Functionalisation of lanthanide complexes via microwave-enhanced Cu(i)-catalysed azide-alkyne cycloaddition

Article abstract of DOI:10.1039/c2dt30569k

Cu^I-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide^III-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, e

Full text of DOI:10.1039/c2dt30569k

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PAPER
Functionalisation of lanthanide complexes via microwave-enhanced
Cu(I)-catalysed azide–alkyne cycloaddition†
Csongor Szíjjártó,a Elias Pershagenb and K. Eszter Borbas*a
Received 10th March 2012, Accepted 26th April 2012
DOI: 10.1039/c2dt30569k
CuI-catalysed azide–alkyne cycloaddition reactions were used to functionalise lanthanideIII-complexes
(Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly
accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl
and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions
proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates.
The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu)
complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl
complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4,
respectively. EuTb17 displayed dual EuIII and TbIII-emission upon antenna-centred excitation.
1,3-dipolar cycloadditions (CuAAC).13 While this reaction is not
Introduction
unprecedented on (1H-pyrazole-1,3-diyl)bis(pyridine) ligands14
and N-protected alkynyl-cyclams15 and -cyclens,16 unmetallated
cyclen scaffolds do not undergo CuAAC, presumably due to
CuI-sequestration by the macrocycle.17,18 Post-complexation
decoration of alkynyl–LnIII-complexes Ln1 and Ln2 have been
reported.17–22 While Ln1-type complexes are competent sub-
strates for CuAAC,19,22 Ln2-complexes have been reported to
react sluggishly, in some cases requiring several days to reach
acceptable levels of conversion.17,18,22d Therefore, conditions
that would enable rapid, high-yielding access to the cyclo-
addition products are required.
The synthesis of f–f bimetallic or higher order structures is an
active research area, spurred by the potential of such constructs
as enhanced luminescent23 and NMR-probes24 and as multimo-
dal imaging agents.25 The chemical similarity across the lantha-
nide series renders selective synthesis of heterometallic edifices
challenging. Several strategies have been explored based on
differences in binding site hardness,26 complex stability,27,28 and
sequential presentation of metal binding sites via the use of
orthogonal protecting groups.29 A select group of reactions,
notably diazotisation,30 and thiol exchange with activated
2,2′-dipyridyl disulfides31 can be employed to assemble kineti-
cally stable lanthanide complexes with complementary reactiv-
ities. An exciting potential application of CuAAC would be the
preparation of multimetallic structures from azido- and alkynyl-
functionalised lanthanide complexes. Multihomometallic lantha-
nide complexes have been reported to form under CuI-catalysis
from Ln2 and bis(azidomethyl)benzene,17,18 and Ln1 and tris-
or hexakis-(azidomethyl)benzene.22g However, the application of
CuAAC to the synthesis of heterometallic LnIII complexes has
not yet been demonstrated, presumably due both to the absence
of suitable azide-carrying lanthanide complexes and the limit-
ations of the available synthetic methodology.
The unique magnetic and luminescent properties of the f-block
metals are widely exploited in medical diagnostics,1 bioassays,2
luminescent imaging,3 and biochemistry and structural biology.4
Luminescent labels incorporating visible-emitting TbIII, EuIII or
SmIII, or near IR-emitting NdIII and YbIII have long enough
excited state lifetimes (μs to ms)5 to enable essentially back-
ground-free imaging of complex specimens by simple time-
resolved techniques.6 Excitation through a light-harvesting
antenna affords large apparent Stokes’ shifts. The narrowness of
the emission bands (10–20 nm fwhm) renders luminescent
lanthanide labels optimal for multiplex detection.7 Applications
encompass the unravelling of the details of ion channel motion,8
and the monitoring of protein–protein9a–c and protein–peptide9d
interactions, while responsive LnIII based probes have been
developed to track enzymatic activity,10 and a bewildering
variety of species ranging from DNA,11a,b to proteins11c and
small molecules and ions.11d–j
When employed as luminescent labels or responsive lumines-
cent probes, LnIII ions have to be incorporated into multidentate
chelating frameworks that confer thermodynamic and kinetic
stability on the complex, and shield the metal ion from the
solvent O–H oscillators, which are effective quenchers of the
LnIII excited states.5,12 Efficient access to a great diversity of
LnIII-complexes could be envisioned via the decoration of
alkyne or azide-functionalised ligands though CuI-catalyzed
aDepartment of Chemistry - BMC, Uppsala University, SE-75123
Uppsala, Sweden. E-mail: eszter.borbas@kemi.uu.se;
Fax: +46-18-4713818; Tel: +46-18-4713786
bDepartment of Organic Chemistry, The Arrhenius Laboratory,
Stockholm University, SE-10691 Stockholm, Sweden
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2dt30569k
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Here we report that microwave irradiation significantly
increases the rate of CuAAC for both alkyne and azide-functio-
nalised lanthanide complexes. In addition to the introduction of
a wide range of azide and alkyne-bearing organic building
blocks, the optimised conditions could be applied to the prep-
aration of heterobimetallic and heterotrimetallic lanthanide com-
plexes. The significant improvements in synthetic methodology
should help CuAAC reach its full potential as a true click reac-
tion for the functionalisation and assembly of lanthanide
complexes.
100 °C, which affected clean, quantitative conversion to the tria-
zole in a simple reaction mixture, rendering product purification
straightforward. It is worth noting that the reaction of Eu2 and A
under the optimised conditions but with conventional heating
(80 °C) did not give rise to appreciable amounts of Eu2A after
1 h, and significant amounts of unconverted La2 were seen even
after 22 h.
Scope of the cycloaddition reaction
Having identified suitable conditions for rapid triazole formation
in the lanthanide complex context, we explored the scope of the
reaction. To this end, a series of LnIII-complexes carrying alkyne
or azide reactive groups were synthesised (Schemes 1 and 2 and
ESI†). Singly reactive complexes Ln1–Ln4 were prepared, as
exemplified by Ln4 (Scheme 2A). Selective monoalkylation of
cyclen was carried out in high yields (76–91%) upon treatment
with 1.2–1.4 equiv. of the required alkyl halide or mesylate.
Only trace amounts of dialkylated products were observed by
TLC and ESI-MS analysis, which were readily removed upon
chromatographic purification (silica, CH2Cl2–MeOH–aq. NH3).
Alkylation of the remaining three secondary nitrogens with tert-
butyl bromoacetate in CH3CN in the presence of Na2CO3
afforded the fully N-alkylated cyclen (9) in 76% yield after
column chromatography on silica gel. The tert-butyl esters were
cleaved quantitatively upon treatment with TFA in CH2Cl2
(1 : 1). Complexation was carried out with either LnCl3 or
Ln(OTf)3 salts in warm methanol. The complexes were obtained
by precipitation from their concentrated methanolic solutions
with diethyl ether.
Results and discussion
Optimisation of the cycloaddition reaction
We started our investigations by aiming for conditions that
enable rapid coupling of alkynyl–lanthanide complex La2 and
benzylic azides A or B (Scheme 1). A large number of Cu-
sources (e.g., CuSO4, Cu(acac)2, Cu(OAc)2, CuBr2, CuCl, CuI,
Cu2O), supporting ligands (TBTA,32 TMEDA,33 DIEA34), sol-
vents (DMSO, DMF, H2O/tBuOH-mixtures), additives (NaAsc,
benzoic acid35) and temperatures (r.t. to 120 °C, oil bath or
microwave heating) were screened by 1H NMR analysis, or
ESI-MS and TLC analysis [silica, CH3CN–H2O (1 : 1), (Rf
La2A = 0.84, Rf La2 = 0.42] (Tables S1 and S2†). We found
that conditions similar to those reported by Imperiali et al. for
the synthesis of 8-hydroxyquinoline-based kinase sensors36 (5%
CuI, 15% AscOH, DMF, methylpiperidine) afforded complete
conversion of La2 and A to the desired product in 30 min at
120 °C in a microwave reactor. Optimised conditions were 1
equiv. Ln2, 1.1 equiv. azide, 5% CuI catalyst, in CH3CN–piper-
idine (4 : 1) or CH3CN–iPr2NH (4 : 1) solvent mixtures at
Scheme 1
Scheme 2
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Table 1 Scope of the cycloaddition reactiona
Ln-
Coupling
partner
Time
(min)
Yield (precipitation/
chromatography)
Entry complex
1
2
3
4
5
6
7
8
La1
Eu1
La2
Eu2
Tb2
La2
Eu2
Eu2
Tb2
La3
Eu3
La4
Eu4
Tb4
La4
Eu4
Tb4
La5
A
A
A
A
A
C
C
D
D
A
A
E
E
E
F
15
15
15
15
15
30
30
60
60
15
15
30
30
30
30
30
30
30
85%/57%
88%
58%/66%
60%/55%
56%/45%
44%
42%
95%
79%
86%
9
10
11
12
13
14
15
16
17
18
90%
96%/16%
82%/34%
79%/36%
91%/29%
98%
37%/33%
47%/44%
Scheme 3
F
F
A
superior yields to chromatographic purification (cf. Table 1,
Entries 12–15). As excess organic substrate and Cu-residues
(presumably bound by the amine additive) remained dissolved,
and the reactions proceeded to completion (thus consuming the
starting LnIII-complex which had solubility similar to the
product), the precipitate contained only the cycloaddition
product. To the best of our knowledge, there has been only a
single previous report on CuAAC-functionalisation of lanthanide
complexes under microwave irradiation.22g The present work
provides a significant expansion of scope.
a Reaction conditions: Lanthanide complex: 1 equiv., coupling partner:
1.1 equiv., CuI (5%), iPr2NH–CH3CN (1 : 4), 0.2 M, 100 °C, microwave
heating.
Bis-alkynyl complex La5 was obtained by dialkylation of
known 1037 with propargyl bromide in the presence of K2CO3 in
CH3CN in quantitative yield, followed by tert-butyl ester clea-
vage and complexation as described above (Scheme 2B).
We found that organic alkyl and aryl azides (A–D) could be
coupled with alkyne-functionalised lanthanide complexes Ln2
under the improved CuAAC conditions (Table 1, Entries 3–9).
Benzyl azide reacted readily with alkynyl lanthanide complexes
that contained the propargyl alkyne motif attached directly to the
cyclen nitrogen (Ln2), as well as those whose the propargyl
alkyne was further removed (as in Ln1; Entries 1, 2). Gunn-
laugsson and co-workers noted that alkynyl cyclen triamides
Ln3 were challenging substrates for CuI-catalyzed azide–alkyne
cycloadditions (CuSO4, NaAsc, various solvents and reaction
temperatures), which failed to react despite forcing conditions.18
They attributed this finding to the presence of primary amide
NH-bonds. Subjecting Ln3 to our cycloaddition conditions
afforded La3A and Eu3A in excellent yield (86% and 90%,
respectively; Entries 10, 11). Additionally, dual modification of
bis-alkynyl complexes 5Ln was also straightforward with excess
benzyl azide (Entry 18). Azido lanthanide complexes Ln4
underwent CuAAC with alkyl (F38) or aryl (E) alkynes (Entries
12–17). In all cases, complete conversion could be achieved in
15–60 min, and isolated yields ranged from moderate to
excellent.
Pure products could be isolated either by precipitation from
the reaction mixture with diethyl ether, or by column chromato-
graphy on silica gel using CH3CN–H2O mixtures. The two
methods afforded the products in comparable yields when
iPr2NH was used as the base in the reaction, and the cyclo-
addition product had good solubility in CH3CN–H2O. Isolation
by precipitation required extensive drying of the isolated pro-
ducts under vacuum (48–96 h at ∼0.2 Torr), as the solids
retained both amines efficiently. When product solubility was
modest in water–CH3CN mixtures, precipitation afforded
Synthesis of heteromultimetallic edifices
To demonstrate the utility of these conditions for multihetero-
metallic complex synthesis, we prepared alkynyl LnIII-complexes
Ln16 (Ln = Tb or La) equipped with coumarin 2-acetamide
antennae (Scheme 3). Dialkyl cyclen 1017 was monoalkylated in
70% yield with chloroacetamide 1239 in the presence of
NaHCO3 in warm acetonitrile. Alkylation of the secondary nitro-
gen in 13 with propargyl bromide afforded 14 in 71% yield after
column chromatography. Tert-butyl ester cleavage and complexa-
tion yielded Ln16, isolated by precipitation from methanolic sol-
ution with Et2O.
The reactions of Ln16 with azide-carrying Eu4 (1.8–2 equiv.)
in the presence of CuI afforded the expected heterobimetallic
complexes TbEu17 and LaEu17 in 60% and 33% isolated yield
after column chromatography (Scheme 4). Additionally, we have
prepared a trimetallic construct containing one LaIII and two
EuIII centres (Scheme 4). Complex LaEu218 was obtained in
34% isolated yield by double cycloaddition of bis-alkynyl La5
with an excess of azide-functionalised Eu4. The base of choice
for the synthesis of multimetallic structures proved to be piper-
idine, presumably due to the better solubility of the starting
materials in the piperidine–CH3CN mixture compared to
iPr2NH–CH3CN. In all cases the molecule ions of the products
with the required isotope distribution pattern were observed by
HR-ESI-MS analysis† [TbEu17: m/z calcd 1406.4100, obsd
i
1406.4519 for the CH3CN + PrOH adduct (from the analysis
solvent); LaEu17: m/z calcd 1285.3064 obsd 1285.3047;
LaEu218: m/z calcd 1716.3254 obsd 1716.3318 for the piper-
idine adduct].
7662 | Dalton Trans., 2012, 41, 7660–7669
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Table 2 Photophysical properties of selected cycloaddition products
Complex (λex/λem
)
τH O (ms)
τD O (ms)
q
2
2
Eu2C (280 nm/590 nm)
Eu2D (280 nm/590 nm)
Tb2D (280 nm/543 nm)
Eu3A (266 nm/614 nm)
Eu4 (397 nm/590 nm)
Tb4 (366 nm/488 nm)
Eu4E (278 nm/615 nm)
Tb4E (278 nm/546 nm)
Eu4F (356 nm/614 nm)
Tb16 (320 nm/544 nm)
EuTb17
1.17
1.13
3.54
1.10
0.61
0.87
1.26
2.12
0.93
0.58
2.83
2.46
2.70
1.64
4.28
1.66
2.22
3.13
2.75
0.72
0.3
0.3
0.1
−0.3a
1.4
2.4
0.1
0.5
0.4b
1.4
(328 nm/699 nm)
(328 nm/545 nm)
EuLa17 (328 nm/699 nm)
LaEu218 (396 nm/699 nm)
1.03
0.68
1.18
0.52
2.67
0.74
2.62
1.49
0.4
0.3
0.3
1.2
a The non-equivalence of the amide N–H’s was taken into consideration
as described in ref. 42. b Data for Tb4F (λex = 356 nm, λem = 543 nm)
0.41 ms (H2O), 2.15 ms (D2O), giving a nominal value of q = 9.7.
parent complex, indicating that while the triazole may coordinate
in Ln4-derivatives to the metal (vide infra), the six-member
chelate thus formed is not sufficiently stable to slow down dia-
stereomer interconversion on the NMR time scale.
Scheme 4
Chemical characterisation
All ligands and intermediates were fully characterised by 1H,
13C NMR, IR and UV-Vis spectroscopy and HR-ESI-MS analy-
sis, and emission spectroscopy, where applicable. Lanthanide
complexes were characterised by IR and UV-Vis spectroscopy,
and HR-ESI-MS analysis. All complexes displayed the expected
isotope distribution pattern. EuIII and TbIII complexes were also
characterised by luminescence spectroscopy (vide infra). In
order to facilitate full characterisation of starting lanthanide com-
plexes and coupling products, the diamagnetic La-analogs of the
Eu and Tb-complexes were also prepared. Overlapping solvent
peaks and peak broadening made integration difficult. However,
Photophysical characterisation
Upon antenna-centred excitation all EuIII- and TbIII-complexes
5
7
5
displayed the expected D0 → FJ (J = 0, 1, 2, 3, 4) and D4 →
7FJ (J = 6, 5, 4, 3) transitions, respectively. TbIII-emission from
Tb4F was poor, and in steady-state mode only antenna fluor-
escence (λem = 400 nm) was seen. The luminescent lifetimes of
the complexes in H2O and D2O were measured (Table 2). From
these data the number of water molecules (q) in the lanthanide
coordination sphere was calculated using q = ALn(1/τH − 1/τD
−
1
BLn),41,42 where A and B are lanthanide-specific values correct-
analysis of the 5–9 ppm region of the H NMR spectrum of the
cycloaddition products was informative, as the triazole CH
∼8 ppm for La1A and La2A), and where present, the CH2
̲
(e.g.
ing for outer-sphere water molecule contributions and the pres-
̲
–
ence of exchangeable NH-oscillators (ATb = 5, AEu = 1.2; BTb
=
Ntriazole peaks (e.g. ∼5.60 ppm for La1A and La2A) could be
observed, and provided additional corroborating evidence for the
identity of the products.
0.06, BEu = 0.25 + 0.075x, x = exchangeable NH oscillators).
Faulkner,17 Lowe20 and Gunnalugsson18 have established that
upon triazole formation the hydration state of Ln2-derivatives
decreases by ∼1 water molecule because of the replacement of a
non-coordinating alkyne by the coordinating triazole in the
ligand. Our observations are in line with these earlier reports, as
all Ln2-derivatives have q = 0.1–0.3. Data on the Ln4 series
seem to point toward a similar trend, with q decreasing upon for-
mation of a coordinating triazole from an azide that is poorly dis-
posed for metal coordination, with q = 1.4 and 2.4 for Eu4 and
Tb4, respectively, and q = 0.1–0.5 for coupling products.
However, these data should be interpreted with caution, given
the sizeable error associated with this measurement. The improb-
ably large q value for Tb4F may be an indication of energy back
transfer from TbIII to the antenna triplet state.38 The number of
EuIII-bound water molecules in LnEu218 was measured to be
1.2, which may reflect the inability of the two EuIII ions to
access the triazoles around the central LaIII efficiently.
1
The H NMR spectra of the EuIII-complexes were typical of
paramagnetic species. The spectra of Eu2- and Eu4-derivatives
were strikingly different.† Products in the Eu2-series displayed a
set of sharp peaks in the −20 ppm to 30 ppm region. Due to the
asymmetry of the complexes, all protons were non-equivalent.
Upon comparison with literature data the four most downfield
shifted signals were assigned to the axial ring protons in square
antiprismic complexes.17,20,40 The exception to this general trend
was the spectrum of Eu2C, which was similar to, albeit much
sharper than the ones of the Eu4-series. The most prominent and
consistent feature in the spectra of the Eu4-series were a set of
broad signals between −13 ppm and −8 ppm. Upon closer
inspection additional downfield shifted, very broad signals
(8.6–9.7, >33 ppm) were seen. The Eu4 cycloaddition product
spectra were not appreciably sharper compared to that of the
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The spectral forms of Eu4, and its derivatives Eu4E and
Eu4F reported on a change of local coordination environment
around the EuIII centre upon triazole formation (Fig. 1, and
EuIII-sensitisation through the antenna can take place in
EuTb17. An additional mechanism, energy transfer from the
TbIII 5D4 level to EuIII cannot be ruled out at this stage.31,43,44
A
5
7
ESI†). The ratio of the D0 → F1 (∼591 nm) and the hypersen-
detailed investigation of the photophysical properties of these
heterobimetallic constructs is underway and will be reported in
due course.
5
7
sitive D0 → F2 (∼614 nm) bands12 increases from I614/I591
=
1.10 in Eu4 to 1.47 in Eu4E and 3.13 in Eu4F. A similar
change was noted for LaEu218 (I614/I591 = 1.24), indicating that
in this heterotrimetallic structure the EuIII-environment is differ-
ent from the one in Eu4.†
Heterobimetallic EuTb17 displayed dual TbIII and EuIII-emis-
sion upon antenna-centred excitation (Fig. 2). EuIII lifetimes
were identical for EuLa17 and EuTb17 (within experimental
error (Table 2)). Hydration states of q = 0.3 and 0.4 were
obtained for EuIII in EuLa17 and EuTb17, respectively; for
EuTb17 a q(Tb) = 0.3 was determined, in line with the expected
complex structures whose LnIII centres are bound in 8-coordinate
chelates. Coumarin 2-amide is a sensitiser for both TbIII and
EuIII,39 and EuIII-excitation spectra of EuLa17 and EuTb17
closely match the absorption spectra (Fig. 2), indicating that
Conclusions
Microwave heating significantly increased the rate of the CuI-
catalysed 1,3-dipolar cycloaddition with trivalent lanthanide
complex substrates. Alkyne and azide-functionalised complexes
reached complete conversion within 5–60 min with both alkyl
and aryl azides and alkynes, respectively, including other lantha-
nide complexes with complementary functionalities. Our method
provided rapid access to pure f–f heterobimetallic and heterotri-
metallic constructs, opening the door for a range of applications
in the biological sciences.
Experimental
General procedures
1H NMR (300 MHz, 400 MHz or 500 MHz) and 13C NMR
(75 MHz, 100 MHz or 125 MHz) spectra were recorded on a
Varian 300, a Varian 400 or a Bruker 500 MHz instrument,
respectively. Spectra were collected in CDCl3 unless noted other-
wise. Chemical shifts were referenced to residual solvent peaks
and are given as follows: chemical shift (δ, ppm), multiplicity (s,
singlet; br, broad singlet; d, doublet, t, triplet; q, quartet; m, mul-
tiplet), coupling constant (Hz), integration. IR experiments were
performed on a Perkin Elmer Spectrum-100 FT-IR spectrometer
equipped with an ATR accessory. HR-ESI-MS analyses were
performed on a Bruker MicroTOF ESI mass spectrometer. For
accurate mass determination of Eu complexes the 153Eu-isotope
was used. Compounds B,45 F,38 Ln1,19 Ln2,17 Ln3,18 2-azi-
doethanol,46 1037 and 1239 were synthesised following literature
methods. All other chemicals were from commercial sources and
used as received. Microwave heating was performed with a
Biotage Initiator instrument. For temperatures and reaction times
Fig. 1 Time-resolved emission spectra of Eu4 (blue, λex = 397 nm,
delay time: 0.05 ms) and Eu4F (red, λex = 356 nm, delay time:
0.05 ms).
see Table
1 and the detailed experimental procedures.
CAUTION: Low molecular weight azides are potentially
explosive.
Chromatography
Preparative chromatography was performed using silica
(230–400 mesh). Thin layer chromatography was performed on
silica-coated aluminum plates. Samples were visualised by UV-
light (254 and 356 nm), or staining with KMnO4/K2CO3 or
cerium ammonium molybdate. The purity of cycloaddition pro-
ducts was assessed by RP-HPLC on an Agilent Technologies
1200 system using an Agilent Eclipse XDB-C18 column (5 μm
× 4.6 mm × 150 mm) with water–CH3CN eluent system
(ramping from 100% water to 100% CH3CN).
Fig. 2 Normalised emission spectra of EuTb17 (black) and EuLa17
(brown) upon antenna-centered excitation (λex = 328 nm), and normal-
ised absorption (blue) and excitation (red, λem = 614 nm) spectra of
EuTb17. The peak marked with an asterisk is from scattered light.
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Photophysical measurements
9. Monoalkylated cyclen 8 (1.35 g, 6.22 mmol) and Na2CO3
(4.35 g, 41.1 mmol) were suspended in CH3CN (100 mL). The
suspension was treated with tert-butyl bromoacetate (4.00 g,
20.5 mmol). The reaction mixture was heated at 70 °C for 21 h,
after which it was allowed to cool back to room temperature.
The mixture was filtered, the filtrate was concentrated, and the
oily residue was purified by column chromatography [silica,
CH2Cl2–MeOH (0 → 10%)] to yield a pale yellow oil (2.77 g,
76%): νmax 2823, 2102, 1725, 1457, 1368, 1310, 1227, 1162,
1116 cm−1; λmax = 273 nm; 1H NMR (500 MHz, CDCl3)
1.34–1.37 (m, 27H), 2.07–3.56 (m, 26H); 13C NMR (125 MHz,
CDCl3) 27.8, 27.9, 49.0, 49.1, 49.4, 49.9, 50.0, 50.3, 51.5, 53.5,
55.6, 56.1, 82.1, 82.5, 172.5, 173.0; HR-ESI-MS calcd
584.4130 obsd 584.4138 [(M + H)+, M = C28H53N7O6], calcd
606.3950 obsd 606.3949 (M + Na)+.
Absorption spectra and fluorescence spectra were collected at
room temperature in H2O unless indicated otherwise. UV-Vis
absorption spectroscopy was performed on a Varian Cary 300
instrument; (sh) denotes shoulder to a peak. Steady state and
time-resolved emission spectra were collected at room tempera-
ture using a Horiba Scientific FluoroMax 4 instrument equipped
with a flash lamp. Hydration states (q) were determined accord-
ing to the method developed by Horrocks,41 and Parker and
Beeby.42 Emission intensity changes were fitted to single expo-
nential decays using the instrument’s software (FluorEssence
Version 3.5.1.20, based on Origin 8.1090). Fitting to double
exponential was less suitable based on R2 and chi.
4. A sample of 9 (2.32 g, 3.98 mmol) was dissolved in
CH2Cl2 (20 mL) and TFA (20 mL). The solution was stirred at
room temperature for 21 h. The volatile components were evap-
orated, and the oily residue was dried under vacuum for 24 h,
affording a yellow, sticky oil (quant): IR 3419, 3068, 2110,
Synthesis
11. Dialkyl cyclen 1037 (926 mg, 2.32 mmol) was dissolved in
CH3CN (25 mL). The solution was treated consecutively with
Na2CO3 (1.23 g, 11.6 mmol) and propargyl bromide (80 wt% in
xylenes, 565 μL, 5.09 mmol). The reaction mixture was warmed
to 45 °C, and the reaction was allowed to proceed for 48 h. The
mixture was cooled back to room temperature, filtered, and the
filtrate was concentrated. Purification of the oily residue by
column chromatography [silica, CH2Cl2–MeOH (0 → 10%)]
yielded a pale yellow, viscous oil (1.09 g, 99%): νmax 3298,
3175, 2977, 2934, 2841, 2116, 1724, 1457, 1393, 1369,
1306 cm−1; λmax = 282 nm (CH2Cl2); 1H NMR (500 MHz,
CDCl3) 1.38 (s, 9H), 1.42 (s, 9H), 2.08–3.35 (m, 25H), 4.07 (br,
1H); 13C NMR (125 MHz, CDCl3) 28.0, 28.1, 43.0, 43.2, 49.1,
49.9, 51.1, 52.2, 53.6, 57.2, 57.5, 72.8, 75.5, 76.2, 79.0, 82.2,
83.3, 169.9, 174.1; HR-ESI-MS calcd 477.3435 obsd 477.3413
[(M + H)+, M = C26H44N4O4], calcd 499.3255 obsd 499.3213
(M + Na)+.
1720, 1667, 1462, 1388, 1352, 1293, 1181, 1126, 1089 cm−1
;
1
λmax = 277 nm (sh) (CH3OH); H NMR (300 MHz, CD3OD)
3.00–3.27 (m, 9H), 3.32–3.42 (m, 9H), 3.54–4.03 (m, 8H); 13C
NMR (75 MHz, CD3OD) 49.4–54.1 (br m), 172.0 (br);
HR-ESI-MS calcd 416.2252 obsd 416.2251 [(M + H)+, M =
C16H29N7O6].
5. A sample of 11 (1.22 g, 2.56 mmol) was dissolved in a
mixture of CH2Cl2 and TFA (1 : 1, 50 mL). Stirring was contin-
ued for 17 h at room temperature. The volatile components were
removed under reduced pressure, and the oily residue was dried
for 24 h under vacuum to yield a dark yellow oil (quant): νmax
3295, 2989, 2873, 2547, 2138, 1727, 1705, 1672, 1465, 1440,
1413, 1303, 1134, 1083, 1014 cm−1; λmax = 279 nm (CH3OH);
1H NMR (500 MHz, CD3OD) 3.15–3.27 (m, 10H), 3.33–3.52
(m, 12H), 4.22 (br, 4H); 13C NMR (125 MHz, CD3OD) 44.3,
48.9, 49.8, 52.4, 72.4, 79.6, 173.3; HR-ESI-MS calcd 365.2183
obsd 365.2181 [(M + H)+, M = C18H28N4O4].
8. 2-Azidoethanol46 (2.15 g, 24.75 mmol) and Et3N (5.2 mL,
37.1 mmol) were dissolved in anhydrous CH2Cl2 (30 mL) under
a N2 atmosphere. The solution was cooled in an ice-water bath.
MsCl (3.12 g, 2.11 mL, 27.22 mmol) was added dropwise. Stir-
ring was continued for 2 h. The reaction mixture was diluted
with dil. aq. HCl. The phases were separated, and the aqueous
layer was extracted once with CH2Cl2. The combined organic
layer was washed with dil. aq. NaHCO3, and dried (MgSO4).
Evaporation of the solvent afforded a yellow oil that was used
13. Dialkylated cyclen 1031 (200 mg, 0.5 mmol), coumarin-
chloroacetamide 1233 (147 mg, 0.5 mmol) and NaHCO3
(210 mg, 2.5 mmol) were heated at 60 °C for 22 h. The sample
was filtered, the filtrate was concentrated, and the oily residue
was purified by column chromatography [silica, CH2C2–MeOH
(50 : 1 → 9 : 1)] affording a pale yellow foam (230 mg, 70%):
νmax 3060, 1728, 1560, 1309, 1156 cm−1; λmax = 275 nm,
1
without further purification (3.11 g, 76%): H NMR (500 MHz,
1
CDCl3) 3.09 (s, 3H), 3.60 (t, J = 5.0 Hz, 2H), 4.35 (t, J =
5.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) 38.0, 50.1, 67.6.
(3.11 g, 76%): A portion of 7 thus prepared (1.21 g, 7.33 mmol)
was added dropwise to a suspension of cyclen (6, 1.55 g,
9.0 mmol) in CHCl3 (13 mL). Stirring was continued for 28 h at
room temperature. The reaction mixture was concentrated, and
the residue was purified by column chromatography [silica,
CH2Cl2–MeOH (0 → 15%), then CH2Cl2–MeOH–sat. aq. NH3
(10 : 10 : 1 → 5 : 5 : 1)] to yield a pale yellow oil (1.35 g, 76%):
νmax 3357, 3041, 2832, 1097, 1458, 1299, 1209, 1171,
1039 cm−1; λmax = 277 nm (CH3OH); 1H NMR (500 MHz,
CDCl3) 2.72 (app s, ∼3.7H), 2.60–2.92 (m, 18H), 3.45 (t, J =
5.8 Hz, 2H); 13C NMR (125 MHz, CDCl3) 39.7, 45.1, 46.3,
47.9, 49.3, 51.3, 54.2; HR-ESI-MS calcd 242.2088 obsd
242.2089 [(M + H)+, M = C10H23N7].
323 nm (CH2Cl2); λem = 400 nm (λex = 323 nm, CH2Cl2); H
NMR (300 MHz, CDCl3) 1.10–1.17 (m, 3H), 1.49 (s, 18H),
2.12 (s, 3H), 2.30 (s, 3H), 2.52–3.46 (m, 22H), 3.64–3.73 (m,
1H), 4.09–4.32 (m, 1H), 6.33 (s, 1H), 7.11 (s, 1H), 7.60 (s, 1H),
9.78 (br, ∼2H); 13C NMR (75 MHz, CDCl3) 13.0, 17.7, 19.0,
28.4, 43.5, 47.2, 49.3, 51.3, 52.3, 57.8, 81.9, 116.2, 117.4,
120.5, 128.0, 131.7, 142.6, 151.8, 152.4, 160.3, 169.5, 170.5;
HR-ESI-MS calcd 658.4174 obsd 658.4168 [(M + H)+, M =
C35H55N5O7].
14. Trialkylated cyclen 13 (184 mg, 0.28 mmol) was dis-
solved in CH3CN (3 mL). K2CO3 (116 mg, 0.84 mmol) was
added, followed by propargyl bromide (37 μL, 80 wt% solution
in xylenes, 0.34 mmol). The reaction mixture was stirred at
45 °C for 16 h. The mixture was filtered, the filtrate was concen-
trated, and the oily residue was purified by column
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 7660–7669 | 7665

View Article Online
General procedure for lanthanide complexation
chromatography [silica, CH2Cl2–MeOH (0% → 10%)] affording
a yellow-white foam (137 mg, 71%): νmax 3304, 2975, 2932,
2831, 1721, 1657, 1625, 1613, 1559, 1499, 1453, 1409, 1387,
The ligand (1.0 equiv.) was dissolved in methanol (∼50 mM),
and the appropriate LnCl3 or Ln(OTf)3 (1.05 equiv.) was added.
The reaction mixture was heated at 45 °C for 24 h. The sample
was concentrated to ∼half of its volume, and was added slowly
to a large amount of Et2O. The white precipitate was collected
by centrifugation. The solid was dissolved in a minimum
amount of MeOH, and a second round of precipitation was
carried out with Et2O. The collected solid was dried under
vacuum for 24 h.
1368, 1309 cm−1; λmax = 274 nm, 321 nm (CH2Cl2); λem
=
1
415 nm (λex = 356 nm, CH2Cl2); H NMR (400 MHz, CDCl3)
1.00–1.47 (m, 21H) 2.05–4.19 (m, 29H), 6.18 (br, 1H),
6.73–6.85 (m, 1H), 7.56 (br, 1H); 13C NMR (100 MHz, CDCl3)
12.8, 17.7, 19.1, 28.2, 28.3, 43.2, 44.2, 48.6, 51.8, 52.8, 55.7,
56.6, 73.0, 81.9, 82.6, 82.8, 115.8, 116.7, 117.0, 118.2, 120.5,
128.1, 128.3, 131.8, 142.0, 142.4, 152.2, 152.3, 160.4, 170.2,
170.5, 172.9; ESI–MS obsd 696.6 (M + H)+, 718.4 (M + Na)+;
HR-ESI-MS calcd 696.4331 obsd 696.4316 [(M + H)+, M =
C38H57N5O7].
La1. 81%; νmax 3243, 1603, 1405 cm−1; λmax = 244 nm; H
1
NMR (500 MHz, DMSO-d6) δ 2.06–3.97 (m, 27H), 9.01 (br),
10.39 (br), 10.51 (br); 13C NMR (125 MHz, DMSO-d6) 48.56,
50.0–53.0 (2 × br), 62.5, 64.9, 74.3, 79.5; HR-ESI-MS calcd
576.1007 obsd 576.0979 [(M − H)−, M = C19H28N5O7La].
La2. 99%; νmax 3362, 2978, 2840, 2722, 2488, 2088, 1599,
15. Pro-ligand 14 (137 mg, 0.197 mmol) was dissolved in
CH2Cl2 (5 mL). TFA (5 mL) was added to the solution, and the
reaction mixture was stirred vigorously for 16 h. The volatile
components were removed under reduced pressure, and the
yellow, oily residue was dried until it solidified (quant): νmax
3293, 2987, 2863, 2537, 2107, 1719, 1658, 1614, 1560, 1413,
1389, 1308, 1276, 1138, 1189 cm−1; λmax = 273 nm, 323 nm
(sh) (CH3OH); λem = 408 nm (λex = 323 nm, CH3OH); 1H NMR
(300 MHz, CD3OD, broad signals made integration difficult)
1.16–1.21 (m, 3H), 2.14 (s, 1H), 2.31–4.22 (m, ∼26H; should
be 30), 6.33–6.36 (m, 1H), 7.41–7.78 (m, 2H); 13C NMR
(75 MHz, CD3OD, not all peaks resolved) 11.6, 12.0, 16.25,
16.33, 17.5, 23.0, 29.6, 43.6–51.0 (broad signal), 114.1, 115.2,
117.9, 128.0, 132.9, 152.1, 153.6, 161.2; ESI-MS obsd 584.4
(M + H)+, 606.4 (M + Na)+; HR-ESI-MS calcd 584.3079 obsd
584.3070 [(M + H)+, M = C30H41N5O7].
1
1442, 1399, 1323 cm−1; λmax = 264 nm; H NMR (500 MHz,
DMSO-d6) δ 2.88–2.99 (m, 15H), 3.31 (m, 2H), 3.55–3.77 (m,
8H); HR-ESI-MS calcd 521.0910 obsd 521.0933 [(M + H)+,
M = C17H25N4O6La].
La4. 88%; νmax 3068, 2350, 2109, 1668, 1461, 1389, 1352,
1
1186 cm−1; λmax = 265 nm; H NMR (500 MHz, DMSO-d6)
2.85–3.16 (m, 18H), 3.56–3.70 (m, 6H), 3.77 (br s, 2H);
HR-ESI-MS calcd 552.1081 obsd 552.1089 [(M + H)+, M =
C16H26LaN7O6].
Eu4. 76%; νmax 3379, 3072, 2846, 2109, 1720, 1668, 1460,
1398, 1389, 1353, 1295, 1182, 1128, 1089 cm−1; λmax
=
=
264 nm; λem = 578, 590, 612, 650, 898 nm (H2O, λex
1
397 nm); H NMR (500 MHz, DMSO-d6) δ −17.89, −15.86,
−7.41, −3.96, 3.03–3.81, 25.1; HR-ESI-MS calcd 566.1230
obsd 566.1210 [(M + H)+, M = C16H27EuN7O6].
D. Coumarin 2 (869 mg, 4.00 mmol) was dissolved in
anhydrous CH2Cl2 (10 mL). The solution was cooled in an
ice-water bath. NaHCO3 (1.01 g, 12.0 mmol) was added, fol-
lowed by the dropwise addition of chloroacetyl chloride
(382 μL, 542 mg, 4.8 mmol). Stirring was continued for
2.5 h, during which time the reaction mixture was allowed to
warm to room temperature. The mixture was diluted with
water, and the phases were separated. The organic phase was
extracted twice with CH2Cl2. The combined organic layer was
washed with dil. aq. NaHCO3, and dried. Evaporation of the
solvent at reduced pressure afforded a white solid that was
used without further purification. The solid thus obtained was
dissolved in DMF (15 mL), and NaN3 (780 mg, 12.0 mmol)
was added. The reaction mixture was stirred at room tempera-
ture overnight. Water and EtOAc were added. The phases were
separated, and the aqueous layer was extracted twice with
EtOAc. The combined organic phase was washed with three
portions of water, and dried (MgSO4). Evaporation of the
solvent and drying under vacuum for 24 h afforded a pale
yellow solid (1.199 g, 99%): λmax = 274 nm, 321 nm
(CH2Cl2); νmax 2982, 2101, 1716, 1699, 1665, 1624, 1613,
Tb4. 75%; νmax 3244, 2115, 1576, 1446, 1408 cm−1; λmax
=
219 nm (sh); λem = 487, 543, 585, 620 nm (H2O, λex = 366 nm);
HR-ESI-MS calcd 572.1271 obsd 572.1263 [(M + H)+, M =
C16H26N7O6Tb].
La5. 87%; νmax 3278, 2103, 1610, 1407 cm−1; λmax
=
264 nm; 1H NMR (500 MHz, DMSO-d6) δ 2.91–2.98 (m, 12H),
3.38 (s, 2H), 3.55 (s, 4H), 3.83 (s, 4H); HR-ESI-MS calcd
501.1012 obsd 501.1012 [(M + H)+, M = C18H25LaN4O4].
La16. 99%; λmax = 275 nm, 320 nm (H2O); νmax 3284, 2976,
2107, 1691, 1595, 1438, 1409, 1273, 1191, 1157, 1085 cm−1
;
1
λem = 448 nm (λex = 350 nm, CH3OH); H NMR (300 MHz,
D2O) 0.98–1.06 (m, 3H), 2.08–2.28 (m, 7H), 2.53 (s, 1H),
2.77–3.93 (m, 25H), 6.13 (s, 1H), 7.15 (s, 1H), 7.60 (s, 1H);
HR-ESI-MS calcd 720.1907 obsd 720.1907 [M+,
C30H39LaN5O7].
M =
Tb16. 99%; λmax = 275 nm, 320 nm (H2O); νmax 3358, 2978,
2844, 2722, 2488, 2088, 1590, 1442, 1399, 1321 cm−1; λem
=
387 (ligand), 486, 544, 587, 620 nm (λex = 320 nm, CH3OH);
HR-ESI-MS calcd 740.2097 obsd 740.2084 [M+,
C30H39N5O7Tb].
M =
1557, 1500, 1444, 1409, 1385, 1353 cm−1
;
1H NMR
(500 MHz, CDCl3) 1.16 (t, J = 7.2 Hz, 3H), 2.30 (s, 3H), 2.44
(d, J = 1.3 Hz, 3H), 3.26–3.33 (m, 2H), 3.60 (d, J = 15.9 Hz,
1H), 4.12–4.19 (m, 1H), 6.33 (d, J = 1.3 Hz, 1H), 7.09 (s,
1H), 7.54 (s, 1H); 13C NMR (125 MHz, CDCl3) 12.9, 17.5,
18.9, 43.9, 51.0, 116.3, 117.6, 120.7, 127.5, 132-1. 142.0,
151.5, 152.4, 160.1, 166.8; HR-ESI-MS calcd 301.1295 obsd
301.1298 [(M + H)+, M = C15H16N4O3], calcd 323.1115 obsd
323.1127 (M + Na)+.
General procedure for cycloadditions
A magnetic stir-bar, the alkynyl- or azido-lanthanide complex
(0.2 mmol), the appropriate azide- or alkyne (1.1 equiv.) and
CuI (5%) were placed in a microwave vial, and the solids were
suspended in a 4 : 1 mixture of CH3CN and the base indicated at
7666 | Dalton Trans., 2012, 41, 7660–7669
This journal is © The Royal Society of Chemistry 2012

View Article Online
1
the experiment (0.2 M). The vial was sealed, and the mixture
was heated at 100 °C for the indicated time. The mixture was
allowed to cool back to room temperature. In those cases where
the product was insoluble in the reaction solvent mixture the pre-
cipitate was collected by centrifugation, and the solid material
was washed with a small amount of CH3CN. The residue was
dissolved in the minimum amount of water containing a small
amount of MeOH, and the solution was freeze-dried. When a
homogeneous solution was obtained after the reaction, the
product was precipitated out with Et2O, the precipitate was col-
lected by centrifugation, and the solid residue was further
purified either by repeated precipitation from MeOH–Et2O, or
column chromatography [silica, CH3CN–H2O (9 : 1 → 2 : 1)].
616, 652, 699 nm (H2O, λex = 280 nm); H NMR (300 MHz,
D2O, only well-resolved signals outside 0–10 ppm reported)
−16.11, −16.64, −8.12, −6.78, −2.31, −1.19, −0.86, −0.83,
−0.27, 33.57; HR-ESI-MS calcd 654.1543 obsd 654.1555
[(M + H)+, M = C23H30EuN7O6], calcd 676.1362 obsd 676.1387
(M + Na)+
i
Eu2D. 60 min, Pr2NH, 95%; tR = 3.27 min (85.85% purity,
contains 12.76% D); νmax 3409, 2973, 2833, 2759, 2720, 2488,
2429, 2104, 1723, 1612, 1466, 1442, 1399, 1329 cm−1; λmax
=
275 nm, 319 nm; λem = 380 nm (ligand), 578, 588, 596, 616,
686, 699 nm (H2O, λex = 280 nm); H NMR (300 MHz, D2O,
1
signals outside 0–10 ppm reported) −19.48, −18.81, −15.06,
−14.15, −13.68, −12.73, −12.05, −10.31, −9.39, −8.94, −8.74,
−8.54, −7.54, −6.98, −6.83, −5.77, −5.29, −4.73, −3.65,
−3.35, −3.18, −2.41, −2.23, −1.19, 10.13, 11.16, 12.24, 12.38,
13.33, 13.98, 14.60, 15.75, 25.65, 26.27, 27.11, 29.20;
HR-ESI-MS calcd 835.2282 obsd 835.2263 [(M + H)+, M =
C32H41EuN8O9], calcd 857.2101 obsd 857.2075 (M + Na)+.
i
La1A. 15 min, Pr2NH, 85%, 57% chrom; νmax 3341, 2979,
2724, 2488, 2187, 2086, 1582, 1443, 1398, 1327 cm−1; λmax
=
1
263 nm; H NMR (300 MHz, D2O) 2.07–4.11 (br m), 5.61 (br,
2H), 7.37–7.43 (m, 5H), 8.02 (br, 1H); HR-ESI-MS calcd
733.1584 obsd 733.1559 [(M + Na)+, M = C26H35LaN8O7].
i
i
Eu1A. 15 min, Pr2NH, 88%; tR = 3.28 min (96.95% purity);
Tb2D. 60 min, Pr2NH, 79%; tR = 3.28 min (85.58% purity,
νmax 3224, 2982, 2482, 2116, 1574, 1442, 1400, 1320 cm−1
;
contains 13.74% D); νmax 3386, 2975, 2107, 1725, 1613, 1443,
1400, 1324 cm−1; λmax = 275 nm, 319 nm; λem = 386 nm
(ligand), 486, 545, 585, 620 nm (H2O, λex = 278 nm);
HR-ESI-MS calcd 841.2323 obsd 841.2339 [(M + H)+, M =
C32H41N8O9Tb], 863.2142 obsd 863.2153 (M + Na)+.
λmax = 260 nm (sh); λem = weak Eu-emission; 1H NMR
(300 MHz, D2O, signals outside 0–10 ppm reported) −17.55,
−16.88, −16.26, −15.89, −14.57, −12.49, −11.79, −11.20,
−9.45, −9.02, −8.42, −8.19, −7.99, −7.66, −7.48, −7.01,
−6.09, −5.03, −4.35, −3.79, −2.73, −1.92, −1.66, −1.19,
−0.65, −0.32, 11.27, 29.89, 30.26, 31.01, 32.39; HR-ESI-MS
calcd 725.1914 obsd 725.1903 [(M + H)+, M = C28H35EuN8O7],
calcd 747.1733 obsd 747.1695 (M + Na)+.
i
La3A. 15 min, Pr2NH; 86%; νmax 3302, 2836, 2100, 1595,
1
1458, 1322, 1148 cm−1; λmax = 264 nm; H NMR (300 MHz,
D2O/CD3OD) 2.15–4.23 (m), 5.76–5.83 (2 × br, 2H), 7.53 (br,
5H), 8.21 (br, 1H); HR-ESI-MS calcd 651.2030 obsd 651.2017
[(M − 2H)+, M = C24H38LaN10O3].
i
La2A. 15 min, Pr2NH, 58%; 66% chrom; νmax 3244, 2978,
2858, 2722, 2488, 1575, 1442, 1399, 1321 cm−1; λmax
=
Eu3A. 15 min, Pr2NH; 90%; νmax 3358, 2978, 2850, 2722,
i
263 nm, 319 nm (sh); 1H NMR (300 MHz, D2O) 2.11–3.06 (m),
5.55–5.62 (m, 2H), 7.32 (br, 5H), 7.95 (br, 1H); HR-ESI-MS
calcd 654.1550 obsd 654.1546 [(M + H)+, M = C24H32LaN7O6],
calcd 676.1370 obsd 676.1371 (M + Na)+.
2487, 2098, 1595, 1442, 1399, 1322 cm−1; λmax = 225 nm,
261 nm; λem = 577, 590, 614, 649, 698 nm (H2O, λex
=
1
280 nm); H NMR (300 MHz, D2O/CD3OD, only well-resolved
peaks outside 0–10 ppm reported) −16.73, −10.11, −8.93,
19.73; HR-ESI-MS calcd 665.2179 obsd 665.2140 [(M − 2H)+,
M = C24H38EuN10O3], also obsd 333.6 (M − H)2+.
i
Eu2A. 15 min, Pr2NH, 60%, 55% chrom: tR = 3.20 min
(95.46% purity); νmax 3356, 2978, 2844, 2759, 2721, 2488,
2098, 1586, 1442, 1398, 1321 cm−1; λmax = 263 nm, 314 nm
La4E. 30 min, Pr2NH; quant., 16% chrom: νmax 3275, 2984,
i
1
(sh); λem = weak Eu-emission (H2O, λex = 280 nm); H NMR
2858, 2741, 2502, 2174, 1008, 1604, 1448, 1396, 1143,
1078 cm−1; λmax = 258 nm; 1H NMR (300 MHz, D2O)
2.10–3.66 (m), 7.37–7.39 (m, 3H), 7.68 (br, 2H), 8.31 (br, 1H);
HR-ESI-MS calcd 654.1573 obsd 654.1550 [(M + H)+, M =
C24H32LaN7O6], calcd 676.1392 obsd 676.1370 [(M + Na)+.
(300 MHz, D2O, signals outside 0–10 ppm reported) −19.38,
−18.65, −14.97, −14.72, −13.4, −12.56, −9.94, −9.36, −9.12,
−8.87, −8.61, −8.07, −7.60, −6.84, −7.14, −6.84, −6.20,
−5.87, −5.62, −5.22, −4.85, −4.42, −1.19, −0.93, −0.88,
−0.73, −0.28, 10.01, 10.76, 12.78, 26.88, 26.33, 26.96, 29.12;
HR-ESI-MS calcd 690.1519 obsd 690.1524 [(M + Na)+, M =
C24H32EuN7O6].
i
Eu4E. 30 min, Pr2NH; quant, 34% chrom: tR = 3.27 min
(97.29% purity); νmax 3386, 2983, 2865, 2502, 2100, 1591,
1461, 1394, 1319 cm−1; λmax = 244 nm; λem = 578, 588, 596,
i
1
Tb2A. 15 min, Pr2NH, 56%, 45% chrom: νmax 3353, 2976,
616, 699 nm (H2O, λex = 278 nm); H NMR (300 MHz, D2O,
2855, 2722, 2484, 2108, 1583, 1442, 1399, 1322 cm−1; λmax
=
signals outside 0–6 ppm reported) −13.09, −12.21, −11.18,
−8.33, (−6.79)–(−5.71), 6.97–7.96; HR-ESI-MS calcd
690.1519 obsd 690.1525 [(M + Na)+, M = C24H32EuN7O6].
262 nm; λem = 413 nm (ligand), 487, 543, 586, 620 nm (H2O,
λex = 280 nm); HR-ESI-MS calcd 696.1560 obsd 696.1569
[(M + Na)+, M = C24H32N7O6Tb].
i
Tb4E. 30 min, Pr2NH; 98%: tR = 3.17 min (99.37% purity);
i
La2C. 30 min, Pr2NH, 44%; tR = 3.20 min (97.49% purity);
νmax 3401, 2983, 2867, 2510, 2102, 1595, 1462, 1395,
1319 cm−1; λmax = 245 nm, 309 nm (sh); λem = 486, 545, 585,
620 (H2O, λex = 278 nm); HR-ESI-MS calcd 696.1560 obsd
696.1568 [(M + Na)+, M = C24H32N7O6Tb].
νmax 3366, 2834, 2720, 2489, 2099, 1587, 1503, 1469, 1443,
1399, 1327, 1155, 1106, 1074 cm−1; λmax = 255 nm, 320 nm
1
(sh); H NMR (300 MHz, D2O, very broad signals) 1.52–3.81
i
(m), 4.94–4.98 (br, ∼2H), 7.48–7.64 (br, ∼5H); HR-ESI-MS
La4F. 30 min, Pr2NH; quant%, 29% chrom; tR = 3.23 min
calcd 640.1394 obsd 640.1389 [(M + H)+, M = C23H30LaN7O6].
(86.54%, contains 6.85% F); νmax 3358, 2978, 2840, 2760,
i
Eu2C. 30 min, Pr2NH, 42%; tR = 3.28 min (99.26% purity);
2723, 2488, 2177, 2087, 1587, 1442, 1399, 1323 cm−1; λmax
=
νmax 3389, 2846, 2727, 2501, 2099, 1591, 1462, 1390, 1318,
266 nm, 345 nm, 405 (sh); 1H NMR (500 MHz, DMSO-d6)
1150, 1089 cm−1; λmax = 249 nm, 320 nm (sh); λem = 578, 588,
1.29 (t, J = 7.0 Hz, 3H), CH2N-signals poorly resolved and
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overlapping with solvent signals, 4.26 (q, J = 7.0 Hz, 2H), 4.65
(br, 2H), 4.97 (br, ∼0.4H), 5.21 (s, 1H), 7.07–7.18 (m, 2H),
7.85–7.86 (m, 1H), 8.37 (br, 1H), 8.72 (s, 1H); HR-ESI-MS
Notes and references
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calcd 846.1585 obsd 846.1558 [(M
+
Na)+,
M
=
C31H38LaN7O11].
i
Eu4F. 30 min, Pr2NH; 98%: tR = 3.18 min (88.71% purity,
contains 7.52% F); νmax 3264, 2984, 2868, 2723, 2495, 2137,
1731, 1704, 1678, 1610, 1505, 1466, 1389, 1304, 1133,
1072 cm−1; λmax = 255 nm, 345 nm, 405 nm (sh); λem = 400 nm
1
(ligand), 578, 589, 614, 651, 698 nm (H2O, λex = 356 nm); H
NMR (300 MHz, D2O, signals outside 0–6 ppm reported)
−13.04, −12.18, −11.19, −8.33, −6.42, 6.43, 6.89, 7.39, 7.54,
7.87, 8.50; HR-ESI-MS calcd 860.1734 obsd 860.1699
[(M + Na)+, M = C31H38EuN7O11].
i
Tb4F. 30 min, Pr2NH; 37%, 33% chrom: tR = 3.23 min
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Res. Tech., 2003, 62, 396.
(66.36% purity, contains 22.71% F); νmax 3359, 2978, 2836,
2761, 2723, 2488, 2183, 2088, 1598, 1441, 1399, 1323 cm−1
;
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λmax = 266 nm, 347 nm, 401 nm; λem = 400 nm (ligand, only
signal in steady-state mode); λem = very faint Tb-emission (50 μs
delay, H2O, λex = 356 nm); HR-ESI-MS calcd 844.1955 obsd
844.1972 [(M + H)+, M = C31H38N7O11Tb].
i
La5A2. 30 min, Pr2NH; 47%, 44% chrom; tR = 9.98 min
(93.60% purity); νmax 3374, 2974, 2837, 2759, 2721, 2487,
1
2099, 1984, 1586, 1442, 1399, 1323 cm−1; λmax = 263 nm; H
NMR (300 MHz, DMSO-d6) 2.05–4.65 (m), 5.61–5.65 (2 × br,
4H), 7.31–7.47 (br m, 10H), 8.29 (br, 2H); HR-ESI-MS calcd
767.2292 obsd 767.2314 [(M + H)+, M = C32H40LaN10O4].
EuLa17. 30 min, piperidine, 33%; tR = 3.26 min (92.51%
purity); νmax 3302, 2971, 2855, 2493, 2098, 1723, 1596, 1454,
1383, 1319, 1275, 1086 cm−1; λmax = 274 nm, 319 nm; λem
=
579, 589, 612, 650, 698 (H2O, λex = 320 nm); 1H NMR
(300 MHz, D2O) −13.13, −12.36, −11.11, −8.37, −6.35,
1.14–3.56, 6.30, 7.36, 7.71, 8.22, 9.56; HR-ESI-MS calcd
1285.3064 obsd 1285.3047 [M+, M = C46H65EuLaN12O13].
EuTb17. 30 min, piperidine, 60%; tR = 3.24 min (93.16%
purity); νmax 3367, 2976, 2843, 2723, 2487, 2099, 1593, 1441,
1398, 1321 cm−1; λmax = 268 nm, 322 nm; λem = 486, 542, 580,
587, 613, 653, 700 nm (H2O, λex = 320 nm); HR-ESI-MS
i
calcd 1406.4100, obsd. 1406.4519 [(M + CH3CN + PrOH)+,
M = C46H65EuN12O13Tb], MALDI-MS 668.1 [calcd 668.2
(M + MeOH + H)2+].
LaEu218. 60 min, piperidine, 34%; νmax 3283, 2950, 2101,
1611, 1408 cm−1; λmax = 220 nm (sh), 264 nm; λem = 578, 589,
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1
614, 648, 699 nm (H2O, λex = 397 nm); H NMR (300 MHz,
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C50H78Eu2LaN18O16].
+
C6H11N), M+
=
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Acknowledgements
Funding from the Swedish Research Council, Carl Tryggers Stif-
telse, and the Departments of Chemistry, Uppsala University and
Organic Chemistry, Stockholm University is gratefully acknowl-
edged. We thank Mr Fredrik Tinnis for compound B, and
Dr James Bruce and Dr Luke Pilarski for critical reading of the
manuscript.
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