Unsymmetrical cruciforms

Article abstract of DOI:10.1021/jo901961a

(Chemical Equation Presented) Five new, unsymmetrical 1,4-distyryl-2,5- bisphenylethynylbenzenes (cruciforms, XF) have been prepared by a sequential Horner reaction of the bisphosphonate of 2,5-diiodo-1,4-xylene with two different aromatic aldehydes. The obtained diiodide was coupled to phenylacetylene under Sonogashira conditions with (Ph₃P) ₂PdCl₂ as catalyst. The resulting XFs carry dibutylamino, pyridyl, cyano, and diphenylamino residues on their styryl arms to give rise to donor-, acceptor-, and donoracceptor-substitutedXFs. The optical properties of theseXFswere investigated.Titration studies using trifluoroacetic acid tracked changes in the electronic structure of the XFs upon protonation. Donor XFs display a blue shift in absorption and emission upon protonation,while the pyridyl-substitutedXF displays red shift in absorption and emission upon protonation. In the case of the donor-acceptor XF carrying a pyridyl and an aminostyryl arm, the first protonation occurs either on the pyridine or on the dibutylamino arm; a red shift is seen in absorption (for the former) and a blue shift is observed in emission (for the latter). The titration studies indicate that the protonated XFs do not display kinetic photoacidity when operating either in dichloromethane or acetonitrile solutions. The trends observed for protonation were mirrored when the XFs bind to metal cations.While the binding constants of the metal cations to theXFs were lower than for that for protons, as in some cases fullmetalation of theXF could not be obtained, the results were qualitatively the same. We did not find dynamic excited-state decomplexation events in theXFs that we have investigated.TheXFs, stilbene derivatives, are different from other reported, similarly structured fluorophores as they show significant ratiometric changes in emission upon metal complexation; thus, distyrylbenzene-derived fluorophores may be, in the end, viable choices as platforms for metal ion detection.

Full text of DOI:10.1021/jo901961a

pubs.acs.org/joc
Unsymmetrical Cruciforms
Juan Tolosa, Kyril M. Solntsev, Laren M. Tolbert, and Uwe H. F. Bunz*
School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta,
Georgia 30332-0400
uwe.bunz@chemistry.gatech.edu
Received September 15, 2009
Five new, unsymmetrical 1,4-distyryl-2,5-bisphenylethynylbenzenes (cruciforms, XF) have been
prepared by a sequential Horner reaction of the bisphosphonate of 2,5-diiodo-1,4-xylene with
two different aromatic aldehydes. The obtained diiodide was coupled to phenylacetylene under
Sonogashira conditions with (Ph3P)2PdCl2 as catalyst. The resulting XFs carry dibutylamino, pyridyl,
cyano, and diphenylamino residues on their styryl arms to give rise to donor-, acceptor-, and donor-
acceptor-substitutedXFs. The opticalproperties of these XFs were investigated. Titrationstudies using
trifluoroacetic acid tracked changes in the electronic structure of the XFs upon protonation. Donor
XFs display a blue shift in absorption and emission uponprotonation, while the pyridyl-substitutedXF
displays red shift in absorption and emission upon protonation. In the case of the donor-acceptor XF
carrying a pyridyl and an aminostyryl arm, the first protonation occurs either on the pyridine or on the
dibutylamino arm; a red shift is seen in absorption (for the former) and a blue shift is observed in
emission (for the latter). The titration studies indicate that the protonated XFs do not display kinetic
photoacidity when operating either in dichloromethane or acetonitrile solutions. The trends observed
for protonation were mirrored when the XFs bind to metal cations. While the binding constants of the
metal cations to the XFs were lower than for that for protons, as in some cases full metalation of the XF
could not be obtained, the results were qualitatively the same. We did not find dynamic excited-state
decomplexation events in the XFs that we have investigated. The XFs, stilbene derivatives, are different
from other reported, similarly structured fluorophores as they show significant ratiometric changes in
emission upon metal complexation; thus, distyrylbenzene-derived fluorophores may be, in the end,
viable choices as platforms for metal ion detection.
Introduction
and compare their properties to those of the corresponding
symmetrical XFs 6-8.1
We disclose in this manuscript the synthesis as well as
photophysical, acidochromic, and metallochromic/metallo-
fluorophoric properties of the five cruciform fluoro-
phores (1,4-distyryl-2,5-bisarylethynylbenzenes, XF) 1-5
Cruciform (XF)2-6 is a catch-all term for diaxial chromo-
phores in which the properties of the two axes can be
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DOI: 10.1021/jo901961a
r
Published on Web 10/27/2009
J. Org. Chem. 2010, 75, 523–534 523
2009 American Chemical Society

Tolosa et al.
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SCHEME 1. Synthesis of 1-5
manipulated independently. In most XFs, the diaxial char-
acter leads, upon suitable decoration with auxochromic
substituents, to spatially separated and therefore indepen-
dently addressable frontier molecular orbitals.7 Unusual
spatially resolved electronic properties result. We previously
investigated XFs 6-8 and demonstrated that these are
attractive metalloresponsive and acidochromic dyes with a
rare two-stage sensory response.1,8
However, there was a cluster of questions that could not be
addressed with the symmetrical XFs 6-8. Are the partially
protonated species stemming from 6-8 spectroscopically
too similar to the spectra of the fully protonated derivatives
or fully nonprotonated or are the subsequent protonation
steps faster than the first one? Is there an influence of
different conjugative pathways upon changing the topology
of the donor and acceptor substituents and their frontier
molecular orbitals? Is there evidence for excited-state decom-
plexation or enhanced complexation upon binding of metal
cations to 1-5?9-11 Conversely, will excited-state photoa-
cidity be enhanced?9 In searching for answers to these
questions, we note that the XFs 1-5 are better suited to do
this, as multiple complexation of identical binding units
occuring in 6-8 can be excluded.10,11
Results and Discussion
Synthesis. Scheme 1 displays the synthesis of 1-5. The
challenging issue was the preparation of the unsymmetrical
stilbenes 10-12. The most straightforward way to obtain
these targets was to react 9 with 1 equiv of KOtBu at 0 °C,
add the first aldehyde, warm to room temperature, add
another 1 equiv of KOtBu, and add the second aldehyde.
These reactions were readily performed in one pot. The
Horner reaction of the more electron-rich aldehyde was
performed first. The intermediates were obtained in yields
between 25 and 41%, less than the statistically expected yield
of 50%. We attribute the decreased yield to the increased
reactivity of the intermediate styrene derivative, giving rise to
the formation of a significant amount of the two symmetrical
Horner products. The overall yields of this mixed Horner
reaction was >90%, and the products were conveniently
separated by column chromatography.12 The introduction
of the secondary axis was achieved by coupling of 10-12 to
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FIGURE 1. Molecular structure of 1-8 and their photophysical properties recorded in dichloromethane.
phenylacetylene to give the XFs 1-5 in yields between 80 and
92% as yellow to orange crystalline materials.
peak is bluer than the major emission peak in n-hexane. For
another reason, the fluorescence quantum yield in acetoni-
trile is too high to be attributed to TICT emission. An
alternative explanation could be the emission from the
monoprotonated species, as shown below. However, the
peak did not disappear upon addition of a large access of
triethylamine. Currently, we are investigating the nature of
this weak emission but will omit it in the current publication
since it is not critical for the understanding of acidochromic
and metalloresponsive properties of novel cruciforms.
Figure 4 displays the absorption and emission spectra of
1-5 in acetonitrile upon exposure of an increasing amount of
trifluoroacetic acid. The full titration traces are displayed in
the Supporting Information. For simplicity, only represen-
tative traces are shown in Figure 4.
Since all of the prepared XFs have basic nitrogen groups,
protonation should change absorption and/or emission sig-
nificantly. Addition of trifluoroacetic acid to 1 leads to a blue
shift in emission as well as in absorption, surprisingly similar
to that observed to the symmetrical compound 6 (Figure 1).
Compound 2 by the same token should be analogous to 7,
and again, the spectral responses toward protonation in
absorption and emission are comparable. A significant red
shift is observed, and the emission intensity of the protonated
species is very low. The compounds 3 and 5 represent model
compounds, and the addition of TFA to 3 leads to strongly
blue emissive species, in which the dibutylamino group is
protonated, while addition of TFA to 5, which is already a
donor-acceptor system, leads to a significantly increased
donor-acceptor character, as the electron-accepting pyri-
dine unit is protonated. A red shift in absorption results,
while the emission is quenched. As a general note, XF species
Photophysics. Figure 1 displays the general photophysical
properties of 1-5, while Figure 2 displays the solvent-
dependent emission of the XFs 1-5. The absorption maxima
of 1-5 are almost independent upon the solvent used, while
the emission maxima change significantly depending upon
the solvent. The absorption and emission spectra of 1-5
were taken in a variety of solvents (see the Supporting
Information) to construct simplified Lippert-Mataga plots
(Figure 3),13 where Δf, the Lippert-Mataga solvent para-
meter, is defined as
Δf ¼ ½ðε -1Þ=ð2ε þ 1Þ - ðn2 -1Þ=ð2n2 þ 1Þꢀ
ð1Þ
The slope of the best fit indicates the charge-transfer
character of the excited states in the molecules 1-5. We find,
not unexpectedly, that compound 4 has the largest charge-
transfer character in the excited state, due to significant
donor-acceptor character. Interestingly, the donor-substi-
tuted 1 has a higher charge-transfer character than the
acceptor-substituted compound 2, while the donor-
acceptor-substituted model compounds 3 and 5 display an
intermediate degree of charge transfer in the excited state as
roughly expected from the substituent patterns. For the
compounds carrying a dibutylamino group (1, 3-5) a small
but detectable blue-shifted band was observed upon excita-
tion at 310 nm. The appearance of this band cannot be
explained by the typical LE-TICT scenario, since the “LE”
(13) (a) Lippert, E. Z. Naturforsch., Part A 1955, 10, 541–545. (b) Lippert,
E.; Moll, F. Z. Elektrochem. 1954, 58, 718–724. (c) Mataga, N.; Kaifu, Y.;
Koizumi, M. Bull. Chem. Soc. Jpn. 1956, 29, 465–470. (d) Reichardt, C.
Chem. Rev. 1994, 94, 2319–2358.
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FIGURE 3. Mataga-Lippert plot of XFs 1-5.
(energy gap law) or overtone coupling of the XFs to the
solvents. Other reasons could be the twisting of the aromatic
system that would lead to nonemissive TICT states.14
The most interesting case is “push-pull” XF 4. The
absorption and emission spectra of 4 resemble those of 8.
The emission quantum yield of 4 (Φ = 0.075) is slightly lower
than that of 8 (Φ = 0.11). The titration of this compound
with TFA gives surprising results. Upon addition of TFA a
red-shift in absorption occurs and then upon addition of
more TFA a blue shift. The final absorption is centered
around 381 nm. In emission the situation is reversed. Upon
addition of TFA first a weak blue-shifted band appears, then
upon addition of more TFA a strongly fluorescent band at
541 nm arises. One should note that at log[TFA] = -4.3 a
formally large negative Stokes shift results. The absorption is
centered at 495 nm, while the emission is centered at 437 nm.
What is the explanation for this seemingly contradictory
behavior? Deconvolution of the titration traces by the
singular value decomposition (SVD)15 reveals three species.
The simulated absorption and emission spectra as well as
their molar fraction present (Figure 5, observed in absorp-
tion, top, and emission, bottom) of which are shown in
Figures 5 and 6. The blue spectra are from the unprotonated
XF and are unsurprising. The red traces represent the spectra
of the doubly protonated XF. Both of these are in accord
with what would be expected from such an XF. However, the
green traces can only be explained if one assumes the
pyridine nitrogen is predominantly protonated in the first
step. That would lead to a situation reminiscent of the one
found for 5, where a red shift in absorption and a total
quenching in emission results. The emission tells a different
story. It is similar to that for 3; i.e., a blue shift in emission is
observed, even though its intensity is much lower. Figure 7
reconciles the processes. Upon addition of TFA either the
pyridine (majority) or the dibutylamino group (minority) of
4 is protonated. The two protonated species are in equilib-
rium with each other. From the UV-vis spectrum and
the emission spectrum one would conclude that the main
form is 4Hþb as the fluorescence intensity is low but the
intensity of the charge-transfer band in absorption that we
assign to 4Hþb is quite intense, explaining the observed
spectroscopic features consistently and without convoluted
FIGURE 2. Vis emission spectra of 1-5 in four different solvents.
with red-shifted emission tend to display lower emissive
quantum yields. Reasons for the decreased quantum yield
are perhaps vibronic coupling of ground and excited states
(14) Rettig, W. Angew. Chem., Int. Ed. Engl. 1986, 25, 971–988.
(15) Program DATAN, www.multid.se.
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FIGURE 4. UV/vis absorption and emission spectra of 1-5 in acetonitrile upon titration with trifluoroacetic acid. Excitation wavelength was
325 nm.
explanations. As the ratio between 4Hþa and 4Hþb repre-
sents an equilibrium, their species distribution is reflected
both in absorption as well as in emission, even though
different species are observed.
J. Org. Chem. Vol. 75, No. 3, 2010 527

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unit. Therefore protonation of the pyridine and the dibuty-
laniline are competitive.
For a more detailed study of the photophysical properties
of 4 in solutions of variable acidity, and to reveal possible
hidden or weakly emitting states we investigated its excita-
tion-emission matrix (EEM). EEM spectroscopy has re-
cently emerged as an effective method for spectroscopic
characterization of multifluorophoric systems.16-19 We col-
lected the emission spectra of the fluorophore at room
temperature scanning the excitation wavelength from 250
to 580 nm at 5 nm increments. In Figure 8, the emission
spectra of the 4 in acetonitrile in the presence of various
amounts of TFA are presented, which allowed the observa-
tion of every emission band and its correlation to the
appropriate excitation wavelength. As predicted by previous
observations, only three emitting species exist and intercon-
vert in solutions of 4 depending on their TFA concentra-
tions.
The apparent ΔpKa values (strictly speaking these are
-log β values, i.e., binding constants, as the titrations were
performed in acetonitrile) as measured in absorption and
emission and obtained by SVD, are similar for 4. To see if this
was representative for the XFs, we also analyzed the absorp-
tion as well as the emission traces of 1-3 and 5 upon addition
of TFA by SVD. Table 1 displays the -log β values as
obtained by UV-vis and emission spectroscopies. In all
cases, the coincidence of the values is very good. This is of
interest, as it suggests that, at least kinetically, the distyr-
ylbenzene derivatives do not show enhanced photoacidity as
do some other aromatic amines in nonaqueous solvents.20 As
we have observed in other contexts,9 proton transfer is
extraordinarily dependent upon solvent reorganization as
well as orientation of the proton carrier (base), resulting in a
significant entropic barrier to such deprotonation.
FIGURE 5. Analysis of the titration of 4. Top: Fitted UV/vis
absorption spectra. Bottom, fitted emission spectra upon exposure
of 4 to trifluoroacetic acid; λmaxexcitation = 310 nm.
The nature of the involved processes is of interest as they
might shed light on the “excited state decomplexation
hypothesis” that is proposed for aminostyrylbenzene deri-
vatives and their fluorescence response toward metal cations.
This hypothesis states that in the excited state aminostilbenes
and their relatives form quinoidal resonance structures in
which the electron pair in the aniline unit(s) is transferred to
the stilbene skeleton and not available for metal coordina-
tion.21 A consequence of this behavior is the observation that
addition of metal salts to such species lead to significant
changes (mostly blue shift) in absorption but to only very
small changes in emission. Perry et al. have demonstrated
this effect in an elegant paper, in which they investigated
crown-ether appended dicyanodistyrylbenzenes and their
optical changes upon metal-ion binding. Inspired by their
FIGURE 6. Species distribution of 4 upon protonation, observed
by absorption (top) and emission (bottom) spectroscopy. Red:
deprotonated species. Blue: unprotonated species. Green: mono-
protonated species.
The spectroscopic properties of 4 differ significantly from
those of the XF 8 in the sense that, as in 8, the protonation of
the dibutylaniline group occurs first, and the protonation of
the pyridine unit subsequently. Pyridines and dibutylanilines
in 8 have sufficiently large differences in pKa values, so that
both in absorption and in emission the di- and the tetra-
protonated species can be discerned, and that only one type
of diprotonated species, resulting from protonation of the
dibutylanilines, occurs. In 4 the situation is more complex, as
the pKa values of the pyridine and the dibutylaniline appear
to be quite similar or the pKa of the pyridinium is even larger
due to the mesomeric effect of the electron donating aniline
(16) Weber, G. Nature 1961, 190, 27–29.
(17) Clower, C.; Solntsev, K. M.; Kowalik, J.; Tolbert, L. M.; Huppert,
D. J. Phys. Chem. A 2002, 106, 3114–3122.
(18) Gill, D. M.; Wright, J. C.; McCaughan, L. Appl. Phys. Lett. 1994, 64,
2483–2485.
(19) Dong, J.; Solntsev, K. M.; Tolbert, L. M. J. Am. Chem. Soc. 2009,
131, 662–670.
(20) (a) Urban, W.; Weller, A. Ber. Bunsen Ges. 1963, 67, 787–791. (b)
Demyashkevich, A. B.; Ivanova, L. L.; Kiselevich, V. R.; Kuzmin, M. G.
Sov. J. Chem. Phys. 1990, 5, 759–767. (c) Ivanova, L. L.; Demyashkevich,
A. B.; Kuzmin, M. G. High Energy Chem. 1984, 18, 99–101. (d) Ivanova,
L. L.; Demyashkevich, A. B.; Kuzmin, M. G. High Energy Chem. 1985, 19,
48–52.
(21) (a) Letard, J. F.; Lapoyade, R.; Rettig, W. Pure Appl. Chem. 1993,
65, 1705–1712. (b) Mathevet, R.; Jonusauskas, G.; Rulliere, C.; Letard, J. F.;
Lapouyade, R. J. Phys. Chem. 1995, 99, 15709–15713.
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FIGURE 7. Analysis of the interaction of protons with 4.
FIGURE 8. Excitation/emission contour plots of XF 4 in acetonitrile in the presence of various amounts of TFA (mM, bottom right corner of
each graph). The difference between the neighboring lines corresponds to the constant intensity difference on a linear scale. Red color
corresponds to higher intensities.
shows that some ligands are capable of coordinating metal
ions with concomitant change of emission color. We were
interested in evaluating if the unsymmetrical XFs 1-5 would
respond similarly to metal ions as their symmetric congeners
6-8. Figure 9 displays a photograph of solutions of 1-5 in
dichloromethane before and after addition of 10 different
metal triflates at saturation. The pictures were taken under
black light illumination at λ = 366 nm. While the addition of
lithium and potassium triflate salts does not lead to any
fluorescence change, the other cations elicit differential
changes in 1-5. The changes are qualitatively similar to
those observed for protonation but do not occur for each XF
with each metal.
TABLE 1. Log β Values for the Protonation of 1-5 by TFA in
Acetonitrile
-log β
XF
basic group
absorption
emission
1
2
3
4
5
NBu2
Pyr
NBu2
Pyr/NBu2
Pyr
4.06
4.08
3.93
5.1/3.41
4.41
4.12
4.10
3.74
5.08/3.30
4.38
work we have exposed 1-5 to different metal triflates in
either dichloromethane or acetonitrile and investigated the
metal-induced changes of absorption and fluorescence in
1-5 (Table 2).
Interaction of the XFs with Metal Ions. Main-group metal
ions and metal cations with d0, d5, and d10 configurations act
typically as positive point charges and in that (and only that)
respect are similar to protons. Our experience with XFs 6-8
Figure 10 displays the corresponding selected absorption
and emission spectra. In the case of XF 1, Mg2þ, Ba2þ
,
Mn2þ, Agþ, Zn2þ, and Sn2þ all lead to a blue shift in
emission, as expected for a coordination of the aniline
nitrogens. Cu2þ leads to a pink or purple emission, which
results from dual emission from the complexed and the
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TABLE 2. Optical Properties of the XFs 1-5
1
2
3
4
5
metal absorption
ion
emission
max (nm)
absorption emission
λ
absorption emission
max (nm)
absorption emission
max (nm)
absorption emission
max (nm)
λ
max (nm)
λ
Φ
λ
max (nm)
max (nm)
Φ
λ
max (nm)
λ
Φ
λ
max (nm)
λ
Φ
λ
max (nm)
λ
Φ
none
Liþ
314, 423
538
0.183
318, 422 540 (433, 451) 0.283
328
327
328
447
449
447
558
447
559
558
558
558
0.521 315, 447
0.407 315, 447
0.512 316, 448
0.097 315, 447
585
583
585
583
0.079 312, 441
578
0.075 313, 423
0.085 317, 450 578 (431) 0.044 313, 423
548
547
548
549
547
NF
NF
NF
NF
NF
NF
NF
0.294
0.277
0.285
0.286
0.226
Kþ
316, 423
328
538
433
0.183
0.082 310, 442
0.082 328
578
527
0.072 313, 422
0.156 313, 423
Mg2þ
0.738 307, 331, 412
327
Ca2þ 320, 421 539 (433, 451) 0.311
0.441 315, 449 581 (441) 0.090 311, 446 577 (432) 0.056 314, 426
Ba2þ
Mn2þ
Cu2þ
Agþ
Zn2þ
Sn2þ
Hþ
329
328
329
328
328
329
326
435
434
433
434
433
433
436
0.666 307, 332, 411
0.662 307, 332, 408
0.560 306, 332, 410
0.580 307, 332, 406
0.098
0.099
0.124
0.089
331
330
320
331
330
331
331
435
435
0.757
0.700
328
329
326
527
526
525
518
525
526
527
0.153 326, 486
0.127 327, 489
0.085 312 (480)
0.050 326, 488
0.155 327, 485
0.133 326, 489
0.196 326, 486
435 (587) 0.428
450
435
435
438
0.612 326, 402
0.726 308, 331, 406 557 (433) 0.107
0.554
0.758
327
327
0.656 307, 332, 410
0.767 306, 334, 410
558
560
0.098
0.097
0.758 333, 381
as in the protonation study. A red shift in absorption, as a
testament to the coordination to the pyridine arm of the XF
4, is mirrored by a blue shift in emission and is apparently
counterintuitive but easy to understand if one looks at the
equilibria displayed in Figure 7. In the event that the metal
cation is bound to the pyridine, the resulting species is
nonfluorescent and red absorptive, while if the aniline moi-
ety is metal coordinated a species forms that will not display
any easily detected changes in absorption but will emit in the
blue. Excited-state decomplexation, or enhanced photoacid-
ity, however, does not seem to be prevalent in any of the
studied XFs, as the lockstep of the changes in absorption and
emission delineates.
FIGURE 9. Panel of the exposure of XFs 1-5 toward an excess of
different metal triflates in dichloromethane. The photograph was
taken using a hand-held UV-vis lamp with a λmax of 366 nm against
a black background.
However, to obtain binding constants of the XFs to metal
cations we performed a titration of XF 1 in acetonitrile with
both manganese and calcium triflates. As in this case only
one binding site is available, complications that would result
from the presence of multiple binding sites are excluded.
Figures 13 and 14 and Table 3 display the details. The XF 1 is
well-behaved, and we were able to extract binding constants
from both the absorption and the emission spectra by
deconvolution of the titration traces by the singular value
decomposition (SVD). According to these data, log βMn = 3.8
from absorption data and log βMn = 4.0 from the emission data.
A similar trend but much smaller numerical values are obtained
for calcium triflate log βCa = 1.8 from absorption data and log
βCa = 1.6 from the emission data. In both cases, the binding
constants derived from absorption and emission are remarkably
close, so that one can conclude that excited-state decomplexation
does not play a significant role for distyrylbenzenes, at least not
under the conditions employed herein.
uncomplexed forms. In 2, coordination of the pyridine group
results in a lowering of the LUMO and a yellow-orange
emission for all cations with exception of Liþ, Kþ, and Ca2þ
.
XF 3, while its absorption and emission are red-shifted,
displays qualitatively the same emission characteristics as 1
upon treatment with metal cations but a red to blue shift is
observed. Metals that coordinate to 4, induce a shift from red
to green, while in the case of 5, which should be analogous to
2, yellow emission is apparent; however, once the metal ions
or protons coordinate(s), the emission of 5 is fully quenched.
According to Figure 10, changes in absorption and emis-
sion upon coordination of an XF to metal cations are in most
cases similar to changes observed upon protonation, even
though in the case of metal cations some do not bind at all,
such as Liþ or Ca2þ to XF 1 in dichloromethane, and some
XF-metal-salt combinations lead to an equilibrium of
bound and unbound XF. In acetonitrile, the concentration
of calcium triflate at least can be pushed sufficiently high to
allow close to full coordination of the XF to the Ca2þ ions.
To further investigate these phenomena and obtain a more
quantitative picture, we titrated 4 with both manganese
triflate and with calcium triflate in acetonitrile (Figures 11
and 12). In principle, these data look very similar to those
obtained for the titration of 4 with trifluoroacetic acid;
however, attempts to fit the data by SVD were unsuccessful,
suggesting that additional equilibria must exist which are
difficult to simulate and play a significant role in these two
cases. Qualitatively though, one observes the same features
Conclusion
We have synthesized the hitherto unknown XFs 1-5 by
sequential double-Horner reaction followed by a
a
Sonogashira coupling and compared their properties to
those of the symmetrical XFs 6-8. We have investigated
the issue of the photoacidity of these XFs as well as of that of
the metallochromicity of the XFs, and we find that they
neither display excited-state decomplexation nor enhanced
photoacidity. This is somewhat contrary to the general belief
and to chemical intuition that stilbene types should show
enhanced photoacidity and excited-state decomplexation
due to the significant participation of quinoidal resonance
530 J. Org. Chem. Vol. 75, No. 3, 2010

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FIGURE 10. UV/vis absorption and emission spectra of 1-5in the presence of protons and selected metal triflates in dichloromethane as solvent. On
the left-hand side absorption data are shown, while on the right-hand side the emission data are displayed. The excitation wavelength was 350 nm.
structures in the excited state. Our results are, however, in full
agreement with our earlier results that distyrylbenzenes and
their derivatives have a significantly different photophysics
and photochemistry from stilbenes.22,23 We also notice that
in donor-acceptor substituted distyrylbenzenes, and XFs
(23) (a) Lewis, F. D.; Sinks, L. E.; Weigel, W.; Sajimon, M. C.; Crompton,
E. M. J. Phys. Chem. A 2005, 109, 2443–2451. (b) Crompton, E. M.; Lewis,
F. D. Photochem. Photobiol. Sci. 2004, 3, 660–668. (c) Lewis, F. D.;
Crompton, E. M. J. Am. Chem. Soc. 2003, 125, 4044–4045.
(22) Solntsev, K. M.; McGrier, P. L.; Fahrni, C. J.; Tolbert, L. M.; Bunz,
U. H. F. Org. Lett. 2008, 10, 2429–2432.
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FIGURE 11. Titration of XF 4 in acetonitrile with calcium triflate: (left) UV/vis absorption; (right) emission. The inset displays the
concentration -log[Ca2þ] in mol L-1. Notice that in acetonitrile the final concentration of calcium triflate can be pushed considerably higher.
As a consequence, close to full metalation of the XF 4 is possible and there is no uncomplexed XF left. The excitation wavelength was 350 nm.
FIGURE 12. Titration of XF 4 in acetonitrile with manganese triflate: (left) UV/vis absorption; (right) emission. The inset displays the
concentration -log[Mn2þ] in mol L-1. The excitation wavelength was 350 nm.
FIGURE 13. Titration of XF 1 in acetonitrile with manganese triflate: (left) UV/vis absorption; (right) emission. The inset displays the
concentration -log[Mn2þ] in mol L-1. The excitation wavelength was 350 nm.
in which aqueous solutions of metal salts disrupt excimers of
these fluorophores but do not lead to significant shifts in
absorption.24 We suspect that the presence of the electron-
accepting -CH2CO2- groups has a detrimental influence on
the basicity of the aniline nitrogen, and coordination of
metal cations will not occur through them. In the case of
1-4, even in polar solvents such as acetonitrile, coordination
to metal cations leads to significant changes in absorption
and particularly in emission; addition of suitable electroni-
cally nondisturbing binding appendages to the amine groups
of the XFs should lead then perhaps to functional metal
TABLE 3. Binding of the XFs 1 to Calcium and Manganese Triflates
-Log β
absorption
amission
Mn2þ
Ca2þ
3.79
1.75
3.98
1.56
are a special case of distyrylbenzenes, the substitution pat-
tern, i.e., where the acceptor is located, seems to be critical.
Indeed, Perry, Marder et al. demonstrated that 2,5-dicyano-
1,4-distyrylbenzenes show little cation-induced shift in emis-
sion upon metal coordination.10a All the cases we have
investigated, however, show quite large shifts in absorption
and emission. Exceptions are water-soluble EDTA-like XFs,
(24) Tolosa, J.; Zucchero, A. J.; Bunz, U. H. F. J. Am. Chem. Soc. 2008,
130, 6498–6506.
532 J. Org. Chem. Vol. 75, No. 3, 2010

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FIGURE 14. Titration of XF 1 in acetonitrile with calcium triflate: (left) UV/vis absorption; (right) emission. The inset displays the
concentration -log[Ca2þ] in mol L-1. The end of the titration is defined by the saturation of the solution with calcium triflate. Full
coordination of 1 to calcium triflate is not possible. The excitation wavelength was 350 nm.
sensory XFs that can be deployed in cell staining and other
biosensory applications.
(E)-Diethyl 2,5-Diiodo-4-[4-di(1-butyl)aminostyryl]benzylpho-
sphonate 10 (General Procedure for Horner Monoalkenylation
A). A solution of diphosphonate 925 (3.15 g, 5.00 mmol) in dry
THF (75 mL) was stirred at 0 °C under N2 while tBuOK (505 mg,
4.50 mmol) was added carefully. After addition, the reaction
mixture was stirred for 3 min. Then, 4-di(1-butyl)amino-
benzaldehyde (933 mg, 4.00 mmol) in dry THF (5 mL) was added
as quickly as possible. After 30-40 min, 75 mL of water, followed
by5 mL ofanaqueoussaturated solutionof NH4Cl, was addedto
quench the reaction. The mixture was extracted with DCM (3 ꢁ
75 mL). The combined organic phases were washed with water
and brine and dried over MgSO4. After filtration, the solvent
was removed in vacuo and the crude mixture was purified by
column chromatography (ethyl acetate/hexanes 1:2) to give 10
as a yellow oil (1.39 g, 49%). 1H NMR, CDCl3 (δ, 300 MHz):
0.97 (t, 6H, J = 7.2 Hz); 1.28 (t, 6H, J = 7.2 Hz); 1.30-1.40 (m,
4H); 1.49-1.60 (m, 4H); 3.20-3.32 (m, 6H); 3.97-4.14 (m,
4H); 6.57 (d, 2H, J = 9 Hz); 6.83 (d, 1H, J = 16 Hz); 6.89 (d,
1H, J = 16 Hz); 7.39 (d, 2H, J = 9 Hz); 7.79 (d, 1H, J = 4 Hz);
7.98 (d, 1H, J = 2 Hz). 13C NMR, CDCl3 (δ, 75 MHz): 148.5,
141.8 (d, J = 3.2 Hz), 140.7 (d, J = 6.4 Hz), 135.8 (d, J = 3.1
Hz), 135.0 (d, J = 9.6 Hz), 133.0, 128.6, 125.0, 123.5, 111.7,
101.6 (d, J = 7.2 Hz), 99.7 (d, J = 4.0 Hz), 62.7 (d, J = 7.2 Hz),
51.0, 37.6 (d, J = 137 Hz), 29.6, 20.5, 16.8 (d, J = 5.6 Hz), 14.3.
The synthesis of 9 provides a partially brominated impurity
which is impossible to separate from the desired compound.25
This makes impossible to obtain elemental analysis for the
precursors of XFs 1-5.
Experimental Section
(E)-1-[4-Di(1-butyl)aminostyryl]-(E0)-4-(4-tert-butylstyryl)-
2,5-bis(phenylethynyl)benzene 1 (General Procedure C). A solu-
tion of 13 (141 mg, 0.252 mmol), PdCl2(PPh3)2 (2%) and CuI
(2%) in 3 mL of a mixture of dry THF/piperidine 2:1 was stirred
for 10 min at room temperature under N2. Phenylacetylene
(257 mg, 2.52 mmol) was added and the reaction was stirred at
room temperature overnight. After reaction time, the mixture was
poured into water and extracted with dichloromethane (DCM) (3
ꢁ 25 mL). The combined organic phases were collected and dried
over MgSO4, and the solvent was evaporated after filtration. The
crude mixture was purified by column chromatography (hexanes/
ethyl acetate 9:1) to provide an orange solid (145 mg, 87%). Mp:
78-81 °C. 1H NMR, CDCl3 (δ, 300 MHz): 0.97 (t, 6H, J = 7.2
Hz); 1.33-1.42 (m, 4H); 1.35 (s, 9H); 1.54-1.66 (m, 4H); 3.31 (t,
4H, J = 7.5 Hz); 6.65 (d, 2H, J = 9 Hz,); 7.20 (d, 1H, J = 16 Hz,);
7.24 (d, 1H, J = 16 Hz); 7.38-7.48 (m, 11H); 7.52 (d, 2H, J = 9
Hz); 7.60-7.68 (m, 5H); 7.89 (broad s, 2H).13C NMR, CDCl3 (δ,
75 MHz): 151.3, 148.3, 138.6, 136.7, 134.9, 131.8, 131.2, 130.0,
128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.4, 126.7, 126.7, 125.9,
125.3, 124.6, 123.6, 123.5, 122.3, 121.7, 120.5, 111.8, 95.3, 95.3, 88.5,
88.3, 51.0, 34.9, 31.5, 29.7, 20.6, 14.3. IR (cm-1): 3037, 2956, 2863,
1604, 1577, 1517, 1511, 1364, 1181, 958.6, 807, 754, 690. MS (EI):
(Mþ) 665. HRMS: 665.3983 (calcd 665.3974). Anal. C, 89.90; H,
8.02; N, 2.15 (calcd C, 90.18; H, 7.72; N, 2.10).
(E)-1-[2-(Pyridin-4-yl)vinyl]-(E0)-4-[4-di(1-butyl)aminostyryl]-
2,5-bis(phenylethynyl)benzene 4. We employed general proce-
dure C, using diiodide 16 (331 mg, 0.499 mmol). The crude
mixture was purified by precipitation in cold ethanol to give an
orange solid (256 mg, 84%). Mp: 138-142 °C. 1H NMR,
CD2Cl2 (δ, 300 MHz): 0.97 (t, 6H, J = 7.2 Hz); 1.33-1.42 (m,
4H); 1.54-1.67 (m, 4H); 3.32 (t, 4H, J = 7.5 Hz); 6.66 (d, 2H,
J = 9 Hz,); 7.20 (d, 1H, J = 16 Hz,); 7.25 (d, 1H, J = 16 Hz);
7.40-7.50 (m, 2H); 7.60-7.69 (m, 6H); 7.88 (d, 1H, J = 16 Hz,);
7.93 (broad s, 2H). 13C NMR, CD2Cl2 (δ, 75 MHz): 150.6, 148.8,
144.8, 139.9, 135.1, 132.3, 131.9, 130.2, 129.7, 129.1, 129.0, 128.9,
128.9, 128.6, 128.4, 127.6, 124.1, 123.5, 123.2, 123.1, 121.8, 121.2,
119.7, 111.9, 96.0, 95.8, 88.1, 87.8, 51.0, 29.8, 20.7, 14.1.
IR (cm-1): 2968, 2868, 1593, 1582, 1522, 1497, 1365, 1181,
961, 803, 756, 686. MS (EI): (Mþ) 610, HRMS: 610.3302
(calcd 610.3314). Anal. C, 88.52; H, 6.87; N, 4.64 (calcd C,
88.48; H, 6.93; N, 4.59).
(E)-1-[4-Di(1-butyl)aminostyryl]-(E0)-4-(4-tert-butylstyryl)-
2,5-diiodobenzene 13 (General Procedure B). A solution of 12
(1.29 g, 2.03 mmol) and 4-di(1-butyl)aminobenzaldehyde (520 mg,
2.23 mmol) in dry THF (25 mL) was stirred at 0 °C under N2 while
tBuOK (250 mg, 2.23 mmol) was added carefully. After
addition, the reaction mixture was stirred for 30 min. Then,
20 mL of water followed by 3 mL of a saturated aqueous
solution of NH4Cl was added to quench the reaction. The
mixture was extracted with DCM (3 ꢁ 50 mL). The combined
organic phases were washed with water and brine and dried
over MgSO4. The crude mixture was purified by column chro-
matography (ethyl acetate/hexanes 1:9) to give 13 as a yellow
1
solid (1.20 g, 83%). Mp: 135-139 °C. H NMR, CDCl3 (δ,
300 MHz): 0.97 (t, 6H, J = 7.2 Hz); 1.33-1.42 (m, 4H); 1.35 (s,
9H); 1.54-1.66 (m, 4H); 3.31 (t, 4H, J = 7.5 Hz); 6.65 (d, 2H,
J = 9 Hz,); 6.85-7.00 (m, 2H); 7.16 (d, 1H, J = 16 Hz,);
7.35-7-55 (m, 7H); 8.01 (broad s, 2H). 13C NMR, CDCl3 (δ,
75 MHz): 151.4, 148.4, 141.5, 139.7, 136.1, 135.5, 134.0,
132.6, 131.4, 129.9, 128.5, 126.7, 125.2, 123.6, 111.5, 100.4,
100.1, 51.0, 34.9, 31.5, 29.8, 20.7, 14.1. IR (cm-1): 3030, 1605,
1518, 1364, 961, 735. MS (EI): (Mþ) 717.
(25) Wilson, J. N.; Windscheif, P. M.; Evans, U.; Myrick, M. L.; Bunz,
U. H. F. Macromolecules 2002, 35, 8681–8683.
J. Org. Chem. Vol. 75, No. 3, 2010 533

Tolosa et al.
JOCFeatured Article
Acknowledgment. We thank the National Science Founda-
tion for generous support (U.B., J.T. NSF CHE 0750275
Cruciform Fluorophores; LMT and KMS NSF CHE-
0809179 excited-state proton transfer). J.T. thanks the Junta
de Comunidades de Castilla La Mancha (Fondo Social
Europeo FSE 2007-2013) for his postdoctoral grant. We thank
Profs J.-S. Yang and W. Rettig for valuable comments. We
thank Katya Kouznetsova for the covert art design.
Supporting Information Available: Spectroscopic data and
synthetic details. This material is available free of charge via the
Internet at http://pubs.acs.org.
534 J. Org. Chem. Vol. 75, No. 3, 2010