Three-stage binary switching of azoaromatic polybase

Article abstract of DOI:10.1021/ol303039s

An OFF-ON-OFF-type three-stage binary switching was realized with an azoaniline-based polybase 1. The optical properties of 1 and [1·2H] ²⁺ are essentially indistinguishable to the naked eye but distinctively different from those of [1·H]⁺ to produce an unusual bell-shaped response as a function of protonation state; the underlying molecular mechanism was unraveled by a combination of experimental and DFT computational studies.

Full text of DOI:10.1021/ol303039s

ORGANIC
LETTERS
2012
Vol. 14, No. 24
6286–6289
Three-Stage Binary Switching of
Azoaromatic Polybase
ꢀ
Ho Yong Lee, Andras Olasz, Chun-Hsing Chen, and Dongwhan Lee*
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington,
Indiana 47405, United States
dongwhan@indiana.edu
Received November 6, 2012
ABSTRACT
An OFFꢀONꢀOFF-type three-stage binary switching was realized with an azoaniline-based polybase 1. The optical properties of 1 and [1 2H]2þ
3
are essentially indistinguishable to the naked eye but distinctively different from those of [1 H]þ to produce an unusual bell-shaped response as a
function of protonation state; the underlying molecular mechanism was unraveled by a combination of experimental and DFT computational
studies.
3
Carbon-based π-conjugation can be structurally engi-
neered with functional groups that respond to external
stimuli. With appropriate structure design, the geometric
and/or electronic properties of such hybrid π-systems can
be modulated in a predictable and controllable fashion.1
Azoaromatics represent one important class of such a
functional motif,2 which have found applications as chemi-
cal sensors and switches that exploit either (i) light-driven
transꢀcis isomerization around the ;NdN; bond for
mechanical signaling3 or (ii) binding-induced perturbation
of the electronic structure of the extended π-conjugation
for optical signaling.4
In this paper, we report three-stage binary signaling of an
azopyrrole system 1 (Scheme 1) having multiple Brønsted
basic sites embedded along the π-conjugated molecular
backbone. Unlike simple ONꢀOFF or OFFꢀON switch-
ing (Scheme 1b) of typical receptors/indicators as chemical
models of logic operation,5 the implementation of three-
stage binary switching, such as the OFFꢀONꢀOFF or
ONꢀOFFꢀON sequence shown in Scheme 1a requires a
structural platform I that has multiple binding sites for
common substrates functioning as an input signal. In addi-
tion, a stepwise and reversible binding event of I should
generate discrete and experimentally identifiable adducts,
(1) (a) Balzani, V.; Venturi, M.; Credi, A. Molecular Devices and
Machines: A Journey into the Nanoworld; WileyꢀVCH: Weinheim, 2003.
(b) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46,
72–191. (c) de Silva, A. P.; Vance, T. P.; West, M. E. S.; Wright, G. D.
Org. Biomol. Chem. 2008, 6, 2468–2481. (d) Stoddart, J. F. Chem. Soc.
Rev. 2009, 38, 1802–1820. (e) Molecular Switches, 2nd ed.; Feringa, B. L.,
Browne, W. R., Eds.; Wiley-VCH: Weinheim, 2011.
(2) (a) The Chemistry of the hydrazo, azo and azoxy groups; Patai, S.,
Ed.; John Wiley & Sons: London, 1975. (b) Tamai, N.; Miyasaka, H. Chem.
Rev. 2000, 100, 1875–1890. (c) Hamon, F.; Djedaini-Pilard, F.; Barbot,
F.; Len, C. Tetrahedron 2009, 65, 10105–10123. (d) Merino, E. Chem.
Soc. Rev. 2011, 40, 3835–3853. (e) Beharry, A. A.; Woolley, G. A. Chem.
Soc. Rev. 2011, 40, 4422–4437.
(3) (a) Russew, M.-M.; Hecht, S. Adv. Mater. 2010, 22, 3348–3360.
(b) Stoll, R. S.; Hecht, S. Angew. Chem., Int. Ed. 2010, 49, 5054–5075.
(c) Yu, H.; Ikeda, T. Adv. Mater. 2011, 23, 2149–2180. (d) Wegner, H. A.
Angew. Chem., Int. Ed. 2012, 51, 4787–4788.
(4) (a) Zollinger, H. Color Chemistry: Syntheses, Properties, and
Applications of Organic Dyes and Pigments, 3rd ed.; VHCA: Zurich,
2003. (b) Chudgar, R. J.; Oakes, J. In Kirk-Othmer Encyclopedia of
Chemical Technology, 5th ed.; John Wiley & Sons: Hoboken, 2007; Vol.
9, pp 349ꢀ430.
(5) (a) de Silva, A. P.; Uchiyama, S. Nat. Nanotechnol. 2007, 2, 399–
410. (b) Szacizowski, K. Chem. Rev. 2008, 108, 3481–3548. (c) An-
ꢀ
dreasson, J.; Pischel, U. Chem. Soc. Rev. 2010, 39, 174–188.
r
10.1021/ol303039s
Published on Web 12/03/2012
2012 American Chemical Society

IIand III(Scheme1a). Mostimportantly, the signaloutput
from the “fully-saturated” product III should be distinc-
tively different from that of the “intermediate” II, but
operationally indistinguishable from that of the initial state
I, so that a bell-shaped response curve (Scheme 1a) is
obtained with an increasing level of input signal.
analogue of pH indicator methyl yellow or methyl orange,
2 has a p-phenylene linker which supports three Brønsted
basic nitrogen atoms constituting the extended π-conjuga-
tion. Previous studies have shown that its protonation
product [2 H]þ exists as a tautomeric mixture of “ammo-
3
nium” and “azonium” species (eq 1).9
When all these functional requirements are satisfied, the
ON signal from such a system is observed only for a finite
input signal window that maximizes the population of II.
By design, the system automatically turns OFF when the
input signal level is either lowered (toward I) or raised
(toward III) away fromthis predefinedzoneof II. A fluoro-
genic polybase reported by de Silva is a seminal example of
such a molecular switch,6 which uses protons as an input
signal to produce a bell-shaped response curve (Scheme 1a)
resulting from pH-dependent PET mechanisms.1c,7
Using 2 as a structural template, we designed 1.10 We
anticipated that the Brønsted basicity of both of the azo
nitrogen atoms, NR and Nβ, in 1 should be enhanced
through contributions from the quinoid-type and zwitter-
ionic resonance structures 1a and 1b (eq 2).
Scheme 1. Chemical Structures of 1 and 2 (top), and Schematic
Representations of (a) Three-Stage vs (b) Two-Stage Binary
Switching upon Substrate (Shown As a Red Sphere) Binding
In CH3CN at T = 298 K, 1 displayed an intense yellow
color, but immediately turned blue upon protonation
(Figure 1a, inset). Such behavior was not unusual for an
azo dye that functions as a simple acidꢀbase indicator. To
our surprise, however, subsequent addition of an increas-
ing amount of acid restored the initial yellow color, which
was visually similar to the neutral 1 (Figure 1a, inset).11
This serendipitous finding of a rather peculiar protona-
tion-dependent color switching did not make any intuitive
sense and invited a detailed investigation.
Our entry into this chemistry was motivated by 2
(Scheme 1), a prototypical azoaniline that we came across
during our studies of electron-rich azo derivatives for
chemical sensing and actuation.8 As a simpler structural
(6) de Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. Chem.
Commun. 1996, 2399–2400.
(7) For conceptually related luminescence-based OFFꢀONꢀOFF
signaling systems responding to protons, see: (a) Fabbrizzi, L.; Gatti,
F.; Pallavicini, P.; Parodi, L. New J. Chem. 1998, 22, 1403–1407.
ꢀ ꢀ
(b) Gunnlaugsson, T.; Leonard, J. P.; Senechal, K.; Harte, A. J.
J. Am. Chem. Soc. 2003, 125, 12062–12063. (c) Han, M.-J.; Gao,
€
L.-H.; Lu, Y.-Y.; Wang, K.-Z. J. Phys. Chem. B 2006, 110, 2364–
ꢀ
2371. (d) Evangelio, E.; Hernando, J.; Imaz, I.; Bardajı, G. G.; Alibes,
ꢀ
Figure 1. (a) A plot of ΔA610
vs ꢀlog[HBF4 OEt2], and
3
nm
R.; Busque, F.; Ruiz-Molina, D. Chem.;Eur. J. 2008, 14, 9754–9763.
yellowꢀblueꢀyellow color switching of 1 (inset: photographic
ꢀ
ꢀ
ꢀ
(e) Pais, V. F.; Remon, P.; Collado, D.; Andreasson, J.; Perez-Inestrosa,
E.; Pischel, U. Org. Lett. 2011, 13, 5572–5575. (f) Chen, Y.; Wang, H.;
Wan, L.; Bian, Y.; Jiang, J. J. Org. Chem. 2011, 76, 3774–3781.
(g) Sadhu, K. K.; Mizukami, S.; Yoshimura, A.; Kikuchi, K. Org.
Biomol. Chem. 2013, in press (DOI: 10.1039/C2OB26630J).
(8) (a) Lee, H. Y.; Song, X.; Park, H.; Baik, M.-H.; Lee, D. J. Am.
Chem. Soc. 2010, 132, 12133–12144. (b) Lee, H. Y.; Jo, J.; Park, H.; Lee,
D. Chem. Commun. 2011, 47, 5515–5517. (c) Jo, J.; Lee, H. Y.; Liu, W.;
Olasz, A.; Chen, C.-H.; Lee, D. J. Am. Chem. Soc. 2012, 134, 16000–
16007.
images). (b) UVꢀvis spectra of 1 inthepresenceof[HBF4 OEt2] =
3
0 (orange), 0.02, 0.04, 0.06, 0.08, 0.10, and 0.12 (blue) mM.
(c) UVꢀvis spectra of 1 in the presence of [HBF4 OEt2] =
3
0.12 (blue), 0.16, 0.20, 0.24, 0.35, 0.47, 0.70, 0.94, 1.20, 1.40, and
1.60 (orange) mM. (d) A reversible color switching monitored by
ΔA610
after addition of HBF4 OEt2 and back-titration with
3
nm
Et3N. For all measurements, [1] = 20 μM in MeCN; T = 298 K.
Org. Lett., Vol. 14, No. 24, 2012
6287

As shown in Figure 1b, the absorption band of 1 at λmax
=
445 nm initially lost its intensity with increasing [Hþ], with
concomitant buildup of a broad longer-wavelength transition
conformation, in which the pyrrolic NꢀH group makes a
hydrogen bond with the azo NR atom (dN3 3 3 N = 2.824 A
for A; 2.707 A for B) to attenuate its basicity. On the other
hand, contribution of the resonance structure 1b (eq 2)
enhances the basicity of the Nβ position to furnish A.
Upon addition of a second equivalent of proton, a single
adduct C emerges as the lowest-energy tautomer of
at λmax = 615 nm along with a blue-shifted feature at λmax =
400 nm. This yellow-to-blue color change, however, was essen-
tially reversed upon further addition of acid (Figure 1c), which
elicited the evolution of a new absorption band at λmax
440 nm and complete disappearance of the features at λmax
615 and 400 nm. Such protonation-driven spectral changes
can be tracked best by a plot of ΔA610 (= changes in the
absorption at λ = 610 nm) vs ꢀlog[Hþ] (Figure 1a), which
produces an OFFꢀONꢀOFF response function (Scheme 1)
with genuine reversibility in the forward (= protonation) and
backward (= deprotonation) scans (Figure 1d).
=
=
[1 2H]2þ (eq 3). Our DFT calculations suggested that
3
alternative isomers D and E (shown below) would be
significantly higher in energy, by ca. 11 and 22 kcal molꢀ1
,
respectively, relative to C. Apparently, C benefits from
charge delocalization through resonance (eq 3), which is
not allowed for D. Adjacent positive charges make E the
most unlikely tautomer.
Inorder to investigate the structural basisofthis unusual
color switching, we carried out 1H NMR titration studies.
As shown in Figure 2, protonation of 1 with HBF4 OEt2 in
3
CD3CN resulted in systematic downfield shifts of the
signals from the phenyl protons that are ortho to the amine
Nγ position. This spectral change is also accompanied by
downfield shifts in the two pyrrolic CꢀH resonances.
From the electronic structure point of view, the singly
protonated A has its (i) HOMO residing at the electron-
rich amino group and the pyrrole π-system and (ii) LUMO
dominated by the azo π* orbital in the middle (Figure 3b).
Figure 2. Partial 1H NMR spectra of 1 (16 mM) in CD3CN in the
presence of (a) 2, (b) 1, and (c) 0 equiv of HBF4 OEt2 (T = 298 K).
3
In contrast, the phenyl CꢀH protons that are ortho to
the azo NR site remain essentially invariant under this
condition. This observation suggests the solution equili-
brium described by eq 3; protonation of 1 occurs at its Nβ
or Nγ position to furnish a mixture of A and B. This
interpretation is consistent with findings made for the
benchmark system 2 (eq 1).9
Figure 3. (a) Energy level diagram and FMO isosurface plots.
(b) FMO isosurface plots of A.
Our subsequent DFT computational studies have
confirmed that A and B share an essentially identical
As a consequence, protonation at the Nβ position
results in a smaller HOMOꢀLUMO gap (2.23 eV) of A
and promotes longer-wavelength electronic transitions
with significant charge-transfer character (Figure 1b).
On the other hand, the HOMOꢀLUMO gap of B
(3.14 eV) is essentially identical to that (3.13 eV) of
(9) (a) Kuroda, Y.; Lee, H.; Kuwae, A. J. Phys. Chem. 1980, 84,
3417–3423. (b) Liwo, A.; Tempczyk, A.; Widernik, T.; Klentak, T.;
Czerminski, J. J. Chem. Soc., Perkin Trans. 2 1994, 71–75. (c) Yatsenko,
A. V.; Chernyshev, V. V.; Kurbakov, A. I.; Schenk, H. Acta Crystallogr.
2000, C56, 892–894. (d) Matazo, D.; Ando, R.; Borin, A.; Santos, P.
J. Phys. Chem. A 2008, 112, 4437–4443.
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Org. Lett., Vol. 14, No. 24, 2012

1 (Figures 3a and S1). The intense blue color of [1 H]þ
thus arises from A.
3
In the doubly protonated C, the amine Nγ site is
effectively decoupled from the π-conjugation (Figure 3a
and S1). The increased HOMOꢀLUMO gap of C (3.21
eV) happens to be close to that (3.13 eV) of 1, which fully
explains their indistinguishable yellow color despite mark-
edly different protonation states (Figure 1a, inset).
The Brønsted acidꢀbase chemistry of 1 is significantly
simplified in its derivative 3 (eq 4), in which protonation at
the NR site is effectively blocked through borylation.10,12
The X-ray structure of 3 (Figure 4a) revealed a signifi-
cant contribution of the quinoid-type resonance structure,
as reflected on the CꢀC bond length alternation in the
phenyl ring (CꢀC = 1.405(1), 1.382(1), 1.417(1), 1.419(1),
1.376(1), and 1.401(1) A) and the relatively long NꢀN
distance (1.310(1) A). This geometric property is reminis-
cent of A (= [1 H]þ) having similar resonance structures
3
Figure 4. (a) X-ray structure of 3 with thermal ellipsoids at 50%
probability (top), and benzoid vs quinoid resonance structures
of A and 3 (bottom). (b) UVꢀvis spectra of 3 (20 μM in CH3CN)
(Figure 4a). Indeed, 3 in MeCN displays an intense blue
color with a broad absorption centered at λmax = 600 nm
(Figure 4b), which “mimics” the optical properties of A
(Figure 1b).
in the presence of [HBF4 OEt2] = 0 (blue), 0.20, 0.22, 0.24, and
3
0.27 (red) mM (inset: photographic images). T = 298 K.
In a manner similar to the conversion of [1 H]þ to
3
[1 2H]2þ (Figure 1c), protonation of 3 resulted in the
disappearance of the longer-wavelength absorption with
3
HOMOꢀLUMO gap of the conjugate acid to produce a
bell-shaped response of OFFꢀONꢀOFF type switching.
A dynamic response to the stimuli in both directions from
the predefined proton concentration window is a defining
feature of the three-stage switch 1, which distinguishes it
from the conventional ONꢀOFF system such as 3. The
operation of the three-stage binary switching of 1 capita-
lizes on the presence of multiple Brønsted basic sites that
communicate through the π-conjugation to modulate the
energy levels of the frontier MOs as a function of proto-
nation level. Efforts are currently underway in our labora-
tory to generalize this concept and structurally elaborate
this proof-of-concept system for applications in chemical
sensing.
concomitant development of a new absorption at λmax
=
500 nm (Figure 4b). This spectral shift is accompanied by
the change in color from blue to pink (Figure 4b, inset).
Unlike the situation in 1, coordination of the Lewis acidic
{BF2}þ fragment disqualifies the NR position from func-
tioning as a Brønsted base. Consequently, protonation can
occur only at the Nγ or Nβ position (Figure S2) to drive a
conventional two-stage switching (eq 5; Scheme 1b).
In summary, two different dye molecules 1 and 3 were
prepared which share a common azopyrrole platform. The
stepwise protonation of 1 elicits differential shifts in the
Acknowledgment. We thanks DTRA/Army Research
Office (W911NF-07-1-0533) for financial support of this
work.
(10) A structurally analogous azopyrrole was investigated previously
as a synthetic precursor to NIR-absorbing molecules: Li, Y.; Patrick,
B. O.; Dolphin, D. J. Org. Chem. 2009, 74, 5237–5243.
(11) In strongly acidic solvent (95% H2SO4), 2 shows similar color
switching behavior.9a
Supporting Information Available. Experimental pro-
cedures, and spectroscopic, X-ray crystallographic, and
computational data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(12) Coordination of {BF2}þ can also lower the energy of the azo
πꢀπ* transition. With appropriate structure design, the trans-to-cis
photoisomerization can be driven by visible light. See: Yang, Y.;
Hughes, R. P.; Aprahamian, I. J. Am. Chem. Soc. 2012, 134, 15221–
15224.
The authors declare no competing financial interest.
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