Novel arene receptors as nitric oxide (NO) sensors

Article abstract of DOI:10.1021/ja020217o

Nitric oxide sensors are based on the reversible, specific, and efficient binding to various types of arene receptors via intermolecular complexes, which are characterized by complete electron delocalization and strong interaction between the donor and ac

Full text of DOI:10.1021/ja020217o

Published on Web 04/26/2002
Novel Arene Receptors as Nitric Oxide (NO) Sensors
Sergiy V. Rosokha and Jay K. Kochi*
UniVersity of Houston, Chemistry Department, Houston, Texas, 77204
Received February 11, 2002
Chart 1
The binding/release kinetics (and thermodynamics) associated
with nitric oxide are highly relevant to number of biological
systems.1 Although many studies have dealt with transition-metal
complexes,2 the question of the reversible, specific, and efficient
binding of NO• by different types of organic compounds generally
remains open. We wish to show how suitable entry into this problem
is revealed by the study of charge-transfer complexes of the
nitrosonium acceptor (NO+) with various aromatic donors (ArH)3
since the intermolecular [1:1] complexes [ArH,NO]+ are charac-
terized by complete electron delocalization arising from strong
donor/acceptor interactions.4 Thus, they are spontaneously formed
(barrierless) via either the binding of nitrosonium with aromatic
donors or the equivalent binding of nitric oxide with their cation
radicals owing to the coupled equilibria in eq 1,
Chart 2
K1
K2
ArH + NO+ {
\ \
} [ArH,NO]+ { } ArH+• + NO• (1)
Table 1. UV-Vis Spectral Data and Equilibrium Constantsa
where the overall equilibrium constant is KET ) K1K2 and the Nernst
0
diarene
E ox
λ (ꢀ)b
K (M-1 c
)
K (M)c
KET
2.1
1
2
relationship defines the free-energy change: ∆GET ) F (E°ox
E°red).5
-
MEA 1.46 334 (7.8) 510 (1.5) 1.3 × 106 1.7 × 10-6
ST1
ST2
ST3
ST4
CAL
1.35 345 (4.6) 590 (5.3) 1.3 × 107 1.3 × 10-5 170
We now find that the corresponding [2:1] complexes are formed
at high arene concentrations. Successful isolation and single-crystal
X-ray crystallography establish the novel sandwich structure II,
which is graphically depicted in Chart 1 together with the “open-
face” sandwich structure I of the [1:1] complex.4
The unusual cofacial arrangement in II is quite reminiscent of
bis-arene complexes of the transition metals; and interring con-
nections of the arene ligands as in III optimize the chelate effect
for effective binding of nitric oxide.6 Indeed, the addition of diarene
ligands (Ar2 in Chart 2) to even dilute solutions of the nitrosonium
acceptor in dichloromethane immediately results in intense purple
colorations with spectral bands near 340 nm and in the 450-600-
nm region similar to those of monoarene complexes.3 The linear
dependence of the band intensities on nitrosonium concentration
indicates that the set of coupled equilibria in eq 2 is greatly shifted
to the intermolecular complex III.
1.45 350 (6.6) 535 (4.5) 5.0 × 105 6.5 × 10-6
3.3
1.55 360 (5.0) 460 (5.1)
1.47 345 (4.0) 575 (5.8) 5.0 × 107 3.0 × 10-8
1.5
3.2
1.45
538 (8.5) 2.0 × 108 1.6 × 10-8
a In dichloromethane at 22 °C. b Wavelength λ in nm, extinction
coefficient ꢀ ( 0.2 in 103 M-1 cm-1 c (30%.
.
K1
\
K2
\
Ar2 + NO+ {
} [Ar2,NO]+ {
} Ar2+• + NO•
(2)
The extinction coefficients of the UV-vis bands evaluated from
the absorption intensities, and the equilibrium constant K1 deter-
mined by the competition method,4 together with K2 for the
dissociative equilibrium and KET for the overall equilibrium, in eq
2 are listed in Table 1. It is important to note that both K1 and
Figure 1. Dependence of free energy of complex formation on the oxidation
potential of various aromatic donors.
various arene donors. Most importantly, consideration of the three-
state equilibria in eqs 1/2 indicates that those systems with weak
arene donors (Eoox > 1.5 V) favor the diamagnetic reagents (ArH
-1
K2 for di-arenes are generally 103 larger than those for the
correspondingly substituted monoarenes.3e
The linear plot in Figure 1 shows the direct relationship of the
free energy for complex formation with the oxidation potential of
and NO+). By contrast, the relatively electron-rich donors (Eo
<
ox
1.5 V) favor the equlibrium shift to the paramagnetic species (ArH+•
and NO•), and the CT complex is only observed at low temperatures.
Complex formation is optimized at the isergonic point, and this is
* To whom correspondence should be addressed. E-mail: jkochi@
mail.uh.edu.
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J. AM. CHEM. SOC. 2002, 124, 5620-5621
10.1021/ja020217o CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Figure 2. Molecular structure of the diarene complex [ST4,NO]+ with all
hydrogens omitted for clarity.
Figure 3. Spectral changes upon the addition of nitric oxide to Ar2/oxidant
systems. [Dashed lines are before and solid lines are after NO addition.]
theoretically confirmed by the LCAO-MO description of the CT
complex showing maximum electronic (donor/acceptor) coupling
when Eoox(arene) ≈ Eored(NO+) ) 1.5 V vs SCE.4 Thus, the best
choice for nitrosonium/nitric oxide complexation based solely on
is completely reversible simply by NO entrainment with a mild air
stream or upon evacuation. We are presently also investigating a
(tunable) electrochemical sensor based on the same basic principle.
electronic factors lies with aromatic donors having Eo ≈ 1.5 V,
ox
and this requirement is satisfied by the diarenes (Table 1). Since
Figure 1 shows that the free-energy gain upon complex formation
is much higher with diarenes than those with monoarenes of
Acknowledgment. We thank S. V. Lindeman for crystallo-
graphic assistance, R. Rathore for providing some of the diarene
donors, and the R. A. Welch Foundation and National Science
Foundation for financial support
comparable Eo value, it is clear that structural factors must also
ox
be evaluated.
X-ray structural analysis reveals that a single molecule of nitric
oxide penetrates deeply within the rather narrow cleft formed by
two cofacial aromatic moieties.6 As a result, the diarene complexes
must be structurally akin to the [2:1] complexes II. However, Figure
1 shows that the free-energy gain in [2:1] complexes is substantially
less than that from the corresponding diarene complexes, and this
supports the importance of the chelate effectsas manifested both
in the enthalpy gain from multibond formation as well as an entropy
loss from one-ligand coordination.7 Moreover for maximum chelat-
ing effect, the binding of the multidentate ligand must also be
organized so that the coordinating (NO) center is encapsulated with
minimal (distortional) penalty (Figure 2). It is also significant that
NO lies within the undistorted calixarene complex [CAL,NO]+
equidistant from the cofacial aromatic planes at an optimal distance
of d ) 2.55 Å,6a as established by the X-ray structures of the [2:1]
complexes of toluene (d ) 2.5 Å) and o-xylene (d ) 2.6 Å).4b In
the other diarene complexes the two distances are nonequivalent,
indicating the second bond provides some additional free-energy
gain, but the rather rigid structure of the stilbenoid ligands (ST1-
4) as well as the dihydroanthracene analogue MEA do not allow
optimal placement of the aromatic ring for NO binding. [For
example, d ) 2.15 and 3.10 Å in [MEA,NO]+, d ) 2.24 and 2.70
Å in [ST1,NO]+, and d ) 2.15 and 2.90 Å in [ST4,NO]+ shown
in Figure 2. As a result CAL forms the most stable NO complex
(Table 1).
The enhanced formation constants of diarene complexes ensure
high sensitivity and specificity for NO binding. These together with
large extinction coefficients of the visible absorption bands allow
selective NO sensors to be designed on the basis of the coupled
equilibria in eq 2. For example, colorless (CH2Cl2) solutions of
either CAL or ST4 with some added oxidant (e.g., PbO2 or Et3-
OSbCl6) persist unchanged for prolonged periods.8 However,
immediately upon the exposure to nitric oxide (gas), the colorless
solutions take on an intense purple coloration (see left table of
contents graphic) diagnostic of the diarene complexes (Figure 3).
The same color change is observed in the solid state with a mull
prepared as an intimate mixture of CAL and PbO2. Exposure of
such a coated (pale gray) alumina plate to nitric oxide produces
the dramatic color change (see right table of contents graphic) which
Supporting Information Available: Experimental details together
with the X-ray crystallographic data and ORTEP diagrams for the [2:1]
complexes: [(toluene)2,NO]+SbCl6- and [(o-xylene)2,NO]+SbCl6- and
the diarene complexes [ST4,NO+]SbCl6 and [MEA,NO+]SbCl6
-
-
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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For experimental details and the X-ray structures of various II and III
complexes, see Supporting Information.
(5) Eo is the reversible oxidation potential of arene donors, and Eo the
ox
red
reduction potential of NO+.
(6) (a) Rathore, R.; Lindeman, S. V.; Rao, K. S.; Sun, D.; Kochi, J. K. Angew.
Chem., Int. Ed. 2000, 39, 2123. (b) Rathore, R.; Kochi, J. K. J. Org.
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(8) (a) Particularly in nonaqueous solutions. (b) Note that this procedure
circumvents the kinetic lability of arene cation radicals. (c) From the results
in Table 1 (eq 2), we estimate the intrinsic NO sensitivity to be ∼1 µM
on the basis of a spectrophotometric resolution of 0.01 in the optical
density; however, for a solid-state device the practical sensitivity will
depend on its design, particularly for application to an aqueous environment.
JA020217O
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