Redox-controlled fluorescence modulation in a BODIPY-quinone dyad

Article abstract of DOI:10.1002/ejoc.200800191

The synthesis and properties of two closely related boron dipyrromethene (BODIPY) derived dyads, incorporating redoxactive quinone units appended at the meso position, are described. For one dyad, the quinone unit is attached directly to the BODIPY core, whereas a phenylene spacer separates the two units in the second compound. Each of the quinone units is readily converted, by both chemical and electrochemical means, to the corresponding hydroquinone derivative. The strong fluorescence normally associated with the BODIPY unit is efficiently quenched in both dyads in their quinone forms. This is attributed to deactivation of the first excited singlet state by a way of an intramolecular electron-transfer process. By comparison, moderately intense fluorescence is observed for the hydroquinone derivative containing the phenylene spacer, but not for the analogous directly coupled dyad. The potential sensing capabilities of the phenylene-spaced BODIPY quinone and hydroquinone dyads, towards reducing and oxidising species such as ascorbate and peroxide, were tested in a biomembrane mimic. A reversible modulation in fluorescence could be readily detected by eye under standard UV-light excitation. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800191

FULL PAPER
DOI: 10.1002/ejoc.200800191
Redox-Controlled Fluorescence Modulation in a BODIPY-Quinone Dyad
Andrew C. Benniston,*[a] Graeme Copley,[a] Kristopher J. Elliott,[a] Ross W. Harrington,[b]
and William Clegg[b]
Keywords: BODIPY / Fluorescence / Molecular devices / Redox chemistry / Sensors
The synthesis and properties of two closely related boron di-
pyrromethene (BODIPY) derived dyads, incorporating redox-
transfer process. By comparison, moderately intense fluores-
cence is observed for the hydroquinone derivative containing
active quinone units appended at the meso position, are de- the phenylene spacer, but not for the analogous directly
scribed. For one dyad, the quinone unit is attached directly
to the BODIPY core, whereas a phenylene spacer separates
the two units in the second compound. Each of the quinone
units is readily converted, by both chemical and electro-
chemical means, to the corresponding hydroquinone deriva-
tive. The strong fluorescence normally associated with the
BODIPY unit is efficiently quenched in both dyads in their
quinone forms. This is attributed to deactivation of the first
excited singlet state by a way of an intramolecular electron-
coupled dyad.
The potential sensing capabilities of the phenylene-spaced
BODIPY quinone and hydroquinone dyads, towards reduc-
ing and oxidising species such as ascorbate and peroxide,
were tested in a biomembrane mimic. A reversible modula-
tion in fluorescence could be readily detected by eye under
standard UV-light excitation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
observed by the human eye, even for nanomolar concentra-
tions of luminophore, while single-molecule detection can
be observed under certain conditions.[9] A general problem
inherent to all luminescent sensors is background noise cre-
ated by other endogenous luminophores that are acciden-
tally excited; time-gated methods using long-lived emit-
ters[10] or delayed emission[11] offer potential solutions to
this predicament. The next problem is to provide a failsafe
means by which the emission intensity can be related to the
property under investigation. This usually requires equip-
ping the fluorophore with ancillary groups that undergo
complexation,[12] redox switching[13] or conformational ex-
change[14] and thereby provide the essential on-off signal.
This procedure can be adapted to design fluorescent sensors
to monitor, for example, local pH,[15] concentrations of ana-
lytes (e.g., Na+, PO43–),[16] drug metabolite products,[17]
toxins,[18] nerve agents[19] and reactive oxygen species
(ROS).[20a,20b]
Introduction
Interest in the development of innovative probes for
monitoring real-time events in micro- to nano-scale envi-
ronments has grown rapidly over the past decade.[1] This
can be traced, in part, to the need for reliable information
on physical and/or chemical events occurring in reaction
volumes that are extremely difficult to access by conven-
tional imaging technology. In specific cases, the capability
to construct miniaturised tools (e.g., nano-electrodes)[2] has
opened up new means by which to monitor in situ growth
of insoluble residues,[3] corrosion,[4] leakage[5] and flow dy-
namics,[6] for example. Although we seem certain to witness
a great expansion in such technology, the accompanying
problem of being able to access ever-smaller dimensions
must not be overlooked. Molecular-scale probes,[7] simply
by virtue of their size, have the advantage of being able to
enter most cavities, pores and cages but need to be equipped
with an appropriate signalling system.
The detection of ROS is a field of great topical interest,
especially in biomedicine, because they have both beneficial
(e.g., smooth muscle relaxation) and harmful (e.g., prema-
ture aging) roles.[21] To this end, fluorescent probes for the
in situ detection of biological activity have been used
widely. A common theme for the mode of action of such
probes requires reaction of the ROS to alter the structure
of the fluorophore, indirectly converting it from non-lumi-
nescent to strongly emissive.[21] Under these conditions, the
structural change may be irreversible, such that the probe
is effectively redundant after detection. In an endeavour
to develop more re-usable redox-responsive fluorescent
Luminescence, in its many disparate forms and including
delayed fluorescence,[8] is generally accepted as being a su-
perior signalling method. Indeed, fluorescence can often be
[a] Molecular Photonics Laboratory, School of Natural Sciences,
Newcastle University,
Newcastle upon Tyne, NE1 7RU, UK
Fax: +44-191 222 6929
E-mail: a.c.benniston@ncl.ac.uk
[b] Crystallography Laboratory, School of Natural Sciences, New-
castle University,
Newcastle upon Tyne, NE1 7RU, UK
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
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A. C. Benniston et al.
FULL PAPER
probes, we have focussed on using the reversible quinone/
hydroquinone couple. This redox pair has been used pre-
viously with ruthenium(II) (polypyridyl) luminophores as
the reporting units,[22a,22b] but such systems have serious
disadvantages; most notably, the emission quantum yields
are rather low under ambient conditions and highly de-
pendent on temperature while the compounds dissolve only
in polar media. To overcome these problems, our attention
has turned to the difluoro borondipyrromethene (BOD-
IPY) dyes because these exhibit intense fluorescence in the
visible region and undergo reductive/oxidative quench-
ing.[23a,23b] The design element demands that the quinone
quenches fluorescence from the BODIPY, due to electron
transfer, but conversion to the corresponding hydroquinone
restores the emission. A well known issue in this type of
sensor concerns how well intramolecular electron transfer
competes with the normal radiative process because this
competition sets the on-off level. This is not a real problem
with long-lived phosphorescence from transition-metal che-
lates[24] but becomes a serious concern with short-lived or-
ganic fluorophores. To allow for this point, we consider two
prototypes that differ according to the linkage between the
dye and the quencher. The first system has the quinone/
hydroquinone unit attached directly to the BODIPY core
while the alternative sensor has a phenylene spacer inserted
between the terminal groups. The two systems show quite
disparate behaviour. The dyads with the spacer show excel-
lent on/off attenuation in fluorescence, and attention is
given to both electrochemical and chemical switching. In
particular, the systems display the capability to act as re-
porters for biologically relevant species in a membrane
mimic.
Scheme 1. Reagents and conditions. (i) DCM, TFA, room temp.;
DDQ; N,N-diisopropylethylamine, BF3·Et2O. (ii) H2, 4 atm, DCM/
MeOH, Pd/C (10%). (iii) H2, 4 atm, DCM/MeOH, Pd/C (10%);
DDQ, THF.
Results and Discussion
Synthesis
after hydrogenation could be taken through to the quinone
derivative, BD-Q, by oxidation with DDQ. The isolated
yield after purification was a respectable 82%. Preparation
of the phenylene-spaced dyad, BD-PQ, was carried out in
a similar manner to that described above but using com-
pound 5. This latter material was prepared in an excellent
90% yield by Suzuki coupling of 3 with the boronic acid 4.
A full range of structural tools, including mass spectrome-
try, 1H, 13C, 19F and 11B NMR spectroscopy, elemental
analysis, and X-ray crystallography, was used to identify
and to confirm purity of the hydroquinone and quinone
derivatives.
The synthetic procedures employed to obtain the desired
dyads are outlined in Scheme 1 and rely heavily on the tried
and tested methods used for the synthesis of other BOD-
IPY derivatives.[25] For preparation of both dyads, the
hydroquinone unit was protected as the benzyl ether rather
than the corresponding methyl ether, because of ease of
removal. In fact, our first synthetic strategy did produce
the methoxy versions (BD-M, BD-PM), but deprotection
(BBr3) resulted in very low yields of the final products.
These two compounds, however, are useful as controls for
subsequent electrochemical and photophysical measure-
ments.
Reaction of commercially available 3-ethyl-2,4-dimethyl-
1H-pyrrole with 1 in CH2Cl2 containing trifluoroacetic
acid, followed by in situ oxidation and chelation with BF2,
Crystal Structure Determination
Several of the BODIPY derivatives crystallised to afford
produced 2 in 50% yield after extensive column chromatog- X-ray diffraction quality samples. Structures were obtained
raphy. A similar procedure, but using 4-bromobenzalde- for 5 (which has three independent molecules in the asym-
hyde, afforded 3 in modest yield. Removal of the benzyl metric unit), BD-Q, BD-PQ, the dimethoxy derivative of
protecting group under reducing conditions afforded BD- BD-PHQ, and the parent BODIPY with no meso substitu-
HQ in near quantitative yield. Although this product was ent, which serves as a reference structure for comparisons.
isolated and purified, it was found that the crude product An exhaustive description of each compound is not pre-
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Redox-Controlled Fluorescence Modulation
sented here, but full details for each structure are given in ling to 10B. As the temperature is raised, the resonances
the Supporting Information. The most interesting structure, show no obvious sign of broadening or coalescence. It
especially with regard to the 19F NMR spectrum discussed would appear that free rotation of the benzene ring is
below, is that of BD-Q as depicted in Figure 1. The molecu- restricted, presumably by the two proximal methyl groups
lar geometry clearly shows the relative positioning of the of the BODIPY unit. This finding agrees with molecular
two quinone oxygen atoms with respect to the fluorine dynamics simulations in a solvent matrix that support a se-
atoms attached at the boron centre. The quinone ring is vere “rocking” of the ring but without full rotation.
exactly perpendicular to the BODIPY fused ring system (di-
hedral angle: 90°). The two intramolecular O···F distances
are 5.572 Å and 8.094 Å on the two sides of the BODIPY
plane. Even the shortest distance is well outside the range
expected to yield appreciable lone-pair:lone-pair repulsion
between oxygen and fluorine atoms. The two molecules in
the unit cell pack in a slightly offset head-to-tail centrosym-
metric arrangement. This motif is a common feature for
BODIPY derivatives.[26] The shortest intermolecular O···F
distance is 3.837 Å.
Figure 2. 19F NMR spectrum recorded for BD-Q in CDCl3 show-
ing the coupling patterns and tentative assignment.
Assuming the measured chemical shift for BD-PQ
(–145.55 ppm) represents an unperturbed fluorine atom, the
more positive chemical shift pattern (–144.97 ppm) must be
associated with Fa (Figure 2). It is known that, because of
the large polarizability of C–F bonds, 19F chemical shifts
are susceptible to weak long-range electronic interac-
tions.[28] Apparently, this is even more so for the B–F bond,
presumably because of the increased electronegativity dif-
ference between the two atoms. As far as we are aware, split-
ting of the fluorine resonances has not been reported pre-
Figure 1. Molecular structure of the quinone derivative BD-Q.
19F NMR Spectroscopy
viously. To see if the phenomenon is unique to the quinone
derivative, the 19F NMR spectrum for BD-M was collected
The most noteworthy NMR spectroscopic finding relates
under identical conditions. The 19F NMR spectrum (see
to the 19F spectrum for BD-Q in CDCl3. In all reported
Supporting Information) is very similar in appearance to
literature references, the 19F NMR spectrum corresponds
that shown in Figure 2. There are, however, subtle differ-
to a single quartet (coupling to 11B: I = 3/2, J ≈ 32 Hz).[27]
ences in the chemical shifts for the two fluorine signals,
Indeed, this pattern was seen for the corresponding spec-
which suggest that the hydridisation state of oxygen has an
trum of BD-PQ. In the case of BD-Q, however, the 19F
effect on the extent of shielding.
NMR spectrum comprises two distinct sets of resonances
that after deconvolution contain 8 lines (Figure 2). The en-
tire set of signals could be simulated as an approximate
Electrochemical Investigations
doublet of quartets using J (11B-19F) = 33.5 Hz, J (11B-19F)
= 31.0 Hz and J (19F-19F) = 108.7 Hz (see Supporting In-
A full investigation, where possible, of the redox behav-
formation). Evidently, this finding is consistent with each iour for the quinone, hydroquinone and dimethoxy deriva-
fluorine atom residing in two distinctly different environ- tives was carried out in CH2Cl2 (0.2  TBATFB) by cyclic
ments. Moreover, the two fluorine atoms (Fa, Fb) can be voltammetry. Because of solubility problems, the cyclic vol-
inequivalent only if rotation of the quinone unit is slow on tammogram for BD-PHQ was obtained from a solution in
the NMR time-scale. To explore the possible rotation dry DMSO. A representative cyclic voltammogram for BD-
dynamics, 19F NMR spectra were recorded for BD-Q in PQ is presented in the Supporting Information and can be
[D8]toluene at temperatures ranging from 303 to 378 K interpreted in terms of the known electrochemical behav-
(Supporting Information). At room temperature, the spec- iour of isolated BODIPY[29] and quinone derivatives.[30] In
trum is similar to that shown in Figure 2, but there is some each case, one-electron oxidation of BODIPY and one-elec-
overlap of signals and satellite peaks from additional coup- tron reduction of the quinone correspond to quasi-revers-
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A. C. Benniston et al.
FULL PAPER
ible processes. Collected in Table 1 are the associated half- the Supporting Information. Collected in Table 2 are asso-
wave potentials (E1/2), vs. Fc+/Fc, for the various oxidation ciated photophysical parameters for the BODIPY deriva-
and reduction processes. There are some important points tives. The lowest-energy energy maximum (λABS) for BD-M
to note regarding the electrochemical data, especially when seen at 521 nm is assigned to the S0–S1 electronic transition
comparing the two quinones.
associated with the BODIPY core. The high molar absorp-
tion coefficient (εmax) is in keeping with previous find-
ings.[32] The significantly broader and less intense band seen
at ca 380 nm corresponds to the S0–S2 transition. The high-
energy absorption band can be attributed to π–π* transi-
tions for the appended dimethoxybenzene unit.
Table 1. Electrochemical data recorded for several of the BODIPY
derivatives as defined in the text.
Cmpd.[a]
E1 [V][b] E2 [V][c] E3 [V][d] E4 [V][e] ∆E [V][f]
BD-M
BD-HQ
BD-Q
BD-PM
BD-PHQ[h]
BD-PQ
–
–
–1.76
–1.58
–1.81[g]
–1.65
–1.50
–1.79
0.61
0.82
0.71
0.73
0.76
0.63
–
0.61
2.37
2.40
2.52
2.38
2.26
2.42
–0.79
–
–
–
–
Table 2. Collection of photophysical parameters for the series of
BODIPY derivatives in CH3CN at room temperature.
0.56[g]
[g]
Compound[a] λABS λEM εmax
[nm] [nm] ₍–1 cm–1
∆νSt
φFLU τFLU
kRAD
[ϫ108 s–1
]
–0.90
–
]
[cm–1
]
[ns]
[a] In dry CH2Cl2 containing 0.2  TBATFB at Pt electrode,
50 mVs–1 scan rate, E values verses Fc+/Fc (E1/2 = 0.44 V). [b]
E1/2 For one-electron reduction of quinone. [c] E1/2 For one-elec-
tron reduction of BODIPY. [d] E1/2 For one-electron oxidation of
BODIPY. [e] E1/2 For one-electron oxidation of hydroquinone. [f]
E3 – E2. [g] No reverse peak observed. [h] In DMSO.
BD-P[b]
BD-M
BD-HQ
BD-Q
BD-PM
BD-PHQ
BD-PQ
521
523
525
529
521
521
523
535
537
539
547
537
537
539
75300
87400
79400
59700
77800
78300
68500
503
499
495
623
573
573
568
0.67
0.68
5.8
6.0
0.48
Ͻ0.05
5.6
1.16
1.13
1.04
–
1.09
1.08
–
0.05
[c]
0.61
0.54
5.0
Ͻ0.05
Evidently, the ease of reduction and oxidation of the
BODIPY core is dependent on the redox state of the ap-
pended group. For both sets of dyad, oxidation and re-
duction is more difficult for the quinone form than for the
hydroquinone derivative. Comparison of BD-Q with BD-
PQ reveals that reduction of the quinone unit is markedly
easier when the unit is attached directly. The corollary is
that removal of an electron from the BODIPY unit is made
more difficult. However, the difference E3 – E1 (see Table 1
for description of peak identities) is relatively constant at
ca. 1.5 eV for the two compounds.
[c]
[a] Abbreviations described in the text. [b] Reference compound is
meso-phenyldifluoroborondipyrromethene. [c] Too small to be mea-
sured accurately.
Room-temperature fluorescence from BD-M is detected
readily in fluid solution, the band shape being a good mir-
ror image of the absorption profile. There is also a good
match between the excitation and absorption spectra. The
small Stokes’ shift (∆νSt) is in line with previous work on
BODIPY compounds and supports the concept of a modest
structural change accompanying excitation.[33] The fluores-
cence quantum yield (φFLU) is comparable to that deter-
mined for BD-P under identical conditions, as is the fluo-
rescence lifetime (τFLU) determined by single-photon count-
ing methods. The decay curve was mono-exponential. The
radiative rate constant (kRAD = φFLU/τFLU) remains com-
parable to literature values. Overall, the methoxy group has
little, if any, effect on the photophysical behaviour of the
BODIPY dye. Inserting a benzene ring between dye and
appended dimethoxybenzene unit has no significant effect
on the measured photophysical properties (Table 2).
Conversion of the dimethoxybenzene group into the
analogous hydroquinone derivative has little effect on the
shape or position of the absorption and fluorescence max-
ima. Even subjecting the spectral profiles to detailed curve-
fitting routines failed to detect significant electronic coup-
ling between the subunits. Furthermore, the Stokes’ shifts
remain highly comparable to those derived for the reference
compounds. There are, however, small perturbations of the
measured emission quantum yields and lifetimes consistent
with quenching of the S1 state localised on the BODIPY
unit by the appended hydroquinone. On the basis of the
electrochemical results, quenching can be attributed to in-
tramolecular electron transfer from the hydroquinone to the
excited state of the BODIPY dye, for which the rate con-
stant (kET) can be determined from Equation (1). Here,
τCOMP and τREF refer to the fluorescence lifetimes of the
Photophysical Studies
Photophysical data, including absorption and fluores-
cence maxima, were collected for all compounds in dry
CH3CN, this being the most suitable solvent to dissolve the
hydroquinone derivatives. For comparative purposes, sim-
ilar data were recorded for the literature compound,
BD-P,[31] containing a phenyl group attached to the meso
position of the BODIPY. As a typical example, a set of
absorption/fluorescence profiles for BD-M are shown in
Figure 3 and the remaining absorption spectra are given in
Figure 3. Typical absorption (black) and fluorescence (grey) spectra
for BD-M in CH3CN at room temperature.
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Redox-Controlled Fluorescence Modulation
compound and its appropriate reference, respectively. The there is a large disparity in emission probabilities for the
derived kET values are markedly different for the two deriv- two forms. The upshot of this finding is that, whereas BD-
atives, despite the comparable thermodynamic driving PQ is non-luminescent, the counterpart, BD-PHQ, displays
forces (∆G0) for light-induced electron transfer. These latter appreciable fluorescence in fluid solution at room tempera-
values were estimated from the peak potentials observed ture. Thus, the molecules exhibit the on/off luminescence
in the cyclic voltammograms and corrected for changes in switching required for sensing applications. The external
electrostatic potential caused by charge separation.[34] There trigger need only serve to interconvert the quinone and hy-
is only a small driving force for electron transfer, with ∆G0 droquinone moieties.
changing from –0.09 eV for DB-PHQ to only 0.03 eV for
DB-HQ. Nonetheless, kET for DB-HQ has a value of
1.9ϫ109 s–1, which is relatively high and accounts for some
Spectroelectrochemical and Chemical Fluorescence
92% of the total deactivation steps. The almost 100-fold
increase in kET found for the directly linked analogue can
be ascribed to the shorter separation distance between the
redox units.
Switching
Having identified the leading candidates for sensing
applications, the next stage involved testing the dyads under
rigorously controlled switching conditions. The first set of
experiments involved electrochemical modification of the
appended quinone group within BD-PQ, using a standard
OTTLE cell set-up and controlled fixed-potential electroly-
sis. The change in fluorescence intensity was monitored
over time following reduction of BD-PQ in DCM (0.2 
TBATFB) at –0.9 V vs. Fc/Fc+. At this reduction potential,
by inspection of the redox data given in Table 1, we expect
to perform one-electron reduction so as to produce the so-
called semiquinone (i.e., Q + e– Ǟ Q–·). Illustrated in Fig-
ure 4 are the corresponding alterations in fluorescence pro-
files, following electrolysis over some 10 min. After this time
there was a noticeable levelling off in fluorescence intensity,
which was taken to indicate complete turnover of BD-PQ.
By switching the potential of the working electrode to
+0.50 V vs. Fc/Fc+, the reverse process could be observed
in which fluorescence intensities decreased over time (Sup-
porting Information). This cycle could be repeated many
times, without any real drop in performance of the system.
To interpret the above observations it is worth noting that
the experiments were carried out in a low-polarity aprotic
solvent, which simplifies somewhat electrochemical pro-
cesses regarding quinones; no protonated forms need to be
considered.[36] The exhaustive reductive electrolysis presum-
ably builds up the concentration of semiquinone at the
working electrode, which is known to disproportionate to
the dianion (2Q–· Ǟ Q2– + Q). The dianion, being a poor
quencher, leads to the observed fluorescence change.
1
1
kET = (
–
)
(1)
τCOMP τref
The absorption profile, including half-widths, found for
BD-PQ is rather similar to that recorded for the control
compound but the small red shift and reduced oscillator
strength noted for BD-PQ suggests weak electronic interac-
tion between the subunits in this case (Table 2). Extremely
weak fluorescence could be detected for BD-Q and BD-PQ
at ambient temperature. Time-resolved fluorescence decay
profiles were dual exponential, comprising a long-lived
component that matched the lifetime of the hydroquinone
derivative and an extremely short-lived component with a
lifetime that could not be properly resolved from the instru-
mental response time (ca. 50 ps). The contribution of the
longer lifetime component could be reduced, but not com-
pletely eradicated, by repeated purification of the samples
by preparative TLC. These findings are consistent with
minor contamination of the quinone derivatives with their
corresponding hydroquinone forms. Hence, it was not pos-
sible to measure accurately φFLU values. However, assuming
that kRAD remains constant for the BODIPY derivatives,
an upper limit for the φFLU of the quinone derivatives is
0.005.
Fluorescence quenching by quinone moieties is well
known and can be attributed to light-induced electron
transfer.[35a,35b] From the cited electrochemical data
(Table 1), ∆G0 values of –0.90 and –0.83 eV, respectively,
can be calculated for BD-Q and BD-PQ. These driving
forces are sufficiently large to ensure that oxidative electron
transfer competes effectively with the radiative event. In this
case, the observed emission yield is set by the level of hydro-
quinone impurities remaining in the sample. Although we
might expect kET to be much higher for the directly linked
analogue than for the phenylene-spaced derivative, this situ-
ation is not apparent from the results presented here. In-
stead, we can only set the lower limit for kET as being
Ͼ2ϫ1010 s–1. It is evident when comparing BD-HQ and
BD-Q, however, that there is not a major on/off fluores-
cence modulation between the two forms. Thus, for sensing
applications, this pair of compounds is rather limited. This
Figure 4. Observed increase in fluorescence intensity upon fixed-
potential reduction of BD-PQ (c ≈ 4 µ) in DCM (0.2  TBATFB)
is not the case for the phenylene-spaced analogues, where using a conventional OTTLE cell.
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Because lipid oxidative stress is a well established cause terations. We expected some oxidation of the BODIPY unit
of cell damage,[37] we were interested to test the reporting by peroxide, which is observed, but the change in fluores-
capabilities of the two redox sensors in a lipid-like environ- cence signal is only ca. 30% over 10 min. By comparison,
ment. To mimic lipid membranes, micelles dispersed in under reducing conditions with ascorbate the change is
water have been used widely,[38] seeing as they can encapsu- fluorescence intensity is only ca. 10%. These two competing
late organic molecules in the hydrophobic core. The two redox reactions presumably take place for BD-PQ and BD-
compounds, BD-PQ and BD-PHQ, are totally insoluble in P, but are much slower than the redox processes at the qui-
water. However, careful sonication of a few milligrams of none/hydroquinone moieties. This seems reasonable con-
each compound in water containing 5% v/v Triton-X and sidering the disparate redox potentials between, for exam-
filtering afforded noticeably coloured solutions. The ab- ple, the quinone and BODIPY subunits (Table 1). Overall,
sorption spectra recorded at 25 °C for separate solutions of chemically induced, reversible cycling of the redox couple
BD-PQ and BD-PHQ (Supporting Information) displayed looks entirely feasible.
the characteristic profiles seen previously (Figure 3). More-
over, the narrow band-shapes support lack of any appreci-
able self-aggregation of the compounds within the micelles.
The concentration of the two solutions, assuming that εmax
Conclusions
By precise positioning of a redox-active unit on the
highly fluorescent BODIPY scaffold it has been possible to
values do not change widely, are similar and around 4 µ.
An especially prevalent ROS is peroxide, and so to test its
produce an extremely responsive on/off fluorescent molecu-
possible detection, sodium percarbonate was added to the
lar probe. Although many different fluorophores have
micelle solution containing BD-PHQ (4 µ) and Na2HPO4
(0.18 ). We considered that under these conditions the
found applications in the sensing field, the BODIPY unit is
emerging as a frontrunner.[39] In fact, the number of BOD-
H2O2 released by the percarbonate would oxidise the hydro-
IPY-based derivatives for applications as probes in the sens-
quinone to quinone, and thus bring about efficient fluores-
ing field, toward species such as cations (i.e., Zn2+, K+,
cence modulation. The dramatic reduction in recorded fluo-
Hg2+, Cd2+),[40–43] gases (O2, NO)[44,45a,45b] and thiols,[46] is
rescence emission (Figure 5) over some 10 min after perox-
growing constantly. It is worth noting that use of BODIPY-
ide formation is fully consistent with the formation of BD-
based molecules for detection of ROS and monitoring lipid
PQ by the proposed chemical transformation. Under con-
oxidation in living cells have been developed.[47–50] The
trol conditions without percarbonate, no change in emis-
technique, however, relies on ratio-imaging and the loss of
sion signal was noted. It was especially encouraging that a
fluorescence caused by direct oxidation of the dye. This
very clear-cut difference in on/off signal was readily observ-
method has the clear disadvantage that the chromophore is
able to the naked eye, as shown in the insert of Figure 5.
destroyed. A more recyclable system is feasible using our
outlined method, but clearly more testing is required using
different ROS, to evaluate parameters such as selectivity,
compound degradation and biocompatibility. We expect to
address these factors at a later date.
Experimental Section
General: Solvents were dried by standard literature methods before
being distilled and stored under nitrogen over 4-Å molecular si-
eves.[51] 1H and 13C NMR spectra were recorded with either a
Bruker AVANCE 300 MHz or a JEOL Lambda 500 MHz spec-
Figure 5. Fluorescence spectra recorded at 25 °C for BD-PHQ
(c ≈ 4 µ) in distilled water containing Triton-X (5% v/v) and
Na2HPO4 (0.18 ), before (dark line) and after (grey line) the ad-
dition of Na2CO3.H2O2. Excitation wavelength λ = 495 nm. Insert
shows a cuvette illuminated with a standard UV-lamp, and the
changes in fluorescence over time during oxidation by peroxide.
1
trometers. Chemical shifts for H and 13C NMR spectra are refer-
enced relative to the residual protiated solvent. The 11B NMR
chemical shift is referenced relative to BF3·Et2O (δ = 0 ppm), and
the 19F NMR chemical shift is given relative to CFCl3 (δ = 0 ppm).
The 19F NMR spectrum for BD-Q was simulated using the pro-
gram NUMARIT. To simplify the calculation, the fluorine coup-
lings to 10B (I = 3) were ignored because of its low relative abun-
dance. Routine mass spectra were obtained using in-house facilities
and elemental analysis was performed at Medac Ltd. Commercial
starting materials, 4-bromobenzaldehyde, 2,5-dihydroxybenzal-
dehye, 3-ethyl-2,4-dimethyl-1H-pyrrole and 2-bromophenyl-1,4-
diol, were used as received. Compound 1 was made by the literature
procedure.[52]
To assess the reversibility of the process, the BD-PQ
(4 µ) solution was treated with sodium ascorbate (1.1 ).
The tenet here is that ascorbate would gradually reduce the
quinone unit and thus switch on fluorescence. Indeed, we
observed a recovery of the fluorescence signal fully consis-
tent with the generation of BD-PHQ (see Supporting Infor-
mation). More encouragingly, control experiments carried
out on BD-P under similar conditions to the above (Sup-
Absorption spectra were recorded with a Hitachi U3310 spectro-
photometer while fluorescence studies were made with a Hitachi
porting Information) showed only modest fluorescence al- F-4500 fluorescence spectrophotometer. Fluorescence spectra were
2710 Eur. J. Org. Chem. 2008, 2705–2713
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Redox-Controlled Fluorescence Modulation
corrected for spectral imperfections using a standard lamp. Mea-
surements were made using optically dilute solutions after deoxy-
genation by purging with dried N2. Fluorescence quantum yields
were measured with respect to BD-P (ΦF = 0.67, MeCN).[53] Cor-
rected excitation spectra were also recorded under optically dilute
conditions. Fluorescence lifetimes were measured by time-corre-
lated, single-photon counting following excitation with an ultra-
short laser diode emitting at 525 nm using a PTI Easylife spectrom-
eter. After deconvolution of the instrumental response function,
the temporal resolution of this set-up was ca. 50 ps.
δ = 158.82, 153.89, 137.82, 136.73, 129.24, 128.84, 128.17, 128.06,
127.83, 122.95, 120.07, 113.34, 71.99, 71.26 ppm. IR (neat): ν =
˜
3494, 3389 (O–H), 2875 (C–H) cm–1.
Preparation of 2: TFA (8 drops) was added dropwise to a stirred
solution of 3-ethyl-2,4-dimethyl-1H-pyrrole (2.16 mL, 16 mmol,
1 equiv.) and 2,5-dibenzyloxybenzaldehyde (2.55 g, 8 mmol,
0.5 equiv.) in DCM (600 mL). The reaction was stirred at room
temperature until TLC showed complete consumption of the alde-
hyde. DDQ (1.82 g, 8 mmol, 0.5 equiv.) was added in a single por-
tion, and the reaction was stirred at room temperature overnight.
N,N-Diisopropylethylamine (15.88 mL, 91 mmol, 5.7 equiv.) and
BF3·Et2O (16.22 mL, 128 mmol, 8 equiv.) were added, and the re-
action was stirred at room temperature for 6 h. The reaction mix-
ture was washed with water (3ϫ100 mL) and brine (3ϫ100 mL).
The separated organic fractions were dried (MgSO4), filtered and
the solvent removed to yield a black/dark-violet residue with a
green tint. The residue was chromatographed on silica gel using
toluene eluant to afford a red solid (2.38 g, 50% yield); m.p. 53–
Cyclic voltammetry experiments were performed using a fully auto-
mated HCH Instruments Electrochemical Analyzer and a three-
electrode set-up consisting of a platinum working electrode, a plati-
num wire counter electrode and a silver wire reference electrode.
Ferrocene was used as an internal standard. All studies were per-
formed in deoxygenated DCM or DMSO containing tetra-N-butyl-
ammonium tetrafluoroborate (TBATFB) (0.2 ) as background
electrolyte. The solute concentrations were typically 0.5 m. Redox
potentials were reproducible to within Ϯ15 mV. Spectroelectro-
chemical fluorescence experiments were performed using a Specac
Ominicell, which was aligned 45° to the excitation source and illu-
minated at 495 nm. Scattered and incident light was removed using
a filter placed before the detector. Fluorescence spectra were im-
ported into the commercial package Origin, baseline corrected and
smoothed. Control experiments, to determine any possible quench-
ing effects of background electrolyte, were carried out by measuring
φFLU and λEM for equimolar solutions of BD-PQ in DCM in the
presence and absence of 0.2  TBATFB; no appreciable changes
were observed.
1
55 °C. H NMR (CDCl3, 300 MHz): δ = 7.35 (m, 10 H), 7.08 (dd,
J = 8.9, JЈ = 2.9 Hz, 1 H), 7.02 (d, J = 8.9 Hz, 1 H), 6.88 (d, J =
2.9 Hz, 1 H), 5.11 (s, 4 H), 2.63 (s, 6 H), 2.38 (q, J = 7.5 Hz, 4 H),
1.39 (s, 6 H), 1.11 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 152.31, 151.85, 148.81, 136.34, 135.79, 135.49,
135.34, 130.89, 129.43, 126.92, 126.74, 126.28, 126.04, 125.78,
125.39, 124.97, 115.86, 115.39, 113.80, 69.66, 69.46, 15.49, 12.83,
10.81, 9.49 ppm. IR (neat): ν = 2962, 2928, 2869 (C–H), 1539,
˜
1475 (C=C, C=N), 1187 (B–F) cm–1. MS (EI): m/z = 592 [M]+.
C37H39BF2N2O2 (592): calcd. C 75.00, H 6.63, N 4.73; found C
74.88, H 6.72, N 4.59.
Preparation of 4: Benzyl bromide (1.51 mL, 12 mmol, 2.4 equiv.) Preparation of 3: TFA (8 drops) was added dropwise to a stirred
was added to a stirred solution of 2-bromo-1,4-dihydroxybenzene
(1 g, 5.29 mmol, 1 equiv.) and K2CO3 (1.02 g, 7.41 mmol,
1.4 equiv.) in acetone (25 mL). The resulting mixture was heated to
reflux until TLC showed complete consumption of the aldehyde.
The reaction mixture was cooled, and the potassium carbonate was
separated via filtration. The reaction solvent was removed under
reduced pressure to yield a grey solid, which was taken up into
DCM (100 mL) and washed with water (100 mL). The organic
layer was separated, dried (MgSO4) and removed to yield the crude
product. This was purified on silica gel using petroleum ether/ethyl
solution of 3-ethyl-2,4-dimethyl-1H-pyrrole (2.16 mL, 16 mmol,
1 equiv.) and 4-bromobenzaldehyde (1.48 g, 8 mmol, 0.5 equiv.) in
DCM (600 mL). The reaction was stirred at room temperature until
TLC showed complete consumption of the aldehyde. DDQ (1.82 g,
8 mmol, 0.5 equiv.) was added in a single portion, and the reaction
was stirred at room temperature overnight. N,N-Diisopropylethyla-
mine (15.88 mL, 91 mmol, 5.7 equiv.) and BF3·Et2O (16.22 mL,
128 mmol, 8 equiv.) were added, and the reaction was stirred at
room temperature for 6 h. The reaction mixture was washed with
water (3ϫ100 mL) and brine (3ϫ100 mL). The separated organic
fractions were dried (MgSO4), filtered and the solvent removed to
acetate (4:1) to afford the product as a white solid (1.76 g, 91%);
1
m.p. 47–49 °C. H NMR (CDCl3, 300 MHz): δ = 7.40 (m, 10 H), yield a black/dark-violet residue with a green tint. The residue was
7.25 (dd, J = 2.4, JЈ = 0.6 Hz), 6.86 (m, 2 H), 5.09 (s, 2 H), 5.00
(s, 2 H) ppm.
chromatographed on silica gel using toluene eluant to afford a dark
red/purple solid (1.73 g, 47% yield); m.p. 240–242 °C. 1H NMR
(CDCl3, 300 MHz): δ = 7.64 (d, J = 8.3 Hz, 2 H), 7.18 (d, J =
8.3 Hz, 2 H), 2.532 (s, 6 H), 2.31 (q, J = 7.5 Hz, 4 H), 1.32 (s, 6
H), 0.98 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ
= 154.65, 138.93, 138.41, 138.15, 135.35, 133.46, 132.63, 131.07,
123.41, 17.39, 14.69, 12.76, 12.16 ppm. MS (EI): m/z = 458 [M]+.
C23H26BBrF2N2 (458): calcd. C 60.16, H 5.71, N 6.10; found C
60.07, H 5.65, N 6.12.
tBuLi (1.7 , 4.01 mL, 6.82 mmol, 1.4 equiv.) was added dropwise
to a stirred solution of the above material (1.8 g, 4.87 mmol,
1 equiv.) in THF (50 mL) at –78 °C, immediately followed by the
dropwise addition of triethyl borate (2.48 mL, 14.6 mmol, 3 equiv.)
at –78 °C. This temperature was maintained for 10 min, after which
the solution was warmed to room temperature and stirred for 2 h.
The reaction was cooled to 0 °C and quenched with a saturated
solution of ammonium chloride (30 mL), followed by removal of
the solvent under reduced pressure. The residue was extracted with
ethyl acetate (3ϫ100 mL), which was washed with water (100 mL)
and brine (100 mL). The organic layer was separated, dried
(MgSO4), and the solvent removed under reduced pressure to yield
the crude product. This was purified on silica gel using petroleum
ether/ethyl acetate (3:2) as eluant to afford the product as a white
solid (1.3 g, 83% yield); m.p. 113–115 °C. 1H NMR (CDCl3,
300 MHz): δ = 7.55 (d, J = 3.1 Hz, 1 H), 7.39 (m, 10 H), 7.05 (dd,
J = 8.9, JЈ = 3.1 Hz, 1 H), 6.92 (d, J = 8.9 Hz, 1 H), 6.49 (br. s, 2
Preparation of 5: The compounds 3 (1.62 g, 3.52 mmol, 1 equiv.)
and 4 (1.29 g, 3.87 mmol, 1.1 equiv.) were dissolved in THF
(50 mL), and the resulting solution was purged with nitrogen for
1 h. To this solution was added a nitrogen-purged aqueous solution
of 2  Na2CO3 (5.5 mL, 11 mmol, 3 equiv.), followed by Pd-
(PPh3)4 (0.123 g, 3 mol-%). The reaction mixture was refluxed over-
night. The THF was removed under reduced pressure and the resi-
due was taken up into DCM (100 mL), which was washed with
brine (2ϫ50 mL), separated and dried (MgSO4). After filtration,
the solvent was removed under reduced pressure, to yield a dark
H), 5.10 (s, 2 H), 5.07 (s, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): red residue. The residue was chromatographed on silica gel using
Eur. J. Org. Chem. 2008, 2705–2713
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2711

A. C. Benniston et al.
FULL PAPER
DCM/petroleum ether (1:1) as eluant to afford a light red solid
(2.11 g, 90% yield); m.p. 78–80 °C. H NMR (CDCl3, 300 MHz):
186.19, 185.57, 155.74, 144.66, 137.67, 137.15, 136.62, 136.30,
133.97, 130.64, 129.93, 17.38, 14.68, 13.20, 12.85 ppm. 11B NMR
(CDCl3, 160 MHz): δ = –0.343 (t, JB-F = 33.0 Hz) ppm. 19F NMR
(CDCl3, 470 MHz): δ = –144.97 (dq, JF-F = 102, JB-F = 32.2 Hz),
1
δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.38 (m, 12 H), 7.12 (d, J = 2.9 Hz,
1 H), 7.04 (d, J = 8.9 Hz, 1 H), 6.97 (dd, J = 8.9, JЈ = 2.9 Hz),
5.11 (s, 2 H), 5.01 (s, 2 H), 2.57 (s, 6 H), 2.33 (q, J = 7.5 Hz, 4 H),
1.36 (s, 6 H), 1.02 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 154.12, 150.76, 140.75, 139.59, 138.79, 137.73,
134.97, 133.14, 132.61, 131.38, 130.51, 128.89, 128.66, 128.40,
128.26, 128.01, 127.83, 127.41, 118.58, 115.96, 115.24, 72.11, 72.44,
–145.75 (dq, JF-F = 102, JB-F = 30.7 Hz) ppm. IR (neat): ν = 2964,
˜
2929, 2872 (C–H), 1656 (C=O), 1544, 1474 (C=C, C=N), 1187 (B–
F) cm–1. MS (EI): m/z = 410 [M]+. C23H25BF2N2O2 (410): calcd.
C 67.33, H 6.14, N 6.82; found C 67.16, H 6.17, N 6.69.
Analytical Data
17.44, 14.75, 12.75, 12.02 ppm. IR (neat): ν = 2962, 2869 (C–H),
˜
BD-HQ: M.p. Ͼ290 °C. 1H NMR (MeOD, 300 MHz): δ = 6.78 (m,
2 H), 6.52 (dd, J = 2.1, JЈ = 1.2 Hz, 1 H), 2.47 (s, 6 H), 2.36 (q, J
= 7.5 Hz, 4 H), 1.54 (s, 6 H), 1.01 (t, J = 7.5 Hz, 6 H) ppm. 13C
NMR (MeOD, 75 MHz): δ = 154.68, 153.05, 148.57, 140.21,
139.62, 134.13, 132.70, 124.80, 119.06, 118.75, 117.50, 18.17, 15.22,
1538, 1475 (C=C, C=N), 1188 (B–F) cm–1. MS (EI): m/z = 668
[M]+. C43H43BF2N2O2 (668): calcd. C 77.24, H 6.48, N 4.19; found
C 76.71, H 6.48, N 4.06.
Preparation of BD-PQ: A stirred solution of 5 (1.8 g, 2.69 mmol,
1 equiv.) and Pd/C 10% (0.7 g) in MeOH (50 mL) was subjected to
hydrogenation at 4 atm pressure until TLC showed complete con-
sumption of both the starting material and the mono-deprotected
intermediate. The reaction mixture was filtered through a pad of
Celite to remove the catalyst, and the reaction solvent removed to
yield the dihydroxy product, which was crudely purified by washing
with petroleum ether. To a stirred solution of the crude product in
THF (50 mL) was added DDQ (1.34 g, 5.91 mmol, 2.2 equiv.). On
addition of DDQ the reaction mixture changed colour from red
to dark purple. When TLC showed complete consumption of the
dihydroxy crude product, the reaction solvent was removed and the
remaining residue was taken into DCM (50 mL), washed with
water, and the combined organic fractions were dried (MgSO4).
The solvent was removed under reduced pressure, yielding a purple
crude product, which was purified on a silica gel using chloroform
as eluant, followed by washing with petroleum ether, to afford the
purple product (1.09 g, 83% yield); m.p. Ͼ290 °C. 1H NMR
(CDCl3, 300 MHz): δ = 7.65 (d, J = 8.3 Hz, 2 H), 7.39 (d, J =
8.3 Hz, 2 H), 6.98 (d, J = 2.2 Hz, 1 H), 6.91 (d, J = 10 Hz, 1 H),
6.86 (dd, J = 10, JЈ = 2.2 Hz, 1 H), 2.53 (s, 6 H), 2.29 (q, J =
7.5 Hz, 4 H), 1.303 (s, 6 H), 0.98 (t, J = 7.5 Hz, 6 H) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 187.46, 186.54, 154.61, 145.49,
139.31, 138.46, 138.33, 137.47, 136.62, 133.71, 133.42, 133.33,
131.01, 130.14, 129.21, 17.39, 14.70, 12.77, 12.09 ppm. 11B NMR
(CDCl3, 160 MHz): δ = –0.153 (t, JB-F = 31.4 Hz) ppm. 19F NMR
(CDCl3, 470 MHz): δ = –145.550 (q, JB-F = 33.1 Hz) ppm. IR
12.89, 11.67 ppm. IR (neat): ν = 3365 (O–H), 2964, 2931, 2872 (C–
˜
H), 1545, 1474 (C=C, C=N), 1195 (B–F) cm–1. MS (EI): m/z = 412
[M]+.
BD-M: Prepared by a similar manner to compound 2. Yield 40%;
1
m.p. 195–196 °C. H NMR (CDCl3, 300 MHz): δ = 6.97 (dd, J =
8.9, JЈ = 2.9 Hz, 1 H), 6.91 (d, J = 8.9 Hz, 1 H), 6.73 (d, J = 2.9 Hz,
1 H), 3.76 (s, 3 H), 3.72 (s, 3 H), 2.53 (s, 6 H), 2.31 (q, J = 7.5 Hz,
4 H), 1.39 (s, 6 H), 0.99 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 155.15, 153.72, 151.38, 138.22, 137.38,
132.77, 131.29, 126.04, 116.06, 115.99, 113.23, 56.57, 56.37, 17.42,
14.78, 12.74, 11.28 ppm. 19F NMR (CDCl3, 470 MHz): δ =
–145.356 (dq, JF-F = 109, JB-F = 33.8 Hz), –146.085 (dq, JF-F
=
109, JB-F = 32.3 Hz) ppm. MS (EI): m/z = 440 [M]+.
BD-PM: Prepared by a similar manner to compound 5. Yield 90%;
m.p. 140–142 °C. 1H NMR (CDCl3, 300 MHz): δ = 7.67 (d, J =
8.3 Hz, 2 H), 7.30 (d, J = 8.3 Hz, 2 H), 6.96 (m, 2 H), 6.88 (dd, J
= 8.9, JЈ = 2.9 Hz, 1 H), 3.84 (s, 3 H), 3.76 (s, 3 H), 2.54 (s, 6 H),
2.31 (q, J = 7.5 Hz, 4 H), 1.37 (s, 6 H), 0.99 (t, J = 7.5 Hz, 6 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 154.70, 154.05, 151.61,
140.78, 139.54, 138.80, 134.84, 133.11, 131.82, 131.36, 130.30,
128.36, 117.27, 114.55, 114.07, 57.22, 56.26, 17.43, 14.76, 12.75,
12.04 ppm. 11B NMR (CDCl3, 160 MHz): δ = –0.106 (t, JB-F
=
31.9 Hz) ppm. 19F NMR (CDCl3, 470 MHz): δ = –145.587 (q,
JB–F = 31.7 Hz) ppm. MS (EI): m/z = 516 [M]+.
Supporting Information (see also the footnote on the first page of
this article): Additional cyclic voltammetry results, X-ray crystallo-
graphic data, NMR spectra and absorption/fluorescence spectra.
(neat): ν = 2964 (C–H), 1656 (C=O), 1538, 1473 (C=C, C=N), 1183
˜
(B–F) cm–1. MS (EI): m/z = 486 [M]+. C29H29BF2N2O2 (486):
calcd. C 71.62, H 6.01, N 5.76; found C 71.03, H 5.79, N 5.31.
Analytical Data
Acknowledgments
BD-PHQ: M.p. Ͼ290 °C. 1H NMR ([D6]DMSO, 300 MHz): δ =
8.96 (br. s, 1 H), 8.83 (br. s, 1 H), 7.74 (d, J = 7.9 Hz, 2 H), 7.34
(d, J = 7.9 Hz, 2 H), 6.79 (m, 2 H), 6.63 (dd, J = 8.5, JЈ = 2.6 Hz,
1 H), 2.44 (s, 6 H), 2.30 (q, J = 7.5 Hz, 4 H), 1.34 (s, 6 H), 0.95 (t,
J = 7.5 Hz, 6 H) ppm. 13C NMR ([D6]DMSO, 75 MHz): δ =
153.44, 150.65, 147.31, 141.13, 139.95, 138.55, 133.14, 132.96,
This work was supported by Newcastle University and the Engi-
neering and Physical Sciences Research Council (EPSRC)(EP/
D032946/1). We thank the EPSRC Mass Spectromery Service at
Swansea for obtaining mass spectra. Prof. William McFarlane is
thanked for collecting the 11B and 19F NMR spectra, while Dr
130.61, 129.84, 127.99, 127.58, 117.64, 116.89, 116.00, 16.77, 14.67, Bruce Tattershall is thanked for help in simulation of the 19F NMR
12.52, 11.75 ppm. IR (neat): ν = 3353, 3522 (O–H), 2964, 2931 (C–
spectroscopic data.
˜
H), 1538, 1474 (C=C, C=N), 1186 (B–F) cm–1. MS (EI): m/z = 488
[M]+.
[1] W. Tan, R. Kopelman, Handbook of Nanostructured Materials
and Nanotechnology (Ed.: H. S. Nalwa), Academic Press, 2000,
4, pp. 621–667.
[2] D. W. M. Arrigan, Analyst 2004, 129, 1157–1165.
[3] P. Ugo, L. M. Moretto, F. Vezzà, ChemPhysChem 2002, 3, 917–
925.
[4] A. Nazarov, D. Thierry, Electrochim. Acta 2004, 49, 2717–2724.
[5] G. Liu, Y. Lin, Y. Tu, Z. Ren, Analyst 2005, 130, 1098–1101.
[6] B. Bourlon, J. Wong, C. Miko, L. Forro, M. Bockrath, Nature
Nanotechnol. 2007, 2, 104–107.
Preparation of BD-Q: A similar procedure was used to that de-
scribed above. 2 (1 g, 1.69 mmol, 1 equiv.), Pd/C 10% (0.3 g),
MeOH (50 mL), DDQ (0.84 g, 3.72 mmol, 2.2 equiv.). Purification:
silica gel DCM eluant, petroleum ether wash. Yield 0.57 g, 82%;
m.p. 169–171 °C. 1H NMR (CDCl3, 300 MHz): δ = 6.94 (d, J =
10.1 Hz, 1 H), 6.89 (dd, J = 10.9, JЈ = 2.2 Hz, 1 H), 6.82 (d, J =
2.2 Hz, 1 H), 2.48 (s, 6 H), 2.30 (q, J = 7.5 Hz, 4 H), 1.83 (s, 6 H),
0.97 (t, J = 7.5 Hz, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ =
2712
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2705–2713

Redox-Controlled Fluorescence Modulation
[7]
[8]
[9]
[32] J. Karolin, L. Strandberg, L. B. A. Johansson, J. Am. Chem.
Soc. 1994, 116, 7801–7806.
[33] Z. Shen, H. Röhr, K. Rurack, H. Uno, M. Spieles, B. Shulz,
G. Reck, N. Ono, Chem. Eur. J. 2004, 10, 4853–4871.
[34] H. Yao, R. Okada, N. Matag, J. Phys. Chem. 1989, 93, 7388–
7394.
[35] a) L. R. Khundkar, J. W. Perry, J. E. Hanson, P. B. Dervan, J.
Am. Chem. Soc. 1994, 116, 9700–9709; b) D. Gust, T. A.
Moore, Science 1989, 244, 35–41.
[36] The Chemistry of the Quinonoid Compounds, vol. 2 (Eds.: S.
Patai, Z. Rappoport) Wiley, 1988. pp. 719.
L. Basabe-Desmonts, D. N. Reinhoudt, M. Crego-Calama,
Chem. Soc. Rev. 2007, 36, 993–1017.
A. C. Benniston, A. Harriman, I. Llarena, C. A. Sams, Chem.
Mater. 2007, 19, 1931–1938.
S. M. Nie, R. N. Zare, Ann. Rev. Biophys. Biomol. Struct. 1997,
26, 567–596.
[10]
[11]
C. Piguet, Chimia 1996, 50, 144–153.
A. C. Benniston, A. Harriman, S. L. Howell, C. A. Sams, Y.-
G. Zhi, Chem. Eur. J. 2007, 13, 4665–4674.
P. J. Jiang, Z. J. Guo, Coord. Chem. Rev. 2004, 248, 205–229.
L. Fabbrizzi, A. Poggi, Chem. Soc. Rev. 1995, 24, 197–202.
K. Rurack, U. Resch-Genger, Chem. Soc. Rev. 2002, 31, 116–
127.
X. M. Gao, Y. L. Zhang, B. H. Wang, New J. Chem. 2005, 29,
579–586.
T. W. Bell, N. M. Hext, Chem. Rev. 2004, 33, 589–598.
E. G. Matveeva, G. Shan, I. M. Kennedy, S. J. Gee, D. W. Stou-
tamire, B. D. Hammock, Anal. Chim. Acta 2001, 444, 103–117.
G. Y. Ma, Q. Cheng, Langmuir 2006, 22, 6743–6745.
[12]
[13]
[14]
[37] T. Káli, E. Hideg, I. Vass, K. Hideg, Free Radical Biol. Med.
1998, 24, 649–652.
[38] J. Gallay, M. Vincent, C. Nicot, M. Waks, Biochem. 1987, 26,
5738–5747.
[15]
[39] R. Ziessel, G. Ulrich, A. Harriman, New J. Chem. 2007, 31,
[16]
[17]
496–501.
[40] Y. Mei, P. A. Bentley, Bioorg. Med. Chem. Lett. 2006, 16, 3131–
3134.
[41] a) J.-P. Malval, I. Leray, B. Valeur, New J. Chem. 2005, 29,
1089–1094; b) M. Baruah, W. Qin, R. A. L. Vallée, D. Beljonne,
T. Rohand, W. Dehaen, N. Boens, Org. Lett. 2005, 7, 4377–
4380.
[18]
[19] S. Bencic-Nagale, T. Sternfeld, D. R. Walt, J. Am. Chem. Soc.
2006, 128, 5041–5048.
[20] a) B. Heyne, V. Maurel, J. C. Sciano, Org. Biomol. Chem. 2006,
4, 802–807; b) B. Heyne, C. Beddie, J. C. Sciano, Org. Biomol.
Chem. 2007, 5, 1454–1458.
[42] A. Coskun, M. Deniz Yilmaz, E. U. Akkaya, Org. Lett. 2007,
9, 607–609.
[21] A. Gomes, E. Fernandes, J. L. F. C. Lima, J. Biochem. Bioph.
Methods 2005, 65, 45–80.
[43] X. Peng, J. Du, J. Fan, J. Wang, Y. Wu, J. Zhao, S. Sun, T. Xu,
J. Am. Chem. Soc. 2007, 129, 1500–1501.
[44] E. J. Park, K. R. Reid, W. Tang, R. T. Kennedy, R. Kopelman,
J. Mater. Chem. 2005, 15, 2913–2919.
[45] a) X. Zhang, H.-S. Zhang, Spectrochim. Acta 2005, 61, 1045–
1049; b) Y. Gabe, T. Ueno, Y. Urano, H. Kojima, T. Nagano,
Anal. Bioanal. Chem. 2006, 386, 621–626.
[46] T. Matsumoto, Y. Urano, T. Shoda, H. Kojima, T. Nagano,
Org. Lett. 2007, 9, 3375–3377.
[47] E. H. W. Pap, G. P. C. Drummen, V. J. Winter, T. W. A. Kooij,
P. Rijken, K. W. A. Wirtz, J. A. F. Op den Kamp, W. J. Hage,
J. A. Post, FEBS Lett. 1999, 453, 278–282.
[48] A. C. Nicolescu, Q. Li, L. Brown, G. R. J. Thatcher, Nitric Ox-
ide 2006, 15, 163–176.
[49] H. D. Guthrie, G. R. Welch, J. Anim. Sci. 2007, 85, 1402–1411.
[50] N. Itoh, J. Cao, Z.-H. Chen, Y. Yoshida, E. Niki, Bioorg. Med.
Chem. Lett. 2007, 17, 2059–2063.
[22] a) V. Goulle, A. Harriman, J.-M. Lehn, J. Chem. Soc., Chem.
Commun. 1993, 1034–1036; b) A. C. Benniston, G. Chapman,
A. Harriman, S. A. Rostron, Inorg. Chem. 2005, 44, 4029–4036.
[23] a) T. Ueno, Y. Uano, H. Kojima, T. Nagano, J. Am. Chem.
Soc. 2006, 128, 10640–10641; b) A. Harriman, L. J. Mallon, G.
Ulrich, R. Ziessel, ChemPhysChem 2007, 8, 1207–1214.
[24] K. Kayanasundaram, Coord. Chem. Rev. 1982, 46, 159–244.
[25] G. Ulrich, R. Ziessel, A. Harriman, Angew. Chem. Int. Ed.
2008, 47, 1184–1201.
[26] B. Herradón, A. Chana, M. Alonso, F. Amat-Guerri, M. Liras,
M. A. Maestro, J. Mol. Struct. 2004, 697, 29–40.
[27] R. Ziessel, L. Bonardi, G. Ulrich, Dalton Trans. 2006, 2913–
2918.
[28] J. G. Pearson, E. Oldfield, F. S. Lee, A. Warshel, J. Am. Chem.
Soc. 1993, 115, 6851–6862.
[29] R. Ziessel, C. Goze, G. Ulrich, M. Céario, P. Retailleau, A.
Harriman, J. P. Rostron, Chem. Eur. J. 2005, 11, 7366–7378.
[30] a) M. Bauscher, W. Mäntele, J. Phys. Chem. 1992, 96, 11101–
11108; b) N. Gupta, H. Linschitz, J. Am. Chem. Soc. 1997, 119,
6384–6391.
[31] P. Toele, H. Zhang, C. Trieflinger, J. Daub, M. Glasbeek, Chem.
Phys. Lett. 2003, 368, 66–75.
[51] W. L. F. Armarego, C. L. L. Chai, Purification of Laboratory
Chemicals, 5th ed., Butterworth-Heineman, London, 2003.
[52] F. Mu, E. Hamel, D. J. Lee, D. E. Pryor, M. Cushman, J. Med.
Chem. 2003, 46, 1670–1682.
[53] A. Loudet, K. Burgess, Chem. Rev. 2007, 107, 4891–4932.
Received: February 18, 2008
Published Online: April 15, 2008
Eur. J. Org. Chem. 2008, 2705–2713
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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