Synthesis of a calix[4]arene derivative for isolation of a stable cation radical salt for use as a colorimetric sensor of nitric oxide

Article abstract of DOI:10.1021/ja0454900

We have designed and synthesized a modified calixarene derivative (1) that allows, for the first time, the isolation of a stable cation radical salt that binds a single molecule of nitric oxide deep within its cavity with remarkable efficiency (K_NO >10⁸ M^-1), as demonstrated by isolation of a crystalline complex [1, NO]⁺ and its characterization by X-ray crystallography as well as by optical spectroscopy. Furthermore, the ready accessibility of the calixarene cation radical will allow the exploration of its use for developing efficient sensing devices for nitric oxide based on the accompanied color changes. Copyright

Full text of DOI:10.1021/ja0454900

Published on Web 09/30/2004
Synthesis of a Calix[4]arene Derivative for Isolation of a Stable Cation Radical
Salt for Use as a Colorimetric Sensor of Nitric Oxide
Rajendra Rathore,* Sameh H. Abdelwahed, and Ilia A. Guzei†
Marquette UniVersity, Department of Chemistry, P.O. Box 1881, Milwaukee, Wisconsin 53201-1881
Received July 27, 2004; E-mail: rajendra.rathore@marquette.edu
Scheme 2. Synthesis of Electroactive Calixarene Derivativesa
The calixarene derivatives are extensively utilized as molecular
platforms for the design and synthesis of novel materials in
supramolecular chemistry.1 The cofacial arrangement of aromatic
moieties in various t-buytlcalix[4]arene conformers (especially in
the 1,3-alternate conformer) creates an electron-rich cavity that
allows the cationic nitrosonium ion (NO+) to penetrate deep inside
the cavity of these molecular hosts.2 To make use of the calixarene
cavity for binding electron-rich guests such as nitric oxide (NO), a
molecule of vital biological importance,3 one would require an
appropriate electronic modification of the aryl groups of calixarenes
to yield an electron-deficient cavity.4 The cation radicals of various
conformers of parent calixarene ethers, formed by 1-electron
oxidation at low temperatures (-78 °C), contain the desired
electron-deficient cavities that may be well suited for binding
electron-rich guests; however, these cation radicals are highly
a Conditions: (a) phenol, AlCL3, toluene, reflux, 71%; (b) n-propyltosyl-
unstable and decompose even at -78 °C upon prolonged storage
(>10 min).5 It is evident that one requires a modified calixarene
derivative that can yield a stable cation radical without altering the
shape and size of the cavity. Rathore et al.6 have recently noted
that the incorporation of 2,5-dimethoxytolyl as an electron donor
on the vertexes of the hexaphenylbenzene core allowed the isolation
of a highly robust hexacation radical salt from hexakis(4-methyl-
2,5-dimethoxybiphenyl)benzene. It was envisioned that the synthesis
of a modified calixarene derivative in which the tert-butyl groups
in parent calixarene are replaced by the same electron-donor groups
(see structure 1) may allow the isolation of a stable cation radical
salt. Moreover, it is expected that the hole will be shared among
the 2,5-dimethoxy-tolyl and the aryl groups of the calixarene core
in its cation radical salt 1+• (See Scheme 1).
ate, Cs2CO3, DMF, 80 °C, 82%; (c) NBS, methanol, 67%; (d) 2,5-
dimethoxytolylmagnesium bromide (4.2 equiv), (PPh3)PdCl2,THF, reflux,
75%.
isolation of a crystalline complex [1, NO]+, and by its characteriza-
tion by X-ray crystallography as follows.
The electroactive calixarene derivative 1 was obtained by a four-
step reaction sequence from the readily available tert-butylcalix-
[4]arene (2) as summarized in Scheme 2. The key step in the
synthesis involved a Kumada-type coupling of tetrabromo-calix-
arene 5 with 2,5-dimethyoxytolylmagnesium bromide in the pres-
ence a catalytic amount of bis-triphenylphosphinepalladium dichlo-
ride in THF in excellent yield (see Scheme 2). The experimental
details and the characterization data for 1 are described in
Supporting Information. Moreover, the structure determination of
tetraarylcalixarene ether 1 by X-ray crystallography confirmed that
the replacement of tert-butyl groups with 2,5-dimethoxytolyl (Ar)
groups did not alter the shape or the size of the cavity in any
significant way (vide infra).
Scheme 1
With the tetraarylcalixarene 1 at hand, we first evaluated its
electron-donor strength and the initial indication of the cation radical
stability by cyclic voltammetry. Thus, an electrooxidation of 1 in
dichloromethane solution (containing n-tetrabutylammonium hexaflu-
orophosphate as a supporting electrolyte) at a scan rate of 200 mV
s-1 showed two reversible oxidation waves together with an
irreversible wave in its cyclic voltammogram (see Figures S1 and
S2 in Supporting Information). A quantitative evaluation of the CV
peak currents with added ferrocene (as an internal standard) revealed
that the first oxidation potential (Eox1 ) 1.07 V vs SCE) was
significantly lower than the second (Eox2 ) 1.27 V) and the higher
oxidation events (Eox3 > 1.55 V). Such an observation of the
splitting of the oxidation waves arising from four Ar groups7 in
the CV of 1 suggests that the oxidation of one of the Ar groups
affects the removal of further electrons from the other three Ar
groups and thus provides the first indication that the aryl groups
are electronically coupled to each other via the calixarene frame-
work (see Scheme 1).7
Accordingly, herein we now report the preparation of a (1,3-
alternate) calix[4]arene ether derivative (1) that allows the prepara-
tion of a stable cation radical either via a chemical or an equivalent
electrochemical oxidation, and the resulting cation radical (with
its intact electron-deficient cavity) shows dramatic color changes
upon exposure to gaseous nitric oxide (NO). Moreover, the
remarkable efficiency of this modified calixarene host toward NO
binding is demonstrated with the aid of optical spectroscopy, by
† Current address: Molecular Structure Laboratory, Department of Chemistry,
University of Wisconsin, Madison, WI.
9
13582
J. AM. CHEM. SOC. 2004, 126, 13582-13583
10.1021/ja0454900 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Figure 2. X-ray crystal structure of NO-bound 1,3-alternate conformer of
tetraarylcalix[4]arene ether [1, NO]+. Hydrogens and hexachloroantimonate
anion (SbCl6-) are omitted for the sake of clarity.
the calixarene core (see Figure 2). The noncovalent interaction of
the cationic calixarene cavity positions NO between the cofacial
aromatic rings (of the calixarene core) at a distance of 2.4 Å that
is substantially shorter than the van der Waals contact (3.2 Å).
Furthermore, the similarity of the bond lengths in dimethoxytolyl
groups both in neutral 1 and its cationic NO-bound complex
suggests that the charge is largely localized on the calixarene core
in [1/NO]+.
In summary, we have designed and synthesized a modified
calixarene derivative that allows, for the first time, the isolation of
a stable cation radical that binds a single molecule of nitric oxide
deep within its cavity with remarkable efficiency (KNO >108 M-1).
Moreover, the ready accessibility of the electron-rich calixarene
donor as well as its (electron-poor) cation radical will allow us to
explore their use for developing efficient sensing devices for nitric
oxide based on the accompanying color changes as well as using
electrochemical techniques.10 These works are being pursued
actively.
-
Figure 1. Spectral changes upon the reduction of MA+• SbCl6 (red) by
an incremental addition of 1 to its cation radical 1+• (green) in CH2Cl2 at
22 °C. Inset: plot of depletion of MA+• (red line, 516 nm) and formation
of 1+• (black squares, 1200 nm) against the number of equivalents of 1
added. Blue spectrum is obtained upon exposure of the green 1+• to gaseous
NO.
The electrochemical reversibility of 1 prompted us to carry out
its oxidation to the corresponding cation radical using the stable
aromatic cation radical salts MA+• SbCl6 as an oxidant (Ered
-
)
1.11 V vs SCE).8 Thus, Figure 1 shows the spectral changes
attendant upon the reduction of 2.2 × 10-4 M MA+• [λmax (log ꢀ)
) 516 nm (3.86)] by incremental additions of 4.1 × 10-3 M 1 at
22 °C in dichloromethane. The presence of well-defined isosbestic
points at λmax ) 465 and 542 nm in Figure 1 are indicative of the
uncluttered character of the electron transfer. Furthermore, a plot
of the depletion of MA+• (i.e., decrease in the absorbance at 516
nm) and formation of 1+• (i.e., increase in the absorbance at 1200
nm) against the increments of added 1 (inset, Figure 1) established
that MA+• was completely consumed after the addition of 1 equiv
of 1; and the resulting absorption spectrum of 1+• [λmax (log ꢀ) )
375 (3.78), 620, 1200 nm] remained unchanged upon further
addition of neutral 1 (i.e., eq 1).
Acknowledgment. We thank the donors of the Petroleum
Research Fund (AC12345), administered by the American Chemical
Society, and National Science Foundation (Career Award) for
financial support.
MA+• + 1 f 1+• + MA
(1)
Supporting Information Available: Preparation and spectral data
for 1 and various intermediates, 1+•, cyclic voltammograms, and X-ray
data for 1 and [1/NO]+ (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
The green-colored 1+• obtained in eq 1 is stable at 22 °C, and
the neutral 1 can be recovered quantitatively upon reduction with
zinc dust. Moreover, the pure calixarene cation radical (1+• SbCl6
-
)
can also be prepared using triethyloxonium hexachloroantimon-
ate as the one-electron oxidant (see Supporting Information).
When the solution of the 1+• was exposed to gaseous nitric oxide
(NO) at 22 °C, the bright green color was immediately replaced
by a dark blue coloration, and the spectrum of the resulting solution
showed a broad absorption band at λmax ) 690 nm (ꢀ690 ) 3000
M-1 cm-1) (see the blue spectrum in Figure 1).
Infrared spectral analysis of the blue solution confirmed that the
N-O stretching band at 1906 cm-1 in [1/NO]+ is characteristically
close to that observed for free nitric oxide (1876 cm-1), and the
high affinity of 1+• toward NO (KNO > 108 M-1)9 allowed the ready
isolation of single crystals of blue [1/NO]+ from a mixture of
dichloromethane and hexanes at 0 °C. X-ray crystallography at
-150 °C established the molecular structure of [1/NO]+ SbCl6- to
consist of a single molecule of NO trapped inside the calixarene
core.
References
(1) (a) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry:
Cambridge, UK, 1989. (b) Ikoda, A.; Tsudera, T.; Shinkai, S. J. Org.
Chem. 2000, 112, 818. (c) Matthews, S. E.; Schmitt, P.; Felix, V.; Drew,
M. G. B.; Beer, P. D. J. Am. Chem. Soc. 2000, 124, 1341.
(2) Rathore, R.; Lindeman, S. V.; Rao, K. S. S. P.; Sun, D.; Kochi, J. K.
Angew. Chem., Int. Ed. 2000, 39, 2123.
(3) (a) Franz, K. J.; Singh, N.; Lippard, S. J. Angew. Chem., Int. Ed. 2000,
39, 2123 and references therein. (b) Rawls, R. Chem. Eng. News 2000,
June 19, 11. (c) Itoh, Y.; Ma, F. H.; Hoshi, H.; Oka, M.; Noda, K.; Ukai,
Y.; Kojima, H.; Nagano, T.; Toda, N. Anal. Biochem. 2000, 287, 203.
(4) For example, see: Steed, J. W.; Juneja, R. K.; Atwood, J. L. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2456.
(5) Rathore, R. Unpublished results.
(6) Rathore, R.; Burns, C. L.; Deselnicu, M. I. Org. Lett. 2001, 3, 2887.
(7) Note that the through-space separation between electron-rich dimethoxy-
tolyl groups is >5 Å, and thus electronic coupling amongst them is feasible
only through the calixarene core.
(8) For the preparation of MA+• SbCl6- (9,10-dimethoxyocta-hydro-1,4:5,8-
dimethanoanthracene cation radical), see: Rathore, R.; Burns, C. L. Org.
Synth. 2003 (procedure being checked).
(9) Binding constant was too large to be determined directly and thus was
estimated using Venus fly trap (Kass ) 3 × 106 M-1 for NO binding)
according to a competition method; see ref 2 for details.
(10) For the other methods of nitric oxide sensing, compare: Hilderbrand, S.
A.; Lim, H. H.; Lippard, S. J. J. Am. Chem. Soc. 2004, 126, 4972 and
references therein.
The effective sharing of the cationic hole among the electroactive
dimethoxytolyl groups and calixarene core (see Scheme 1) allows
a single molecule of NO to be completely encapsulated deep inside
the calixarene cavity and is distributed equally between chemically
equivalent distal aromatic pairs that form the cylindrical cavity of
JA0454900
9
J. AM. CHEM. SOC. VOL. 126, NO. 42, 2004 13583