Macrocycles with switchable exo/endo metal binding sites

Article abstract of DOI:10.1021/ja906474z

We report herein the synthesis and metal complexation properties of two macrocyclic hosts that contain two 2,2′-bipyridines and two urea groups. These hosts take advantage of the conformationally mobile 5,5′-positions of the bipyridines to give metal binding sites that are dynamic. By simple bond rotation, these hosts can exchange an interior (endo) situated metal binding site for an exterior (exo) binding site. We examine the solid-state structures of the two free hosts and two coordination complexes ([Cd(host 1)(H ₂O)(NO₃)₂] and [Ag₂(host 2)](SO ₃CF₃)₂) using X-ray crystallography. Analysis of these crystal structures suggests that the bipyridine groups within the hosts are able to rotate to access multiple conformations including the desired exo and endo conformations. We also investigate the binding affinity of these new ligands in solution by UV-vis titrations with a series of metal nitrate salts (Ag, Cd, Zn, Ni, Mn, Fe, Co, Cr, and Cu) to afford discrete metal complexes. Some complexes showed a slow subsequent assembly to yield coordination polymers. Thus, these systems may afford unique insights into the process of metal organic framework formation.

Full text of DOI:10.1021/ja906474z

Published on Web 11/12/2009
Macrocycles with Switchable exo/endo Metal Binding Sites
Lei-lei Tian,† Chun Wang,† Sandipan Dawn,† Mark D. Smith,† Jeanette A. Krause,‡
and Linda S. Shimizu*,†
Department of Chemistry and Biochemistry, UniVersity of South Carolina, Columbia, South
Carolina 29208, and The Richard C. Elder X-ray Crystallography Facility, Department of
Chemistry, UniVersity of Cincinnati, Cincinnati, Ohio 45221
Received July 31, 2009; E-mail: shimizul@mail.chem.sc.edu
Abstract: We report herein the synthesis and metal complexation properties of two macrocyclic hosts that
contain two 2,2′-bipyridines and two urea groups. These hosts take advantage of the conformationally
mobile 5,5′-positions of the bipyridines to give metal binding sites that are dynamic. By simple bond rotation,
these hosts can exchange an interior (endo) situated metal binding site for an exterior (exo) binding site.
We examine the solid-state structures of the two free hosts and two coordination complexes ([Cd(host
1)(H2O)(NO3)2] and [Ag2(host 2)](SO3CF3)2) using X-ray crystallography. Analysis of these crystal structures
suggests that the bipyridine groups within the hosts are able to rotate to access multiple conformations
including the desired exo and endo conformations. We also investigate the binding affinity of these new
ligands in solution by UV-vis titrations with a series of metal nitrate salts (Ag, Cd, Zn, Ni, Mn, Fe, Co, Cr,
and Cu) to afford discrete metal complexes. Some complexes showed a slow subsequent assembly to
yield coordination polymers. Thus, these systems may afford unique insights into the process of metal
organic framework formation.
Introduction
flexibility are two important factors that determine the selectivity
of macrocyclic hosts and their host-guest complex stability.16-18
The synthesis and properties of macrocyclic compounds have
been a priority in host-guest chemistry and molecular recogni-
tion because of their applications in ion transport,1-5 chemosens-
ing and imaging,6-12 metallo-enzyme mimics,13,14 catalysis, and
nuclear waste treatment.15 Cavity size and conformational
During the binding process the host undergoes conformational
readjustment in order to arrange its binding sites complementary
to the guest.19 Although difficult to measure, rigidly preorga-
nized hosts may have higher complexation activation energies
that could lead to slower guest binding kinetics.20-23 In contrast,
conformationally mobile hosts may adjust rapidly to changing
conditions and could be potentially more useful receptors in
sensing applications because of their fast response time,
reversible binding, and the possibility of detecting binding by
means of altered conformations.24-26 The interplay between
rigidity and flexibility is a fascinating issue in supramolecular
chemistry and is an area that we are beginning to explore with
hosts that potentially contain dynamic exo/endo binding sites.
Our group has reported bis-urea macrocycles that are readily
synthesized and self-assembled into columnar structures with
guest accessible channels.27-29 Our previous research has
concentrated on adjusting the size and shape of the rigid
macrocycles using different building blocks such as m-xylene,
phenyl ether, or benzophenone. In this paper, we explored the
† University of South Carolina.
‡ University of Cincinnati.
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Macrocycles with Switchable Metal Binding Sites
A R T I C L E S
feasibility of incorporating bipyridine functional groups in the
macrocyclic framework through connections that tolerate bond
rotation. The two macrocyclic hosts each contain two 2,2′-
bipyridine units that can freely rotate. These bipyridines are
bridged by either free ureas (host 1) or triazinanone-protected
ureas (host 2). Simple bond rotation should enable the metal
binding sites to flip from the interior of the macrocycle to its
exterior and give rise to different conformational isomers. To
test if this “switchable” design would affect the host’s ability
to bind metals, we examined a series of host metal complexes
in both the solid state and in solution. We compared their
structure and binding affinity with what has been observed for
other bipyridines. Metal cations that match the interior of the
hosts by having suitable ionic radii and coordination preferences
for the geometrically constrained set of bipyridines were
expected to show a preference for binding inside the cavity
(endo). In contrast, metals with other coordination preferences
or with larger ionic radii were expected to prefer to bind to the
host when the bipyridines are rotated outward in an exo
orientation. Therefore, the metal binding event should shift the
host to the conformation most suitable for complexation.
Further assembly of these discrete metal-ligand complexes
either by metal coordination of the macrocycles that adopt exo
conformations or by hydrogen bonding of the ureas should yield
coordination polymers or metal organic frameworks (MOFs).
MOFs are a new class of porous materials that are able to absorb
molecules ranging in size from H2 to large buckyballs.30-34
Currently, a number of groups are exploring methods to
incorporate functionality into MOFs to modulate their physical
and chemical properties.35-40 Strategies include preinstallation
of the functional groups prior to or during the synthesis of the
MOFs or by “postsynthetic modification”.35-40 Indeed, recently
urea functionalized MOFs have been synthesized through
postsynthetic modification of Yaghi’s isoreticular metal-organic
framework-2 (IRMOF-3).39,40 Sometimes the MOF fails to
crystallize into the desired structure because of the presence of
the new functional groups. In these cases, it is difficult to discern
if the functional group has interrupted the metal-ligand
interactions that are central to MOF formation or if other factors
are to blame. The macrocycles reported in this manuscript have
the potential to evaluate the metal-ligand assembly in the
presence of the urea functional groups. They enable the study
of the initial coordination events in solution and allow us to
examine their further assembly by spectroscopic methods. Thus,
these systems could provide unique insight into the process of
MOF synthesis.
Linear ligands that contain two or more 2,2′-bipyridine
units41,42 have been used to connect metal centers in a well-
defined spatial arrangement for applications in sensing,43,44
helical assembly,45 chiral molecular recognition,46,47 photonics
and optoelectronics, and electrochemistry applications.48-50 The
2,2′-bipyridine group has also be incorporated into macrocycles,
which may constrain the metal binding site to a well-defined
size and shape. This special feature of macrocycles has the
potential to enhance the ligand’s selectivity toward particular
metal ions of complementary size. For example, two 2,2′-
bipyridines can be connected at positions 4 and 4′ to yield
macrocycles that direct the coordination sites to the exterior of
the macrocyclic cavity. These exo-ligands are used as building
blocks for the construction of one-dimensional coordination
polymers51 or binuclear complexes with interesting electro-
chemical properties.52 Alternatively, connection of the 2,2′-
bipyridines at positions 6 and 6′ affords macrocycles with
interior coordination sites. These endo-ligands have the two
bipyridines preorganized for binding and are capable of com-
plexation of specific metal cations with complementary size.53,54
Few macrocycles have been reported that connect the 2,2′-
bipyridines through their 5,5′ positions as this connection allows
for both exo and endo coordination modes.55-61 A phenylacet-
ylene macrocycle from Schlu¨ter’s group with two opposing 2,2′-
bipyridines can coordinate with 2 equiv of [Ru(bipy)2Cl2] to
form the doubly exo-cyclical complex (Figure 1c).59 As a result
of the large cavity size (∼13.7 Å × 7.3 Å)60 and relatively rigid
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Shimizu, L. S. Chem. Commun. 2008, 3909–3911.
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A R T I C L E S
Tian et al.
Figure 1. Comparison of bipyridine macrocycles that allow the binding sites to “flip” dynamically between exo and endo conformations. (a) Host 1 (∼8.2
Å × 2.0 Å); (b) host 2 (∼7.9 Å × 3.0 Å); (c) the phenylacetylene macrocycle (∼13.7 Å × 7.3 Å);59 (d) the twistophane macrocycle.61
Scheme 1. Schematic Representation of the Coordination Modes
in Macrocycles That Are Able To Flip the Coordination Site from
cycles showed different host:guest stoichiometries when screened
an Interior (endo) to an Exterior (exo) Position
a nonlinear least-squares regression method. The two macro-
against a series of metal guests. Tetradentate host 1 prefers
mononuclear complexes, whereas host 2 prefers to form
binuclear complexes. This difference is likely due to the
presence of additional basic tertiary aliphatic amines on the
triazinanone groups, which makes this host a hexadentate ligand.
In addition, the rigidity of the fused six-membered ring of the
triazinanone as well as the sterics of the attached tert-butyl group
also affects the structure of the coordination complexes. These
different binding modes also play a role in the further supramo-
lecular assembly of these small complexes, and we probed these
assembled structures by X-ray crystallography and light scattering.
Results and Discussion
Our target macrocycles incorporated two 5,5′-disubstituted
2,2′-bipyridine and two ureas (free ureas 1 or triazinanone-
protected ureas 2) with flexible methylene connections. We used
molecular modeling to probe the conformations of these
macrocycles. A Monte Carlo search using Spartan62 with MMFF
predicted that in the lowest energy structures of the macrocycles
architecture, only exo-coordination was observed. Baxter re-
ported a dehydroannulene framework that incorporated two 2,2′-
1 and 2 are quite similar, and the 2,2′-bipyridine units adopt
anti-coplanar configurations with the pyridine nitrogens nearly
perpendicular to the macrocycle plane (Figure 2). Such a
conformation provides a central void, in which the distance
between the van der Waals surfaces of diagonal pyridyl nitrogen
atoms was estimated as 3.2-3.0 Å.63 Parallel alignment of the
2,2′-bipyridine units with respect to the plane of the macrocycle
forms the smallest recognition site (∼1 Å). In solution, free
rotation of 2,2′-bipyridine units provides an adjustable cavity
that should be able to accommodate most transition metals,
whose ionic radii typically range between 0.5-1.8 Å. Although
the two macrocycles have many similarities, host 1 contains
bipyridine units into a chiral twisted architecture with a small
central void (Figure 1d). The cavity enforced a tetrahedral
arrangement of nitrogen lone pair electrons to favor endo
coordination of metals and showed potential applications in the
detection and monitoring of Zn2+ in biological media.61
In comparison, the metal binding sites in hosts 1 and 2 should
dynamically flip between exterior and interior positions (Scheme
1). Thus both exo and endo coordination modes should be
accessible, and the metal coordination preference, size, and
shape should dictate which coordination conformation is
favored. Given the relatively small cavity size of hosts 1 and 2
(∼ 8.2 Å × 2.0 Å for 1 and ∼ 7.9 Å × 3.0 Å for 2), we
predicted that endo coordination could be possible for smaller
transition metal ions that preferred to form tetrahedral, square
planar, or octahedral complexes. Hosts 1 and 2 were screened
for their ability to bind a series of metal salts using UV-vis
spectroscopy. Binding stoichiometries were evaluated by JOB
plot analysis, and the association constants were estimated using
(62) Spartan 04 for Macintosh, v 1.1.1; Wavefunction, Inc.: Irvine, CA.,
2007.
(63) Distance between van der Waals surfaces of atoms was calculated as
(internuclear distance)-(sum of van der Waals radii of atoms
involved). The distance between the van der Waals surfaces of two
opposite pyridyl nitrogen atoms.
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A R T I C L E S
Figure 2. Spartan calculated models of the host 1 and host 2.62 Monte Carlo searches of the conformer distribution at ground state with Molecular Mechanics
(MMFF) suggest the lowest energy structures of (a) host 1 and (b) host 2 do not adopt either exo or endo conformations. The distance between the van der
Waals surfaces of the pore defining pyridine nitrogens is estimated as 3.2 and 3.0 Å, respectively.
Scheme 2. Synthesis of Bipyridine-Containing Hosts
free urea units, which are superb hydrogen-bonding groups as
well as potential sites for anion binding. In comparison, host 2
contains no hydrogen bond donors but has basic tertiary aliphatic
nitrogens within the triazinanone group that could be a potential
site for polynuclear coordination complexes.
We next compared the solid-state structures of macrocycles
1 and 2. The crystal structures provide a conformational
“snapshot”, and the macrocycles are likely to adopt different
conformations in solution. The two hosts have similar structures
in the solid state (Figure 3). Both are centrosymmetric, with
the two urea carbonyls pointed in opposite directions. Neither
host displayed the proposed exo- or endo-bipyridine conforma-
tions. Instead, much like Spartan predictions, the 2,2′-bipyridine
units adopted twisted anti conformations with N3-C5-C8-N4
dihedral angles for 1 of 24.6° and N4-C7-C10-N5 for 2 of
32.1°. Two diagonal nitrogen atoms face inward toward the
macrocycle ring (with dihedral angles of 67.2° for 1 and 60.2°
for 2) with the other two diagonal nitrogen atoms pointing
outward the macrocycle (with dihedral angles of 38.6° for 1
and 40.1° for 2). The void spaces of these cavities calculated
from the crystal structures are smaller than the theoretical
predictions from Spartan calculations in the gas phase.63 The
cavity size for coordination was determined by the distance
The next step was to synthesize these hosts and to study their
solid-state structures to see what conformations they adopt. Bis-
urea macrocycle 2 was synthesized in two steps. Bromination
of 5,5′-dimethyl-2,2′-dipyridyl with N-bromosuccinimide af-
forded the dibromide, which cyclized under basic conditions
with triazinanone to yield the triazinanone-protected host 2
(Scheme 2). Colorless plate crystals of 2 suitable for X-ray
diffraction studies were grown by slow diffusion of n-hexane
into a saturated dichloromethane solution of host 2. The tri-
azinanone groups were deprotected to the ureas with diethanol-
amine in acidic water/methanol to afford host 1 (90% yield),
which formed crystals suitable for X-ray diffraction upon
cooling of the deprotection solution.
Figure 3. X-ray crystal structure of (a) macrocycle 1 and (b) macrocycle 2 with top view and side view, respectively. The distance between the van der
Waals surfaces of two opposite pyridyl nitrogen atoms (N4 to N4a, dashed line) is about 2.0 Å for 1 and 3.0 Å for 2.
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Tian et al.
Table 1. Ionic Radii of Some Commonly Used Metal Ionsa
Cr3+ Mn2+ Fe3+ Co2+
Ni2+
Cu2+ Zn2+ Cd2+
Ag+
radius (Å) 0.62 0.83 0.65 0.75 0.69 0.73 0.74 0.95 1.00
a Values are for six-coordination, with the exception of Ag, which is
for four-coordination.64
Figure 5. Extended structure of complex [Cd(host 1)(H2O)(NO3)2]. (a)
Top view. (b) Side view showing the 1·Cd2+ layer connected through 1D
linear N(5)H(5) · · ·O(2)dC hydrogen-bonding with ligands alternately
slanted up and down in the layer. (c) A sketch of the layered structure
illustrating the distance between the Cd2+ atoms.
yield an endo-type structure that affords a stable host 1·Cd2+
complex. The 2,2′-bipyridines adopt a nearly planar conforma-
tion with N-C-C-N dihedral angles of 5.2°, and the four
nitrogen donors point inward for efficient coordination with
Cd2+. The van der Waals distance between pyridine nitrogens
of the recognition site decreased from 2.0 Å in the free
macrocycle to 1.2 Å. As a consequence, the cadmium atom
(radius ≈ 0.95 Å) is located slightly above the macrocyclic
cavity, ∼1.77 Å above the mean plane of the macrocycle. The
asymmetric unit of the crystal consists of one Cd(1)(H2O)2+
cation and two unique nitrate anions (one coordinated to the
metal center and the other situated out of coordination sphere).
Each Cd2+ atom is coordinated to four nitrogen atoms of
bipyridines (Cd-N ) 2.382(3)-2.436(3) Å) and to two oxygen
atoms of the chelating nitrate group (Cd-O ) 2.371(5)-2.557(4)
Å) and an oxygen of water (Cd-O ) 2.346(3) Å), respectively.
The coordination environment of cadmium can be described as
distorted octahedral. Indeed, it appears that host 1 can rotate
and is able to access endo-type conformations as evidenced by
this cadmium coordination complex.
Examination of the extended structure shows that urea
carbonyl pointed in opposite directions as observed in other bis-
urea macrocycles; however, the typical three-centered urea
hydrogen bonds were not formed. As predicted by Hunter, the
urea carbonyl forms one hydrogen bond to the NH on a
neighboring macrocycle, but the basic nitrate counterion com-
petes with the carbonyl for the other urea NH’s, presumably
because it is now more basic than an oxygen that is already
involved in one hydrogen bond.65 Thus, the individual host
1·Cd2+ monomers are held together by a single chain of NH to
urea carbonyl interactions with a distance of 2.805(4) Å from
N(5)H(5) · · · O(2)dC and an angle of 175°. The 1 · Cd2+
complexes are arranged alternately slanting up and down in the
layer, and the adjacent Cd · · ·Cd distance within each row is
kept at 8.43 Å (Figure 5). The remaining three urea N-H and
one CdO on macrocycle formed hydrogen-bonding interactions
with nitrate ions and water molecules (N(1)H(1) · · ·O(6) 2.938(6)
Å, N(2)H(2) · · ·O(7) 2.918(7) Å, O(3)H(3A) · · ·O(1) 2.838(4) Å,
N(6)H(6)· · ·O(8) 2.973(5) Å, O(3)H(3B) · · ·O(9) 2.772(4) Å). We
are currently investigating if columnar assembly could be
Figure 4. Crystal structure of complex [Cd(Ligand 1)(H2O)(NO3)2]. (a)
Top view of displacement ellipsoid plot with ellipsoids drawn at the 40%
probability level. The minor nitrate disorder component was omitted, and
atom H6 was obscured. (b) Side view showing the tilting of H6 toward the
nitrate O7.
between the van der Waals surfaces of two opposite pyridyl
nitrogen atoms (N4 to N4a). The value is approximately 2.0 Å
for 1 and 3.0 Å for 2. In solution, we expect that the bipyridine
rings freely rotate and access the exo and endo conformations
that are preorganized for metal complexation. Given both
Spartan calculations and X-ray data, we investigated metal
cations with van der Waals radii of e1 Å (Table 1) as these
should be free to form complexes with both the endo and exo
conformations of the two hosts.
Crystal Structure of Host·Metal Complexes. We next inves-
tigated the formation of host ·metal complexes. The hosts were
individually mixed in 1:1 ratio with metal salts [AgCF3SO3,
AgNO3, Cd(NO3)2, Zn(CF3SO3)2, Zn(NO3)2, Cu(NO3)2, and
Ni(NO3)2]. We used slow evaporation methods for crystallization
of the less soluble host 1 in THF (10-5-10-4 mol L-1). The
greater solubility of host 2 allowed the use of solvent diffusion
methods in which the metal salts were dissolved in MeOH and
layered on top of a solution of 2 in CH2Cl2 (10-3-10-2 mol
L-1). X-ray quality single crystals were obtained for the host
1·Cd2+ and host 2·Ag+ complexes. Colorless plates of 1·Cd2+
were obtained by slow evaporation of the mixture of 1 and
Cd(NO3)2 in THF (10-5 M, 1:1 molar ratio). The crystal structure
revealed the formation of the mononuclear neutral complex
Cd(1)(H2O)(NO3)2 with a 1:1 host:guest stoichiometry (Figure
4). The Cd2+ atom was accommodated on the top of 1 and
coordinated to both of the 2,2′-bipyridines. Host 1 underwent
significant conformation adjustments from its unbound state to
(64) Shannon, R. D. Acta Crystallogr., Sect. A: Found. Crystallogr. 1976,
A32, 751–767.
(65) Hunter, C. A. Angew. Chem., Int. Ed. 2004, 43, 5310–5324.
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Macrocycles with Switchable Metal Binding Sites
A R T I C L E S
Figure 7. (a) Homochiral polymeric helix structure viewed perpendicular
to the crystallographic c axis. (b) Infinite partially interlaced porous structure
viewed parallel to the c axis.
geometries in the solid state.67-69 It appears that silver(I)
preferentially selected the exo conformation of host 2, which
supplies the 2,2′-bipyridine and a neighboring tert-butyl-amine
as ligands.
The coordination of Ag+ between two macrocycles leads to
an infinite three-dimensional polymeric structure, crystallizing
in the chiral tetragonal space group P43212. The silver coordina-
tion induces an interplanar angle of 81.6° between two
neighboring macrocycles, affording helical one-dimensional
coordination polymers along the c axis with the pitch length of
32.6 Å as shown in Figure 7a. Typically, helical systems arising
from achiral starting materials show an equal distribution of P-
and M-helices, making them overall racemic. In this case, the
helical coordination polymer was built by a 43 right-handed
screw axis symmetry element and was homochiral. An intercon-
nected network formed by the further assembly of these helices
is shown in Figure 7b. Because each macrocycle molecule
coordinates four silvers and forms two orthogonally arranged
helices through the long c axis and short a axis, respectively, a
view from the c axis shows an infinite partially interlaced porous
structure with chiral channels. To date, only a few examples of
helical coordination polymers with homochirality have been
reported.70-72 We are currently evaluating other host 2·Ag+
crystals to see if the other enantiomer crystallizes separately.
Such chiral porous structures are rare and show potential in
asymmetric catalysis, chiral sensing and separation.73-75
Complexation Behaviors of Host 1 in Solution. The solid-
state structures of the free hosts and the two metal complexes
suggested that both endo and exo metal coordination modes were
accessible for these hosts. We next sought to evaluate whether
Figure 6. X-ray crystal structures of macrocycle 2 · Ag+ complex
{[Ag2(host2)](SO3CF3)2 ·unknown solvate}. (a) 30% probability displace-
ment ellipsoid plot of the polymeric framework repeating unit, with atom
labeling sequence. Hydrogen atoms omitted. (b) The coordination environ-
ment of the silver atom in 2·Ag+.
favored with metal salts that have less basic counterions, such
as triflate, perchlorate, and acetate.
X-ray quality single crystals (colorless plate) of 2·Ag+
{[Ag2(2)](SO3CF3)2 ·unknown solvate} were obtained by solvent
diffusion method (layering technique)66 and revealed the metal
coordinated in the exo coordination mode. Although the crystals
were grown from a 1:1 ratio of host to metal salt, the crystalline
complex displayed a 1:2 host:guest stoichiometry. Figure 6 gives
a perspective view of the local coordination environment around
the one crystallographically unique Ag(I) atom. The Ag(I) atom
adopted a distorted trigonal planar configuration. The silver (Ag+
radius ∼1.0 Å for four-coordination, as three-coordination was
not tabulated64) preferred an exo-coordination mode and was
accommodated out of the macrocyclic cavity. Two sp2 nitrogen
atoms from one 2,2′-bipyridine chelate the Ag+ in bidentate
fashion, and there was an additional interaction between the
Ag+ and sp3 nitrogen from tert-butyl-amine on a neighboring
macrocycle in monodentate fashion (Figure 6b). The N-Ag-N
angles range from 72.1° to 144.8°, and the Ag-N(t-Bu)
distances range from 2.2 to 2.3 Å.
In the presence of silver, host 2 adopted an elliptic “bowl”
shape with the 2,2′-bipyridines in a planar conformation to
coordinate with silver atom, different from the conformation
observed in the free host. The four nitrogen donors on 2,2′-
bipyridine units point slightly outward with the urea carbonyls
and the nitrogen donors also located in opposite directions to
minimize dipole interactions. The tert-butyl units move from
parallel in pure host to vertical, likely as a result of increased
steric hindrance upon coordination. Although silver(I) usually
favors linear two coordinate geometry with nitrogen donors, it
can afford complexes with a number of different coordination
(67) ComprehensiVe Coordination Chemistry; Wilkinson, G., Ed.; Perga-
mon: Oxford, 1987; Vol. 5, p 786.
(68) Khlobystov, A. N.; Blake, A. J.; Champness, N. R.; Lemenovskii,
D. A.; Majouga, A. G.; Zyk, N. V.; Schro¨der, M. Coord. Chem. ReV.
2001, 222, 155–192.
(69) Steel, P. J.; Fitchett, C. M. Coord. Chem. ReV. 2008, 252, 990–1006.
(70) Ezuhara, T.; K.; Aoyama, Y. J. Am. Chem. Soc. 1999, 121, 3279–
3283.
(71) Xu, Y.; Han, L.; Lin, Z. Z.; Liu, C. P.; Yuan, D. Q.; Zhou, Y. F.;
Hong, M. C. Eur. J. Inorg. Chem. 2004, 4457–4462.
(72) Maggard, P. A.; Stern, C. L.; Poeppelmeier, K. R. J. Am. Chem. Soc.
2001, 123, 7742–7743.
(73) Tarducci, C.; Badyal, J. P. S.; Brewer, S. A.; Willis, C. Chem.
Commun. 2005, 406–408.
(66) A solution of AgCF3SO3 (4 mg, 0.015 mmol) in methanol (0.75 mL)
was layered on top of a solution of 2 (10 mg, 0.015 mmol) in CH2Cl2
(0.75 mL). Colorless block-like crystals of Ag+ ·2 complex formed
within two weeks.
(74) Kitagawa, S.; Kitaura, R.; Noro, S. Angew. Chem., Int. Ed. 2004, 43,
2334–2375.
(75) Mueller, U.; Schubert, M.; Teich, F.; Puetter, H.; Schierle-Arndt, K.;
Pastre, J. J. Mat. Chem. 2006, 16, 626–636.
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A R T I C L E S
Tian et al.
Figure 8. (a) JOB plot for host 1 and Cd(NO3)2 in THF and methanol mixed solvent (v/v ) 99:1). The total concentration of 1 and metal salts was kept
constant at 2.1 × 10-5 mol L-1. The molar fraction of the metal salts varied in the range of 0.1-0.9, λobs ) 325 nm.76 (b) Titration curves of 2 solution (10-6
M) in THF at 298 K upon addition of aliquots of Cd(NO3)2.
Figure 9. (a) JOB plot for host 1 and AgNO3 in THF and methanol mixed solvent (v/v ) 99:1). The total concentration of 1 and metal salts was kept
constant at 2.1 × 10-5 mol L-1. The molar fraction of the metal salts varied in the range of 0.1-0.9, λobs ) 325 nm. (b) Titration curves of 2 solution (10-6
M) in THF at 298 K upon addition of aliquots of AgNO3.
complexes with similar host:guest ratios can be formed in
solution and to measure their association constants. Will specific
metals show preference for one coordination mode over another?
Or alternatively, will each metal form multiple complexes with
both exo and endo coordination modes giving rise to several
host:guest complexes? To investigate the metal ion binding
properties of these macrocyclic ligands, we studied guest
complexation by both host 1 and 2 using titration curves based
on UV-vis spectroscopic analysis. UV-vis absorption spectra
were recorded upon gradual addition of metal salts to the
solution of macrocycle host. The titration curves obtained
enabled the study of the binding process and provided a means
to quantify complex stability. During the process, all nitrate salts
were used to minimize the possible effects caused by counter-
anions. Host:guest stoichiometry was determined through
continuous variation plots (JOB plots).76
We first examined the interaction of host 1 with Cd(NO3)2
in solution as it was already known that this guest formed a
1:1 complex with the metal bound in an endo mode in the solid
state. The UV-vis spectrum of free uncoordinated 1 (solvent
THF/methanol (v/v ) 99:1)) displayed absorption maxima at
283 nm with a shoulder at 300 nm. The wavelength and shape
of the absorption band remained invariant over the concentration
range of 2.1 × 10-6 to 2.1 × 10-5 mol L-1 in THF, suggesting
that 1 did not aggregate in dilute solution (see Supporting
Information). Upon addition of cadmium salts to the solution
of 1, the main absorption of free host 1 at 283 nm decreased,
and at the same time, a new absorption generated at 304 nm,
which can be assigned to charge transfer (CT) absorption of
the forming metal complexes (Figure 8b). A clear isosbestic
point at 296 nm was observed in the titration curves, indicating
the formation of a single new complex. The absorbance at 325
nm was used to construct a JOB plot (Figure 8a). The JOB plot
shows two lines that intersect at a mole ratio of 0.5, indicative
of a 1:1 host:guest stoichiometry between host 1 and Cd2+
,
which is consistent with the crystal structure. The steep
intersecting lines suggested a high association constant. Given
the JOB plot data and clear isosbestic point, we assume that
during the titration process only three species exist: host, guest,
and the host-guest complex. The binding constants between
host 1 and Cd2+ was estimated with the nonlinear least-squares
regression method to be very high, 1.5 × 108 M-1
.
We next examined the binding of silver (AgNO3) by host 1,
which was expected to have a preference for exo coordination,
as observed in the crystal structure with host 2. The JOB plot
also exhibited a 1:1 host:guest stoichiometry between host 1
and silver. Similar to the previous example, the addition of silver
salts to the solution of 1, the main absorption of free host 1 at
283 nm decreased as a new absorption generated at 293 nm
(Figure 9b). In contrast to the host 1·Cd complex, the titration
with the silver does not display an ideal isosbestic point and
showed a small drift. In addition the CT absorption of the new
complex became very broad with concurrent increase baseline
absorption at longer wavelength. The baseline absorption
increase may reflect a visible phenomenon, and the mixture of
host 1 and silver became turbid over time (within hours). We
have not yet obtained crystals of this complex suitable for X-ray
crystallography. In comparison, the absorption spectrum for
(76) Hirose, K. J. Inclusion Phenom. Macrocyclic Chem. 2001, 39, 193–209.
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17626 J. AM. CHEM. SOC. VOL. 131, NO. 48, 2009

Macrocycles with Switchable Metal Binding Sites
A R T I C L E S
Table 2. Association Constants81 between Host 1 and Metal Ions
at 298 K
Scheme 3. Sketch of the Two Types of Coordination Modes of
Host 1
Cd2+
Zn2+
Mn2+
radius (Å)
Ka (M-1
0.97
0.74
0.46
)
1.5 × 108
5.0 × 107
3.4 × 106
complex of 1 and cadmium showed a very smooth baseline,
and the corresponding solution of the complex remained
transparent over time. Our hypothesis is that these differences
in spectral features may be associated with two distinct
coordination modes: an endo coordination for cadmium, as
observed in the crystal structure, versus an exo coordination
for the silver, which could potentially further assemble to yield
oligomers and polymers. Such an assembly process could
include a number of different association constants.
coordination geometry. Indeed, both the high binding constant
observed for Cd2+ in solution and the coordination complex
observed in the solid state, indicated that Cd2+ was well matched
in size, shape, and coordination geometry for the endo conformer
of host 1. In addition, the observed 1:1 binding stoichiometry
in solution and the clear isosbestic point lead us to propose that
the complex host 1·Cd2+ in the solution state was similar in
structure to the endo-coordination complex observed in the solid
state. We surmise that the host 1·Zn2+ and the host 1·Mn2+
are also endo-coordination complexes. These three metals may
be more flexible in choosing coordination geometries and
coordination numbers due to their full or half occupied d atomic
orbitals and may be able to better coordinate to the four pyridines
of host 1, which are constrained by the macrocycle.
The slight drift of the isosbestic point for the second series
of metals (Ag+, Co2+, Ni2+, and Cu2+) suggested that there may
be several steps or intermediates in the host-guest complexation
process. Our hypothesis is that these metals form exo-coordina-
tion complexes. The binding of a metal to an exo-oriented
bipyridine would leave open sites for further coordination with
an exo-oriented bipyridine from a second macrocycle. Such
complexes may further assemble into oligomers (Scheme 3),
although overall they would still display 1:1 host:guest stoi-
chiometry, which we observed in the JOB plots. The separate,
stepwise coordination of the metal center may not give a clear
isosbestic point as several intermediates are formed.82 The
growth of the oligomer over time could lead to polymers with
lower solubility.
In the titrations of host 1 with this second set of metal nitrate
salts (Ag+, Co2+, Ni2+, and Cu2+), we observed an increase in
the baseline absorbance at longer wavelengths (Figure 8b and
Supporting Information). Such an increase could result from
poor solubility of the metal complex, from the intrinsic
absorption of the metal complexes, or from Rayleigh scattering
induced by long coordination oligomers or polymers. We probed
the origin of this baseline absorption by a light transmittance
study using a UV-vis spectrophotometer at a fixed wavelength
of 800 nm and by Gel Permeation Chromatography (GPC).
Common organic compounds generally show no absorption at
800 nm,83 which was true for free host 1 and the host 1
complexes with Cd2+, Zn2+, and Mn2+. The transmittance
To further investigate the issue of size, we next screened a
series of metal salts with ionic radii between 0.46 and 0.74 Å
(Mn2+, Fe3+, Co2+, Ni2+, Cu2+, and Zn2+) with the expectation
that some of these metals might favor endo coordination as
observed in the solid state for Cd2+. Each metal was screened
with host 1 using UV titrations and JOB plots. With the
exception of Fe3+, all of the metals tested clearly displayed the
formation of 1:1 host:guest complexes by JOB plot studies
(Supporting Information). In contrast, for Fe3+ the JOB plot
showed no maximum, and its host:guest stoichiometry could
not be determined, suggesting that Fe3+ might form multiple
weak complexes. All other metals showed titration curves where
the main absorption of free host 1 at 283 nm decreased as a
new absorption was generated at longer wavelengths, suggesting
the formation of metal complexes. However, only two metals,
Mn2+ and Zn2+, displayed a single isosbestic point and a smooth
baseline, similar to what was observed in the case of cadmium.
Our hypothesis is that these three metals (Cd2+, Mn2+, and Zn2+
(r ≈ 0.74-0.95 Å)) form discrete host:guest complexes with
only three species (host, guest, and the host-guest complex)
in solution. A second set of metals (Ag+, Co2+, Ni2+, Cu2+ (r
≈ 0.69-1.0 Å)) displayed no fixed isosbestic point and showed
an increase in the baseline absorption at longer wavelengths,
suggesting multiple intermediates are generated before a final
1:1 complex is formed. Clearly these metals span a range of
sizes and no simple correlation was observed.
The binding constants between host 1 and the metal ions that
show 1:1 stoichiometry with clear isosbestic points (Cd2+, Zn2+,
and Mn2+) were determined with the nonlinear least-squares
regression method.76 Values of the association constants (Ka)
were determined using standard UV titration methods at
concentrations around 10-6 M and are summarized in Table 2.
Host 1 shows higher affinity for Cd2+ (Ka ) 1.5 × 108 M-1
)
versus Zn2+ or Mn2+ (Cd2+ > Zn2+ > Mn2+). This is quite
different from the Irvings-Williams order, which refers to the
relative stabilities of complexes formed by a metal ion in water.
Simple bipyridines and linear oligobipyridines adhere to the
Irving-Williams series in many solvents.77-80 The deviation
from this order experimentally suggests something unusual is
occurring, perhaps selection of the cation to match the cavity
formed from the host’s endo conformation based on size and
(81) Titrations were performed by adding small aliquots (3-5 µL) of guest
solution (10-4 mol L-1) in THF and MeOH mixed solution (v/v ) 99:1)
into 2 mL of host solution (10-6 mol L-1) in THF and MeOH mixed
solution (v/v ) 99:1) by using a microsyringe. UV-vis absorption
changes were monitored during the titration. The difference in absorbance
(∆A) of the host in the presence of the guest and absence of the guest
was recorded, and the data were plotted against [guest].
(82) Giansante, C.; Ceroni, P.; Venturi, M.; Balzani, V.; Sakamoto, J.;
Schluter, A. D. Chem.sEur. J. 2008, 14, 10772–10781.
(83) Ravi, P.; Dai, S.; Tam, K. C. J. Phys. Chem. B 2005, 109, 22791–
22798.
(77) Gong, H. Y.; Wang, D. X.; Zheng, Q. Y.; Wang, M. X. Tetrahedron
2009, 65, 87–92.
(78) Abe, Y.; Wada, G. Bull. Chem. Soc. Jpn. 1981, 54, 3334–3339.
(79) Kaim, W. J. Am. Chem. Soc. 1982, 104, 3833–3837.
(80) Tori, Y.; Yazaki, T.; Kaizu, Y.; Murasato, S.; Kobayashi, H. Bull.
Chem. Soc. Jpn. 1969, 42, 2264–2267.
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A R T I C L E S
Tian et al.
Table 3. Transmittance Changes at 800 nm over Time for Host
1·Metal Complexes
maxima at 285 nm with a shoulder at 305 nm. Upon addition
of silver salts to the solution of 2, spectral changes similar to
those of host 1 were observed: the main absorption of free host
2 at 285 nm decreased and concurrently a new CT absorption
of complex was generated at longer wavelengths (295 nm). The
JOB plot analysis in solution revealed a 1:2 host:guest stoichi-
ometry between host 2 and silver nitrate (Figure 10a). The UV
titration for the host 2·Ag+ complex displayed a clear isosbestic
point, smooth baseline absorption, and a narrow peak-width of
CT absorption band. These observations suggest that in contrast
to the polymer assembly observed in the solid state, a discrete
1:2 host 2·Ag+ complex was rapidly formed in solution.
Given the structure of the 1:2 host 2·Ag+ complex observed
in the solid state, it is likely that the triazinanone amine acts as
additional donor site to enhance the coordination potential of
the single 2,2′-bipyridine. Therefore, we propose a binuclear
coordination structure for host 2·Ag+ complex in solution at
these low concentrations (10-5 M) where two metal ions are
coordinated above and below the macrocyclic plane of 2 with
the central silver coordinated to the bipyridine and the tri-
azinanone tertiary amine (Scheme 4).
light transmittance (%)
complex
0 min
10 min
30 min
60 min
1· Cd2+
1· Ag+
1· Cu2+
1· Ni2+
99.8
100.1
100.1
100.0
99.8
98.0
99.4
99.8
99.8
86.4
96.6
97.3
99.8
84.3
81.0
81.2
changes at 800 nm of the equivalent mixtures between 1 and
metals in THF solution (10-4 M) were monitored. Table 3 shows
the transmittance changes at 800 nm of the mixtures between 1
and metals in THF solution. Although the host 1·Cd2+ complex
did not show any change in light transmittance over time, the
silver, copper and nickel complexes all showed a decrease in
transmittance at 800 nm and over time become visibly turbid.
GPC was further conducted on the freshly prepared host
1·Cu2+ complex in THF (1:1 molar ratio), which showed clear
scattering at 800 nm. Although most of the complex remained
on the membrane filter, a chromatogram of the filtrate displayed
a broad peak with an average molecular weight of ca. Mn )
26300 (Mw/Mn ) 1.622) (see Supporting Information). Under
the same conditions no peak was observed in this high-
molecular-weight region for pure 1. These preliminary studies
suggest that tetradentate host 1 may be forming some oligomeric
complexes with Ag+, Co2+, Ni2+, and Cu2+. We will report more
on these in due course.
Next we examined the ability of hexadentate host 2 to form
coordination complexes in solution. In the solid state, this host
formed a 1:2 host 2·Ag+ complex with the silver and was
coordinated in a bidentate fashion between a 2,2′-bipyridine
from one macrocycle to an sp3 nitrogen of the triazinanone on
a second macrocycle. We were curious to see if host 2 would
form discrete 1:2 host:guest complexes in solution or if
polymeric coordination complexes would be observed. The
UV-vis spectrum of free uncoordinated 2 displayed absorption
We further studied the complexation properties of host 2 in
solution with a series of other transition metal ions (Cd2+, Zn2+,
Cu2+, Ni2+, Co2+, Fe3+, Mn2+, and Cr3+). Some metals (Fe3+, Mn2+
and Cr3+) displayed very weak interactions with host 2 and the
host:guest stoichiometry could not be determined by JOB plots.
Host 2 showed high affinity for other metals, including Cd2+, Zn2+,
Cu2+, Ni2+, and Co2+. JOB plots for host 2 and this series of metals
are consistent with the metals forming host:guest complexes with
1:2 stoichiometries. In addition, each of the respective UV titration
curves displayed clear isosbestic points and smooth baseline
absorptions (see Supporting Information).
The binding constants for the 1:2 host 2·metal complexes
were estimated with nonlinear least-squares regression methods
with two binding constants that represent the two coordination
steps (Table 4). On first observations, one notes that the K1
Figure 10. JOB plot for host 2 and (a) AgNO3, (b) Cd(NO3)2 in THF and methanol mixed solvent (v/v ) 99:1). The total concentration of 2 and metal salts
was kept constant at 1.5 × 10-5 mol L-1. The molar fraction of the metal salts varied in the range of 0.1-0.9, λobs ) 325 nm. Titration curves of 2 solution
(10-6 M) in THF at 298 K upon addition of aliquots of (a) AgNO3 and (b) Cd(NO3)2.
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17628 J. AM. CHEM. SOC. VOL. 131, NO. 48, 2009

Macrocycles with Switchable Metal Binding Sites
A R T I C L E S
Table 4. Binding Constants between Host 2 and Metal Ions at 298 K
Ag+
Cd2+
Zn2+
Cu2+
Ni2+
Co2+
K1 (M-1
K2 (M-1
)
)
1.6 × 106
8.1 × 106
1.9 × 106
1.7 × 108
4.6 × 107
1.4 × 108
1.4 × 105
6.9 × 102
very small
3.3 × 105
4.3 × 103
4.1 × 104
Scheme 4. Schematic Representation of Complex of Host 2 with
suggesting that something unusual was occurring that differed
from typical bipyridines. Complexes of tetradentate host 1 with
Cd2+, Zn2+, and Mn2+ showed high binding constants, and we
predict that in solution these complexes have the metal bound
within the macrocyclic cavity. A second series of metal nitrate
salts also showed 1:1 binding with host 1 but UV titration curves
showed no clear isosbestic point and significant increases were
observed in the baseline at longer wavelengths. Our hypothesis
is that these metals form exo-coordination complexes that may
further associate into oligomers. We are currently studying this
series and are trying to establish their structure by solid-state
methods.
In contrast, the hexadentate host 2 displayed more uniform
interactions with the series of metal nitrate salts tested. All the
metals tested showed 1:2 host:guest stoichiometry and clear
isosbestic points in their UV titrations. The metal complex
stabilities followed the expected Irving-Williams order as
indicated by their Ka’s. The different complexation behaviors
of host 2 is likely due to the presence of additional basic tertiary
amines that enhance the coordination potential of single 2,2′-
bipyridine and likely stabilizes exo complexation of these metals.
The reported hosts combined bipyridine metal binding sites
with a second functional group (ureas in host 1 and tertiary
amines in host 2). The additional functionality has the potential
to guide further assembly of the metal complexes into coordina-
tion polymers, as observed in the helical structure of the host
2·Ag+ complex. Alternatively, these pendent functional groups
open up new possibilities for anion binding and catalysis. We
are currently focused on assessing these new hosts as building
blocks for 3D supramolecular self-assembly and will report on
this in due course.
Silver
values were large and range from a high of 1.7 × 108 (for Cu2+)
to 1.6 × 106 (for Ag+). Host 2 binding affinities followed the
order of Cu2+ > Co2+ > Ni2+ > Fe3+ and Mn2+, as predicted by
the Irving-Williams order.77 In contrast to host 1, it appears
that host 2, shows no unusual size effects in the complexation
process. The binding constants are similar to what is observed
for simple 2,2′-bipyridines.78-80 We propose that host 2 binds
this series of metals via a single conformation, an exo conformer,
which would be expected to give 1:2 binding stoichiometry in
contrast to the endo conformer. The K2 values were found to
be much smaller than K1, the expected result of electrostatic
repulsion between two metal centers. The lower K2 values were
consistent with stable 1:2 host:guest complexes, which generally
had lower propensities to form oligomers.
In summary, we have synthesized two new macrocyclic
ligands containing conformationally mobile 2,2′-bipyridine
groups bridged by either ureas or triazinanone units. The flexible
connections appeared to allow the metal binding sites to freely
rotate and thus favor the structures that best accommodate the
guest. The solid-state structures demonstrated that the bipyridine
units adopted similar conformations in both free hosts, in which
the bipyridines did not adopt either endo or exo orientations.
Complexation of Cd2+ by host 1 resulted in a switch in the
bipyridine conformation to favor an endo structure, in which
the four bipyridine nitrogens were pointed inward coordinating
to a single cadmium atom. This host 1 · Cd2+ complex
[Cd(1)(H2O)(NO3)2] formed layered structures with regular
8.426 Å Cd · · · Cd spacing enforced by one-dimensional
NH· · ·OdC hydrogen bonding. Complexation of silver ion by
host 2 also caused a conformational change in the host and the
bipyridine ligands twisted outward to afford an exo-coordination
site for the host 2·Ag+ structure ([Ag2(2)](SO3CF3)2 ·unknown
solvate). These solid-state structures demonstrated that the metal
binding site was able to access multiple conformations. We are
beginning to explore large metals (Eu, Er, and Ru) whose size
should have a preference for exo-coordination modes. Such
complexes may have interesting optical properties.
Acknowledgment. The authors gratefully acknowledge support
in part for this work from the NSF (CHE-071817), from the
Petroleum Research Fund (44682), and from a grant from the
University of South Carolina, Office of Research and Health
Sciences. Synchrotron data were collected through the SCrALS
(Service Crystallography at Advanced Light Source) program at
Beamline 11.3.1 at the Advanced Light Source (ALS), Lawrence
Berkeley National Laboratory. The ALS is supported by the U.S.
Department of Energy, Office of Energy Sciences Materials
Sciences Division, under contract DE-AC02-05CH11231.
Supporting Information Available: 1H, 13C, and variable
1
temperature H NMR spectra of hosts; X-ray crystallographic
files in CIF format for 1, 2, [Cd(1)(H2O)(NO3)2], and
[Ag2(2)](SO3CF3)2. This material is available free of charge via
the Internet at http://pubs.acs.org.
In solution, the two hosts displayed different types of
complexation behavior. Host 1 consistently formed complexes
with 1:1 host:guest stoichiometry and showed relative metal
complex stabilities that differed from the Irving-Williams order,
JA906474Z
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J. AM. CHEM. SOC. VOL. 131, NO. 48, 2009 17629