Lanthanide luminescent switches: Modulation of the luminescence of bis-macrocyclic based Tb(III) conjugates in water by H+, Na + and K+

Article abstract of DOI:10.1039/b509230m

The synthesis of four bis-macrocyclic conjugates made from the coupling of either diaza-15-crown-5 ethers (1 and 3) and diaza-18-crown-6 ethers (2 and 4) to either amide or carboxylate functionalized cyclen (1,4,7,10- tetraazacyclododecane), and their corresponding cationic Tb(III) complexes, Tb·1, Tb·2, and neutral complexes Tb·3 and Tb·4 are described. The effect on the ground, singlet excited states and the Tb(III) emission, was investigated either as a function of pH or the concentration of several Group I and II cations, upon excitation at 300 nm. The ground state and singlet excited states of the Tb(III) complexes were found to be modulated by ions such as H⁺, Na⁺ or K⁺, signifying the recognition of these ions by the crown ether receptors. In acidic media, below pH 4, the Tb(III) emission was highly pH sensitive, gradually increasing with large orders of magnitude of luminescence enhancements. For Tb·1 and Tb·2 complexes, the Tb(III) emission was also 'switched on' in alkaline media above pH 8. At pH 7.4, the recognition of Na⁺ or K⁺ also gave rise to a significant change in the Tb(III) emission due to the modulation of the antenna-receptor moieties by these ions. For Tb·1 and Tb·3 the largest changes were seen for Na⁺, whereas for Tb·2 and Tb·4 the largest changes were seen for K⁺. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b509230m

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F U L L P A P E R
Lanthanide luminescent switches: modulation of the luminescence
of bis-macrocyclic based Tb(III) conjugates in water by H+, Na+
and K+†
Thorfinnur Gunnlaugsson* and Joseph P. Leonard
Department of Chemistry, Centre for Synthesis and Chemical Biology, Trinity College Dublin,
Dublin 2, Ireland. E-mail: gunnlaut@tcd.ie; Fax: + 353 1 671 2826; Tel: +353 1 608 3459
Received 29th June 2005, Accepted 19th July 2005
First published as an Advance Article on the web 23rd August 2005
The synthesis of four bis-macrocyclic conjugates made from the coupling of either diaza-15-crown-5 ethers
(1 and 3) and diaza-18-crown-6 ethers (2 and 4) to either amide or carboxylate functionalized cyclen
(1,4,7,10-tetraazacyclododecane), and their corresponding cationic Tb(III) complexes, Tb·1, Tb·2, and neutral
complexes Tb·3 and Tb·4 are described. The effect on the ground, singlet excited states and the Tb(III) emission, was
investigated either as a function of pH or the concentration of several Group I and II cations, upon excitation at
300 nm. The ground state and singlet excited states of the Tb(III) complexes were found to be modulated by ions such
as H+, Na+ or K+, signifying the recognition of these ions by the crown ether receptors. In acidic media, below pH 4,
the Tb(III) emission was highly pH sensitive, gradually increasing with large orders of magnitude of luminescence
enhancements. For Tb·1 and Tb·2 complexes, the Tb(III) emission was also ‘switched on’ in alkaline media above
pH 8. At pH 7.4, the recognition of Na+ or K+ also gave rise to a significant change in the Tb(III) emission due to the
modulation of the antenna-receptor moieties by these ions. For Tb·1 and Tb·3 the largest changes were seen for Na+,
whereas for Tb·2 and Tb·4 the largest changes were seen for K+.
macrocycle that hosts the Tb(III) ion and function as the
Introduction
luminescence emitting moiety. To the best of our knowledge,
The development of luminescent signalling systems is an active
these are one of the first examples of such bis-macrocyclic
area of research in supramolecular chemistry.1–4 These include
lanthanide based luminescent switches.18
the development of luminescent switches, logic gate mimics,
machines and, in particular, sensors.1–10 Classically, transition
metal ion complexes have often been employed in the design of
such luminescent devices.11 Recently, lanthanide ion complexes
have also been developed as alternative metal ion based emission
moieties.1,12,13 Ions like Nd(III), Sm(III), Eu(III), Tb(III), Er(III)
and Yb(III), all possess long lived excited states, occurring in
the millisecond or microsecond timescale. Moreover, they emit
at long wavelengths, with large sharp and narrow emission
band structures. However, their excited states are, nevertheless, a
Laporte-forbidden f–f transition, which makes direct excitation
difficult. Nonetheless, the development of metal sensitization
using antennae, by covalently incorporating one or more
sensitizing chromophore into the coordinating ligand, or by
self-assembly, overcomes this drawback.1,12–14 Furthermore, by
modifying the antenna, for instance, by incorporating a receptor
moiety as an integrated part of the antenna, it is possible
to modulate the sensitization process, which in turn yields
responsive luminescent devices.1,12,13,14
We are interested in the development of such responsive
lanthanide ion complexes and we have developed systems where-
upon the emission is either ‘switched on’ or ‘off ’, by cations,
anions or neutral molecules.1,15,16 In this paper we present the
synthesis of several Tb(III) complexes Tb·1, Tb·2, Tb·3 and Tb·4,
as Na+ or K+ switches, and the photophysical evaluation of
Results and discussion
these complexes as a function of pH or the concentration of
Design and synthesis of ligands 1–4 and their corresponding
Tb(III) complexes
several group I and II ions in pH 7.4 buffered solutions.17 These
bis-macrocyclic complexes comprise of a diaza-15-crown-5 or a
diaza-18-crown-6 macrocycle, as combined antenna/receptors,
that are tethered to a cyclen (1,4,7,10-tetraazacyclododecane)
Our design is based on the use of the crown ether receptors 7
and 8 as key intermediates (Scheme 1). These are formed by
using o-anisidine moieties as a part of the crown ether receptor
so that the methoxy groups can participate in the coordination
of the targeted ions, and as such increase both sensitivity and
the selectivity of the Na+ or K+ recognition.19 Indeed, X-
ray crystallographic evaluations of these two receptors in the
presence of Na+ and K+, have indeed shown this to be the case.
† Electronic supplementary information (ESI) available: 22 figures
including binding studies of 13 and 14, various bindings studies of the
Tb(III) complexes discussed, the effect of temperature and degassing on
the Tb(III) emission and the crystal structure of 14 and the corresponding
K+ complex. See http://dx.doi.org/10.1039/b509230m
3 2 0 4
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Scheme 1 Synthesis of 1–4 and their corresponding Tb(III) complexes.
The ions were found to be coordinated to the oxygens of the ring,
the nitrogens of the aniline units and the two methoxy groups.20
The synthesis of ligands 1–4 and their Tb(III) complexes are
shown in Scheme 1. Thea-chloroamides 7 and 8 were synthesised
by stirring the amino compounds 5 and 6, respectively, in 1,4-
dioxane with 1.1 equivalents of a-chloroacetic anhydride and
Na2CO3 at room temperature. This gave both products in yields
of ca. 62% following purification by column chromatography.
The synthesis of 5 and 6 have previously been reported by us
involving the transformation of 2-methoxyaniline in several high
yielding steps to give 13 and 14 as intermediates (see later).20 The
nitration of 13 and 14 was achieved using NaNO2 in aerated
water and glacial acetic acid. Compounds 5 and 6 were then
obtained by catalytic hydrogenolysis. The synthesis of 1, 2, 11
and 12 involved stirring equimolar amounts of 7 or 8 with 921a
or 1021b in refluxing MeCN in the presence of Cs2CO3. Both
1 or 2, were obtained in 77% yields in a sufficiently pure state
for complexation to Tb(III). It is worth noting that using either
flash silica or alumina column chromatography failed to afford
the desired products in any purer state. Both 11 and 12 were,
successfully purified and obtained as oils in ca. 56% yield after
treating the crude materials to alumina column chromatography,
by initially using DCM–THF (70 : 30) as an eluent, followed by
a gradient elution to DCM–THF–MeOH (60 : 30 : 10) as the
final solvent system. Both 11 and 12 were finally subjected to
acid hydrolysis using TFA in DCM yielding 3 and 4 in 82 and
89% yields, respectively.
number of peaks related to the complexes where the isotopic
distribution patterns of the Tb(III) complexes were clearly
distinguishable.
Ground and singlet excited state investigation of the Tb(III)
complexes of 1–4
We carried out investigations of the photophysical properties of
this range of complexes as a function of pH, and group I and
II metal ions in water, where the changes in the ground state,
the singlet excited state and the lanthanide excited state (5D4)
were monitored. The results discussed below, focus on the effect
of the ground and the singlet excited state of Tb·1 and Tb·2 as
representatives of these complexes.
We first evaluated the effect of pH upon the ground state and
the singlet excited states of the above complexes. It was foreseen
that the ground state properties of these complexes would be
greatly effected by pH due to the stepwise protonation of the
two aryl amines as well as the potential deprotonation of the sec-
ondary amide. In the case of Tb·1, at pH ∼ 12, (using tetramethyl
ammonium hydroxide, TMAOH), two main absorption bands
were observed at 211 nm (log e = 5.43, determined by linear
regression analysis) and 251 nm (log e = 4.09) with a shoulder
at 279 nm (log e = 4.03). Upon acidification (using dilute HCl)
to neutral pH, a hypsochromic shift was observed in the 211 nm
band with a concomitant hypochromic effect which resulted in
the absorption being shifted to 200 nm (log e = 5.34). When the
pH was decreased further to pH ∼ 1, a slight bathochromic shift
occurred, resulting in a maximum at 203 nm (log e = 5.37) with
concomitant hyperchromic effect. Considerable changes were
also observed in the longer wavelength band at the 251 nm band
and in the shoulder at 279 nm, Fig. 1, which was assigned to
the ICT character of the molecule (see later). The 251 nm band
experienced a hypochromic effect as the pH was decreased from
pH 12 → 6. However, as the pH was decreased even further
a second protonation process occurred where a hyperchromic
effect was observed for this band. A bathochromic shift was
also observed in the 251 nm band as the pH was decreased
from pH 12 → 8, which resulted in a shift in the maximum to
279 nm. As the pH was decreased further a hypochromic effect
was observed which reached a minimum absorption at ca. pH ∼
2, resulting in a decrease in the absorbance intensity of ca. 54%.
These results clearly demonstrate the complexity of the several
protonation steps involved.
Synthesis of the lanthanide complexes of ligands 1–4 involved
stirring the aforementioned ligands and 1.1 equivalents Tb(III)
triflate in freshly distilled MeCN for approximately 15 h, under
an atmosphere of dry argon, followed by precipitation from
dry diethyl ether. The Tb·1 and Tb·2 complexes were purified
by alumina column chromatography using DCM–THF (30 :
70) as the initial solvent system, followed by a gradient elution
using DCM–THF–MeOH (30 : 60 : 10), giving the complexes in
yields of ca. 35%. However, both Tb·3 and Tb·4 were obtained
in yields of ca. 80% after precipitation from diethyl ether and
1
did not require further purification. The H NMR (CD3CN)
spectra of all the complexes showed large chemical shifts for
the axial and the equatorial protons of the cyclen ring and
the –CH2– spacers, due to the presence of the paramagnetic
lanthanide ion.22 For Tb·1, these resonances appeared at 68.59,
41.76, 23.72, 18.13, 10.36, 8.69, 7.05, 6.77, 6.56, 5.58, 5.25,
4.82, 4.27, 1.42 ppm, respectively, suggesting that the complex
adopted a square antiprism geometry around the lanthanide
ion in solution.23 In all cases the ESMS spectrum showed a
We propose that the main changes described above are due
to three protonation steps. Two of these we assigned to the
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2
3 2 0 5

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Fig. 1 Absorption spectra of Tb·1 (10 lM aqueous solution) as a
function of pH. See text for description. (Inset: Absorbance of Tb·1
at 279 nm as a function of pH.).
Fig. 2 Fluorescence of Tb·1 as a function of pH (10 lM solution, slit
widths 9 nm, excitation at 300 nm), where the emissions quenched in
acidic media. These changes were fully reversible. Note: Emission band
at 336 nm is due to Raman scattering of water. (Inset: Fluorescence
profile of Tb·1 as a function of pH at 378 nm (10 lM), excitation at
300 nm.).
protonation both the aniline moieties in Tb·1, with pKa2 and
pKa3 of 5.5 ( 0.2) and ca. 3.0 ( 0.2), respectively. Of these
two aniline moieties, the one adjacent to the lanthanide ion
would be expected to give rise to relatively larger changes in the
absorption spectra due to the presence of an internal charge
transfer (ICT) process, as a result of the electron donating
amine and the electron withdrawing amide. Because of this ICT
character, the aniline lone pair is also significantly delocalized
and any protonation would be quite difficult, except at low
pH. We thus assign the pKa3 to this moiety, whereas pKa2 is
due to the protonation of the remaining aniline moiety. The
secondary amide is also adjacent to the lanthanide ion, where it
inductively experiences the charge of the lanthanide ion. These
combined effects make the secondary amide more acidic and
more accessible to deprotonation, and we assign the pKa1 = 11
( 0.2) to this moiety. A plot of the changes in the absorption
spectra at 279 nm as a function of pH is shown in Fig. 1, as an
insert, demonstrating these multiple steps. Similar pH studies
were performed on all the other complexes, and all showed
comparable changes to those reported above.
of 1 lM to 0.8 M, a bathochromic shift was observed in the
200 nm band, which was accompanied by a hyperchromic effect
that resulted in a formation of a new absorption maximum at
ca. 223 nm (log e = 5.03), and an isosbestic point at ca. 248 nm.
However, at higher concentrations the isosbestic point was less
visible. More importantly, a concomitant hypochromic effect
was also observed in the 276 nm band, which resulted in a
33% decrease in the absorption intensity, Fig. 3. The observed
changes in the 276 nm band were attributed to the coordination
of the aniline nitrogens of the aza crown ring to K+, which upon
binding to the ion are no longer, or only partially, delocalised
into the aromatic system, thus reducing the inherent ICT process.
The concomitant changes in the fluorescence of Tb·1 in
aqueous solution were also monitored upon excitation at
300 nm, where there was a large change in the absorption
spectrum between the alkaline and acidic media, Fig. 1. As with
the ground state it was expected that the emission spectra would
be pH dependent, and this was indeed found to be the case. At
neutral pH a major emission maxima was observed at 378 nm,
Fig. 2. Upon titration of a basic solution of Tb·1 with acid,
a decrease was observed in the intensity of this band with a
total reduction of 87% at pH ∼ 1. A plot of the changes of the
intensity as a function of pH is shown in Fig. 2 as an insert.
Again, complicated changes were observed, suggesting three
protonation/deprotonation steps, which are almost identical to
that seen in the ground state. It should also be noted that at pH
∼ 4, the Tb(III) emission began to appear, at 490 and 546 nm,
respectively (the J = 6 and J = 5 bands), overlapping with
the fluorescence emission. This clearly demonstrated that the
lanthanide luminescence was highly pH responsive, but only at
low pH. Similar pH experiments were also performed on Tb·2,
Tb·3 and Tb·4. All showed the same trend as for Tb·1.
Fig. 3 The changes in the absorption spectra of Tb·2 (30 lM) as a
function of K+, where the absorption decreases upon increasing K+
concentration.
Analysis of the changes observed upon titrating Tb·2 with K+
indicated 1 : 1 binding. From these changes a binding constant
of log b = 1.3 ( 0.1) was determined for the K+ binding, which
is rather weak. This could be due to the fact that the aniline unit
adjacent to the Tb(III) ion makes the nitrogen lone pair more
delocalized and less available to participate in the K+ binding.
This became clear by evaluating the changes in the absorption
spectra of the model compounds 13 and 1420 at 250 nm, when
these receptors were subjected to such titrations in MeOH–H2O
(50 : 50) solution. As for the pH titration earlier, the main
changes occurred at shorter wavelengths. Nevertheless, there
were also changes between 270 and 310 nm. For 14, a sigmoidal
curve indicating a sensitivity to K+ over two log units from
pKa 2–4, when plotting the changes at 250 nm, from which
a binding constant log b = 3.9 ( 0.1) was determined, which
Ground and singlet excited state investigation Tb(III) complexes
of 1–4 as a function of Na+ and K+ at pH 7.4
We evaluated the effect of titrating a solution of the respective
lanthanide complexes with either Na+ or K+ (as Cl− or AcO−
solutions) In the case of Tb·2, a Tb(III) complex designed as
a luminescent sensor/switch for K+, a titration was performed
in a 0.1 M TRIS buffered solution at pH 7.4. As demonstrated
before, two absorption bands were visible prior to the addition of
KOAc. Upon addition of stock solution of KOAc over a range
3 2 0 6
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2

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is significantly stronger binding than seen for the lanthanide
complexes. Similar results were observed for 13 with Na+, which
gave log b = 3.1 ( 0.1). Studies on all the other lanthanide
complexes showed comparable changes in absorption spectra as
seen for Tb·2 in the presence of cations such as Na+ or K+ and
all showed that the sensitivity for the ions was at a relatively high
concentration range.
changes occurred. From these changes we determined that the
Tb(III) emission was ‘switched on’ with ca. 40 and 14-fold order
of magnitude enhancements in acidic media for Tb·1 and Tb·2,
respectively, and with ca. 22- and 10-fold order of magnitude
enhancements in alkaline media for Tb·1 and Tb·2, respectively.
Looking at Fig. 5, it is clear that the pH dependence gives rise
to an ‘inverted-bell-shaped’ pH profile. This pH dependence was
found to be fully reversible, and comparable results were also
found when this experiment was repeated using other acids such
as dilute H2SO4, indicating that there was no anion effect.
Analysis of the fluorescent emission dependence of all of the
lanthanide complexes were also carried out in the presence of
either Na+ or K+ in a similar manner to that described above
for Tb·2. The emission spectra of Tb·1 showed a decrease in the
emission of the 378 nm band of almost 50% upon titration
with Na+. The presence of the J = 6 and J = 5 bands
from the Tb(III) emissions were also observed at higher ion
concentrations, as seen previously for the pH titration of Tb·1;
clearly demonstrating that the Tb(III) emission was modulated
upon the recognition of the ion by the antenna/receptor. The
results for each of the other Tb(III) complexes mirrored those
seen here for Tb·1.
Fig. 5
as a function of pH (10 lM, kexc
The changes in the Tb(II=I) e3m00isnsimon) uatsi5n4g6dnilmutfeoHr TCbl·t1itarantdioTnbo·2f
alkaline (TMACl) solution. These changes were fully reversible.
Lanthanide luminescence investigations of the Tb(III) complexes
of 1–4
From the changes in the 546 nm transitions shown in Fig. 5,
we were able to determine two pKa values of 2.8 ( 0.2) and
11.2 ( 0.2) for Tb·1. As before the latter pKa was attributed to
the deprotonation of the delocalized aniline moiety adjacent to
the metal ion. This assignment is also supported by the rational
that the aniline furthest from the lanthanide complex is too
far to allow an efficient energy transfer (ET) to modulate the
Tb(III) emission. This supports the results observed previously
for the pH dependence of the singlet excited state, where the
Tb(III) emission was only observed in highly acidic media. When
this experiment was performed using the structurally similar
complex Tb·2, Fig. 5, the same pH dependence was observed,
and pKa of 3.0 ( 0.2) and 11.0 ( 0.2) were determined. We
also evaluated the changes in the Tb(III) emission in degassed
solution, as we have previously demonstrated that Tb(III) having
quinoline antennae are prone to quenching due to back energy
transfer from the 5D4 to the T1 of the antenna where it is
quenched by O2. However, for the above Tb(III) complexes,
only a minor enhancement was observed, indicating that this
quenching pathway was absent.
Similar pH experiments were also performed on the charge
neutral triacetate based complexes Tb·3 and Tb·4. At pH = 7,
the Tb(III) emissions of both complexes were weak, indicating
that the emission was ‘switched off ’. When the pH was decreased
below pH 4.0, a significant enhancement was observed for the
Tb(III) emission where the J = 5 transition (at pH 0.3) had been
‘switched on’ by a factor of ca. 46. Interestingly, both complexes
were shown to be pH independent above pH 4.0, Fig. 6. As
before, the changes were attributed to the protonation of the
aromatic amine of the diaza crown ether adjacent to the Tb(III)
centre.
The lanthanide complexes Tb·1–4 were all analysed in terms
of their lanthanide luminescence with respect to pH, Na+ and
K+ titration in a similar manner to that discussed above by
excitation at 300 nm where there was a significant difference in
the absorption spectra between the free and the complexed re-
ceptor/antenna. We first evaluated the effect of the pH response
of the cationic complex Tb·1, in aqueous solution as a function of
pH from pH 12 → 1 (using time gating techniques). The Tb(III)
7
emission, corresponding to the 5D4 → FJ transitions (J = 6, 5, 4
and 3, where 5D4 Tb(III), E = 20 500 cm−1) occurring at 490, 546,
586 and 622 nm, respectively, showed a dramatic sensitivity to its
pH environment. The overall changes can be seen in Fig. 4. To
investigate this further, the changes in the 546 nm transition were
analyzed by plotting them as a function of pH, Fig. 5. From these
changes it can be concluded that the Tb(III) emission is highly
pH dependent, much more so than in the fluorescence spectra.
Most importantly, the Tb(III) emission in the pH range of ca.
4.1–9.6, is almost fully ‘switched off ’, whereas in both acidic
media (below pH ∼ 4) or basic media (above pH ∼ 9.6) dramatic
This striking difference between Tb·1 and Tb·2, which display
‘on–off –on’ switching as a function of pH, and Tb·3 and Tb·4,
showing ‘on–off ’ switching as a function of pH, is intriguing.
The main difference between these four complexes is the
coordination environment of the Tb(III) ion, which for Tb·1
and Tb·2 consists of four carboxylic amides yielding overall
cationic complexes, whereas for Tb·3 and Tb·4 the coordination
is through a single carboxyl amide (the receptor/antenna) and
three acetates, giving an overall charge neutral complex. Hence,
Fig. 4 The overall changes in the Tb(III) emission of Tb·1 (10 lM; kexc
300 nm) as a function of pH from pH 12 → 1.5.
=
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2
3 2 0 7

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The measurements were first recorded at neutral pH and
pD, where the emission was, in all cases, ‘switched off ’. When
recorded in water, lifetimes of 0.16, 0.18, 0.77 and 0.47 ms
were determined for Tb·1–4, respectively. Noticeably, the overall
charge neutral complexes give substantially longer excited state
lifetimes than the cationic equivalents. A similar trend was also
observed in D2O. These results clearly support our findings
that the coordination environment does additionally affect the
lanthanide ion emission. However, the difference between the
charge neutral and the cationic complexes were again apparent
as the Tb·1 and Tb·2 lifetimes were almost identical in both
media. At the same time, the neutral complexes were on average
30% longer. As predicted, these results also demonstrate that all
the complexes have a single bound water molecule under neutral
pH conditions (see q in Table 1).
When the lifetimes were determined in acidic solution at
pH ∼ 1 considerable changes were observed. Firstly, a significant
increase was observed for s of all the complexes in both H2O
and in D2O. Lifetimes of 0.91 ms, 1.29 ms, 1.31 ms and 1.23 ms
being determined for Tb·1–4, respectively when measured in
H2O. This indicated that unlike that at pH 7, all the complexes
had similar lifetimes. Furthermore, all the complexes were shown
to have q ∼ 1. Lifetime analysis for Tb·1 and Tb·2 at pH ∼ 12
produced similar results. However, the most interesting trend
was seen for the determination of the q-values between these
Fig. 6 The changes in the Tb(III) emission of Tb·3 and Tb·4 at 546 nm,
as a function of pH. These changes were fully reversible.
to investigate the differences in the pH dependence on the basis
of a possible coordination effect, we carried out detailed lifetime
studies of all of the Tb(III) complexes in H2O and D2O, as a
function of pH or pD using the Horrrocks equation:24
qTb(III) = 5.0[(1/sH − 1/sD O) − 0.06]
O
2
2
complexes at pH ∼ 12. Here the sH for Tb·1 and Tb·3 on one
O
2
We conducted a study of our complexes by direct excitation
of the lanthanide complexes, at 365 nm as such direct excitation
should consequently give information of the coordination
environment of the metal ion itself, independent of the efficiency
of the sensitization process. The results are presented in Table 1.
hand, and Tb·2 and Tb·4 on the other hand, were all of similar
magnitude. However, only Tb·1 and Tb·2 produced meaningful
q-values of ca. 1, whereas Tb·3 and Tb·4 gave inconclusive
q-values of −0.35 and −2.5, respectively. Even though, this
method does not conclusively explain why the tetra-amide based
Table 1 Determination of excited state lifetimes and q-values
sH O/ms
kH O/ms−1
sD O/ms
kD O/ms−1
q ( 0.5)
2
2
2
2
pH 7
Tb·1
Tb·2
Tb·3
Tb·4
0.16(1)
0.18(1)
0.77(8)
0.47(0)
6.21(1)
5.52(4)
1.28(5)
2.12(7)
0.17(0)
0.18(9)
1.04(8)
0.53(0)
5.88(2)
5.29(1)
0.95(4)
1.88(6)
1.3
0.9
1.4
0.9
pH 1
Tb·1
Tb·2
Tb·3
Tb·4
0.90(5)
1.29(3)
1.31(2)
1.23(3)
1.10(5)
0.77(3)
0.76(2)
0.81(1)
1.15(9)
1.99(0)
2.23(2)
2.01(7)
0.86(3)
0.50(2)
0.44(8)
0.49(6)
0.9
1.1
1.3
1.3
pH 12
Tb·1
Tb·2
Tb·3
Tb·4
1.06(4)
0.42(5)
1.13(4)
0.41(4)
0.94(0)
2.34(8)
0.88(2)
2.41(5)
1.55(8)
0.48(1)
1.11(9)
0.35(2)
0.64(1)
2.07(5)
0.89(3)
2.84(0)
1.2
1.1
NA
NA
Saturated with NaCla
Tb·1
Tb·3
0.43(9)
0.80(9)
2.27(8)
1.23(6)
0.51(6)
1.06(5)
1.93(9)
0.93(9)
1.4
1.2
Saturated with KCla
Tb·2
Tb·4
0.57(3)
0.48(9)
1.74(5)
2.04(7)
0.65(2)
0.56(6)
1.53(3)
1.76(8)
0.8
1.1
a As the q-value does not change in the presence of (saturated concentrations) NaCl or KCl it can be concluded that the complex is kinetically stable
in the presence of these ions, and that the chloride anion is not coordinated to the lanthanide ion. Using NaOAc gave similar results, confirming that
the counterion was not displacing the metal bound water molecule and hence increasing the Tb(III) emission due to displacement of the quenching
water molecule.
3 2 0 8
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2

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ligands show this dual pH behaviour and the carboxylates do
not, this experiment suggests a possible change in the Tb(III)
coordination environment as a potential cause. One scenario is
that the pendent arms can be more affected by the pH than
previously anticipated. However, as the pH-titrations were fully
reversible it is unlikely that this leads to dissociation of the
metal ion from the cyclen moiety. Further studies of model
compounds are necessary to fully elucidate this mechanism and
we are currently undertaking these investigation.
was also observed when these measurements were repeated using
NaOAc. However, as the emission was not fully ‘switched on’,
we were unable to determine accurate binding values from these
changes. Similar titration experiments were also performed on
Tb·1 in buffered solutions using KCl or LiCl, Fig. 8. In the case
of KCl the emission was enhanced by ca. 3-fold after the addition
of 1.23 M whereas, a 4-fold enhancement was observed for Li+
at the same concentration. This demonstrates that the size of the
aza crown ether discriminates the selectivity of the recognition
process as expected and that Na+ gives the largest luminescent
enhancements and is selectively detected. Similar measurements
were carried out on Tb·3. Here, the response to Na+, K+ and Li+
mirrored the results observed for Tb·1, indicating that, unlike
that seen in the pH titrations above, the Tb(III) emission of both
systems was modulated to the same extent in the presence of
these Group I ions, see ESI.†
The relatively high concentration needed to ‘switch the
emission on’ for these systems is worth commenting on. We
attributed the changes in the sensitivity of the lanthanide ion
complexes described herein, in comparison to that observed for
13 and 14 above, to be due to enhanced delocalization of the
aniline nitrogen lone pair of the aryl amide moiety adjacent
to the luminescent moiety which makes it less available to
coordination of either Na+ or K+. Although these complexes
operate at rather high concentrations this does not however,
detract from the fact that the Tb(III) emission can be modulated
by an ionic input, e.g. a metal based emission can nevertheless be
tuned by the recognition of a group I ion species, in kinetically
stable lanthanide complexes, with a large order of magnitude
difference in their ‘off ’ to ‘on’ stages.
Switching the Tb(III) emission of Tb·1 and Tb·3 with Na+ and
several other competitive group I and II ions at pH 7.4
As discussed above we had demonstrated that the ground state
and the singlet excited states of the antennae were modulated
upon recognition of either Na+ or K+ (as Cl− or AcO− solutions)
it was thus anticipated that the same would be the case for
the Tb(III) emission. The results of the titration of Tb·1 in
water with NaCl at pH 7.4 are depicted in Fig. 7. It shows
that prior to the addition of Na+ the complex was only weakly
emissive, and that upon gradual titration with NaCl solution
the emission was gradually ‘switched on’, demonstrating that
5
7
the Tb(III) emission was modulated by Na+. Of the D4 → FJ
transitions, the strongest emission changes were observed for
the 546 nm transition with 7-fold enhancement. The changes in
the intensity of this band as a function of the concentration of
Na+ and other ions tested are shown in Fig. 8. It is important
to note that the luminescent enhancement was not observed
until at high concentration and that no further titrations were
carried out above 1.23 M. The same concentration dependence
The changes in the lifetime of the Tb(III) excited state in the
presence of Na+ were also measured for these complexes, and
the results of these are shown in Table 1. These demonstrated
a significant enhancement from 0.16 ms, in the free form, to
0.48 ms upon Na+ complexation for Tb·1. This indicates at least
a partial coordination of Na+ to the aniline nitrogen in a similar
way to protonation causing modulation of the Tb(III) emission.
From these measurements we determined a value of q = 1.4
which indicates that the counter ion Cl− ion does not displace
the metal bound water molecule. The changes in the lifetimes,
support the idea that the triplet energy of the antenna/receptor
had increased upon binding of Na+ in a similar way to that
discussed previously for the pH titration.
Switching the Tb(III) emission of Tb·2 and Tb·4 with K+ and
several other competitive group I and II ions at pH 7.4
Identical ion titrations to those shown above were performed on
Tb·2 and Tb·4, which were designed to be selective towards K+
ions. As before, the Tb(III) emission was substantially modulated
by K+, as the emission was ‘switched on’ in the presence of
K+. These were also significantly larger enhancements than
seen for the Na+ analogues above, with ca. 31-fold luminescent
enhancement being determined for Tb·2. However, again these
only occurred at relatively high concentrations. As observed for
the Na+ complexes earlier, the q-value was measured to be ca.
∼ 1, and the lifetimes showed similar trends in comparison to
those determined at pH ∼ 1 or ∼7, Table 1. These titrations were
also carried out using a range of other metal chloride salts such
as Na+, Li+, Mg2+ and Ca2+ to demonstrate the selectivity of
Tb·2 toward K+ and the results of these are presented in Fig. 9.
Unlike that seen for the smaller diaza-15-crown-5 ethers earlier,
no enhancement was observed in the Tb(III) emission when Tb·2
was titrated with Li+. This was expected as the receptor of Tb·2
was designed for K+ and would be too large to efficiently bind
Li+. For Na+ the emission was also modulated with ca. 6-fold
luminescence enhancement. Titrations of Tb·2 with Ca2+ and
Mg2+ showed 8- and 3-fold enhancements respectively (at higher
concentrations).
Fig. 7 The changes in the Tb(III) emission of Tb·1 (4 lM; kexc = 300 nm)
as a function of Na+ where the emission is ‘switched on’.
Similar titrations were also performed on Tb·4, in buffered
Fig. 8 The changes in the Tb(III) emission of Tb·1 as a function of pM,
where M = Na+, K+ and Li+.
pH 7.4 solution. The largest changes were seen for K+ which
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2
3 2 0 9

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at 100 MHz using a Bruker Spectrospin DPX-400 instrument.
Infrared spectra were recorded on a Mattson Genesis II FTIR
spectrophotometer equipped with a Gateway 2000 4DX2–66
workstation. Oils were analyzed using NaCl plates, solid samples
were dispersed in KBr and recorded as clear pressed discs. Mass
spectroscopy was carried out using HPLC grade solvents. Mass
spectra were determined by detection using Electrospray on
a Micromass LCT spectrometer, using a Shimadzu HPLC or
Water’s 9360 to pump solvent. The whole system was controlled
by MassLynx 3.5 on a Compaq Deskpro workstation. All
spectroscopic studies were carried out on solutions of complexes
in water or in buffered solutions at 10, 8 or 4 lM. Buffered
solutions consisted of 0.1 M TRIS Buffer and 0.1 M TMACl
at pH 7.4. Solutions were 5 mL, 10 mL or 20 mL. Uv-vis
spectroscopy analysis was carried out on a Shimadzu UV-2401
PC UV-Vis spectrophotometer. Studies were carried out on fast
scan mode with slit widths of 1.0 nm, using matched quartz cells.
Excitations were carried out at 300 nm unless otherwise stated.
Fluorescence and luminescence measurements were made on a
Perkin Elmer LS 50B or Varian Carey Eclipse
Fig. 9 The changes in the Tb(III) emission of Tb·2 as a function of pM,
where M = Na+, K+, Ca2+, Mg2+ and Li+.
resulted in an overall 40-fold luminescent enhancement. The
selectivity of this sensor/switch towards K+ was demonstrated
in titration experiments performed using Na+, Li+, Ca2+ and
Mg2+ chloride salts. Titrations of Tb·4 with Ca2+ and Mg2+
both resulted in a 9-fold enhancement, whereas no change was
observed for Li+. As in the case of Tb·2, the luminescence was
enhancedfor all oftheabove ions except Li+. These results clearly
indicated that the changes in the receptor part of the conjugate
has to take place for modulation of the Tb(III) emission to occur,
and that unlike the smaller crown-ether receptors, the Li+ is not
strongly complexed, or recognised, and hence does not lead to
modulation of the Tb(III) emission.
When the emission of these complexes was recorded in the
presence of high concentrations of either Na+ or K+, respectively,
but in degassed solutions, no luminescent enhancements were
observed indicating the absence of any back energy transfer to
the T1 of the antennae. The stability of all the above complexes
was also investigated by recording the delayed lanthanide
luminescence over a period of days and weeks. On all occasion
the Tb(III) emission was observed under identical experimental
conditions, which demonstrated that the complexes were stable
to Tb(III) ion dissociation over this period of time.
General procedure for the formation of a-chloroamides (7 and 8)
Compound 5, (0.559 g, 1.256 mmol) [or 6, (0.687 g, 1.40 mmol)
in the case of 8] was placed into a 50 mL single neck RBF
along with 1,4-dioxane (99+%, ACS grade) (20 mL). To this was
added 1.1 equivalents of Na2CO3. This solution was stirred at
room temperature. To this a solution of 1,4-dioxane (99+%, ACS
grade) (10 mL), containing 1.1 equivalents of a-chloroacetic
anhydride was added. The resulting solution was stirred at room
temperature overnight. The solution was then reduced and the
resulting residue was dissolved in water (50 mL) and the pH was
adjusted to pH 1 with conc. HCl. The solution was then washed
with DCM (2 × 30 mL). The aqueous phase pH was adjusted to
pH 14 with KOH pellets and washed with DCM (2 × 30 mL).
The organic phase was dried over CaCl2 and reduced to a crude
oil. The oil was run down an alumina column using a gradient
elution of DCM to DCM–THF (30 : 70).
2-Chloro-N -{3-methoxy-4-[13-(2-methoxyphenyl)-1,4,10-
trioxa-7,13-diazacyclopentadec-7-yl]phenyl}acetamide (7).
Compound 7 was produced as an oil. (0.409 g, 62.26% yield).
Calc. for C26H37N3O6Cl: [M + H] m/z = 522.2371. Found:
522.2374 (+ 0.6 ppm); dH (CDCl3, 400 MHz) 8.30 (s, 1H, N–H),
7.30 (s, 1H, Ar–H), 7.03 (t, 1H, J = 8.0 Hz, Ar–H), 6.98 (d,
1H, J = 5.5 Hz, Ar–H), 6.94–6.83 (m, 4H, Ar–H), 4.18 (s, 2H,
Cl–CH2), 3.83 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 3.74–3.61
(m, 12H, –OCH2CH2O–), 3.49–3.40 (m, 8H, –OCH2CH2O–);
dC (CDCl3, 100 MHz) 163.59, 153.29, 153.0, 140.55, 137.77,
131.72, 122.24, 121.42, 121.10, 120.75, 112.25, 111.95, 105.03,
71.19, 71.05, 70.77, 69.80, 69.80, 69.71, 55.52, 55.39, 53.28,
53.25, 52.65, 52.65, 49.92; MS (MeCN, ES+) m/z Expected:
521.2. Found: 522.2 (M + H); IR mmax/cm−1: 3033, 3199, 3116,
3055, 2946, 2869, 1684, 1606, 1541, 1509, 1452, 1411, 1350,
1239, 1175, 1110, 1030, 926, 857, 801, 745.
Conclusion and summary
The synthesis and characterization of several bis-macrocyclic
ligands 1–4 and the photophysical evaluation of the Tb(III) lan-
thanide complexes Tb·1, Tb·2, Tb·3 and Tb·4 were undertaken.
Photophysical analysis of these complexes showed that all these
complexes were stable in solution, and that both the ground state
and the singlet excited states were effected or modulated by the
presence of ions such as H+, Na+ or K+. We established that the
Tb(III) emission was pH independent over the pH window of
4–8, where it was ‘switched off. In buffered pH 7.4 solution, the
Tb(III) luminescence emission was, however, found to be greatly
modulated by either Na+ or K+, where the sensitivity and the
luminescent enhancements was in all cases related to the size
of the receptor e.g. this was most clearly seen for Tb·2 and Tb·4
where Li+ did not modulate the Tb(III) emission whereas K+ did.
2-Chloro-N -{3-methoxy-4-[16-(2-methoxyphenyl)-1,4,10,13-
tetraoxa-7,16-diazacyclooctadec-7-yl]phenyl}acetamide (8).
Compound 8 was produced as an oil. (0.490 g, 61.67% yield).
Calc. for C28H41N3O7Cl: [M + H] m/z = 566.2633. Found:
566.2642 (+ 1.6 ppm); dH (CDCl3, 400 MHz) 8.39 (s, 1H, N–H),
7.34 (s, 1H, Ar–H), 7.17–7.11 (m, 2H, Ar–H), 6.98–6.95 (m,
2H, Ar–H), 6.91 (t, 1H, J = 8.0 Hz, Ar–H), 6.85 (d, 1H, J =
8.0 Hz, Ar–H), 4.21 (s, 2H, Cl–CH2), 3.85 (s, 3H, OCH3), 3.84
(s, 3H, OCH3), 3.60–3.51 (m, 24H, –OCH2CH2O–); dC (CDCl3,
100 MHz) 163.64, 153.38, 153.15, 139.40, 136.55, 132.00,
122.50, 121.80, 121.53, 120.77, 112.29, 111.89, 104.94, 70.58,
69.98, 69.88, 55.57, 55.42, 52.79, 52.73, 42.98; MS (MeCN,
ES+) m/z Expected: 565.2. Found: 566.2 (M + H); IR mmax/cm−1
3272, 3186, 3106, 3042, 2936, 2872, 1688, 1607, 1543, 1502,
Experimental
Starting materials were obtained from Sigma Aldrich, Strem
Chemicals and Fluka. Columns were run using Silica gel 60
(230–400 mesh ASTM) or Aluminum Oxide (activated, Neutral,
Brockmann I STD grade 150 mesh). Solvents used were HPLC
1
grade unless otherwise stated. H NMR spectra were recorded
at 400 MHz using a Bruker Spectrospin DPX-400 instrument.
Tetramethylsilane (TMS) was used as an internal reference
standard, with chemical shifts expressed in parts per million
(ppm or d) downfield from the standard. 13C NMR were recorded
3 2 1 0
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2

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1453, 1411, 1352, 1288, 1240, 1174, 1109, 1031, 991, 914, 858,
815, 730.
400 MHz) [Partial NMR only] 10.82 (1H, N–H), 7.36 (d, 1H
J = 8.52 Hz, Ar–H), 7.29 (s, 1H, Ar–H), 6.99 (d, 1H, J = 7.5 Hz,
Ar–H), 6.82–6.78 (m, 2H, Ar–H), 6.75 (t, 1H, J = 7.5 Hz,
Ar–H), 6.68 (d, 1H, J = 8.0 Hz, Ar–H), 1.32 (s, 9 H, tert-butyl
CH3), 1.30 (s, 18 H, tert-butyl CH3); dC (CDCl3, 100 MHz)
172.37, 171.94, 170.03, 152.60, 151.00, 135.31, 134.75, 127.67,
122.07, 120.90, 120.18, 112.02, 111.18, 104.95, 81.54, 81.31,
69.69, 69.28, 67.42, 55.30, 55.11, 54.89, 52.39, 52.14, 27.51,
27.44; MS (MeCN, ES+) m/z Expected: 1043.6. Found: 1044.6
(M + H), 1066.7 (M + Na), 522.8 (M + 2H)/2; IR mmax/cm−1
3420, 2974, 2857, 1728, 1680, 1607, 1512, 1454, 1368, 1311,
1165, 1105, 1008, 852, 755, 598.
General synthesis of 1, 2, 11 and 12
Compound 7, (0.2815 g, 0.658 mmol) [or 8, (0.468 g, 0.828 mmol)
in the case of 2] and 1 equivalent of 9 [or 10 in the case of 11
and 12] was placed into a 50 mL single-neck RBF. To this was
added 1 equivalent of Cs2CO3 and 40 mL of dry MeCN. The
solution was kept under dry conditions in an argon atmosphere
and stirred at 72 ◦C for 72 h. The resulting mixture was cooled
to room temperature and filtered through Celite. In the case
of 1 and 2, MeCN was removed under vacuum and the crude
material dissolved in CHCl3 (40 mL). This was washed with
water (5 × 20 mL). The organic phase was separated dried over
MgSO4 and reduced to give the desired product in a relatively
pure state. (Yields ca. 70%). In the case of 11 and 12, MeCN
was removed under vacuum to produce a crude oil. The crude
oil was dissolved in a small quantity of DCM and placed onto a
dry alumina column that was washed with DCM–THF (70 : 30)
which was slowly changed by gradient dilution to DCM–THF–
MeOH (60 : 30 : 10).
General synthesis of 3 and 4
The triester, 11 (or 12) (0.162 mmol) was placed into a 25 mL
single neck RBF. To this was added DCM (12 mL) and TFA
(5 mL). The solution was stirred for 24 h at room temperature.
The solvent was removed under reduced pressure and the acid
chased off by the addition and evaporation of successive portions
of DCM (2 × 10 mL), MeOH (2 × 10 mL) and diethyl ether
(2 × 10 mL). The resulting residue was dissolved into MeOH
(0.25 mL) to which ether (10 mL) was added dropwise yielding
the desired product as a solid. This was filtered off, washed with
cold ether and dried under vacuum. Both gave yields of >80%.
N-{3-Methoxy-4-[13-(2-methoxyphenyl)-1,4,10-trioxa-7,13-
diazacyclopentadec-7-yl]phenyl}-2-(4,7,10-tris(dimethylcarbamoyl)-
methyl-1,4,7,10-tetraazacyclododec-1-yl)acetamide (1). Com-
pound 1 was formed in ca. 77% yield. Calc. for C46H77N10O9:
[M + H] m/z = 913.5875. Found: 913.5858 (−1.9 ppm); dC
(CDCl3, 100 MHz) 170.30, 170.21, 170.07, 153.0, 152.6, 151.3,
140.16, 135.60, 125.29, 122.06, 121.30, 120.66, 120.50, 111.55,
104.25, 71.01, 70.89, 70.82, 70.51, 69.47, 55.17, 54.74, 54.36,
53.13, 52.92, 52.33, 52.21, 51.84, 36.82, 36.26, 35.23, 34.92; MS
(MeCN, ES+) m/z Expected: 912.5. Found: 913.5 (M + H),
456.9 (M + 2H)/2; IR mmax/cm−1 3420, 2937, 2855, 1647, 1510,
1451, 1403, 1260, 1238, 1217, 1108, 1030, 859, 810, 747, 629,
489.
[4,7-Bis(carboxymethyl)-10-({3-methoxy-4-[13-(2-methoxy-
phenyl)-1,4,10-trioxa-7,13-diazacyclopentadec-7-yl]phenylcar-
bamoyl}methyl)-1,4,7,10-tetraazacyclododec-1-yl]acetic
acid
(3). Compound 3 was formed in ca. 82% yield. Calc. for
C40H62N7O12: [M + H peak] m/z = 832.4456. Found: 832.4462
(+0.6 ppm); dH (CD3CN, 400 MHz) 10.88 (br s, 1H), 8.41 (br s,
1H), 7.57 (br s, 2H, Ar–H), 7.51 (s, 1H, Ar–H), 7.38–7.36 (m,
2H, Ar–H), 7.12–7.10 (m, 1H, Ar–H), 7.04 (s, 1H, Ar–H), 3.84
(br s, 6H), 3.61 (br s, 10H), 3.43–3.38 (m, 16H), 3.18 (br s, 20H);
MS (MeCN, ES+) m/z Expected: 831.44. Found: 832.3 (M +
H), 854.3 (M + Na), 416.6 (M + 2H)/2, 278.1 (M + 3H)/3; IR
mmax/cm−1 3429, 3104, 2958, 2924, 2854, 1683, 1504, 1461, 1375,
1355, 1203, 1181, 1127, 1104, 828, 801, 721, 689, 620, 598, 516.
N-{3-Methoxy-4-[16-(2-methoxyphenyl)-1,4,10,13-tetraoxa-
7,16-diazacyclooctadec-7-yl]phenyl}-2-(4,7,10-tris(dimethyl)-
carbamoylmethyl-1,4,7,10-tetraazacyclododec-1-yl)acetamide
(2). Compound 2 was formed in ca. 77% yield. Calc. for
C48H81N10O10: [M + H] m/z = 957.6137. Found: 957.6188
(+5.3 ppm); dC (CDCl3, 100 MHz) 170.28, 170.22, 170.07,
153.08, 152.80, 143.61, 138.80, 135.58, 125.27, 122.37, 121.63,
121.22, 120.47, 111.43, 104.16, 70.26, 69.54, 55.15, 54.78,
54.30, 52.93, 52.52, 52.42, 51.83, 36.82, 36.25, 35.22, 34.93; MS
(MeCN, ES+) m/z Expected: 956.6. Found: 957.6 (M + H),
979.0 (M + Na) 478.9 (M + 2H)/2; IR mmax/cm−1 3417, 2955,
2923, 2854, 1644, 1538, 1504, 1454, 1402, 1260, 1240, 1104,
1030, 812, 750.
[4,7-Bis(carboxymethyl)-10-({3-methoxy-4-[16-(2-methoxy-
phenyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-7-yl]phenylcar-
bamoyl}methyl)-1,4,7,10-tetraazacyclododec-1-yl]acetic
acid
(4). Compound 4 was formed in ca. 89% yield. Calc. for
C42H66N7O13: [M + H peak] m/z = 876.4719. Found: 876.4722
(+ 0.4 ppm); dH (CD3CN, 400 MHz) 10.88 (br s, 1H), 8.64
(br s, 1H), 7.59 (br s, 1H), 7.45 (br s, 1H), 7.27 (br s, 3H), 7.18
(s, 1H,), 7.07–7.01 (br m., 3H, Ar–H), 4.25–4.08 (br m., 4H,
Ar–H), 3.80 (br s, 9H), 3.48 (s, 27H), 3.15 (br s, 12H), 2.65 (br s,
2H); dC (CD3CN, 100 MHz) 173.18, 169.82, 169.43, 165.46,
154.50, 138.10, 126.41, 123.68, 121.12, 118.12, 115.26, 111.59,
102.99, 68.52, 66.62, 57.68, 56.36, 55.12, 54.45, 53.96, 53.36,
53.17, 52.84, 50.99, 49.33, 48.37, 46.80, 44.01; MS (MeCN,
ES+) m/z Expected: 875.4. Found: 876.5 (M + H), 898.5 (M +
Na), 439.1 (M + 2H)/2, 292.8 (M + 3H)/3; IR mmax/cm−1 3429,
3104, 2957, 2921, 2880, 1688, 1512, 1462, 1353, 1202, 1178,
1123, 1093, 827, 764, 719, 690, 618, 569, 513.
[4,7-Bis-tert-butoxycarbonylmethyl-10-({3-methoxy-4-[13-
(2-methoxyphenyl)-1,4,10-trioxa-7,13-diazacyclopentadec-7-
yl]phenylcarbamoyl}methyl)-1,4,7,10-tetraazacyclododec-1-yl]-
acetic acid tert-butyl ester (11). Compound 11 was formed
in ca. 57% yield. Calc. for C52H86N7O12: [M + H peak] m/z =
1000.6334. Found: 1000.6307 (−2.8 ppm); dC (CDCl3, 100 MHz)
172.58, 172.09, 170.18, 152.52, 151.20, 140.13, 135.48, 134.93,
122.05, 121.16, 120.64, 120.55, 112.27, 111.63, 105.35, 81.57,
81.52, 70.69, 70.41, 69.45, 67.63, 56.47, 55.50, 55.31, 55.08,
53.04, 52.72, 52.41, 52.22, 27.69, 27.62; MS (MeCN, ES+) m/z
Expected: 999.6. Found: 1000.6 (M + H), 1022.6 (M + Na),
500.7 (M + 2H)/2; IR mmax/cm−1 3428, 2975, 2854, 1728, 1681,
1607, 1504, 1454, 1368, 1312, 1228, 1166, 1106, 1008, 852, 756,
597.
General synthesis of Tb(III) complexes
Compounds 1 or 2 (∼100 mg, ∼0.1 mmol) and Ln(III) tri-
flouromethane sulfonate (0.1 mmol) were added to a 5 mL single
neck RBF that contained 3 mL of freshly dried MeCN. The
solution was freeze–pump–thawed three times, placed under
an argon atmosphere and left stirring at reflux for 24 h. The
resulting solution was cooled to room temperature and then
dropped slowly onto dry diethyl ether (50–70 mL). In the case of
Tb·1 and Tb·2 the diethyl ether was decanted to leave these
complexes in a crude state. These were dissolved in a small
quantity of DCM and placed onto dry alumina plugs that were
washed with DCM–THF (70 : 30) which was slowly changed
by gradient dilution to DCM–THF–MeOH (60 : 30 : 10) to
[4,7-Bis-tert-butoxycarbonylmethyl-10-({3-methoxy-4-[16-
(2-methoxyphenyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadec-
7-yl]phenylcarbamoyl}methyl)-1,4,7,10-tetraazacyclododec-1-
yl]acetic acid tert-butyl ester (12). Compound 12 was formed
in ca. 36% yield. Calc. for C54H90N7O13: [M + H peak]
m/z = 1044.6597. Found: 1044.6619 (+ 2.1 ppm); dH (CDCl3,
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2
3 2 1 1

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afford the desired products. In the case of Tb·3 and Tb·4, a
white precipitate was collected. The solvent was decanted off
and the white solid was washed with cold ether (2 × 5 mL). The
resulting solid was dried under vacuum.
6 J. F. Callan, A. P. de Silva and N. D. McClenaghan, Chem. Commun.,
2004, 2048; A. P. de Silva and N. D. McClenaghan, Chem.–Eur. J.,
2004, 10, 574.
7 A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley,
C. P. McCoy, J. T. Rademacher and T. E. Rice, Chem. Rev., 1997, 97,
1515.
Tb·1. was formed in 36% yield. Calc. for C46H77N10O9Tb:
[M + H peak] m/z = 1072.5128. Found: 1072.5160 (+ 3.0 ppm);
dH (CD3CN, 400 MHz) 68.59, 41.76, 23.72, 18.13, 10.36, 8.69,
7.05, 6.77, 6.56, 5.58, 5.25, 4.82, 4.27, −1.42; dF (CD3CN,
376 MHz) −77.68; MS (MeCN, ES+) m/z Expected: 1072.51.
Found: 356.92 (M/3), 609.82 (M + [Triflate])/2, 684.76 (M +
2[Triflate])/2; IR mmax/cm−1 3425, 2955, 2924, 2873, 1624, 1560,
1511, 1461, 1356, 1258, 1158, 1119, 1082, 1030, 957, 823, 756,
638, 573, 517.
8 T. Gunnlaugsson, H. D. P. Ali, M. Glynn, P. E. Kruger, G. M. Hussey,
F. M. Pfeffer, C. M. G. Dos Santos and J. Tierney, J. Fluoresc.,
2005, 15, 287; F. M. Pfeffer, A. M. Buschgens, N. W. Barnett, T.
Gunnlaugsson and P. E. Kruger, Tetrahedron Lett., 2005, 46, 6579;
T. Gunnlaugsson, A. P. Davis, J. E. O’Brien and M. Glynn, Org.
Biomol. Chem., 2005, 3, 48; T. Gunnlaugsson, A. P. Davis, G. M.
Hussey, J. Tierney and M. Glynn, Org. Biomol. Chem., 2004, 2, 1856;
T. Gunnlaugsson, J. P. Leonard and N. S. Murray, Org. Lett., 2004,
6, 1557.
9 T. Gunnlaugsson, C. T. Lee and R. Parkesh, Org. Lett., 2003, 5, 4065;
T. Gunnlaugsson, C. T. Lee and R. Parkesh, Org. Biomol. Chem.,
2003, 1, 3265; T. Gunnlaugsson, J. M. Kelly, M. Nieuwenhuyzen
and A. M. K. O’Brien, Tetrahedron Lett., 2003, 44, 8571; T.
Gunnlaugsson, A. P. Davis, J. E. O’Brien and M. Glynn, Org. Lett.,
2002, 4, 2449.
10 V. Balzani, Photochem. Photobiol. Sci., 2003, 2, 459; K. A.
O’Donaghue, J. M. Kelly and P. E. Kruger, Dalton Trans., 2004,
13; M. A. O’Neill and J. K. Barton, Top. Curr. Chem., 2004, 236, 67;
N. Armaroli, Photochem. Photobiol. Sci., 2003, 2, 73; L. Fabbrizzi,
M. Licchelli and P. Pallavicini, Acc. Chem. Res., 1999, 32, 846; M.
Licini and J. A. G. Williams, Chem. Commun., 1999, 1943.
11 S. Faulkner and J. L. Matthews, in Comprehensive Coordination
Chemistry, 2nd edn, vol. 9, Application of Coordination Complexes,
ed. M. D. Ward, Elsevier, Amsterdam, 2003; J.-C. G. Bu¨nzli and C.
Piguet, Chem. Rev., 2002, 102, 1897; J.-C. G. Bu¨nzli and C. Piguet,
Chem. Soc. Rev., 1999, 28, 347; D. Parker, Coord. Chem. Rev., 2000,
205, 109.
Tb·2. was
formed
in
32%
yield.
Calc.
for
C51H82N10O20S3F9Tb·2THF: C, 41.07; H, 5.72; N, 8.12.
Found: C, 40.93; H, 5.44; N, 7.63;. Calc. for C48H81N10O10Tb:
[M + H peak] m/z = 1116.5391. Found: 116.5390 (−0.1 ppm);
dH (CD3CN, 400 MHz) 77.2 (br s), 55.7 (br s), 46.9 (br s), 22.51
(br s), 17.52 (br s), 15.65 (br s), 9.31–8.62 (m), 5.39 (br s),
4.77 (br s), 3.85 (br s), 3.55 (br s), 2.92 (br s), 2.51 (br s),
1.74 (br s), −73.14 (s), −89.81 (s), −97.28 (s); dF (CD3CN,
376 MHz) −78.52; MS (MeCN, ES+) m/z Expected: 1116.53.
Found: 371.60 (M/3), 631.84 (M + [Triflate])/2, 706.74 (M +
2[Triflate])/2; IR mmax/cm−1 3427, 2924, 2877, 1624, 1561, 1511,
1461, 1411, 1354, 1258, 1159, 1119, 1088, 1030, 957, 823, 756,
638, 573, 516.
Tb·3. was formed in 93% yield. Calc. for C40H59N7O12Tb:
[M + H peak] m/z = 988.3475. Found: 988.3458 (−1.7 ppm);
dH (CD3CN, 400 MHz) 7.13, 3.38, 1.94, 1.09, −3.56; MS (MeCN,
ES+) m/z Expected 987.34. Found: 988.26 (M + H), 494.67 (M +
2H)/2, 1010.34 (M + Na), 505.65 (M + Na)/2; IR mmax/cm−1
3481, 3111, 2987, 2927, 1612, 1504, 1460, 1408, 1276, 1257, 1165,
1086, 1030, 802, 760, 721, 639, 574, 517.
12 S. Faulkner, B. P. Burton-Pye, T. Kahn, L. R. Martin, S. D. Wray
and P. J. Sakabara, Chem. Commun., 2002, 1668.
13 R. S. Dickins, S. Aime, A. S. Batsanov, A. Beeby, M. Botta, J. I.
Bruce, J. A. K. Howard, C. S. Love, D. Parker, R. D. Peacock and H.
Puschmann, J. Am. Chem. Soc., 2002, 124, 12697.
14 T. Gunnlaugsson, A. J. Harte, J. P. Leonard and K. Senechal, Chem.
Commun., 2004, 782; T. Gunnlaugsson, A. J. Harte, J. P. Leonard and
K. Senechal, J. Am. Chem. Soc., 2003, 125, 12062; T. Gunnlaugsson,
C. P. McCoy and F. Stomeo, Tetrahedron Lett., 2004, 45, 8403;
Gunnlaugsson, A. J. Harte, J. P. Leonard and M. Nieuwenhuyzen,
Supramol. Chem., 2003, 45, 505; T. Gunnlaugsson, A. J. Harte, J. P.
Leonard and M. Nieuwenhuyzen, M., Chem. Commun., 2002, 2134.
15 T. Gunnlaugsson, Tetrahedron Lett., 2001, 42, 8901; T. Gunnlaugs-
Tb·4. was formed in 98% yield. Calc. for C42H63N7O13Tb:
[M + H peak] m/z = 1032.3737. Found: 1032.3741 (+ 0.4 ppm);
dH (CD3CN, 400 MHz) 7.65, 7.28, 6.98, 6.18, 5.48, 4.04, 3.59,
3.43, 1.34, 1.28, 1.14, 0.75, −1.47; MS (MeCN, ES+) m/z
Expected: 1031.37. Found: 1032.23 (M + H), 516.56 (M +
2H)/2, 344.73 (M + 3H)/3; IR mmax (cm−1) 3444, 2924, 2885,
1611, 1545, 1459, 1408, 1260, 1169, 1080, 1031, 841, 802, 761,
721, 640, 575, 518.
son, D. A. Mac D
o´naill and D. Parker, J. Am. Chem. Soc., 2001, 123,
12866; T. Gunnlaugsson, D. A. Mac Do´naill and D. Parker, Chem.
Commun., 2000, 93; O. Reany, T. Gunnlaugsson and D. Parker, Chem.
Commun., 2000, 473.
16 A communication describing some of the work discussed herein
was recently published: T. Gunnlaugsson and J. P. Leonard, Chem.
Commun., 2003, 2424.
Acknowledgements
17 Other examples of bis-macrocylic cyclen complexes include: C. Li
and W. T. Wong, Tetrahedron Lett., 2004, 45, 6055; S. J. A. Pope,
A. M. Kenwright, V. A. Boote and S. Faulkner, Dalton Trans., 2003,
3780; C. Li and W.-T. Wong, Chem. Commun., 2002, 2034.
18 A. T. Harootunian, J. P. Y. Kao, B. K. Eckert and R. Y. Tsien,
J. Biol. Chem., 1989, 264, 19458; A. P. de Silva, H. Q. N. Gunaratne,
T. Gunnlaugsson and M. Nieuwenhuyzen, Chem. Commun., 1996,
1967.
19 T. Gunnlaugsson, H. Q. N. Gunaratne, M. Nieuwenhuyzen and
J. P. Leonard, J. Chem. Soc., Perkin Trans. 1, 2002, 1954; T.
Gunnlaugsson and J. P. Leonard, J. Chem. Soc., Perkin Trans. 2, 2002,
1980.
This work was supported by National Pharmaceutical Biotech-
nology Center, Bio Research Ireland, Enterprise Ireland (post-
graduate scholarship to JPL), Trinity College Dublin, Center for
Synthesis and Chemical Biology and Kinerton Ltd. We thank
Dr John E. O’Brien for his assistance.
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3 2 1 2
D a l t o n T r a n s . , 2 0 0 5 , 3 2 0 4 – 3 2 1 2