Intramolecular sensitisation of lanthanide(III) luminescence by acetophenone-containing ligands: The critical effect of para-substituents and solvent

Article abstract of DOI:10.1039/b105966c

Tetraazamacrocyclic ligands have been prepared in which three of the four nitrogen atoms are functionalised with carboxylate donors and the fourth is alkylated with apara-substituted acetophenone group {-CH₂C(O)C₆H₄-X, whe

Full text of DOI:10.1039/b105966c

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Intramolecular sensitisation of lanthanide(III) luminescence
by acetophenone-containing ligands: the critical effect of
para-substituents and solvent
Andrew Beeby,* Lisa M. Bushby, Davide Maffeo and J. A. Gareth Williams*
Department of Chemistry, University of Durham, South Road, Durham, UK DH1 3LE
Received 5th July 2001, Accepted 5th October 2001
First published as an Advance Article on the web 28th November 2001
Tetraazamacrocyclic ligands have been prepared in which three of the four nitrogen atoms are functionalised with
carboxylate donors and the fourth is alkylated with a para-substituted acetophenone group {–CH2C(O)C6H4–X,
where X = H, OMe, NMe2}. The europium(), gadolinium() and (for X = H) terbium() complexes of these
potentially octadentate ligands have been prepared. The unsubstituted and methoxy-substituted ligands sensitise the
europium() emissive state with high efficiency in aqueous solution. Calculation of the pure radiative lifetime, based
on the contribution of the 5D0
7F1 transition to the total integrated emission intensity, has allowed an estimate
of the efficiency of energy transfer to be made. Sensitisation of europium luminescence also occurs in the complex
of the dimethylamino-substituted ligand but the process is highly solvent-dependent: very efficient sensitisation is
observed in dichloromethane and DMSO, but the complex is non-emissive in water and only slightly emissive in
acetonitrile. UV-Visible absorption spectra indicate that in all the solvents investigated, the carbonyl oxygen of
the ligand is directly coordinated to the metal ion. The intensity of the hypersensitive 5D0
7F2 transition in
the three complexes mirrors the degree of polarisation of the ketone C᎐O bond.
᎐
particularly suitable as sensitisers,6 provided that there is a
reasonable match between the triplet energy and the emissive
level (or a higher excited level) of the lanthanide such that ηET
is also optimal (the energy gap should, however, be at least
1500 cmϪ1 if back energy transfer to the chromophore is to be
minimised). A striking recent example of ketone-sensitised
lanthanide luminescence is to be found in the 1 : 1 complex
formed between Eu(fod)3 (Hfod = 1,1,1,2,2,3,3-heptafluoro-7,7-
dimethyloctane-4,6-dione) and Michler’s ketone, 4,4Ј-bis(N,NЈ-
dimethylamino)benzophenone, in benzene solution.7 Here, the
substituted benzophenone acts as an auxiliary ligand and sensi-
tises the metal ion very efficiently. Our recent work investigated
stable, water soluble Eu3ϩ and Tb3ϩ complexes of a ligand
incorporating a benzophenone group covalently-bound via an
amide linker, which gave impressive quantum yields in aqueous
solution.6 We report here on the preparation of related tetra-
azamacrocyclic ligands incorporating para-substituted aceto-
phenone groups directly linked (via the CH2 group) to one of
the nitrogen atoms of the macrocycle, such that the ketone oxy-
gen can potentially act as a donor to a bound lanthanide ion.
The ketone-sensitised luminescence of the europium complexes
of these ligands is described.
Introduction
Although first observed 60 years ago,1 the sensitisation of
lanthanide luminescence by organic chromophores is a subject
which continues to attract a great deal of attention, owing
primarily to its potential use in luminescent probes and sensors
and for light amplification and frequency conversion.2–4 Two
characteristic properties of lanthanide luminescence are central
to such applications, namely the long lifetimes of emission
under ambient conditions and the line-like nature of the emis-
sion spectra. Many applications require water-soluble com-
plexes and this poses a challenge in the design and preparation
of suitable complexes, since the lanthanide() ions have a high
affinity for water molecules as ligands and their excited states
are efficiently quenched by water. Successful complexes will
have high thermodynamic and kinetic stability with respect to
metal ion dissociation and ideally saturate the coordination
shell of the metal ion, to prevent water molecules from binding.
The incorporation of appropriate organic chromophores into
the complex to act as efficient sensitisers of the lanthanide
excited states is also an important objective in overcoming the
problem of the very low extinction coefficients of the Ln3ϩ ions
(typically ε < 1).
Studies on several chromophores have demonstrated the
importance of the triplet state in the energy transfer process.5
The overall quantum yield of luminescence, φlum, is determined
by the triplet yield of the chromophore (φT), the efficiency
of energy transfer (ηET) and the efficiency of metal centred
luminescence (ηLn):
Results and discussion
Synthetic routes
Ligands based on the tetraazamacrocycle 1,4,7,10-tetraaza-
cyclododecane (cyclen) tri- or tetra-N-substituted with
carboxylate donors are well-known to form lanthanide()
complexes of exceptional kinetic and thermodynamic stab-
ility.3,8,9 For example, the Gd3ϩ complex of the tetraacetate is
sufficiently stable for use in vivo in millimolar quantities as
a contrast agent for MRI.9 The ketone-substituted ligands
L1–L3 were synthesised in order to explore the efficacy of
ꢀlum = ꢀTؒηETؒηLn
(1)
We have recently demonstrated that aromatic ketones with
n,π* triplet states, which have high triplet quantum yields, are
48
J. Chem. Soc., Dalton Trans., 2002, 48–54
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b105966c

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acetophenones as sensitisers of the metal excited state in the
europium complexes. The synthetic routes to the compounds
are summarised in Scheme 1. Reaction of cyclen with three
equivalents of tert-butylbromoacetate in chloroform at room
temperature for 72 hours, in the presence of one equivalent of
potassium carbonate, led primarily to the tert-butyl ester of
DO3A, 4, which could be separated from small amounts of the
tetra- and di-alkylated macrocycle by chromatography on silica.
The ester was subsequently alkylated with the appropriate α-
bromoacetophenone, 1a–3a, in acetonitrile in the presence of a
catalytic amount of KI and potassium carbonate as the base.
Compounds 2a and 3a were prepared from the parent para-
substituted acetophenones. It is well-known that the bromin-
ation of arylmethylketones often leads to a complex mixture
of products because aromatic ring substitution and bromine
addition to the enol form often compete effectively with radical
side-chain halogenation. Competitive ring bromination is
particularly facile in amino-substituted compounds, due to the
activating effect of the electron-donating amino group. We
adopted routes to these compounds based on recently described
procedures for the efficient, selective preparation of side-chain
brominated compounds. The para-methoxy-substituted com-
pound was prepared by bromination of 4Ј-methoxyaceto-
phenone using HBr in the presence of tert-butylhydroperoxide,
a combination of reagents that has been reported recently
for in situ generation of positive halogen species avoiding
the hazards associated with the preparation of tert-butyl-
hypobromite, and which leads to selective side-chain bromin-
ation of acetophenone itself, with no ring bromination.10 We
found this method to be equally selective for side-chain bromin-
ation of the para-methoxy substituted compound. 2-Bromo-
4Ј-dimethylaminoacetophenone was prepared in three steps
from 4Ј-dimethylaminoacetophenone according to a literature
procedure.11
Following alkylation of the secondary amine in 4 with the
α-bromoketones, the tert-butyl esters (1b–3b) were cleaved
using trifluoroacetic acid, to generate the ligands L1–L3. The
europium and gadolinium complexes were prepared by reaction
with an equimolar amount of the lanthanide() nitrate in
aqueous solution and subsequently purified by chromatography
on a short column of alumina. The terbium() complex of L1
was prepared similarly. All the complexes were characterised
by electrospray mass spectrometry. Although the large para-
magnetism and severe line-broadening associated with the
gadolinium() and terbium() ions prohibited NMR analysis,
the smaller shifts and narrower line-widths induced by euro-
1
pium() allowed the H NMR spectra of the europium com-
plexes to be recorded, revealing in each case the well-established
pattern of resonances characteristic of square-antiprismatic
complexes found with related ligands.12
Scheme 1
J. Chem. Soc., Dalton Trans., 2002, 48–54
49

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Photophysical properties
Phosphorescence of the gadolinium complexes. Aqueous and
EPA† solutions of the Gd3ϩ complexes showed no luminescence
at room temperature but, upon cooling to 77 K, displayed
intense phosphorescence with some vibrational structure, due
to emission from the n–π* triplet state of the chromophore.
From the positions of the highest energy band in the spectrum,
the triplet energy of GdL1 was determined to be 25600 200
cmϪ1 in EPA (25300 cmϪ1 in H2O). As observed for the singlet
excited state, introduction of the methoxy or dimethylamino
substituents led to a progressive reduction in the energy of the
triplet state: a value of 24500 200 cmϪ1 was determined for
GdL2 (EPA and H2O), and 21000 200 cmϪ1 for GdL3 in EPA
(20000 cmϪ1 in H2O). Phosphorescence lifetimes in EPA at 77 K
were determined to be 10.4, 7.9 and 15.9 ms for the three com-
plexes respectively.
Absorption spectra. The complexes of L1 displayed ground-
state absorbance maxima at 265 nm in aqueous solution, a
value not significantly different from that of the free ligand
or acetophenone itself. The corresponding band in the 4Ј-
methoxy-substituted complexes, GdL2 and EuL2, was red-
shifted to 305 nm due to conjugation of the electron-donating
methoxy group with the carbonyl acceptor; again, the spectrum
of the complex was not significantly different from that of the
ligand.
The more strongly donating dimethylamino group has a
much larger effect on the π–π* singlet excited state in L3, shift-
ing the band to 339 nm. Moreover, the band is more red-shifted
in the complexes by 30 nm, with a maximum at 372 nm and
extending to beyond 400 nm (Fig. 1). This is indicative of a
EuL1 and EuL2: emission spectra and lifetimes. In each case,
the triplet states are much too low in energy to act as sensitisers
of the lowest energy excited state of gadolinium() [E(6P7/2) =
32000 cmϪ1], but are appropriately placed for potential sensi-
tisation of europium() [E(5D0) = 17300, E(5D1) = 19000 cmϪ1].
Upon excitation into the π–π* bands, both EuL1 and EuL2 did
indeed display intense metal-centred luminescence, both in
alcohol and aqueous solution. The luminescence excitation
spectra corresponded well with the ground-state absorption
spectra, confirming that the emission was due to sensitisation
by the chromophore and (based on previous studies)5,6 prob-
ably via the triplet state of the acetophenone.
Lifetimes of emission are summarised in Table 1. From
the values in H2O and D2O, the hydration number q (which
provides an indication of the number of metal-bound water
molecules) was determined using the Horrocks equation13 to be
1.24 and 1.20 for EuL1 and EuL2 respectively. After correction
for the weaker effect of outer-sphere water molecules,14 these
values are reduced to 1.10 and 1.05 respectively, clearly indicat-
ing that there is one metal-bound water molecule in both cases.
This is consistent with observations on the complexes of struc-
turally related octadentate amide ligands where a metal-bound
water molecule increases the coordination number to nine12
and, as noted above, supports the proposal that the carbonyl
oxygen is coordinated to the metal, preventing the entry of a
second water molecule.
Fig. 1 Absorbance spectra of L3 (---) and of EuL3 (—) in ethanol
solution at 293 K.
much stronger interaction of the carbonyl group with the metal
ion in this case, giving rise to a complex with a higher charge-
transfer character. For example, an effect of this type has been
reported recently upon coordination of Michler’s ketone [4,4Ј-
bis(N,N-dimethylamino)benzophenone] to Eu(fod)3 in benzene,
where a ground-state complex is formed characterised by an
intense absorption band centred at 414 nm.7 The authors
attribute this to a bathochromic shift of the first singlet–singlet
excited state noting that, since excitation of this transition
moves the electron density towards the carbonyl group, the
presence of the lanthanide ion would be expected to have a
large effect on its energy. However, coordination only occurred
in non-coordinating solvents. In contrast, in the present
instance, the carbonyl group remains bound even in aqueous
solution, presumably because the seven other ligating sites
of the macrocyclic ligand are able to maintain it in a position
suitable for binding.
The emission spectra of the two complexes EuL1 and EuL2
5
were very similar (Fig. 2). A sharp D0
7F0 band of modest
intensity at 579.8 nm is observed in each case. The relative con-
tribution of the purely magnetic dipole 5D0 7F1 transition to
the total integrated emission intensity is similar for both com-
5
plexes, but the hypersensitive D0
7F2 band is rather more
intense in EuL2 (vide infra).
Overall quantum yields of metal-centred luminescence, φlum
,
Such geometric factors should also favour binding of the
carbonyl group in the complexes of L1 and L2, despite the fact
that no shifts in the absorption bands are observed in these
cases. The absence of a red-shift in these complexes does not,
however, mean that the carbonyl group remains uncoordinated,
as evident from the following control experiment. Upon mixing
4,4Ј-dimethoxybenzophenone and Eu(fod)3 in toluene, no sig-
nificant red-shifts nor new bands were observed in the absorp-
tion spectra, in contrast to the observations with Michler’s
ketone. Nevertheless, the europium emission intensity was sub-
stantially increased upon excitation at 365 nm, indicative of
sensitisation of the metal by the benzophenone and hence com-
plex formation by coordination of the ketone to the lanthanide
ion. Moreover, the two complexes were found to contain only
one metal-coordinated water molecule (vide infra), in contrast
to the two water molecules found in complexes of related ligands
offering heptadentate coordination (e.g. those of 1,4,7,10-
tetraazacyclododecane-1,4,7-triacetate, DO3A), lending fur-
ther support to the proposal that the ketone oxygen is indeed
coordinated to the metal.
upon excitation of the acetophenone group are given in Table 1.
In order to assess the efficiency of energy transfer ηET using
these quantum yields, an estimate of both φT and ηLn is required
[eqn. (1) above]. Given that the sensitiser has an n,π* triplet
state, and also that the lanthanide ions have high spin–orbit
coupling constants, it is appropriate to assume that φT (the
quantum yield of triplet formation) is close to 1.6 The efficiency
of metal-centred luminescence, ηLn, can be calculated from the
observed emission lifetime τobs, provided that the pure radiative
lifetime τR is available, since:
ηLn = τobs/τR
(2)
† EPA refers to the solvent system: ethanol/isopentane/diethyl ether
in the ratio 2/5/5 by volume. This solvent offers excellent properties
for measurement of spectra and lifetimes at low temperature, with
little tendency for cracking. The solubility of the complexes in EPA,
although minimal, is sufficient to obtain solutions with suitable
absorbances.
50
J. Chem. Soc., Dalton Trans., 2002, 48–54

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Table 1 Photophysical parameters of the europium and gadolinium (data in italics) complexes of L1–L3 a
e
e
Complex
ET/cmϪ1 b
Absorbance λmax/nm
τH O/msc
τD O/msc
qd
φH O
φD O
2
2
2
2
LnL1
LnL2
LnL3
25600
25300
24500
24500
21000
20000
265
305
375
0.62
2.26
2.18
—
1.10
1.05
—
0.006
0.098
—
0.021
0.34
—
0.63
f
a For the terbium complex of ligand L1: τH O = 1.60 ms, τD O = 2.6 ms, q = 0.98; φH O = 0.12, φD O = 0.23. b Triplet energy of the acetophenone
2
2
2
2
chromophore 200 cmϪ1, as estimated from the phosphorescence spectra of the gadolinium complexes at 77 K. c Lifetimes of the europium-centred
emission monitored at 593 nm, 293 K; uncertainty 5%. d q is the hydration state (number of coordinated water molecules) as determined from τH O
2
and τD O using the equation of Parker et al.14 e Quantum yields of the europium complexes at 293 K, measured using cresyl violet in methanol and
2
rhodamine 101 in acidified ethanol as standards; uncertainty 10%. f EuL3 was non-emissive in aqueous solution.
Table 2 Calculated values of τR, ηLn, ηET and Σknr for EuL1 and EuL2
a
using experimentally determined quantities τobs, φlum and [I(0,1)/Itot
]
EuL1
H2O
EuL2
H2O
D2O
D2O
[I(0,1)/Itot
τR/ms
kR/sϪ1
τobs/ms
ηLn
φlum
ηET
Σknr/sϪ1
]
0.24
7.37
136
0.25
7.74
129
2.26
0.29
0.21
0.72
0.22
6.65
150
0.21
6.62
151
2.18
0.33
0.34
1.0
0.62
0.63
0.084
0.058
0.71
0.094
0.093
0.99
1480
313
1440
308
a [I(0,1)/Itot] is the relative contribution of the 5D0
7F1 band intensity,
I(0,1), to the total integrated emission intensity, Itot; τR is the pure radia-
tive lifetime determined from [I(0,1)/Itot] using the method described in
the text; kR is the radiative rate constant = 1/τR; ηLn is the efficiency of
metal-centred luminescence obtained using eqn. (2); ηET is the efficiency
of energy transfer calculated using eqn. (1) and assuming that φT = 1;
Σknr (the sum of the non-radiative decay constants) = [(1/τobs) Ϫ kR].
given a value for the spontaneous emission probability A(0,1)
of the 5D0
7F1 transition and using eqn. (4), it is possible to
estimate τR from the relative contribution of this band to the
experimentally determined emission spectrum:
1/τR = A(0,1)/β(0,1) = A(0,1)[Itot/I(0,1)]
(5)
Fig. 2 Emission spectra of EuL1 (a) and EuL2 (b) in solution in D2O at
293 K. The excitation wavelength was 265 and 305 nm respectively;
excitation and emission bandpasses of 2.5 nm.
where [Itot/I(0,1)] is the ratio of the total integrated intensity of
the corrected europium() emission spectrum to the intensity
of the 5D0
7F1 band. The spontaneous emission probability,
The pure radiative lifetime of europium() in different
environments can be estimated from the emission spectrum
as follows.15 The total radiative relaxation rate kR (=1/τR) of
A(0,1), can be determined directly from the theoretically calc-
ulated dipole strength of this transition, leading to a value of
32.4 sϪ1 in aqueous solution.‡
5
the emissive excited state, D0, is the sum of the spontaneous
For complexes EuL1 and EuL2, the results of these calc-
ulations [eqns. (1)–(3)], using the relative contribution of the J1
band in the corrected emission spectrum together with the
experimentally determined values of τobs and φlum, leads to the
values of τR, ηLn, ηET and Σknr given in Table 2. It can be seen
that the energy transfer efficiencies are high in each case and
especially so for the methoxy-substituted system. The introduc-
tion of the methoxy substituent lowers the triplet energy by
about 1000 cmϪ1 (Table 1), leading to a better match with the
emission probabilities, A(0,J), to the lower 7FJ levels.
kR = ΣJ A (0,J)
(3)
The relative contribution of each 5D0
7FJ transition to the
spectrum, the branching ratio β, is the ratio of the intensity
of the band to the total intensity in the corrected emission
spectrum, and is determined by the spontaneous emission
probability:
β(0,J) = A(0,J)/ΣJ A(0,J) = A(0,J)/kR = A(0,J)ؒτR (4)
‡ Application of the Einstein coefficient to express the rate of relax-
ation from an excited state ψJ to a final state ψJЈ under a magnetic dipole
mechanism leads to: A(ψJ, ψJЈ) = {64π4σ3/3h(2J ϩ 1)}ؒn3ؒSmd(ψJ, ψJЈ),
where σ is the energy gap between the two states (cmϪ1), n is the refrac-
tive index of the medium and Smd(ψJ, ψJЈ) is the magnetic dipole line
strength.17 This last quantity has been calculated theoretically for the
The forbidden lanthanide() (f–f ) emission bands consist
of magnetic dipole (MD) and induced electric dipole (ED)
transitions. The former are virtually independent of the ion’s
surroundings, in contrast to the latter where the geometry and
ligating atoms have a significant effect on the transition prob-
5D0
7F1 transition of Eu3ϩ in a number of studies and verified
experimentally; we have used the value of Kirby and Richardson18
(884 × 10Ϫ8 Debye2) together with an energy of 17010 cmϪ1 as the
baricentre of the transition and n = 1.334 for H2O, leading to the value
abilities. The 5D0
7F1 (J1) band of Eu3ϩ centred at 593 nm is
entirely MD and consequently has an oscillator strength that is
independent of the ligand field and complex symmetry.16 Thus,
of 32.4 sϪ1
.
J. Chem. Soc., Dalton Trans., 2002, 48–54
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Table 4 Calculated values of τR, ηLn, ηET and Σknr for EuL3 in different
solventsa
Table 3 Relative contributions of the 5D0
7FJ bands in the emission
spectra of the europium complexes of L1, L2 and L3 in ethanol solution,
293 K
MeOH
EtOH
iPrOH
DMSO
EuL1
EuL2
EuL3
[I(0,1)/Itot
]
0.14
4.31
232
0.15
4.27
234
0.15
4.26
235
0.69
0.16
0.10
0.62
7900
0.12
2.79
359
1.29
0.46
0.35
0.96
418
J0/J1
J2/J1
J3/J1
J4/J1
1.11
0.67
0.20
0.78
0.40
1.43
0.23
0.97
0.15
3.22
0.23
2.74
τR/ms
kR/sϪ1
τobs/ms
ηLn
φlum
ηET
Σknr/sϪ1
0.12
0.35
0.029
0.014
0.48
0.082
0.086
1.05
5
5
acceptor D1 and D0 states of the europium ion. As expected,
ηET does not change significantly on going from H2O to D2O,
and the main factor that limits the observed luminescence
quantum yield of these complexes is the rather low efficiency of
metal-centred luminescence, even in D2O.
1220
2630
a Parameters are defined in the footnotes to Table 2.
EuL3: emission spectra and lifetimes. The behaviour of EuL3
is very different from that of the complexes discussed above.
The emission spectrum recorded in ethanol solution upon excit-
ation of the dimethylaminobenzene group is shown in Fig. 3.
Fig. 4 Integrated emission intensity of EuL3 in several solvents (λex
370 nm) plotted against dielectric constant.
=
of the emission was observed in DMSO and alcohol solutions,
and the measured lifetime was found to vary substantially with
solvent (Table 4). Emission in CH3CN, CH2Cl2 and CHCl3
displayed non-exponential decay kinetics, possibly due to the
slow exchange between the two species with and without a
metal-bound water molecule.20
Fig. 3 Emission spectrum of EuL3 in solution in ethanol at 293 K;
λex = 370 nm; bandpass = 2.5 nm.
The very sensitive dependence of the emission intensity and
lifetime on solvent is probably a combination of effects, as
revealed by applying the above analysis of spectra and lifetimes
to EuL3. The results of this treatment are summarised in Table
4, which show that the solvent has not only an effect on the
non-radiative decay pathways, but also a profound influence on
both the pure radiative lifetime and the efficiency of energy
transfer. The pure radiative lifetime is significiantly shorter in
DMSO than in alcohols, whilst the non-radiative decay path-
ways (Σknr) are less significant, which together account for the
substantially higher quantum yield observed in DMSO. The
efficiency of energy transfer is close to unity.
The hypersensitive ∆J = 2 transition now dominates the spectra,
being much more intense than the ∆J = 1 band. The ratio of the
5
integrated intensity of each of the D0
7FJ bands to the
5D0
7F1 intensity for the three complexes are given in Table 3.
A clear trend may be discerned: the relative intensity of the
∆J = 2 transition increases progressively upon going from
the unsubstituted to the methoxy- and subsequently the
dimethylamino-substituted complexes. The induced electric
dipole ∆J = 2 transition in europium is hypersensitive: its inten-
sity is highly dependent on both the coordination geometry and
identity of the coordinating atoms. Attempts to explain hyper-
sensitivity have been based on static-coupling models (eg. Judd–
Ofelt theory) and on dynamic coupling (or ligand polarisation)
mechanisms. In the latter, the intensity of hypersensitive tran-
sitions is related explicitly to the dipolar polarisabilities of
the ligand atoms or groups, (as well as to the geometry of the
complex).19 Thus, the distinctive increase in the intensity of the
∆J = 2 band may be rationalised in terms of the more polarised
Conclusion
In summary, the complexes reported here represent a new class
of compound in which an acetophenone group covalently
linked to the macrocyclic ligand is able to bind to the coordin-
ated lanthanide ion, promoting efficient energy transfer from
chromophore to metal. Introduction of a methoxy substituent
into the para position of the acetophenone further increases
the efficiency, whilst a dimethylamino substituent leads to high
emission intensities in non-aqueous solvents only.
Ar᎐C–OϪ character of the ketone carbonyl group upon intro-
᎐
duction of the increasingly electron-donating methoxy and
dimethylamino substituents. The observed trend confirms, then,
that the ketone group is coordinated to the metal ion in each of
the three complexes.
The total emission intensity of EuL3 was found to be very
sensitive to the solvent. In particular, despite the reasonable
quantum yields in non-aqueous solvents (Table 4), no emission
was detectable in aqueous solution (H2O or D2O). For the other
solvents examined, luminescence was observed in each case,
although the intensity varied erratically (Fig. 4), showing no
correlation with the dielectric constant, nor with other solvent
parameters such as that of Reichardt. Monoexponential decay
Experimental
General
Cyclen was supplied by Strem and used as supplied. The prep-
aration of 4Ј-dimethylamino-2-bromoacetophenone followed
procedures described recently in the literature starting from
4Ј-aminoacetophenone,11 which was obtained from Aldrich.
52
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2-Bromoacetophenone and 4Ј-methoxyacetophenone are also
available commercially. Chromatography was carried out on
silica gel (60, 40–63 µm, Fluorochem) or on alumina (neutral,
Brockmann I). Solvents were Analar or HPLC grade, and
water was purified by the Milli Q system. Proton and 13C NMR
spectra were recorded on a Varian Mercury-200 (200 and 50.3
MHz respectively) or a Unity-300 (300 and 75.5 MHz). Proton
spectra were referenced to residual protio solvent resonances
and 13C spectra to the solvent carbon resonance. Electrospray
mass spectra were measured on a VG Platform II instrument.
UV-Visible absorbance spectra were recorded using a Unicam
UV-2 spectrometer using quartz cuvettes of 1 cm path-
length. Steady-state emission spectra were recorded using an
Instruments S.A. Fluromax and lifetimes were measured using
a Perkin-Elmer LS 50B instrument. An Oxford Instruments
variable temperature liquid nitrogen cryostat (DN1704) was
used for recording the phosphorescence spectra of the chromo-
phores at 77 K. Elemental analyses were carried out using an
Exeter Analytical E-440 Analyser.
127.7, 126.6, 81.1, 81.0, 59.2, 54.6, 52.5, 52.0 (br), 49 (br), 26.9,
26.8. m/z (ESϩ): 633 (M ϩ Hϩ).
1-(4Ј-Methoxy-2-acetophenone)-4,7,10-tris(tert-butoxycarb-
oxymethyl)-1,4,7,10-tetraazacyclododecane, 2b. Compound 2b
was prepared in a similar manner, starting from 4 (800 mg,
1.55 mmol), potassium carbonate (258 mg, 1.86 mmol) and
4Ј-methoxy-2-bromoacetophenone (426 mg, 1.86 mmol). The
solvent was again acetonitrile and the reaction time 96 h at
reflux. Work-up and purification was carried out in the same
way, and the desired compound eluted from the column under
very similar conditions to 1b; yield 55%. δH (CDCl3, 300 MHz):
7.77 (2 H, d, J = 8.7, H2Ј), 6.82 (2 H, d, J = 8.7 Hz, H3Ј), 3.76
(3 H, s, OCH3), 3.40–2.10 (24 H, m, CH2CH2 ring and CH2
acetates), 1.34 [27 H, s, C(CH3)3]. δC (CDCl3, 50.3 MHz):
197.6, 172.5, 163.7, 130.4, 129.7, 128.5, 113.7, 113.5, 81.9, 81.8,
59.6, 55.5, 55.4, 53 (br), 49 (br), 27.7, 27.6. m/z (ESϩ): 685
(M ϩ Hϩ).
1-(4Ј-Dimethylamino-2-acetophenone)-4,7,10-tris(tert-butoxy-
carboxymethyl)-1,4,7,10-tetraazacyclododecane, 3b. This com-
pound was prepared similarly, from 4 (750 mg, 1.46 mmol),
caesium carbonate (570 mg, 1.75 mmol) and 4Ј-dimethylamino-
2-bromoacetophenone (354 mg, 1.46 mmol). Solvent, reaction
time, work-up and purification was as above, with the desired
compound requiring slightly more polar conditions for elution
from the column (Rf = 0.5 in 4% MeOH–CH2Cl2); yield 53%.
δH (CDCl3, 200 MHz): 7.76 (2 H, d, J = 9.0), 6.61 (2 H, d, J =
9.0 Hz), 3.60–2.10 (24 H, m, CH2CH2 ring, CH2 acetate),
3.05 [6H, s, N(CH3)2], 1.45 [27 H, s, C(CH3)3]. δC (CDCl3,
75.5 MHz): 196.5, 173.0, 172.8, 153.8, 129.8, 123.7, 110.7, 82.0,
81.9, 59.4, 55.9, 55.7, 53 (br), 49 (br), 40.1, 28.0. m/z (ESϩ): 698
(M ϩ Naϩ).
Syntheses
4Ј-Methoxy-2-bromoacetophenone, 2a. A solution of tert-
butylhydroperoxide (70% aq.) (0.42 mL, 3.30 mmol) was added
to a cooled mixture of HBr (48% aq.) (0.56 mL, 3.30 mmol)
in dioxane (15 mL) and the mixture was stirred for 5 minutes.
4Ј-Methoxyacetophenone was added to this solution at room
temperature and the mixture stirred for 30 minutes, before
being heated at 60 ЊC for 72 h. The solvent was removed under
reduced pressure, the residue taken into 10 mL of water and
extracted with dichloromethane (3 × 20 mL). After drying over
magnesium sulfate and removal of solvent, the desired product
was obtained in 85% yield. δH (CDCl3, 300 MHz): 7.95 (2 H, d,
J = 8.9, H2Ј), 6.94 (2 H, d, J = 8.9 Hz, H3Ј), 4.39 (2 H, s, CH2),
L1–L3. The tris-acetate ligands L1–L3 were prepared by
hydrolysis of the tris-tert-butylesters using the following pro-
cedure. Trifluoroacetic acid (20 equiv.) was added to a solution
of the tris-ester (200 mg) in dichloromethane (5 mL), and the
solution stirred at room temperature for 24 h. The solvent was
removed under reduced pressure and the residue washed with
more dichloromethane (3 × 5 mL). Water was then added, and
the pH adjusted to 6–7 using HCl (aqueous, 1 M).
3.86 (3 H, s, CH ). δ (CDCl , 75.5 MHz): 190.0 (C᎐O), 164.2
(C–COCH2), 132.3 and 131.4 (aromatic CH), 114.1 (C–OMe),
55.7 (CH2), 30.9 (CH3). m/z (ESϩ): 253 (100%, M ϩ Naϩ).
᎐
3
C
3
1,4,7-Tris(tert-butoxycarboxymethyl)-1,4,7,10-tetraazacyclo-
dodecane, 4. Tert-butylbromoacetate (3.33 g, 17.08 mmol) in
solution in chloroform (100 mL) was added dropwise over 4
hours to a stirred solution of 1,4,7,10-tetraazacyclododecane
(1 g, 5.69 mmol) in chloroform (300 mL) in the presence of
potassium carbonate (786 mg, 5.69 mmol). After addition was
complete, the solution was stirred at room temperature for
72 hours. Inorganic salts were then separated by filtration and
the solvent removed from the filtrate under reduced pressure.
The residue was purified by chromatography on silica, gradient
elution CH2Cl2 to 5% MeOH–CH2Cl2, Rf = 0.5 (7% MeOH–
CH2Cl2). Yield = 73%. δH (CDCl3, 300 MHz): 3.36 (4 H, s, 2 ×
CH2 acetates), 3.27 (2 H, s, CH2 unique acetate), 3.08–2.86
(16 H, br m, CH2CH2 ring), 1.44 [27 H, s, C(CH3)3]. Spectrum
in agreement with literature data.21 m/z (ESϩ): 515 (M ϩ Hϩ).
Lanthanide(III) complexes. The lanthanide() complexes
were prepared by addition of an equimolar amount of the
lanthanide() nitrate to an aqueous solution of the ligand
(concentration ca. 40 mM). After refluxing for 24 h, alumina
(2 g) was added and the solvent removed under reduced pres-
sure until the solid was dry and free-flowing. The alumina with
adsorbed complex was added to the top of a short column
of alumina, and eluted with CH2Cl2/20% MeOH–CH2Cl2. The
electrospray ionisation mass spectrum of each complex gave,
as the major peak, [M ϩ Hϩ] or [M ϩ Naϩ]. Owing to the
large paramagnetism associated with the gadolinium() and
terbium() ions, analysis by NMR is not feasible for these
complexes, but is possible for europium() where the shifts are
not as large and the line-widths narrower. A full assignment of
the individual resonances, however, requires a dipolar shift
analysis which is beyond the objectives of the current work;
nevertheless, the spectra show very clearly the characteristic
pattern of resonances shown previously to be typical of such
complexes, in which the rigidity imposed by the metal ion leads
to the inequivalence of the four protons of each ethylene unit in
the macrocycle.12
1-(2-Acetophenone)-4,7,10-tris(tert-butoxycarboxymethyl)-
1,4,7,10-tetraazacyclododecane, 1b. A solution of 4 (750 mg,
1.46 mmol), 2-bromoacetophenone (355 mg, 1.75 mmol),
potassium carbonate (242 mg, 1.75 mmol) and a catalytic
amount of KI in acetonitrile (5 mL) was heated at reflux with
stirring for 96 h. The solvent was removed under reduced pres-
sure and the residue taken up into aqueous sodium hydroxide
solution (1 M, 10 mL), from which the product was extracted
into dichloromethane (3 × 10 mL). After drying over potassium
carbonate and removal of solvent, the crude product was puri-
fied by chromatography on alumina, gradient elution from
CH2Cl2 to 2% MeOH–CH2Cl2, Rf = 0.5 (2% MeOH–CH2Cl2).
Yield = 58%. δH (CDCl3, 300 MHz): 7.89 (2 H, d, J = 7.5, H2Ј),
7.57 (1 H, t, J = 7.5, H4Ј), 7.45 (2 H, t, J = 7.5 Hz, H3Ј), 2.30–3.50
(24 H, br m, CH2CH2 ring and CH2 acetates), 1.45 [27 H, s,
C(CH3)3]. δC (CDCl3, 75.5 MHz): 198.6, 171.8, 134.5, 133.7,
For example, for [EuL3], δH (D2O, 200 MHz): 36.3 (1 H), 32.0
(1 H), 31.4 (1 H), 30.6 (1 H) (Hax); 6.1 (4 H, aromatic H); 3.3
(6 H, N(CH3)2); 1.8 (1 H), Ϫ1.2 (1 H), Ϫ1.7 (1 H), Ϫ2.6 (1 H),
Ϫ3.0 (1 H), Ϫ4.6 (1 H), Ϫ6.2 (1 H), Ϫ7.1 (1 H), Ϫ8.8 (3 H
overlapping), Ϫ10.4 (1 H), Ϫ11.5 (1 H), Ϫ12.9 (1 H), Ϫ14.8
(4 H overlapping), Ϫ15.7 (1 H), Ϫ16.7 (1 H) (8 Heq, remaining
J. Chem. Soc., Dalton Trans., 2002, 48–54
53

View Article Online
7 M. H. V. Werts, M. A. Duin, J. W. Hofstraat and J. W. Verhoeven,
Chem. Commun., 1999, 799.
8 For a review, see: V. Alexander, Chem. Rev., 1995, 95, 273.
9 Gadolinium() complexes for use in MRI, including those of
DOTA and related ligands, have been the subject of a recent
comprehensive review: P. Caravan, J. J. Ellison, T. J. McMurry and
R. B. Lauffer, Chem. Rev., 1999, 99, 2293.
10 N. B. Barhate, A. S. Gajare, R. D. Wakharkar and A. V. Bedekar,
Tetrahedron, 1999, 55, 11127.
4 Hax, CH2CO). m/z (ESϩ): 680.1612 (M ϩ Naϩ, calculated
value for C24H34N5O7EuNa = 680.1568).
Similarly, m/z (ESϩ): EuL1: 635 (M ϩ Naϩ); GdL1: 618 (M ϩ
Hϩ); TbL1: 619 (M ϩ Hϩ); EuL2: 667.1266 (M ϩ Naϩ, cal-
culated value for C23H31O8N4EuNa = 667.1252); found C 36.82,
H 4.89, N 7.32% (C23H31O8N4Euؒ5H2O requires C 37.60,
H 5.59, N 7.63%); GdL2: 671 (M ϩ Naϩ); found C
36.84, H 4.82, N 7.45% (C23H31O8N4Gdؒ5H2O requires C 37.35,
H 5.55, N 7.58%); GdL3: 685 (M ϩ Naϩ).
11 Z. Diwu, C. Beachdel and D. H. Klaubert, Tetrahedron Lett., 1998,
39, 4987.
12 R. S. Dickins, J. A. K. Howard, C. L. Maupin, J. M. Moloney,
D. Parker, J. P. Riehl, G. Siligardi and J. A. G. Williams, Chem. Eur.
J., 1999, 5, 1095–1105.
Acknowledgements
13 W. De W. Horrocks, Jr. and D. R. Sudnick, Acc. Chem. Res., 1981,
14, 384.
14 A. Beeby, I. M. Clarkson, R. S. Dickins, S. Faulkner, D. Parker, L.
Royle, A. S. de Sousa, J. A. G. Williams and M. Woods, J. Chem.
Soc., Perkin Trans. 2, 1999, 493–504.
We thank the EPSRC and Opsys Limited for a CASE award
(L. M. B.), the University of Durham for a studentship (D. M.)
and the Royal Society and the Nuffield Foundation for grants
towards the purchase of equipment.
15 W. T. Carnall, in Handbook on the Physics and Chemistry of Rare
Earths, eds. K. A. Gschneidner, Jr. and L. Eyring, North Holland
Publishing Co., Amsterdam, 1979, ch. 24; A similar treatment has
been applied by others; for example, M. H. V. Werts, Ph.D. Thesis,
University of Amsterdam, 2000.
16 (a) R. D. Peacock, Struct. Bonding (Berlin), 1975, 22, 83; (b) A. F.
Kirby, D. Foster and F. S. Richardson, Chem. Phys. Lett., 1983, 95,
507.
17 The methods by which the spontaneous emission probabilities may
be calculated have been discussed widely, for example, ref. 15 or:
M. J. Weber, T. E. Varitimos and B. H. Matsinger, Phys. Rev. B,
1973, 8, 47.
References
1 S. I. Weissman, J. Chem. Phys., 1942, 10, 214.
2 N. Sabbatini, M. Guardigli and J.-M. Lehn, Coord. Chem. Rev.,
1993, 123, 201.
3 D. Parker and J. A. G. Williams, J. Chem. Soc., Dalton Trans., 1996,
3613.
4 M. P. Oude Wolbers, F. C. J. M. van Veggel, F. G. A. Peters, E. S. E.
van Beelen, J. W. Hofstraat, F. A. J. Geurts and D. N. Reinhoudt,
Chem. Eur. J., 1998, 4, 772.
5 For example: B. Alpha, R. Ballardini, V. Balzani, J.-M. Lehn,
S. Perathoner and N. Sabbatini, Photochem. Photobiol., 1990, 52,
299; A. Beeby, D. Parker and J. A. G. Williams, J. Chem. Soc., Perkin
Trans. 2, 1996, 1565; A. Beeby, S. Faulkner, D. Parker and J. A. G.
Williams, J. Chem. Soc., Perkin Trans. 2, 2001, 1268.
6 A. Beeby, L. M. Bushby, D. Maffeo and J. A. G. Williams, J. Chem.
Soc., Perkin Trans. 2, 2000, 1281.
18 A. F. Kirby and F. S. Richardson, J. Phys. Chem., 1983, 87, 2544.
19 The dynamic coupling model has been developed in terms of a
polarisability tensor α(L) of the ligand: S. F. Mason, R. D. Peacock
and B. Stewart, Mol. Phys., 1975, 30, 1829.
20 A. S. Batsanov, A. Beeby, J. I. Bruce, J. A. K. Howard, A. M.
Kenwright and D. Parker, Chem. Commun., 1999, 1011.
21 M. Woods, Ph.D. Thesis, University of Durham, 1998.
54
J. Chem. Soc., Dalton Trans., 2002, 48–54