Remarkably selective recognition of iodobenzene derivatives by a macrocyclic bis-PtII metallohost

Article abstract of DOI:10.1002/chem.201101650

We designed and synthesized self-assembled bis-Pt^II dimer 14 BF₄ with quino[8,7-b][1,10]phenanthroline as an extended π-face contact area, which acts as the first artificial receptor with high affinity toward iodinated aromatic compo

Full text of DOI:10.1002/chem.201101650

DOI: 10.1002/chem.201101650
Remarkably Selective Recognition of Iodobenzene Derivatives by a
Macrocyclic Bis-PtII Metallohost
Robert Trokowski,[a] Shigehisa Akine,[a, b] and Tatsuya Nabeshima*[a, b]
Abstract: We designed and synthesized
self-assembled bis-PtII dimer 1·4BF4
with quinoACHTUNGTRENNUNG[8,7-b]ACHTUNGTRENNUNG[1,10]phenanthroline
titration revealed a high affinity of 14+
towards haloarenes, with exceptionally
large association constants for 2-iodo-
phenol (Ka =16000mꢀ1) and 1,2-diiodo-
benzene (Ka =21000mꢀ1), which are
93- and 140-fold higher, respectively,
than the values obtained for 24+. In ad-
dition, 14+ showed a remarkably high
affinity and selectivity toward 2,6-diio-
dophenol (Ka =35000mꢀ1), which is an
important substructure of the thyroid
hormone T4. X-ray crystallography and
theoretical calculations strongly suggest
that “side-on” iodine···aromatic-plane
interactions and p–p stacking contrib-
ute to the strong 1,2-diiodobenzene
and 2,6-diiodophenol binding. The re-
sults obtained here give unique and
valuable insight into the nature of halo-
gen atom interactions in their “side-
on” region with an electropositive aro-
matic plane, which may provide useful
guidance for designing artificial recep-
tors for iodinated biomolecules.
as an extended p-face contact area,
which acts as the first artificial receptor
with high affinity toward iodinated aro-
matic compounds significantly based
on noncovalent iodine···aromatic-plane
interactions in a “side-on” fashion. De-
spite their structural similarity to a pre-
viously reported metallohost 24+ that
bears 2,2’:6’,2’’-terpyridine units, a dra-
matic change in selectivity toward sub-
stituted benzene derivatives was ob-
Keywords: iodine · macrocycles ·
molecular recognition · platinum ·
self-assembly
1
served for 14+. H NMR spectroscopic
Introduction
The appropriate combination of several noncovalent interac-
tions, including halogen bonds,[1] can result in strong and
precise molecular recognition. In particular, because of an
anisotropic distribution of electron density around the halo-
gen nucleus, iodine atoms in iodine-containing substances
are able to participate in noncovalent interactions with elec-
tron-rich atoms or groups in a “head-on” way (Scheme 1) to
form more efficient halogen bonding in artificial[2] and bio-
logical recognition systems[3] when compared to the other
halogens. For example, I···O halogen-bonding and hydro-
phobic effects simultaneously contribute to the recognition
of thyroid hormones by their specific receptors.[3a,d,e] Elec-
tron-deficient species such as protons of hydrogen-bond
donors and metal ions can, on the other hand, also interact
Scheme 1. The “side-on” and “head-on” interacting regions of the iodine
atom in an iodoarene.
ꢀ
ꢀ
with halogen atoms in organic molecules to make C X···H
n+
C[4] and C X···M bonds[5,6] in which “side-on” interactions
ꢀ
are often observed (Scheme 1). As hydrogen-bond accept-
ors, iodides and fluorides respectively form the weakest and
ꢀ
ꢀ
strongest noncovalent C X···H C interactions among the
halides. Although many examples of such hydrogen bonds
n+
ꢀ
and C X···M interactions have been reported, noncova-
[a] Dr. R. Trokowski, Dr. S. Akine, Dr. T. Nabeshima
Graduate School of Pure and Applied Sciences
University of Tsukuba
lent “side-on” interactions between the electron-deficient ar-
omatic plane and the electron-rich side periphery[7] of an
iodine atom in iodinated compounds have rarely been inves-
tigated.[8] In these limited studies, “side-on” interactions be-
tween the iodine atoms and the aromatic surface of the
metal complexes were suggested. However, the noncovalent
interactions with the iodinated benzene derivatives were not
elucidated clearly enough to enable application of the “side-
on” interactions to the design of artificial receptors. We re-
cently reported the quantitative synthesis and binding prop-
erties of self-assembled bis-PtII dimer 2·4BF4,[9] which can
act as a synthetic receptor because of its ability to selective-
1-1-1 Tennodai, Tsukuba
Ibaraki 305-8571 (Japan)
Fax : (+81)29-853-4507
E-mail: nabesima@chem.tsukuba.ac.jp
[b] Dr. S. Akine, Dr. T. Nabeshima
Tsukuba Research Center for
Interdisciplinary Materials Science
University of Tsukuba, 1-1-1 Tennodai
Tsukuba, Ibaraki 305-8571 (Japan)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101650.
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Chem. Eur. J. 2011, 17, 14420 – 14428

FULL PAPER
ly bind to electron-rich aromatic compounds such as benze-
tant model for designing molecular recognition systems
ꢀ
nediols through attractive noncovalent p–p stacking and C
based on noncovalent iodine···aromatic-plane interactions.
H···O interactions. The parallel arrangement of the two elec-
tron-deficient aromatic terpyridine planes in 2·4BF4 inspired
us to utilize a similar rectangular framework for recognizing
halogenated aromatic compounds on the basis of the “side-
on” interaction mode between the PtII·ligand planes and the
halogen atoms (Scheme 2), although the binding constants
Results and Discussion
[1,10]phenanthroline (dpya)[10] is a tridentate
QuinoACTHNUGTRENNUG[8,7-b]ACHUTNGTRENNGUN
chelator structurally similar to 2,2’:6’,2’’-terpyridine, which
has often been employed as a
building unit for various metal-
lo-supramolecular
architec-
tures[14,15] because of its strong
coordination ability to metal
ions. Since the aromatic plane
of dpya has a more extended p-
electron area than that of ter-
pyridine, metallohosts that con-
sist of dpya moieties would be
expected to show stronger and
more selective guest recogni-
tion due to various noncovalent
ꢀ
interactions (p–p stacking, C
H···p, cation···p, and so on) for
which an aromatic p-electron
surface is responsible. Despite
the structural similarity to ter-
pyridine, only a few metal com-
plexes of dpya have been re-
ported.[11] In addition, no dpya
derivative has been utilized to
construct supramolecular sys-
tems to date. We predicted,
however, that with its etheno
bridging moiety to enhance
metal-binding affinities (as seen
Scheme 2. Design of novel metallohosts for recognition of iodoarenes on the basis of the “side-on” interaction
mode.
of 2·4BF4 with chlorinated benzene derivatives were small.
To enhance these noncovalent aromatic interactions, we de-
signed and synthesized the self-assembled bis-PtII dimer
1·4BF4 with extended p-face contact areas. The aromatic
in the differing coordination properties of 2,2’-bipyridine
and 1,10-phenanthroline[16]) dpya should also exhibit strong
coordination ability toward a PtII ion[17] to give the corre-
sponding square-planar complex.
[1,10]phenanthroline (dpya)[10–12] is
plane of quinoACHTUNGTRENNUNG[8,7-b]AHCTUNGTRENNGUN
large enough to effectively interact with a variety of ben-
zene derivatives that bear small substituents such as halogen
atoms. In addition, it has been reported that a larger aro-
matic p-electron surface in some metal complexes can result
in a larger binding affinity to iodine substituents.[8] Thus, we
envisaged that the dpya-containing metallohost 14+ would
Synthesis of self-assembled bis-PtII dimer: Ligand 6 was pre-
pared by a two-step process as outlined in Scheme 3. A pal-
ladium-catalyzed Suzuki cross-coupling reaction of 4[12a] with
the phenylboronic pinacol ester derivative 3[9] yielded 5a,
which was partially aromatized to 5b (detected by ESI-MS;
Figure S1 in the Supporting Information). Subsequent aro-
matization of 5a and 5b produced crystalline 6, which was
characterized by a variety of analytical techniques, including
NMR spectroscopy, ESI-mass spectrometry, elemental anal-
ysis, and X-ray crystallography. The single-crystal X-ray
structure shows that the nitrogen atoms (N2, N4) in ligand 6
(Figure 1) are oriented in the same direction, and the dihe-
dral angle between the plane of the terminal pyridyl ring
and the plane of the central pyridyl ring of the dpya moiety
is about 728. Compound 1·4BF4 was quantitatively synthe-
show more precise and stronger guest recognition than 24+
.
Gratifyingly, the host 14+ exhibited a surprisingly high bind-
ing affinity toward iodo-substituted benzene derivatives
such as 1,2-diiodobenzene, 2-iodophenol, and 2,6-diiodophe-
nol, which are substructures of the thyroid hormones T3 and
T4.[13] This high binding affinity is considered to result from
a combination of several intermolecular interactions, includ-
ing “side-on” iodine···aromatic-plane and p–p stacking inter-
actions. To the best of our knowledge, this result is the first
example of an artificial receptor with high affinity toward
iodinated aromatic compounds, thereby providing an impor-
sized by the reaction of the ligand 6 with [Pt
ACHUTGTNNERNUG(cod)HCATUNGTNER(NUGN MeCN)2]-
1
AHCTUNGTRENNUNG
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14421

T. Nabeshima et al.
incorporates a solvent benzene
molecule inside the cavity. It is
noteworthy that the conforma-
tional geometry of the ligand
moieties in 14+ did not signifi-
cantly differ from that in the
uncomplexed 6. The angle be-
tween the ancillary pyridyl ring
and the plane of the central
pyridyl ring of the dpya moiety
in the 14+·benzene complex re-
mained
almost
unchanged
(about 748). The mean distance
between the two parallel planes
of the central pyridyl rings in
the dpya moieties is 7.05 ꢁ.
The resultant cavity is occupied
by one benzene molecule. This
clearly indicates that this bis-
PtII dimer 14+ is suitable for
recognition of planar aromatic
molecules.
Scheme 3. Synthesis of 1·4BF4: a) [PdACTHUNRGTENNG(U PPh3)4], K2CO3, dioxane; b) Pd/C, C6H5NO2; c) [PtACHUTGNTREN(NUGN cod)I2], AgBF4,
CH3CN.
Figure 1. Crystal structure of 6 with thermal ellipsoids plotted at the 20%
probability level. Hydrogen atoms are omitted for clarity.
spectrum of 1·4BF4 indicated the quantitative formation of
one single symmetric species that showed significant down-
field shifts of the pyridyl protons (H8 and H9; see Scheme 2
for atom numbering) due to PtII coordination and upfield
shifts of the dpya protons (H1), which are probably attribut-
able to a shielding effect by the coordinated terminal pyridyl
ring (Figure S2 in the Supporting Information). Convincing
Figure 2. Crystal structure of 14+·benzene with thermal ellipsoids plotted
at the 50% probability level. Solvent molecules, PF6 counterions, and
hydrogen atoms are omitted for clarity.
ꢀ
evidence to support the formation of dimer 62·PtII (=14+
)
2
was provided by ESI-MS analysis (m/z 352.58 for 14+
,
499.11 for [1+BF4]3+, and 792.17 for [1+2BF4]2+ (Figure S3
in the Supporting Information).
Recognition of aromatic guests by 14+ and 24+: The com-
plexation ability of 14+ with benzene derivatives in solution
Single crystals of the metallohost suitable for X-ray crys-
tallography were successfully obtained when the counterions
1
was studied by H NMR spectroscopy. Titration experiments
ꢀ
were exchanged for PF6 . The X-ray crystallographic analy-
in [D6]DMSO showed binding affinities of 14+ toward elec-
tron-rich benzenediols such as 1,4-benzenediol that were 8–
9 times higher than those of 24+. It is particularly worth
sis (Figure 2) revealed a rectangular dimeric self-assembled
structure that consisted of the ligand 6 and platinum(II) that
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Iodobenzene Derivatives
FULL PAPER
Table 1. Association constants for various aromatic guests with 1·4BF4
(Ka,1) and 2·4BF4 (Ka,2).[a]
protons have been used to determine the association con-
stants by nonlinear least-squares regression. The Ka values
of 14+ and 24+ with various guests are summarized in
Table 1. It is apparent that replacement of the terpyridine
units of 24+ by dpya building blocks significantly changed
the recognition properties. The overall binding affinity
toward planar aromatic compounds increased along with a
particularly significant difference in binding affinity toward
halogenated benzene derivatives. Compared to 24+, the
binding affinity enhancement toward the haloarenes was at
least 20-fold. A maximum enhancement of binding of 140-
fold was observed with 1,2-diiodobenzene. It is noteworthy
that the binding affinity tendency of 14+ and 24+ toward 1,2-
diiodobenzene, 2-iodophenol, and benzene-1,2-diol is oppo-
site. The calculated electrostatic potential surfaces (Fig-
ure S6 in the Supporting Information) of the aromatic com-
pounds showed that there is an electronegative “side-on”
region around the iodine atoms that can contribute to non-
covalent interactions of the iodine atoms with the electro-
positive surfaces (vide infra) of dpya. From an electrostatic
point of view, hydroxy-substituted benzene derivatives
would form more stable complexes through p–p stacking in-
teractions with electron-poor cationic hosts because the aro-
matic guests have a significantly more negative electrostatic
potential surface over the aromatic ring than the haloarenes
(Figure S7 in the Supporting Information). The binding ten-
dency of 24+ is consistent with this hypothesis. However,
this situation is not the case in 14+. Thus, it is reasonable to
assume that strong but different noncovalent interactions
between the large surface of dpya and the iodine atoms sig-
nificantly contribute to the observed binding strength of 14+
toward the iodobenzene derivatives. This finding is in agree-
ment with the results reported by Yamauchi and co-work-
ers.[8] They suggested that the stability enhancement is
caused by weak bonding interactions between the iodine
atom and the pyridine ring in ternary CuII p-stacked com-
plexes. Moreover, the electrostatic potential surfaces of
chlorobenzene, bromobenzene, and iodobenzene (Fig-
ure S7)[18] show that these halobenzenes have nearly the
same negative electrostatic potential over their rings. Conse-
quently, electrostatic interactions should have a similar con-
tribution to the guest binding. However, interactions be-
tween 14+ and monohalogenated benzenes increase when
switching from chloro- to bromo-, and then to iodobenzene
(Ka =114, 255, and 403mꢀ1, respectively). Notably, 14+ binds
iodobenzene more strongly than phenol (Ka =257mꢀ1). This
result strongly suggests the important contribution of halo-
gen···p “side-on” interactions to the binding affinity of 14+
with the iodinated benzene derivatives. In complexes of 14+
and 24+ with disubstituted benzene derivatives, the position
of the substituents of the guests also significantly affects
their binding affinity. In the series of diiodobenzenes,
ortho>meta>para selectivity was observed. The highest af-
finity of 14+ toward 1,2-diiodobenzene is likely the result of
efficient noncovalent interactions of both of the iodine
atoms with the p faces of the dpya units. The X-ray crystal
structure of the complex of 14+ with 1,2-diidodobenzene
Guest
Ka,1 [mꢀ1
]
Ka,2 [mꢀ1
]
Ka,1/Ka,2
2,6-diiodophenol
1,2-diiodobenzene
2-iodophenol
35000ꢁ6000
21000ꢁ3000
16000ꢁ2000
10000ꢁ1700
4600ꢁ300
3040ꢁ160
2240ꢁ140
2200ꢁ90
2100ꢁ100
1700ꢁ80
1650ꢁ90
1490ꢁ70
1240ꢁ80
890ꢁ30
700ꢁ20
146ꢁ10
172ꢁ3
102ꢁ5
50
140
93
98
8.7
8.9
–
9.1
–
57
20
–
46
44
–
–
27
–
1,3,5-tribromobenzene
benzene-1,4-diol
benzene-1,3-diol
1,3-diiodobenzene
benzene-1,2-diol
1,3,5-trichlorobenzene
1,4-dibromobenzene
1,4-diiodobenzene
1,3-dibromobenzene
1,2-dibromobenzene
1,4-dichlorobenzene
1,3-dichlorobenzene
iodobenzene
530ꢁ30[b]
341ꢁ13[b]
–
243ꢁ25[b]
–
30ꢁ2
81ꢁ5
–
27ꢁ2
20ꢁ2[b]
487ꢁ13
–
–
403ꢁ13
1,2-dichlorobenzene
phenol
bromobenzene
chlorobenzene
benzene
298ꢁ19
11ꢁ2[b]
257ꢁ10
–
–
–
–
–
255ꢁ6
–
–
–
–
114ꢁ6
36ꢁ4
1,4-difluorobenzene
18ꢁ2
[a] Determined by 1H NMR spectroscopy ([D6]DMSO, 258C). [b] Re-
ported previously.[9]
noting that 14+ showed a surprisingly high binding affinity
toward iodinated benzene derivatives (Table 1). The
1H NMR spectra of the host 14+ upon addition of increasing
amounts of 1,2-diiodobenzene are shown in Figure 3. Con-
Figure 3. 1H NMR spectral changes upon addition of 1,2-diiodobenzene
to 1·4BF4 (1 mm, [D6]DMSO, 258C). See Scheme 2 for proton numbering
of 14+
.
vincing evidence to support the formation of this host–guest
complex is a large upfield shift of the 1,2-diiodobenzene
protons (Ha and Hb in Figure 3). Job plots from the
1H NMR spectra showed the 1:1 binding stoichiometry (Fig-
ure S4 in the Supporting Information), and the formation of
the 1:1 complex was also confirmed by ESI-MS analysis
(Figure S5 in the Supporting Information). In all of the titra-
tions, the downfield shifts of the well-separated H8 pyridyl
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14423

T. Nabeshima et al.
tion. Excellent similarity between the solution and solid-
state structures of the 14+·1,2-diiodobenzene complex was
supported by NOESY measurements, in which NOE corre-
lations were observed between the inner cavity protons (H6,
H7, and H8) of 14+ and the Ha protons of 1,2-diiodobenzene
(Scheme 4). Additionally, the Hb protons of 1,2-diiodoben-
Scheme 4. Illustration of observed intermolecular NOE correlations be-
tween 14+ and 1,2-diiodobenzene.
zene exhibited a larger upfield shift (Ddꢂ1.84; Figure 6)
than the Ha protons (Ddꢂ0.83). The single-crystal X-ray dif-
fraction structure of the 14+·1,2-diiodobenzene complex
thoroughly elucidates the larger upfield shift, because in the
solid the Hb protons are located at the position that is most
affected by the anisotropic effect of the dpya planes.
Figure 4. Crystal structure of 14+·1,2-diidodobenzene with thermal ellip-
soids plotted at the 20% probability level. Solvent molecules, PF6 coun-
terions, and hydrogen atoms are omitted for clarity.
ꢀ
(Figure 4) clearly shows that 1,2-diiodobenzene is deeply
buried inside the cavity. Both of the iodine atoms make van
der Waals contacts with carbon atoms of the dpya units with
ꢀ
the shortest interatomic C···I contact near 3.8 ꢁ (C44 I1,
ꢀ
C8 I2). In addition, p–p stacking interactions were found
between the host and guest aromatic rings with the shortest
ꢀ
ꢀ
interatomic contact at about 3.4 ꢁ (C77 C1, C77 C41).
Thus, the two dpya units of 14+ are no longer parallel to
each other and give a slightly tilted structure; the iodine
side of 14+ is more widely open to accommodate the two
iodine atoms. The electrostatic potential surface was deter-
mined by using theoretical calculations based on the X-ray
host structure to confirm that the inner dpya walls provide a
positively charged binding cavity (Figure 5). Interestingly,
the surface of the inner walls is more positive than that of
the outside as seen in 24+. This result again supports the hy-
pothesis that the cavity should be suitable for arene recogni-
Figure 6. 1H NMR spectrum of a mixture of 1·4BF4 and 1,2-diiodoben-
zene ([1·4BF4]=6 mm, [1,2-diiodobenzene]=3 mm, [D6]DMSO, 258C),
>98% of the guest in bound form.
Interestingly, compared to its selectivity for diiodoben-
zenes, the selectivity of 14+ toward benzenediols, dichloro-
benzenes, and dibromobenzenes was reversed, and a para>
meta>ortho trend was observed. This selectivity strongly
suggests that additional noncovalent interactions with inside
ꢀ
ꢀ
ꢀ
cavity protons such as C H···O, C H···Cl, and C H···Br in-
fluence the binding of benzenediols, dichlorobenzenes, and
dibromobenzenes by 14+. Interestingly, the para>meta>
ortho trend is more significant in the series of dichloroben-
zenes than with dibromobenzenes. This fact may suggest
ꢀ
that the larger bonding strength of C H···halogen interac-
tions more effectively determines the binding selectivity.
The para>meta>ortho binding selectivity trend of 14+
toward benzenediols was also observed for the terpyridine-
based dimer 24+, which we have previously reported.[9] We
found that the protons of 24+ inside the cavity form multiple
Figure 5. Electrostatic potential surface of 14+ calculated by DFT
(B3LYP, 6-31G*, single-point calculation[19]) with the crystal structure of
14+ as input.
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Iodobenzene Derivatives
FULL PAPER
ꢀ
ꢀ
C H···O hydrogen bonds with the oxygen atoms of guest
benzenediol molecules. It is therefore reasonable to assume
3.434(11) ꢁ (C21 O1*; the H···O distance is 2.55 ꢁ and the
ꢀ
C H···O angle is 155.148). The centrosymmetric crystal
structure of 14+·benzene-1,4-diol clearly indicates that both
hydroxy groups of benzene-1,4-diol can simultaneously in-
teract with the host sidewall with the C H···O interaction.
On the other hand, only one of the hydroxy groups of ben-
zene-1,3- and -1,2-diols can participate in the C H···O inter-
action because of the shorter OH OH distances (Figure 7b
ꢀ
that C H···O hydrogen bonding also controls the binding of
benzenediols by 14+. X-ray crystallographic analysis clearly
rationalized the selectivity of 14+ toward benzene-1,4-diol
(Figure 7a). In the crystal structure, the guest benzene-1,4-
diol is held inside the cavity between the two platinum-con-
taining aromatic planes. The mean distance between the two
parallel planes of the central pyridyl rings in the dpya moiet-
ies is 6.72 ꢁ, indicative of the efficient p–p stacking interac-
tions between 14+ and benzene-1,4-diol. In addition to the
parallel-displaced p–p stacking interactions, there are signif-
ꢀ
ꢀ
ꢀ
and c). This difference may account for the selectivity of 14+
toward benzene-1,4-diol among the three isomers. It should
also be noted that the highest association constant among
the investigated guests was observed for 2,6-diiodophenol.
The association constant of 35000mꢀ1 is much higher than
those of the three diiodobenzenes (1650–21000mꢀ1) or 2-io-
dophenol (16000mꢀ1). This result clearly indicates that both
of the halogen atoms and the
ꢀ
icant C H···O hydrogen bonds between the sidewall protons
of the cavity of 14+ and the hydroxy oxygen atoms of ben-
zene-1,4-diol. For example, the shortest C···O distance is
hydroxy group contribute to the
strong binding. The X-ray struc-
ture also confirmed that 2,6-
diiodophenol is suitably sand-
wiched between the two dpya
moieties of 14+ (Figure 8). It is
well known that the 2,6-diiodo-
phenyl fragment is seen in thy-
roid hormones such as thyroxin
and triiodothyronine as well as
their precursor, diiodotyrosine.
The platinum-containing frame-
work of 14+ that bears cationic,
large
p-aromatic
surfaces
should therefore be potentially
useful as the binding part of a
receptor that can selectively
bind such thyroid hormone de-
rivatives.
Conclusion
Coordination of 6 to PtII quan-
titatively gave the macrocyclic
metallodimer
14+
,
which
showed efficient recognition of
planar aromatic guest mole-
1
cules as evidenced by H NMR
spectroscopy and X-ray diffrac-
tion studies. The metallorecep-
tor 14+ was designed on the
basis of rational derivatization
of previously reported 24+
through the extension of the p-
recognition area. Despite their
structural similarity, a dramatic
change in selectivity toward
substituted benzene derivatives
was observed for 14+ compared
Figure 7. Crystal structures of a) 14+·benzene-1,4-diol, b) 14+·benzene-1,3-diol, and c) 14+·benzene-1,2-diol with
thermal ellipsoids plotted at the 50% probability level. Solvent molecules, counterions, and hydrogen atoms
are omitted for clarity.
to 24+ 1H NMR spectroscopic
.
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T. Nabeshima et al.
Synthesis of compound 5a: Compound 4[12a] (6.69 g, 15.2 mmol), 3[9]
(4.96 g, 17.6 mmol), and tetrakis(triphenylphosphane)palladium(0)
(0.88 g, 0.76 mmol) were placed in a 250 mL round-bottomed flask. Diox-
ane (100 mL) degassed through three freeze–pump–thaw cycles and po-
tassium carbonate (5.25 g, 38.0 mmol) was added, and the resulting mix-
ture was then stirred at 808C for 16 h. The mixture was poured into
water and extracted with chloroform (80 mL four times). The combined
organic layer was dried over anhydrous magnesium sulfate. The solvents
were removed and the crude product was purified by column chromatog-
raphy (CHCl3/MeOH/Et3N 50:6:1) to give a mixture of 5a and 5b (6.2 g,
about 80%), which was used in the next step without further purifica-
tion.
Synthesis of compound 6: The mixture of 5a and 5b (1.84 g, about
3.6 mmol), 10% Pd/C (1.37 g), and nitrobenzene (110 mL) were placed
together into a 250 mL round-bottomed flask. The resulting mixture was
then stirred at 1508C under argon for 3.5 h. The reaction mixture was
then cooled, the catalyst was filtered through a celite bed, and the filter
cake was washed with methanol and dichloromethane. Solvents were re-
moved under reduced pressure and the residue was subjected to column
chromatography (CHCl3/MeOH/NH3aq 50:6:0.03) on silica gel to afford 6
(1.24 g, 2.43 mmol, 68%) as
a
white solid. M.p. ꢃ3008C; 1H NMR
(400 MHz, [D6]DMSO): d=7.46 (dd, J=7.9, 4.8 Hz, 1H), 7.61 (d, J=
7.1 Hz, 1H), 7.64 (t, J=7.6 Hz, 1H), 7.72 (d, J=9.2 Hz, 2H), 7.76 (d, J=
7.6 Hz, 1H), 7.86 (t, J=7.8 Hz, 1H), 7.89–7.92 (m, 3H), 8.01 (d, J=
9.2 Hz, 2H), 8.11 (s, 1H), 8.14 (s, 1H), 8.14–8.19 (m, 2H), 8.55–8.57 (m,
3H), 9.00 (d, J=2.1 Hz, 1H), 9.27 ppm (d, J=3.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=123.61, 123.78, 125.07, 126.18, 126.32, 126.66,
126.92, 127.04, 127.40, 128.84, 129.19, 129.38, 129.77, 134.52, 136.13,
136.42, 136.62, 138.73, 141.22, 141.25, 145.81, 146.41, 146.85, 148.39,
148.75, 150.15 ppm; ESI-MS (positive): m/z: 511 [M+H]+; elemental
analysis calcd (%) for C36H22N4·1.3H2O: C 80.97, H 4.64, N 10.49; found:
C 80.87, H 4.63, N 10.12.
Figure 8. Crystal structure of 14+·2,6-diiodophenol with thermal ellipsoids
plotted at the 20% probability level. Solvent molecules, PF6 counter-
ions, and hydrogen atoms are omitted for clarity.
ꢀ
Synthesis of bis(m-{7-
[1,10]phenanthroline-kN1,kN1’,kN1’’})diplatinum(4+)
(1·4BF4): Silver tetrafluoroborate (168 mg, 0.863 mmol) was added to a
suspension of (cycloocta-1,5-diene)diiodoplatinum(II) (230 mg,
G
ACHTUNGTRENNUNG[8,7-b]-
AHCTUNGTRENNUNG
titration revealed a high affinity of 14+ towards haloarenes,
with exceptionally large association constants for 2-iodophe-
nol
(Ka =16000mꢀ1)
and
1,2-diiodobenzene
(Ka =
0.413 mmol) in acetone (5 mL), and the mixture was stirred for 10 min.
Then the AgI precipitate was removed by filtration, and the solvent was
evaporated. The obtained residue was dissolved in acetonitrile (10 mL)
and then added to a solution of 6 (109 mg, 0.213 mmol) in acetonitrile
(70 mL). The reaction mixture was stirred at room temperature for
3 days. The solvents were evaporated to dryness, and the residue was
treated with acetone. The yellow solid was filtered off, washed with
water, then acetone, and dried in vacuum to afford 1·4BF4 (185 mg,
0.0918 mmol, 86%). 1H NMR (400 MHz, [D6]DMSO): d=7.84 (d, J=
7.6 Hz, 2H), 7.89 (d, J=9.4 Hz, 4H), 7.90 (t, J=7.9 Hz, 2H), 7.94 (s,
2H), 7.99 (t, J=7.6 Hz, 2H), 8.03 (s, 2H), 8.08 (dd, J=8.2, 5.3 Hz, 4H),
8.08 (d, J=7.9 Hz, 2H), 8.13 (J=7.9 Hz, 2H), 8.13 (dd, J=8.4, 5.1 Hz,
2H), 8.20 (d, J=9.4 Hz, 4H), 8.20 (d, J=7.6 Hz, 2H), 8.41 (d, J=5.3 Hz,
4H), 8.81 (dt, J=8.4, 1.5 Hz, 2H), 8.98 (d, J=8.1 Hz, 4H), 9.33 (d, J=
5.1 Hz, 2H), 9.52 ppm (d, J=1.3 Hz, 2H); 13C NMR (100 MHz,
[D6]DMSO): d=126.21, 126.55, 127.19, 127.42, 128.22, 128.48, 128.86,
129.09, 129.35, 129.43, 129.56, 130.36, 130.70, 132.18, 132.51, 135.48,
139.14, 139.51, 140.11, 140.73, 141.64, 144.43, 149.89, 151.04, 151.48,
154.36 ppm; ESI-MS (positive): m/z: 352.58 [14+]; elemental analysis
calcd (%) for C72H44B4F16N8Pt2·CH3CN·1.8CHCl3: C 45.19, H 2.44, N
6.26; found: C 45.19, H 2.65, N 6.40.
21000mꢀ1), which are 93- and 140-fold higher, respectively,
than the values obtained for 24+. In addition, 14+ showed a
remarkably high affinity and selectivity toward 2,6-diiodo-
phenol (Ka =35000mꢀ1), which is an important substructure
of the thyroid hormone T4. Structural analyses strongly sug-
gest that “side-on” iodine···aromatic plane interactions and
p–p stacking contribute to the strong 1,2-diiodobenzene and
2,6-diiodophenol binding. The results obtained here give
unique and valuable insight into the nature of halogen atom
interactions in their “side-on” region with an electropositive
aromatic plane, which may provide useful guidance for de-
signing artificial receptors for iodinated biomolecules.
Experimental Section
General: All of the chemicals were of reagent grade and were used as re-
ceived. The NMR spectroscopic experiments were performed using a
Bruker AVANCE400 spectrometer. [D6]DMSO was used in all the NMR
spectroscopic titration measurements as the solvent of choice due to the
low solubility of 1·4BF4 in other common solvents. The chemical shifts
were measured from the internal TMS reference. All the NMR spectro-
scopic data were processed using the iNMR software (version 2.3.1).
Mass spectra under the conditions of electrospray ionization were record-
ed using an Applied Biosystems Qstar/Pulsar i. Elemental analyses were
performed using a Yanagimoto CHN corder MT-6. Melting points were
obtained using a Yanaco melting-point apparatus and are uncorrected.
2,6-Diiodophenol was synthesized according to the literature.[20]
1H NMR spectroscopic titration: For each complex, 11 samples were pre-
pared with an increasing guest/host ratio. For each one, a stock solution
(250 mL) of host (4 mm) was mixed with a varying amount of a stock solu-
1
tion of guest, and the volume was adjusted to 500 mL. All H NMR spec-
troscopic titration measurements were performed at least twice and were
carried out at 258C (controlled by the temperature-control system of the
NMR spectrometer).
X-ray structure determination: Single crystals of 6 suitable for X-ray
crystallography were obtained by the slow diffusion of diethyl ether into
a solution of 6 in dichloromethane. Single crystals of 1·4PF6·benzene
complex were obtained by the slow diffusion of benzene into a solution
14426
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 14420 – 14428

Iodobenzene Derivatives
FULL PAPER
of 1·4BF4 in DMSO that contained 50 equiv of nBu4N·PF6. Single crystals
of the host–guest complexes of 14+ were obtained by the slow diffusion
of benzene into a mixture of 1·4BF4, guest, and 50 equiv of nBu4N·PF6 in
DMSO. The X-ray diffraction intensities were collected with MoKa radia-
tion (l=0.71069 ꢁ) at 120 K by using a Rigaku R-AXIS RAPID diffrac-
tometer. The reflection data were corrected for Lorentz and polarization
factors, and for absorption using the multiscan method. The structure was
solved by Patterson methods (DIRDIF 99[21]) and refined by full-matrix
least-squares on F2 by using all the data (SHELXL 97[22]). The crystallo-
graphic data are summarized in Tables 2, 3, and 4.
Table 4. Crystallographic data (continued).
Compound
1·4PF6·1,4-C6H4[OH]2·
4DMSO·5C6H6
1·4PF6·2.33C6H3I2OH·
2DMSO·0.33C6H6
formula
Mr
C116H104F24N8O6P4Pt2S4
2804.37
C92H67.33F24I4.67N8O4.33P4Pt2S2
2980.59
monoclinic
C2/c
65.719(5)
14.7112(13)
30.962(2)
90.00
96.7679(16)
90.00
29726(4)
12
crystal system
space group
a [ꢁ]
b [ꢁ]
c [ꢁ]
triclinic
P1
¯
11.8059(8)
14.7076(9)
16.8096(13)
98.035(2)
106.941(2)
91.0846(18)
2759.2(3)
1
a [8]
b [8]
Table 2. Crystallographic data.
g [8]
V [ꢁ3]
Z
Compound
6
1·4PF6·4DMSO·5C6H6 1·4PF6·1,2-C6H4I2·
1.4DMSO·6.6C6H6
T [K]
120
1.688
0.0641
0.1765
120
1.998
0.1166
0.3144
formula
Mr
C36H22N4
510.58
monoclinic triclinic
C110H98F24N8O4P4Pt2S4 C120.4H96F24I2N8O1.4P4Pt2S1.4
1calcd [gcmꢀ3
]
2694.26
2946.00
triclinic
R1[a] (I>2s(I))
crystal
system
space
group
a [ꢁ]
b [ꢁ]
c [ꢁ]
a [8]
[a]
wR2 (all data)
1
¯
¯
2
2
2
2
2
=
P21/n
P1
P1
2
[a] R1 =Sj jFo jꢀjFc j j/SjFo j ; wR2 ={S[w(FoꢀFc) ]/S[w(Fo) ]} .
10.23(2)
25.32(4)
10.235(16) 15.6832(5)
90.00
108.40(6)
90.00
2515(7)
4
13.3367(5)
14.1431(4)
13.9884(13)
14.1274(14)
29.345(2)
90.088(2)
92.782(2)
105.682(3)
5576.1(9)
2
C6H4(OH)2·6DMSO·3C6H6), and CCDC-827328 (6) contain the supple-
mentary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
89.3924(9)
73.2174(11)
72.0142(11)
2683.76(15)
1
b [8]
g [8]
V [ꢁ3]
Z
T [K]
1calcd
120
1.348
120
1.667
120
1.755
Acknowledgements
[gcmꢀ3
]
[a]
R1
0.0613
0.1131
0.0367
0.0906
0.0871
This work was supported by Grants-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan.
(I>2s(I))
wR2[a] (all
data)
0.2497
1
2
2
2
2
2
=
2
[a] R1 =Sj jFo jꢀjFc j j/SjFo j ; wR2 ={S[w(FoꢀFc) ]/S[w(Fo) ]} .
[1] For reviews, see: a) P. Metrangolo, G. Resnati, Chem. Eur. J. 2001, 7,
2511–2519; b) P. Metrangolo, H. Neukirch, T. Pilati, G. Resnati,
Acc. Chem. Res. 2005, 38, 386–395; c) P. Politzer, P. Lane, M. C.
Concha, Y. Ma, J. S. Murray, J. Mol. Model. 2007, 13, 305–311;
d) Halogen Bonding: Fundamentals and Applications (Eds.: P. Me-
trangolo, G. Resnati), Springer, Berlin, 2008; e) P. Metrangolo, G.
Resnati, Science 2008, 321, 918–919.
[2] a) J. P. M. Lommerse, A. J. Stone, R. Taylor, F. H. Allen, J. Am.
Chem. Soc. 1996, 118, 3108–3116; b) P. Metrangolo, F. Meyer, T.
Pilati, G. Resnati, G. Terraneo, Angew. Chem. 2008, 120, 6206–
6220; Angew. Chem. Int. Ed. 2008, 47, 6114–6127; c) R. Bertani, P.
Sgarbossa, A. Venzo, F. Lelj, M. Amati, G. Resnati, T. Pilati, P. Me-
trangolo, G. Terraneo, Coord. Chem. Rev. 2010, 254, 677–695; d) G.
Cavallo, P. Metrangolo, T. Pilati, G. Resnati, M. Sansotera, G. Terra-
neo, Chem. Soc. Rev. 2010, 39, 3772–3783.
[3] a) P. Auffinger, F. A. Hays, E. Westhof, P. S. Ho, Proc. Natl. Acad.
Sci. USA 2004, 101, 16789–16794; b) A. R. Voth, F. A. Hays, P. S.
Ho, Proc. Natl. Acad. Sci. USA 2007, 104, 6188–6193; c) A. R.
Voth, P. Khuu, K. Oishi, P. S. Ho, Nat. Chem. 2009, 1, 74–79; d) Y.
Lu, T. Shi, Y. Wang, H. Yang, X. Yan, X. Luo, H. Jiang, W. Zhu, J.
Med. Chem. 2009, 52, 2854–2862; e) P. Metrangolo, G. Resnati, Nat.
Chem. 2011, 3, 260.
Table 3. Crystallographic data (continued).
Compound
1·2PF6·2BF4·1,2-C6H4[OH]2·
1·4PF6·1,3-C6H4[OH]2·
6DMSO·3C6H6
8DMSO·2C6H6
formula
Mr
crystal system
space group
a [ꢁ]
b [ꢁ]
c [ꢁ]
a [8]
C106H110B2F20N8O10P2Pt2S8
C108H104F24N8O8P4Pt2S6
2804.41
2766.24
monoclinic
C2/c
33.767(2)
15.5570(10)
25.7970(15)
90.00
triclinic
¯
P1
13.4345(9)
14.1445(8)
15.7840(8)
92.7808(16)
108.4957(17)
104.8879(19)
2721.1(3)
1
120
1.711
0.0695
0.2133
b [8]
116.7028(14)
90.00
12106.4(13)
4
g [8]
V [ꢁ3]
Z
T [K]
120
1.518
0.0687
0.2117
1calcd [gcmꢀ3
]
R1[a] (I>2s(I))
[a]
wR2 (all data)
[4] a) L. Brammer, E. A. Bruton, P. Sherwood, Cryst. Growth Des.
2001, 1, 277–290; b) Y. Lu, Y. Wang, Z. Xu, X. Yan, X. Luo, H.
Jiang, W. Zhu, J. Phys. Chem. B 2009, 113, 12615–12621.
1
2
2
2
2
2
=
2
[a] R1 =Sj jFo jꢀjFc j j/SjFo j ; wR2 ={S[w(FoꢀFc) ]/S[w(Fo) ]} .
[5] For a review, see: R. J. Kulawiec, R. H. Crabtree, Coord. Chem. Rev.
1990, 99, 89–115.
[6] For iodoarenes as ligands for transition metals, see: a) R. H. Crab-
tree, J. W. Faller, M. F. Mellea, J. M. Quirk, Organometallics 1982, 1,
1361–1366; b) C. H. Winter, W. R. Veal, C. M. Garner, A. M. Arif,
J. A. Gladysz, J. Am. Chem. Soc. 1989, 111, 4766–4776; c) R. J. Ku-
CCDC-827322 (1·4PF6·4DMSO·5C6H6), CCDC-827323 (1·2PF6·2BF4·1,2-
C6H4(OH)2·8DMSO·2C6H6),
C6H4I2·1.4DMSO·6.6C6H6),
CCDC-827324
(1·4PF6·1,2-
CCDC-827325
(1·4PF6·2.33C6H3I2OH·0.33C6H6·2DMSO), CCDC-827326 (1·4PF6·1,4-
C6H4(OH)2·4DMSO·5C6H6),
CCDC-827327
(1·4PF6·1,3-
Chem. Eur. J. 2011, 17, 14420 – 14428
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14427

T. Nabeshima et al.
lawiec, J. W. Faller, R. H. Crabtree, Organometallics 1990, 9, 745–
755; d) T. M. Gomes-Carneiro, R. D. Jackson, J. H. Downing, A. G.
Orpen, P. G. Pringle, J. Chem. Soc. Chem. Commun. 1991, 317–319;
e) J. Powell, M. Horvath, A. Lough, J. Chem. Soc. Chem. Commun.
1993, 733–735; f) J. Powell, M. J. Horvath, A. Lough, J. Chem. Soc.
Dalton Trans. 1996, 1669–1677; g) M. D. Butts, B. L. Scott, G. J.
Kubas, J. Am. Chem. Soc. 1996, 118, 11831–11843; h) H. N. Aliyu,
R. D. Gillard, J. D. Honeywill, P. Lightfoot, J. Rocha, Polyhedron
1996, 15, 2409–2419; i) P. J. Albietz, Jr. B. P. Cleary, W. Paw, R. Ei-
senberg, J. Am. Chem. Soc. 2001, 123, 12091–12092.
1999, 140, 5901–5906; c) A. Wojtczak, V. Cody, J. R. Luft, W. Pang-
born, Acta Crystallogr. Sect. D 2001, 57, 1061–1070; d) B. Sandler, P.
Webb, J. W. Apriletti, B. R. Huber, M. Togashi, S. T. Cunha Lima, S.
Juric, S. Nilsson, R. Wagner, R. J. Fletterick, J. D. Baxter, J. Biol.
Chem. 2004, 279, 55801–55808.
[14] For reviews on terpyridine-containing supramolecules, see:
a) A. M. W. Cargill Thompson, Coord. Chem. Rev. 1997, 160, 1–52;
b) H. Hofmeier, U. S. Schubert, Chem. Soc. Rev. 2004, 33, 373–399;
c) I. Eryazici, C. N. Moorefield, G. R. Newkome, Chem. Rev. 2008,
108, 1834–1895; d) E. C. Constable, Coord. Chem. Rev. 2008, 252,
842–855.
[7] T. Clark, M. Hennemann, J. S. Murray, P. Politzer, J. Mol. Model.
2007, 13, 291–296.
[15] For terpyridine-containing cleft hosts, see: a) R. D. Sommer, A. L.
Rheingold, A. J. Goshe, B. Bosnich, J. Am. Chem. Soc. 2001, 123,
3940–3952; b) A. J. Goshe, J. D. Crowley, B. Bosnich, Helv. Chim.
Acta 2001, 84, 2971–2985; c) A. J. Goshe, I. M. Steele, C. Ceccarelli,
A. L. Rheingold, B. Bosnich, Proc. Natl. Acad. Sci. USA 2002, 99,
4823–4829; d) A. J. Goshe, I. M. Steele, B. Bosnich, J. Am. Chem.
Soc. 2003, 125, 444–451; e) J. D. Crowley, A. J. Goshe, B. Bosnich,
Chem. Commun. 2003, 392–393; f) J. D. Crowley, A. J. Goshe, B.
Bosnich, Chem. Commun. 2003, 2824–2825; g) J. D. Crowley, A. J.
Goshe, I. M. Steele, B. Bosnich, Chem. Eur. J. 2004, 10, 1944–1955;
h) A. J. Goshe, I. M. Steele, B. Bosnich, Inorg. Chim. Acta 2004, 357,
4544–4551; i) J. D. Crowley, I. M. Steele, B. Bosnich, Eur. J. Inorg.
Chem. 2005, 3907–3917; j) J. D. Crowley, B. Bosnich, Eur. J. Inorg.
Chem. 2005, 2015–2025; k) J. D. Crowley, I. M. Steele, B. Bosnich,
Inorg. Chem. 2005, 44, 2989–2991.
[16] a) K. Yamasaki, M. Yasuda, J. Am. Chem. Soc. 1956, 78, 1324;
b) R. H. Holyer, C. D. Hubbard, S. F. A. Kettle, R. G. Wilkins,
Inorg. Chem. 1965, 4, 929–935.
[17] For reviews on platinum-based supramolecules, see: a) M. Fujita, K.
Umemoto, M. Yoshizawa, N. Fujita, T. Kusukawa, K. Biradha,
Chem. Commun. 2001, 509–518; b) P. H. Dinolfo, J. T. Hupp, Chem.
Mater. 2001, 13, 3113–3125; c) B. H. Northrop, Y.-R. Zheng, K.-W.
Chi, P. J. Stang, Acc. Chem. Res. 2009, 42, 1554–1563.
[8] a) T. Sugimori, H. Masuda, O. Yamauchi, Bull. Chem. Soc. Jpn.
1994, 67, 131–137; b) F. Zhang, A. Odani, H. Masuda, O. Yamauchi,
Inorg. Chem. 1996, 35, 7148–7155; c) F. Zhang, T. Yajima, H.
Masuda, A. Odani, O. Yamauchi, Inorg. Chem. 1997, 36, 5777–5784.
[9] a) R. Trokowski, S. Akine, T. Nabeshima, Chem. Commun. 2008,
889–890; b) R. Trokowski, S. Akine, T. Nabeshima, Dalton Trans.
2009, 10359–10366.
[10] a) E. Koft, F. H. Case, J. Org. Chem. 1962, 27, 865–868; b) T. R.
Kelly, R. L. Lebedev, J. Org. Chem. 2002, 67, 2197–2205.
[11] a) C.-Y. Hung, T.-L. Wang, Y. Jang, W. Y. Kim, R. H. Schmehl, R. P.
Thummel, Inorg. Chem. 1996, 35, 5953–5956; b) J. H. Groen, A.
de Zwart, M. J. M. Vlaar, J. M. Ernsting, P. W. N. M. van Leeuwen,
K. Vrieze, H. Kooijman, W. J. J. Smeets, A. L. Spek, P. H. M. Budze-
laar, Q. Xiang, R. P. Thummel, Eur. J. Inorg. Chem. 1998, 1129–
1143; c) H. Chen, R. Tagore, S. Das, C. Incarvito, J. W. Faller, R. H.
Crabtree, G. W. Brudvig, Inorg. Chem. 2005, 44, 7661–7670; d) C.
Duboc, V. Astier-Perret, H. Chen, J. Pꢂcaut, R. H. Crabtree, G. W.
Brudvig, M.-N. Collomb, Inorg. Chim. Acta 2006, 359, 1541–1548;
e) G. D. Jones, J. L. Martin, C. McFarland, O. R. Allen, R. E. Hall,
A. D. Haley, R. J. Brandon, T. Konovalova, P. J. Desrochers, P.
Pulay, D. A. Vicic, J. Am. Chem. Soc. 2006, 128, 13175–13183; f) S.
Zein, C. Duboc, W. Lubitz, F. Neese, Inorg. Chem. 2008, 47, 134–
142; g) S. Zein, F. Neese, J. Phys. Chem. A 2008, 112, 7976–7983.
[12] For related “U-shaped” terpyridine ligands and their complexes,
see: a) D. Sielemann, A. Winter, U. Flçrke, N. Risch, Org. Biomol.
Chem. 2004, 2, 863–868; b) A. Winter, J. Hummel, N. Risch, J. Org.
Chem. 2006, 71, 4862–4871; c) K. Sꢂnꢂchal-David, A. Hemeryck, N.
Tancrez, L. Toupet, J. A. G. Williams, I. Ledoux, J. Zyss, A. Boucek-
kine, J.-P. Guꢂgan, H. Le Bozec, O. Maury, J. Am. Chem. Soc. 2006,
128, 12243–12255.
[18] N. Hallowita, E. Udonkang, C. Ruan, C. E. Frieler, M. T. Rodgers,
Int. J. Mass Spectrom. 2009, 283, 35–47.
[19] Spartan ’04, Wavefunction, Irvine, CA, 2004.
[20] M. Jereb, M. Zupan, S. Stavber, Chem. Commun. 2004, 2614–2615.
[21] P. T. Beurskens, G. Beurskens, R. de Gelder, S. Garcia-Granda,
R. O. Gould, R. Israel, J. M. M. Smits, The DIRDIF-99 Program
system, Crystallography Laboratory, University of Nijmegen, Nijme-
gen, The Netherlands, 1999.
[13] a) R. L. Wagner, J. W. Apriletti, M. E. McGrath, B. L. West, J. D.
Baxter, R. J. Fletterick, Nature 1995, 378, 690–697; b) M. Gurnell,
O. Rajanayagam, M. Agostini, R. J. D. Clifton-Bligh, T. Wang,
P. M. J. Zelissen, F. van der Horst, A. van de Wiel, E. Macchia, A.
Pinchera, J. W. R. Schwabe, V. K. K. Chatterjee, Endocrinology
[22] SHELXL 97, program for crystal structure refinement: G. M. Shel-
drick, Acta Crystallograph. Sect. A 2008, 64, 112–122.
Received: May 30, 2011
Published online: November 16, 2011
14428
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 14420 – 14428