 1 H, H3-Ar),
8.70 (s, 1 H, CHϭN), 9.04 (m, 1 H, H6-Ar). C21H28BrN2O5Re
(654.57): calcd. C 38.53, H 4.31, N 4.28, Br 12.21; found C 38.40,
H 4.35, N 4.24, Br 12.31.
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[I01455]
Eur. J. Inorg. Chem. 2002, 1219Ϫ1225
1225