Diols and anions can control the formation of an exciplex between a pyridinium boronic acid with an aryl group connected via a propylene linker

Article abstract of DOI:10.1039/c0cc03099f

The exciplex formation between a pyridinium boronic acid and phenyl group connected via a propylene linker can be monitored using fluorescence. Addition of pinacol affords a cyclic boronate ester with enhanced Lewis acidity that increases the strength of

Full text of DOI:10.1039/c0cc03099f

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Diols and anions can control the formation of an exciplex between a
pyridinium boronic acid with an aryl group connected via a propylene
linkerw
Yan-Jun Huang,ab Yun-Bao Jiang,b Steven D. Bull,a John S. Fossey*c and Tony D. James*a
Received 6th August 2010, Accepted 3rd September 2010
DOI: 10.1039/c0cc03099f
The exciplex formation between a pyridinium boronic acid and
phenyl group connected via a propylene linker can be monitored
using fluorescence. Addition of pinacol affords a cyclic boronate
ester with enhanced Lewis acidity that increases the strength of
its cation–p stacking interaction causing a four-fold fluorescence
enhancement.
Cation–p interactions have been widely exploited in supra-
molecular chemistry, where they play pivotal roles in the
design of host–guest assemblies1 and synthetic receptors.2
These type of interactions have also proven useful for synthesis,3
where their presence has been invoked to explain the selectivity
of nucleophilic catalysts,4 cyclopropanations,5 cycloadditions,6
and various nucleophilic additions.7 In the biological arena
cation–p interactions have been implicated in many biomolecular
recognition events,8 whilst they also play an important role in
stabilising the secondary and tertiary structures of proteins.9
We have recently reported on the stacking behaviour of
pyridinium cations10 2 (Fig. 1) that contain a phenyl group
connected to a pyridine fragment via a propylene linker
(Avasthi and co-workers have described this type of spacer
as a Leonard linker).11,12 The enhanced cation–p stacking
interactions (Fig. 2) in these pyridinium species 2, relative to
the parent pyridine 1, enabled us to develop a fluorescence
sensor for common alkylating agents such as methyl iodide.13
Herein we report that this methodology has been exploited for
the development of a novel pyridine–boronic acid 4 that can
function as a cation–p stacking fluorescence sensor for diols.
We initially targeted preparation of a new type of pyridinium
salt 3a whose nitrogen atom is attached to a phenyl group via a
propylene linker. This was easily achieved via treatment of
pyridine with 1-bromo-3-phenylpropane at reflux for 24 hours
to give 1-(3-phenylpropyl)pyridinium bromide 3a in quantitative
yield.14 Fluorescent analysis of this pyridinium salt 3a revealed
a characteristic exciplex consistent with the presence of a
strong cation–p stacking interaction. This results in strong
fluorescence occurring in non-polar solvents, with a reduced
Fig. 1 Pyridine 1 and N-alkyl-pyridinium salts 2–4.
Fig. 2 The relative concentration of stacked cation–p interactions of
N-alkyl-pyridinium species 2/3 can be measured using the fluorescence
of their resultant exciplexes.
fluorescence in polar solvents (Fig. 3). It was found that the
strength of the exciplex emission of this type of pyridinium
species was highly dependent on the nature of its associated
counter anion. Therefore, addition of excess tetrabutylammonium
fluoride and tetrabutyl ammonium chloride to pyridinium
bromide 3a in CH2Cl2 resulted in quenching of the fluorescence.15
While addition of tetrabutylammonium hexafluorophosphate
to pyridinium bromide 3a gave pyridinium hexafluorophosphate
3d which exhibited a 2.6 fold enhancement in fluorescence
(Fig. 4).15
a Department of Chemistry, University of Bath, Claverton Down,
Bath, BA2 7AY, UK. E-mail: t.d.james@bath.ac.uk
b Department of Chemistry, College of Chemistry and Chemical
Engineering, and the MOE Key Laboratory of Analytical Sciences,
Xiamen University, Xiamen 361005, China
c School of Chemistry, University of Birmingham, Edgbaston,
Birmingham, West Midlands, B15 2TT, UK.
E-mail: j.s.fossey@bham.ac.uk
w Electronic supplementary information (ESI) available: Synthetic
procedures for the preparation of pyridinium salts 3a, 4a and 4b,
and fluorescence analysis data are provided. See DOI: 10.1039/
c0cc03099f
Boronic acids are capable of reversible formation of strong
covalent bonds with the hydroxyl groups of diols to form
cyclic boronate esters.16 Formation of this type of cyclic
c
8180 Chem. Commun., 2010, 46, 8180–8182
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Fig. 3 Fluorescence spectra of 3a (1.0 Â 10À4 mol LÀ1) in different
solvents, 25 1C. lex 260 nm.
Fig.
5
Titration of pyridinium boronic acid chloride 4a
(1.0 Â 10À4 mol LÀ1) in CH2Cl2 with pinacol at 25 1C. lex 260 nm.
addition of pinacol did not affect the fluorescence intensity of
pyridinium bromide 3a, or pyridinium boronic acid hexafluoro-
phosphate 4b.22
Formation of cyclic boronate esters from a boronic acid and
diol is known to enhance the Lewis acidity of the boron
centre.16,23 Therefore, it is proposed that addition of pinacol
to 4a affords boronate ester 5 that exhibits enhanced cation–p
interactions between its pyridinium fragment and its aryl
group.24 This enhanced cation–p interaction increases the
fluorescence response of this system because more of the
fluorescent exciplex is formed. The fluorescence response of
bromide salt 3a is not affected by the addition of pinacol,
because this system does not contain a boronic acid fragment
to act as a recognition site for pinacol. Addition of ethanol
does not affect the fluorescence response of chloride salt 4a
because only cyclic boronate ester results in enhanced Lewis
acidity. In the case of hexafluorophosphate salt 4b, addition of
pinacol does not cause a fluorescence enhancement indicating
that the counter anion plays an important role in the diol
controlled exciplex formation (Scheme 1).
Fig. 4 Fluorescence spectra of 3a (1.0 Â 10À4 mol LÀ1) in the
presence of added anions ClÀ, FÀ and PF6 (1.0 Â 10À4 mol LÀ1),
À
25 1C. lex 260 nm.
boronate ester leads to an increase in the Lewis acidity of the
boron atom, with this change in acidity having been exploited
many times for sensing molecules that contain diol functionality.
Consequently, we were interested in exploring the fluorescent
response of pyridinium boronic acid 4a towards the presence
of diols. Pyridinium boronic acids like 4 have pKa values
between 3.6–4.4,17 which contrasts favourably with the pKa
value of 8.70 for phenylboronic acid.18 This lower pKa value
of pyridinium boronic acid 4 is attributed to the formation of a
neutral zwitterionic pyridinium hydroxyboronate species, with
diol binding resulting in the formation of anionic tetrahedral
boronate species, that are potentially very useful for the design
of receptors that bind diols at neutral pH.
In conclusion, we have shown that it is possible to modulate
cation–p stacking interactions using external inputs, and that
those changes can be monitored using the fluorescence of the
exciplex formed between the pyridinium boronic acid and the
phenyl group connected through a propylene spacer. We are
currently exploring the use of this signalling motif in more
demanding polar solvent systems where we believe we will be
able to exploit these type of cation–p stacking interactions for
the development of fluorescence sensors for saccharides.
The Catalysis and Sensing for our Environment (CASE)
consortium are thanked for networking opportunities, the
Pyridinium boronic acid chloride 4a was prepared by
treatment of 4-(5,5-dimethyl-1,3,2-dioxanborinanyl)pyridine
with 1-bromo-3-phenylpropane at reflux for 48 hours in
acetonitile, followed by purification using ion exchange
chromatography that results in removal of the diol protecting
group and counterion exchange to afford 4a in 60% yield.
Subsequent addition of potassium hexafluorophosphate to a
methanol solution of chloride 4a gave hexafluorophosphate 4b
in 95% yield as a white solid.19
Addition of tetrabutylammonium fluoride, chloride and
bromide salts to the hexafluorophosphate 4b in CH2Cl2
resulted in quenching of the fluorescence,20 in line with the
fluorescence response previously observed for bromide 3a in
CH2Cl2. Addition of pinacol to 4a in CH2Cl2 caused a 4-fold
fluorescence enhancement (Fig. 5), whilst addition of ethanol
resulted in essentially no change in fluorescence.21 In contrast,
Scheme 1 Cation–p stacking geometry is favoured when pinacol is
added to 4a to afford boronate ester 5.
c
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Royal Society and the Universities of Xiamen, Birmingham
and Bath are thanked for support. YJH thanks the China
Scholarship Council (CSC) for support through a scholarship
to work at the University of Bath. JSF acknowledges ERDF
AWM II.
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c
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This journal is The Royal Society of Chemistry 2010