(Neocuproin)zinc Thiolates: Attempts at Modeling Cobalamin-Independent Methionine Synthase

Article abstract of DOI:10.1002/ejic.200300501

Several new complexes [(neo)Zn(SR)₂] [neo = neocuproin (2,9-dimethylphenanthroline)] have been synthesized and structurally characterised. They react in a stepwise fashion with the alkylating agents CH₃I and (CH₃)₂SO₄ to afford the thioethers CH₃SR and first the mixed complexes [(neo)Zn(SR)X] (X = I, CH₃SO₄) and then [(neo)ZnX₂]. Similar alkylations occur with benzyl iodide, but not with trimethyl phosphate in nonpolar media. Under these conditions, thiolate exchange with [PPN]SR does not occur which indicates that the alkylations take place at the zinc-bound thiolates. In polar solvents (methanol, DMSO), thiolate exchange occurs readily, and at higher temperatures (CH₃)₃PO₄ also acts as an alkylating agent which indicates that under these conditions free thiolate is available in solution. Qualitative kinetic data support the associative alkylation mechanism in nonpolar media and the change of mechanism in polar media. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300501

FULL PAPER
(Neocuproin)zinc Thiolates: Attempts at Modeling Cobalamin-Independent
Methionine Synthase
Jan Seebacher,[a] Mian Ji,[a] and Heinrich Vahrenkamp*[a]
Keywords: Zinc / Metal complexes / Thiolates / Bioinorganic chemistry
Several new complexes [(neo)Zn(SR)2] [neo = neocuproin
(2,9-dimethylphenanthroline)] have been synthesized and
structurally characterised. They react in a stepwise fashion
with the alkylating agents CH3I and (CH3)2SO4 to afford the
thioethers CH3SR and first the mixed complexes
[(neo)Zn(SR)X] (X = I, CH3SO4) and then [(neo)ZnX2]. Sim-
lates. In polar solvents (methanol, DMSO), thiolate exchange
occurs readily, and at higher temperatures (CH3)3PO4 also
acts as an alkylating agent which indicates that under these
conditions free thiolate is available in solution. Qualitative
kinetic data support the associative alkylation mechanism in
nonpolar media and the change of mechanism in polar me-
ilar alkylations occur with benzyl iodide, but not with trime- dia.
thyl phosphate in nonpolar media. Under these conditions,
thiolate exchange with [PPN]SR does not occur which indi-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
cates that the alkylations take place at the zinc-bound thio- Germany, 2004)
Introduction
and ZnS4 complexes[20] and studied the alkylation of an
NiN4S complex,[21] and very recently Darbre[22] found that
the ZnN2S2 complex [Zn(MEPA)2] previously reported by
us[23] can be methylated with trimethyl phosphate. So far
the alkylation of a close model complex, i.e. one with
ZnNS3 coordination, has not been studied. In the cases
where mechanistic investigations were undertaken, they
indicated that the thiolates are alkylated in the zinc-bound
state and the resultant thioethers are subsequently released.
Only in the alkylation of anionic [Zn(SR)4]2Ϫ, which was
studied as a model for the Ada repair protein, was it ob-
served that the thiolate dissociates from zinc prior to being
attacked by the alkylating agent.[24]
In recent years the well-investigated classes of zinc en-
zymes, i.e. those for hydrolytic reactions and those of the
alcoholdehydrogenase family, have been accompanied by a
new class responsible for thiolate alkylations. Their most
prominent function is the synthesis of methionine from
homocysteine.[1,2] Other thiolate-alkylating enzymes include
betain:homocysteine
S-methyltransferase,[3]
protein
prenyltransferases[4Ϫ6] like farnesyl transferase,[7] meth-
anol:CoM methyltransferase,[8] and the Ada repair pro-
tein.[9,10] It is believed that all these enzymes activate the
thiol by attaching it to zinc as a thiolate.[5,11] We were able
to show that this correlates with the ability of low-coordi-
nate zinc to lower the pKa of zinc-bound water to 7 or be-
low, thereby generating ZnϪOH species under physiological
conditions which react with thiols to produce ZnϪSR spe-
cies and water.[12]
Our own contributions to this field have so far consisted
of the investigation of (pyrazolylborato)zinc thiolate (Tp*
ZnϪSR) complexes, i.e. ZnN3S systems. During the syn-
thetic studies[25Ϫ28] it was found that such complexes are
easily formed in neutral solutions from TpZnϪOH and the
corresponding thiol, i.e. their formation does not require a
base. Detailed mechanistic studies[29,30] then revealed that
the alkylation of their thiolates occurs intramolecularly and
that the zincϪsulfur bond is broken after the formation of
the thioether. The drawback of the model chemistry using
TpZnϪSR complexes is that their zinc coordination is dif-
ferent from that in the enzyme (ZnNS3) and that they are
not reactive toward the biological alkylating agents N-meth-
yltetrahydrofolate or organic phosphates nor analogues
thereof in the form of alkylammonium salts or trimethyl
phosphate.
In cobalamin-independent methionine synthase[13] and
several of the related enzymes,[14] zinc is attached to the
protein by one histidine and two cysteinate residues and
bears a labile ligand, typically water. Thereby its coordi-
nation in the resting state is ZnNS2O, and after substrate
attachment it is ZnNS3. Several compounds modeling
methionine synthase with zinc complexes have approxi-
mated this coordination. Darensbourg[15] alkylated ZnN2S2
species, Carrano[16Ϫ18] various ZnN2SX and ZnN2S2 spe-
cies, Parkin[19] a ZnS4 complex, Riordan prepared ZnNS3
[a]
Institut für Anorganische und Analytische Chemie der
Universität Freiburg
With the hope of increasing the reactivity of the zinc
thiolates and to approximate the natural binding situation
of zinc we therefore set out to investigate zinc thiolates with
Albertstr. 21, 79104 Freiburg, Germany
Fax: (internat.) ϩ 49-761/203-6001
E-mail: vahrenka@uni-freiburg.de
Eur. J. Inorg. Chem. 2004, 409Ϫ417
DOI: 10.1002/ejic.200300501
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
409

J. Seebacher, M. Ji, H. Vahrenkamp
FULL PAPER
a more sulfur-rich ligand environment. This paper describes uses zinc bis[bis(trimethylsilyl)]amide as the base and the
the chemistry of ZnN2S2 systems and work on ZnNS3 and zinc precursor, which is added to a mixture of the thiol
ZnS4 systems is in progress. Ideally one would have taken a and neocuproin.
pyrazolylborate-derived tripodal N2S ligand to study
In complexes 1aϪe, the monodentate thiolates were va-
(N2S)ZnϪSR complexes for this purpose. Since such a li- ried so as to have aliphatic, benzylic, and aromatic substitu-
gand is not available as yet, however, we resorted to an ap- ents, and among the aromatic substituents the electron den-
propriate chelating N2 ligand and the corresponding sity and the steric bulk were varied. The same aliphatic/
(N2)Zn(SR)2 complexes. Based on previous favourable ex- benzylic/aromatic variation was the reason for the choice of
perience with such complexes[31Ϫ34] we opted for neocup- the three bidentate thiolate ligands in 1fϪh. Specifically in
roin (neo, 2,9-dimethylphenanthroline). This paper reports 1h the thiolate ligand is benzylic at one sulfur atom and
the syntheses and structures of some new [(neo)Zn(SR)2] aromatic at the other, and it was hoped that this would be
complexes and reactivity studies related to the stepwise re- reflected in the reactivity of the two thiolate functions.
moval of their thiolate ligands as thioethers by means of
All complexes 1 are yellow crystalline solids. Their IR
alkylation with various alkylating agents under a variety spectra are not diagnostic since there are hardly any band
of conditions.
shifts for the ligands upon coordination to zinc. Similarly
the 1H NMR spectra are characteristic only for the thiolate
ligands (see Exp. Sect.), while the neocuproin resonances
[typical values in CDCl3: δ ϭ 3.1 (s, CH3), 7.5 (d, J ϭ
8.4 Hz, 4-H), 7.9 (s, 5-H), 8.3 (d, J ϭ 8.4 Hz, 3-H) ppm]
show only very small shifts upon coordination.
Four of the eight bis(thiolate) complexes were subjected
to structural determinations. One typical example of each
of the monodentate (1c) and bidentate thiolates (1h) are
presented as Figures 1 and 2. A summary of selected bond
Results and Discussion
(Neocuproin)zinc Bis(thiolate) Complexes
The neocuproin ligand is favourable for stable and tetra-
hedral zinc complexes. It has already been observed that
this is also true for bis(thiolate) complexes.[31Ϫ34] For the
simple bis(thiolates), the benzenethiolate,[34] and the
phenylethanethiolate[31] have also been structurally charac-
terized and we now contribute the bis(thiolates) 1aϪh.
Their preparation can be achieved with comparable yields
by two alternative methods. The first of these consists of the
successive treatment of sodium methoxide with the thiol,
hydrated zinc perchlorate and then neocuproin. The other
Figure 1. Molecular structure of complex 1c
Figure 2. Molecular structure of complex 1h
www.eurjic.org Eur. J. Inorg. Chem. 2004, 409Ϫ417
410
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

(Neocuproin)zinc Thiolates
FULL PAPER
lengths and angles for all four structures is given in Table 1.
The table shows {as does the comparison with previously
reported [(neo)Zn(SR)] complexes[31,33,34]} that the ZnϪN
and ZnϪS bond lengths are rather constant, irrespective of
the electronic nature of the thiolate ligands. Likewise the
NϪZnϪN angle is fixed to its low value due to the steric
constraints of the neocuproin ligand. The only variable
quantities are the SϪZnϪS and NϪZnϪS angles. While the
chelating bis(thiolate) in 1h fixes the SϪZnϪS angle near
the tetrahedral value, it can extend to almost 140° in the
absence of any restraints, as in 1c. The average size of the
NϪZnϪN angle which is large for 1h and small for 1c is a
mere consequence of the size of the SϪZnϪS angles.
Alkylations with benzyl iodide were performed with the
chelate complexes 1f and 1g. They were slightly faster than
the methyl iodide reactions and yielded the thioether thio-
late complexes 3f and 3g.
˚
Table 1. Bond lengths [A] and angles [°] for complexes 1
1c
1d
1g
1h
ZnϪS1
ZnϪS2
ZnϪN1
ZnϪN2
SϪZnϪS 137.62(5)
NϪZnϪN 78.85(1)
2.266(2)
2.267(2)
2.121(4)
2.121(4)
2.287(1)
2.289(2)
2.104(2)
2.103(2)
120.76(2)
80.34(7)
2.249(1)
2.260(1)
2.115(3)
2.122(3)
123.58(5)
79.1(1)
2.271(3)
2.275(3)
2.081(8)
2.062(8)
108.4(1)
81.3(3)
SϪZnϪN 103.0Ϫ109.7 106.6Ϫ118.4 109.6Ϫ113.6 114.8Ϫ119.2
Alkylation Reactions
Crystals of 3g suitable for an X-ray analysis were ob-
tained. Figure 3 shows the molecular shape which is an in-
dication of the intramolecular nature of the alkylation reac-
tions. The coordination of zinc in 3g largely resembles that
in the bis(thiolate) complexes 1. Notably the NϪZnϪS
angles are spread over a range of 14°, and the SϪZnϪI
angle is close to the tetrahedral value.
As before,[30] the most convenient reagent for alkylation
of the zinc-bound thiolates was methyl iodide. With the ex-
ception of 1e all thiolates 1 were treated with 1 mol-equiv.
of CH3I in chloroform. Clean reactions occurred with the
bis(thiolates) 1aϪc resulting in the liberation of the thio-
ether CH3SR and isolation of the iodide thiolate com-
plexes 2aϪc. Complex 1d reacted too slowly at room tem-
perature, but yielded decomposition products at elevated
temperatures which prevented the isolation of pure 2d. Of
the chelating bis(thiolates), 1f and 1g underwent clean re-
lease of one thiolate function, producing 2f and 2g with
thioether thiolate ligands. The asymmetric chelating bis(thi-
olate) 1h was found by NMR observation to be, as ex-
pected, more reactive at the benzylthiolate than at the phe-
nylthiolate function, yet the methylation of the benzylthiol-
ate unit did not go to completion before methylation of
the phenylthiolate began. As a result the thioether thiolate
complex 2h, like 2d, could only be identified by its NMR
spectroscopic data.
˚
Figure 3. Molecular structure of 3g; selected bond lengths [A] and
angles [°]: ZnϪI 2.580(1), ZnϪS 2.244(2), ZnϪN1 2.082(5),
ZnϪN2 2.074(5); SϪZnϪI 111.87(6), N1ϪZnϪN2 80.8(2),
N1ϪZnϪS 118.2(2), N2ϪZnϪS 122.6(2), N1ϪZnϪI 110.6(1),
N2ϪZnϪI 109.0(1)
When 2 equiv. of methyl iodide were allowed to react
with 1aϪc, 1f, and 1g, complete removal of the thiolate
ligands occurred and the resultant methyl thioethers could
be identified by their 1H NMR spectra. The remaining zinc
complex (neo)ZnI2 was isolated from the reactions of 1c
and 1f and characterised and its crystal structure deter-
Eur. J. Inorg. Chem. 2004, 409Ϫ417
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
411

J. Seebacher, M. Ji, H. Vahrenkamp
FULL PAPER
mined (see Exp. Sect.). It was observed that the second step
of the alkylations is not significantly slower than the first
step. This also means that even with 1 equiv. of methyl
iodide part of the starting materials 1 are converted into
(neo)ZnI2 and 2 equiv. of the thioether, which in some cases
hampered the isolation of the mixed complexes 2.
We have previously observed[30] that dimethyl sulfate is
as good as methyl iodide for the alkylation of zinc-bound
thiolates, but that the low stability of the resultant
zincϪ(methyl sulfate) complexes creates preparative prob-
lems. This was not so pronounced in the present study.
Complexes 1a, b, f, and g were chosen for the dimethyl sul-
fate reactions, representing two cases each of monodentate
and chelating bidentate thiolates. Treatment with 1 equiv.
of dimethyl sulfate produced the corresponding methyl thi-
oethers, as evidenced by 1H NMR spectroscopy. The result-
ant zinc complexes 4, of which 4f and g still contain the
thioether as a ligand, were isolated in good yields. They are
methyl sulfate complexes which are stable at room tempera-
ture. Yet both their NMR spectra and their elemental
analyses showed that they were not pure, and attempts at
purifying them by recrystallisation only increased their im-
purity content.
˚
Figure 4. Molecular structure of 5; selected distances [A] and
angles [°] in the complex cation: ZnϪO 2.138(2), ZnϪN1 2.093(2),
ZnϪN2 2.130(2), ZnϪN3 2.059(2), ZnϪN4 2.135(2), (Zn)OϪS
1.465(2), SϭO 1.435(2) and 1.437(2), SϪO(C) 1.592(2);
N2ϪZnϪN4 161.9(1), O1ϪZnϪN1 119.5(1), O1ϪZnϪN3
119.8(1), N1ϪZnϪN3 120.7(1); in the methyl sulfate anion: SϭO
1.394(3), 1.430(5) and 1.420(7), SϪO(C) 1.589(10)
The major piece of information from the structure of 5
is the demonstration of the existence of zincϪ(alkyl sulfate)
binding. The coordination of the zinc ion in 5 is somewhere
between square-pyramidal and trigonal-bipyramidal. The
suggested square-pyramidal coordination is impossible be-
cause the four methyl groups of the neocuproin ligands
prevent a symmetric basal arrangement. The alternative
trigonal-bipyramidal coordination is impossible because of
the small intra-chelate-ligand NϪZnϪN angles. The molec-
ular shape of 5 and its bonding parameters closely resemble
those in the corresponding nitrate complex.[35] The SϭO
bond lengths in the ligated and the free methyl sulfate
groups do not differ significantly. This holds specifically for
the SϪO(Zn) bond which is much closer in length to the
SϭO bonds than to the real single bonds SϪO(C). This
situation resembles that in the zincϪ(organyl phosphate)
complexes[36,37] and, just as for the latter, indicates that
there is a considerable amount of ionic character in the
ZnϪO bond.
A more ‘‘biological’’ alkylating agent is trimethyl phos-
phate, since the Ada repair protein dealkylates alkyl phos-
phates by transferring the alkyl groups from phosphate to
thiolate.[9,10] As before,[30] we also found here that trimethyl
phosphate does not alkylate the thiolate ligands of com-
plexes 1 in nonpolar media. It has, however, been reported
in the literature[22,24] that in strongly polar solvents and at
elevated temperatures the alkylation does take place. This
could be reproduced by us using complex 1c. Heating equi-
molar amounts of 1c and PO(OMe)3 in DMSO to 80 °C
for 2 weeks produced an almost quantitative formation (by
NMR) of MeSC6H4-p-CH3 and a good isolated yield of the
phosphate complex 6. Likewise with a fivefold amount of
PO(OMe)3 nearly quantitative formation of the bis(phos-
phate) complex 7 took place. The harsh reaction conditions
required due to the low alkylating strength of trimethyl
phosphate most probably involve a change in the mecha-
nism of the alkylation. As suggested before,[22,24] we con-
Treatment of 4a, b, f, or g with an excess of dimethyl
sulfate resulted in complete release of the corresponding
methyl thioethers just as in the methyl iodide reactions, but
the fate of the remaining zinc species is unclear. No evi-
dence for the formation of [(neo)Zn(OSO3CH3)2] was ob-
tained. Only in one case could a small amount of a crystal-
line product be isolated from the reaction of 1f. A structural
determination, the result of which is shown in Figure 4,
identified this product as complex 5.
5: [(neo)2ZnϪOSO3Me](OSO3Me)
412
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2004, 409Ϫ417

(Neocuproin)zinc Thiolates
FULL PAPER
clude (see below) that in these cases free thiolate is liberated
and alkylated without the involvement of zinc.
6: [(neo)Zn(SϪp-Tol)OPO(OMe)2]
7: [(neo)Zn{OPO(OMe)2}2]
The biological alkylating agent in cobalamin-indepen-
dent methionine synthase is N5-methyltetrahydrofolic acid,
a methylammonium salt. Two synthetic analogues, N,N,N-
trimethylanilinium iodide and N-methyltetrahydroquinoxal-
inium iodide, were found to be good mimics,[38] yet they
showed no methylating tendency even towards 1b, the most
reactive of the thiolates investigated here even at elevated
temperatures.
Figure 5. Kinetic traces (by 1H NMR) for the reaction of 1h (0.005
) with a four-fold excess of CH3I in chloroform at 300 K
Mechanistic Considerations
The question of whether the alkylation occurs at the zinc-
bound or at the free anionic thiolates was addressed with
the same procedures as used in our preceding work.[30] Both
thiolate exchange experiments and kinetic investigations led
to the conclusion that the [(neo)Zn(SR)2] complexes just
like the Tp*ZnϪSR complexes undergo intramolecular al-
kylation, i.e. they do not dissociate in nonpolar media.
The thiolate exchange experiments were monitored by 1H
NMR spectroscopy. In no case could a replacement of SR
in [(neo)Zn(SR)2] by SRЈ from [PPN]SR be observed in
chloroform. In methanol, however, fast exchange between
[(neo)Zn(SBn)2] (1b) and NaSEt took place. Starting with
a 1:1 mixture of the reagents, an equilibrium was reached
in which [(neo)Zn(SBn)2] and [(neo)Zn(SEt)2] exist in a 10:1
ratio. When treating [(neo)Zn(SBn)2] with the chelating thi-
Finally, another argument in favour of a dissociative al-
kylation process in polar media (i.e. a nondissociative pro-
cess in chloroform) was found in the comparison of reac-
tion speeds: in methanol the reaction between 1b and
methyl iodide is roughly one order of magnitude faster than
in chloroform. As for the thiolate exchange reactions and
for the alkylations with trimethyl phosphate (see above) the
simplest explanation for this is the existence of free anionic
thiolate in the polar medium.
Conclusions
The present work represents the second step in our in-
olate Na2(SCH2ϪC6H4ϪCH2S), a quantitative conversion vestigations on modeling biological thiolate alkylations
into the chelating dithiolate complex 1g and NaSBn oc- with tetrahedral zinc complexes. After the ZnN3S situation
curred within minutes. The driving force for this reaction is in (pyrazolylborato)zinc thiolates the ZnN2S2 situation in
the precipitation of 1g from the methanolic solution.
(neocuproin)zinc thiolates was addressed. Again, the ac-
Kinetic data were accumulated for several of the alky- cumulated evidence indicates that the thiolates are alkylated
lation reactions under pseudo-first-order conditions. Yet in in the zinc-bound state. Furthermore, while the coordi-
no case could they be fitted cleanly by assuming first-order nation environment of zinc in the enzymes could be ap-
behaviour. The reasons for this are mainly due to the early proximated, the alkylating agents had to be much stronger
onset of the second alkylation step and precipitation of than the naturally occuring N-methyltetrahydrofolate.
some of the mixed iodide thiolate complexes 2. A character-
It was found that both thiolate ligands in the
istic plot is displayed in Figure 5 which shows in the trace [(neo)Zn(SR)2] complexes are alkylated in a stepwise fa-
at the bottom the formation of the doubly alkylated bis(thi- shion. When, as in complex 1h, both an aromatic and a
olate) and in the trace at the top the appearance and sub- benzylic thiolate are offered, the benzylic one as expected
sequent disappearance of the monoalkylated species 2h.
reacts first, although not significantly faster than the aro-
A qualitative estimate of the second-order rate constant matic one. Compared with the [Tp*ZnϪSR] complexes the
could be obtained for the reaction of 1g with an excess of [(neo)Zn(SR)2] complexes are more reactive due to their
methyl iodide. By comparing initial rates at identical con- more electron-rich ZnN2S2 situation.
centrations with those of the previously reported Tp*
ZnϪSR/MeI reaction[30] a value of kЈЈ of the order of 10Ϫ4 cannot encapsulate the zinc ion, thereby approximating its
Ϫ1sϪ1 was obtained. This is considerably slower than for enzymatic environment. This would call for tripodal N2S
Unlike the pyrazolylborate ligands the neocuproin ligand

[Tp*ZnϪSR] complexes, but compares favourably with the ligands, possibly derived from the pyrazolylborates. The
kЈЈ value obtained by Carrano[18] for the MeI methylation synthesis of such ligands is still a challenge. Similar tripodal
of an [(N2O)ZnϪSPh] complex. There still exist too few ligands of the NS2 and S3 type exist, however,[39,40] and we
second-order rate constants for such alkylations to allow a are investigating thiolate alkylations of [L·ZnϪSR] com-
meaningful discussion, however.
plexes derived from them.
Eur. J. Inorg. Chem. 2004, 409Ϫ417
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
413

J. Seebacher, M. Ji, H. Vahrenkamp
FULL PAPER
Complex 1f: Like 1a from Zn[N(SiMe3)2]2 (1.71 g, 4.42 mmol),
neo·H2O (1.00 g, 4.42 mmol) and ethanedithiol (0.41 g, 4.4 mmol).
Yield 1.12 g (69%) of 1f as a yellow solid, m.p. 270 °C (dec.).
C16H16N2S2Zn (365.84): calcd. C 52.53, H 4.41, N 7.66, S 17.87;
found C 52.59, H 4.44, N 7.59, S 17.10. 1H NMR (CDCl3): δ ϭ
3.03 (s, 4 H, CH2) ppm.
Experimental Section
General: For general working and measuring procedures, see ref.[41]
Starting materials were obtained commercially, except for
Zn[N(SiMe3)2]2,[42] o-(mercaptomethyl)thiophenol,[43] and o-bis-
(mercaptomethyl)benzene.[44] The methyl thioethers resulting from
the methylations have been described[45Ϫ48] and were identified by
Complex 1g: Like 1c from Zn(ClO4)2·6H2O (0.447 g, 1.20 mmol),
o-bis(mercaptomethyl)benzene (0.204 g, 1.20 mmol), NaOMe
1
their H NMR spectra. The PPN salts of the thiols were prepared
by cation exchange as described.[49]
(2.45 mmol of
a 0.25  solution), and neo·H2O (0.272 g,
1.20 mmol). Yield 0.240 g of 1g as a light yellow powder and, after
reducing the volume of the filtrate and cooling, 0.030 g of 1g as
yellow crystals. Total yield 0.270 g (51%) of 1g, m.p. 270 °C (dec.).
C22H20N2S2Zn (441.94): calcd. C 59.79, H 4.56, N 6.34, Zn 14.80;
found C 58.14, H 4.45, N 6.01, Zn 13.70. H NMR (CDCl3): δ ϭ
4.03 (s, 4 H, CH2), 7.12Ϫ7.18 (m, 2 H, Ph), 7.35Ϫ7.39 (m, 2 H,
Elemental Analyses: All new compounds were characterized by el-
emental analyses which were satisfactory in most cases. Yet, as
mentioned in the text, several of the alkylation reactions yielded
product mixtures, from which the expected products could not be
isolated in a fully pure form. For these products four elements were
analyzed, giving an overall satisfactory picture for 1b, 1e, 1g, 4a, 4b,
and 4g. Only for 2f, 3f, and 4f was the purity obviously insufficient.
1
Ph) ppm.
Complex 1h: Like 1c from Zn(ClO4)2·6H2O (2.62 g, 7.04 mmol), o-
(mercaptomethyl)thiophenol (1.10 g, 7.04 mmol), NaOMe (0.807 g,
14.9 mmol), and neo·H2O (1.59 g, 7.04 mmol). Yield 1.56 g of 1h
as a yellow powder and, after reducing the volume of the filtrate
and cooling, 0.16 g of 1h as yellow crystals. Total yield 1.72 g (58%)
of 1h, m.p. 265 °C (dec.). C21H18N2S2Zn (427.91): calcd. C 58.95,
H 4.24, N 6.55, S 14.99; found C 58.49, H 3.78, N 6.02, S 14.34.
1H NMR (CD3OD): δ ϭ 3.97 (s, 2 H, CH2), 6.95Ϫ7.07 (m, 2 H,
Ar), 7.27Ϫ7.32 (m, 1 H, Ar), 7.46Ϫ7.55 (m, 1 H, Ar) ppm.
Complex 1a: A solution of Zn[N(SiMe3)2]2 (1.71 g, 4.42 mmol) in
toluene (50 mL) was added slowly with stirring to a solution of
neo·H2O (1.00 g, 4.42 mmol) and ethanethiol (0.66 mL, 550 mg,
8.8 mmol) in toluene (100 mL) over a period of 2 h. A light yellow
precipitate resulted which was filtered and washed two times each
with toluene (3 mL) and diethyl ether (3 mL). 1a (1.50 g, 86%) re-
mained as a light yellow powder, m.p. 250 °C (dec.). C18H22N2S2Zn
(395.91): calcd. C 54.61, H 5.60, N 7.08, Zn 16.52; found C 53.02,
H 5.64, N 6.75, Zn 15.89. 1H NMR (CDCl3): δ ϭ 1.16 [t, J ϭ
7.4 Hz, 6 H, CH3(Et)], 2.46 [q, J ϭ 7.4 Hz, 4 H, CH2(Et)] ppm.
Alkylations with Methyl Iodide
2a: Complex 1a (500 mg, 1.26 mmol) and MeI (79 µL, 180 mg,
1.26 mmol) in chloroform (40 mL) were stirred for 2 d. Reduction
of the volume in vacuo to 20 mL and layering with diethyl ether
(10 mL) yielded 2a (17 mg, 3%) as a colourless powder, m.p. 300
°C (dec.). C16H17IN2SZn (461.68): calcd. C 41.63, H 3.71, N 6.07,
Zn 14.16; found C 41.00, H 3.58, N 5.86, Zn 14.63. 1H NMR
(CDCl3): δ ϭ 1.33 [t, J ϭ 7.3 Hz, 3 H, CH3(Et)], 2.73 [q, J ϭ
7.3 Hz, 2 H, CH2(Et)] ppm.
Complex 1b: Similar procedure to that for 1a from Zn[N(SiMe3)2]2
(1.71 g, 4.42 mmol), neo·H2O (1.00 g, 4.42 mmol), and benzylmer-
captan (1.10 g, 8.84 mmol). Yield 2.10 g (91%) of 1b as light yellow
powder, m.p. 148 °C. C28H26N2S2Zn (520.05): calcd. C 64.67, H
5.04, N 5.39, Zn 12.57; found C 65.98, H 5.27, N 4.87, Zn 11.49.
1H NMR (CDCl3): δ ϭ 3.54 [s, 4 H, CH2(Bn)], 6.65Ϫ6.71 (m, 6
H, Bn), 6.86Ϫ6.91 (m, 4 H, Bn) ppm.
Complex 1c: A solution of Zn(ClO4)2·6H2O (0.372 g, 1.00 mmol)
in methanol (80 mL) was added very slowly with stirring to a solu-
tion of p-thiocresol (0.248 g, 2.00 mmol) and NaOMe (0.108 g,
2.00 mmol) in methanol (100 mL) over a period of 3 h; neo·H2O
(0.208 g, 1.00 mmol) in methanol (15 mL) was then added and the
mixture stirred overnight. The volume was reduced to 30 mL in
vacuo, the precipitate filtered, dried in vacuo, and recrystallized
from hot methanol; 1c (0.41 g, 79%) resulted as yellow crystals,
m.p. 207 °C. C28H26N2S2Zn (520.05): calcd. C 64.67, H 5.04, N
5.39, S 12.33; found C 64.54, H 5.53, N 5.59, S 12.25. 1H NMR
([D6]DMSO): δ ϭ 1.89 [s, 6 H, CH3(Tol)], 6.28 (d, J ϭ 8.0 Hz, 4
H, Tol), 6.64 (d, J ϭ 8.0 Hz, 4 H, Tol) ppm.
2b: Complex 1b (100 mg, 0.19 mmol) and MeI (12 µL, 27.3 mg,
0.19 mmol) in chloroform (25 mL) were stirred for 2 d. The volume
was reduced to 1 mL in vacuo. The precipitate was filtered and
washed three times with cold chloroform (1 mL) leaving behind 2b
(90 mg, 89%) as a colourless solid, m.p. 270 °C (dec.) which was
not analytically pure. C21H19IN2SZn (523.75): EI MS: m/z (%) ϭ
399.2 (100) [Mϩ Ϫ C6H5CH2S], 314.2 (30) [C6H5CH2SZnI]. 1H
NMR (CDCl3): δ ϭ 3.54 (s, 2 H, CH2), 7.02Ϫ7.12 (m, 5 H, Ph)
ppm.
2c: Like 1b with 1c (133 mg, 0.26 mmol) and MeI (36 mg,
0.26 mmol) for one week. Yield 56 mg (40%) of 2c as a light yellow
solid, m.p. 200 °C. C21H19IN2SZn (523.75): calcd. C 48.16, H 3.66,
Complex 1d: Similar to 1a from Zn[N(SiMe3)2]2 (1.46 g,
3.77 mmol), neo·H2O (0.785 g, 3.77 mmol), and p-nitrothiophenol
(1.17 g, 7.54 mmol). Recrystallization from toluene yielded 1d as
dark yellow crystals (1.05 g, 48%), m.p. 213 °C. C26H20N4O4S2Zn
(581.99): calcd. C 53.66, H 3.46, N 9.63, S 11.02; found C 53.45,
H 3.53, N 9.78, S 10.76. 1H NMR (CDCl3): δ ϭ 7.20 (d, J ϭ
8.0 Hz, 4 H, Ar), 7.54 (d, J ϭ 8.0 Hz, 4 H, Ar) ppm.
1
N 5.35, S 6.12; found C 48.00, H 3.99, N 5.42, S. 5.75. H NMR
([D6]DMSO): δ ϭ 1.89 [s, 3 H, Me(Tol)], 6.29 (d, J ϭ 7.8 Hz, 2 H,
Tol), 6.64 (d, J ϭ 7.8 Hz, 2 H, Tol) ppm.
2f: Like 1a with 1f (250 mg, 0.68 mmol) and MeI (97 mg,
0.68 mmol). Yield 167 mg (48%) of 2f as light yellow crystals, m.p.
210 °C (dec.). C17H19IN2S2Zn (507.78): calcd. C 40.21, H 3.77, N
5.52, Zn 12.88; found C 36.29, H 3.08, N 5.10, Zn 12.40. 1H NMR
(CDCl3): δ ϭ 2.16 (s, 3 H, SCH3), 2.77Ϫ2.89 (m, 2 H, CH2),
2.91Ϫ3.02 (m, 2 H, CH2) ppm.
Complex 1e: Like 1c from Zn(ClO4)2·6H2O (0.093 g, 0.25 mmol),
2,6-diphenylthiophenol (0.131 g, 0.50 mmol), NaOMe (0.027 g,
0.50 mmol), and neo·H2O (0.052 g, 0.25 mmol). Yield 0.114 g
(57%) of 1e as yellow crystals, m.p. 260 °C (dec.). C50H38N2S2Zn 2g: Complex 1g (500 mg, 1.13 mmol) and MeI (161 mg, 1.13 mmol)
(796.39): calcd. C 75.41, H 4.81, N 3.52, S 8.05; found C 74.35, H in chloroform (40 mL) were stirred for 1 d. The resultant precipi-
4.95, N 3.45, S 7.97. H NMR (CDCl3): δ ϭ 6.74Ϫ6.92 (m, 18 H, tate was filtered, washed with diethyl ether, and dried in vacuo,
Ar), 7.11Ϫ7.16 (m, 8 H, Ar) ppm. leaving behind 2g (302 mg, 47%) as a colourless powder, m.p. 220
1
414
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2004, 409Ϫ417

(Neocuproin)zinc Thiolates
FULL PAPER
°C (dec.). C23H23IN2S2Zn (583.87): calcd. C 47.31, H 3.97, N 4.80,
the crystals left behind 4f (25 mg, 12%), m.p. 270 °C (dec.).
Zn 11.20; found C 47.16, H 3.89, N 4.67, Zn 12.50. 1H NMR C18H22N2O4S3Zn (491.97): calcd. C 43.95, H 4.51, N 5.69, Zn
(CDCl3): δ ϭ 2.02 (s, 3 H, SMe), 3.90 [s, 2 H, CH2(Ar)], 3.96 [s, 2
H, CH2(Ar)], 6.57Ϫ6.70 (m, 1 H, Ar), 6.72Ϫ6.84 (m, 1 H, Ar), ppm): δ ϭ 2.06 (s, 3 H, SMe), 2.72Ϫ2.85 (m, 2 H, CH2), 2.91Ϫ3.01
13.29; found C 42.15, H 3.84, N 6.22, Zn 13.62. 1H NMR (CDCl3,
6.87Ϫ6.95 (m, 1 H, Ar), 6.97Ϫ7.05 (m, 1 H, Ar) ppm.
(m, 2 H, CH2), 3.69 (s, 3 H, OMe) ppm. The crystals amounted to
5 mg (2%) of 5, m.p. 254 °C, which was identified by the struc-
tural determination.
Alkylations with Benzyl Iodide
3f: Complex 1f (250 mg, 0.68 mmol) and benzyl iodide (149 mg,
0.68 mmol) in chloroform (50 mL) were stirred for 1 d. Layering
with hexane yielded 3f (323 mg, 81%) as a colourless powder, m.p.
330 °C (dec.) which was filtered and dried in vacuo.
C23H23IN2S2Zn (583.87): calcd. C 47.31, H 3.97, N 4.80, S 10.98;
found C 48.61, H 4.33, N 4.52, S 10.14. 1H NMR (CDCl3): δ ϭ
2.79Ϫ2.85 (m, 2 H, CH2), 2.91Ϫ2.99 (m, 2 H, CH2), 3.79 [s, 2 H,
CH2(Bn)], 7.23Ϫ7.40 (m, 5 H, Ph) ppm.
4g: Like 1f with 1g (500 mg, 1.13 mmol) and (MeO)2SO2 (107 µL,
143 mg, 1.13 mmol), yield 4g (520 mg, 81%) as a colourless powder,
m.p. 160 °C. C24H26N2O4S3Zn (568.07): calcd. C 50.74, H 4.61, N
4.93, Zn 11.50; found C 48.82, H 4.34, N 4.96, Zn 11.47. 1H NMR
(CDCl3): δ ϭ 1.89 (s, 3 H, SMe), 3.70 (s, 3 H, OMe), 3.76 (s, 2 H,
CH2), 3.83 (s, 2 H, CH2), 6.02Ϫ6.17 (m, 1 H, C6H4), 6.30Ϫ6.45
(m, 1 H, C6H4), 6.47Ϫ6.63 (m, 2 H, C6H4).
Methylations of 1c with Trimethyl Phosphate
3g: Like 1f with 1g (567 mg, 1.28 mmol) and benzyl iodide (279 mg,
1.28 mmol). Yield 228 mg (27%) of 3g as colourless crystals, m.p.
220 °C (dec.). C29H27IN2S2Zn·0.5CHCl3 (659.97 ϩ 119.38): calcd.
With 1 Equiv.: Complex 1c (200 mg, 0.38 mmol) and PO(OMe)3
(54 mg, 0.38 mmol) in DMSO (10 mL) were stirred at 80 °C for 2
weeks. All volatiles were then removed in vacuo at 80 °C. The resi-
due was washed with diethyl ether and dried in vacuo, leaving be-
hind 6 (135 mg, 67%) as a light yellow powder, m.p. 148 °C.
C23H25N2O4PSZn (521.89): calcd. C 52.93, H 4.83, N 5.37, S 6.14;
found C 53.56, H 4.92, N 6.32, S 7.08. 1H NMR ([D6]DMSO): δ ϭ
1.91 [s, 3 H, CH3(Tol)], 3.30 (d, J ϭ 5.2 Hz, 6 H, OMe), 6.34 (d,
J ϭ 7.0 Hz, 2 H, Tol), 6.70 (d, J ϭ 7.2 Hz, 2 H, Tol) ppm.
1
C 49.23, H 3.85, N 3.98; found C 49.68, H 3.79, N 4.18. H NMR
(CDCl3): δ ϭ 3.64 [s, 2 H, CH2(Ph)], 3.81 [s, 2 H, CH2(Ph)], 3.91
[s, 2 H, CH2(Ph)], 6.54Ϫ6.62 (m, 1 H, Ar), 6.68Ϫ6.75 (m, 1 H, Ar),
6.84 (d, J ϭ 7.6 Hz, 1 H, Ar), 7.00 (d, J ϭ 7.6 Hz, 1 H, Ar),
7.05Ϫ7.30 (m, 5 H, Ar) ppm.
Twofold Methylations
With 1c: Complex 1c (103 mg, 0.20 mmol) and CH3I (450 mg,
3.2 mmol) in chloroform (25 mL) were stirred for 2 d. All volatiles
were then removed in vacuo and the residue washed with diethyl
ether (2 mL) and dichloromethane (2 mL), leaving behind
(neo)ZnI2 (48 mg, 46%) as a colourless powder, m.p. 320 °C (dec.).
Crystals for the structure determination were obtained by recrystal-
lization from chloroform. C14H12I2N2Zn (527.46): calcd. C 31.88,
H 2.29, N 5.31; found C 31.67, H 2.41, N 5.04. 1H NMR (CDCl3):
δ ϭ 3.25 (s, 6 H, CH3), 7.78 (d, J ϭ 8.4 Hz, 2 H, HB), 7.95 (s, 2
H, HC), 8.47 (d, J ϭ 8.4 Hz, 2 H, HA).
With 2 Equiv.: As above with 1c (100 mg, 0.19 mmol) and
PO(OMe)3 (133 mg, 0.95 mmol), yielded 7 (85 mg, 85%) as a light
yellow powder, m.p. 142 °C. C18H24N2O8P2Zn·H2O (523.73 ϩ
18.02): calcd. C 39.91, H 4.84, N 5.17; found C 39.89, H 5.02, N
4.69. 1H NMR (CDCl3): δ ϭ 1.50 (s, 2 H, H2O), 3.59 (d, J ϭ
10.9 Hz, 12 H, OMe) ppm.
NMR Experiments: For all alkylation reactions described above,
from which zinc complexes were isolated, the resultant alkyl thio-
ethers which are known compounds[45Ϫ48] were identified by 1H
NMR spectroscopy, specifically by their characteristic S-methyl
resonances. The NMR spectroscopic data showed that none of the
reactions were clean, i.e. decomposition reactions and subsequent
alkylations set in before the first alkylation step was complete. In
those cases where the resultant zinc complexes could not be iso-
lated, i.e. in the CH3I methylations of 1d and 1h and the double
methylations with CH3I and (CH3O)2SO2, the information on the
reaction course rests on the NMR spectroscopic data alone. Like-
wise the qualitative determinations of reaction rates were done by
1H NMR spectroscopy. This concerns the rates for methylations
versus benzylations, for single versus double methylations and for
methylations in chloroform versus methanol.
With 1f: Complex 1f (50 mg, 0.14 mmol) and CH3I (2.27 g,
16.0 mmol) in chloroform (25 mL) were stirred for 1 week. Workup
as above yielded (neo)ZnI2 (12 mg, 17%).
Methylations with Dimethyl Sulfate
4a: Complex 1a (281 mg, 0.71 mmol) and (MeO)2SO2 (67 µL,
89 mg, 0.71 mmol) in chloroform (40 mL) were stirred for 2 d. Re-
duction of the volume to 20 mL in vacuo and layering with diethyl
ether yielded a precipitate which was filtered and washed twice with
diethyl ether (5 mL), leaving behind 4a (285 mg, 90%) as a colour-
less powder, m.p. 300 °C (dec.). C17H20N2O4S2Zn (445.88): calcd.
C 45.79, H 4.52, N 6.28, Zn 14.67; found C 43.48, H 4.15, N 6.07,
Zn 14.26. 1H NMR (CDCl3): δ ϭ 1.34 [t, J ϭ 7.3 Hz, 3 H,
CH3(Et)], 2.58 [q, J ϭ 7.3 Hz, 2 H, CH2(Et)], 3.68 (s, 3 H, OMe)
ppm.
Thiolate Exchange: 1. A mixture of 1b (9.9 mg, 19.0 µmol) and
NaSEt (1.6 mg, 19.0 µmol) in CD3OD (0.5 mL) reached equilib-
rium within 1 h. The intensity ratio of the benzyl CH2 singlets for
1b vs. NaSBn was 10:1. 2. 1b (12.3 mg, 23.8 µmol) and
Na2[SCH2ϪC6H4ϪCH2S] (5.1 mg, 23.8 µmol) in CD3OD
(0.25 mL) immediately produced a light yellow precipitate of 1g.
1H NMR of the solution showed that no more 1b remaind and the
major organic component was NaSBn.
4b: Like 1a with 1b (150 mg, 0.29 mmol) and (MeO)2SO2 (27 µL,
36 mg, 0.29 mmol), yielded 4b (146 mg, 99%) as a colourless pow-
der, m.p. 150 °C. C22H22N2O4S2Zn (507.95): calcd. C 52.02, H 4.37,
N 5.52, Zn 12.87; found C 48.70, H 4.42, N 5.25, Zn 11.57. 1H
NMR (CDCl3): δ ϭ 3.66 (s, 3 H, OMe), 3.72 (s, 2 H, CH2),
6.36Ϫ6.51 (m, 3 H, Ph), 6.76Ϫ6.85 (m, 2 H, Ph) ppm.
Kinetic Measurements: The measurements were performed on
0.005Ϫ0.02  CDCl3 solutions of the zinc complex. Kinetic traces
were recorded at 10-min intervals for reaction mixtures containing
4f: Complex 1f (160 mg, 0.44 mmol) and (MeO)2SO2 (45 µL,
60 mg, 0.48 mmol) in chloroform (20 mL) were stirred for 2 d. Lay-
ering with hexane (30 mL) yielded, within one week, a mixture of
a colourless powder and colourless crystals, which was filtered,
washed with diethyl ether, and dried in vacuo. Manual removal of
1
4Ϫ10 mol-equiv. of CH3I. The intensities of isolated H NMR res-
onances were recorded. In all cases it was observed that the second
alkylation sets in before the first half-life of the first alkylation is
Eur. J. Inorg. Chem. 2004, 409Ϫ417
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
415

J. Seebacher, M. Ji, H. Vahrenkamp
FULL PAPER
Table 2. Crystallographic details
1c
1d
1g
1h
3g
(neo)ZnI2
5
Empirical formula
Formula mass
Crystal size [mm]
Space group
Z
C28H26N2S2Zn C26H20N4O4S2Zn C22H20N2S2Zn·CH2Cl2 C21H18N2S2Zn C29H27IN2S2Zn C14H12I2N2Zn C30H30N4O8S2Zn
520.00 581.95 526.82 427.86 659.97 703.23 704.10
0.3 ϫ 0.2 ϫ 0.1 0.3 ϫ 0.3 ϫ 0.2 0.3 ϫ 0.2 ϫ 0.2 0.3 ϫ 0.2 ϫ 0.2 0.4 ϫ 0.2 ϫ 0.2 0.4 ϫ 0.2 ϫ 0.2 0.5 ϫ 0.5 ϫ 0.4
Pbca
P21/c
P21/c
P21/n
P21/c
P21/n
P21/c
8
4
4
4
4
4
4
˚
a [A]
15.929(1)
11.056(1)
28.218(1)
90
12.369(5)
18.502(7)
12.005(5)
90
12.794(3)
14.928(3)
13.356(3)
90
9.722(4)
16.288(6)
11.688(5)
90
8.011(2)
37.246(7)
10.485(4)
90
8.287(1)
14.221(2)
13.765(2)
90
17.739(4)
13.653(3)
12.885(3)
90
˚
b [A]
˚
c [A]
α [°]
β [°]
γ [°]
90
90
116.651(6)
90
115.38(3)
90
92.116(7)
90
117.09(2)
90
103.376(3)
90
105.85(3)
90
3
˚
V [A ]
4969.5(5)
1.39
2455.4(16)
1.57
2304.6(8)
1.52
1849.6(13)
1.54
2785.2(13)
1.57
1578.2(3)
2.22
3002(1)
1.56
dcalcd. [g cmϪ3
]
µ(Mo-Kα) [mmϪ1
hkl range
]
1.18
1.21
1.49
1.56
2.16
5.46
1.02
h: Ϫ21 to 21
k: Ϫ14 to 14
l: Ϫ37 to 37
43154
h: Ϫ16 to 11
k: Ϫ23 to 24
l: Ϫ15 to 16
15529
h: Ϫ14 to 15
k: 0 to 18
l: Ϫ16 to 0
4725
h: Ϫ12 to 11
k: Ϫ19 to 9
l: Ϫ11 to 15
5544
h:-9 to 0
k: 0 to 45
l: Ϫ11 to 12
5842
h: Ϫ9 to 9
k: Ϫ15 to 15
l: Ϫ15 to 15
10802
h: Ϫ20 to 19
k: Ϫ16 to 15
l: 0 to 14
10671
Reflections measured
Independent reflections 6163
5941
4521
3991
5450
2269
5507
Obsd. reflections
[I Ͼ 2σ(I)]
3094
4627
3339
1357
3603
1735
4495
Parameters
298
334
271
235
316
172
438
Reflections refined
R1 (obsd. reflections)
wR2 (all reflections)
6163
0.056
0.156
5941
0.031
0.091
ϩ0.5/Ϫ0.4
4521
0.049
0.161
ϩ0.6/Ϫ0.8
3991
0.076
0.272
ϩ0.8/Ϫ1.1
5450
0.051
0.161
ϩ0.8/Ϫ1.0
2269
0.023
0.051
ϩ0.5/Ϫ0.5
5507
0.036
0.125
ϩ1.6/Ϫ0.5
Residual density [e/AϪ3] ϩ0.6/Ϫ0.6
˚
[4]
[5]
M. H. Gelb, Science 1997, 275, 1750Ϫ1751.
K. E. Hightower, C. A. Fierke, Curr. Opin. Chem. Biol. 1999,
3, 176Ϫ181.
H. Zhang, M. C. Seabra, J. Deisenhofer, Structure 2000, 8,
241Ϫ251.
H. W. Park, S. R. Boduluri, J. F. Moomaw, P. J. Casey, L. Beese,
reached. This virtually prevented the determination of rate con-
stants. Detailed investigations were made for the CH3I methylation
of 1g and 1h. Taking the data for the first hour of the methylation
of 1g (ca. 40% conversion), pseudo-first-order rate constants could
be obtained which were roughly 100 times smaller than those for
the methylation of TpPh,MeZnϪSBn under similar conditions.[30]
The methylation of 1h, for which the kinetic traces are displayed in
Figure 5, is about one order of magnitude faster.
[6]
[7]
Science 1997, 275, 1800Ϫ1801.
[8]
[9]
K. Sauer, R. Thauer, Eur. J. Biochem. 1997, 249, 280Ϫ285.
L. C. Myers, M. P. Terranova, A. E. Ferentz, G. Wagner, G. L.
Verdine, Science 1993, 261, 1164Ϫ1167.
L. J. Sun, C. K. Yim, G. L. Verdine, Biochemistry 2001, 40,
11596Ϫ11603.
Structural Determiantions:[50] Crystals were obtained as described
in the Exp. Sect. Diffraction data were recorded at room temp. [1g,
1h, 3g, (neo)ZnI2, 5] and at Ϫ90 °C (1c, 1d) with a Nonius CAD4
(5) or a Bruker Smart CCD diffractometer [1c, 1d, 1g, 1h, 3g,
(neo)ZnI2]. Empirical absorption corrections were applied for 1c,
1d, 1g, 1h, 3g, and (neo)ZnI2. The structures were solved with direct
methods and refined anisotropically using the SHELX[51] program
suite. Hydrogen atoms were included at fixed distances and iso-
tropic temperature factors 1.2 times those of the atoms to which
they are attached. Parameters were refined against F2. Drawings
were produced with SCHAKAL.[52] Table 2 lists the crystallo-
graphic data.
[10]
[11]
R. G. Matthews, C. W. Goulding, Curr. Opin. Chem. Biol. 1997,
1, 332Ϫ339.
[12]
[13]
H. Vahrenkamp, Acc. Chem. Res. 1999, 32, 589Ϫ596.
K. Peariso, Z. S. Zhou, A. E. Smith, R. G. Matthews, J. E.
Penner-Hahn, Biochemistry 2001, 40, 987Ϫ993.
S. A. Ensign, Biochemistry 2001, 40, 5845Ϫ5853.
C. A. Grapperhaus, T. Tuntulani, J. H. Reibenspies, M. Y. Dar-
ensbourg, Inorg. Chem. 1998, 37, 4052Ϫ4058.
B. S. Hammes, C. J. Carrano, Inorg. Chem. 1999, 38,
4593Ϫ4600.
B. S. Hammes, C. J. Carrano, Inorg. Chem. 2001, 40, 919Ϫ927.
B. S. Hammes, C. R. Warthen, D. C. Crans, C. J. Carrano, J.
Biol. Inorg. Chem. 2001, 6, 82Ϫ90.
B. M. Bridgewater, T. Fillebeen, R. A. Friesner, G. Parkin, J.
Chem. Soc., Dalton Trans. 2000, 4494Ϫ4496.
S. J. Chiou, J. Innocent, C. G. Riordan, K. C. Lam, L. Liable-
Sands, A. L. Rheingold, Inorg. Chem. 2000, 39, 4347Ϫ4353.
M. S. Ram, C. G. Riordan, R. Ostrander, A. L. Rheingold,
Inorg. Chem. 1995, 34, 5884Ϫ5892.
[14]
[15]
[16]
[17]
[18]
Acknowledgments
[19]
[20]
[21]
[22]
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie. We thank Drs. W. Deck
and H. Brombacher for help with the crystal-structure determi-
nations.
[1]
M. Machuqueiro, T. Darbre, J. Inorg. Biochem. 2003, 94,
193Ϫ196.
U. Brand, H. Vahrenkamp, Inorg. Chem. 1995, 34, 3285Ϫ3293.
J. J. Wilker, S. Lippard, Inorg. Chem. 1997, 36, 969Ϫ978.
R. Alsfasser, A. K. Powell, S. Trofimenko, H. Vahrenkamp,
Chem. Ber. 1993, 126, 685Ϫ694.
R. G. Mathews, J. T. Drummond, Chem. Rev. 1990, 90,
1275Ϫ1290.
[23]
[24]
[25]
[2]
J. Eichel, J. C. Gonzales, M. Hotze, R. G. Mathews, J. Schröder,
Eur. J. Biochem. 1995, 230, 1053Ϫ1058.
[3]
A. P. Breksa, T. A. Garrow, Biochemistry 1999, 38,
13991Ϫ13998.
416
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
Eur. J. Inorg. Chem. 2004, 409Ϫ417

(Neocuproin)zinc Thiolates
FULL PAPER
M. Förster, R. Burth, A. K. Powell, T. Eiche, H. Vahrenkamp,
Chem. Ber. 1993, 126, 2643Ϫ2648.
H. Bürger, W. Sawodny, U. Wannagat, J. Organomet. Chem.
1965, 3, 113Ϫ120.
A. Lüttringhaus, K. Hägele, Angew. Chem. 1955, 67, 304Ϫ305.
J. J. Mayerle, S. E. Denmark, P. V. dePamphilis, J. A. Ibers, R.
H. Holm, J. Am. Chem. Soc. 1975, 97, 1032Ϫ1045.
P. Bonviccini, A. Levi, V. Lucchini, G. Scorrano, J. Chem. Soc.,
Perkin Trans. 2 1972, 2267Ϫ2269.
[26]
[41]
[42]
M. Ruf, R. Burth, K. Weis, H. Vahrenkamp, Chem. Ber. 1996,
129, 1251Ϫ1257.
[27]
R. Burth, H. Vahrenkamp, Z. Anorg. Allg. Chem. 1998, 624,
381Ϫ385.
M. Rombach, H. Vahrenkamp, Inorg. Chem. 2001, 40,
6144Ϫ6150.
[43]
[44]
[28]
[29]
U. Brand, M. Rombach, H. Vahrenkamp, Chem. Commun.
[45]
[46]
[47]
[48]
[49]
[50]
1998, 2717Ϫ2718.
U. Brand, M. Rombach, J. Seebacher, H. Vahrenkamp, Inorg.
[30]
D. Villemin, M. Hachemi, Synth. Commun. 1996, 26,
2449Ϫ2460.
R. C. Chambers, C. L. Hill, J. Am. Chem. Soc. 1990, 112,
Chem. 2001, 40, 6151Ϫ6157.
R. Burth, H. Vahrenkamp, Inorg. Chim. Acta 1998, 228,
193Ϫ199.
A. Meißner, W. Haehnel, H. Vahrenkamp, Chem. Eur. J. 1997,
3, 261Ϫ267.
M. Tesmer, H. Vahrenkamp, Eur. J. Inorg. Chem. 2001,
1183Ϫ1188.
K. J. Jordan, W. F. Wacholtz, G. A. Crosby, Inorg. Chem. 1991,
30, 4588Ϫ4593.
A. J. Pallenberg, T. M. Marschner, D. M. Barnhart, Polyhedron
[31]
8427Ϫ8433.
[32]
T. Okajima, Z. H. Wang, Y. Fukazawa, Chem. Lett. 1991, 1,
37Ϫ40.
W. F. Law, C. Kim, M. Y. Darensbourg, A. L. Rheingold, J.
Am. Chem. Soc. 1989, 111, 3591Ϫ3597.
[33]
[34]
CCDC-215926 (1c), -215927 (1d), -215928 (1g), -215929 (1h),
-215930 (3g), -215932 [(neo)ZnI2], and -215931 (5) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html [or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: (in-
ternat.) ϩ 44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
G. M. Sheldrick, SHELXS-86 and SHELXL-93, Programs for
Crystal Structure Determination, University of Göttingen, 1986
and 1993.
[35]
1997, 16, 2711Ϫ2719.
K. Weis, M. Rombach, M. Ruf, H. Vahrenkamp, Eur. J. Inorg.
[36]
Chem. 1998, 263Ϫ270.
K. Weis, H. Vahrenkamp, Eur. J. Inorg. Chem. 1998, 271Ϫ274.
G. P. Tuszynski, M. Frederick, R. G. Kallen, J. Am. Chem. Soc.
[37]
[51]
[52]
[38]
1975, 97, 7359Ϫ7370.
M. Tesmer, M. Shu, H. Vahrenkamp, Inorg. Chem. 2001, 40,
4022Ϫ4029.
[39]
E. Keller, SCHAKAL for Windows, Universität Freiburg, 2001.
Received July 24, 2003
[40]
M. Shu, R. Walz, B. Wu, J. Seebacher, H. Vahrenkamp, Eur. J.
Early View Article
Inorg. Chem. 2003, 2502Ϫ2511.
Published Online November 19, 2003
Eur. J. Inorg. Chem. 2004, 409Ϫ417
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
417