Dimeric molecular capsules under redox control

Article abstract of DOI:10.1021/ja045587m

A new tetraferrocenylurea calix[4]arene was prepared in order to investigate its dimerization properties. ¹H NMR spectroscopic data clearly established that this calixarene forms stable dimeric molecular capsules in chloroform solution. The dim

Full text of DOI:10.1021/ja045587m

Published on Web 10/29/2004
Dimeric Molecular Capsules under Redox Control
Kwangyul Moon and Angel E. Kaifer*
Center for Supramolecular Science and Department of Chemistry, UniVersity of Miami,
Coral Gables, Florida 33124-0431
Received July 22, 2004; E-mail: akaifer@miami.edu
The design and self-assembly of molecular capsules is a very
active topic of research in modern chemistry.1 A well-established
methodology for the assembly of these supramolecular structures
relies on the formation of kinetically stable, hydrogen-bonded
dimers between two calix[4]arenes, each functionalized with four
urea groups on its upper rim.2 The groups of Rebek and Bo¨hmer
have independently shown that two molecules of tetraphenylurea
calix[4]arenes (similar to 1, but with different aliphatic chains in
the lower rim) interact head-to-head to form a robust seam of hy-
drogen bonds between the four urea groups in each of the calixarene
upper rims, giving rise to a dimer with S8 symmetry. In this work,
we demonstrate that the functionalization of the urea groups with
redox-active, terminal ferrocenyl residues gives rise to calixarene
hosts (compound 2) that can also form kinetically stable dimers
(molecular capsules). However, the reversible oxidation of the ferro-
cene groups induces the destabilization of the dimers and their
redox-controlled dissociation.
Figure 1. Partial 1H NMR spectra (300 MHz) of 2 in (A) CDCl3 and 5%
DMSO-d6 solution and (B) in pure CDCl3.
The preparation of calixarenes 1, 2, 4, and 5 followed established
methodology (see Supporting Information for details). Compound
2 was synthesized using the reaction of the corresponding tetraamino
calix[4]arene3 with ferrocene acyl azide. This reagent was prepared
by treatment of ferrocene carboxylic acid with diphenyl phosphoryl
azide in dry dichloromethane. The 1H NMR spectrum of 2 in CDCl3
only shows the characteristic peak patterns expected for the
kinetically stable head-to-head dimer (Figure 1B). For instance, the
spectrum shows two doublets (7.54 and 5.95 ppm) for the calixarene
aromatic protons, with the typical meta coupling constant of 2.1
Hz. These two signals have their origin on the different microen-
vironments created by the “locked” urea groups since one of the
aromatic protons faces the N-H urea protons and the other faces
the carbonyl group. Interestingly, the ferrocene protons on the
cyclopentadienyl ring attached to the urea also split [5.19 and 4.05
ppm for the adjacent protons (labeled “e” in Figure 1) and 4.55
and 4.05 ppm for the “f” protons], revealing the overall rigidity of
the structure. Addition of 5% DMSO-d6 to this solution disrupts
the hydrogen bonding and leads to a completely different spectrum
that corresponds to monomeric 2 (Figure 1A). These data provide
unequivocal evidence for the formation of kinetically stable dimers
(molecular capsules) by compound 2 in CDCl3 solution. Clearly,
the functionalization of the upper rim ureas with terminal ferrocenyl
residues does not alter the self-assembly properties of these calix-
[4]arenes.
Chart 1. Structures of the Tetraurea Calix[4]arenes Used in This
Work. In Compound 2, Fc Stands for -(C5H4)Fe(C5H5).
(Figure 2). The voltammetric data reveal that the ferrocene residues
behave as independent redox centers, undergoing oxidation at very
similar potentials and exhibiting undetectable electronic com-
munication among them. On the other hand, the shape of the
voltammetric wave observed in these experiments departs from
that expected for a perfectly reversible electrochemical oxidation
process. Specifically, the anodic and cathodic peak currents are
dissimilar, and distortions due to the low solubility of the oxidized
form may also affect the voltammetric behavior. For comparison,
the cyclic voltammogram of the model ferrocenyl-urea compound
3 shows the reversible oxidation of the ferrocene residue at a half-
wave potential of +0.31 V (Supporting Information).
1H NMR spectroscopic experiments indicate that 2 is present as
a dimer in CDCl3/CD3CN (10:3, v/v), while larger ratios of
CD3CN in the solution lead to dimer dissociation. Thus, the
electrochemical behavior of 2 was investigated in CHCl3/CH3CN
(10:1, v/v) solution containing 0.2 M tetrabutylammonium hexa-
fluorophosphate (supporting electrolyte). Cyclic voltammetry of 1.0
mM 2 in this solvent system reveals a single wave at a half-wave
potential of +0.28 V versus Ag/AgCl that corresponds to the one-
electron oxidation of the four ferrocene groups in each calixarene
Upon oxidation, calixarene 2 contains four paramagnetic ferro-
cenium units that broaden and shift considerably the 1H NMR
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J. AM. CHEM. SOC. 2004, 126, 15016-15017
10.1021/ja045587m CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Redox Control on the Dimerization Equilibrium of
Tetraferrocenylurea Calix[4]arene 2
Figure 2. Cyclic voltammetric behavior on a glassy carbon electrode (0.071
cm2) of a CHCl3/CH3CN (10:1, v/v) solution containing 1.0 mM 2 and 0.2
M TBAPF6. Scan rate ) 0.1 V/s.
dimeric molecular capsule by two identical redox-active compo-
nents. We are continuing the investigation of these systems in the
hope that they may become useful for controlled drug release and
related applications.
signals of the nearby protons in this molecule. However, the lower
rim aliphatic protons are clearly observed and can be utilized to
determine the diffusion coefficient (Do) of oxidized 2 using PGSE
NMR techniques.4 After oxidation with trifluoroacetic acid (TFA),
Acknowledgment. The authors are grateful to the NSF for the
generous support of this work (to A.E.K., CHE-0240295).
we measured a value of 7.5 × 10-6 cm2/s in pure CDCl3 for 24+
,
Supporting Information Available: Synthetic details, cyclic
voltammogram for 3, FT-IR data for 2 and 3, and NMR data for model
compounds 4 and 5. This material is available free of charge via the
Internet at http://pubs.acs.org.
while the same experiment with reduced 2 yielded a value of 3.8
× 10-6 cm2/s. The 2-fold increase of the Do values upon oxidation
of the ferrocene groups constitutes very strong evidence for the
oxidation-induced dissociation of the dimer.
FT-IR spectroscopy also proved very useful for monitoring
dimerization in the oxidized state. For instance, the carbonyl region
of the FT-IR spectrum of a 2.8 mM 2 solution in CHCl3 shows the
amide I peak (CdO stretch) at 1657 cm-1, which is consistent with
its involvement in hydrogen bonding. Oxidation of 2 with TFA
leads to extensive changes in this spectral region, with the main
peaks observed at 1783 and 1698 cm-1 (Supporting Information).
These peak positions strongly suggest that the carbonyl groups are
no longer involved in hydrogen bonding interactions. Could
electronic effects related to the oxidation of the ferrocene groups
be responsible for the frequency shifts observed? We investigated
the FT-IR spectra of compound 3 to answer this question. The amide
I peak of 3 was observed at 1678 (before oxidation) and 1683 cm-1
(after TFA oxidation). Therefore, electronic effects are not respon-
sible for the large frequency shifts observed upon oxidation of 2.
Furthermore, we also investigated the FT-IR spectra of 2 in CHCl3
solution also containing 5% DMSO, which is enough to prevent
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1
dimer formation according to our H NMR spectroscopic experi-
ments. In this medium, the amide I peak shifted from 1693 to 1698
cm-1 upon TFA oxidation, again a ∼5 cm-1 blue shift consistent
with that detected upon oxidation of 3.
1H NMR spectroscopic data obtained with model compounds 4
and 5 provide additional support for the disruption of the dimeric
molecular capsule when positive charges are present on the
calixarene upper rim (Supporting Information). Therefore, all our
data reveal that the stable dimers of tetraferrocenylurea calix[4]-
arene 2 undergo dissociation upon oxidation of the ferrocene groups
(Scheme 1). The four positive charges acquired by each calixarene
after chemical or electrochemical oxidation give rise to strong
electrostatic repulsions between the two oxidized halves of the
dimeric molecular capsule. The dimerization equilibrium of 2 may
thus be controlled by its oxidation state. As far as we know, this is
the first reported example of redox control on the formation of a
(3) Rinco´n, A. M.; Prados, P.; de Mendoza, J. J. Am. Chem. Soc. 2001, 123,
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