Complexation of Sc3N@C80 endohedral fullerene with cyclic Zn-bisporphyrins: Solid state and solution studies

Article abstract of DOI:10.1021/jo200154d

We report the synthesis of two cyclic β-pyrrole unsubstituted meso-tetraphenyl bisporphyrins in which the porphyrin units are connected by two 2,3-hexadiynyl-1,6-dioxo or two hexyl-1,6-dioxo spacers, respectively. Both cyclic porphyrin dimers exist in sol

Full text of DOI:10.1021/jo200154d

ARTICLE
pubs.acs.org/joc
Complexation of Sc3N@C80 Endohedral Fullerene with Cyclic
Zn-Bisporphyrins: Solid State and Solution Studies
Laura P. Hernꢀandez-Eguía,† Eduardo C. Escudero-Adꢀan,† Julio R. Pinzꢀon,‡ Luis Echegoyen,*,‡ and
Pablo Ballester*,†,§,^
†Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països Catalans 16, 43007 Tarragona, Spain
§Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys, 23, 08018, Barcelona, Spain
^Departament de Química, Universitat de les Illes Balears (UIB), 07071 Palma de Mallorca, Spain
‡Department of Chemistry, University of Texas at El Paso (UTEP), Biosciences Building Room 4.132, 500 W. University Avenue,
El Paso, Texas 79968-0519, United States
S Supporting Information
b
ABSTRACT: We report the synthesis of two cyclic β-pyrrole unsubstituted meso-tetraphenyl
bisporphyrins in which the porphyrin units are connected by two 2,3-hexadiynyl-1,6-dioxo or
two hexyl-1,6-dioxo spacers, respectively. Both cyclic porphyrin dimers exist in solution as
mixtures of two conformational isomers. In the solid state, the receptor with diynyl spacers
forms a 1:1 complex with the icosahedral (Ih) isomer of the trimetallic nitride endohedral
fullerene Sc3N@C80. In this complex the receptor adopts a scoop-shaped conformation having
a dihedral angle of 87.25ꢀ between the two porphyrin planes. The hexyl spaced analogue,
however, adopts a similar conformation upon encapsulation of one molecule of Sc3N@C80 in a
self-assembled dimeric capsule. The capsular complexes pack in columns and render the
fullerene units completely isolated. In toluene solution, 1H NMR experiments indicate that the
endohedral fullerene Sc3N@C80 is exclusively bound by the expanded isomer of both dimers.
UV-vis and fluorescence titration experiments confirmed the existence of strong π-π
interactions between the fullerene Sc3N@C80 and the flexible bisporphyrin dimer with hexyl
spacers. At micromolar concentration, the flexible receptor forms only a 1:1 complex with the endohedral fullerene with stability
constant value of Ka = 2.6 ( 0.3 ꢀ 105 M-1
.
’ INTRODUCTION
that exhibits a perfect parallel arrangement of the porphyrin rings
(dihedral angle of 0ꢀ).5 The hexyldioxo spacers are in fact too
long and have to fold in order to adjust the Zn-porphyrin-Zn-
porphyrin to the ideal distance of 12.35 Å for sandwiching C60.
Surprisingly, none of the 15 solid state structures of 1:1 com-
plexes involving endohedral C80 fullerenes and monoporphyrins
retrieved from a search of the Cambridge Structure Database
using “C80” as the query for the compound names displayed the
sandwich binding motif typically observed for C60/C70 binding
monoporphyrins. In addition and to the best of our knowledge,
there are no examples reported of solid state structures of
trimetallic nitride endohedral fullerenes bound to cyclic porphyr-
in dimers or any other type of molecular receptor.6,7
Evidence of attractive fullerene-porphyrin interactions was
first discovered in cocrystallates of fullerenes (C60 and C70) with
monoporphyrins.1 Generally, in these solid state structures it was
observed that the porphyrin formed 1:1 complexes with the
fullerenes.2 The fullerenes are sandwiched between two porphyr-
in units belonging to adjacent 1:1 complexes, and the porphyrin
planes display either a parallel (cofacial) or tilted (zigzag)
arrangement probably due to the maximization of intermolecular
interactions in the packing of the lattice. More recently, the
geometry of 1:1 inclusion complexes formed by cyclic dimers of
porphyrins and fullerenes has also been investigated by X-ray
crystallography and in solution.3 For example, the inclusion
We undertook this work to evaluate the complexation proper-
ties of two cyclic bisporphyrin receptors with the icosahedral
(Ih) isomer of C80 filled with scandium nitride (Sc3N@C80).8
Herein we describe the synthesis of two new β-pyrrole un-
substituted cyclic Zn-porphyrins dimers 3 Zn2 and 4 Zn2
complex of C60 with a cyclic free base porphyrin dimer 1 H4
3
having 1,3-butadiynyl spacers reveals a clamshell-like conforma-
tion for the receptor.4 The porphyrin units are tilted with respect
to each other providing a fullerene-bite angle of 52ꢀ between
their planes. The authors stated that presumably the short
distance between the two porphyrins of the dimer does not
allow accommodating C60 in a parallel conformation of the
receptor. On the other hand, Aida, Saigo, et al. reported that
3
3
(Figure 1) having aryl groups in all meso positions and containing
linker chains analogous to the ones previously reported by Aida
the elongated cyclic dimer 2 Zn2 with flexible hexyldioxo spacers
(O-(CH2)6-O) forms a solid state inclusion complex with C60
Received: January 21, 2011
Published: March 18, 2011
3
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2011 American Chemical Society
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Scheme 1. Synthesis of Cyclic Porphyrin Dimers 3 Zn2 and
3
4 Zn2 Used in This Study
3
diphenylporphyrin. Instead, we decide to approach the prepara-
tion of dimer 4 using the synthetic strategy described by Aida and
Saigo in the preparation of cyclic bisporphyrin receptor 2.9
Figure 1. Line drawings of several cyclic bisporphyrin receptors.
and Saigo.9 We report unprecedented results obtained in the
solid state binding studies of the endohedral fullerene with these
cyclic bisporphyrin receptors, as well as some spectroscopic and
thermodynamic data of their interaction in solution. Molecular
modeling studies suggested that the optimum distance between
the Zn-porphyrin rings of a cyclic dimer in parallel arrangement
and sandwiching one C80 molecule is 14.3 Å. This separation
distance can be easily spanned by flexible hexyldioxo or pentyl-
dioxo spacers (O-(CH2)n-O; n = 5 or 6) connecting the meta
position of trans-phenyl-substituted porphyrins. It is well-known
that pyrrole-β-substituted porphyrins experience an increase in
π-basicity compared with their unsubstituted counterparts and
tend to adopt a shallow concave conformation to avoid steric
clashes between meso and β-pyrrolic substituents. Both effects
are important for the stabilization of the supramolecular aggre-
gates they form with fullerenes. Additionally, the β-pyrrole
substituents surround the fullerene surface to establish weak
CH-π interactions.10
We decided to use a non-β-pyrrole-substituted monoporphyr-
in bearing four meso-aryl substituents, trans-5, in the construction
of the cyclic dimers used in this study. The incorporation of the
meso-mesityl substituents was engineered as an alternative to the
β-pyrrole substitution with the aim of retaining the π-basic
properties of the porphyrin unit. Moreover, the facially encum-
bering methyl groups of the meso-mesityl substituents were
expected to induce a shallow concave cavity on the porphyrin
faces. We also envisaged that the o-methyl groups in the mesityl
substituent could engage in CH-π interactions to increase the
van der Waals contacts with the bound fullerene as β-pyrrole
substituents ussually do.
’ RESULTS AND DISCUSSION
Synthesis. Porphyrins of the ABAB-type like trans-5 H2
3
(Scheme 1) can be prepared by condensing a 5-aryl-substituted
dipyrromethane with an aromatic aldehyde.12 For the synthesis
of monoporphyrin trans-5 H2 we chose to condense 5-mesityl-
3
dipyrromethane 7 with 3-propargyloxibenzaldehyde 8. The use
of sterically hindered 5-dipyrromethanes tends to reduce the
scrambling in MacDonald-type 2 þ 2 condensations and mini-
mize the formation of the cis-A2B2-type porphyrin.13 We applied
the conditions described by Lindsey et al.13 to the reaction of 7
with 8 and isolated trans-5 H2 in 26% yield after two consecutive
3
column chromatography purifications on silica. The treatment of
trans-5 H2 with zinc acetate using standard conditions afforded
3
metalated trans-5 Zn in almost quantitative yield. After stirring a
3
methylene chloride solution of trans-5 Zn, open to air, with a
3
high molar excess of copper(I) chloride and N,N,N0,N0-tetra-
methylethylenediamine (TMEDA) during, 4 h we obtained, after
the usual workup, a dark red solid.14,9
1
The H NMR analysis of an aliquot of the reaction crude
dissolved in CHCl3-d indicated the presence of the proton
signals expected for dimer 3 Zn2 with 2,3-hexadiynyl-1,6-dioxo
3
spacers. Not unexpectedly, we also observed proton signals
corresponding to ditopically coordinated TMEDA molecules
included in the cavity of 3 Zn2.9 The X-ray analysis of a crystal
3
grown from the above CHCl3-d solution confirmed the existence
of the inclusion complex TMEDA⊂3 Zn2 also in the solid state
3
(Figure 2). In order to obtain the uncoordinated cyclic dimer
3 Zn2, we dissolved the reaction crude obtained from the Hay
3
coupling in dichloromethane and added a few drops of 4 N HCl
solution in dioxane to promote the complete demetalation of the
In the course of this work the syntheses of cyclic bisporphyrin
host 6 Zn2, possessing aryl substituents in the four meso positions
3
and pentyldioxo linker chains, was published.11 The synthetic
procedure for 6 relied on a low yielding nontemplate macrocycli-
zation reaction between a 5,15-bis[30-(5-bromopentyl)phenyl]-
10,20-diphenylporphyrin and trans-bis(30-hydroxydiphenyl)-
porphyrin units. We obtained uncoordinated cyclic dimer 3 Zn2
in an overall yield of 58% after subsequent metalation of the free
3
base porphyrin 3 H4 with zinc. Finally, the catalytic hydrogena-
3
tion of 3 Zn2 using 10% Pd/C as catalyst and 2.5 bar of hydrogen
3
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Figure 2. Side and top views of the TMEDA⊂3 Zn2 complex. The
3
Figure 4. (a) Solid state structure of the Sc3N@C80⊂3 Zn2 complex.
bisporphyrin receptor is shown in stick representation, TMEDA and Zn
atoms as CPK models. Hydrogen atoms of the receptor are omitted for
clarity. Notice the adaptability of the cavity size to the ditopic binding of
the diamine and the linearity of the 2,3-butadiynyl linkers.
3
Hydrogen atoms are omitted for clarity and the fullerene is shown in
CPK representation. (b) Zigzag arrays of the Sc3N@C80⊂3 Zn2
3
complexes in the crystal packing. C80 molecules are depicted as the
van der Waals surface, and solvent molecular are omitted for clarity.
of the expanded one. Dimer 4 Zn2 containing fully saturated
3
linker chains displays a completely analogous dynamic and
conformational behavior with a similar isomer ratio.
Solid State Studies. To our delight, we were able to char-
acterize the solid state structures of complexes formed by both
cyclic dimers 3 Zn2 and 4 Zn2 with Sc3N@C80. The X-ray
3
3
diffraction analysis of a single-crystal grown by slow evaporation
from a p-xylene solution containing butadiynyldioxo linked cyclic
receptor 3 Zn2 and 2 equiv of Sc3N@C80 revealed a 1:1
3
inclusion complex, Sc3N@C80⊂3 Zn2. The asymmetric unit is
3
made up of one cyclic receptor, one Sc3N@C80 endofullerene,
and 2.5 p-xylene molecules. The shell of the endofullerene is
disordered over three positions, and the included Sc3N was
modeled over five different positions. In the crystal structure, the
receptor adopts a scoop-like conformation that fully includes the
endohedral fullerene (Figure 4). The dihedral angle between the
two pophyrin planes (four nitrogen mean plane) is 87.25ꢀ. The
porphyrin rings show a reduced concavity to adapt to the convex
surface of the fullerene. In each ring, two trans-meso carbon atoms
are slightly outward from the four-nitrogen mean plane and the
other two are inward. The displacement distances are in the
range of 0.38-0.14 Å. The shortest separation between a carbon
atom of C80 and the Zn-porphyrin centers is 2.961 Å. This value
suggests the existence of strong π-π interactions between the
porphyrins and Sc3N@C80. Many hydrogen atoms of the
substituents of the porphyrin rings are involved in CH-π inter-
actions with the included guest. The crystal packing shows the
formation of a zigzag chain of Sc3N@C80 and cyclic receptors
forming a rod. Overall, it closely resembles the packing motif
Figure 3. CAChe minimized structures of the two conformational
isomers proposed for cyclic dimer 3 Zn2.
3
pressure afforded, after column chromatography purification, the
flexible cyclic dimer 4 Zn2 with hexyldioxo spacers in 55% yield.
3
As a result of their conformational flexibility, both cyclic
porphyrin dimers, 3 Zn2 and 4 Zn2, exist in solution as mixtures
3
3
of the two conformational isomers.15 The 1H NMR spectrum of
3 Zn2 in CHCl3-d showed two different sets of signals for the
3
β-pyrrole protons. The major conformer showed two doublets
resonating at δ = 8.80 and 8.50 ppm (J = 4.6 Hz) for the β-pyrrole
protons (see Supporting Information). The minor conformer
featured four doublets resonating at δ = 8.8, 8.74, 8.44, and 8.41
ppm (J = 4.6 Hz), respectively, for the β-pyrrole protons. Based
on the number of proton signals observed in each set, we assigned
an expanded conformation to the major isomer and a collapsed
conformation to the minor one (Figure 3).
When dimer 4 Zn2 adopts the expanded conformation, it
recently described for the C60⊂1 H4 complex.4 The distances
3
3
possesses two planes of symmetry, as well as a C2 axis perpendi-
cular to the porphyrin rings. Consequently, the four pyrrole units
of each porphyrin ring experience the same magnetic micro-
environment and the β-pyrrole protons resonate as two doublets.
The minor isomer, however, having a collapsed conformation,
features a C2 axis but lacks one of the symmetry planes that are
perpendicular to the porphyrin rings and renders the pyrrole
rings in each porphyrin unit chemically nonequivalent. A 2D-
ROESY experiment showed that the two conformers are in-
volved in a slow chemical exchange process with respect to the
between the centers of adjacent Sc3N@C80 belonging to the
same rod are 11.9 and 11.3 Å. This value is consistent with the
outer diameter of C80, suggesting that the adjacent endohedral
fullerenes are in van der Waals contact with each other. This
structure suggests potential uses of these complexes in organic
photovoltaic (OPV) applications.
The closest fullerene belonging to a neighboring rod is at a
distance of 14.35 Å. Adjacent rods pack to form layers that stack
on top of each other. The 1:1 complexes of different layers are
slightly tilted. Most likely, the uncovered π surface of the
included Sc3N@C80 prefers to be involved in these interesting
fullerene-fullerene interactions rather than forming π-π inter-
actions with the porphyrin rings of other 1:1 inclusion com-
plexes. In fact, this binding behavior is completely in line with the
1
chemical shift time scale of the H NMR spectrum, and that is
why resolved proton signals are observed for each conformer.
The integration of the resolved proton signals allowed us to
calculate a ratio of 80:20 for the conformational isomers in favor
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Figure 5. Solid state structure of the molecular capsule Sc3N@C80⊂-
(4 Zn2)2. Hydrogen atoms are omitted for clarity, the fullerene and the
3
cyclic receptors are shown in stick representation with each bisporphyrin
in a different color (red and blue), and the Sc3N is depicted as a CPK
mode. (b) Columnar arrangement of the molecular capsules in the
packing of the crystal. Sc3N@C80 molecules are depicted as the van der
Waals surface, and solvent molecular are omitted for clarity.
Figure 6. (a) Front and side views of the superimposed cyclic dimers
(red, hexadiynyldioxo spaced 3 Zn2 and yellow, hexyldioxo spaced
3
4 Zn2) with the conformation adopted in the solid state on binding
3
Sc3N@C80, hydrogen atoms are omitted for clarity. (b) Calculated
volumes for the molecular capsule (4 Zn2)2 after removing the en-
3
capsulated Sc3N@C80 (top) and for Sc3N@C80 after deleting the
included Sc3N (bottom). The wide portals present in the capsule were
locked with benzene molecules to fully close the cavity before perform-
ing the volume calculation using the Swiss-pdb software.18
observations made in the solid state structures of the 1:1
complexes of monoporphyrin binding endohedral fullerenes.
The binding motif of a fullerene sandwiched between two
adjacent porphyrin rings which is common for C60/C70 was
never detected.
In solution, Aida et al. reported the formation under stoichio-
metric control of similar 2:1 complexes between a methylrhodium
Surprisingly, the X-ray diffraction analysis of a single crystal
grown from a p-xylene solution of the hexyldioxo linked cyclic
cyclic bisporphyrin 9 Rh2 with much shorter -O(CH2)4-O-
receptor 4 Zn2 with 2 equiv of Sc3N@C80 revealed the forma-
3
3
butyldioxo linkers and C60/C70.17 The observation of this type
of complexes was rationalized by the fact that the short spaced
tion of an unexpected 2:1 encapsulation complex. Two cyclic
receptors self-assemble to form a supramolecular capsule that
traps one molecule of Sc3N@C80 in its interior (Figure 5).
The complex possesses one C2 symmetry plane, and the
asymmetric unit contains one cyclic receptor and half of the
encapsulated endohedral fullerene. Each monomer of the cyclic
receptor in the 2:1 complex also adopts a scoop-shaped con-
formation similar to the one observed for the butadiynyl linked
host 9 Rh2 must adopt a geometry in which the porphyrin units
3
are tilted with respect to one another to accommodate the
fullerenes in combination with an inherently large affinity of
organorhodium porphyrin toward fullerenes. For the hybrid host
9 RhZn only 1:1 complexes were observed with C60. Also
3
relevant is that 2:1 complexes have not been described in solution
or in the solid state for the interaction of analogous hexyldioxo
spaced metallo cyclic porphyrins 2 Zn2 and 2 Rh2 with C60/C70.
equivalent 3 Zn2 in the 1:1 complex. However, the dihedral angle
3
between the two porphyrin planes (four nitrogen mean plane)
decreases slightly to 81.27ꢀ. In this complex the porphyrin rings
are almost completely planar. One of the hexyldioxo linker chains
of the porphyrin dimer is disordered over two positions. The C80
shell is also disordered over two positions generated by the 2-fold
axis while the Sc3N, although highly disordered, is mainly located
on two hypothetical planes that are perpendicular to the porphyr-
in rings of the dimer. The supramolecular capsules form a
columnar arrangement through direct intermolecular interac-
tions, as well as by the intermediacy of a p-xylene molecule
sandwiched between two porphyrin units. The endofullerenes are
placed at center to center distances in the range of 19-20 Å. It is
worth noting that the encapsulation of the Sc3N@C80 in the 2:1
capsular complexes precludes the possibility of establishing direct
π-π interactions between adjacent fullerenes. The calculated
volume for the cavity of the molecular capsule is 1053 Å3, and the
van der Waals volume of the included endohedral Sc3N@C80 is
698 Å3, to yield a packing coefficient value of 0.66 for the resulting
complex (Figure 6).16 Moreover, the calculated volume of the
interior of the C80 cage is 55 Å3, and the van der Waals volume of
the trapped Sc3N is 41 Å3, resulting in a second packing
coefficient value of 0.75. Overall, the architecture of the capsule
displays two different levels of reversible and irreversible molec-
ular encapsulation with different packing coefficients and can be
considered as another example of a “hetero bucky onion”17
3
3
We hypothesize that the larger volume of Sc3N@C80 in combina-
tion with its different electronic polarization contributes to the
formation of the 2:1 complex Sc3N@C80⊂(4 Zn2)2.
3
Different single crystals from those described for
Sc3N@C80⊂(4 Zn2)2 also grew from the same p-xylene solu-
3
tion. X-ray diffraction analysis demonstrated that they corre-
spond to a solvate of Sc3N@C80.19 The packing of the lattice
shows that each Sc3N@C80 is surrounded by 12 molecules of p-
xylene that establish π-π and CH-π interactions plus six
adjacent Sc3N@C80 molecules within a van der Waals interaction
distance (Figure 7).
Solution State Studies. 1H NMR Experiments. We briefly
studied the interaction of the cyclic bisporphyrins 3 Zn2 and
3
4 Zn2 with the endohedral fullerene Sc3N@C80 by means of 1H
3
NMR titration experiments (Figure 8). The addition of approxi-
mately 0.5 equiv of Sc3N@C80 to a 1 mM toluene-d8 solution of
either of the two dimers produced a noticeable upfield shift to the
β-pyrrole protons but only to those assigned to the major isomer.
On the contrary, the chemical shifts of the β-pyrrole protons of
the minor isomer remained completely unaltered, although their
intensity was clearly diminished compared to the ratio found for
the free state of the receptor. Taken together, these observations
indicate that the endohedral fullerene Sc3N@C80 is exclusively
bound by the expanded isomer of the dimers, reinforcing our
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Figure 7. Top and side views of a section of the crystal packing of the
solvate of Sc3N@C80. Solvent molecules are represented in CPK and the
fullerene with van der Waals surface. The central fullerene is shown in
yellow.
Figure 9. (a) UV-vis titration of [3 Zn2] = 9.13 ꢀ 10-7 M with
3
Figure 8. Changes in the region of the β-pyrrole protons during the 1H
NMR titration of [4 Zn2] = 9 ꢀ 10-4 M (left) and [3 Zn2] = 9.1 ꢀ 10-4
Sc3N@C80 in toluene and (b) corresponding fluorescence titration;
0-36 equiv of guest added. Insets: experimental data fitted to the
theoretical isotherm for a 1:1 binding model. Changes in λ = 421 nm for
the UV-vis data and λ= 642 nm for the fluorescence titration.
3
3
(right) with Sc3N@C80 in toluene-d8: (a) 0 equiv, (b) ∼0.5 equiv, and
(c) ∼ 1.2 equiv of Sc3N@C80 added. Minor proton signals correspond-
ing to the collapsed isomer of the cyclic receptor are indicated with an
asterisk.
the addition of slightly more than 1 equiv of Sc3N@C80 induced
additional downfield shifts of the β-pyrrole protons and in the
case of 4 Zn2 the complete disappearance of the signals assigned
previous assignment of the two conformational isomers. Clearly,
the selective consumption of the expanded isomer drives the
conformers’ equilibrium toward the production of additional free
expanded cyclic dimer at the expense of the collapsed isomer, and
this explains the observed reduction of the intensity for the
proton signals. The chemical shift changes observed for the
β-pyrrole protons of the expanded isomer are more pronounced
for the complexation process of Sc3N@C80 with the hexyldioxo
3
to the collapsed isomer. For this receptor the pyrrole protons also
became better defined at this point. Most likely, this is due to the
predominance of the 1:1 complex in solution under these
conditions.21
UV-vis and Fluorescence Experiments. To reduce the
amount of fullerene Sc3N@C80 used in the binding experiments,
we decided to use absorption and emission spectroscopies to
probe the interaction with the cyclic dimer 4 Zn2. The titrations
linker dimer 4 Zn2 than with the unsaturated parent compound
3
3
were carried out in toluene using constant micromolar concen-
trations of the dimers and adding incremental amounts of
Sc3N@C80. Figure 9a and b depicts the changes in the absorption
and emission spectra, respectively, obtained during the titrations
3 Zn2. In striking contrast, only the complexation of Sc3N@C80
3
with 4 Zn2 produced a significant broadening of the signals of
3
the β-pyrrole protons that shift. This different behavior could be
in principle assigned to the formation of a 1:1 complex with
higher thermodynamic and kinetic stability between the
Sc3N@C80 and 4 Zn2 than with 3 Zn2, as previously reported
of 4 Zn2 with Sc3N@C80. The fluorescent titrations were done
3
by excitation at the isosbestic point (427 nm) observed in the
3
3
UV-vis titration.22 During the titration experiment the Soret
for related cyclic bisporphyrin binding with C60/C70.3 However,
the high association constant value determined for the 1:1
band of 4 Zn2 experiences a red-shift of 5 nm with a decrease in
3
intensity, indicating that the binding takes place through π-π
electronic interactions. The molar-ratio graphical method was
used to derive a 1:1 stoichiometry for the complex formed in
solution.23 The nonlinear fit of the absorption titration data to a
1:1 complexation model allowed the calculation of the association
Sc3N@C80⊂4 Zn2 complex (vide infra) together with the ob-
3
servation of the 2:1 complex Sc3N@C80⊂(4 Zn2)2 in the solid
3
state suggests the existence in solution of intermediate exchange
equilibria between the free receptor and complexes with different
stoichiometries to be responsible for the broadening of the
protons signals. However other dynamic processes like an
oscillatory guest motion cannot be ruled out.20,17 Unfortunately,
constant value (Ka) for Sc3N@C80⊂4 Zn2 as 2.3 ꢀ 105 M-1
.
3
Fluorescence titration experiments also confirmed the existence
1
of strong π-π interactions between the fullerene Sc3N@C80 and
the results derived from variable temperature H NMR experi-
the bisporphyrin dimer 4 Zn2.
ments were not sufficient to clarify this point. For both receptors,
3
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The steady state fluorescence of free 4 Zn2 was efficiently
The light brown mixture produced was stirred for 30 min under argon
atmosphere. After this time, the solution was diluted with additional
CH2Cl2 (50 mL) and immediately washed with 0.1 N NaOH (200 mg,
50 mL) and water (50 mL). The organic phase was dried and evaporated
under reduced pressure at 40 ꢀC afforded a brownish oil. The oil was
triturated with cyclohexane yielding 7 as a white solid that was collected
by filtration and washed with additional cyclohexane (0.32 g, 12.7%). 1H
NMR (400.1 MHz, CDCl3, 25 ꢀC) δ (ppm) 7.96 (bs, 2H, NH), 6.89
(s, 2H), 6.68 (s, 2H), 6.17 (q, 2H, J = 2.97 Hz), 6.03 (s, 2H), 5.93 (s, 1H,
meso-H), 2.29 (s, 3H), 2.08 (s, 6H).
3
quenched by the incremental addition of Sc3N@C80, presumably
via photoinduced electron transfer from the receptor to the
fullerene. The fluorescence titration gave a Ka value of 2.9 ꢀ 105 M-1,
which is acceptably close with the value from the absorption
titration. The stability constant of the 1:1 complex Sc3N@C80⊂4
3
Zn2 is 1 order of magnitude larger than for C70⊂4 Zn2.24 Most
3
likely, the greater size of Sc3N@C80 enables an increase in the
aromatic surface interaction between the host and the guest
although the different electronic polarization of the endohedral
fullerene Sc3N@C80 might also contribute to the stronger
binding.
Synthesis of 3-(Prop-2-ynyloxy)benzaldehyde (8)27. To a solution of
2 g (16.38 mmol) of m-hydroxybenzaldehyde and 2.92 g (24.57 mmol)
of propargyl bromide in dry CH3CN (50 mL) were added 3.40 g (24.57
mmol) of K2CO3 and 0.216 g (0.819 mmol) of 18-crown-6. The
solution was refluxed overnight under N2. At the end of the reaction
time a solid has appeared in the reaction mixture. The solid was collected
and washed with CH3CN. Compound 8 (2.6 g, 99%) was obtained after
purification by flash column chromatography on silica of the filtered
crude product. 1H NMR (400.1 MHz, CDCl3, 25 ꢀC) δ (ppm) 10.01 (s,
1H), 7.49 (m, 3H), 7.27 (m, 1H), 4.78 (d, 2H, J = 2.32 Hz), 2.57 (t, 1H,
J = 2.32 Hz).
’ CONCLUSIONS
In conclusion, we have synthesized two macrocyclic bisporphyrin
receptors for the inclusion of fullerenes. We report that receptor
3 Zn2 with hexadiynildioxo spacers forms a 1:1 inclusion com-
plex in the solid state with Sc3N@C80 in which the porphyrin
units are not parallel-oriented but tilted. The crystal packing
reveals a zigzag arrangement of the 1:1 complexes and that the
fullerene guests are in van der Waals contact. The more flexible
3
Synthesis of Zn-5,15-bis(3-propargyloxyphenyl)-10,20-bis(1,3,5-
trimethylphenyl)-porphyrin (trans-5 Zn). A solution of 0.499 g (3.11
3
hexyldioxo spaced host 4 Zn2 produced a capsule-type 2:1
3
mmol) of 3-(prop-2-ynyloxy)benzaldehyde, 8, and 0.823 g (3.11 mmol)
complex in the solid state. The Sc3N@C80⊂(4 Zn2)2 assembly
of 2,20-(mesitylmethylene)bis(1H-pyrrole), 7, in 100 mL of CHCl3 was
3
can be considered as an evolved example of hetero “bucky onion”
displaying two different levels of molecular encapsulation. The
capsular complexes pack in columns and render the fullerene
units completely isolated. Solution studies indicate the formation
of inclusion complexes between the cyclic receptors and the
endohedral fullerene that are stabilized through π-π interac-
tions. At micromolar concentration, using absorption and emis-
sion spectroscopies, we detected for the binding of Sc3N@C80
purged with Ar for 10 min. Then 0.146 g (1.027 mmol) of BF3 O(Et)2
3
was added. The solution was stirred at room temperature for 1 h, and
then DDQ was added. The mixture was stirred at room temperature for
an additional 1 h. The solvent was evaporated under diminished
pressure. The residual solid was purified by column chromatography
on silica gel with hexane/dichloromethane/triethylamine (50/50/1) as
eluent. The third fraction collected was concentrated in vacuo to afford
trans-5 H2 as a purple solid (0.290 mg, 26%). This fraction was analyzed
3
with 4 Zn2the exclusive formation of a 1:1 complex for which we
by HPLC (CH3CN:H2O-0.1%TFA 1 mL/min, 420 nm, sample dis-
solved in CH3CN) eluting as a single peak with a retention time of 21
3
calculated a stability constant value of Ka = 2.6 ( 0.3 ꢀ 105 M-1
.
To the best of our knowledge, this is the first report of solid state
structures of an endohedral fullerene bound to molecular bis-
porphyrin receptors and the second one reporting binding
studies in solution with synthetic molecular receptors.25
min. 0.270 mg (0.335 mmol) of trans-5 H2 purple solid were treated
3
with 0.614 g (3.35 mmol) of Zn(OAc)2 in 40 mL of a CH2Cl2/CH3OH
(3/1): The resulting solution was covered with aluminum foil to protect
it from light, and stirred at room temperature overnight. Then, the
solvent was evaporated in vacuo and the metalated porphyrin, trans-
5 Zn, (0.230 g, 85%) was obtained after purification of the crude by flash
3
’ EXPERIMENTAL SECTION
chromatography on neutral aluminum oxide using a gradient of
CH2Cl2/THF (100:0 to 90:10) as eluent. 1H NMR (400.1 MHz,
CDCl3, 25 ꢀC) δ (ppm) 9.00 (d, 4H, J = 4.73 Hz), 8.85 (d, 4H, J =
5.06 Hz), 7.93 (m, 4H), 7.67 (t, 2H, J = 7.76 Hz), 7.38 (dd, 2H, J = 8.44
and 2.30 Hz), 7.34 (s, 4H), 4.83 (t, 4H, J = 1.84 Hz), 2.69 (s, 6H), 2.58
(t, 2H, J = 2.36 Hz), 1.91 (s, 12H); HR-MS (MALDI) m/z calcd for
C56H44N4O2Zn (Mþ) 868.2750, found 868.2740 (1 ppm); UV-vis
(toluene) λmax (ε, M-1 cm-1) 423 (586731.92).
General Methods. All commercial reagents, unless otherwise
noted, were reagent grade and used without further purification.
Solvents were of HPLC grade quality, obtained commercially and used
without further purification. Anhydrous solvents were obtained from a
solvent purification system (SPS). Pyrrole was freshly distilled under
1
vacuum just prior to use. H NMR spectra were recorded on a 400.1
MHz for 1H NMR and 100.6 MHz for 13C {1H}) and a 500.1 MHz for
1H NMR and 125.6 MHz for 13C {1H} NMR spectrometers. UV-vis
spectra were measured on a UV-vis spectrophotometer and the
measurements of fluorescence were obtained on a luminescence spec-
trometer. High resolution mass spectra were obtained using a MALDI-
TOF mass spectrometer. High performance liquid chromatography
analyses were performed on a chromatograph equipped with a UV-
vis detector. Analytical gel permeation chromatography (GPC) was
carried out on a toluene (7.8 ꢀ 300 mm) column with 100% toluene.
GPC purification was carried out on a column (19 ꢀ 300 mm) with
100% toluene. Flash column chromatography was performed with
Silica gel.
Synthesis of TMEDA⊂3 Zn2. To 200 mL of CH2Cl2 solution
3
containing 137 mg (0.157 mmol) of trans-5 Zn and 1.09 g (11.02
3
mmol) of copper(I) chloride was added 1.3 mL (11.02 mmol) of
TMEDA. The mixture was stirred for 4 h under air and at room
temperature. During this time the reaction mixture changes its color
from fuchsia to green. At the end, the reaction mixture was washed with
water, dried over Na2SO4, and evaporated to dryness. An aliquot of the
crude product (0.219 g, 75%) was purified by preparative GPC (column
in toluene, 1 mL/min; 420 nm; 1 mg/mL; inject 5 μL) with major peak
eluting at 7.45 min and minor peak at 6.75 min. The peak at 6.75 min is
assigned to polymers formed in the reaction The peak eluting at 7.45 min
Synthesis of 2,20-(Mesitylmethylene)bis(1H-pyrrole) (7)26. A solu-
tion of 1.417 g (9.56 mmol) of mesitylaldehyde in 25.7 g (382 mmol) of
freshly distilled pyrrole was degassed by flushing an argon flow for 20
corresponds to the diacetylenic bisporphyrin complex TMEDA⊂3 Zn2.
3
1H NMR (400.1 MHz, CDCl3, 25 ꢀC) δ (ppm) 8.64 (d, 8H, J = 3.30
Hz), 8.40 (d, 8H, J = 3.30 Hz), 8.01 (d, 4H, J = 6.84 Hz), 7.64 (t, 4H,
J = 7.79 Hz), 7.25 (s, 8H), 7.12 (s, 4H), 6.91 (d, 4H, J = 7.31 Hz), 4.38
min. Then, 0.136 g (0.956 mmol) of BF3 (OEt)2 was added by syringe.
3
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The Journal of Organic Chemistry
ARTICLE
(s, 8H), 2.62 (s, 12H), 2.61 (s, 12H), 1.28 (s, 12H), -3.62 (s, 12H, CH3
of coordinated TMEDA), -5.03 (s, 4H, CH2 of coordinated TMEDA)
’ ACKNOWLEDGMENT
L.P.H.-E. and P.B. are grateful for funding from MICINN
(CTQ2008-00222/BQU, Consolider Ingenio 2010 Grant CSD2006-
0003), DURSI (2009SGR6868) and ICIQ Foundation. L.E. and
J.R.P. gratefully acknowledge generous support from the U.S.
National Science Foundation, grant DMR-0809129.
Synthesis of Diacetylenic Bisporphyrin (3 Zn2). The reaction crude
3
containing the acetylenic bisporphyrin coordinated with TMEDA,
TMEDA⊂3 Zn2, obtained above was dissolved in a minimum amount
3
of CH2Cl2 and treated with few drops of a solution of HCl 4 N indioxane.
The resulting green mixture was stirred for 30 min and diluted with
additional CH2Cl2. The organic phase was washed with water, dried,
filtered, and evaporated to dryness. The obtained crude was purified by
preparative GPC (toluene column, flow 6 mL/min, injections 20 mg/
mL), collecting the second peak eluting at 7.31 min that corresponds to
’ REFERENCES
(1) Sun, Y. P.; Drovetskaya, T.; Bolskar, R. D.; Bau, R.; Boyd,
P. D. W.; Reed, C. A. J. Org. Chem. 1997, 62, 3642–3649.
(2) Boyd, P. D. W.; Hodgson, M. C.; Rickard, C. E. F.; Oliver, A. G.;
Chaker, L.; Brothers, P. J.; Bolskar, R. D.; Tham, F. S.; Reed, C. A. J. Am.
Chem. Soc. 1999, 121, 10487–10495.
(3) Tashiro, K.; Aida, T. Chem. Soc. Rev. 2007, 36, 189–197.
(4) Nobukuni, H.; Shimazaki, Y.; Uno, H.; Naruta, Y.; Ohkubo, K.;
Kojima, T.; Fukuzumi, S.; Seki, S.; Sakai, H.; Hasobe, T.; Tani, F. Chem.—
Eur. J. 2010, 16, 11611–11623.
(5) Zheng, J. Y.; Tashiro, K.; Hirabayashi, Y.; Kinbara, K.; Saigo, K.;
Aida, T.; Sakamoto, S.; Yamaguchi, K. Angew. Chem., Int. Ed. 2001,
40, 1858–1861.
(6) Perez, E. M.; Martin, N. Pure Appl. Chem. 2010, 82, 523–533.
(7) Perez, E. M.; Martin, N. Chem. Soc. Rev. 2008, 37, 1512–1519.
(8) Elliott, B.; Yu, L.; Echegoyen, L. J. Am. Chem. Soc. 2005,
127, 10885–10888.
(9) Tashiro, K.; Aida, T.; Zheng, J. Y.; Kinbara, K.; Saigo, K.;
Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 1999, 121, 9477–9478.
(10) Takahashi, O.; Kohno, Y.; Nishio, M. Chem. Rev. 2010,
110, 6049–6076.
(11) Vaijayanthimala, G.; Krishnan, V.; Mandal, S. K. J. Chem. Sci.
(Bangalore, India) 2008, 120, 115–129.
(12) Lee, C. H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427–11440.
(13) Littler, B. J.; Ciringh, Y.; Lindsey, J. S. J. Org. Chem. 1999,
64, 2864–2872.
(14) Anderson, S.; Anderson, H. L.; Sanders, J. K. M. J. Chem. Soc.,
Perkin Trans. 1995, 1, 2247–2254.
the pure diacetylenic bisporphyrin 3 H4 (0.180 g, 62%). A solution of 98
3
mg (0.061 mmol) of 3 H4 in 36 mL of a mixture of CH2Cl2/ CH3OH
3
(3:1) was treated with 0.40 g (1.217 mmol) of Zn(OAc)2. The reaction
mixture was covered with aluminum foil to protect it from light and
stirred at room temperature overnight. The reaction can be monitored
using alumina TLC plates and CH2Cl2/hexane (1/1) as eluent. At the
end of the reaction, the solvent was evaporated and 3 Zn2 was obtained
3
as a purple solid (62 mg, 58.6%) after purification of the crude by flash
chromatography on neutral aluminum oxide using a gradient of CH2Cl2/
THF (100:0 to 90:10) as eluent. 1H NMR (400.1 MHz, CDCl3, 25 ꢀC) δ
(ppm) 8.80 (d, 8H, J = 4.74 Hz, H2), 8.49 (d, 8H, J = 4.74 Hz, H1), 7.81
(d, 4H, J = 7.30 Hz, H4), 7.66 (s, 4H, H3), 7.61 (t, 4H, J = 7.30 Hz, H5),
7.33 (dd, 4H, J = 8.51 and 2.43 Hz, H6), 7.18 (s, 4H, H7), 6.79 (s, 4H,
H8), 4.78 (s, 8H, H9), 2.48 (s, 12H, H10), 1.77 (s, 12H, H11), 0.76
(s, 12H, H12), see Figure S4 for proton assignments; HR-MS (MALDI)
m/z calcd for C112H84N8O4Zn2 (Mþ) 1732.5193, found 1732.5244
(3 ppm); UV-vis (toluene) λmax (ε, M-1 cm-1) 418 (789190.67).
Synthesis of Bisporphyrin Cyclic Dimer (4 Zn2). To a 10 mL THF
3
solution containing 38 mg of 3 Zn2 (0.023 mmol) was added 14 mg of
3
Pd/C suspended previously in 4 mL of THF. The obtained suspension
was stirred under H2 at 2.5 bar during 15 h. The progress of the reaction
was monitored using silica TLC plates and CH2Cl2/hexane (1/1) as
eluent. After this time, the reaction was filtered over Celite to remove the
catalyst and the organic solvent evaporated in “vacuo”. The solid reaction
crude was purified by column chromatography on neutral alumina using
(15) Golubchikov, O. A.; Mamardashvili, N. Z.; Semeikin, A. S. Zh.
Org. Khim. 1993, 29, 2445–2452.
CH2Cl2 as eluent to yield 4 Zn2 as a purple solid (20 mg, 55%). 1H NMR
3
(16) Mecozzi, S.; Rebek, J. Chem.—Eur. J. 1998, 4, 1016–1022.
(17) Ouchi, A.; Tashiro, K.; Yamaguchi, K.; Tsuchiya, T.; Akasaka,
T.; Aida, T. Angew. Chem., Int. Ed. 2006, 45, 3542–3546.
(18) Swiss-Pdb Viewer Deep View v4.0, http://spdbv.vital-it.ch/.
(19) Stevenson, S.; Lee, H. M.; Olmstead, M. M.; Kozikowski, C.;
Stevenson, P.; Balch, A. L. Chem.—Eur. J. 2002, 8, 4528–4535.
(20) Tashiro, K.; Hirabayashi, Y.; Aida, T.; Saigo, K.; Fujiwara, K.;
Komatsu, K.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 2002,
124, 12086–12087.
(400.1 MHz, CDCl3, 25 ꢀC) δ (ppm) 8.77 (d, 8H, J = 4.67 Hz, H2), 8.62
(d, 8H, J = 4.67 Hz, H1), 7.79 (d, 4H, J = 7.27 Hz, H4), 7.58 (t, 4H, J = 7.27
Hz, H5), 7.48 (s, 4H, H3), 7.26 (dd, 4H, J = 7.27 and 2.60 Hz, H6), 7.24
(s, 4H, H7), 7.17 (s, 4H, H8), 4.01 (t, 8H, J = 6.23 Hz, H9), 2.63 (s, 12H,
H12), 1.85 (m, 8H, H11), 1.72 (s, 12H, H13), 1.50 (m, 8H, H10), 1.47
(s, 12H, H14), see Figure S5 for proton assignments; HR-MS (MALDI)
m/z calcd for C112H100N8O4Zn2(Mþ) 1748.6445, found1748.6248 (11
ppm); UV-vis (toluene) λmax (ε, M-1 cm-1) 419 (772176.67).
(21) Assuming a noncooperative binding process a value for the
stability constant of the 2:1 complex can be statistically estimated as K =
Km2 = 4 ꢀ 1010 M-2. Km is the microscopic binding constant value for
’ ASSOCIATED CONTENT
the interaction of Sc3N@C80 with 4 Zn2. The Km was calculated from
3
Supporting Information. 1H NMR spectra of trans-
S
the UV-vis titration using a simple 1:1 binding model. The simulated
speciation profiles considering the formation of both 1:1 and 2:1
complexes indicate that the 2:1 complex is formed at a negligible extent
in the concentration range in which the UV-vis and fluorescence
titrations have been performed. This result supports the simplification
of the binding model used for the mathematical analysis of these titration
data. On the contray, at 0.9 mM concentration and with 0.5 equiv of
b
5 Zn, TMEDA⊂3 Zn2, 3 Zn2, and 4 Zn2. ROESY spectra of
3
3
3
3
the mixture of conformational isomers for 3 Zn2 and 4 Zn2.
3
3
General procedures used in the spectroscopic titrations and the
mathematical analysis of the data obtained. Comments on the
single crystal X-ray diffraction data and X-ray crystallographic
files (in CIF format) for the complexes TMEDA⊂3 Zn2,
Sc3N@C80 the speciation profile shows that [4 Zn2 ] = 8.5 ꢀ 10-5
,
3
3
[1:1] = 1.0 ꢀ 10-4 M, and [2:1] = 3.5 ꢀ 10-4 M and with 1 equiv
Sc3N@C80⊂3 Zn2, Sc3N@C80⊂(4 Zn2)2, and the p-xylene
3
3
[4 Zn2 ] = 1.0 ꢀ 10-6, [1:1] = 4.8 ꢀ 10-4 M, and [2:1] = 1.9 ꢀ 10-4 M.
solvate of Sc3N@C80. This material is available free of charge
via the Internet at http://pubs.acs.org.
3
(22) Solladie, N.; Walther, M. E.; Gross, M.; Figueira Duarte, T. M.;
Bourgogne, C.; Nierengarten, J.-F. Chem. Commun. 2003, 2412–2413.
(23) Beltranporter, A.; Beltranporter, D.; Cervilla, A.; Ramirez, J. A.
Talanta 1983, 30, 124–126.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: pballester@iciq.es; echegoyen@utep.edu.
(24) Hernꢀandez-Eguía, L. P. Ph.D. Thesis, Universitat Rovira i
Virgili, Tarragona, 2010.
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ARTICLE
(25) Gil-Ramirez, G.; Karlen, S. D.; Shundo, A.; Porfyrakis, K.; Ito,
Y.; Briggs, G. A. D.; Morton, J. J. L.; Anderson, H. L. Org. Lett. 2010,
12, 3544–3547.
(26) Lee, C. H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427–11440.
(27) Srinivasan, R.; Uttamchandani, M.; Yao, S. Q. Org. Lett. 2006,
8, 713–716.
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