Biomimetic thiolate alkylation with zinc pyrazolylbis(thioimidazolyl)borate complexes

Article abstract of DOI:10.1002/ejic.200500276

The NS₂ZnX coordination in thiolate-alkylating zinc enzymes is reproduced in (tripod)ZnX complexes with substituted pyrazolylbis(thioimidazolyl)borate tripod ligands. Intermediate (tripod)Zn nitrates and perchlorates are converted into (tripod) Zn thiolates, including the biologically relevant homocysteinate. Methylation with CH₃I converts these to (tripod)ZnI and the corresponding thioethers CH₃SR, including methionine. A kinetic investigation has shown the alkylations to be intramolecular S_N2 processes that take place at the zinc-bound thiolates. They are considerably faster for the (NS₂)Zn thiolates than for the (N₂S)- and (N₃)Zn-thiolates with similar pyrazolylborate-derived tripod ligands, in agreement with Nature's choice of an NS₂ donor set for zinc. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejic.200500276

FULL PAPER
Biomimetic Thiolate Alkylation with Zinc Pyrazolylbis(thioimidazolyl)borate
Complexes
[a]
[a]
[a]
[a]
Mohamed M. Ibrahim, Guosen He, Jan Seebacher, Boumahdi Benkmil, and
Heinrich Vahrenkamp*[
a]
Keywords: Bioinorganic chemistry / Enzyme models / N,S ligands / Thiolates / Zinc
The NS
2
ZnX coordination in thiolate-alkylating zinc en-
lations to be intramolecular S
the zinc-bound thiolates. They are considerably faster for the
(NS )Zn thiolates than for the (N S)- and (N )Zn-thiolates
with similar pyrazolylborate-derived tripod ligands, in agree-
ment with Nature’s choice of an NS donor set for zinc.
N
2 processes that take place at
zymes is reproduced in (tripod)ZnX complexes with substi-
tuted pyrazolylbis(thioimidazolyl)borate tripod ligands. Inter-
mediate (tripod)Zn nitrates and perchlorates are converted
into (tripod)Zn thiolates, including the biologically relevant
2
2
3
2
homocysteinate. Methylation with CH
3
I converts these to
SR, includ-
(tripod)ZnI and the corresponding thioethers CH
3
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
ing methionine. A kinetic investigation has shown the alky-
as well as the tris(pyrazolyl)borate as N
tripods.[13] During
3
these studies it became obvious that the tripods of the pyr-
Introduction
In two classes of zinc enzymes, a subgroup of the alcohol
dehydrogenases and a subgroup of the thiolate alkylating
enzymes, the zinc ion is in the unusual (NS )ZnX coordina-
azolylborate type are the best substitutes for the biological
[14]
ligand environment of zinc, as observed before,
due to
2
their synthetic variability, which allows the encapsulation of
the metal in a favorable way. It therefore seemed promising
to us to use sulfur-containing pyrazolylborate ligands for
studies of this kind, that is, to investigate the alkylation of
L·Zn-SR complexes in which the ligands L are pyrazolylbo-
rate-derived tripods with N S, NS , and S donor sets. A
tion, with N representing histidine, S representing cystein-
ate, and X being the catalytic site.[
1,2]
Thus, as a complex
the (NS )ZnX unit is an uncharged molecular species, and
2
the reacting substrates (alkoxides or thiolates) convert this
into an anionic complex upon coordination to zinc. Obvi-
ously, this is of advantage for the reactions to be catalyzed
2
2
3
complete series of such ligands with substituted thioimid-
(removal of a hydride from the α-carbon of the alkoxide or
azolyl groups as sulfur donors is available now: after Reglin-
attack of the alkylating agent at the zinc-bound thiolate)
due to the enhanced electron density at the substrates.
On the other hand, it is difficult to reproduce these bond-
ing situations and chemical reactions in coordination com-
pounds of zinc. At present, alcohol dehydrogenase model-
ing has not gone beyond structural mimics, and thiolate
alkylation has not yet been achieved for a thiolate bound
to zinc in an anionic complex. Thiolate alkylation in other
types of zinc complexes has, however, been performed in a
[15]
ski’s discovery of the tris(thioimidazolyl)borates,
Par-
[16]
[17]
kin and ourselves introduced the pyrazolylbis(thioimi-
dazolyl)borates, and very recently we added the final mem-
[18]
ber, the bis(pyrazolyl)(thioimidazolyl)borates.
[
3]
Following our introductory study on the alkylation of
[13]
tris(pyrazolyl)boratozinc thiolates,
in the second part of
the investigation we used the bis(pyrazolyl)(thioimidzolyl)-
[19]
boratozinc thiolates.
The major, and unexpected, obser-
vation of this study was that the thiolate alkylations are
slower than those of the tris(pyrazolyl)boratozinc thiolates,
despite the increased electron density of the complexes. It
remained to be demonstrated, however, that the trend con-
tinued for the (pyrazolyl)bis(thioimidazolyl)boratozinc thi-
olates. This is the subject of the present study, which is the
third in the series. Work on part four, concerning the
tris(thioimidazolyl)boratozinc thiolates, is in progress.
The zinc thiolate complexes of the present study, repre-
[
4,5]
number of cases. Thus, thiolates bound to ZnN O,
2
[
5–7]
[8]
[9]
ZnN S,
ZnNS2, and ZnS units have been subjected
2
3
to alkylations by our competitors in this field. The only
anionic thiolate complex used for such reactions,
2
– [10]
Zn(SPh)4
,
was found to dissociate prior to alkylation.
Our own contributions to this field have involved zinc
thiolates with bidentate N2[ and tridentate N S ligands,
11]
[12]
2
[
a] Institut für Anorganische und Analytische Chemie der Uni- senting the (NS
2
)Zn-SR ligand environment, are the closest
versität Freiburg,
structural models of the thiolate-alkylating zinc enzymes so
Albertstr. 21, 79104 Freiburg, Germany
Fax: +49-761-203-6001
[
2,3]
1
2
far.
We chose L and L as the NS ligands. The substi-
2
E-mail: vahrenka@uni-freiburg.de
tution pattern on their pyrazolyl and thioimidazolyl groups
4070
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejic.200500276
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Biomimetic Thiolate Alkylation with Zinc Complexes
FULL PAPER
was meant to provide encapsulation of the zinc ion in a
hydrophobic pocket. This was achieved for the pyrazolyl
units in the usual way[ by 3-phenyl-5-methyl substitution.
The thioimidazolyl units bear N-phenyl groups with ortho
substituents. This was found to be favorable for encapsul-
ation as it induces the phenyl substituents that point away
from the zinc centers to rotate such that their ortho posi-
tions get placed nearer to the metal.[
14]
20]
2
Figure 1. Molecular structure of HL . Relevant distances [Å] and
angles [°]: B–N 1.555, 1.534 and 1.550(4), C–S 1.677 and 1.695(3);
N–B–N 108.1, 110.2, and 111.7(3); S···N 3.10; S···O 3.27.
1
2
Ligands L and L
1
[17]
2
L has been described by us previously,
and L was
prepared by the same procedure from equimolar amounts
of the thioimidazole and the pyrazole together with KBH4
2
in boiling toluene. In order to purify L it had to be sub-
jected to column chromatography over silica gel. As a result
Basic Complexes
of this the anionic ligand was protonated and isolated as
While with the tris(pyrazolyl)borate ligands the starting
2
the molecular species HL . This is not unprecedented in the point for all functional zinc complexes are the Zn–OH com-
[21,22]
[14]
chemistry of the tris(pyrazolyl)borates.
We are, how- pounds, these compounds have not been isolated yet with
[
17]
ever, not aware of the existence of the protonated form of the pyrazolylbis(thioimidazolyl)borate ligands.
Instead,
a pyrazolylborate-based heteroscorpionate like HL . After perchlorate and nitrate were found to be labile enough to
2
2
2
isolating HL it was straightforward to convert it into KL , be displaced from zinc by even weakly coordinating donors.
the standard form of all these tripod ligands, by treating it Therefore, in addition to complexes 1a and 1b already de-
1
[17]
with KOH in methanol.
scribed for ligand L ,
the corresponding complexes 2a
2
2
The identity of HL was revealed by an X-ray structure and 2b were prepared here for ligand L . They resulted from
2
2
determination (Figure 1). Compound HL can be consid- the reaction of HL with the zinc salts in methanol. It can
ered a zwitterion, with the positive charge on the proton- be assumed that 2a and 2b, just like 1a and 1b,[17] contain
ated pyrazole nitrogen and the negative charge on boron. the oxoanions attached to zinc through one of their oxygen
Although the pyrazole nitrogen is the only reasonable posi- atoms. As considerable amounts of complexes 1 and 2 are
tion for protonation, the NH hydrogen could not be located lost in the isolation process, further reactions with them
with certainty or refined freely. The geometry around the were usually carried out by using them in situ.
boron atom is close to ideally tetrahedral, and the B–N
When doing reactions with complexes 1 and 2, or when
bond lengths are in the normal range for pyrazolylbo- trying to prepare further LZn-X complexes by combining
[
22]
[17]
rates. Unlike in the complexes of such ligands where the KL and ZnX , we observed many times, as before,
that
2
N and S donor atoms are locked in place by coordination these systems have a very high tendency to dismutate into
to the metal, they seem to be locked in this free ligand by ZnL and ZnX . This is one of the reasons why the desired
2
2
weak hydrogen bonds. One of these attaches one of the LZn–OH complexes have evaded us so far and why the de-
thioimidazole sulfur atoms to the oxygen atom of a co-crys- rivative chemistry with LZn units is not nearly as rich as
tallized methanol molecule, and the other links the pyrazole that of the tris(pyrazolyl)boratozinc units. For example, the
2
2
nitrogen atom with the other thioimidazole sulfur atom. attempted syntheses of L Zn acetate from HL and zinc
This latter hydrogen bond serves as a reminder that the pro- acetate resulted in 3b. The structure of 3b (see Table 1 below
ton in question may actually be bound to sulfur rather than and data deposited under CCDC-268609) complements
[
16,17]
to nitrogen.
those of other related ZnL complexes.
2
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M. M. Ibrahim, G. He, J. Seebacher, B. Benkmil, H. Vahrenkamp
FULL PAPER
reaction conditions. Only with the least electron-rich p-ni-
trothiophenolates was it easy to obtain the LZnSR com-
plexes.
Complexes 5a–c and 6d were prepared from the perchlo-
On the other hand, halides coordinate readily to these rates 1b and 2b and the corresponding thiolates. Complex
[
17]
LZn units. Like other such LZn halide complexes,
the 5d could be obtained in a one-pot synthesis from p-nitrothi-
1
iodides 4a and 4b were prepared here from the ligands and ophenol, NaOCH , Zn(NO ) ·6H O, and KL . Likewise,
ZnI . They were fully characterized, including structure de- the homocysteine derivative 5e, which is the closest repre-
3 3 2 2
2
terminations for reference purposes, as they are one of the sentation of the reactive intermediate in the synthesis of
products of each of the alkylation reactions described be- methionine from homocysteine by cobalamine-independent
[
2]
low.
methionine synthase reported so far, was prepared from
N-acetylhomocysteine ethyl ester, NaOH, Zn(NO ) ·6H O,
and KL in methanol. As mentioned above, 5a and 5b are
3
2
2
1
very labile, dismutating in solution to [Zn(SR) ] and the
2
n
ZnL complex 3a.
2
The structure of 4b is shown in Figure 2, mainly for com-
parison with the structure of the free ligand in Figure 1.
The tetrahedral coordination of zinc (bond angles 104–
1
13°) and the Zn–N, Zn–S, and Zn–I bond lengths corre-
[
17,23]
spond to those reported for related LZnI complexes.
2
One can say that in HL the proton of the N–H···S hydro-
gen bond has the same role as the zinc ion in 4b in fixing
the orientation of the pyrazole and one thioimidazole of
the ligand, but that in 4b coordination to zinc overcomes
the tendency of the second thioimidazole to point away
from the center of the molecule. This comparison offers one
explanation for the high tendency of formation of the ZnL2
complexes, in which also only two donor units of the tripod
are fixed, while the third is free and pointing away from the
complex center.
The structures of the two most stable thiolate complexes
5d and 6d) were determined. They are closely related, mak-
(
ing it sufficient to display only the structure of 6d in Fig-
ure 3. The coordination of zinc is severely distorted tetrahe-
dral, with the largest angle (ca. 123°) being that between
the pyrazole nitrogen and the thiolate sulfur and the small-
est angle (ca. 101°) being that between the pyrazole nitrogen
and one of the thioimidazolyl sulfurs. The Zn–N and Zn–
S distances concerning the tripod ligand compare well with
those in the other pyrazolylbis(thioimidazolyl)boratozinc
[
17]
complexes (this work and ref. ). The Zn–S (thiolate) bond
lengths of 2.28 Å in both 5d and 6d are not much different
2
Figure 2. Molecular structure of L ZnI (4b). Relevant bond lengths
[Å]: Zn–N 2.039(3), Zn–S 2.338 and 2.320(2), Zn–I 2.533(2).
Thiolates
While the preparation of (tripod)ZnSR complexes for the
[
13]
tris(pyrazolyl)borate
and bis(pyrazolyl)(thioimidazolyl)-
[
18]
borate tripods is straightforward, in this case it required
careful control of the reaction conditions. The high ten-
dency of formation of the bis(ligand)complexes 3 and the
oligomeric zinc bis(thiolates) prevented the isolation of
2
most of the desired thiolate complexes with tripod L , and
Figure 3. Molecular structure of the thiolate complex 6d. Relevant
bond lengths [Å]: Zn–S (tripod) 2.362(1) and 2.341(1), Zn–S (thiol-
complexes of tripod L only when carefully controlling the ate) 2.285(1), Zn–N 2.038(3).
it allowed the isolation of the alkyl- and benzylthiolate
1
4072
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Inorg. Chem. 2005, 4070–4077

Biomimetic Thiolate Alkylation with Zinc Complexes
FULL PAPER
from those in the related zinc p-nitrothiophenolate com- of CH I. From the SCH signal intensities, recorded for at
3
3
[13]
plexes of a tris(pyrazolyl)borate
and a bis(pyrazolyl)- least five t½ intervals (see Figure 4), the pseudo-first-order
thioimidazolyl)borate ligand[
19]
[2.25 and 2.25 Å (av.) rate constants were obtained according to ln(I – I ) =
(
t
0
respectively]. A notable feature of the structure of 6d is the ln(I – I ) – k ×t.
ϱ
0
obs
orientation of one of the o-dimethylphenyl rings. As antici-
pated, it is rotated to such a degree that one of the methyl
groups contributes to the encapsulation of the zinc ion in a
similar way as the phenyl substituent on the pyrazole ring.
Methylation Reactions
[
13,19]
As before for the N - and N S-ligated zinc thiolates,
3
2
all thiolate complexes 5 and 6 were subjected to methylation
with methyl iodide in chloroform. In each case the reactions
1
proceeded according to Equation (1) and, according, to H
NMR spectroscopy, they were quantitative. The solid reac-
tion products LZnI (4a and 4b) were isolated, and the thioe- NO resulting from the reaction of 5d with a sixfold excess of CH I.
1H NMR signals of CH
Figure 4. Intensities of the CH
3
3
SC
6
H
4
-p-
3
2
thers CH SR were identified by NMR spectroscopy; there
3
were no other reaction products in the solutions.
The log plots for five different excess concentrations of
CH I were linear with correlation coefficients greater than
3
LZnSR + CH I Ǟ LZnI + CH SR
(1) 0.995. The resulting kobs values, plotted against the CH3I
3
3
concentrations (see Figure 5), define regression lines pass-
The ethyl and benzyl thiolates 5a and 5b reacted within ing through the origin with correlation coefficients greater
minutes, whereas the phenyl and homocysteinyl thiolates 5c than 0.998. The second-order rate constants of the thiolate
and 5e needed about an hour. Even the methylations of the alkylations, taken from the slopes of these regression lines,
p-nitrothiophenolates 5d and 6d came to completion within are 8.5(1)×10–3  s for 5d and 1.5(1)×10  s for
–1
–1
–3 –1 –1
a few hours. This is in marked contrast to the reactions of 6d.
the N - and N S-ligated zinc-p-nitrothiophenolates. Those
3
2
of the tris(pyrazolyl)borates were found not to proceed at
all at room temperature,[ and those of the bis(pyrazolyl)-
13]
(thioimidazolyl)borates took weeks to come to completion.
These observations lead to the rough estimate that the NS2-
ligated zinc thiolates react about two orders of magnitude
faster than the N - and N S-ligated ones. Further work is
3
2
needed to quantify this statement.
The popular alternative alkylating agent trimethylphos-
phate was also used here. We had found before that, under
forcing conditions (i.e. in boiling DMSO), it does lead to
[11]
methylation of neocuproinzinc bis(thiolates) and of zinc
[
12]
thiolates bearing a tridentate N S ligand. Yet, even under
2
Figure 5. Plot of the pseudo-first-order rate constants against the
I concentration for the methylation of 5d.
these forcing conditions, it reacted extremely slowly with CH
the zinc thiolates bearing tripodal N S ligands. This was
3
[19]
2
now observed for complex 5d too. In boiling DMSO it took
Again, the clean second-order reactions support the
three days to methylate about one third of the thiolate with statement that the alkylations occur at the zinc-bound thiol-
[
2,3]
PO(OMe) . While this is again about one to two orders of ates, as proposed for the enzymes.
At present their rates
3
magnitude faster than the corresponding methylation of the can be compared only to one another, as comparable rates
complex ligated with a bis(pyrazolyl)(thioimidazolyl)bo- for other p-nitrothiophenolate complexes are not available.
[
19]
rate, it demonstrates again that zinc thiolate model com- The fact that 5d reacts faster than 6d can be explained by
plexes are not nearly as reactive as the thiolate-alkylating electronic as well as steric effects: due to the o-methoxy sub-
zinc enzymes, which employ such mild alkylating agents as stituents 5d is slightly more electron-rich than 6d, and the
methyl tetrahydrofolate.[
2]
better encapsulation of the reactive center of 6d (see dis-
Kinetic data were obtained for the methylations of 5d cussion above) renders the latter less reactive. The fact that
and 6d with methyl iodide in CDCl at 300 K. We found it the thiolate complexes of this study are considerably more
3
1
[13]
convenient to record the intensity of the H NMR signal of reactive than the previously studied ones with N
the SCH group of the resulting p-nitrothioanisole during N S tripods certainly relates to the fact that sulfur donor
and
3
[
19]
3
2
the kinetic runs. Complexes 5d and 6d were treated under ligands render the zinc ion, and hence the thiolate attached
pseudo-first-order conditions with a four- to tenfold excess to it, more electron-rich.
Eur. J. Inorg. Chem. 2005, 4070–4077
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M. M. Ibrahim, G. He, J. Seebacher, B. Benkmil, H. Vahrenkamp
FULL PAPER
2
.25 [s, 6 H, Me(Ph)], 2.29 [s, 6 H, Me(Ph)], 2.92 [s, 3 H, Me(pz)],
Conclusions
6.78 [s, 1 H, H(pz)], 6.80 [d, J = 2.2 Hz, 2 H, H(im)], 7.20 [d, J =
The present study, the third in our series on thiolate alky- 2.2 Hz, 2 H, H(im)], 7.29 (m, 1 H, Ar), 7.33 (s, 3 H, Ar), 7.42 (m,
lations of zinc complexes with pyrazolylborate-derived li- 2 H, Ar), 7.64 (m, 3 H, Ar), 7.96 (m, 2 H, Ar) ppm.
gands, has yielded model complexes in which the (NS2)
2
b) KL : 20 mL of a 0.1  solution of KOH in methanol (2.00 mmol)
2
ZnSR ligand environment of the zinc ion correctly repro- was added dropwise to a solution of HL (1.15 g, 2.00 mmol) in
duces that in the thiolate alkylating zinc enzymes like cobal- 20 mL of methanol. The solvent was removed in vacuo, the residue
amin-independent methionine synthase. The simple alka- dissolved in dichloromethane, and the product precipitated by ad-
dition of petroleum ether (50–70°C). Recrystallization from dichlo-
romethane/heptane by slow evaporation yielded 0.71 g (58%) of
KL as a colorless powder, m.p. 240°C (dec.). C32
614.69): calcd. C 62.53, H 5.25, N 13.67, S 10.43; found C 62.75,
H 5.42, N 13.28, S 10.14. H NMR (CDCl ): δ = 1.92 [s, 6 H,
3
Me(Ph)], 1.96 [s, 6 H, Me(Ph)], 2.16 [s, 3 H, Me(pz)], 6.24 [s, 1 H,
H(pz)], 6.43 [s, 2 H, H(im)], 6.47 [s, 2 H, H(im)], 6.98 (s, 1 H, Ar),
nethiolate complexes are labile, indicating that the electron-
richness in these systems is reaching a borderline, compar-
2
2
–
H32BKN
6
S
2
able to the situation in the Zn(SR)4 species, among which
the alkanethiolates have been inaccessible to date. Never-
theless, the homocysteinate complex could be prepared and
methylated to yield methionine, which is the closest repro-
duction so far of the last step of enzymatic methionine syn-
thesis.
(
1
7
.05 (m, 5 H, Ar), 7.30 (m, 2 H, Ar), 7.62 (m, 3 H, Ar) ppm.
2
Complex 2a: A solution of HL (0.057 g, 0.10 mmol) in 20 mL of
methanol was added with stirring to a solution of Zn(NO
0.030 g, 0.10 mmol) in 20 mL of methanol. After stirring for 15 h
The mechanistic investigation of the alkylation reactions
has shown them to be second order and probably intramol-
3 2 2
) ·6H O
(
ecular again. They are significantly faster than the alky- the solvent was removed in vacuo and the residue dissolved in
lations of the Zn-SR complexes with N and N S tripod 20 mL of dichloromethane. After washing with water the dichloro-
3
2
ligands, as expected due to their increased electron-richness. methane solution was filtered through celite. The filtrate was then
reduced to 5 mL in vacuo. Slow diffusion of n-pentane into the
solution yielded 32 mg (46%) of 2a as colorless crystals, m.p. 215°C
This relates well with Nature’s choice of an NS donor set
2
for zinc in the thiolate-alkylating enzymes.
2
–
(dec.). C32
13.95, S 9.12; found C 54.98, H 4.49, N 13.36, S 8.73. H NMR
CDCl ): δ = 1.89 [s, 6 H, Me(Ph)], 1.93 [s, 6 H, Me(Ph)], 2.43 [s,
H, Me(pz)], 6.36 [s, 1 H, H(pz)], 6.77 [d, J = 2.1 Hz, 2 H, H(im)],
.01 [d, J = 2.1 Hz, 2 H, H(im)], 7.04 (s, 2 H, Ar), 7.13–7.31 (m, 2
7 3 2
H32BN O S Zn (702.98): calcd. C 54.67, H 4.59, N
Nature, however, also uses a Zn(SR)
system to deal-
4
1
kylate phosphate esters in the Ada repair protein.[ Thus,
24]
(
3
model systems in the form of zinc complexes with an (S3)
Zn-SR composition are also a valuable subject of investiga-
tion. We are at present studying such a model system em-
ploying the tris(thioimidazolyl)boratozinc thiolates. The re-
sults of this study are to be published as the fourth part of
our series on tripod-zinc thiolate complexes.
3
7
H, Ar), 7.45 (m, 6 H, Ar), 7.75 (s, 1 H, Ar) ppm.
Complex 2b: Prepared as 2a from HL2 (0.115 g, 0.20 mmol) in
5
4
0 mL of methanol and Zn(ClO
0 mL of methanol. Yield: 67 mg (45%) of 2a as colorless crystals,
32BClN Zn (740.43): calcd. C 51.91, H 4.36,
N 11.35, S 8.66; found C 52.26, H 4.83, N 11.20, S 8.65. H NMR
CDCl ): δ = 1.70 [s, 3 H, Me(Ph)], 1.77 [s, 3 H, Me(Ph)], 1.83 [s,
H, Me(Ph)], 1.86 [s, 3 H, Me(Ph)], 2.45 [s, 3 H, Me(pz)], 6.59 [s,
H, H(pz)], 6.79 [s, br, 2 H, H(im)], 6.95 [s, br, 2 H, H(im)], 7.00
4 2 2
) ·6H O (0.074 g, 0.20 mmol) in
m.p. 194°C. C32
H
6 4 2
O S
1
(
3
1
3
Experimental Section
General: For the general working and measuring procedures, see
[
25]
1 [17]
[26]
ref.
Ligand L ,
5-methyl-3-phenylpyrazole,
and N-(o-di-
(
s, 2 H, Ar), 7.10 (m, 4 H, Ar), 7.48 (m, 3 H, Ar), 7.87 (m, 2 H,
[27]
methylphenyl)thioimidazole
were prepared according to the
Ar) ppm.
published procedures. All other starting materials were commer-
cially available. The methyl thioethers resulting from the methyl-
Complex 3b: This complex formed during an attempted synthesis
2
2
of L Zn acetate. It was prepared as 2a from HL (0.115 g,
.20 mmol) and Zn(OAc) ·6H O (0.044 g, 0.20 mmol). Workup
yielded 144 mg (59%) of 3b as colorless crystals, m.p. 210°C (dec.).
Zn (1216.6): calcd. C 63.19, H 5.30, N 13.82, S
[
28–31]
[13]
ations,
including N-acetylmethionine ethyl ester, have been
0
2
2
1
described and were identified by their H NMR spectra, which are
also reported in ref.
[
13]
64 64 2 12 4
C H B N S
1
A frequent problem with the elemental analyses of this kind of
complexes is that the carbon values are outside the accepted range.
When this was the case here, at least one additional analysis value
10.54; found C 62.76, H 5.37, N 13.71, S 10.48. H NMR (CDCl ):
3
δ = 1.60 [s, 3 H, Me(Ph)], 1.79 [s, 3 H, Me(Ph)], 1.83 [s, 3 H,
Me(Ph)], 1.88 [s, 3 H, Me(Ph)], 2.66 [s, 3 H, Me(pz)], 6.28 [s, 1 H,
H(pz)], 6.43 [d, J = 2.1 Hz, 2 H, H(im)], 6.49 [d, J = 2.1 Hz, 2 H,
H(im)], 6.99 (s, 1 H, Ar), 7.02 (m, 2 H, Ar), 7.06 (s, 1 H, Ar), 7.17
(S or Zn) was determined.
2
2
Ligand HL : a) HL : A mixture of 5-methyl-3-phenylpyrazole
(
m, 3 H, Ar), 7.28 (m, 2 H, Ar), 7.84 (m, 2 H, Ar) ppm.
(
(
4.20 g,
26.5 mmol),
N-(2,3-dimethylphenyl)-2-thioimidazole
(0.72 g, 13.3 mmol) was finely
1
5.42 g, 26.5 mmol), and KBH
4
Complex 4a: A solution of KL (301 mg, 0.49 mmol) in 50 mL of
ground and heated to 100°C in vacuo for 2 h. Then, 400 mL of
methanol was slowly added dropwise, with stirring, to a solution
freshly distilled toluene were added and the mixture refluxed at
2
of anhydrous ZnI (155 mg, 0.49 mmol) in 30 mL of methanol. The
1
60°C in an oil bath for a week. The solvent was then removed in
resulting colorless precipitate was filtered off and the filtrate was
reduced in vacuo to 20 mL to produce a precipitate of raw 4a. Slow
diffusion of toluene into a solution of raw 4a in dichloromethane
yielded 257 mg (69%) of 4a as colorless crystals, m.p. 230°C (dec.).
vacuo, the residue dissolved in dichloromethane, and filtered
through celite. Chromatography through a 3×30 cm silica gel col-
umn with a gradient solvent system (dichloromethane/acetone,
2
2
00:0 Ǟ 200:4) yielded raw HL . Repeating the chromatography
C
30
H
28BIN
6 2 2
O S Zn (771.83): calcd. C 46.69, H 3.66, N 10.89, S
2
1
yielded 5.32 g (69%) of HL as a colorless powder, m.p. 194°C.
(576.60): calcd. C 66.78, H 5.60, N 14.60, S 11.14;
8.31; found C 45.79, H 3.95, N 10.75, S 8.25. H NMR (CDCl ):
3
C
32
H33BN
6
S
2
δ = 2.49 [s, 3 H, Me(pz)], 3.85 (s, 6 H, OMe), 6.15 [s, 1 H, H(pz)],
6.91–7.95 [m, 17 H, H(im) + Ar] ppm.
1
found C 66.69, H 5.93, N 13.95, S 10.49. H NMR (CDCl
3
): δ =
4074
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2005, 4070–4077

Biomimetic Thiolate Alkylation with Zinc Complexes
FULL PAPER
yellow powder, m.p. 200°C.
2
Complex 4b: Prepared as 2a from HL (57 mg, 0.10 mmol) and an-
279 mg (43%) of 5d as
a
hydrous ZnI
orless crystals, m.p. 240°C (dec.). C32
C 50.05, H 4.20, N 10.94, S 8.35; found C 49.84, H 3.96, N 10.95,
2
(52 mg, 0.16 mmol). Yield: 37 mg (48%) of 4b as col-
36 7 4 3
C H32BN O S Zn (799.09): calcd. C 54.11, H 4.04, N 12.27, S
12.04; found C 54.68, H 4.24, N 12.60, S 10.75. H NMR (CDCl ):
3
δ = 2.51 [s, 3 H, Me(pz)], 3.82 (s, 6 H, OMe), 6.31 [s, 1 H, H(pz)],
6.92 [d, J = 2.1 Hz, 2 H, H(im)], 7.01 [d, J = 2.1 Hz, 2 H, H(im)],
1
H
32BIN Zn (767.88): calcd.
6
S
2
1
S 8.03. H NMR (CDCl
Me(Ph)], 2.40 [s, 3 H, Me(pz)], 6.32 [s, 1 H, H(pz)], 6.73 [d, J =
.1 Hz, 2 H, H(im)], 7.01 [d, J = 2.1 Hz, 2 H, H(im)], 7.11 (m, 3
3
): δ = 1.93 [s, 6 H, Me(Ph)], 2.08 [s, 6 H,
7.35 (m, 11 H, Ar), 7.55 (d, J = 8.8 Hz, 2 H, C
6 4 2
H NO ), 7.83 (m,
2
2 H, Ar), 8.11 (d, J = 8.8 Hz, 2 H, C NO ) ppm.
6
H
4
2
H, Ar), 7.19 (s, 2 H, Ar), 7.30 (m, 3 H, Ar), 7.40 (m, 3 H, Ar)
ppm.
Complex 5e: Prepared as 5d from N-acetylhomocysteine ethyl ester
3 2
168 mg, 0.82 mmol), NaOH (21.7 mg, 0.82 mmol), Zn(NO )
(
1
Complex 5a: A solution of 33 µL (28 mg, 0.45 mmol) of ethanethiol
·4H O (214 mg, 0.82 mmol), and KL (506 mg, 0.82 mmol). Yield:
2
in 5 mL of methanol was deprotonated by addition of 1.8 mL
390 mg (56%) of 5e as a colorless powder, m.p. 200°C (dec.).
(
0.45 mmol) of a 0.25  solution of NaOCH
3
in methanol. A solu-
C H BN O S Zn (849.19): calcd. C 53.75, H 4.98, N 11.55, S
11.33; found C 53.62, H 4.84, N 11.75, S 11.46. H NMR ([D6]
3
8
42
7
5 3
1
tion of Zn(ClO ·6H O (112 mg, 0.30 mmol) in 15 mL of meth-
4
)
2
2
1
anol and then a solution of KL (186 mg, 0.30 mmol) in 40 mL of
methanol were added dropwise to this solution with stirring. After
stirring for 4 d the volume of the solution was reduced to 15 mL
in vacuo. Filtration yielded raw 5a, which was dissolved in dichlo-
romethane. Slow diffusion of n-hexane into this solution precipi-
tated 126 mg (59%) of 5a as a colorless powder, m.p. 215°C (dec.).
DMSO): δ = 1.15 [t, J = 6.8 Hz, 3 H, CH (Et)], 1.69–1.93 (m, 2 H,
3
CH ), 1.85 [s, 3 H, CH (Ac)], 2.45 [s, 3 H, CH (pz)], 2.65–2.76 (m,
2
3
3
2 H, CH ), 3.78 (s, 6 H, OMe), 4.07 [q, J = 6.8 Hz, 2 H, CH (Et)],
2
2
4.31 (m, 1 H, CH), 6.47 [s, 1 H, H(pz)], 6.75–7.66 [m, 15 H, H(im)
+ Ar], 7.91 (m, 2 H, Ar), 8.13 (m, 1 H, NH) ppm.
Complex 6d: A solution of p-nitrothiophenol (33 mg, 0.20 mmol)
in 30 mL of methanol was deprotonated with 0.8 mL of a 0.25 
solution of NaOH in methanol (0.20 mmol). This solution was
C
32
H33BN
6
O
2
S
3
2 2
Zn·0.25CH Cl (706.05 + 21.23): calcd. C 53.26, H
4
.64, N 11.56, S 13.23; found C 53.27, H 4.43, N 11.76, S 13.01.
1
H NMR (CDCl
s, 3 H, Me(pz)], 2.54 [q, J = 7.4 Hz, 2 H, CH
OMe), 5.29 (s, 0.5 H, CH Cl ), 6.31 [s, 1 H, H(pz)], 6.69–6.85 (m,
H, Ar), 6.91 [d, J = 2.0 Hz, 2 H, H(im)], 6.99 [d, J = 2.0 Hz, 2
H, H(im)], 7.02–7.05 (m, 4 H, Ar), 7.34 (m, 2 H, Ar), 7.36–7.58
m, 3 H, Ar), 7.95 (d, J = 7.0 Hz, 2 H, Ar) ppm.
3
): δ = 1.32 [t, J = 7.4 Hz, 3 H, CH
3
(SEt)], 2.48
2
slowly added dropwise, with stirring, to a solution of KL (123 mg,
[
2
(SEt)], 3.71 (s, 6 H,
0
.20 mmol) in 50 mL of methanol. The resulting yellow precipitate
was filtered off and dried in vacuo to yield 81 mg (51%) of 6d as
a yellow powder, m.p. 225°C (dec.). C38 Zn (795.15):
calcd. C 57.40, H 4.56, N 12.33, S 12.10; found C 57.41, H 4.68,
2
2
2
7 2 3
H36BN O S
(
1
3
N 12.37, S 11.98. H NMR (CDCl ): δ = 1.89 [s, 6 H, Me(Ph)],
Complex 5b: Prepared as 5a from 54 µL (56 mg, 0.45 mmol) of ben-
2.07 [s, 6 H, Me(Ph)], 2.43 [s, 3 H, Me(pz)], 6.34 [s, 1 H, H(pz)],
6.75 [d, J = 2.1 Hz, 2 H, H(im)], 6.93 (d, J = 9.0 Hz, 2 H,
C H NO ), 7.02 [d, J = 2.1 Hz, 2 H, H(im)], 7.09 (s, 1 H, Ar), 7.13
1
zylmercaptan, Zn(ClO
186 mg, 0.30 mmol). Yield: 128 mg (55%) of 5b as a colorless pow-
der, m.p. 190°C (dec.). C37 Zn (768.12): calcd. C 57.86,
H 4.59, N 10.94, S 12.52; found C 57.26, H 4.59, N 11.87, S 11.63.
4 2 2
) ·6H O (112 mg, 0.30 mmol), and KL
(
6
4
2
H35BN
6
O
2
S
3
(s, 1 H, Ar), 7.19 (m, 7 H, Ar), 7.36 (m, 2 H, Ar), 7.46 (d, J =
9.0 Hz, 2 H, C H NO ) ppm.
6
4
2
1
H NMR (CDCl
3
): δ = 2.36 [s, 3 H, Me(pz)], 3.62 (s, 6 H, OMe),
Methylation Reactions: Methyl iodide was used as a 1  solution
in chloroform. Equimolar amounts (0.1–0.2 mmol) of methyl io-
dide and one of the complexes 5 or 6 were combined in 5 mL of
chloroform (for 5e DMSO was used as the solvent). Reactions were
3
6
7
.38 [s, 2 H, CH (Bz)], 6.31 [s, 1 H, H(pz)], 6.69–6.76 (m, 2 H, Ar),
.90 [d, J = 2.2 Hz, 2 H, H(im)], 6.96 [d, J = 2.2 Hz, 2 H, H(im)],
.01–7.05 (m, 4 H, Ar), 7.19 (m, 2 H, Ar), 7.30 (m, 2 H, Ar), 7.34
2
(
(
m, 1 H, Ar), 7.39 (d, J = 1.8 Hz, 2 H, Ar), 7.52 (m, 3 H, Ar), 7.91
d, J = 7.0 Hz, 2 H, Ar) ppm.
1
followed by H NMR spectroscopy and were found to produce the
resulting thioethers quantitatively. After 10 min (5a, 5b), 2 h (5c,
5e), or 1 d (5d, 6d) the solvent was removed in vacuo. The residue
was washed with two 3-mL portions of diethyl ether and then dried
in vacuo. The remaining solid was pure 4a or 4b, as seen from the
Complex 5c: A solution of thiophenol (45 mg, 0.41 mmol) in 15 mL
of methanol was deprotonated by addition of a 0.25  solution of
NaOCH
added dropwise with stirring to a solution of 1b (306 mg,
.41 mmol) in 40 mL of chloroform. After stirring for 12 h the sol-
3
in methanol (1.64 mL, 0.41 mmol). This solution was
1
H NMR spectrum. Of the resulting thioethers, CH SEt was found
3
0
in the condensate and the others in the diethyl ether extracts, which
vent was removed in vacuo and the residue treated with 20 mL of
dichloromethane. The dichloromethane extract was filtered and the
filtrate evaporated to dryness. Recrystallization from dichlorometh-
ane/methanol (1:1) yielded 194 mg (63%) of 5c as a colorless pow-
also contained part of the iodide complexes 4.
Complex 5a (44 mg, 0.062 mmol) gave 45 mg (94%) of 4a.
Complex 5b (48 mg, 0.062 mmol) gave 43 mg (89%) of 4a.
Complex 5c (87 mg, 0.12 mmol) gave 70 mg (79%) of 4a.
Complex 5d (88 mg, 0.11 mmol) gave 54 mg (64%) of 4a.
Complex 5e (5.1 mg, 006 mmol) gave 2.5 mg (55%) of 4a.
Complex 6d (72 mg, 0.09 mmol) gave 33 mg (48%) of 4b.
Kinetic Measurements: The standard solutions of complexes 5d and
der, m.p. 225°C (dec.). C36
6 2 3
H33BN O S Zn (754.09): calcd. C 57.34,
H 4.41, N 11.14, S 12.76; found C 56.87, H 4.36, N 10.85, S 12.63.
1
H NMR (CDCl
.34 [s, 1 H, H(pz)], 6.72 (m, 2 H, Ar), 6.82 [d, J = 2.0 Hz, 2 H,
H(im)], 6.97 [d, J = 2.0 Hz, 2 H, H(im)], 7.22 (m, 2 H, Ar), 7.29
m, 2 H, Ar), 7.36 (d, J = 1.8 Hz, 2 H, Ar), 7.39 (m, 1 H, Ar],
.50–7.60 (m, 5 H, Ar), 7.92 (m, 2 H, Ar) ppm.
3 3
): δ = 2.48 [s, 3 H, CH (pz)], 3.79 (s, 6 H, OMe),
6
(
7
Complex 5d: A solution of p-nitrothiophenol (125 mg, 0.81 mmol)
in 30 mL of methanol was treated with 5.0 mL of a 0.25  solution
of NaOH in methanol (1.25 mmol), thereby turning red. A solution
3
6d and of methyl iodide in CDCl (99.8%) were kept in the dark.
All reagents and the cavity of the NMR spectrometer were thermo-
statted to 300.0 K before the measurements. The reagents were
of Zn(ClO
4
)
2
·6H
2
O (240 mg, 0.81 mmol) in 15 mL of methanol was
combined immediately prior to the measurements. The intensities
1
slowly added dropwise, with stirring, to the red solution, which
turned yellow. Finally, a solution of KL (500 mg, 0.81 mmol) in
of the H NMR resonance of the SCH
3
protons of the resulting p-
1
nitrothioanisole were recorded automatically every 100 s and stored
for digital data processing. Each kinetic run was repeated once, and
the averaged data were used for the calculations.
50 mL of methanol was slowly added with stirring, upon which a
yellow precipitate formed. Filtration and drying in vacuo yielded
Eur. J. Inorg. Chem. 2005, 4070–4077
www.eurjic.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4075

M. M. Ibrahim, G. He, J. Seebacher, B. Benkmil, H. Vahrenkamp
FULL PAPER
Table 1. Crystallographic details.
HL2
3b
4a
4b
5d
6d
Empirical formula
C
32
H33BN
6
S
2
·
C
64
H
64
B
2
N
12
S
4
Zn·
C
30
H28BIN
6
O
2
S
2
Zn
C
32
H32BIN
6
S
2
Zn·
C
36
H32BN
7
O
4
S
3
Zn·
C
38
7 2 3
H36BN O S Zn
CH
3
OH
2H
2
O
CH
2
Cl
2
½CH OH
3
Molecular mass
Crystal size [mm]
Space group
Z
576.60 + 32.04 1216.57 + 36.03
771.78
0.2×0.1×0.1
767.88 + 84.93
0.2×0.2×0.2
¯
P1
799.09 + 13.96
0.2×0.1×0.1
¯
P1
795.15
0.4×0.2×0.2
¯
P1
0.2×0.2×0.2
0.4×0.2×0.2
P1
¯
P2
1
2
1
2
1
P2
1
/c
4
2
4
2
4
2
a [Å]
b [Å]
c [Å]
α [°]
13.630(3)
14.235(3)
16.681(4)
90
90
90
3236(1)
1.24
0.20
h: –17 to 18
k: –19 to 19
l: –21 to 22
29296
13.522(2)
14.939(2)
16.844(3)
80.214(3)
83.039(3)
74.849(3)
3226(1)
1.29
11.662(3)
13.804(3)
20.201(5)
90
95.976(4)
90
3234(1)
1.59
1.88
h: –15 to 15
k: –18 to 18
l: –26 to 26
28220
7780
3014
10.112(9)
11.852(10)
17.166(14)
90.30(1)
105.71(1)
108.49(1)
1869(2)
1.49
12.863(2)
13.359(3)
23.601(5)
95.950(4)
100.031(4)
100.469(4)
3888(1)
1.39
10.163(3)
11.762(4)
17.824(6)
90.908(6)
102.198(7)
110.860(6)
1936(1)
1.38
β [°]
γ [°]
3
V [Å ]
d(calcd.) [gcm–3]
µ(Mo-K
hkl range
α
) [mm–1]
0.56
1.77
0.84
0.84
h: –17 to 17
k: –19 to 20
l: –22 to 21
29306
15099
6692
h: –13 to 13
k: –15 to 16
l: –22 to 22
16947
8763
5308
h: –15 to 15
k: –15 to 15
l: –28 to 28
28935
13656
5949
h: –13 to 11
k: –15 to 15
l: –22 to 23
11567
8225
3719
Measured reflections
Independent reflections
Observed refl. [I Ͼ 2σ(I)]
Parameters
7863
4858
396
801
388
415
954
469
Refined reflections
7863
15099
7780
8763
13656
8225
R
1
(obsd. reflections)
wR (all reflections)
Resid. e density [eÅ–3]
0.061
0.175
+0.6/–0.4
0.063
0.198
+0.9/–0.6
0.063
0.242
+0.8/–1.4
0.042
0.121
+1.1/–1.0
0.075
0.246
+1.7/–0.6
0.054
0.125
+0.6/–0.6
2
–
The initial concentration of 5d was adjusted to 0.010  for all seven
measurements, during which the concentrations of CH I were
.040, 0.050, 0.060, 0.070, 0.080, 0.090, and 0.100 . The resulting
[4] B. S. Hammes, C. J. Carrano, Inorg. Chem. 2001, 40, 919–927.
[5] B. S. Hammes, C. R. Warthen, D. C. Crans, C. J. Carrano, J.
Biol. Inorg. Chem. 2001, 6, 82–90.
3
0
[
6] C. A. Grapperhaus, T. Tuntulani, J. H. Reibenspies, M. Y. Dar-
ensbourg, Inorg. Chem. 1998, 37, 4052–4058.
7] M. Machuqueiro, T. Darbre, J. Inorg. Biochem. 2003, 94, 193–
196.
k
obs values for these concentrations were 3.4, 4.0, 5.0, 5.7, 6.7, 7.5,
–
4 –1
and 8.2×10 s , respectively.
[
The initial concentration of 6d was adjusted to 0.033 for all five
measurements, during which the concentrations of CH
3
I were
[8] S. J. Chiou, C. G. Riordan, A. L. Rheingold, Proc. Natl. Acad.
0
.167, 0.209, 0.251, 0.293, and 0.335. The resulting kobs values for
Sci. USA 2003, 100, 3695–3700.
[9] B. M. Bridgewater, T. Fillebeen, R. A. Friesner, C. Parkin, J.
Chem. Soc., Dalton Trans. 2000, 4494–4496.
–
4 –1
these concentrations were 2.3, 2.9, 3.7, 4.2, and 4.9×10 s ,
respectively.
Structure Determinations:[32] Crystals of HL , 3b, and 5d were ob-
tained by cooling saturated CH
by diffusion of toluene into a CH
and 6d by cooling saturated CH Cl
[
[
10] J. J. Wilker, S. Lippard, Inorg. Chem. 1997, 36, 969–978.
2
11] J. Seebacher, M. Ji, H. Vahrenkamp, Eur. J. Inorg. Chem. 2004,
2
Cl
2
/CH
Cl
/n-pentane solutions. Diffrac-
3
OH solutions, those of 4a
solution, and those of 4b
409–417.
2
2
[
12] M. Ji, H. Vahrenkamp, Eur. J. Inorg. Chem. 2005, 1398–1405.
2
2
[13]
U. Brand, M. Rombach, J. Seebacher, H. Vahrenkamp, Inorg.
tion data were recorded at room temp. with a Bruker Smart CCD
diffractometer. Empirical absorption corrections (SADABS) were
Chem. 2001, 40, 6151–6157.
[14] H. Vahrenkamp, Acc. Chem. Res. 1999, 32, 589–596.
[15] M. Garner, J. Reglinski, I. Cassidy, M. D. Spicer, A. R. Ken-
nedy, Chem. Commun. 1996, 1975–1976.
applied. The structures were solved by direct methods and refined
anisotropically using the SHELX program suite.[
33]
Hydrogen
[
16] C. Kimblin, B. M. Bridgewater, D. G. Churchill, T. Hascall, G.
atoms were included with fixed distances and isotropic temperature
factors 1.2-times those of their attached atoms. Parameters were
Parkin, Inorg. Chem. 2000, 39, 4240–4243.
[17] M. Shu, R. Walz, B. Wu, J. Seebacher, H. Vahrenkamp, Eur. J.
Inorg. Chem. 2003, 2502–2511.
2
[34]
refined against F . Drawings were produced with SCHAKAL.
Table 1 lists the crystallographic details.
[
[
[
[
[
18] B. Benkmil, M. Ji, H. Vahrenkamp, Inorg. Chem. 2004, 43,
212–8214.
19] M. Ji, B. Benkmil, H. Vahrenkamp, Inorg. Chem. 2005, 44,
518–3523.
20] M. M. Ibrahim, M. Shu, H. Vahrenkamp, Eur. J. Inorg. Chem.
005, 1388–1397.
21] A. Looney, G. Parkin, A. L. Rheingold, Inorg. Chem. 1991, 30,
099–3101.
22] S. Trofimenko, Scorpionates, Imperial College Press, London,
999.
8
Acknowledgments
3
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie. We are indebted to Drs.
W. Deck and H. Brombacher for help with the structure determi-
nations and to Mrs. P. Klose for assistance in the laboratory.
2
3
1
[
1] S. Ramaswamy, H. Eklund, B. V. Plapp, Biochemistry 1994, 33,
[23] C. Kimblin, T. Hascall, G. Parkin, Inorg. Chem. 1997, 36,
5230–5237 and references cited therein.
5680–5681.
[
[
2] R. G. Matthews, Acc. Chem. Res. 2001, 34, 681–689.
[24] L. C. Myers, M. P. Terranova, A. E. Ferentz, G. Wanger, G. L.
Verdine, Science 1993, 261, 1164–1167.
3] G. Parkin, Chem. Rev. 2004, 104, 699–767.
4076
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2005, 4070–4077

Biomimetic Thiolate Alkylation with Zinc Complexes
FULL PAPER
2
[
[
[
[
[
[
[
25] M. Förster, R. Burth, A. K. Powell, T. Eiche, H. Vahrenkamp,
Chem. Ber. 1993, 126, 2643–2648.
26] A. Rheingold, R. L. Ostrander, B. S. Haggerty, S. Trofimenko,
Inorg. Chem. 1994, 33, 3666–3676.
27] A. L. Johnson, J. C. Kauer, D. C. Sharma, R. I. Dorfmen, J.
Med. Chem. 1969, 12, 1024–1028.
28] P. Bonviccini, A. Levi, V. Lucchini, G. Scorrano, J. Chem. Soc.,
Perkin Trans. 2 1972, 2267–2269.
[32] CCDC-268614 (for HL ), -268609 (for 3b), -268610 (for 4a),
-268611 (for 4b), -268612 (for 5d) and -268613 (for 6d) contain
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge Crys-
tallographic Data Center via www.ccdc.cam.ac.uk/data_requ-
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Received: March 30, 2005
Published Online: September 8, 2005
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