Lanthanide Complexes that Respond to Changes in Cyanide Concentration in Water

Article abstract of DOI:10.1002/anie.201702296

Cyanide ions are shown to interact with lanthanide complexes of phenacylDO3A derivatives in aqueous solution, giving rise to changes in the luminescence and NMR spectra. These changes are the consequence of cyanohydrin formation, which is favored by the c

Full text of DOI:10.1002/anie.201702296

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Accepted Article
Title: Lanthanide complexes that respond to changes in cyanide
concentration in water
Authors: Stephen Faulkner, Jack Routledge, Xuejian Zhang, Michael
Connolly, Manuel Tropiano, Octavia Blackburn, Alan
Kenwright, Paul Beer, and Simon Aldridge
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201702296
Angew. Chem. 10.1002/ange.201702296
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10.1002/anie.201702296
Angewandte Chemie International Edition
COMMUNICATION
Lanthanide complexes that respond to changes in cyanide
concentration in water
Jack D. Routledge,a Xuejian Zhang,a Michael Connolly,a Manuel Tropiano,a Octavia A. Blackburn,a
Alan M. Kenwright,b Paul D. Beer,a Simon Aldridgea,* and Stephen Faulknera,*
Abstract: Cyanide ions are shown to interact with lanthanide
complexes of phenacylDO3A derivatives in aqueous solution, giving
rise to changes in the luminescence and NMR spectra. These
changes are the consequence of cyanohydrin formation, favoured by
the coordination of the phenacyl carbonyl group to the lanthanide
centre. These complexes display minimal affinity for fluoride and can
detect cyanide at <1 µM concentrations. By contrast, lanthanide
complexes with DOTAM derivatives display no affinity for cyanide in
water, but respond to changes in fluoride concentration.
chromophore centred triplet state, which transfers energy into
the lanthanide excited state manifold.[9] The effectiveness of this
energy transfer step is dependent upon the separation between
the lanthanide centre and the donor triplet state. Furthermore,
two mechanisms of energy transfer are possible: a Förster
mechanism involving through-space energy transfer,[10] or a
Dexter exchange mechanism that involves a through-bond
process.[11] We have previously shown that the Dexter
mechanism dominates wherever a through bond pathway is
available (even up to distances in excess of 2 nm), and that it is
generally much more effective than Förster energy transfer,
owing to the limited spectral overlap between chromophore
emission spectra and lanthanide absorption spectra.[12]
Furthermore, we and others have explored the coordination of
fluoride by positively charged lanthanide complexes in solution
in water.[13] We have shown that fluoride coordination to the
metal can have profound consequences for the spectroscopic
behaviour of these systems, and demonstrated that this arises
through changes to the magnetic anisotropy at the metal centre.
The detection of fluoride has also been accomplished by
emissive systems featuring pendant BMes2 units, although here
too typically with a competing response to cyanide.[14]
T
he detection of cyanide and fluoride ions has proved to be of
considerable interest in medical/environmental monitoring, in
part because both ions provide a possible route for the detection
of agents used in chemical weapons.[1,2] A number of strategies
have been devised that rely upon the interaction of these anions
with Lewis acidic centres, with the exploitation of boron-
containing receptors to this end dating back as far as the early
1960s.[3,4] However, while such approaches are highly effective
in non-competitive solvents, their effectiveness generally
decreases as water is introduced to the system. Systems
capable of the detection of cyanide in pure water are very rare
indeed, with a landmark exception being Gabbaï’s phosphonium
borane which signals the presence of cyanide down to the 0.2
ppm EPA regulatory threshold.[5,6] One potential problem
characteristic of such compounds, however, is the competing
response often encountered with fluoride and hydroxide.[3,7]
These ions also have high binding affinities for the widely
used -BMes2 function (Mes = 2,4,6-Me3C6H2), and consequently
place a limit not only on compatible ranges of pH, but also on
practical sensing applications, e.g. in drinking water.
In the current manuscript we outline an alternative approach,
in which kinetically stable lanthanide complexes (Eu.1 and Eu.2)
are used to probe cyanide concentration. These complexes
contain a phenacyl group that coordinates to the metal centre
through the carbonyl oxygen, while additionally providing an
antenna chromophore that can be used to sensitize formation of
the lanthanide emissive state. Thus, coordination has two
effects: it facilitates energy transfer from the chromophore to the
lanthanide while simultaneously polarizing the carbonyl group
and increasing its susceptibility to attack by external
nucleophiles. Such a binding event has the potential to disrupt
the chromophore, removing the possibility of a through-bond
sensitization mechanism, and changing the effectiveness of
energy transfer. While cyanohydrin formation of this type has
previously been employed in the detection of cyanide,[15,16] its
use in conjunction with lanthanide emission offers a hitherto
unexplored mechanism for signal amplification.
Luminescent lanthanide complexes have been widely
exploited in imaging and assay, where their long-lived emission
can be readily separated from short lived fluorescence- giving
rise to very low detection limits.[8] The electric-dipole forbidden
nature of f-f absorption transitions mean that aryl chromophores
are frequently used to sensitize the formation of lanthanide
excited states: though some f-f transitions are magnetic dipole
allowed, or can be hypersensitive to symmetry, their intensity is
generally too low to be of practical use for direct sensitization.
For most lanthanide complexes, sensitization is achieved via the
Complexes Ln.1 and Ln.2 were synthesized from the well-
known triester, 3,[17] as shown in Scheme 1. Reaction of 3 with
[a]
[b]
Dr J.D. Routledge, Mr X. Zhang, Dr M. Connolly, Dr M. Tropiano, Dr
O. Blackburn, Prof P.D. Beer, Prof S. Aldridge, Prof S. Faulkner
Inorganic Chemistry Laboratory, Department of Chemistry,
University of Oxford, South Parks Road, Oxford, OX1 3QR, UK
E-mail: Stephen.Faulkner@chem.ox.ac.uk
Simon.Aldridge@chem.ox.ac.uk
Dr A.M. Kenwright
Department of Chemistry, Durham University, Lower Mountjoy,
South Road, Durham, DH1 3LE, UK
O
O
O
t-BuO
t-BuO
O
O
O
O
O
O
t-BuO
t-BuO
O
N
N
N
N
N
N
N
a
Ln
b,c
N
N
N
H
N
N
O
O
O
Ot-Bu
Ot-Bu
O
Ln.1 X = F
Ln.2 X = Br
3
4
Supporting information for this article is given via a link at the end of
the document.
X
X
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10.1002/anie.201702296
Angewandte Chemie International Edition
COMMUNICATION
Scheme 1. Synthesis of ligands and complexes. Reagents and conditions: a)
dihaloacetophone, KI, K2CO3, MeCN, 80 oC, 48 h; b) TFA, DCM, room
temperature, 24 h; c) Ln(OTf)3, MeOH, 60oC, 2 d.
2-chloro-4'-fluoroacetophenone or 2,4'-dibromoacetophenone,
using a procedure derived from that already used to prepare
other phenacyl DO3A derivatives,[18] afforded the protected pro-
ligands 4a and 4b, respectively. Deprotection with trifluoroacetic
acid and subsequent complexation with the appropriate
lanthanide triflate yielded the respective metal complexes. The
NMR spectra of the europium complexes (Eu.1 and Eu.2) are
very similar, and bear strong resemblance to the spectra
reported for other lanthanide complexes of phenacylDO3A
derivatives.[18] Resonances corresponding to the axial ring
protons are observed in the range 25-36 ppm (for the dominant
diastereoisomer) and are consistent with a broadly square anti-
prismatic (SAP) geometry at the metal centre.
Figure 1. Changes in the Eu.1 emission spectra in H2O upon addition of KCN;
λex = 266 nm, exit slits 1 nm. Start of titration (black), end of titration (red; 1.5
equiv.) and intermediate concentrations (grey).
environment, the lack of a dramatic change in the relative
intensities of the peaks in the spectrum is consistent with the
continued coordination of water.
Both complexes also exhibited sensitized luminescence in
aqueous solution, and the lifetimes in H2O and D2O were used
to calculate the inner sphere hydration at the metal centre using
the equation:
The changes in the relative ratios of the intensities of the
peaks in the spectrum corresponding to the 5D0-7Fn transitions
were then used to estimate binding constants for association
with cyanide (Table 2) using DYNAFIT to model behaviour and
assess binding models.[20] While these 1:1 stoichiometric binding
constants are relatively low in magnitude, little directly
comparable data is available in pure water, and the apparent
selectivity over fluoride, especially for Eu.2, is high (vide infra).
Interaction with hydroxide can be ruled out under these
conditions: in studies on related systems we have shown that
the pKa of the complexed ligand is >10.2.[18]
q =1.2(tH2O-1 – tD2O-1 – 0.25)
where q is the number of inner sphere water molecules, and
tH2O-1 and tD2O-1 are the observed luminescence lifetimes in H2O
and D2O, respectively (in milliseconds).[19] The results are
summarized in Table 1, and show that both Eu.1 and Eu.2
feature nine-coordinate lanthanide ions with one bound solvent
molecule.
Table 2. Affinity constants for cyanide and fluoride.
Table 1. Photophysical properties of Eu.1 and
KCN/M-1
KF/M-1
Eu.2 in aqueous solution.
Eu.1
Eu.2
Eu.5
94.2 [80.3 – 110.7]
142.7 [135.9 – 173.1]
No binding
2.1 [1.9-2.3]
1.5 [1.46-1.57]
26.1 [24.9-27.4]
q
t
H2O/ms
tD2O/ms
Eu.1
Eu.2
0.62
0.61
2.16
2.52
1.1
1.2
95% confidence limits are shown in square brackets
The 1H NMR spectra of Eu.1 and Eu.2 also exhibited marked
changes when cyanide was added. These are exemplified in
Figure 2, which clearly shows the emergence of new species
upon the addition of cyanide to Eu.1. Combined with the
luminescence data and the associated binding constants, it is
clear that there is a well-defined interaction between cyanide
and the europium complex, since collisional quenching would
not explain the observed behaviour. It is also clear that the new
species is in slow exchange with Eu.1 on the timescale of the
NMR experiment.
Addition of cyanide to aqueous solutions of Eu.1 and Eu.2
resulted in a dramatic reduction in the observed luminescence
intensity in each case. The luminescence lifetimes in water,
however, remained unchanged within error, even following the
addition of a large excess of cyanide, suggesting that there is no
displacement of water from the inner coordination sphere of the
lanthanide metal. Furthermore, the steady state emission
spectra of Eu.1 (Figure 1) show that the change in emission
intensity is broadly consistent across all the peaks in the
5
lanthanide emission spectrum. Given that the D0-7F2 transition
in europium(III) species is hypersensitive to local coordination
Figure 2. 1H NMR spectra of Eu.1 without cyanide (black) and with cyanide
(red) (D2O, 298 K, 400 MHz).
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10.1002/anie.201702296
Angewandte Chemie International Edition
COMMUNICATION
responds only to changes in fluoride concentration, and is
unresponsive to cyanide. This raises the prospect of
differentiating between the two ions using lanthanide probes and
thereby enabling not only effective methods for probing cyanide
With coordination of cyanide to the metal being ruled out on
the basis of the essentially unchanged luminescence lifetimes,
an interaction between the ligand and cyanide can be
hypothesized. It is well known that cyanide reacts with carbonyl
compounds to form cyanohydrins, a phenomenon presumably
exacerbated in the case of the systems studied here by
coordination of the carbonyl oxygen at europium (Scheme 2).
Crucially, such a binding event would also rationalize the
spectroscopic observations made above. Thus, formation of the
cyanohydrin derivative disrupts the interaction between the
phenacyl chromophore and the lanthanide centre, ruling out a
Dexter exchange mechanism by disrupting the through-bond
pathway for exchange, and enforcing a less efficient through
space pathway for energy transfer. Thus, cyanide uptake in this
fashion lowers the intensity of the observed emission. NMR-wise,
the bulk of the cyanide group in a cyanohydrin will inevitably
influence the balance between SAP and TSAP (twisted square
anti-prismatic) coordination at the lanthanide centre, and the
increase in intensity of resonances corresponding to TSAP
isomers (e.g. the peaks around 20 ppm in Figure 2) can
therefore be ascribed to cyanohydrin formation. These
observations are borne out by changes in the IR spectra
(particularly to the band at 1713 cm-1 corresponding to the
carbonyl region, see SI Figure s4) and by observed changes to
the 13C NMR of the corresponding lutetium complex Lu.1 on
addition of cyanide (SI Figure s5).
contamination of (fluoridated) drinking water, but also
a
mechanism for distinguishing cyanide-containing chemical
warfare agents such as GA (Tabun) from fluorophosphonate
esters such as GB (Sarin) and GD (Soman).
In summary, our results have shown that ligand structure
can be exploited in the design of ion responsive systems. It is
possible to use the Lewis acidity of the lanthanide centre to
change the behaviour of coordinated chromophores, and thus
modulate the intensity of emission. The preparation of
complexes that exhibit this response in water at low (mM)
concentrations opens the door to the development of effective
and stable responsive complexes that can be used in
challenging environments.
Acknowledgements
The Authors acknowledge the Universities of Oxford and
Durham for support. The research leading to these results has
received funding from the European Research Council under the
European
Union’s
seventh
Framework
Programme
(FP7/2007_2013)/ERC-Advanced Grant Agreement Number
267426.
Keywords: detection • cyanide • fluoride • lanthanide complexes
F
• energy transfer
O
O
O
O
HN
O
F
O
O
O
O
HN
O
N
O
N
N
N
N
N
N
N
CN-
Ln
Ln
Ln
N
[1]
[2]
a) M. A. Holland, L. M. Kozlowski, Clinical Pharmacy 1986, 5, 737-741;
b) D. A. Dzombak, R. S. Ghosh, G. M. Wong-Chong (eds), Cyanide in
Water and Soil: Chemistry, Risk and Management, Taylor and Francis,
Boca Raton, Florida, 2005; c) F. Baud, Hum. Exp. Toxicol. 2007, 26,
191.
N
N
O
O
N
O
NH
F
CN
O
O
O
O
F
NH
X
Ln.5
X
Figure 3. (left) Proposed interaction between phenacyl DO3A complexes and
cyanide in water; (right) non-phenacyl ‘control’ systems Ln.5.
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To obtain further evidence for the proposed detection
mechanism, we also investigated whether cyanide interacts with
other lanthanide containing systems, in particular using complex
Eu.5 to assess whether any interaction occurs in the absence of
the pendant ketone function. In this case, no change was
observed in either the luminescence or NMR spectra following
addition of cyanide, lending further credence to the hypothesis
that cyanide interacts with the carbonyl group in the phenacyl
chromophore.
[3]
[4]
[5]
J. Havir, Collect. Czech. Chem. Commun. 1961, 26, 1775-1783.
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The US EPA maximum contaminant level (MCL) for free CN- in
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With this in mind, we also explored fluoride binding by Eu.1,
Eu.2 and Eu.5. As might be expected, given the greater residual
charge on the lanthanide centre, Eu.5 displayed dramatically
higher affinity for fluoride than the phenacylDO3A derivatives
(Table 2). In all cases, we can infer binding of fluoride at the
lanthanide centre from the changes in the luminescence spectra
(and particularly from changes to the relative intensities of the
hypersensitive 5D0-7F2 transition). Thus, Eu.1 and Eu.2 both
respond to cyanide in water, but respond only weakly to fluoride
(and respond to the two ions in different ways) while Eu.5
[6]
[7]
[8]
[9]
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[11]
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[20]
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10.1002/anie.201702296
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Lanthanide complexes of phenacyl-
Jack Routledge, Xuejian Zhang,
Michael Connolly, Manuel Tropiano,
Octavia A. Blackburn, Alan M.
Kenwright, Paul D. Beer, Simon
Aldridge and Stephen Faulkner
DO3A
derivatives
signal
the
presence of cyanide in aqueous
solution, through changes in their
luminescence and NMR spectra
brought about by cyanohydrin
formation. These complexes display
minimal affinity for fluoride and can
Page No. – Page No.
detect
concentrations.
cyanide
at
<1
m M
Lanthanide complexes that respond
to changes in cyanide concentration
in water
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