Fluorescent boron bis(phenolate) with association response to chloride and dissociation response to fluoride

Article abstract of DOI:10.1021/ic800204q

Addition of chloride ions to boron bis(phenolate) 5 in dichloromethane solution produces a selective fluorescence decrease. The fluorescence change is believed to be caused by associative hydrogen bonding between the chloride ion and two boronic acid groups. While addition of fluoride ions to bis(phenolate) 5 generates a purple colorimetric response, the colorimetric response is caused by fluoride induced B-O bond cleavage and air oxidation of the phenolate anion formed by this dissociation.

Full text of DOI:10.1021/ic800204q

Inorg. Chem. 2008, 47, 6236-6244
Fluorescent Boron Bis(phenolate) with Association Response to
Chloride and Dissociation Response to Fluoride
Ewan Galbraith,† Thomas M. Fyles,‡ Frank Marken,† Matthew G. Davidson,*,† and Tony D. James*,†
Department of Chemistry, UniVersity of Bath, Bath BA2 7AY, U.K., and Department of Chemistry,
UniVersity of Victoria, Victoria BA2 7AY, Canada
Received February 8, 2008
Addition of chloride ions to boron bis(phenolate) 5 in dichloromethane solution produces a selective fluorescence
decrease. The fluorescence change is believed to be caused by associative hydrogen bonding between the chloride
ion and two boronic acid groups. While addition of fluoride ions to bis(phenolate) 5 generates a purple colorimetric
response, the colorimetric response is caused by fluoride induced B-O bond cleavage and air oxidation of the
phenolate anion formed by this dissociation.
Introduction
acid coordination via orbital overlap has received a lot of
attention, and receptors containing boron2 (our particular
focus), silicon,3tin,4,5 and mercury6 have all emerged.
The anion recognition or binding event is most often
transduced into an optical or electrochemical response. A
chromogenic response is attractive from a qualitative point
of view, in that a naked-eye visualization of the presence of
a target anion avoids spectroscopy or any other analysis.
Phosphorescence has seen limited use, with fluorescence
being the most widespread signaling method.
Fluorescence is an excellent method of communicating a
recognition event. The ability to relay information remotely,
for example, from within living tissue, widens the potential
of a fluorescent sensor for practical use. Response in the
submillisecond time frame is achievable, and active fluoro-
phores can be located with subnanometer accuracy, allowing
real-time, real-space monitoring.7
An increasing amount of research effort has been devoted
to the design and development of novel chemosensors for
anions.1 Anion sensor design poses a greater challenge to
chemists than the more established field of cation sensors.
Anions are larger than their respective isoelectronic cations
and hence possess a lower charge to radius ratio, meaning
any electrostatic binding interactions are less effective.
Anions possess a high solvation energy and protonation of
anions at low pH can also be an issue, so receptors have to
operate within a useful pH range. Another challenge to
overcome is that anionic species are not restricted to simple
geometry, for example, trigonal planar carboxylate and
tetrahedral phosphate ions. Hydroxylic solvents are able to
form strong hydrogen bonds with anions, and so a sensor
may also have to successfully compete with any such
interactions.
Anion recognition can be achieved via a number of
different noncovalent binding modes. Electrostatic interac-
tions, which have the inherent drawback of the presence of
a competing counterion, can be used alone or cooperatively
with hydrogen bonding interactions. The directionality of
hydrogen bonding can allow receptors of a complementary
shape to the target anion to be designed, allowing differentia-
tion between various guest species. Electron-deficient Lewis
Sensitivity is another attractive aspect of using fluorescent
systems, with single guest molecule recognition being
observable with the use of modern instrumentation.8 The
(2) Yamaguchi, S.; Akiyama, S.; Tamao, K. J. Am. Chem. Soc. 2001,
123, 11372–11375.
(3) Tamao, K.; Hayashi, T.; Ito, Y. J. Organomet. Chem. 1996, 506, 85–
91.
(4) Newcomb, M.; Blanda, M. T.; Azuma, Y.; Delord, T. J. J. Chem.
Soc., Chem. Commun. 1984, 1159–1160.
(5) Newcomb, M.; Madonik, A. M.; Blanda, M. T.; Judice, J. K.
Organometallics 1987, 6, 145–150.
* To whom correspondence should be addressed. E-mail: m.g.davidson@
bath.ac.uk (M.G.D.), t.d.james@bath.ac.uk (T.D.J.).
(6) Yang, X.; Knobler, C. B.; Hawthorne, M. F. Angew. Chem., Int. Edit.
Engl. 1991, 30, 1507–1508.
†
University of Bath.
University of Victoria.
(7) Bissell, R. A.; de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L. M.;
Maguire, G. E. M.; Sandanayake, K. R. A. S. Chem. Soc. ReV. 1992,
21, 187–195.
‡
(1) Sessler, J. L.; Gale, P. A.; Cho, W. S. Anion Receptor Chemistry;
Royal Society of Chemistry: London, 2006.
(8) Sauer, M. Angew. Chem., Int. Edit. 2003, 42, 1790–1793.
6236 Inorganic Chemistry, Vol. 47, No. 14, 2008
10.1021/ic800204q CCC: $40.75  2008 American Chemical Society
Published on Web 05/28/2008

Fluorescent Boron Bis(phenolate)
impact on the system undergoing analysis is minimal as
concentrations are typically in the order of 10-6 M. This
efficiency combined with the versatility of fluorescent sensors
has led to several commercial uses, including point-of-care
diagnostic monitoring and blood gas analysis in hospitals.9,10
Fluoride is the smallest anion, with a high charge density
and a hard Lewis basic nature that result in unusual chemical
properties. The determination of the presence of fluoride is
not merely an interesting academic challenge, with fluoride
having an important role in a diverse array of biological,
medical, and technological processes applications.
It has been well documented for some time that fluoride
plays an important role in dental health,11 and a great deal
of interest has focused on its potential in treatment of
osteoporosis.12,13 Fluoride is easily absorbed but is excreted
slowly from the body, which can result in chronic poisoning.
Overexposure to fluoride can lead to acute gastric and kidney
problems.14 In several Less Economically Developed Coun-
tries excess fluoride levels in drinking water has been linked
to fluorosis, a debilitating bone disease. UNICEF estimates
that “fluorosis is endemic in at least 25 countries across the
globe. The total number of people affected is not known,
but a conservative estimate would number in the tens of
millions.” Hazardous levels may be as low as 1 ppm,
requiring sensitive detection.
Fluoride detection is important in a number of military
applications. The refinement of uranium in nuclear weapons
manufacture requires fluoride monitoring.15 GB, more com-
monly known as Sarin (isopropyl methylphosphonofluori-
date) was the nerve agent employed by the Aum Shinrikyu
cult in the terrorist attacks that occurred in Tokyo in 1995.
Fluoride is a product of hydrolysis of Sarin (and Soman, a
related G-type agent), and the ability to monitor fluoride
exposure of victims and the surrounding environment after
an incident would be of great value.16,17
As a result of this diversity, the development of sensitive
and selective methods of fluoride detection under environ-
mental conditions has been of particular focus in the field
of anion recognition. It is also relevant to note the medical
emphasis of the need for a fluoride sensor, reiterating
fluorescence as a desirable signaling method because of the
potential for intracellular use.
chloremia) and low (hypochloremia) levels of chloride can
be dangerous and are often indicative of kidney problems.
Chloride in the form of salt water is a major contaminant of
groundwater, percolating through landfill liners and causing
corrosion of steel.18 In soil typical levels are 100 ppm, and
chloride levels in the oceans are about 0.5 M.
Fluoride concentrations can be determined by 19F analysis
or the specific ion electrode method.19,20 These systems,
although well established, possess some disadvantages. The
latter is a membrane electrode containing single crystals of LaF3,
a method which is accurate but fragile and time-consuming.21
19F NMR spectroscopy can only be used reliably on the
micromolar scale typical to most NMR spectroscopic studies.
Neither system can be used to study biological processes in
vivo, alternative systems allowing intracellular monitoring
would be infinitely preferable to researchers.
Fluoride sensors have attracted a lot of research attention
over recent years, many exploiting the interaction of Lewis-
acidic boron with fluoride or hydrogen bonding interactions.
Sessler et al. have reported a number of fluoride sensors
based on pyrrole hydrogen bond donors.22–24 as well as off
the shelf fluoride sensors consisting of amides, amines, and
phenols.25 Smith et al. have also used phenol based receptors
as hydrogen bond donors.26
Boron forms trivalent, trigonal planar complexes such as
B(OMe)3 and BF3. The characteristic empty 2p orbital at
the boron center controls the Lewis acidic chemistry of
boron.27–28 Boron centered fluoride receptors were first
studied by Katz, who trapped fluoride ions between two
electron accepting boron atoms in 1,8 naphthalendiylbis-
(dimethylborane).29 The bridging was confirmed by the
presence of large 19F-1HMe coupling.
Our group were the first to use fluorescence to detect
fluoride binding events.31 Excellent selectivity in aqueous
solution at pH 5.5 was obtained using very simple boronic
acids. Kubo et al. has developed a novel sensor system in
which anions induce self-organization of phenyl boronic
acids and alizarin. In the presence of fluoride or acetate ions,
the three components (alizarin, boronic acid, and the anion)
self-assemble switching “on” the fluorescence.32–34
(18) Cosentino, P.; Grossman, B.; Shieh, C.; Doi, S.; Xi, H.; Erbland, P.
J. Geotech. GeoenViron. Eng. 1995, 121, 610–617.
(19) Konieczka, P.; Zygmunt, B.; Namiesnik, J. Bull. EnViron. Contam.
Tox. 2000, 64, 794–803.
Chloride (usually from sodium chloride) is essential for
human health, regulating blood pressure, maintaining me-
tabolism and the acid-base balance within the body. Typical
levels are at around 0.1 M in blood serum. High (hyper-
(20) Itai, K.; Tsunoda, H. Clin. Chim. Acta 2001, 308, 163–171.
(21) Frant, M. S.; Ross, J. W. Science 1966, 154, 1553.
(22) Black, C. B.; Andrioletti, B.; Try, A. C.; Ruiperez, C.; Sessler, J. L.
J. Am. Chem. Soc. 1999, 121, 10438–10439.
(9) He, H. R.; Mortellaro, M. A.; Leiner, M. J. P.; Young, S. T.; Fraatz,
R. J.; Tusa, J. K. Anal. Chem. 2003, 75, 549–555.
(10) Schlebusch, H.; Paffenholz, I.; Zerback, R.; Leinberger, R. Clin. Chim.
Acta 2001, 307, 107–112.
(23) Anzenbacher, P.; Try, A. C.; Miyaji, H.; Jursikova, K.; Lynch, V. M.;
Marquez, M.; Sessler, J. L. J. Am. Chem. Soc. 2000, 122, 10268–
10272.
(24) Mizuno, T.; Wei, W. H.; Eller, L. R.; Sessler, J. L. J. Am. Chem. Soc.
2002, 124, 1134–1135.
(11) Kirk, L. K. Biochemistry of the Halogens and Inorganic Halides;
Plenum Press: New York, 1991.
(25) Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154–157.
(26) Winstanley, K. J.; Sayer, A. M.; Smith, D. K. Org. Biomol. Chem.
2006, 4, 1760–1767.
(12) Kleerekoper, M. Endocrinol. Metabol. Clin. North Amer. 1998, 27,
441.
(13) Briancon, D. ReV. Rhum. 1997, 64, 78–81.
(14) Michigami, Y.; Kuroda, Y.; Ueda, K.; Yamamoto, Y. Anal. Chim.
Acta 1993, 274, 299–302.
(27) Fenwick, J. T. F.; Wilson, J. W. J. Chem. Soc., Dalton Trans. 1972,
1324–1326.
(28) Jacobson, S.; Pizer, R. J. Am. Chem. Soc. 1993, 115, 11216–11221.
(29) Worm, K.; Schmidtchen, F. P.; Schier, A.; Schafer, A.; Hesse, M.
Angew. Chem. Int. Ed. Engl. 1994, 33, 327–329.
(30) Katz, H. E. J. Org. Chem. 1985, 50, 5027–5032.
(31) Cooper, C. R.; Spencer, N.; James, T. D. Chem. Commun. 1998, 1365–
1366.
(15) Xu, S.; Chen, K. C.; Tian, H. J. Mater. Chem. 2005, 15, 2676–2680.
(16) Sohn, H.; Letant, S.; Sailor, M. J.; Trogler, W. C. J. Am. Chem. Soc.
2000, 122, 5399–5400.
(17) Zhang, S. W.; Swager, T. M. J. Am. Chem. Soc. 2003, 125, 3420–
3421.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6237

Galbraith et al.
Scheme 1. Structure of 1 (Rear Tertiary Butyl Groups Removed for Clarity) and Preparation of 4 and 5 from 2 and 3
Gabba¨ı et al. have used a diboron species to bind fluoride
and create a UV-based colorimetric sensor which is not
affected by the presence of water. The association with the
fluoride ion is higher than that observed with monofunctional
borane receptors.35 The same group have also utilized
mercury for its ability to induce phosphorescence of hydro-
carbon chromophores in a heteronuclear mercury-boron
bidentate Lewis-acid species.36 The naphthalene backbone
enforces the proximity of the two Lewis-acidic centers,
leading to a higher binding constant than with Mes3B,
confirming cooperativity between the two Lewis acid species.
There are far fewer selective chloride sensors in the
literature. Zhang has developed a reversible and accurate
system for chloride levels in diluted serum samples, but the
sensor suffers from interference from salicylate.37 The sensor
is bound to a polymer film, providing an example of the
potential of such systems for “real-world” applications. Duan
and Meng have reported a tris benzyoimidazolium as a
fluorescent chemosensor for chloride.38 Diamond et al. have
developed a tetrasubstituted calix[4]arene which displays
chloride selective excimer quenching.39 The chloride ions
are thought to bind to the urea protons in the cavity, forcing
the pyrene units apart.
pound 1 was prepared using organoboron derivatization of
a tetralithiated 4-t-butylcalix[4]arene,40 and a similar protocol
was used for preparation of compounds 4 and 5 (Scheme
1). n-Butyllithium was added dropwise to a solution of the
starting phenol in toluene. After heating overnight at 100
°C, the resulting mixture was cooled and dichlorophenylbo-
rane was added. Following subsequent washing with water,
4 and 5 were afforded in good yields.
Structural Characterization of Arylboronates 4 and
5. Crystals of 4 were obtained by slow evaporation of a
supersaturated hexane solution, and the structure was determined
by X-ray crystallography (Figure 1). The molecular structure
of arylboronate 4 is as expected. On the supramolecular level,
dimeric association occurs via intermolecular hydrogen bonding
interactions between two molecules of 4. A short O-H· · ·O
hydrogen bond [O(3)-H(3) · · ·O(1); H · · ·O distance, 2.03(3)
Å, O · · ·O distance, 2.864(2) Å, O-H· · ·O angle, 160(2) °] is
accompanied by a O-H· · ·π interaction in which the O(1)-H(1)
vector is directed at the face of the aryl ring [O(1)-H(1) · · ·X,
where X ) centroid of C(51)-C(56); H · · ·X distance, 2.53(2),
O· · ·X distance, 3.190(1) Å].
A single crystal of 5 was obtained via slow evaporation
from toluene, and the molecular structure elucidated by X-ray
diffraction. In 5 · H2O, the aryl rings adopt a “butterfly”
conformation (approximate C2V symmetry). Other features
of the molecular structure are as expected. The supramo-
Results and Discussion
Synthesis of Arylboronates 4 and 5. Our previous work
has shown that the bis(bora)calix[4]arene 1 acts as a sensor
for tetra-n-butylammonium fluoride (TBAF) in chloroform.41
To probe the factors affecting fluoride binding we decided
to prepare a range of structurally related boronates. Com-
(32) Kubo, Y.; Ishida, T.; Kobayashi, A.; James, T. D. J. Mater. Chem.
2005, 15, 2889–2895.
(33) Kubo, Y.; Ishida, T.; Minami, T.; James, T. D. Chem. Lett. 2006, 35,
996–997.
(34) Kubo, Y.; Kobayashi, A.; Ishida, T.; Misawa, Y.; James, T. D. Chem.
Commun. 2005, 2846–2848.
(35) Chiu, C. W.; Gabbai, F. P. J. Am. Chem. Soc. 2006, 128, 14248–
14249.
(36) Melaimi, M.; Gabbai, F. P. J. Am. Chem. Soc. 2005, 127, 9680–9681.
(37) Zhang, W.; Rozniecka, E.; Malinowska, E.; Parzuchowski, P.; Mey-
erhoff, M. E. Anal. Chem. 2002, 74, 4548–4557.
(38) Bai, Y.; Zhang, B. G.; Xu, J.; Duan, C. Y.; Dang, D. B.; Liu, D. J.;
Meng, Q. J. New J. Chem. 2005, 29, 777–779.
(39) Schazmann, B.; Alhashimy, N.; Diamond, D. J. Am. Chem. Soc. 2006,
128, 8607–8614.
Figure 1. Molecular structure of 4 showing O-H· · ·O and O-H· · ·π
interactions between the two independent molecules of the asymmetric
unit.
6238 Inorganic Chemistry, Vol. 47, No. 14, 2008

Fluorescent Boron Bis(phenolate)
Figure 2. Molecular structure of 5·H2O: (a) One arylboronate unit highlighting the 50:50 disorder of the B-OH and H2O groups (H atoms of the disordered
H2O not located in the X-ray structure, H atoms other than those involved in H-bonding omitted for clarity, thermal ellipsoids at the 50% probability level);
(b) the dimeric structure highlighting the H2O-filled cavity generated by the two orthogonal arylboronate units (all H atoms omitted for clarity and dashed
lines between O atoms identifying short (<3.2 Å) O · · ·O distances and probable O-H· · ·O hydrogen bond interactions).
lecular structure consists of two orthogonal molecules of 5
assembled around two water molecules. In the solid state,
disorder of the hydrogen atoms of the B-OH and H2O units
precludes detailed analysis of the hydrogen bonding interac-
tions involved (Figure 2).
Subsequently, crystals of 5 were also grown under
rigorously anhydrous conditions. In the absence of water, 5
adopts a “propeller” conformation of approximate C2 sym-
metry (Figure 3a) and associates into a two-dimensional
supramolecular array via a series of O-H · · · π interactions
(Figure 3b,c).41
changes from colorless to yellow (4) or purple (5) are
observed. In both cases, NMR spectroscopic analysis clearly
indicates TBAF-mediated cleavage of the boron-aryloxide
bond, an observation in agreement with a recent report by
Bresner et al.42 These observations led us to investigate the
addition of fluoride to the parent phenols 2 and 3, and they
also exhibited similar color changes to those observed with
4 and 5 (Figure 4). In the light of the similar behavior of
both phenols and arylboronates in the presense of fluoride,
a feasible mechanism for this colorimetric response involves
a common phenolate anion intermediate obtained via either
fluoride-mediated deboronation or deprotonation, followed
by ambient oxidation to a colored radical as shown in
Scheme 2. Precedent for these mechanisms exists. For
example, fluoride-mediated deprotonation of phenol-based
Colorimetric Response to Fluoride of Phenols (2 and
3) and Arylboronates (4 and 5). On addition of an excess
of TBAF to solutions of 4 or 5 in chloroform dramatic color
(40) Arimori, S.; Davidson, M. G.; Fyles, T. M.; Hibbert, T. G.; James,
T. D.; Kociok-Ko¨hn, G. I. Chem. Commun. 2004, 1640–1641.
(41) Broder, C. K.; Davidson, M. G.; Forsyth, V. T.; Howard, J. A. K.;
Lamb, S.; Mason, S. A. Cryst. Growth Des. 2002, 2, 163–169.
(42) Bresner, C.; Day, J. K.; Coombs, N. D.; Fallis, I. A.; Aldridge, S.;
Coles, S. J.; Hursthouse, M. B. Dalton Trans. 2006, 3660–3667.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6239

Galbraith et al.
Figure 3. (a) Molecular structure of 5. H atoms other than those of B-OH omitted for clarity, thermal ellipsoids at the 50% probability level; (b) the
supramolecular structure of 5; (c) details of intermolecular interactions in 5. All H atoms other than those of B-OH omitted for clarity. Dashed lines
between H atoms and centroid (X) identify short (2.46 Å) H · · ·π distances with a O-H-X angle of 127°. Lattice toluene (C7H8) omitted for clarity.
anion sensors has been observed43 (as has deprotonation of
mediated deboronations are known.42 The colorimetric
response of two viologen based anion hosts toward carboy-
N-H groups of other anion sensors44–53) and fluoride-
6240 Inorganic Chemistry, Vol. 47, No. 14, 2008

Fluorescent Boron Bis(phenolate)
TBAOH show that the peaks observed at -0.3 V and +0.1
V versus SCE are associated with this phenoxyl dianion.
Clearly the fluoride anions have removed the boronic acid
residues and liberated phenoxyl dianion (Scheme 2), which
in the presence of the electrode or dioxygen quickly
undergoes multielectron oxidation to the colored diradical.
The voltammetric peaks at -0.3 V and +0.1 V versus SCE
may be regarded as diagnostic for fluoride. However, when
tetra-n-butylammonium chloride (TABCl) is added to 5
(Supporting Information), no easy to oxidize fragments are
formed and no color change is observed. Upon addition of
chloride a new signal at 1.3 V versus SCE is detected, and
this signal can be assigned to chloride oxidation.
UV spectroscopy was used to investigate the interaction
of compound 3 in dichloromethane solution with various anions
including F-, Cl-, Br-, and H2PO4- as their tetra-n-butylam-
monium salts. The compound exhibited a dramatic response to
fluoride with a new peak appearing at 580 nm. Figure 6 shows
the extremely high selectivity against a range of common anions.
No visible color change is apparent with the addition of any
anion besides fluoride. Similar UV spectra were obtained for
the addition of F-, Cl-, Br-, and H2PO4- as their tetra-n-
butylammonium salts to compound 5.
The fluorescence spectrum of 5 in dichloromethane was
recorded. The excitation spectrum showed two peaks, one
at 251 nm and another one of lower energy at 289 nm.
Exciting at 289 nm, a fairly intense emission peak is
observed, with a maximum at 370 nm. As expected, after
one equivalent of TBAF is added the fluorescence/the peak
is almost completely quenched. Quenching of the fluores-
cence in this case is attributed to fluoride mediated debor-
onation (Scheme 2).
Fluorescence spectroscopy was then used to study the
effect of chloride ion concentration on the fluorescence
spectrum of 5 in CH2Cl2 (Figure 7).
The quenching is nonlinear, and fits a 2:1 model with a
log K ) 4.5. It is important to note that any model including
a 1:1 complex does not fit the data, that is, a 1:1 model or
a 1:1 and 2:1 mixed model (Figure 8).
We believe that addition of chloride causes a conforma-
tional change between the staggered “chicken-wire” structure
shown in Figure 3 and a hydrogen bonded cavity as in Figure
2, with the chloride acting in a similar role to the water
molecule (Figure 2) and forming hydrogen bonds with four
B-OH moieties from two molecules of 5. This conforma-
tional change affects the π systems of the two phenyl rings
and hence the fluorescence intensity of the emission.
A similar titration was repeated with tetra-n-butylammo-
nium (TBABr) bromide to probe the selectivity. At 10.0 mM
halide ion, the relative intensity for chloride is 0.21 and for
bromide 0.86.
The alcohol precursor 3 was also studied by fluorescence
spectroscopy (1.0 mM). The compound was excited at 257
nm producing an emission peak at 308nm, the intensity of
which changes negligibly with increasing chloride concentra-
tion.56 Addition of TBAF causes complete fluorescence
quenching attributed to fluoride mediated deprotonation
(Supporting Information). For the monoboronic acid system
Figure 4. Colorimetric response of 2 and 3 (1 mM) to the addition of
fluoride (5 mM) in dichloromethane after 30 s.
lates has also been shown to be due to the formation of
viologen radicals.54
To investigate the anion and radical formation (Scheme
2), electrochemical measurements were conducted on 5 using
cyclic voltammetry and differential pulse voltammetry modes
(Figure 5). In the absence of fluoride, a colorless solution of
5 (1.0 mM) in acetonitrile exhibits a chemically irreversible
oxidation peak at 1.8 V versus SCE (see Figure 5i) at a
boron-doped diamond electrode with wide potential win-
dow.55 Addition of 0.2 mM TBAF immediately causes a
decrease in the peak response at 1.8 V versus SCE and the
appearance of a new peak at 1.5 V versus SCE, which can
be tentatively assigned to the monofluoride adduct shown
in Scheme 2. For TBAF concentrations of 0.4 mM and
higher, two new peak responses at -0.3 V and +0.1 V versus
SCE are observed, which can be assigned to the oxidation
of the phenoxyl dianion to a colored phenoxyl diradical. In
complementary cyclic voltammetry experiments (not shown)
both peak responses are observed to be chemically irrevers-
ible. For applied potentials positive of about 0.0 V versus
SCE the characteristic purple color of the phenoxyl diradical
is observed at the electrode surface. Furthermore, additional
experiments with the parent phenol 3 in the presence of
(43) Lee, K. H.; Lee, H.-Y.; Lee, D. H.; Hong, J.-I. Tetrahedron Lett. 2001,
42, 5447–5449.
(44) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Tierney, J.; Ali, H. D. P.;
Hussey, G. M. J. Org. Chem. 2005, 70, 10875–10878.
(45) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Shi, A. J.
Chem. Commun. 2002, 758–759.
(46) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E. Org. Biomol.
Chem. 2003, 1, 741–744.
(47) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Pfeffer, F. M.; Hussey,
G. M. Tetrahedron Lett. 2003, 44, 8909–8913.
(48) Costero, A. M.; Jose Banuls, M.; Jose Aurell, M.; Ward, M. D.; Argent,
S. Tetrahedron 2004, 60, 9471–9478.
(49) Boiocchi, M.; Del Boca, L.; Gomez, D. E.; Fabbrizzi, L.; Licchelli,
M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507–16514.
(50) Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. J. Org. Chem. 2005,
70, 5717–5720.
(51) Boiocchi, M.; Del Boca, L.; Esteban-Go´mez, D.; Fabbrizzi, L.;
Licchelli, M.; Monzani, E. Chem.sEur. J. 2005, 11, 3097–3104.
(52) Gomez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Org. Biomol.
Chem. 2005, 3, 1495–1500.
(53) Evans, L. S.; Gale, P. A.; Light, M. E.; Quesada, R. Chem. Commun.
2006, 965–967.
(54) Dickson, S. J. ; Wallace, E. V. B. ; Swinburne, A. N. ; Paterson, M. J.
; Lloyd, G. O. ; Beeby, A. , Belcher, W. J. ; Steed, J. W. New J. Chem.
2008, in press.
(55) Compton, R. G.; Foord, J. S.; Marken, F. Electroanalysis 2003, 15,
1349–1363.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6241

Galbraith et al.
Scheme 2. Fluoride-Mediated Deboronation (4 or 5) or Deprotonation (2 or 3) Followed by Atmospheric Oxidation to a Colored Radical
1H spectra were recorded at 300.22 MHz, 11B spectra at 96.32 MHz,
and {1H}13C at 75.50 MHz. Chemical shifts (δ) are expressed in
parts per million and are reported relative to the residual solvent
peak or to tetramethylsilane as an internal standard in 1H and {1H}-
13C spectra. Chemical shifts (δ) are expressed in parts per million
and are reported relative to boron trifluoride diethyl etherate as an
external standard in 11B spectra. The multiplicities and general
assignments of the spectroscopic data are denoted as singlet (s),
doublet (d), triplet, (t), quartet (q), quintet (quin), doublet of doublets
(dd), doublet of doublets of doublets (ddd), doublet of triplets (dt),
triplet of triplets (tt), unresolved multiplet (m), apparent (app), broad
singlet (bs), and aryl (Ar).
Mass Spectra. Mass spectra were recorded by the EPSRC
National Mass Spectrometry Service Centre, Swansea. Electron
impact (EI) and chemical ionization (CI) analyses were performed
in positive ionization mode. Low resolution EI and CI measurements
were performed on a Micromass Quattro II triple quadrupole
instrument, with ammonia as the CI reagent gas. Electrospray
4 excitation at 251 nm produced a weaker fluorescence
emission at 308 and 330 nm, the intensity of which changes
negligibly with increasing chloride concentration. Addition
of TBAF causes fluorescence quenching attributed to fluoride
mediated deboronation (Supporting Information). These
results clearly indicate that the two boronate functionalities
of 5 are required for fluorescence quenching by chloride ions.
Experimental Section
General Procedures. Solvents and Reagents. Solvents and
reagents were reagent grade unless stated otherwise and were
purchased from Frontier Scientific Europe Ltd., Lancaster Synthesis
Ltd. and Sigma-Aldrich Company Ltd. and were used without
further purification, unless stated otherwise.
Nuclear Magnetic Resonance Spectra. Nuclear magnetic
resonance spectra were run in chloroform-D. 1H, 11B, and 13C
spectra were measured using a Bruker AVANCE 300 spectrometer.
Figure 5. Differential pulse voltammograms (modulation time 0.05 s, modulation amplitude 25 mV) for the oxidation of 1.0 mM 5 in acetonitrile (0.1 M
NBu4PF6) at a 3 mm diameter boron-doped diamond electrode in the presence of (i) 0 mM, (ii) 0.2 mM, (iii) 0.4 mM, (iv) 0.6 mM, (v) 0.8 mM, and (vi)
1.0 mM fluoride.
6242 Inorganic Chemistry, Vol. 47, No. 14, 2008

Fluorescent Boron Bis(phenolate)
measurements were conducted on either a Finnigan MAT95 high
resolution double focusing mass spectrometer or a MAT900 high
resolution double focusing mass spectrometer with tandem ion trap.
For EI and CI measurements heptacosa (perfluorotributylamine) was
used as the reference compound. Both low and high resolution fast
atom bombardment (FAB or liquid secondary ion mass spectrom-
etry, LSIMS) analyses were performed, in positive or negative
ionization mode, on either a Finnigan MAT95 high resolution
double focusing mass spectrometer or a MAT900 high resolution
double focusing mass spectrometer with tandem ion trap, using
meta-nitrobenzyl alcohol (NBA) as the matrix liquid.
Elemental Analyses. Elemental analyses were performed by the
Department of Chemistry, University of Bath, using an Exeter
Analytical Inc. CE-440 elemental analyzer.
Melting Points. Capillary melting points were determined using
a Bu¨chi 535 melting point apparatus. The readings were taken from
a mercury-in-glass thermometer and are reported uncorrected as
the meniscus point (unless stated otherwise), rounded to the nearest
1 °C with a heating ramp rate of 0.5 °C min-1. In instances where
a reproducible liquid meniscus could not be obtained, the onset
point (onset) was recorded instead and is noted. Where the sample
changed color or evolved gas during or after the melt, thermal
decomposition (dec) is noted.
Figure 6. UV spectra of 3 in dichloromethane (0.1 mM for F- and 1.0
mM for Cl-, Br-, and H2PO4--) upon addition of F- (0.5 mM), Cl- (5
mM) Br- (5 mM), and H2PO4 (5 mM) as tetra-n-butylammonium salts.
Fluorescence Measurements. Fluorescence measurements were
performed on a Perkin-Elmer luminescence spectrophotometer LS
50B, utilizing Starna Silica (quartz) cuvettes with 10 mm path
lengths, four faces polished. Data was collected via the Perkin-
Elmer FL Winlab software package. All solvents used in fluores-
cence measurements were HPLC or Fluorescence grade and the
water was deionized.
Electrochemical Measurements. Voltammetric and differential
pulse voltammetric data were obtained with a microAutolab III
system (Ecochemie) and in a conventional three-electrode cell. The
counter and reference electrodes were platinum gauze and a
saturated calomel electrode (SCE), respectively. A 3 mm diameter
boron-doped diamond disk electrode was obtained from Windsor
Scientific (Slough, U.K.). All measurements were conducted under
argon (BOC, U.K.) and at 20 +/- 2 °.
Single Crystal Preparation and Crystallographic Methods.
Single crystals were obtained by dissolving the compounds in
hexane or toluene. Good quality crystals were obtained overnight.
Crystallographic data for 4 and 5 are available as Supporting
Information. Data were collected on a Nonius KappaCCD diffrac-
tometer. Structure solution was performed using SHELX8657 and
refinement was by full-matrix least-squares on F2 using SHELX97
software. Selected data is shown in Table 1.
Figure 7. Fluorescence spectra of 5 in dichloromethane (1.0 mM, λ 289
nm) with increasing concentration of chloride (0-15.0 mM).
Synthesis (2,6-Di-tert-butylphenyl)hydrogenphenylboronate.
2,6-Di-tert-butylphenol (1.00 g, 4.85 mmol) was dissolved in dry
toluene (40 mL) and stirred in a nitrogen atmosphere. N-butyllithium
(1.6 mM in hexanes, 3.33 mL, 5.33 mmol) was added dropwise by
syringe and the mixture heated at 100 °C overnight. After cooling
the reaction to RT, dichlorophenylborane (700µL, 5.33 mmol) was
introduced and heating continued for a further 18 h. The white
precipitate dissolved in the subsequent thrice washing with water
(3 × 60 mL), and after drying over MgSO4 and the solvent removed
in vacuo, an off-white solid was obtained (1.366 g, 91%); δH (300
MHz, CDCl3, Me4Si) 1.31 (s, 18H, C(CH3)3), 4.07 (bs, 1H, B-OH),
6.98 (1H, t, JHH 7.5, Ar-H), 7.28 (2H, d, JHH 7.9, Ar-H), 7.43
Figure 8. Plot illustrating the quenching action of increasing concentration
of chloride on the fluorescence of 5.
ionization measurements were performed in both positive and
negative ionization modes (ES+ and ES- respectively). For low
resolution measurements the sample was loop injected into a stream
of 1:1 methanol/dichloromethane, on a Waters ZQ4000 single
quadrupole mass spectrometer or Mariner API-TOF with reflectron
detector mass spectrometer. High resolution EI, CI, ES+, and ES-
3
3
(56) Smith, D. K. Org. Biomol. Chem. 2003, 1, 3874–3877.
(57) Sheldrick, G. M. SHELX-86, Computer Program for Crystal Structure
Determination; University of Go¨ttingen: Go¨ttingen, Germany, 1986.
(58) Sheldrick, G. M. SHELX-97, Computer Program for Crystal Structure
Refinement; University of Go¨ttingen: Go¨ttingen, Germany, 1997.
Inorganic Chemistry, Vol. 47, No. 14, 2008 6243

Galbraith et al.
Table 1. Summary of Crystallographic Data for Compounds 4 and 5
4
5·H2O
5·C7H8
C48H62B2O4
empirical formula
formula weight
crystal color
crystal size, mm
crystal system
space group
a, Å
C20H27BO2
310.23
C41H56B2O5
650.48
724.60
colorless
0.20 × 0.20 × 0.10
monoclinic
P21/a
12.0120(1)
14.4200(1)
21.9640(2)
105.101(1)
3673.08(5)
8
colorless
0.10 × 0.10 × 0.05
monoclinic
C2/c
19.1590(3)
21.4040(3)
19.1280(6)
90.674(1)
7843.5(3)
8
colorless
0.25 × 0.13 × 0.13
monoclinic
C2/c
26.7710(6)
8.6100(2)
18.6130(5)
95.412(1)
4271.1(2)
4
b, Å
c, Å
R, deg
V, Å3
Z
T, K
150(2)
1.122
0.069
0.71073 (Mo KR)
52
1.042
0.0474
150(2)
1.102
0.070
0.71073 (Mo KR)
52
1.005
0.0609
150(2)
1.127
0.069
0.71073 (Mo KR)
56
1.023
0.0555
Dcalc, g cm-3
µ, mm-1
λ,Å
2θmax, deg
GOF (F2)
R1 [I > 2R(I)]
wR2 (all data, F2)
0.1186
0.1592
0.1683
(3H, m, Ar-H), 7.95 (2H, ddd, 3JHH 1.5, 3JHH 3.0, 3JHH 6.8, Ar-H);
δB (96 MHz, CDCl3) 20.0; m/z (CI+) found 310.2099 [M]+.
Expected value for C20H27O2B 310.2423.
in sensor materials, where a one off response to the presence
of fluoride is required. For example, early warning badges
to report the release of fluoride containing nerve agents such
as sarin.16,17
Bis(3,5-di-tert-butyl-4(hydrogenphenylboronoxy)phenyl)meth-
ane. 4,4′-Methylenebis(2,6-di-tert-butylphenol) (1.00 g, 2.35mmol)
was dissolved in 40 mL dry toluene under nitrogen. During rapid
stirring, N-butyllithium (1.6 M in hexanes, 4.95 mmol, 3.09 mL)
was added dropwise and the mixture heated at 100 °C overnight.
Upon cooling, dichlorophenylborane (680 µL, 5.18 mmol) was
added and heating at 100 °C reinitiated for an additional 12 h. The
resulting white suspension was washed three times with water (60
mL), dried over MgSO4, and the solvent removed in vacuo to afford
a yellow oil. Recrystallization gave the title compound as an off-
white powder (1.250 g, 84%); mp 162-164 °C (dec); δH (300
MHz, CDCl3, Me4Si) 1.29 (36H, s, Ar-(CH3)3), 3.88 (2H, s,
Ar-CH-Ar′), 7.11 (4H, s, Ar-H), 7.41 (6H, m, Ar-H), 7.94 (4H,
s, Ar-H); δC (75 MHz, CDCl3, Me4Si) 32.02, 35.93, 42.22, 127.06,
128.77, 131.88, 135.31, 136.12, 142.26, 148.88; δB (96 MHz,
CDCl3) 20.0; m/z (method of ionization) 650.4546 [M + NH]+.
The phenols 2 and 3 described above were converted into
aryl boronates 4 and 5, where 5 has been found to act as a
fluorescent sensor for chloride ions in dichloromethane. Since
only compound 5 displays this fluorescence response, we
propose that the chloride ion is hydrogen bonding to both
BOH groups in 5. This is a similar binding motif to that
observed in the crystal structure of 5 · H2O (Figure 2).
Our group is currently developing chloride receptors based
on the general structure of 5 · H2O that are stable to fluoride
and work under aqueous conditions.
Acknowledgment. T.D.J. and E.G. wish to acknowledge
the University of Bath and Beckman-Coulter for support.
+
The calculated mass of C41H54B2O4.NH4 is 650.4546.
Elemental Analysis. Expected C ) 77.86%, H ) 8.61% for
C41H54B2O4. Found C ) 77.80%, H ) 8.63% (average of two
measurements).
Note Added after ASAP Publication. There was a
reformat of references in the version published ASAP May
28, 2008; the corrected version published ASAP June 4,
2008.
Conclusions
A range of substituted phenols were tested for colorimetric
responses to fluoride and other anions in solution. Several
compounds were found to selectively deprotonate in the
presence of fluoride ions and form a highly colored and stable
radical species. Thus, simple, commercially available sub-
strates have been shown to act as colorimetric sensors for
fluoride. We envision these simple molecules being employed
Supporting Information Available: Figures with UV and
fluorescence spectra of 2-5 (PDF) and CIF files for 4, 5·H2O,
and 5·C7H8. This material is available free of charge via the Internet
at http://pubs.acs.org.
IC800204Q
6244 Inorganic Chemistry, Vol. 47, No. 14, 2008