Formation, preservation, and cleavage of the disulfide bond by vanadium

Article abstract of DOI:10.1002/chem.200390207

Reaction of the disulfide {HpicanS}₂ (HpicanS is the carboxamide based on picolinate (pic) and o-mercaptoaniline (anS); the {} brackets are used to denote disulfides) with [VOCl₂(thf)₂] leads to reductive scission of the d

Full text of DOI:10.1002/chem.200390207

FULL PAPER
Formation, Preservation, and Cleavage of the Disulfide Bond by Vanadium
Dongren Wang, Axel Behrens, Mahin Farahbakhsh, Jessica G‰tjens, and Dieter Rehder*[a]
Abstract: Reaction of the disulfide
{HpicanS}2 (HpicanS is the carboxamide
based on picolinate (pic) and o-mercap-
toaniline (anS); the {} brackets are used
to denote disulfides) with [VOCl2(thf)2]
leads to reductive scission of the disul-
fide bond and formation of the mixed-
(salanS)] (2a), or [VCl(tmeda)-
(vananS)] (2b). The disulfide bond re-
mains intact in the aerial reaction be-
tween {HsalanS}2 and [VCl3(thf)3] to
yield the VV complex [VOCl{salanS}2]
(3), where (salanS)2À coordinates
through the two phenolate and one of
À
to form the complexes [VO{vananS}2]
(4a) or [VO{napanS}2] (4b). In 4a and
4b, the phenolate and imine functions,
and presumably also one of the disul-
fide-S atoms, coordinate to VIV. 2-Mer-
captophenyl-2'-pyridinecarboxamide
(H2picanS) retains its identity in the
valence (VIV/VV) complex anion [(OV- the imine functions. The S S bond is
presence of VIII
; reaction between
picanS)2m-O]À (1), with the dianionic
ligand coordinating through the pyri-
dine-N atom, the deprotonated amide-N
atom, and thiophenolate-S atom. Re-
also preserved as [VO(van)2] or [V O- [VCl3(thf)3] and H2picanS yields [V-
(nap)2] (Hnap ˆ 2-hydroxynaphthalene-
1-carbaldehyde) is treated with bis-
(2-aminophenyl)disulfide, {anS}2, a re-
action which is accompanied by conden-
sation of the aldehyde and the diamine,
and complexation of the resulting bis-
(Schiff bases) {HvananS}2 or {HnapanS}2
{picanS}2]À (5). The dithiophenolate
2,6-bis(mercaptophenylthio)dimethylpy-
ridine (6a) is oxidized, mediated by
VO2‡, to the bis(disulfide) octathiadi-
aza-cyclo-hexaeicosane 6b. The rele-
vance of these reactions for the speci-
ation of vanadium under physiological
conditions is addressed. [HNEt3]-1 ¥
À
ductive cleavage of the S S bond is also
observed as [VCl2(tmeda)2] (tmeda ˆ
tetramethylethylenediamine) is treated
with the disulfides {HsalanS}2 or {Hvan-
anS}2 (HsalanS and HvananS are the
Schiff bases formed between o-mercap-
toaniline and salicylaldehyde (Hsal)
or vanillin (Hvan), respectively), yield-
ing the VIII complexes [VCl(tmeda)-
0.5NEt3,
3 ¥ 3CH2Cl2,
{HsalanS}2,
Keywords: amides
¥
biomimetic
[HNEt3]-5, and 6b ¥ 4THF have been
characterized by X-ray diffraction anal-
ysis.
synthesis ¥ disulfides ¥ S ligands ¥
vanadium
the formation of an intermediate where the organic sulfide is
in contact with the active center, since formation of sulfoxide
from prochiral sulfides occurs enantioselectively. Likewise,
sulfide- and disulfide vanadium intermediates supposedly
form in the enatioselective oxo transfer to sulfides[6, 7] and
disulfides[8] with oxovanadium Schiff base[6, 8] and oxovana-
dium ethanolamine systems.[7]
An additional, and an equally important aspect of the
vanadium sulfur interaction is the redox and nonredox
inhibition by vanadate of phosphatases containing cysteine
in their active centers.[9, 10] Vanadate may coordinate to the
active center cysteinate, forming a coordination environment
very much reminiscent of that in haloperoxidases, with the
exception that histidine is replaced by cysteinate.[11] Inhibition
of a protein tyrosine phosphatase by vanadate has been
noted as a possible key step[12] in the insulin-mimetic action of
inorganic and organic (coordination) compounds of vanadi-
um.[13]
Introduction
There is continuing interest in studies towards the coordina-
tion of thiofunctional ligands to vanadium[1] in the context of
enzymes containing vanadium in the active center, since these
investigations can model the specific bonding situation and
thus reactivity of the vanadium cofactor. Examples are
vanadium-nitrogenase from Azotobacter, where vanadium–
in analogy to its molybdenum counter-part–is coordinated
to, inter alia, three sulfides,[2] and vanadium-containing nitrate
reductase from A. vinelandii,[3] which–again in analogy to the
more common Mo analogue[4]–probably contains dithiolen-
ate (as a constituent of a pyranopterin moiety) attached to the
oxo metal center. Furthermore, the sulfide peroxidase
activity of vanadate-dependent haloperoxidases[5] suggests
[a] Prof. Dr. D. Rehder, Dr. D. Wang, Dipl.-Chem. A. Behrens, Dr. M.
Farahbakhsh, Dipl.-Chem. J. G‰tjens
Institut f¸r Anorganische und Angewandte Chemie
Universit‰t Hamburg, 20146 Hamburg (Germany)
Fax : (‡49)40-4123-2893
Vanadium complexes undergo a complex speciation pattern
in extra- and intracellular body fluids, including hydrolysis,
ligand exchange, and redox chemistry, the knowledge of which
E-mail: dieter.rehder@chemie.uni-hamburg.de
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D. Rehder et al.
FULL PAPER
is a precondition for understanding physiological effects of
vanadium compounds. Several solution speciation studies
modeling this situation with glutathione and related ligands
have been carried out recently.[14, 15] The particularly impor-
tant intracellular tripeptide glutathione GSH (where SH
represents cysteine) and its oxi-
me 1b) formed in this case is a dinuclear, oxo-bridged, mixed-
valence anionic VIVVV complex containing the tridentate
amide ligand picanS2À (NNS2À). The counterion in this
reaction, which has been carried out in the presence of NEt3
‡
to capture the protons formed, is [HNEt3] .
dized form GSSG, which are
present in millimolar concen-
trations and can redox-interact
18]
with vanadium,[16
have been
shown to form a variety of
complexes with VO2‡ in aque-
ous solution, including com-
plexes with thiolate coordina-
tion to the vanadyl ion.[14, 15]
The present study is designed
to evidence the extent and
quality of interactions between
vanadium in various oxidation
states and multifunctional li-
gands containing disulfide or
thiolate functions, and thus
modeling interactions of vana-
dium with peptides and pro-
teins having cystine or cysteine
constituents.
Results and Discussion
An overview comprising the
ligands and complexes em-
ployed or characterized in this
work is shown in Schemes 1a
(ligands) and 1b (complexes).
Cleavage of the disulfide bond:
We have previously shown[19]
that the disulfide 2,2'-dithiodi-
benzaldehyde is reduced in a
two-electron reduction by
[VCl3(thf)3] to form, in the
presence of 2-mercaptoaniline,
a chlorooxovanadium(v) com-
plex stabilized by the tridentate
(SNS) Schiff base ligand origi-
nating from the condensation of
mercaptoaniline and the prod-
uct of the disulfide reduction,
2-mercaptobenzaldehyde
[Eq. (1)]. As shown in Equa-
tion (2) for the reaction be-
tween [VOCl2(thf)2] and the
disulfide {HpicanS}2, {HNNS}2
(letters in italics correspond to
ligand functions), reductive
cleavage of the sulfur sulfur
bond can also be initiated by
(VIVO)2‡. Anion 1 (see Sche-
Scheme 1. Overview of the ligands (a) and complexes (b) employed or characterized. pic ˆ picolinate, anS ˆ o-
mercaptoaniline, sal ˆ salicylaldehyde, van ˆ vanillin, nap ˆ 2-hydroxynaphthalene-1-carbaldehyde. The picanS
ligands are carboxamides, the ligands salanS, vananS, and napanS are Schiff bases. Braces {} indicate disulfides.
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Cleavage of Disulfide Bond by Vanadium
1805 1813
The additional oxygen atom presumably stems from
residual water in the solvent THF; the second electron
needed in this reaction may originate from a second vanadyl
ion. The n(CONH) associated with {HpicanS}2, 1626 cmÀ1, is
shifted to 1596 cmÀ1 in 1, indicative of deprotonation of the
amide in picanS2À. Both nitrogen atoms, and the thiolate
formed by reduction, coordinate to the vanadium center.
V1, is in an about ideal square-pyramidal array with the
doubly bonded oxo group in the apical position and vanadium
displaced from the plane N1N2S1O3 by 0.0272 ä, the other,
V2, is in a somewhat distorted tetragonal-pyramidal environ-
ment, quantified by an angular t parameter of 0.26 (t ˆ 0 for
an ideal square pyramid, t ˆ 1 for an ideal trigonal bipyr-
amid). V2 is 0.1161 ä above the plane spanned by the three
ligand functions and the bridging oxygen O3. O3 is not exactly
ˆ
There is a broad band for the n(V O) at 991 with a shoulder at
981 cmÀ1. The room-temperature EPR spectrum of 1 in THF
shows two superimposed eight-line systems (coupling of the
electron to the 51Vnucleus (nuclear spin ˆ 7/2)) with signifi-
cantly different g0 and A0 values, namely g0 ˆ 1.983 and A0 ˆ
82  10À4 cmÀ1 for component 1, and g0 ˆ 1.97 and A0 ˆ 101 Â
10À4 cmÀ1 for component 2. The electron is thus not delocal-
ized over the two vanadium sites; the two different vanadium
sites, in which the single electron can reside, are about equally
populated.
in the center of the two vanadium ions; d(V1 O3) ˆ 1.749(2),
À
À
d(V2 O3) ˆ 1.866(2) ä; the angle V1-O-V2 amounts to
ˆ
135.06(10)8. The V O moieties are arranged in between the
perpendicular and the syn configuration; the torsion angle
O1,V1,V2/O2,V2,V1 is 40.228 and thus differs from the
situation encountered in other mixed-valence dinuclear
vanadium complexes such as anti-[{VO(tacn)}2m-O] (176.58,
tacn is a functionalized triazacyclononane),[20] syn-[{VO(sal-
ser)}2m-O]À (11.68, sal-ser is the Schiff base from salicylalde-
hyde and serine),[21] or [{VO(sal-ala)}2m-O]À (83.78).[22] The
The inequivalence of the two oxo-linked building blocks of
the dinuclear anion 1 is also revealed by the crystal structure
determination of [Et3NH]-1 ¥ 0.5NEt3 (Figure 1). For selected
À
d(V S) are comparable to those in most other thiolate
complexes of VIV and VV (compare the discussion in
reference [19]). Not unexpectedly, they are substantially
shorter than in thioether complexes.[19, 23] The bonds to the
pyridine-N atom are again in the usual range,[24] the bonds to
the amide nitrogen atoms (N2 and N4), 2.042(2) and
2.031(2) ä, are slightly longer than reported in the literature
(mean d(V Namide) ˆ 2.014 ä[25]).
À
As can be expected for a VII compound, [VCl2(tmeda)2]
(tmeda ˆ N,N,N',N'-tetramethylethylenediamine) also reduc-
tively splits the disulfide bond in the double Schiff base
disulfides derived from 2,2'-diaminodiphenyl disulfide and
salicylaldehyde ({HsalanS}2) or 2-hydroxynaphthalene-1-car-
baldehyde ({HvananS}2), HONSSNOH; see the idealized
Equation 3. The structures of the disulfides are described
below. VII is oxidized to VIII, and the resulting Schiff base
thiolates salanS2À and vananS2À substitute one tmeda and one
chloro ligand to form the monochlorovanadium complexes 2a
and 2b. The reaction is conducted in THF, yielding mixtures
of 2 and the hydrochloride of tmeda; 2 can be isolated in
analytically pure form by diffusion of pentane into the THF
solution. The Raman spectrum of 2 no longer exhibits the
band between 500 and 550 cmÀ1 typical of the disulfide
Figure 1. Structure of [Et3NH][(OVpicanS)2m-O], [Et3NH]-1, (ORTEP
plot; 50% probability level) including one molecule of NEt3 of crystal-
lization per 2 units of [Et3NH]-1.
bonding parameters see Table 1. The counterion (N5) is
linked to one of the doubly bonded oxo groups (O2) by an
bridge.[26] The n(HC N) is shifted by 10 cmÀ1 on coordination
À
ˆ
N H ¥¥¥ O bond (2.856 ä). While one of the vanadium centers,
Table 1. Selected bond lengths [ä] and angles [8] of vanadium complexes.
1
3[a]
5
À
À
À
À
V1 O1
1.6111(18)
1.7496(17))
2.3307(7)
2.092(2)
V2 O2
1.612(2)
1.866(2)
2.3458(7)
2.097(2)
2.031(2)
V O2
À
V Cl
1.589(3)
2.3690(14)
1.925(3)
1.986(3)
2.117(4)
1.304(6)
1.308(6)
2.0699(17)
V N1
À
V N3
2.1141(19)
2.1141(18)
2.0582(18)
2.0777(18)
2.3481(7)
2.3868(7)
À
À
V1 O3
V2 O3
À
À
À
À
V1 S1
V2 S2
V O1
V N2
À
À
À
À
V1 N1
V2 N3
V O3
V N4
À
À
À
À
V1 N2
2.042(2)
V2 N4
V N1
V S1
À
À
N1 C15
V S2
À
V1-O3-V2
O3-V1-O1
O3-V1-S1
O3-V1-N1
O3-V1-N2
S1-V1-N1
N1-V1-N2
S1-V1-N2
135.06(10)
109.01(9)
92.84(6)
90.96(8)
146.47(8)
145.45(6)
76.70(8)
81.40(6)
N2 C12
À
O3-V2-O2
O3-V2-S2
O3-V2-N3
O3-V2-N4
S2-V2-N3
N3-V2-N4
S2-V2-N4
111.64(9)
92.92(6)
87.99(8)
136.81(8)
152.52(6)
78.24(8)
82.47(6)
S1 S2
N1-V-S1
N3-V-S2
N2-V-N4
S1-V-S2
N2-V-N1
N2-V-N3
N2-V-S1
N2-V-S2
159.91(6)
153.63(6)
173.52(7)
103.47(3)
77.98(7)
97.03(7)
83.17(5)
152.52(6)
Cl-V-N1
O1-V-O3
Cl-V-O2
Cl-V-O3
O1-V-N1
156.83(10)
142.55(13)
103.71(13)
87.52(10)
86.38(14)
[a] Additional parameters for the disulfide moiety are provided in Table 3
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D. Rehder et al.
FULL PAPER
(1613 and 1611 in 2a and 2b, 1603 and 1601 cmÀ1 in free
{HsalanS}2 and {HvananS}2).
the two sulfur atoms S1 and S2 and the second imine group
(N2) remain uncoordinated, the closest contact being that
between Vand S1 (4.29 ä), that is, clearly beyond the sum of
the van der Waals radii. Despite this, the bond length
À
d(S1 S2) ˆ 2.070(2) is widened with respect to this distance
in the free ligand {HsalanS}2 (2.026 ä; vide infra), but
À
compares to d(S1 S2) in metal complexes in which the sulfur
33]
binds to the metal.[30
The coordination sphere of 3 is
Preservation of the disulfide bond: The mechanism of the
rupture of the disulfide bond as catalyzed by metals may
involve intermediate coordination of the electrophilic metal
supplemented by the doubly bonded oxo group and a chloro
ligand. Vanadium, in a slightly distorted square-pyramidal
environment (t ˆ 0.28), is displaced from the tetragonal plane
formed by O1, O2, N1, and Cl by only 0.089 ä. All bond
lengths involving vanadium are normal. The bonding param-
eters of {salanSÀ}2 in complex 3 will be discussed in a broader
context below.
Reaction of [VO(van)2] (Hvan ˆ o-vanillin) or [VO(nap)2]
(Hnap ˆ 2-hydroxynapthalene-1-carbaldehyde), [VO(OO)2]
(OOÀ is the aldehydo ligand) in Equation (5), with diamino-
diphenyl disulfide ({anS}2) in dry THF yields the complexes
4a and 4b derived from the double Schiff-base ligands
{HsalanS}2 and {HvananS}2 (see Scheme 1), which form by
in situ condensation. The structure for 4 proposed in
Scheme 1b is based on spectroscopic characteristics and
elemental analyses. Thus, the IR bands (Table 2) character-
istic of the aldehyde group of [VO(OO)2] and the amino
groups of {anS}2 are no longer present in 4. Instead, new IR
ion to (one of the sulfurs of) the disulfide.[27, 28] Disulfide
[29]
¬
complexes have been known since the work by Br‰nden,
although no such complex has so far been structurally
characterized for vanadium. Our own efforts to prepare
vanadium complexes of disulfides have lead to a structurally
characterized complex with an intact, though uncoordinated,
disulfide in the coordination sphere, 3, and to disulfide
complexes, structurally not characterized, where one of the
sulfurs probably coordinates to vanadium, namely the com-
plexes 4a and 4b, see Scheme 1b. The reactions leading to 3
and 4 are presented in idealized form in Equations (4) and (5).
ˆ
absorptions appear for the newly formed HC N moiety.
Table 2. Selected IR characteristics of the complexes 4 and their pre-
cursors.
Compound 3 is obtained from the reaction between
[VCl3(thf)3] and {HsalanS}2 in CH2Cl2 in the presence of
triethylamine as a proton scavenger. Oxygen present in the
solution oxidizes VIII to oxovanadium(v), which coordinates to
ˆ
ˆ
À
n(NH2)
n(CHO)
n(HC N)
n(V O)
n(V S)
VO(van)2
VO(nap)2
{anS}2
4a
1657
1686
958
978
the dianionic ligand {salanSÀ}2, ÀONSSNOÀ. The character-
3373, 3297
À1
ˆ
ˆ
istic n(V O) lies at 992 cm . The n(HC N) of the free ligand,
1613 cmÀ1, is split into two bands in 3, shifted to 1627 and
1607 cmÀ1, corresponding to uncoordinated and coordinated
imine-N atoms in the complex. This situation is corroborated
by the X-ray diffraction analysis of 3 ¥ 3CH2Cl2 (Figure 2;
selected bonding parameters are collated in Table 1). Al-
1603
1617
985
982
362
358
4b
The coordination of one of the sulfur atoms of the disulfide
bond is supported by a n(VS) around 362 cmÀ1 and the
parallel (z) component of the EPR spectroscopic hyperfine
coupling constant Az ˆ 162  10À4 cmÀ1. Using the partial az
values provided by Chasteen[34] and Kabanos et al.[35] for
imine-N (44.1), phenolate-O (38.9), and thiophenolate-S
(35.3) atoms, the calculated Az originating from an SNO2
equatorial donor set amounts to 156.9 Â 10À4 cmÀ1. We
suppose, however, that a disulfide-S atom is a clearly weaker
ligand than a thiolate-S atom and hence gives rise to a larger
partial contribution than the latter, resulting in the observed
value.
though {salanSÀ}2 usually functions as a pentadentate li-
33]
gand,[30
only three of its functions are employed in
coordination here, namely the two phenolate oxygen atoms
O1 and O3, and one of the imine nitrogen atoms (N1), while
Thiolato complexes, and the formation and characterization
of disulfides: VIII does not redox interact with thiolates; the
anionic VIII thiolato complex 5 has thus been obtained by
direct reaction of [VCl3(thf)3] with the amide ligand H2picanS
(Scheme 1a) in dry THF plus NEt3. Addition of triethylamine
is necessary to promote deprotonation of the amide group and
its coordination, along with the pyridine-N atom and the
thiophenolate-S atom, to the vanadium center. A triethylam-
Figure 2. Structure of [VOCl{salanS}2] (3) (ORTEP plot; 50% probability
level), including the three CH2Cl2 molecules of crystallization.
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Cleavage of Disulfide Bond by Vanadium
1805 1813
monium ion is the counterion for 5. Complex 5 contains two
nonequivalent picanS2À ligands, as evidenced by two amide
bands in the IR spectrum (1611 and 1586; free H2picanS:
1690 cmÀ1), and by the molecular structure as revealed by
X-ray structure analysis (Figure 3). The complex is distorted
Figure 4. Structure of 6b (ORTEP plot; 50% probability level).
Figure 3. Structure of [Et3NH][V(picanS)2], [Et3NH]-5 (ORTEP plot;
50% probability level).
octahedral. The two tridentate ligands occupy meridional
positions, with the two amide-N atoms N2 and N4 trans to
each other. Bonding parameters (Table 1) are in the usual
Figure 5. Structure of {HsalanS}2 (ORTEP plot; 50% probability level).
The two independent molecules in the unit cell are shown.
À
range, except for the d(V Namide) distances 2.058(2) and
2.078(2) ä, which are considerably longer than corresponding
parameters reported in the literature (mean 2.014 ä[25]).
On the other hand, thiolates can be oxidized to disulfides in
the presence of VO2‡,[36 38] a reaction that can be accompanied
by an abstraction of the oxo group[37, 38] and concomitant
formation of non-oxo VIV complexes.[38] The VO2‡-mediated
oxidation of thiolate has also been observed for the reaction
between the dithiolate 6a and [VO(acac)2] (acac ˆ
acetylacetonate(1 À )), which leads to the cyclic bis(disulfide)
6b (see Scheme 1a). For the overall reaction we propose the
sequence represented by Equation (6), in which the initiating
step is the deoxygenation of the vanadyl group (Equa-
tion (6a)), followed by oxidation of thiolate to disulfide by
VIV (Equation (6b)), and reconstitution of the vanadyl moiety
by oxygen (Equation (6c)). The net reaction is therefore
aerial oxidation of the thiolate, catalyzed by the vanadyl ion.
{salanSÀ}2 of compound 3 are summarized in Table 3. The unit
cell of {HsalanS}2 contains two independent molecules in the
™perpendicular∫ orientations to each other (Figure 5).
The two phenyl rings C5,C6,C9,C12,C20,C8 and
(C5,C6,C9,C12,C20,C8)# in 6b (point group C2) are parallel
to each other; the distance between the two planes, 3.35 ä
(the offset of the ring centers is 1.84 ä) suggests interaction.
Bonding parameters are about equal for the three disulfides
À
and, with the exception of d(S S), also in the range noted for
other disulfides.[39] The d(S S) in 6b and {HsalanS}2 are
À
significantly shorter than in disulfides in general (av (2.072 Æ
0.08) ä)[39] and, as far as 6b is concerned, other cyclic
bis(disulfides) such as tetrathia-cyclo-eicosanes in particular
À
(2.083(1) ä).[36, 37] On the other hand, d(S S) of {salanS }2 in 3
À
À
falls within the range of average S S distances in neutral
disulfides, and in complexes where {salanSÀ}2 coordinates in
the pentadentate fashion, including coordination of one of the
sulfurs.[30 33] Quite in contrast, the angles S-S-C in {salanSÀ}2 in
3 are narrowed with respect to uncomplexed {HsalanS}2 and
other disulfides, where the a(S-S-C) range from 102.6 to
104.88, and this is also the case for the dihedral angle C1,S1,S2/
C10,S2,S1, 72.148 in 3, narrowed with respect to the corre-
sponding angle in {HsalanS}2 (82.348) and other disulfides (av
(82.1 Æ 5.4)8). These differences apparently are due to the
2-SH ‡ VO2‡
!
2-SÀ ‡ VIV ‡ H2O
(6a)
(6b)
(6c)
2VIV ‡ 2-SÀ
!
2VIII ‡ -SS-
2VIII ‡ ³2O2 ‡ H2O
!
2VO ‡ 2H
2‡
‡
1
The cyclo-hexaeicosane 6b (Figure 4) and the disulfide
{HsalanS}2 (Figure 5) were characterized by X-ray diffrac-
tion analysis. Selected structural data, including those for
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D. Rehder et al.
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Table 3. Bonding parameters of structurally characterized disulfides.
À
d(S S)
À
d(S C)
S-S-C/C'-S-S
a(S-S-C)
Dihedral angle
{HsalanS}2
2.026(2)
2.027(2)
2.0699(17)
2.039(3)
C1: 1.782(2), C14: 1.786(3)
C27: 1.785(3), C40: 1.785(3)
C1: 1.780(5), C10: 1.782(5)
C5: 1.778(8), C7: 1.812(9)
C1: 104.64(9), C14: 105.40(11)
C27: 105.36(11), C40: 105.30(10)
C1: 100.30(16), C10: 98.95(16)
C5: 104.7(3), C7: 104.4(3)
82.34
80.39
72.14
87.13
{salanSÀ}2 in 3
6b
specific steric situation in 3. Participation of the sulfur of
{salanSÀ}2 in coordination gives rise to further narrowing, see,
for example, 55.48 in [NiCl{salanS}2] (55.48).[33]
Experimental Section
Physical measurements: Elemental analyses (C, H, N) were carried out on
an Heraeus CHNO-Rapid analyser. IR spectra were recorded on a Perkin-
Elmer 1720 spectrometer, using KBr pellets or nujol spreadings between
KBr crystal plates. 1H spectra were recorded on a Varian Gemini 200 MHz
spectrometer with the usual parameter settings. EPR spectra were
measured with a Bruker ESP 300E spectrometer at 9.74 GHz in 4 mm
vials and concentrations of 1 5 mm at room temp. and at 97 K. Parameter
adaptions were carried out with the program SimFonia (Bruker).
Conclusion
With the present study we have provided evidence, including
structural support, that vanadium, in its physiologically
relevant oxidation state iv (and iii[40, 41]) can form, break,
and preserve the disulfide bond when interacting with organic
disulfides and thiolates. The formation of disulfides via thiyl
radicals has been shown to occur when thiolates such as
cysteine are treated with vanadium(v) complexes.[42, 43] This
reaction is of considerable relevance for the removal of VV in
the intracellular medium (and hence for the detoxification of
vanadate(v), an inhibitor of ATPases[44]), where glutathione
(GSH) is a potent reducing agent,[16, 17, 45, 46] being itself
oxidized to GSSG, although GSH can also be a slow and
rather ineffectual reducing agent in vitro.[47] As shown by
Equation (6), vanadyl ions (VIVO)2‡ are able to catalyze the
aerial oxidation of thiolates. Under physiological conditions, a
similar reaction can take place in the extracellular medium,
and may also be anticipated for the cytoplasm in the presence
of cytoplasmatic oxygen, superoxide, or peroxide. GSSG
makes up about 1 2% of the overall GSH ‡ GSSG (2
3 mm) in erythrocytes;[48, 49] the reformation of GSH from
GSSG, commonly achieved by the action of NADH, might
also be mediated by VO2‡; see Equation (1). Vanadyl ions can
therefore attain a dual role in the GSH/GSSG transformation.
In addition, VO2‡ can stabilize the disulfide bond ([Eq. (5)])
and thiolates by coordination. As was shown by solution
speciation studies, this stabilization includes GSH, for which
several vanadyl complexes have been proposed where cys-
teinate participates in coordination.[15 17, 50] Another candidate
for direct stabilization of thiolates is VIII, which coordinates
thiolates without concomitant redox events. Where VO3‡ is
formed in redox interactions with disulfides, complex forma-
tion with the resulting thiolate ([Eqs. (1, 2)]) or the precursor
disulfide ([Eq. (4)]) can occur. Transmitted again to the
situation in biofluids, vanadium in its oxidation states v, iv,
and iii can be anticipated to be a subtle regulator of the GSH/
GSSG equilibrium, and corresponding equilibria concerning
other peptides with cysteine residues, by scavenging, redox-
transforming and releasing thiolates and disulfides. To what
extent cysteine and cystine moieties undergo redox interac-
tion in the presence of vanadium also depends on the extent of
their stabilization by complexation.
X-ray structure analyses: X-ray structure analyses were carried out in the q/
2q scan mode either on an Enraf-Nonius CAD4 diffractometer with CuKa
irradiation (graphite monochromator, l ˆ 1.54178 ä) at 173(2) K ({Hsa-
lanS}2), or on a Bruker SMART Apex CCD diffractometer with MoKa
irradiation (graphite monochromator, l ˆ 0.71073 ä) at 153(2) K. For the
solution and refinement of the structures, the program package
ShelXTL 5.1 (Bruker 1998) was employed. Hydrogen atoms were placed
into calculated positions and included in the last cycles of refinement. The
‡
protons directly attached to the nitrogen atoms of the [HNEt3] counter-
ions of 1 and 5 were located. Disorder of C62 (the CH3 group of one of the
ethyl substituents of the NEt3 of crystallization in compound [Et3NH]-1 ¥
0.5NEt3) was treated with a 60:40% model. Disorder of one of the
CH2Cl2 molecules in 3 ¥ 3CH2Cl2 was treated in the following way: Cl6
versus Cl7 ˆ 50:50%, Cl8 versus Cl9/Cl10 ˆ 50:50%, and Cl9 versus
À
Cl10 ˆ 30:20%. The five C Cl bond lengths in this model were fixed.
Crystal and refinement data are collated in Tables 4 and 5. CCDC-192885
([Et3NH]-5), CCDC-192866 (3 ¥ 3CH2Cl2), CCDC-192887 ([Et3NH]1 ¥
NEt3), CCDC-192888 ({HsalanS}2), and CCDC-192889 (6b) contain
the supplementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.can.ac.uk/conts/retrieving.html
(or from the Cambridge Crystallographic Centre, 12 Union Road,
Cambridge CB21EZ, UK; Fax: (‡44)1223-336033; or deposit@ccdc.cam.
ac.uk).
Starting materials: These were obtained from commercial sources or
prepared according to literature procedures: [VOCl2(thf)2],[51]
[VCl3(thf)3],[52] {HpicanS}2 and H2picanS,[53] 6a ¥ HCl,[54] and [VCl2(tme-
da)2].[55] The precursors [VO(aldehyde)2] were prepared and identified as
described below, and used directly in the syntheses of 4a and 4b:
[VO(o-vanillin)2]: o-Vanillin (7.6 g, 0.05 mol), VOSO ¥ 5H2O (6.32 g,
4
0.025 mol), and NaOAc ¥ 3H2O (6.8 g, 0.05 mol) were dissolved in deoxy-
genated water/ethanol 1.25:1 (80 mL). The solution was stirred for 2 h at
room temperature. The green precipitate was collected by filtration,
washed with ethanol and diethyl ether, and then dried in vacuo. Yield:
À1
À
ˆ
14.7 g (80%); IR (KBr): nÄ ˆ 3032 (C Harom), 978 (V O), 737 cm (arom.
aldehyde).
[VO(2-hydroxynaphthalene-1-carbaldehyde)2]: 2-hydroxynaphthalene-1-
carbaldehyde (8.6 g, 0.05 mol), VOSO4 ¥ 5H2O (6.32 g, 0.025 mol), and
NaOAc ¥ 3H2O (6.8 g, 0.05 mol) were dissolved in deoxygenated water/
ethanol 1.25:1 (80 mL). The solution was stirred for 4 h at room temper-
ature. The green precipitate was collected by filtration, washed with
ethanol and ether, and dried in vacuo. Yield: 14.3 g (70%); IR (KBr): nÄ ˆ
3050 (C Harom), 982 (V O), 746 cmÀ1 (arom. aldehyde).
À
ˆ
Preparation of the specific compounds
N,N'-{1,1'-dithiobis(phenylene)}bis(salicylideneimine) ({HsalanS}2): A sol-
ution of 2,2'-diaminodiphenyl disulfide (2.48 g, 10 mmol) in methanol
(30 mL) was warmed to 408C and treated by stirring with salicylaldehyde
1810
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0908-1810 $ 20.00+.50/0
Chem. Eur. J. 2003, 9, No. 8

Cleavage of Disulfide Bond by Vanadium
1805 1813
Table 4. Crystal data and structure refinement of complexes.
[Et3NH]-1 ¥ 0.5NEt3
3 ¥ 3CH2Cl2
[Et3NH]-5
empirical formula
C30H39.5N5.5O5S2V2
C29H24Cl7N2O3S2V
540.93
P1
C30H32N5O2S2V
609.67
P1
molecular mass [gmolÀ1
]
≈
≈
≈
space group
a [ä]
P1
8.7500(4)
10.8826(5)
18.4756(8)
90.678(1)
102.990(1)
96.984(1)
1700.16(13)
2
11.9662(9)
13.2090(10)
13.7553(10)
65.150(1)
84.3596(1)
65.950(1)
1473.9(2)
2
10.6472(9)
10.9097(9)
12.8210(11)
88.555(2)
70.753(1)
89.178(2)
1405.5(2)
2
b [ä]
c [ä]
a [8]
b [8]
g [8]
volume [ä3]
Z
1calcd [gcmÀ3
]
1.029
0.51
536
1.030
0.50
522
1.441
0.54
636
m [mmÀ1
F(000)
]
crystal size [mm]
q range [8]
limiting indices
0.41 Â 0.24 Â 0.14
1.13 25.00
À 10 < h < 10
À 12 < k < 12
À 21 < l < 21
32275
0.60 Â 0.30 Â 0.29
1.69 25.00
À 11 < h < 14
À 15 < k < 15
À 16 < l < 14
9640
0.58 Â 0.24 Â 0.07
2.17 27.50
À 13 < h < 13
À 7 < k < 13
À 16 < l < 14
9289
reflections collected
unique reflections
R(int)
5982
0.0377
6036
0.0283
6022
0.0212
refined parameters
Goof on F 2
433
1.107
395
1.108
368
0.932
final R1, wR2 [I > 2s(I0)]
R1, wR2 (all data)
diff. peak and whole [eäÀ3
0.0368 0.1006
0.0423, 0.1114
0.889, À0.295
0.0709, 0.1715
0.0790, 0.1789
1.106, À1.099
0.0415, 0.0858
0.0586, 0.0909
0.483, À0.411
]
Table 5. Crystal data and structure refinement of disulfides.
(60 mL), dried in vacuo and recrystallized from chloroform/DMF (1:1;
30 mL). Pure, yellow {HsalanS}2 cystallized from this solution within
two days in the form of small cubes suitable for an X-ray structural
analysis. Yield 3.93 g (86%); 1H NMR ([D6]DMSO, TMS): d ˆ 12.59
{HsalanS}2
6b ¥ 4THF
empirical formula
C26H20N2O2S2
456.56
P1
12.166(10)
12.380(12)
16.84(2)
70.50(7)
69.35(7)
89.84(7)
2219(4)
C54H62N2O4S8
1059.54
P21/c
8.6681(17)
28.111(5)
10.775(2)
molecular mass [gmolÀ1
]
À
ˆ
(s, 1H; Ph OH), 9.04 (s, 1H; N CH), 7.76 7.00 ppm (m, 8H; aromatic
≈
À
À
ˆ
H); IR (KBr): nÄ ˆ 3459 (O H), 3053 (C Harom), 1613 (C N), 1493
space group
a [ä]
b [ä]
c [ä]
a [8]
b [8]
g [8]
volume [ä3]
Z
ˆ
À
À
À
(C C), 1464 (CH S), 1280 (O H), 1183 (CH S wagging), 753 (o-subst.
À1
À
À
arom.), 713 (C S), 463 cm (S S); elemental analysis calcd (%) for
C26H20N2O2S2 (456.56): C 68.40, H 4.42, N 6.14; found: C 68.30, H 4.39,
N 6.11.
93.485(4)
N,N'-{1,1'-dithiobis(phenylene)}bis(3-methoxysalicylideneimine) ({Hvan-
anS}2): This disulfide was prepared in an analogous fashion to {HsalanS}2,
using o-vanillin (3.04 g, 20 mmol) dissolved in methanol (50 mL). Recrys-
tallization from CHCl3/DMF (1:1; 40 mL) yielded orange needlelike
crystals of {HvananS}2 ¥ 0.25DMF. Yield 4.55 g (85%); IR (KBr): nÄ ˆ 3050
2620.7(9)
2
1.343
0.388
1120
4
1calcd [gcmÀ3
]
1.367
2.388
952
m [mmÀ1
F(000)
]
À
À
ˆ
ˆ
À
(C Harom), 2838 (C HOMe), 1611 (C N), 1566 (C C), 1455 (CH S), 1276
À
À
À
(O H), 1250 (Ph OMe), 1194 (CH S wagging), 780 and 758 (o-subst.
À1
crystal size [mm]
q range [8]
limiting indices
0.45 Â 0.40 Â 0.30
3.00 76.40
À 15 < h < 5
À 15 < k < 15
À 21 < l < 19
9845
0.82 Â 0.30 Â 0.14
2.03 26.50
À 9 < h < 10
À 34 < k < 34
À 12 < l < 13
16166
À
À
arom.), 734 (C S), 455 cm (S S); elemental analysis calcd (%) for
C28H24N2O4S2 ¥ 0.25DMF (534.90): C 64.55, H 4.85, N 5.89; found: C 64.50,
H 4.25, N 5.62.
[Et3NH][{VO(N-2-mercaptophenyl-2'-pyridinecarboxamide)}2O]
([Et3NH]-1): [VOCl2(thf)2] (282 mg, 1 mmol), N,N'-[dithiobis(phenylene)-
bis(pyridinecarboxamide)] ({HpicanS}2) (458 mg, 1 mmol) and NEt3
(303 mg, 3 mmol) were dissolved in absolute THF (100 mL). The solution
was refluxed overnight under N2, and then filtered. The precipitate was a
reflections collected
unique reflections
R(int)
9324
0.0094
5389
0.0960
refined parameters
Goof on F 2
594
1.069
307
1.182
mixture of complex [Et3NH]-1 and [NEt3H]Cl. IR (KBr): nÄ ˆ 1626, 1596
À1
ˆ
ˆ
À
(C O), 991 and 981 sh (V O), 463 cm (V S).
final R1, wR2 [I > 2s(I0)]
R1, wR2 (all data)
diff. peak and whole [eäÀ3
0.0443, 0.1203
0.0463, 0.1226
0.367, À0.554
0.1385, 0.3192
0.1662, 0.3347
1.011, À0.794
Dark green crystals of [HNEt3]-1 ¥ 0.5NEt3 with the same IR characteristics
were obtained by redissolving the precipitate in CH2Cl2, and keeping the
solution at À208C. The room-temperature EPR spectra of the crystals of
[HNEt3]-1 dissolved in THF gave a two-component spectrum with the
]
following parameters: g0 ˆ 1.983 and 1.97, A0 ˆ 82 and 101  10À4 cmÀ1
.
(2.1 mL, 20 mmol). The yellow suspension thus obtained was refluxed for
2 h. This reaction mixture was cooled in an ice bath, whereupon a yellow
solid precipitated, which was filtered off, washed with cold methanol
[VCl{N-1-thiophenyl(salicylideneiminate)}tetramethylethylenediamine]
(2a): A yellow solution of {HsalanS}2 (457 mg, 1 mmol) in THF (20 mL)
was warmed to 608C, and then treated dropwise, in an inert gas
Chem. Eur. J. 2003, 9, No. 8
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/03/0908-1811 $ 20.00+.50/0
1811

D. Rehder et al.
FULL PAPER
atmosphere, with a blue solution of [VCl2(tmeda)2] (339 mg, 1 mmol) in
THF (10 mL). The resulting brown solution was refluxed overnight to yield
a red-brown precipitate, which was filtered off. The filtrate was concen-
trated until saturation. Red-brown microcrystals of 2 were obtained within
weeks by diffusion of pentane under a N2 atmosphere into the THF
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (grants
RE 431/13-3 and 18-1) and the Fonds der Chemischen Industrie. Part of the
work was carried out in the frame work of COST project D12-0027-99.
À
solution. Yield 260 mg (60%); IR (KBr): nÄ ˆ 3058 (C Harom), 1603, 1598
ˆ
ˆ
À
À
(C N), 1573 (C C), 1448 (CH S), 1285 (CH S wagging), 759 and 743 (o-
subst. arom.), 421, 389 cmÀ1 (V S, V Cl); elemental analysis calcd (%) for
C19H25ClN3OSV(429.89): C, 53.09, H 5.86, N 9.77, O 3.72; found: C 52.89, H
5.95, N 9.45, O 3.75.
À
À
[1] D. Rehder, Coord. Chem. Rev. 1999, 182, 297 322.
[2] J. Chen, J. Christiansen, R. C. Tittsworth, B. J. Hales, S. J. George, D.
Coucouvanis, S. P. Cramer, J. Am. Chem. Soc. 1993, 115, 5509 5515.
[3] J. J. A. Cooney, H. K. Joshi, R. Codd, C. K. Kennedy, J. H. Enemark,
221st ACS Natl. Mtg., San Diego 2001, abstract no. INOR 501.
[VCl{N-1-thiophenyl(3-methoxysalicylideneiminate)}tetramethylethylene-
diamine] (2b): This compound was prepared in an analagous fashion to 2a.
Yield: 248 mg (36%) of a dark brown microcrystalline powder; IR (KBr):
ƒ
[4] M. J. Romao, J. Knablein, R. Huber, J. J. Moura, Progr. Biophys.
À
À
ˆ
ˆ
nÄ ˆ 3050, 3021 (C Harom), 2832 (C HOMe), 1601 (C N), 1566, 1548 (C C),
Molec. Biol. 1997, 68, 121 144.
[5] H. B. ten Brink, H. L. Holland, H. E. Schoemaker, R. Wever, Eur. J.
Biochem. 2001, 268, 132 138.
[6] C. Bolm, F. Bienewald, Angew. Chem. 1995, 107, 2883 2885; Angew.
Chem. Int. Ed. Engl. 1995, 34, 2883 2884.
À
À
À
1442 (CH S), 1246 (Ph OMe), 1187 (CH S wagging), 757 and 746 (o-
subst. arom.), 445, 402 cmÀ1 (V S, V Cl); elemental analysis calcd (%) for
C20H27ClN3O2SV(459.91): C 52.23, H 5.92, N 9.14, O 6.96; found: C 52.23,
H 6.05, N 8.79, O 7.25.
À
À
[VOCl{N,N'-[1,1'-dithiobis(phenylene)]bis(salicylideneiminato)}]
(3):
[7] D. Rehder, G. Santoni, G. M. Licini, C. Schulzke, B. Meier, Coord.
Chem. Rev. in press.
[8] G. Liu, D. A. Cogan, J. E. Ellman, J. Am. Chem. Soc. 1997, 119, 9913
9914.
[9] J. E. Banabe, L. A. Echegoyen, B. Pastrona, M. Martinez-Maldonado,
J. Biol. Chem. 1987, 262, 9555 9560.
[10] D. C. Crans, C. M. Simone, Biochemistry 1991, 30, 6734 6741.
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1997, 36, 15 23.
[12] B. I. Posner, R. Faure, J. W. Burgess, A. P. Bevan, D. Lachance, G.
Zhang-Sun, I. G. Fantus, J. B. Ng, D. A. Hall, B. Soo Lum, A. Shaver, J.
Biol. Chem. 1994, 269, 4596 4604.
[13] D. Rehder, J. Costa Pessoa, C. F. G. C. Geraldes, M. M. C. A. Castro,
T. Kabanos, T. Kiss, B. Meier, G. Micera, L. Pettersson, M. Rangel, A.
Salifoglou, I. Turel, D. Wang, J. Biol. Inorg. Chem. 2002, 7, 384 396.
{HsalanS}2 (457 mg, 1 mmol) and [VCl3(thf)3] (373 mg, 1 mmol) were
dissolved in absolute CH2Cl2 (100 mL). Triethylamine (405 mg, 4 mmol)
was added, and the solution was refluxed overnight under nitrogen. After
filtration, the filtrate was cooled to À208C to give, within 2 months, dark
green, temperature-labile crystals of 3 ¥ 3CH2Cl2, which were suitable for
an X-ray structure analysis, along with bulk material of a mixture of 3 and
ˆ
ˆ
À
[NEt3H]Cl. IR (KBr): nÄ ˆ 1627, 1606 (C N), 992 (V O), 422 (S S), 389,
369 cmÀ1 (V S, V Cl).
À
À
[VO{N,N'-[1,1'-dithiobis(phenylene)]bis(3-methoxysalicylideneiminate)}]
(4a): Diaminodiphenyl disulfide, {anS}2, (248 mg, 1 mmol) and [VO-
(o-vanillin)2] (369 mg, 1 mmol) were dissolved in absolute THF (100 mL).
The solution was refluxed overnight under N2, and then filtered. The
filtrate was evaporated to dryness and further dried under vacuum. Yield:
À
630 mg (80%) of a golden yellow powder; IR (KBr): nÄ ˆ 3054 (C Harom);
¬
[14] J. Costa Pessoa, I. Tomaz, T. Kiss, P. Buglyo, J. Inorg. Biochem. 2001,
À1
ˆ
ˆ
À
2998, 2831 (OCH3), 1607 (C N), 984 (V O), 419 cm (V S); EPR (THF):
g0 ˆ 1.975, A0 ˆ 93  10À4 cmÀ1; gxy ˆ 1.983, gz ˆ 1.954, Axy ˆ 60, Az ˆ 162 Â
10À4 cmÀ1; elemental analysis calcd (%) for C28H22N2O5S2V(581.05): C
57.83, H 3.81, N 4.82, S 11.03; found: C 58.48, H 4.46, N 4.67, S 10.84.
84, 259 270.
¬
[15] J. Costa Pessoa, I. Tomaz, T. Kiss, E. Kiss, P. Buglyo, J. Biol. Inorg.
Chem. 2002, 7, 225 240.
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661.
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1981, 20, 5795 5799.
[VO{N,N'-[dithiobis(phenylene)]bis(5,6-benzosalicylideneiminate)}] (4b):
This was prepared, following the procedure for 4a, from {anS}2 (248 mg,
1 mmol) and [VO(2-hydroxynaphthalene-1-carbaldehyde)2] (410 mg,
1 mmol) in THF (100 mL). Yield: 630 mg (80%) of a dark brown powder;
[18] J. Li, G. Elgberg, D. C. Crans, Y. Shechter, Biochemistry 1996, 35,
8314 8318.
[19] H. Nekola, D. Wang, C. Gr¸ning, J. G‰tjens, A. Behrens, D. Rehder,
Inorg. Chem. 2002, 41, 2379 2384.
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P. Thornton, J. Chem. Soc. Dalton Trans. 1992, 1745 1749.
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501 508.
[24] A. D. Keramidas, A. B. Papaioannou, A. T. Vlahos, T. A. Kabanos, G.
Bonas, A. Makriyannis, C. P. Rapropoulou, A. Terzis, Inorg. Chem.
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A. Terzis, T. A. Kabanos, Inorg. Chem. 2000, 39, 2977 2985.
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[27] D. P. N. Satchell, Chem. Soc. Rev. 1977, 6, 345 371.
[28] J. L. Kice, Acc. Chem. Res. 1968, 1, 58 64.
À1
À
ˆ
ˆ
À
IR (KBr): nÄ ˆ 3055 (C Harom), 1617 (C N), 982 (V O), 418 (V S)cm
;
EPR (THF): g0 ˆ 1.969, A0 ˆ 94  10À4cmÀ1; elemental analysis calcd (%)
for C34H22N2O3S2V(621.62): C 65.69, H 3.57, N 4.51, S 10.31; found: C 64.89,
H 4.42, N 4.38, S 10.71.
[HNEt3][V(N-2-mercaptophenyl-2'-pyridinecarboxamide)2] ([HNEt3]-5):
[VCl3(thf)3] (373 mg, 1 mmol) and N-2-mercaptophenyl-2'-pyridinecarbox-
amide (H2picanS) (231 mg, 1 mmol) were dissolved in absolute THF
(60 mL). Triethylamine (405 mg, 4 mmol) was added, and the solution
refluxed overnight. The resulting brown precipitate was filtered off and the
filtrate kept in the refrigerator. Microcrystalline [HNEt3]-5, containing
variable admixtures of [Et3NH]Cl, was collected by filtration and dried
under vacuum. Yield: 0.25 g (80% with respect to [VCl3(thf)3]); IR (KBr):
À
ˆ
nÄ ˆ 3044 (C Hpyr), 2976, 2672, 2498 (HNEt3), 1611, 1586 (C O),
À1
À
À
363 nas(V S), 320 cm ns(V S). Dark red crystals of [HNEt3]-5 suitable
for an X-ray structure analysis were obtained by recrystallization from
CH2Cl2.
1,4,5,8,14,17,18,21-Octathia-11,24-diaza-cyclohexaeicosane (6b): 2,6-Bis-
(mercaptophenylthio)dimethylpyridine hydrochloride (6a ¥ HCl) (470 mg,
1.1 mmol) was dissolved in THF (15 mL) and treated with water-free
sodium acetate (246 mg, 3.3 mmol) and [VO(acac)2] (265 mg, 1.1 mmol).
The deeply blue solution was stirred for 1.5 h at room temperature and
refluxed for an additional hour. A light blue precipitate of unidentified
composition formed, which was filtered off. From the filtrate, a few
colorless crystals of 6b ¥ 4THF were recovered after standing for three
weeks at 48C. Due to the low yield, an elemental analysis was not carried
out. A selected crystal was used for the X-ray structure determination. IR
¬
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1812
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Received: September 17, 2002 [F4434]
Chem. Eur. J. 2003, 9, No. 8
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