pH dependent self-assembly of dimetallic lanthanide complexes

Article abstract of DOI:10.1039/b412329h

pH dependent self-association has been observed in a series of DO3A-derived lanthanide complexes bearing a carboxylate group that can act as a bridging ligand at high pH, switching on the luminescence from the lanthanide.

Full text of DOI:10.1039/b412329h

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pH Dependent self-assembly of dimetallic lanthanide complexes{
Stephen Faulkner* and Benjamin P. Burton-Pye
Received (in Cambridge, UK) 10th August 2004, Accepted 8th October 2004
First published as an Advance Article on the web 19th November 2004
DOI: 10.1039/b412329h
4-chloromethylbenzoate gave access to compound 4. Cleavage of
the tert-butyl esters was accomplished by treatment with
trifluoroacetic acid in dichloromethane, yielding the monoester 5.
The terbium and europium complexes were prepared by reaction
of 5 with the appropriate lanthanide trifluoromethanesulfonate.
Hydrolysis in aqueous base and subsequent neutralisation
unmasked carboxylate bearing complex, Ln.1.
pH dependent self-association has been observed in a series of
DO3A-derived lanthanide complexes bearing a carboxylate
group that can act as a bridging ligand at high pH, switching on
the luminescence from the lanthanide.
Luminescent lanthanide complexes have been widely applied in
bioassay and imaging applications.1,2 The luminescence from
lanthanide ions is long-lived, allowing lanthanide-centred signals to
be separated from fluorescent backgrounds. This is particularly
important in biological applications. The study of lanthanide
luminescence has tended to centre on the properties of europium
and terbium complexes, though more recently, the properties of
near-IR luminescent complexes have been exploited to broaden the
range of potential sensitizers.3–6
Having prepared the complexes Ln.1 and Ln.5, we then
investigated their photophysical properties in isolation. All
complexes gave line-like emission spectra characteristic of the
lanthanide ions under study, while the benzoate group proved an
effective sensitizer for lanthanide-centred emission. Luminescence
lifetimes of the complexes in H2O and D2O are shown in Table 1.
These can be used to calculate the numbers of bound solvent
molecules around the metal centre using the equation
There has also been considerable interest in the synthesis of
polynuclear lanthanide complexes.7–9 We recently reported the
synthesis of a hetero-trinuclear lanthanide complex, and demon-
strated that one lanthanide can be used to sensitise the
luminescence of another in such a system.10 This complex contains
q 5 ALn(kH O 2 kD O 2 B)
2
2
where ALn and B are constants for a given lanthanide (1.2 ms and
0.25 ms21 for Eu3+, 5 ms and 0.06 ms21 for Tb3+), kH O and kD O
a
series of covalently linked binding sites, and relatively
2
2
are the observed rate constants for luminescence.16
complicated synthetic strategies are required to achieve differentia-
tion between these sites. Our interest in the photophysical
interactions between lanthanide ions led us to conclude that a
coordination chemistry approach would provide the ideal tool to
investigate such heteronuclear assemblies in solution: the flexibility
of such an approach more than outweighs the fact that the kinetic
stability of such systems is likely to be relatively low.
Calculated values for q are also shown in Table 1. It may be seen
that the values of q for Ln.1 are significantly lower than those
Heptadentate ligands derived from azamacrocycles exhibit
interesting anion binding properties, with a range of ions of
biological importance.11–14 Such systems have also been shown to
interact with aryl carboxylic acids. We now report the synthesis of
the carboxybenzyl DO3A derivative (1). This is a ligand in which
seven of the donor groups can chelate to a single metal centre,
while the benzyl group bears a carboxylic acid which can act as a
bridging group to a second metal centre. These molecules represent
an important development in that they allow self-assembly
processes to be used to study the properties of polynuclear
lanthanide complexes. Furthermore, these systems show pH
dependent self-association and thus have potential as pH sensors
in which the spectrum, quantum yield and luminescence lifetime
change as a result of self-assembly.
Ln.1 was synthesised using the procedures outlined in
Scheme 1.{ 1,4,7,10-tetraazacyclododecane (2) was treated with
tert-butylbromoacetate, yielding the well-known tert-butyl ester
of DO3A (3).15 Reaction of this product with methyl
{ Electronic supplementary information (ESI) available: Fig. S1: Change
of form and increase in intensity of the europium centred emission between
pH 2 and 8. See http://www.rsc.org/suppdata/cc/b4/b412329h/
*Stephen.Faulkner@man.ac.uk
Scheme 1 Synthesis of ligands and complexes.
Chem. Commun., 2005, 259–261 | 259
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Scheme 2 pH Dependent self-association of Ln.1.
Table 1 Luminescence lifetimes and calculated inner sphere hydra-
tion numbers (q) for the complexes under study
b
WH O (%)
Complex
l
ex/nm
lem/nm
t
H O/ms
t
D O/ms
q
2
2
2
Eu.1 (pH 8)
Eu.1 (pH 2)
Tb.1 (pH 8)
Tb.1 (pH 2)
Eu.5 (pH 8)a
Tb.5 (pH 8)a
a
274
274
274
274
274
274
616
616
545
545
616
545
0.53
0.37
1.73
1.24
0.39
1.23
1.26
1.29
2.73
2.73
1.62
2.58
1.0
7
0.2
64
30
0.9
29
2.0
0.8
1.8
2.1
1.8
Luminescence lifetimes and q values were constant across the pH
b
range of these experiments. Quantum yields were calculated relative
to quinine sulfate. Errors are ¡10%.
observed for Ln.5. This may be rationalized on the basis that Ln.5
has two water molecules bound at the metal centre; indeed, the q
values obtained are consistent with those observed for other
DO3A derivatives.
Fig. 1 Emission spectra at pH 2 (solid line) and pH 8 (dotted line),
normalised at 616 nm to show the variation in the relative intensities of the
emission lines at 595 and 616 nm.
In the case of Ln.1 the observed values of q are considerably
lower at neutral and high pH, and are also pH dependent
(Scheme 2). This can be explained by invoking self-association of
the complex in solution. At neutral pH, the carboxylate group is
deprotonated, and able to act as a ligand, displacing water from
another lanthanide complex. By contrast, under acid conditions,
the carboxylate is protonated, and the carboxylate group is unable
to displace water from the metal centre. Such association is
unlikely to occur in Ln.5, as the carboxymethyl group is a very
poor ligand for lanthanide ions.
raised, the spectrum becomes more complex, indicating the
formation of a second species, likely to be the result of self-
association.
Such self-association, and the concomitant change in lumines-
cence lifetime (see Fig. S1, ESI{), potentially provides a means for
monitoring pH. The luminescence at high pH is much more
intense than at low pH, as well as being much longer lived, the
variation in lifetime and intensity can potentially be used as a
probe of pH. Further studies are ongoing to explore the
possibilities of related gadolinium containing species as pH
dependent contrast agents.
Fig. 1 shows time-gated luminescence spectra for the europium
complex at low and high pH, and associated time resolved
decays are shown in Fig. S1, ESI{. The differences are clear and
dramatic. The emission at low pH is much less intense than that at
high pH. This is probably a result of displacement of water from
the metal centre, but there may also be a contribution from the
coordination of a sensitising chromophore. Furthermore, it can be
seen that the relative intensities of the peaks at 595 and 616 nm
change with changing pH, indicating a change in local environ-
ment at the lanthanide centre (Fig. 1). Similar changes in the
relative intensities of these peaks have been used by others as the
basis of ratiometric probes for pH and p[HCO32]:17 such probes
have the advantage that they can be used to determine pH without
their concentration being known. This is also true in the case of
Ln.1, and provides an additional check on the validity of such
measurements.
The authors thank the University of Manchester and EPSRC
for support.
Stephen Faulkner* and Benjamin P. Burton-Pye
Department of Chemistry, University of Manchester, Oxford Road,
Manchester, UK M13 9PL. E-mail: Stephen.Faulkner@man.ac.uk;
Fax: +44 161 275 4616; Tel: +44 161 275 4659
Notes and references
{ All compounds gave satisfactory analytical data: Selected data for Eu.1;
m/z (MALDI) 669 (MK+), 896 (MK2(alpha)+), 1259 (2M+), 1297 (2MK+),
1527 (2MK2(alpha)+): dH (pH 2) 16.83, 13.91, 10.52, 9.84, 9.49, 8.81, 7.61,
7.21, 3.88, 3.33, 3.10, 2.78, 2.16, 1.08, 0.95, 20.25, 25.78, 211.84, dH
(pH 10) 8.01, 7.64, 6.91, 3.90, 3.3, 2.75, 0.9, 26.0, 210, 216, 220.
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Further evidence for our hypothesis is provided by the mass
spectrum, which shows clear evidence for the existence of a peak
corresponding to the dimer. 1H NMR spectroscopy on the
europium complex is also supportive of this hypothesis. In this
case, a single species is observed at low pH. However, as the pH is
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