Sensitization of europium(III) luminescence by benzophenone-containing ligands: Regioisomers, rearrangements and chelate ring size, and their influence on quantum yields

Article abstract of DOI:10.1021/ic701113c

A series of europium(III) complexes based on the macrocyclic azacarboxylate structure, DO3A, have been investigated, incorporating benzophenone appended at N10 of the macrocycle via linkers containing amide bonds (H₃DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid). Complexes [EuL ^1-3] incorporate N¹⁰-CH₂CONH-BP linkers (BP = benzophenone), which allow formation of a five-membered chelate ring containing the metal ion upon chelation of the amide oxygen; these three isomeric complexes differ from one another in the substitution position of the BP unit, namely para, meta, and ortho for L¹, L², and L³ respectively. The quantum yields of europium luminescence sensitized via the chromophore are found to be highly dependent upon the position of substitution, being 20 times smaller for the ortho compared to the para-substituted complex. A related para-substituted BP complex [EuL⁴], prepared by an unusual Michael reaction of the azamacrocycle with a BP-containing acrylamide, incorporates an additional methylene unit in the linker, namely N ¹⁰-CH₂CH₂CONH-BP. Despite the longer linker, this complex equals the luminescence quantum yield achieved with [EuL ¹] (Φ_lum = 0.097 and 0.095, respectively, in H ₂O at 298 K). Analysis of the pertinent kinetics reveals that the decreased energy transfer efficiency in this complex, arising from the longer donor-acceptor distance, is compensated by an increased radiative rate constant. Under basic conditions, the ortho-substituted complex [EuL³] undergoes an intramolecular rearrangement to generate an unprecedented complex [EuL₅] incorporating a 4-phenyl-2-hydroxyquinoline unit directly bound to the ring nitrogen. Although this complex is a poor emitter, an analogous complex obtained from 2-amino-acetophenone, which generates 4-methyl-2-hydroxyquinoline during the corresponding rearrangement, is an order of magnitude more emissive while still benefiting from relatively long-wavelength absorption. The emission from this complex is pH sensitive, being dramatically quenched under mildly basic conditions.

Full text of DOI:10.1021/ic701113c

Inorg. Chem. 2007, 46, 9438−9449
Sensitization of Europium(III) Luminescence by
Benzophenone-Containing Ligands: Regioisomers, Rearrangements and
Chelate Ring Size, and Their Influence on Quantum Yields
Andrew J. Wilkinson,† Davide Maffeo,† Andrew Beeby,† Clive E. Foster,‡ and J. A. Gareth Williams*,†
Department of Chemistry, UniVersity of Durham, South Road, Durham, DH1 3LE U.K. and
Fujifilm Imaging Colorants Ltd, P.O. Box 42, Hexagon House, Blackley, Manchester, M9 8ZS
U.K.
Received June 6, 2007
A series of europium(III) complexes based on the macrocyclic azacarboxylate structure, DO3A, have been investigated,
incorporating benzophenone appended at N10 of the macrocycle via linkers containing amide bonds (H3DO3A
)
-
1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid). Complexes [EuL1 3] incorporate N10
−CH2CONH−BP linkers
(BP
) benzophenone), which allow formation of a five-membered chelate ring containing the metal ion upon
chelation of the amide oxygen; these three isomeric complexes differ from one another in the substitution position
of the BP unit, namely para, meta, and ortho for L1, L2, and L3 respectively. The quantum yields of europium
luminescence sensitized via the chromophore are found to be highly dependent upon the position of substitution,
being 20 times smaller for the ortho compared to the para-substituted complex. A related para-substituted BP
complex [EuL4], prepared by an unusual Michael reaction of the azamacrocycle with a BP-containing acrylamide,
incorporates an additional methylene unit in the linker, namely N10
this complex equals the luminescence quantum yield achieved with [EuL1] (Φlum
in H2O at 298 K). Analysis of the pertinent kinetics reveals that the decreased energy transfer efficiency in this
complex, arising from the longer donor acceptor distance, is compensated by an increased radiative rate constant.
−CH2CH2CONH−BP. Despite the longer linker,
)
0.097 and 0.095, respectively,
−
Under basic conditions, the ortho-substituted complex [EuL3] undergoes an intramolecular rearrangement to generate
an unprecedented complex [EuL5] incorporating a 4-phenyl-2-hydroxyquinoline unit directly bound to the ring nitrogen.
Although this complex is a poor emitter, an analogous complex obtained from 2-amino-acetophenone, which generates
4-methyl-2-hydroxyquinoline during the corresponding rearrangement, is an order of magnitude more emissive
while still benefiting from relatively long-wavelength absorption. The emission from this complex is pH sensitive,
being dramatically quenched under mildly basic conditions.
Introduction
had recently been put forward by Dexter4 and by Fo¨rster,5
highlighting the importance of the sensitizer triplet state in
acting as the donor to energetically appropriate excited states
of the lanthanide ions.
Much of the recent interest in this process has been
stimulated by the application of lanthanide complexes as
luminescent probes and sensors in biological systems.6-8
Here, the long lifetime of the metal-centered emission, which
is normally not quenched by molecular oxygen, allows the
The sensitization of lanthanide(III) luminescence by
organic chromophores was first reported by Weissman 65
years ago.1 Detailed investigations into the mechanism of
energy transfer were made by Crosby and co-workers in
pioneering studies during the 1960s.2,3 They examined the
process in the context of the theories of energy transfer that
* To whom correspondence should be addressed. E-mail: j.a.g.
williams@durham.ac.uk.
† University of Durham.
(4) Dexter, D. L. J. Chem. Phys. 1953, 21, 836.
(5) Fo¨rster, T. Fluoreszenz organischer Verbindungen; Vandenchoeck und
Ruprecht: Go¨ttingen, Germany, 1951.
(6) For an early example of a heterogeneous bio-assay, see: Sitari, H.;
Hemmila, I.; Pettersson, K.; Lo¨vgren, T. Nature 1983, 301, 258.
(7) Gabourdes, M.; Bourgine, V.; Mathis, G.; Bazin, H.; Alpha-Bazin,
B. Anal. Biochem. 2004, 333, 105.
‡ Fujifilm Imaging Colorants Ltd.
(1) Weissman, S. I. J. Chem. Phys. 1942, 10, 214.
(2) Crosby, G. A.; Alire, R. M.; Whan, R. E. J. Chem. Phys. 1961, 34,
743.
(3) Whan, R. E.; Crosby, G. A. J. Mol. Spectrosc. 1962, 8, 315. Crosby,
G. A.; Whan, R. E.; Freeman, J. J. J. Phys. Chem. 1962, 66, 2493.
9438 Inorganic Chemistry, Vol. 46, No. 22, 2007
10.1021/ic701113c CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/28/2007

Sensitization of Europium(III) Luminescence
Scheme 1. Structures of the Complexes [EuL1]-[EuL6] Investigated
use of time-resolved detection to discriminate between the
luminescence of the probe and the ubiquitous, short-lived
auto-fluorescence. Only those complexes that are stable and
soluble in water, with high thermodynamic and kinetic
stability with respect to metal-ion dissociation, are realistic
candidates for such applications. These criteria are analogous
to those that must be met by gadolinium complexes for use
as contrast agents in magnetic resonance imaging (MRI).9-11
The highly polydentate, seven to nine-coordinating ligands
based on aza-carboxylates, -phosphinates, and -phophonates,
that have been developed for in vivo use in MRI,12 are also
suitable core ligand structures for biocompatible luminescent
complexes because of the high stabilities they offer. On the
other hand, to optimize luminescence, it is also necessary to
limit the ingress of water molecules into the inner coordina-
tion sphere of the metal ion, which otherwise offer the excited
states a facile pathway of nonradiative deactivation through
energy transfer into O-H vibrations.13-15 In addition, given
the low extinction coefficients of lanthanide f-f transitions
(ꢀ typically <1 mol-1 dm3 cm-1), the ligand should prefer-
ably also incorporate an aromatic-sensitizing group to absorb
light more efficiently and populate the lanthanide excited
state by energy transfer.9,16,17,18 A popular strategy for ligand
design has been to use the DOTA structure as the core
(DOTA ) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraac-
etate, the Gd3+ complex of which is the MRI contrast agent
DOTAREM) and to covalently link the sensitizer unit to
one of the four arms through an amide bond (e.g., as in
Scheme 1).11,16,19,20
in This Study
absorption and time-resolved emission spectroscopy.21 The
overall quantum yield of luminescence, Φlum, should then
be favored by a high value of the quantum yield of triplet
formation, ΦT, of the sensitizer, because
Φlum ) ΦTηetkrτobs
(1)
The role of the sensitizer triplet state in the energy transfer
process has been conclusively confirmed for several chro-
mophores by a combination of triplet-triplet transient
where ηet is the efficiency of energy transfer and where the
product of kr (the radiative rate constant of the lanthanide)
and τobs (the observed luminescence lifetime) is the efficiency
of emission from the lanthanide, ηLn. Previously, it has been
noted that molecules with n,π* triplet states, such as aromatic
ketones, typically have high triplet-quantum yields and small
singlet-triplet energy gaps, and hence should be attractive
as sensitizers of lanthanide luminescence.22 We reported high
efficiencies of luminescence from Eu3+ and Tb3+ complexes
incorporating benzophenone as a sensitizer in aqueous
solution.22 Acetophenones, also with n,π* triplet states,
similarly proved effective.23,24 Meanwhile, acridones,25 aza-
xanthones, and azathioxanthones26 have also been explored
(8) For reviews of the potential utility of single-component complexes as
responsive luminescent probes in biological media, see, for example:
(a) Parker, D.; Williams, J.A.G. Responsive Luminescent Lanthanide
Complexes. In Metal Ions in Biological Systems, Volume 40: The
lanthanides and their interactions with biosystems; Sigel, A., Sigel,
H., Eds.; Marcel Dekker: New York, 2003. (b) Bu¨nzli, J.-C.G.
Luminescent Lanthanide Probes as Diagnostic and Therapeutic Tools.
In Metal Ions in Biological Systems, Volume 42; Sigel, A., Sigel, H.,
Eds.; Marcel Dekker: New York, 2004.
(9) Parker, D.; Williams, J. A. G. J. Chem. Soc., Dalton Trans., 1996,
3613.
(10) Aime, S.; Botta, M.; Fasano, M.; Terreno, E. Chem. Soc. ReV. 1998,
27, 19.
(11) Parker, D.; Dickins, R. S.; Puschmann, H.; Crossland, C.; Howard, J.
A. K. Chem. ReV. 2002, 102, 1977.
(21) For examples, see: Alpha, B.; Ballardini, R.; Balzani, V.; Lehn, J.-
M.; Perathoner, S.; Sabbatini, N. Photochem. Photobiol. 1990, 52,
299. Beeby, A.; Parker, D.; Williams, J. A. G. J. Chem. Soc., Perkin
Trans. 2 1996, 1565. Beeby, A.; Faulkner, S.; Parker, D.; Williams,
J. A. G. J. Chem. Soc., Perkin Trans. 2 2001, 1268.
(22) Beeby, A.; Bushby, L. M.; Maffeo, D.; Williams, J. A. G. J. Chem.
Soc., Perkin Trans. 2 2000, 1281.
(23) Beeby, A.; Bushby, L. M.; Maffeo, D.; Williams, J. A. G. J. Chem.
Soc., Dalton Trans. 2002, 48.
(24) Quici, S.; Cavazzini, M.; Raffo, M. C.; Armelao, L.; Bottaro, G.;
Accorsi, G.; Sabatini, C.; Barigelletti, F. J. Mater. Chem. 2006, 16,
741.
(25) Dadabhoy, A.; Faulkner, S.; Sammes, P. G. J. Chem. Soc., Perkin
Trans. 2 2002, 348.
(26) Atkinson, P.; Findlay, K. S.; Kielar, F.; Pal, R.; Parker, D.; Poole, R.
A.; Puschmann, H.; Richardson, S. L.; Stenson, P. A.; Thompson, A.
L.; Yu, J. Org. Biomol. Chem. 2006, 4, 1707.
(12) (a) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem.
ReV. 1999, 99, 2293. (b) Woods, M.; Woessner, D. E.; Sherry, A. D.
Chem. Soc. ReV. 2006, 35, 500.
(13) Freeman, J. J.; Crosby, G. A. J. Phys. Chem. 1963, 67, 2717. Freeman,
J. J., Lawson, D. E.; Crosby, G. A. J. Mol. Spectrosc. 1964, 13, 399.
(14) Kropp, J. L.; Windsor, M. W. J. Chem. Phys. 1963, 39, 2769; idem,
ibid, 1965, 42, 1599.
(15) Haas, Y.; Stein, G. J. Phys. Chem. 1971, 75, 3677.
(16) Parker, D. Chem. Soc. ReV. 2004, 33, 156.
(17) Bu¨nzli, J.-C. G.; Piguet, C. Chem. Soc. ReV. 2005, 34, 1048.
(18) Bu¨nzli, J.-C. G. Acc. Chem. Res. 2006, 39, 53.
(19) For, recent reviews, see: Gunnlaugsson, T.; Leonard, J. P. Chem.
Commun. 2005, 3114. Leonard, J. P.; Gunnlaugsson, T. J. Fluores-
cence 2005, 15, 585.
(20) Gunnlaugsson, T.; Leonard, J. P.; Se´ne´chal, K.; Harte, A. J. J. Am.
Chem. Soc. 2003, 125, 12062.
Inorganic Chemistry, Vol. 46, No. 22, 2007 9439

Wilkinson et al.
Scheme 2. The Synthetic Strategy Used to Prepare the Para, Meta, and Ortho-Substituted Benzophenone Complexes [EuL1]-[EuL3] (a), and the
Complex [EuL4] Incorporating the Additional Carbon Atom in the Pendent Amide Arm (b)
as sensitizers, the most effective of which also benefit from
high triplet-quantum yields.
resulting 2-hydroxyquinoline pendants as sensitizers of Eu3+
luminescence under neutral and basic conditions.
In this work, we have sought to investigate further the
properties and utility of benzophenone as a sensitizer of
europium luminescence in single-component, water-soluble
complexes. Three distinct areas are explored:
(i) the influence of substitution position (o-, m-, or p-) at
the benzophenone unit on the luminescence properties of the
complex, revealing that Φlum is very different for the three
regioisomers,
(ii) comparison of the use of a classical three-atom
macrocycle-to-sensitizer linker (five-membered chelate ring
with the metal ion), with a four-atom linker generated from
an acrylamide and giving a six-membered chelate. We
demonstrate that the latter can provide an attractive and
potentially versatile alternative strategy to the frequently used
R-haloamides, without compromising luminescence quantum
yields, and
Results and Discussion
Ligand Design and Synthetic Strategy. The synthesis
of the three isomeric ligands HL1-HL3 was carried out by
alkylation of DO3But (the tris-tert-butyl ester of DO3A )
1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid) with
the bromoacetamides 1-3 obtained upon acetylation of
ortho, meta, and para-aminobenzophenone with bromoacetyl-
bromide (part a of Scheme 2). The intermediate DO3But is
attractive in such syntheses of mono-N-functionalized DO3A
derivatives because it can be obtained upon the alkylation
of cyclen with tert-butylbromoacetate in the presence of
NaHCO3 as the base with reasonable selectivity over the bis
and tetrakis compounds.25 Moreover, after the functional-
ization of the fourth NH group, the tert-butyl groups can be
deprotected under mild nonaqueous conditions, using trif-
luoroacetic acid at room temperature to reveal the desired
carboxylate functionality (part a of Scheme 2). In these
compounds, there is a three-atom linker (-CH2-CO-NH-)
(iii) for the ortho-linked isomer, we report on an unusual
rearrangement reaction that leads to unprecedented N-arylated
complexes and assess the contrasting effectiveness of the
9440 Inorganic Chemistry, Vol. 46, No. 22, 2007

Sensitization of Europium(III) Luminescence
between the macrocyclic nitrogen atom and the aromatic ring
of the chromophore. As noted above, this arrangement is
typical of a large number of structurally related complexes,
prepared in a similar manner by alkylation of cyclen with
R-haloamides.11,16,19,20 When the ligands bind to the metal
ion, this three-atom linker arrangement favors coordinate-
bond formation between the polarizable amide oxygen and
the metal and leading to a five-membered chelate ring
(Scheme 1, [EuL1-3]).
specifically associated with this arm at elevated temperatures
(up to 60 °C). The change from the five- to the six-membered
chelate has no apparent detrimental effect on the stability of
the complex in solution. This is unsurprising, given that the
complex is based on the DO3A core, numerous studies
having revealed that this core structure can tolerate func-
tionalization of the fourth-ring nitrogen atom by a variety
of units, including non-coordinating ones, without loss of
stability of the lanthanide complexes.11,29
In a distinctly different strategy for activating the chro-
mophore for N-substitution of the macrocycle, acrylamide 4
was prepared by reaction of para-aminobenzophenone with
acryloyl chloride in the presence of a base. The resulting
acrylamide underwent a conjugate Michael addition reaction
with DO3But upon refluxing in acetonitrile solution; after
deprotection of the t-butyl esters, ligand H3L4 was obtained
(part b of Scheme 2). In this case, the extended four-atom
linker (-CH2-CH2-CO-NH-) would lead to a six-
membered chelate, if the amide carbonyl oxygen does indeed
coordinate to the metal ion (Scheme 1, [EuL4]). The use of
such six-membered chelates within DOTA-based lanthanide
complexes has scarcely been investigated, despite the
plethora of compounds incorporating five-membered chelat-
ing amides. Perhaps the most closely related binding motif
comes from very recent work by Borbas and Bruce, who
elegantly appended rhodamine and nucleobases onto a cyclen
ring via peptide coupling reactions with ethylamine units.27
The complexation of aminocarboxylate ligands like H3L1-
H3L4 to lanthanide ions is promoted by the presence of a
base to take up the three protons released per molecule of
ligand. Typically, the protonated ligands are treated with a
base to pH ∼8, prior to the addition of the lanthanide salt
and refluxing of the resulting mixture; strongly basic
conditions are normally avoided to prevent the formation of
the lanthanide(III) hydroxide.28 This method led successfully
to the europium complexes of ligands H3L1, H3L2, and H3L4,
which could be purified by column chromatography on
alumina. The novel complex [EuL4], incorporating the longer
The Ortho-Substituted Isomer: An Unexpected Rear-
rangement. Attempted complexation of the ortho-linked
ligand H3L3 under the conditions used to obtain [EuL1-2
]
and [EuL4] did not give the expected complex [EuL3]. The
electrospray ionization mass spectrum of the product was
indicative of a single europium-containing species, but the
observed mass was 18 units lower than for the meta and
para isomers, suggesting elimination of a water molecule and
possible rearrangement to the complex [EuL5] (Scheme 1).
1
This was supported by analysis of the H NMR spectrum,
which showed only six protons assignable to NCH2CO
groups, compared to the total of eight expected and observed
for the other isomers. To investigate the resulting compound
more fully, identical synthetic conditions were used to
prepare the analogous complex of the diamagnetic yttrium-
(III) ion. Y3+ is comparable in size to Eu3+ and binds to
DOTA in a similar manner.30 The simpler 1H NMR spectrum
of the resulting diamagnetic complex was consistent with
the proposed structure and the presence of the 2-hydrox-
yquinoline unit.
A likely mechanism for the rearrangement is shown in
Scheme 3. This pathway is only open to the ortho-
aminobenzophenone derivative because only in this case does
the attack of the enolate ion result in the formation of a
favored six-membered ring. The rearrangement was also
found to proceed in the absence of lanthanide(III) ions;
refluxing H3L3 in aqueous NaOH for 24 h gave a pale-yellow
solid whose EI mass spectrum {m/z ) 566 ([M+H]+) and
1
588 ([M+Na]+)} and H NMR spectrum were consistent
1
four-atom linker, displays a H NMR spectrum in D2O
with the rearranged ligand, [L5]3-. Indeed, related rearrange-
ments to form 4-hydroxyquinoline derivatives were observed
over a century ago.31 Interestingly, however, no such reaction
was observed for the t-butyl-protected ester precursor upon
refluxing an ethanolic solution in the presence of an organic
base, triethylamine. To establish the generality of the
rearrangement, the methyl derivative, [EuL6], was also
prepared via a strictly analogous procedure (Scheme 4),
starting from the N-alkylation of DO3But with N-(2-
acetylphenyl)-2-bromoacetamide (viz. the bromoacetamide
formed by acetylation of 2-aminoacetophenone with bro-
moacetyl bromide). Because the OH group of hydroxyquino-
lines can be removed, for example, via reduction of the
spanning the range +33 to -20 ppm that is very similar to
that of [EuL1]. This indicates that the additional CH2 unit
does not significantly influence the structure of the complex
compared to compounds with a conventional amide linker.
A total of 26 proton signals (each with integral ) 1) are
clearly resolved (excluding the aromatic signals and the
exchangeable NH): 16 for the cyclen ring, 6 for the acetate
arms, and 4 for the amide-containing arm. That the latter
four are each resolved is very strong evidence that the amide
oxygen is coordinated rigidly to the metal forming the
anticipated six-membered chelate; an unbound, freely rotating
arm, in contrast, would be expected to lead to only two CH2
signals of integral ) 2. This is consistent with the hydration
state of the metal determined by luminscence, which implies
an eight-coordinate complex (vide infra). Variable temper-
ature 1H NMR spectra reveal no evidence of loss of rigidity
(29) Clarkson, I. M.; Beeby, A.; Bruce, J. I.; Govenlock, L. J.; Lowe, M.
P.; Mathieu, C. E.; Parker, D.; Senanayake, K. New J. Chem. 2000,
24, 377.
(30) Parker, D; Pulukkody, P. K.; Smith, F. C.; Batsanov, A.; Howard, J.
A. K. J. Chem. Soc., Dalton Trans. 1994, 689.
(31) Camps, Arch. Pharm. (Weinheim, Germany), 1899, 237, 687 (Beilstein
Citation 1010058).
(27) Borbas, K. E.; Bruce, J. I. Chem. Commun. 2006, 4596.
(28) Aime, S.; Botta, M.; Dickins, R. S.; Maupin, C. L.; Parker, D.; Riehl,
J. P.; Williams, J. A. G. J. Chem. Soc., Dalton Trans. 1998, 881.
Inorganic Chemistry, Vol. 46, No. 22, 2007 9441

Wilkinson et al.
Scheme 3. Suggested Mechanism for the Formation of the Rearranged ortho-Aminobenzophenone Derivatized DO3A Complex under Basic
Conditions, (i.e., [EuL3] f [EuL5])
Scheme 4. Rearrangement and Complexation of a 2-Aminoaceto-
remarkably well-resolved resonances associated with the CH2
protons, suggesting that the conformation is restricted even
in the absence of a metal ion, in contrast to the normally
broad signals associated with the fluxional nature of the
noncomplexed ligands. Again, the complex is highly stable
in aqueous solution and tolerates, for example, several days
at pH 1. As noted above for [EuL4], this high stability is
associated with the DO3A core, which persists essentially
irrespective of the nature of the substituent introduced onto
the fourth-ring nitrogen atom.
phenone Derivatized DO3A Ligand, H3Lpre-6, Generating [EuL6]
tosylate, this rearrangement may be useful as a straightfor-
ward route to quinolin-3-yl N-arylated macrocycles.
Complexes of aromatic chromophores directly attached to
cyclen rings have been little studied, with research almost
invariably focusing on compounds with alkyl spacer units.
Classical N-arylation reactions of cyclen are only achievable
with electron-poor arenes such as fluorinated nitrobenzenes,
requiring high temperatures and extended reaction times,
except for the most-active arylating agents like 2,4,6-
trichloro-1,3,5-triazine.33 Attachment of a wider range of
haloarenes by palladium-catalyzed N-arylation reactions has
been reported recently, but yields are low.34 To our knowl-
edge, the only reported lanthanide complexes of N-arylated
cyclens are the Eu(III), Gd(III), and Tb(III) complexes of
the N-nitrophenyl and anilino derivatives of DO3A,33b and
there are no previous examples of lanthanide(III) complexes
based on cyclen incorporating metal-bound N-aryl substit-
uents.
Although crystals of the rearranged complexes [EuL5] and
[EuL6] suitable for X-ray diffraction analysis could not be
obtained, consideration of the likely molecular geometry of
the macrocycle is of interest. In complexes of DOTA and
N-alkylated DO3A derivatives, the N-pendent groups are
twisted with respect to the N4 plane, resulting in the typical
square-antiprismatic and twisted square-antiprismatic geom-
etries.32 In [EuL5] and [EuL6], however, the direct connection
of an aromatic ring to the macrocycle will enforce a planar
geometry for the organic part of the five-membered Eu-
N-C-C-O ring, restricting the twisting of the N4 and O4
planes and potentially inducing a change in the normal
puckering of the cyclen ring. Evidence for such a distortion
in geometry is provided by the 1H-1H COSY NMR
spectrum, where cross-peaks between protons separated by
many bonds may be observed when they are brought into
close spatial proximity. A number of additional cross-peaks
are observed, of particular note being those between the axial
protons at 41.8 and 30.8 ppm, and between the equatorial
protons at 1.6 and -9.1 ppm. This is consistent with a change
in puckering of the ring from a C4 symmetric form (Figure
1, geometry I) toward a C2 symmetric form (geometry II).
Returning to the synthesis of [EuL3], it finally proved
possible to obtain this complex, without competitive rear-
rangement, by ensuring that the pH of the solution for
complexation was maintained at 6 or below, with the solution
being heated to only 40 °C.
(33) (a) Koike, T.; Gotoh, T.; Aoki, S.; Kimura, E.; Shiro, M. Inorg. Chim.
Acta 1998, 270, 424. (b) Terreno, E.; Boniforte, P.; Botta, M.; Fedeli,
F.; Milone, L.; Mortillaro, A.; Aime, S. Eur. J. Inorg. Chem. 2003,
3530. (c) Subat, M.; Borovik, A. S.; Ko¨nig, B.; J. Am. Chem. Soc.
2004, 126, 3185.
1
In addition, H NMR spectroscopy of Na3L5, the crude
product from rearrangement of the free ligand, exhibits
(34) (a) Subat, M.; Ko¨nig, B.; Synthesis 2001, 1818. (b) Burdette, S.C.;
Lippard, S.J. Inorg. Chem., 2002, 41, 6816. (c) Beletskaya, I. P.;
Averin, A. D.; Bessmertnykh, A. G.; Denat, F.; Guilard, R. Tetrahe-
dron Lett. 2002, 43, 1193.
(32) (a) Aime, S.; Botta, M.; Ermondi, G. Inorg. Chem. 1992, 31, 4291.
(b) Di Bari, L.; Pescitelli, G.; Sherry, A. D.; Woods, M. Inorg. Chem.
2005, 44, 8391.
9442 Inorganic Chemistry, Vol. 46, No. 22, 2007

Sensitization of Europium(III) Luminescence
Figure 3. Ground-state absorbance spectra of [EuL5] (solid line) and
[EuL6] (dashed line) in aqueous solution at 295 K. The literature numerical
absorbance data (λmax values) for 3-aminoquinolin-2-ol are included for
comparison (filled circles).36
Figure 1. Effect of ring puckering on the geometries of lanthanide(III)-
coordinated cyclen derivatives. I ) C4-symmetric conformation of the
macrocycle normally observed in DOTA complexes. II ) Dashed lines
represent additional 1H-1H COSY cross-peaks observed in the N-aryl-
substituted complexes.
Figure 4. Emission spectra of [EuL1] (solid line, λex ) 280 nm), [EuL2]
(dashed line, λex ) 250 nm), and [EuL3] (dotted line, λex ) 280 nm), in
aqueous solution at 295 K. Excitation and emission band-passes ) 2.5 nm.
In contrast, the rearranged complexes [EuL5] and [EuL6]
absorb out to a much-longer wavelength (Figure 3), consis-
tent with the proposed quinoline rearrangement product and
matching well with literature λmax absorbance values for the
model chromophore, 3-aminoquinolin-2-ol.36 The phenyl-
substituted derivative [EuL5] is a little red-shifted with respect
to the methyl-derivative [EuL6], no doubt due to the increased
extent of conjugation in the former.
Luminescence of the Benzophenone-Substituted Com-
plexes [EuL1-4]. Upon excitation into the π-π* bands of
[EuL1-3], an emission characteristic of transitions from the
5D0 excited-state of europium(III) is observed (Figure 4). The
profiles of the spectra (i.e., the relative intensity of bands
and the fine structure of each) are almost identical to one
another, suggesting that the environment at the metal is little
affected by the substitution position of the chromophore.
Luminescence excitation spectra (monitored in the ∆J ) 2
band, 615-619 nm) match the absorption spectra, confirming
the sensitization of europium(III) emission by the organic
chromophore. Notable features include a single, symmetric
∆J ) 0 band, consistent with the low symmetry of the
complex and with a single emitting species being present.
Figure 2. Ground-state absorbance spectra of [EuL1] (solid line), [EuL2]
(dashed line), and [EuL3] (dotted line) in aqueous solution at 295 K.
Photophysical Properties of the Europium Complexes.
Ground-State Absorption. Absorption spectra of the eu-
ropium(III) complexes [EuL1-3] in the UV-visible region
are shown in Figure 2. Two absorption bands are resolved
for the ortho isomer [EuL3] (λmax ) 231 and 259 nm),
whereas a shoulder at around 262 nm is clearly discernible
on the high-energy side of the broad band of [EuL1] (λmax
291 nm). The meta isomer [EuL2], on the other hand, appears
to display only a single, rather more-intense band (λmax
)
)
247 nm). However, although only one band may be resolved,
ZINDO calculations suggest that two bands should be present
for all three isomers, relating to excitation of an electron
from a π orbital localized on the unsubstituted phenyl ring
and from a π orbital localized on both phenyl rings.35 Where
a single feature is observed, this is probably a combination
of two unresolved bands of similar energy. The notable red-
shift for the para isomer is attributed to the increased
delocalization across the amide group.
(35) ZINDO electronic spectra calculations were performed on 2-amino-
N-(benzoylphenyl)-acetamide structures at the MM3 optimised ge-
ometries using the CaChe 6.1.1 software package, Fujitsu Limited,
2003.
(36) Baxter, I.; Swan, G. A. J. Chem. Soc. C 1967, 2446.
Inorganic Chemistry, Vol. 46, No. 22, 2007 9443

Wilkinson et al.
Table 1. Luminescence Data (Lifetimes, τobs and Quantum Yields,
lum) for the Europium(III) Complexes [EuL1-4] in H2O and D2O and
the Calculated q Values
Table 2. Calculated Photophysical Parameters for [EuL1-4] in H2O
Using the Experimentally Determined Quantities [I(0,1)/Itot], kobs ()
1/τobs), and Φlum
Φ
[EuL1] para [EuL2] meta [EuL3] ortho [EuL4] extra C
[EuL1] para [EuL2] meta [EuL3] ortho [EuL4] extra C
a
H2O τ/msa
0.61
0.095
2.26
0.38
1.05
0.60
0.015
2.22
0.16
1.09
0.59
0.004
2.14
0.027
1.08
0.61
0.097
2.03
0.35
0.99
[I(0,1)/Itot
krb/s-1
k
]
0.21
154
1640
0.094
0.095
1.01
0.22
147
1670
0.088
0.015
0.17
0.22
144
1690
0.085
0.004
0.05
0.16
202
b
Φlum
D2O τ/msa
obs/s-1
1640
0.12
0.097
0.81
1440
b
Φlum
ηLn
qc
Φlum
c
ηet
a Lifetimes of metal-centered emission monitored at 616 nm, 295 K;
uncertainty (5%. b Quantum yields of europium emission, λex ) 280 nm,
295 K, measured using an aqueous solution of [Ru(bpy)3]2+ as a standard;46
uncertainty (20%. c q is the hydration state as determined by the equation
of Parker et al.37
∑knrb / s-1
1490
1520
1550
a Estimated uncertainty (5%. b Estimated uncertainty (10%. c Estimated
uncertainty (20%.
para-, through meta-, to ortho-substitution. A detailed analysis
may be performed by consideration of the parameters in eq
1. Although the natural radiative rate constant, kr, cannot be
directly measured, it has been proposed that an estimate of
this parameter may be obtained from the ratio of the
integrated emission intensity of the D0 f F1 transition
(purely magnetic dipole in character) to the total integrated
emission intensity (eq 3, where A(0,1) ∼ 32.4 s-1).38
Luminescence lifetimes and quantum yields of [EuL1-3
]
in H2O and D2O, together with corresponding values for the
six-membered chelate analogue [EuL4], are summarized in
Table 1. The solution hydration numbers, q, (i.e., the number
of inner-sphere, metal-bound water molecules) were deter-
mined by the empirical relationship devised by Parker et al.
(eq 2, where x is the number of N-H oscillators; in this
case, x ) 1).37 Values of 1.07 and 1.08 were determined for
[EuL2] and [EuL3] respectively, very close to the value of
1.05 found previously for [EuL1] and indicative of only a
single inner-sphere water molecule in each case.
5
7
A(0,1)
kr )
(3)
[I(0,1)/Itot]
The values of the key parameters obtained from this
analysis are listed in Table 2. It is clear that, whereas the
values of kr and ∑knr are of a similar order of magnitude for
all three complexes, the emission intensity is limited by the
product of ΦTηet. Benzophenone and its simple para-
substituted derivatives are known to have triplet-quantum
yields of near unity, hence ΦT ∼ 1;39 meta- derivatives are
expected to be similar. Thus, the efficiency of energy transfer
from the sensitizing chromophore to the europium(III) ion,
ηet, is essentially unity for [EuL1], whereas the decrease in
luminescence quantum yield in going to [EuL2] is seen to
arise from a decrease in ηet, from 1 to ∼0.17. This drop may
be due to an increase in the distance between the donor and
acceptor, accompanying the rotation of the benzophenone
moiety in [EuL2] about the N-Ar bond into a sterically
favored position that is more distant from the metal center.
Given the steep distance-dependence of energy transfer
mechanisms,4,5 even a small change in the distance has a
significant effect on ηet. In the case of [EuL3], which is by
far the most weakly emissive of the three complexes, a
further deleterious effect may be the rapid and competitive
deactivation of the singlet and triplet states of the sensitizer
via vibronic coupling involving an intramolecular hydrogen
bond, or an excited-state proton transfer, between the amide
NH and the benzophenone CdO.40,26 In other words, ΦT is
compromised and is probably the limiting factor in determin-
ing Φlum in this instance, rather than ηet.
q
Eu ) 1.2[(τH O-1 - τD O-1) - (0.25 + 0.075x)] (2)
2
2
Significantly, the data for [EuL4] give a similar value for
q of 0.99. These results provide evidence for the binding of
the amide carbonyl group to the metal in each case,
preventing the entry of a second water molecule. This is fully
expected for [EuL1-3] incorporating the three-atom linker,
where a five-membered chelate will result, on the basis of
the large number of structurally related complexes investi-
gated.11,16,19,20,37 On the other hand, there is little precedence
for the use of a four-atom linker to give a six-membered
chelate, as in [EuL4]. It is evident from the q data that the
amide oxygen remains bound to the metal ion by forming a
six-membered chelate, even in aqueous solution, despite the
lower anticipated stability of the six- versus five-chelate ring
size. In their system referred to earlier, Borbas and Bruce
have also concluded, on the basis of luminescence-based
measurement of q, that amide binding in a six-membered
chelate persists in aqueous solution.27 There is a danger of
over-interpreting small differences in q values, which are
perhaps best considered as guidelines. However, that the
value of q for [EuL4] is slightly less than the very self-
consistent values among the series [EuL1-3] may perhaps
be a genuine reflection of the fact that the potentially
quenching N-H oscillator is positioned further from the
metal ion in [EuL4]; the energy transfer being expected to
be strongly distance-dependent, the correction factor of 0.075
ms-1 in eq 1 is therefore probably a slight overestimate in
this case.
(38) A detailed discussion to this approach is provided in ref 23. See also:
Werts, M. H. V.; Jukes, R. T. F.; Verhoeven J. W. Phys. Chem. Chem.
Phys. 2002, 4, 1542.
(39) Sandros, K. Acta Chem. Scand. 1969, 23, 2815; Chattopadhyay, S.
K.; Kumar, C. V.; Das, P. K. J. Photochem. 1985, 30, 81.
(40) For a structurally related chromophoric unit exhibiting such deactiva-
tion, see: Neumann, M. G.; Gehlen, M. H.; Encinas, M. V.; Allen,
N. S.; Corrates, T.; Pernado, C.; Catalina, F. J. Chem. Soc., Faraday
Trans., 1997, 1517.
Comparison of the relative luminescence quantum yields
for the three complexes shows a clear-cut decrease from
(37) Beeby, A.; Clarkson, I. M.; Dickins, R. S.; Faulkner, S.; Parker, D.;
Royle, L.; de Sousa, A. S.; Williams, J. A. G.; Woods, M. J. Chem.
Soc., Perkin Trans. 2 1999, 493.
9444 Inorganic Chemistry, Vol. 46, No. 22, 2007

Sensitization of Europium(III) Luminescence
Table 3. Luminescence Data (Lifetimes, τobs, and Quantum Yields,
lum) for the Europium(III) Complexes [EuL5] and [EuL6] in H2O and
D2O, and the Calculated q Values
Φ
[EuL5] R ) phenyl
[EuL6] R ) methyl
H2O
D2O
qc
τ/msa
0.62
0.003
2.02
0.011
1.06
0.62
0.052
2.05
0.18
1.04
b
Φlum
τ/msa
b
Φlum
a Lifetimes of metal-centered emission monitored at 616 nm, 295 K;
uncertainty (5%. b Quantum yields of europium emission, λex ) 280 nm,
295 K, measured using an aqueous solution of [Ru(bpy)3]2+ as a standard;46
uncertainty (20%. c q is the hydration state as determined by the equation
of Parker et al.37
confirming the sensitization of europium(III) emission by
the organic chromophore. The profiles of the emission spectra
for the two complexes are identical, suggesting that the
environment at the metal is little affected by substitution at
the four position of the quinoline ring. With respect to
[EuL1-4], there is relatively little variation in the form of
the emission spectra (compared, for example, to tris-â-
diketonate complexes such as Eu(TTFA)3), evidence that
there is a similar set of donor atoms with a similar symmetry.
The most notable differences are an increase in intensity of
the hypersensitive ∆J ) 2 band and a larger separation of
the two components of the ∆J ) 1 emission band. These
changes imply an increase in polarizability of the axial
donor,41 as may perhaps be expected for a change from an
amide carbonyl group to a phenol.
Lifetimes for emission in H2O and D2O are summarized
in Table 3. The solution hydration numbers q were again
assessed using eq 2, giving values of 1.06 and 1.04 for [EuL5]
and [EuL6], respectively. These values indicate that there is
only a single inner-sphere water molecule in each case,
strongly suggesting the binding of the quinoline hydroxyl
substituent in the eighth coordination site.
The luminescence quantum yield of [EuL6] in H2O is 0.052
(Table 3). Although at first sight it is inferior to to [EuL1]
and [EuL4], it should be noted that this performance is
achieved at substantially longer excitation wavelengths. In
particular, [EuL6] can be excited at wavelengths of 340-
350 nm, where the absorption is still strong (ꢀ440 ∼ 2200
mol-1 dm3 cm-1). Efficient excitation at wavelengths beyond
the glass cutoff around 330 nm, and beyond the range of
absorption by aromatic amino acids, is important for practical
applications in biological media, yet the range of complexes
that satisfy this criterion that are stable in water and emit
strongly is still relatively limited.11,16,19,26,42,43,44,45
Figure 5. Emission spectra of [EuL5] and [EuL6] in aqueous solution at
295 K; λex ) 340 nm; band-passes ) 2.5 nm. The inset shows the absorption
(solid line) and excitation spectra (dashed line, λem ) 619 nm) of [EuL5].
The Effect of the Extra Methylene Unit in [EuL4].
Comparison of the two para-substituted complexes [EuL1]
and [EuL4] reveals an intriguing result, namely their remark-
ably similar luminescence quantum yields (Table 1). Con-
sideration of the data derived in Table 2 indicates that,
whereas the efficiency of energy transfer ηet shows a modest
decrease, this is counterbalanced by a significant increase
in the radiative rate constant kr (from around 150 to 200 s-1),
promoting luminescence over nonradiative decay from the
excited state of the metal. The net result is that Φlum is almost
identical for the two complexes. The decrease in ηet is
expected because the longer linker in [EuL4] will lead to a
larger separation between the donor sensitizer and the
acceptor metal ion. The increase in kr, on the other hand,
was not anticipated, but is presumably due to an increase in
asymmetry around the metal ion, perhaps associated with a
twisting of the longer arm to allow the amide to coordinate,
increasing the oscillator strength of the hypersensitive ∆J
) 2 transition and thus the overall radiative rate constant.
The above hypothesis, if correct, might be expected to
apply to the corresponding complexes of other lanthanides.
The terbium complex [TbL4] was therefore prepared, and
its luminescence compared to that of [TbL1], which had been
studied previously.22 In this case, the overall luminescence
quantum yield actually proved to be higher for the complex
with the longer linker: Φlum ) 0.27 and 0.41 for [TbL1]
and [TbL4] respectively, in H2O at 298 K; (corresponding
values in D2O are 0.41 and 0.63). For terbium, kr cannot be
estimated simply from the emission spectrum. However,
because Φlum is higher for [TbL4], despite the longer
sensitizer-metal distance that is expected to attenuate ηet,
this implies that kr must be substantially increased. The
emission and excitation spectra of [TbL4] are provided in
the Supporting Information.
Interestingly, the luminescence quantum yield of the
phenyl derivative [EuL5] is an order of magnitude smaller
(41) Dickins, R. S.; Parker, D.; Bruce, J. I.; Tozer, D. J. Dalton Trans.
2003, 1264.
(42) For example, the performance is comparable to a carbostyril-124-
substituted cyclen-based complex, but offering a more accessible and
lower-cost sensitizer unit: D. Parker and J. A. G. Williams, J. Chem.
Soc., Perkin Trans. 2 1996, 1581.
(43) Bekiari, V.; Lianos, P. Langmuir 2006, 22, 8602.
(44) Vendevyver, C. D. B.; Chauvin, A.-S.; Comby, S.; Bu¨nzli, J.-C. G.
Chem. Commun. 2007, 1716.
(45) Yu, J.; Parker, D.; Pal, R.; Poole, R. A.; Cann, M. J. J. Am. Chem.
Soc. 2006, 128, 2294. Pandya, S.; Yu, J.; Parker, D. Dalton Trans.
2006, 2757.
Rearranged Complexes [EuL5] and [EuL6]: Sensitiza-
tion by the 2-Hydroxyquinoline Unit. Upon excitation into
the ligand absorption bands of [EuL5] and [EuL6], an
5
emission characteristic of transitions from the D0 excited
state of europium(III) is observed (Figure 5). Luminescence
excitation spectra (monitored at 700 nm) match the absorp-
tion spectra (shown for [EuL5] in the inset to Figure 5),
Inorganic Chemistry, Vol. 46, No. 22, 2007 9445

Wilkinson et al.
transfer process. Such quenching, in which the Eu3+ center
is transiently reduced, is not uncommon for europium(III),9
being the most readily reduced of the lanthanide(III) ions.
The quenching is also accompanied by a change in the
spectral profile: the hypersensitive ∆J ) 2 band is enhanced
relative to the ∆J ) 1 bands. Such a change is suggestive
of an increase in the polarizability of the axial donor, which
would be consistent with deprotonation of the bound -OH
group.41
Summary and Concluding Remarks. The use of amide
linkers for the incorporation of organic sensitizers into the
macrocyclic azacarboxylate skeleton, DO3A, has emerged
over the past decade as an important method for accessing
robust, water-soluble luminescent lanthanide complexes. The
demonstration in this work that, for a given sensitizer, a
longer four-atom linking unit (H3L4 versus H3L1-3) can
provide a facile route to equally efficient emitters, could open
up an alternative methodology for introducing a wide range
of functionalities. Indeed, the superior results for [TbL4]
compared to [TbL1], in terms of the overall luminescence
quantum yield, suggest that a detailed assessment of com-
plexes incorporating the sensitizer within a six- as opposed
to five-membered chelate may be particularly rewarding.
Within the series of isomeric complexes [EuL1-3], the
position of substitution of the benzophenone-sensitizing
moiety is found to be crucial in determining Φlum, probably
reflecting small changes in the sensitizer-acceptor distance
(e.g., the decreased efficiency in going from para- to meta-
substituted systems) or the introduction of deactivating
pathways for the sensitizer excited state, as in [EuL3]. An
unusual rearrangement reaction open to the latter complex
leads to a rare example of an N-arylated azamacrocyclic
complex. The corresponding rearranged complex [EuL6],
obtained starting from 2-aminoacetophenone, emits with
reasonable efficiency in water and can be excited at
practicable wavelengths around 350 nm, making it a poten-
tially interesting system for applications in aqueous media.
Its pH-sensitive emission over mildly basic conditions could
also render it useful as a luminescent pH sensor amenable
to time-resolved detection methods.
Figure 6. Evolution of the emission spectrum of [EuL6] in aqueous solution
with increasing pH (KOH). The spectra shown are at pH values of 7.4, 8.6,
9.3, 9.8, 10.9, 11.7, acquired under identical condtions: λex ) 340 nm,
band-passes 3.0 nm, 295 ((1) K.
Table 4. Calculated Photophysical Parameters for [EuL5] and [EuL6] in
H2O Using the Experimentally Determined Quantities τobs, Φlum, and
[I(0,1)/Itot
]
[EuL5]
[EuL6]
a
[I(0,1)/Itot
obs/ms
]
0.16
0.62
197
1420
0.003
0.03
0.17
0.62
196
1420
0.052
0.43
τ
krb/s-1
∑knrb / s-1
Φlum
ΦTηet
c
a Estimated uncertainty (5%. b Estimated uncertainty (10%. c Estimated
uncertainty (20%.
than that for the methyl derivative [EuL6], despite similar
luminescence lifetimes. Analysis using eqs 1 and 3 reveals
that this difference stems exclusively from a difference in
the product of ΦTηet between the two complexes (Table 4).
Possible origins of this difference include: (i) phenyl
substitution on the hydroxyquinoline chromophore having a
detrimental effect upon the triplet-quantum yield, ΦT; (ii)
the value of ηet being lowered by increased separation
between the sensitizer and the metal center, perhaps due to
the additional steric demand associated with the phenyl
group; (iii) the energy of the sensitizer triplet state being
lowered by phenyl substitution, perhaps to such an extent
that back-energy transfer is introduced, serving to attenuate
the overall efficiency of luminescence. We note, however,
that degassing the sample led to no increase in Φlum, contrary
to what has frequently been observed in those instances
where back-energy transfer plays a role.21
The intense emission of an aqueous solution of [EuL6] is
almost completely eliminated upon increasing the pH. The
effect is fully reversible; the emission is restored upon the
addition of dilute acid. Representative emission spectra at a
selection of pH values between 7.4 and 11.7 are shown in
Figure 6. Evidently, the complex undergoes a reversible
deprotonation over this range, which is most likely associated
with the -OH group of the hydroxyquinoline (or its
zwitterionic form). The dramatic quenching of the emission
is probably due to the increase in electron density of the
chromophore that accompanies deprotonation, facilitating the
transient oxidation, and hence deactivation, of its excited state
by a photoinduced electron transfer or ligand-to-metal charge-
Experimental Section
Cyclen was purchased from Strem and used as supplied. The
three isomeric ω-amino-benzophenones are commercially available
and were obtained from Aldrich. The synthesis and characterization
of [EuL1] have been described previously.22 Chromatography was
carried out on a silica gel (60, 40-63 µm, Fluorochem) or on
alumina (neutral, Brockman I). Solvents were Analar or HPLC
grade, and water was purified by the Milli Q system. Proton and
13C{1H} NMR spectra were recorded on Varian instruments
operating at the frequencies indicated; proton spectra were refer-
enced to residual protio solvent resonances and 13C to the solvent
carbon resonance. Electrospray mass spectra were measured on a
VG Platform II, or a Micromass LCT spectrometer, with methanol
as the carrier solvent; high-resolution spectra were recorded at the
EPSRC National Mass Spectrometry Service Centre, Swansea.
Synthesis and Characterization. The procedures used for the
synthesis of N-(3-Benzoyl-phenyl)-2-bromo-acetamide, 2, N-(2-
Benzoyl-phenyl)-2-bromo-acetamide, 3, N-(2-Acetyl-phenyl)-2-
9446 Inorganic Chemistry, Vol. 46, No. 22, 2007

Sensitization of Europium(III) Luminescence
bromo-acetamide, and N-(4-Benzoyl-phenyl)acrylamide, 4, and the
details of their characterization are described in the Supporting
Information.
at room temperature under a nitrogen atmosphere for 2 days. The
progress of the reaction was followed by TLC (silica, CH2Cl2/
MeOH, 95/5). The solvent was removed under reduced pressure,
and the residue was added to water (50 mL) and then extracted
into dichloromethane (3 × 50 mL). Drying over MgSO4 and
removal of the solvent under reduced pressure gave the desired
product, (t-Bu)3L3, as a brown solid (2.40 g, 87%). 1H NMR
(CDCl3, 300 MHz) δ ) 11.27 (1H, br s, NH), 8.23 (1H, d, J )
8.1, H6), 7.79 (2H, d, J ) 8.0, H2′), 7.56 (1H, tt, J ) 7.4, 1.2, H4′),
7.51 (1H, td, J ) 8.1, 1.5, H5), 7.42-7.47 (3H, m, H3 & H3′), 7.12
(1H, td, J ) 7.5, 1.0, H4), 3.35 (2H, s, CH2), 3.25 (4H, s, CH2),
3.11 (2H, s, CH2), 2.72-2.91 (16H, m, NCH2CH2N), 1.46 (9H, s,
10-((3-Benzoyl-phenylcarbamoyl)methyl)-1,4,7,10-tetraazacy-
clododecane-1,4,7-tris(acetic acid tert-butyl ester), (t-Bu)3L2.
1,4,7,10-Tetraazacyclododecane-1,4,7-tris(acetic acid tert-butyl es-
ter) (3.76 g, 7.31 mmol), N-(3-benzoyl-phenyl)-2-bromo-acetamide,
2, (2.32 g, 7.29 mmol), cesium carbonate (7.36 g, 22.6 mmol), and
a few grains of potassium iodide were stirred in acetonitrile (150
mL) at room temperature under a nitrogen atmosphere for 2 days.
The progress of the reaction was followed by TLC (silica, CH2-
Cl2/MeOH, 95/5). The solvent was removed under reduced pressure,
and the residue was added to water (100 mL) and then extracted
into dichloromethane (3 × 100 mL). Drying over MgSO4 and the
removal of the solvent under reduced pressure gave the desired
product (t-Bu)3L2 as a brown solid (4.77 g, 87%). 1H NMR (CDCl3,
300 MHz) δ ) 11.16 (1H, br s, NH), 8.65 (1H, d, J ) 7.9, H6),
8.49 (1H, s, H2), 8.33 (2H, d, J ) 7.6, H2′), 7.90-8.12 (5H, m, H4,
H5, H3′ & H4′), 3.71 (2H, s, CH2), 3.68 (2H, s, CH2), 3.65 (4H, s,
CH2), 3.26-3.40 (12H, m, NCH2CH2N), 3.14 (4H, br s, NCH2-
CH2N), 1.93 (9H, s, tBu), 1.89 (18H, s, tBu). MS(ES+) m/z ) 774
([M+Na]+).
t
tBu), 1.39 (18H, s, Bu). MS(ES+) m/z ) 752 ([M+H]+), 774
([M+Na]+).
[EuL3]. A solution of 10-((2-benzoyl-phenylcarbamoyl)methyl)-
1,4,7,10-tetraazacyclododecane-1,4,7-tris-(acetic acid tert-butyl es-
ter) (154 mg, 0.20 mmol) in 80% TFA in dichloromethane (2 mL)
was stirred at room temperature for 3 days. The reaction could be
followed by 1H NMR (D2O). Removal of the solvent under reduced
pressure followed by washing with dichloromethane (3 × 20 mL)
and then diethyl ether (3 × 20 mL) gave 10-((2-benzoyl-phenyl-
carbamoyl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(ace-
tic acid) as a pale-brown solid, which was used without further
purification. 1H NMR (D2O, 400 MHz) δ ) 7.72 (2H, d, J ) 7.8,
arom), 7.66 (1H, t, J ) 7.5, arom), 7.64 (1H, t, J ) 8.1, arom),
7.48-7.53 (3H, m, arom), 7.46 (1H, d, J ) 8.1, arom), 7.40 (1H,
t, J ) 7.9, arom), 2.70-3.97 (24H, br m, CH2). MS(ES+) m/z )
584 ([M+H]+), 606 ([M+Na]+). This was redissolved along with
europium(III) nitrate pentahydrate (95 mg, 0.22 mmol) in water (3
mL), the solution was carefully adjusted to pH 6 with NaOH
solution (2 mol dm-3) (NOTE: The reaction must not be carried
out under more basic conditions, otherwise [EuL5] is obtained),
and heated to 40 °C for 24 h. After cooling to room temperature,
the solvent was removed under reduced pressure. The residue was
redissolved in ethanol and all of the undissolved material was
removed by filtration. Removal of the solvent under reduced
pressure and purification of the residue by column chromatography
(alumina, CH2Cl2/MeOH, gradient elution from 100/0 to 85/15)
gave the desired product as a colorless solid (82 mg, 55%), mp
>250 °C. 1H NMR (D2O, 500 MHz) δ ) 33.95 (1H, s, Hax), 31.01
(1H, s, Hax), 29.37 (1H, s, Hax), 28.71 (1H, s, Hax), 7.00-10.00
(9H, m, arom), 1.60 (1H, s), 1.39 (1H, s), -1.01 (1H, s), -3.15
(1H, s), -3.81 (1H, s), -4.78 (1H, s), -4.91 (1H, s), -8.04 (1H,
s), -8.48 (2H, s), -9.89 (1H, s), -11.58 (1H, s), -12.44 (1H, s),
-13.31 (1H, s), -13.55 (1H, s), -13.68 (1H, s), -14.37 (1H, s),
-15.48 (1H, s), -16.50 (1H, s), -18.29 (1H, s). MS(ES+) m/z )
756 ([M+Na]+). Anal. Calcd for C29H34N5O8Eu(H2O)4: C, 43.3;
H, 5.3; N, 8.7. Found C, 43.1; H, 5.4; N, 8.5.
[EuL2]. A solution of 10-((3-benzoyl-phenylcarbamoyl)methyl)-
1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid tert-butyl ester)
(3.55 g, 4.72 mmol) in 80% TFA in dichloromethane (50 mL) was
stirred at room temperature for 3 days. The reaction could be
followed by 1H NMR (D2O). Removal of the solvent under reduced
pressure followed by washing with dichloromethane (2 × 100 mL)
and then diethyl ether (2 × 100 mL) gave 10-((3-benzoyl-
phenylcarbamoyl)methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris-
(acetic acid), H3L2, as a pale-brown solid, which was used without
1
further purification. H NMR (D2O, 400 MHz) δ ) 7.84 (1H, s,
arom), 7.76 (3H, d, J ) 7.5, arom), 7.71 (1H, t, J ) 7.3, arom),
7.49-7.58 (4H, m, arom), 3.86 (8H, br s, CH2), 3.29 (16H, br s,
NCH2CH2N). MS(ES+) m/z ) 584 ([M+H]+), 606 ([M+Na]+).
This was redissolved along with europium(III) nitrate pentahydrate
(3.00 g, 7.01 mmol) in water (100 mL). The solution was adjusted
to pH 6 with NaOH solution (2 mol dm-3) and heated under reflux
at 100 °C for 24 h. After cooling to room temperature, the solvent
was removed under reduced pressure. The residue was redissolved
in ethanol, and all of the undissolved material was removed by
filtration. Removal of the solvent under reduced pressure and
purification of the residue by column chromatography (alumina,
CH2Cl2/MeOH, gradient elution from 100/0 to 95/5) gave the
desired product as a colorless solid (1.67 g, 48%), mp >250 °C.
1H NMR (D2O, 500 MHz) δ ) 34.2 (1H, s, Hax), 31.4 (1H, s, Hax),
30.2 (1H, s, Hax), 30.0 (1H, s, Hax), 8.7-7.8 (9H, m, arom), 1.1
(1H, s, Heq), -0.5 (2H, s, Heq & Hax′), -3.0 (1H, s, Heq), -3.9
(2H, s, Heq & Hax′), -5.1 (1H, s, Heq′), -7.9 (2H, s, Heq′ & Heq′),
-8.1 (1H, s, Heq′), -10.7 (1H, s, CH2CO), -11.9 (1H, s, Hax′),
-12.2 (1H, s, CH2CO), -12.5 (1H, s, Hax′), -13.8 (1H, s, CH2-
CO), -13.9 (1H, s, CH2CO), -14.9 (1H, s, CH2CO), -15.1 (1H,
s, CH2CO), -16.2 (1H, s, CH2CO), -17.5 (1H, s, CH2CO). MS-
(ES+) m/z ) 756 ([M+Na]+). HRMS(ES+) m/z ) 734.1702
([M+H]+); calc. for EuC29H35N5O8, 734.1692. Anal. Calcd for
C29H34N5O8Eu(H2O)2.5: C, 44.8; H, 5.1; N, 9.0. Found C, 43.9; H,
5.4; N, 8.8.
Europium(III) 10-(2-Hydroxy-4-phenylquinolin-3-yl)-1,4,7,-
10-tetraazacyclododecane-1,4,7-trisacetate [EuL5]. A solution of
10-((2-benzoyl-phenylcarbamoyl)methyl)-1,4,7,10-tetraazacyclodode-
cane-1,4,7-tris(acetic acid tert-butyl ester), (t-Bu)3L3, (1.78 g, 2.37
mmol) in 80% TFA in dichloromethane (25 mL) was stirred at
room temperature for 3 days. The reaction could be followed by
1H NMR (D2O). Removal of the solvent under reduced pressure
followed by washing with dichloromethane (3 × 50 mL) and then
diethyl ether (3 × 50 mL) gave 10-((2-benzoyl-phenylcarbamoyl)-
methyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid) as a
pale-brown solid, which was used without further purification. This
was redissolved along with europium(III) nitrate pentahydrate (1.03
g, 2.41 mmol) in water (30 mL). The solution made basic (to pH
8) with NaOH solution (2 mol dm-3) and heated under reflux at
100 °C for 24 h. After cooling to room temperature, the solvent
10-((2-Benzoyl-phenylcarbamoyl)methyl)-1,4,7,10-tetraazacy-
clododecane-1,4,7-tris(acetic acid tert-butyl ester), (t-Bu)3L3.
1,4,7,10-Tetraazacyclododecane-1,4,7-tris(acetic acid tert-butyl es-
ter) (1.88 g, 3.65 mmol), N-(2-benzoyl-phenyl)-2-bromo-acetamide
(1.16 g, 3.65 mmol), cesium carbonate (3.68 g, 11.3 mmol), and a
few grains of potassium iodide in acetonitrile (75 mL) were stirred
Inorganic Chemistry, Vol. 46, No. 22, 2007 9447

Wilkinson et al.
was removed under reduced pressure. The residue was redissolved
in ethanol and all of the undissolved material was removed by
filtration. Removal of solvent under reduced pressure and purifica-
tion of the residue by column chromatography (alumina, CH2Cl2/
MeOH, gradient elution from 100/0 to 50/50) gave [EuL4] as a
(2 mol dm-3) and heated under reflux at 100 °C for 24 h. After
cooling to room temperature, the solvent was removed under
reduced pressure. The residue was dissolved in ethanol and all of
the undissolved material was removed by filtration. Removal of
the solvent under reduced pressure and purification of the residue
by column chromatography (alumina, CH2Cl2/MeOH, gradient
elution from 100/0 to 50/50) gave the desired product as a colorless
1
colorless solid (1.14 g, 68%), mp >250 °C. H NMR (D2O, 500
MHz) δ ) 41.8 (1H, s, Hax), 41.2 (1H, s, Hax), 35.3 (1H, s, Hax),
30.8 (1H, s, Hax), 8.9 (1H, s, arom), 8.3 (2H, s, arom), 7.2 (1H, s,
arom), 6.5 (1H, s, Heq), 5.7 (1H, s, arom), 5.5-4.0 (4H, obscured
by H2O, arom), 3.6 (1H, s, Heq), 1.6 (1H, s, Heq′), -1.9 (1H, s,
Heq), -2.6 (1H, s, Hax′), -5.6 (1H, s, Heq′), -5.9 (1H, s, Heq), -6.7
(1H, s, Hax′), -9.1 (1H, s, Heq′), -10.7 (1H, s, Heq′), -13.1 (1H, s,
1
solid (150 mg, 36%), mp >250 °C. H NMR (D2O, 500 MHz) δ
) 43.1 (1H, s, Hax), 42.4 (1H, s, Hax), 35.4 (1H, s, Hax), 30.3 (1H,
s, Hax), 6.8 (1H, s, Heq), 5.8 (1H, s, arom), 5.6 (1H, s, arom), 5.6
(1H, s, arom), 5.2 (1H, s, Heq), 3.9 (1H, s, arom), 3.3 (3H, s, Me),
1.1 (2H, s, Heq′), -1.3 (1H, s, Hax′), -2.0 (1H, s, Heq), -5.0 (1H,
s, Heq′), -6.4 (1H, s, Hax′), -6.8 (1H, s, Heq), -9.6 (1H, s, Heq′),
-11.5 (1H, s, Heq′), -13.7 (1H, s, Hax′), -14.3 (1H, s, CH2CO),
-15.1 (1H, s, Hax′), -15.5 (1H, s, CH2CO), -17.7 (1H, s, CH2-
CO), -18.9 (1H, s, CH2CO), -20.2 (1H, s, CH2CO), -20.3 (1H,
s, CH2CO). MS(ES+) m/z ) 676 ([M+H]+). HRMS(ES+) m/z )
676.1291 ([M+Na]+); Calcd for EuC24H30N5O7Na, 676.1255. Anal.
Calcd for C24H30N5O7Eu(H2O)4: C, 39.8; H, 5.3; N, 9.7. Found C,
39.3; H, 5.3; N, 9.5.
Hax′), -14.0 (1H, s, Hax′), -14.9 (1H, s, CH2CO), -16.0 (1H, s,
CH2CO), -18.0 (1H, s, CH2CO), -18.9 (1H, s, CH2CO), -19.2
(2H, s, CH2CO). MS(ES+) m/z ) 716 ([M+H]+), 738 ([M+Na]+).
MS(ES-) m/z ) 714 ([M-H]-). HRMS(ES+) m/z ) 733.1862
([M+NH4]+); Calcd for EuC29H36N6O7, 733.1852. Anal. Calcd for
C29H32N5O7Eu(H2O): C, 47.5; H, 4.7; N, 9.6. Found C, 47.0; H,
4.9; N, 9.0.
A sample of the yttrium complex of this ligand, [YL5], was also
prepared in an analogous manner to that for (t-Bu)3L3, (156 mg,
0.21 mmol) and yttrium(III) nitrate (85 mg, 0.31 mmol), giving
the desired product as a colorless solid (87 mg, 62%), mp
10-((4-Benzoyl-phenylcarbamoyl)ethyl)-1,4,7,10-tetraazacy-
clododecane-1,4,7-tris(Acetic Acid tert-Butyl Ester), (t-Bu)3L4.
The tris-(tert-butyl)ester of DO3A (500 mg, 0.97 mmol), potassium
carbonate (137 mg, 1.07 mmol), and N-(4-benzoylphenyl)acryla-
mide, 4 (243 mg, 0.97 mmol), were stirred in acetonitrile (20 mL)
at reflux for 48 h. The solvent was removed under a vacuum, and
the residue was taken up into aqueous NaOH (1M, 20 mL), from
which the product was extracted into dichloromethane (3 × 20 mL).
The residue was purified by column chromatography over alumina.
The column was first washed with dichloromethane before the title
compound was eluted using 97% CH2Cl2/3% MeOH (Rf ) 0.5 by
1
>250 °C. H NMR (D2O, 400 MHz) δ ) 7.67 (1H, t, J ) 7.5,
arom), 7.58-7.63 (4H, m, arom), 7.39-7.42 (2H, m, arom), 7.23
(1H, t, J ) 7.6, arom), 7.02 (1H, d, J ) 8.1, arom), 1.16-4.20
(22H, m, CH2). MS(ES+) m/z ) 674 ([M+Na]+).
10-((2-Acetyl-phenylcarbamoyl)methyl)-1,4,7,10-tetraazacy-
clododecane-1,4,7-tris(Acetic Acid tert-Butyl Ester), H3Lpre-6
.
1,4,7,10-Tetraazacyclododecane-1,4,7-tris(acetic acid tert-butyl es-
ter) (1.88 g, 3.65 mmol), N-(2-acetyl-phenyl)-2-bromo-acetamide
(934 mg, 3.65 mmol), cesium carbonate (3.69 g, 11.3 mmol), and
a few grains of potassium iodide in acetonitrile (75 mL) were stirred
at room temperature under a nitrogen atmosphere for 2 days. The
progress of the reaction was followed by TLC (silica, CH2Cl2).
The solvent was removed under reduced pressure, and the residue
was added to water (50 mL) and then extracted into dichlo-
romethane (3 × 50 mL). Drying over MgSO4 and removal of the
solvent under reduced pressure gave the desired product as a brown
solid (1.93 g, 76%). Attempted purification by column chroma-
tography (silica, CH2Cl2/MeOH) at this stage resulted in decom-
position, and therefore the product was used directly in the next
step, with purification being carried out after the complexation step.
1H NMR (CDCl3, 400 MHz) δ ) 12.27 (1H, br s, NH), 8.67 (1H,
d, J ) 8.5, arom), 7.83 (1H, d, J ) 7.9, arom), 7.51 (1H, t, J )
7.7, arom), 7.11 (1H, 7.6, arom), 3.39 (2H, s, CH2), 3.28 (4H, s,
CH2), 3.20 (2H, s, CH2), 2.75-3.00 (16H, m, NCH2CH2N), 1.45
1
TLC on alumina in 98% CH2Cl2/2% MeOH); (497 mg, 67%). H
NMR (CDCl3, 200 MHz) δ ) 8.1-7.2 (9H, m, arom), 3.4-2.2
t
(26H, br m, ring, acetate CH2, NCH2), 1.45 (27H, s, Bu). MS-
(ES+): m/z ) 788 (M+Na+).
[EuL4] and [TbL4] were prepared by the hydrolysis of (t-Bu)3L4
using TFA in dichloromethane followed by treatment of a neutral-
ized aqueous solution with the respective lanthanide nitrate salt, as
described for complexes [EuL2] and [EuL3] above. Rf ) 0.5 by
TLC on alumina in 90% CH2Cl2/10% MeOH in both cases. [EuL4].
1H NMR (D2O, 500 MHz, all 35 nonexchangeable protons are
resolved, although definitive assignment of each one is not possible)
δ ) 32.5 (1H, s, Hax), 32.1 (1H, s, Hax), 31.0 (1H, s, Hax), 29.7
(1H, s, Hax), 10.4 (2H, s, arom), 8.35 (2H s, arom), 7.70 (2H, s,
arom), 7.50 (1H, s, arom), 7.38 (2H, s, arom), 0.9 (1H, s), 0.7 (1H,
s), 0.5 (1H, s), -1.0 (1H, s), -2.1 (1H, s), -2.6 (1H, s), -2.9
(1H, s), -4.5 (1H, s), -5.3 (1H, s), -6.1 (1H, s), -7.5 (1H, s),
-8.1 (1H, s), -8.6 (1H, s), -10.2 (1H, s), -11.9 (1H, s), -12.0
(1H, s), -13.5 (1H, s), -15.7 (1H, s), -16.5 (1H, s), -17.1 (1H,
s), -18.7 (1H, s), -19.4 (1H, s). MS(ES+) m/z ) 745 (M+H)+.
HRMS(ES+) m/z ) 768.1648 (M+Na)+; Calcd for C30H36N5O8-
Na151Eu, 768.1652. Anal. Calcd for C30H36N5O8Eu(H2O)4: C, 44.0;
H, 5.4; N, 8.6. Found C, 43.4; H, 5.7; N, 8.2. [TbL4]. MS(ES+)
m/z ) 745 (M+H)+. HRMS(ES+) m/z ) 776.1715 (M+Na)+;
Calcd for C30H36N5O8NaTb, 776.1712. Anal. Calcd for C30H36N5O8-
Tb(H2O)3.5: C, 44.1; H, 5.3; N, 8.6. Found C, 43.7; H, 5.4; N, 8.0.
Photophysical Measurements. Absorption spectra were mea-
sured on a Biotek Instruments XS spectrometer, using quartz
cuvettes of 1 cm path length. Steady-state luminescence spectra
were measured using a Jobin Yvon FluoroMax-2 spectrofluorimeter,
fitted with a red-sensitive Hamamatsu R928 photomultiplier tube;
the spectra shown are corrected for the wavelength dependence of
the detector, and the quoted emission maxima refer to the values
t
t
(9H, s, Bu), 1.41 (18H, s, Bu). MS(ES+) m/z ) 690 ([M+H]+),
712 ([M+Na]+).
[EuL6]. A solution of 10-((2-acetyl-phenylcarbamoyl)methyl)-
1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid tert-butyl es-
ter), H3Lpre-6, (440 mg, 0.64 mmol) in 80% TFA in dichloromethane
(5 mL) was stirred at room temperature for 3 days. Removal of
the solvent under reduced pressure followed by washing with
dichloromethane (3 × 25 mL) and then diethyl ether (3 × 25 mL)
gave 10-((2-acetyl-phenylcarbamoyl)methyl)-1,4,7,10-tetraazacy-
clododecane-1,4,7-tris(acetic acid) as a pale-brown solid, which was
1
used without further purification. H NMR (D2O, 400 MHz) δ )
8.06 (1H, d, J ) 8.8, arom), 8.03 (1H, d, J ) 8.0, arom), 7.64 (1H,
t, J ) 7.8, arom), 7.34 (1H, t, arom), 3.90 (8H, br s, CH2), 3.34
(16H, br s, NCH2CH2N), 2.67 (3H, s, Me). This was redissolved
along with europium(III) nitrate pentahydrate (412 mg, 0.96 mmol)
in water (15 mL). The solution was made basic with NaOH solution
9448 Inorganic Chemistry, Vol. 46, No. 22, 2007

Sensitization of Europium(III) Luminescence
after correction. Luminescence quantum yields were determined
by the method of continuous dilution, using [Ru(bpy)3]Cl2 in air-
equilibrated aqueous solution (φ ) 0.028)46 as the standard;
estimated uncertainty in φ is (20% or better. The quantum yields
of the europium(III) complexes obtained in this way displayed
excellent consistency with the relative values obtained by using
[EuL1] as a secondary standard.
Acknowledgment. We thank the University of Durham
for a studentship to D.M., EPSRC and Avecia Ltd for a
CASE studentship to A.J.W., and the EPSRC National Mass
Spectrometry Service Centre for several mass spectra. Dr.
Lisa Bushby is thanked for recording lifetimes and quantum
yields of [EuL4] and [TbL4].
Samples for time-resolved measurements were excited at 355
nm using the third harmonic of a Q-switched Nd:YAG laser. The
luminescence was detected with a Hamamatsu R928 photomultiplier
tube and recorded using a digital storage oscilloscope, before
transfer to a PC for analysis. The estimated uncertainty in the quoted
lifetimes is (5%.
Supporting Information Available: Excitation spectra of Eu-
(III) complexes, emission and excitation spectra of [TbL4], details
of synthesis and characterization of the aromatic precursors, and
1H NMR spectra of the Eu(III) and Y(III) complexes. This material
is available free of charge via the Internet at http://pubs.acs.org.
IC701113C
(46) Nakamaru, K. Bull. Chem. Soc. Jpn. 1982, 55, 2697.
Inorganic Chemistry, Vol. 46, No. 22, 2007 9449