Unusual Magnetic Field Responsive Circularly Polarized Luminescence Probes with Highly Emissive Chiral Europium(III) Complexes

Article abstract of DOI:10.1002/anie.202012133

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |g_lum| up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral Eu^III complexes, promoting an exciting development to the field of magneto-optics. The |g_lum| of the ⁵D₀ → ⁷F₁ transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δg_lum and the magnetic field strength. These Eu^III complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution.

Full text of DOI:10.1002/anie.202012133

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Unusual Magnetic Field Responsive Circularly Polarized
Luminescence Probes with Highly Emissive Chiral Eu(III)
Complexes
Authors: Junhui Zhang, Lixiong Dai, Alexandra M. Webster, Wesley
Ting Kwok Chan, Steven L. Cobb, and Ga-Lai Law
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202012133
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10.1002/anie.202012133
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RESEARCH ARTICLE
Unusual Magnetic Field Responsive Circularly Polarized
Luminescence Probes with Highly Emissive Chiral Eu(III)
Complexes
Junhui Zhang,[a][b] Lixiong Dai,[a][b] Alexandra M. Webster,[c] Wesley Ting Kwok Chan,[a] Steven L.
Cobb[c] and Ga-Lai Law*[a][b]
[a]
Dr. G. -L. Law, J. Zhang, L. Dai, W. T. K. Chan
Department of Applied Biology and Chemical Technology
State Key Laboratory of Chemical Biology and Drug Discovery
The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China
E-mail: galai.law@polyu.edu.hk
[b]
[c]
Dr. G. -L. Law, J. Zhang, L. Dai
The Hong Kong Polytechnic University Shenzhen Research Institute
Shenzhen 518000, PR China
A. M. Webster, Dr. S. L. Cobb
Department of Chemistry
Durham University, South Road, Durham DH1 3LE, U.K.
Supporting information for this article is given via a link at the end of the document.
Abstract: Chirality is ubiquitous within biological systems where
many of the roles and functions are still undetermined. Given this,
there is a clear need to design and develop sensitive chiral optical
probes that can function within a biological setting. Here we report the
design and synthesis of magnetically responsive Circularly Polarized
diversity in the use of CPL has been further stimulated by recent
technological developments such as chiral luminescence
microscopy.[8-9] The challenge now lies in the development of
chiral complexes with both high CPL and quantum yields that are
suitable for in vitro studies.
Luminescence
(CPL)
complexes
displaying
exceptional
Due to the selection rules for CPL, which is reliant on
magnetic dipole-allowed transitions, an innate feature of some
transitions in lanthanides luminescence, large CPL signal can be
observed in certain transitions of lanthanide complexes.
According to theoretical studies, the relationship between the glum
photophysical properties (quantum yield up to 31% and |glum| up to
0.240) by introducing chiral substituents onto the macrocyclic
scaffolds. Magnetic CPL responses are observed in these chiral
Eu(III) complexes, promoting an exciting development to the field of
5
7
magneto-optics. The |glum| of the D0 → F1 transition increases by
20% from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship
between the Δglum and the magnetic field strength. These Eu(III)
complexes with magnetic CPL responses, provides potential
development to be used in CPL imaging applications due to improved
sensitivity and resolution.
and the lanthanide transitions can be described as glum =
4|Mba|/|Pab|·cosτab,[10] where |Pab| and |Mba| are the electric and
magnetic dipole transition moment vectors respectively, hence
the most suitabletransition to give a large magnitude for a strong
Introduction
Chirality plays an essential role in all living matter, it can be
observed from macroscopic to microscopic worlds, from human
hands to natural amino acids. It exists in biological activities,
including cellular uptake processes, metabolism and in protein
structures. Significant efforts have been devoted to reveal its
underlying existence in nature. To date, methodologies involving
circular dichroism (CD) and circularly polarized luminescence
(CPL) have proven to be valuable techniques that can be used to
probe chiral information.[1-2] CPL and magnetic circularly polarized
luminescence (MCPL), which are the emission analogs of CD and
magnetic circular dichroism (MCD) respectively, provide a
powerful and highly sensitive way to determine the conformation
of biological macromolecules in solution and hence give a better
understanding of their activities.[3-5] The advantage that CPL
offers over CD is that it can provide chiroptical information of the
excited states of compounds to correlate with the local chiral
structural changes dynamically[6]. For example, CPL studies have
been used to discriminate the ratio of ADT/ATP in solution[7]. The
Scheme 1. Molecular structures of EuL1-6 (top). Peptoid used for conjugation
for EuL7 (bottom), (A) piperidine/DMF (1:5, v/v); (B) DMF, (R)(SAP)EuL3, NMM,
PyBop; (C) 95% TFA, 3% water, 2% TIPS.
1
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dissymmetry factor (glum) is at the magnetic- dipole allowed, but
in the main cyclization step. The configurations of the chiral
substituents on all these macrocyclic scaffolds were maintained,
confirmed by the crystal structure of the isopropyl chiral cyclen
intermediate (Figure S74). After deprotection of these macrocyclic
scaffolds, another coupling reaction was further conducted to
incorporate the new chromophore - the detailed synthetic
procedures are shown in the SI - this is then followed by the
addition of ethyl 2-bromoacetate to form the pendant arms on the
scaffold. Subsequent deprotection of the ethyl groups on the
pendant arms by LiOH gave the final ligand.
In the complexation procedure, europium chloride
hexahydrate was added to the deprotected ligand L1-6 in water
and refluxed for 16 hours. After purification by reversed-phase
semi-preparative HPLC, the pure SAP isomers of the Eu(III)
complexes (unless stated) were obtained for analysis and
measurements.
electric-dipole forbidden D0 → F1 transition.[10-12] Compared to
small chiral organic molecules (|glum| typically within 10-3 – 10-1
range)[13-15], typical glum of chiral lanthanide complexes can reach
≥0.1.[11, 16-19] In addition to distinguished glum values, the sharp and
narrow signature emission bands, long lifetimes and large
pseudo-Stokes’ shifts of the chromophores, as well as the
lanthanide ions’ spherical nature which eliminates the problem of
anisotropy,[20] are all factors that attributes to lanthanide
complexes being ideal for use in imaging applications. However,
to date, there are still only limited examples of lanthanide
complexes used in CPL applications, due to the difficulties in the
design and synthetic work.
5
7
Herein, we report a new series of highly emissive, CPL
europium probes, EuL2-7, with excellent stability and water
solubility rendering it suitable to the development of biological
sensors (Scheme 1). In our ligand design, chiral substituents were
To demonstrate that these Eu(III) complexes are suitable for
introduced to the macrocyclic scaffolds, achieving 4 chiral centers, cellular studies, a CPPo, Npmb-NLys-Npcb-NLys-NH2, which can
which suppress ring inversion and ‘lock’ the isomers in place,
eliminating interconversion between isomers. By the use of a
reversed-phase HPLC equipped with an achiral column, these
geometric isomers can be easily separated and hence reduces
the difficulties in the purification and synthetic methodology. The
selection of a suitable rigid chromophore and effective sensitiser
was performed through the screening strategy reported in our
prior work.[21] The quantum yields of EuL2-7 improved
significantly compared with the achiral EuL1 due to the modified
chiral DOTA chelators.[22]
More importantly, other than the intrinsic CPL properties, we
further examined the effect of an external magnetic field on our
compounds. This work builds on earlier publications of Riehl and
Richardson, both of them studied the induced MCPL under static
external magnetic field from naturally optically inactive probes,
and lately by Yoshikawa et al.[23-25] As postulated, applying an
external magnetic field induced stronger CPL signals and higher
glum values were obtained for EuL2-7 with obvious trends in MCPL
enhancement, making these Eu(III) complexes suitable as
magneto-optical probes.[26-27]
With these promising results, we attempted to enhance the
biocompatibility of these Eu(III) complexes. As a proof of concept,
a cell penetrating peptoid (CPPo) was introduced to the carboxylic
linker handle on the chromophore. This is use to show the
functionalisation capabilities for developing more robust and
specific probes that can be used for tracking specific cellular
organelles in biological imaging.[28] Upon successful peptoid
conjugation, we found this led to an even higher quantum yield,
and at the same time demonstrates the feasibility and potential of
these Eu(III) complexes as imaging probes and tags where
functionalisation does not sacrifice the desirable photophysical
properties.
selectively localize in the
conjugation as proof of concept. The peptoid was conjugated via
Gly-Gly linker to form the complex (R)EuL7. Peptoid
conjugation was performed using the highly biocompatible
carboxylic linker in (R)(SAP)EuL3 in 3 steps (Scheme 1).
The photophysical properties of these complexes were then
studied and are summarised in Table 1. For the UV
mitochondria,[28] was used for
a
measurements, EuL1-7, all complexes display
a similar
absorption spectrum as well as extinction coefficient in 0.1 M
HEPES buffer, resulting from the same chromophore
incorporated in the structure. Hence, we selected EuL3 with the
ethyl chiral backbone for discussion. The absorption band of
(SAP)EuL3 with a maximum at 333 nm (ɛ350nm of EuL1-7: ~ 18000
mol-1dm3cm-1) (Figure S3), is assigned as the π-π* transition of
the chromophore. There is no observable ligand emission peak in
the spectra of the europium complexes. This indicates efficient
energy transfer of the ligand-to-metal and is consistent with the
calculated ηsens, which mostly lie within the range of 80-90%.
According to the data in Table 1, the quantum yields of SAP
isomers are generally much higher than that of the TSAP(EuL3).
This may be due to the higher ηsens (80-90%) in SAP isomers than
that of the TSAP (74%), thus giving rise to better ligand-to-metal
energy transfer and hence higher quantum yields and brightness.
Compared with the achiral EuL1, the chiral EuL2-7 showed
significant increase in quantum yields by simply varying the chiral
substituent on the backbone. The only exception here is
(TSAP)EuL3, which we propose is due to the difference in the
isomer conformation (Figure 1A & 1B). Upon conjugation of the
peptoid to (R)(SAP)EuL3 , where the -OH group is replaced by
the peptoid to give (R)EuL7, the photophysical properties of
(R)EuL7 were found to be enhanced as shown by a slight
increase in quantum yield when compared to the other chiral
europium complexes. The luminescence lifetimes for EuL1-7
were measured in water and D2O. Extremely long lifetimes were
Results and Discussion
obtained in the millisecond range for the main Eu (5D0
→
7F2)
transition. The q values of these Eu(III) complexes are consistent,
all close to 0, according to Parker’s and Horrocks’ equations.[29-30]
This implies no water molecules are coordinated to the first
coordination sphere of the Eu(III) metal center. Furthermore, the
chiral groups introduced to the macrocyclic scaffolds also shield
the lanthanide metal center from water coordination, hence any
quenching by OH oscillators is eliminated. All these factors in the
structural design play an important role to attribute to the high
EuL1-6 ((R)EuL3 and (R)EuL7)) are in S(R) configuration
and synthesized from the S(R) isomer of natural amino acids.
Unless stated, the handedness of Eu(III) complexes is in S
configuration. The synthesis of chiral cyclens with methyl or ethyl
substituents was reported in our previous publication.[22] The other
chiral cyclens were also synthesised by using the same strategy
with catalysis of the 3-membered ring intermediates by Lewis acid
boron trifluoride diethyl etherate to form 12-membered scaffolds
2
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Table 1. Photophysical properties of EuL1-7 measured in 0.1 M HEPES, pH 7.3, at 298 K, excited at 350 nm, with 380 nm long pass filter.
EuL1
18.4±0.4
0.976±0.09
1.71±0.08
0.23
EuL2
27.0±0.3
1.09±0.08
1.93±0.007
0.18
(SAP)EuL3
28.0±1.5
1.30±0.02
2.14±0.01
0.06
(TSAP)EuL3
19.8±1.8
1.06±0.02
1.65±0.09
0.10
(R)EuL3
26.3±0.6
1.21±0.05
2.14±0.004
0.13
EuL4
25.6±0.8
1.35±0.006
2.21±0.005
0.05
EuL5
24.1±0.7
1.33±0.006
2.15±0.002
0.04
EuL6
26.7±0.2
1.26±0.02
2.10±0.003
0.08
(R)EuL7
31.3±1.1
1.39±0.004
2.06±0.003
-0.02
Φ (%)[a]
τH2O (ms)[b]
τD2O (ms)[b]
Q[c]
Q[d]
0.14
0.10
-0.01
0.03
0.05
-0.02
-0.03
0.01
-0.08
ΦEuEu (%)
ηsens (%)
R[e]
24.3±1.8
74.6±3.4
2.61
29.2±1.4
92.4±4.1
2.53
30.9±1.5
90.3±1.9
2.54
26.6±1.9
74.4±3.1
2.50
32.2±0.7
81.6±3.4
2.48
32.5±0.7
78.8±1.3
2.54
32.4±0.6
74.2±3.4
2.52
31.9±0.2
83.7±1.5
2.45
33.2±0.2
94.5±2.5
2.55
B[f]
3312
4860
5040
3564
4734
4608
4338
4806
5634
[a] Relative to quinine sulfate in 0.1 M H2SO4 (λex = 350 nm, Φ = 0.577). Estimated errors of quantum yield and lifetime are ±15% and ±10% respectively. [b]
Measuring the 5D0 → 7F2 transition. [c] Calculated by Parker’s equation.[29] [d] Calculated by Horrocks’ equation.[30] [e] I(5D0 → 7F2)/I (5D0 → 7F1).[31] [f] B = ɛ350nmΦ[32]
quantum yields obtained for these Eu(III) complexes.[33-34] To
study the energy transfer pathway, (SAP)GdL3 was synthesized
for low temperature studies at 77 K. Due to the similar ionic radii
of Gd(III) to the Eu(III) cation, the Gd cation is commonly used as
a surrogate for such measurements as it has a highly lying excited
state above 30000 cm-1, which typically prevents energy transfer
from the ligand to the metal. Hence instead, the excited energy
decay radiatively as either fluorescence from the singlet state or,
due to the heavy atom effect of the proximal Gd(III), which
promotes intersystem crossing, as phosphorescence from the
triplet state of the ligand.[35]
configuration, the emission spectra (Figure 1C) shows distinct
splitting patterns for these isomers due to their different
geometries in the DOTA platform. Comparing their emission
spectra, the SAP and TSAP isomers can be identified through the
5D0 → F1, D0 → F2 and D0 → F4 transition bands. In ΔJ = 1
transition, larger spectral splitting is observed in the SAP isomer,
giving rise to three well-identifiable peaks, however a relatively
broad peak was observed for the TSAP isomer. In the ΔJ = 2
transition, only one peak can be observed in the SAP isomer as
the transitions caused by the SAP
7
5
7
5
7
Insight to either a fluorescence or phosphorescence decay
can be further corroborated by comparing lifetime measurements
as well as comparing the emission maxima at room temperature
and 77 K. From the emission spectrum of (SAP)GdL3 at room
temperature, the emission maximum is at 455 nm with a
monoexponential lifetime, 7.49 µs. At 77 K, the emission
maximum is at 405 nm and its monoexponential lifetime is 6.69
µs. These two emissions are assigned as ligand fluorescence
from excited 1S1* and 1S2* states and are confirmed by the short
microsecond lifetimes obtained. Moreover, the emission
maximum at 77 K is blue shifted compared to the room
temperature spectrum, this implies that energy transfer is directly
from the ligand’s singlet excited states, rather than the triplet
states, to the Eu(III) metal center; this phenomenal is not
uncommon.[36] Through unit conversion, the excited 1S1* and 1S2*
states are around 21930 cm-1 and 24813 cm-1, which are 2904
5
5
cm-1 (ΔE: 1S1*→ D1) and 3314 cm-1 (ΔE: 1S2*→ D2) away from
the accepting levels of Eu(III) (Figure S15). According to the
energy gap law, ΔE within 2500-3500 cm-1 is ideal for efficient
energy transfer and this is consistent with the ηsens of EuL2-7.[37-
38]
As aforementioned, these Eu(III) complexes, EuL2-7 are all
in the SAP form, except (TSAP)EuL3 (Figure 1A & 1B) which
was isolated in order to study the properties of these geometric
isomers.[39] Here, the TSAP isomer existed as the minor peak,
observed in the HPLC trace and were separated by an achiral
reversed phase HPLC. (SAP)EuL3 and (TSAP)EuL3 are
geometric isomers with the same chiral ethyl group in (S)
Figure 1. A) Front view of SAP (left) and TSAP (right); B) Top-down view of
SAP (left) and TSAP (right), atoms are represented as spheres with different
color: europium (red), oxygen (blue), nitrogen (black); C) Emission spectra of
(SAP)EuL3 (top) and (TSAP)EuL3 (bottom), excited at 350 nm, in 0.1 M
HEPES buffer, pH 7.3, with 380 nm long pass filter.
3
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ligand-field splitting are approximately at the same energy levels,
but for TSAP, the energy levels of these transitions are different,
which resulted in an extra minor peak near the main peak. In ΔJ
= 4, a less resolved peak was observed with greater peak overlap
in the SAP isomer, whereas the TSAP shows a clear defined peak
separation.[40-41] The spectral splitting in SAP and TSAP of these
(SAP)EuL3 and (TSAP)EuL3 also shows a similar pattern to the
parent chiral ethyl DOTA analogue (Figure S10). The differences
of these SAP and TSAP isomers have also been confirmed by
NMR spectra (see SI p.78), which is also similar to the NMR of
their parent chiral DOTA.[22, 42] Larger chemical shifts in the NMR
for the proton set in SAP isomer were observed from 15 to 30 ppm,
while the TSAP isomer showed relatively centralized proton
signals from around 10 to 15 ppm.
Table 2. glum values of EuL2-7 in 0.1 M HEPES, pH 7.3.
Transition
EuL2
5D0 → 7F1
-0.193
-0.222
0.221
5D0 → 7F2
0.052
(SAP)EuL3
(R)(SAP)EuL3
(TSAP)EuL3
EuL4
0.059
-0.058
0.059
0.228
-0.202
-0.240
-0.212
0.222
0.049
EuL5
0.058
EuL6
0.071
To reveal the chiroptical information in biomacromolecules,
such as proteins, cellular organisms, CPL compounds need to be
(R)EuL7
-0.059
water soluble, stable, highly emissive with large glum which is
11, 43-47]
difficult to balance simultaneously.[8,
In our previous
Solvent effects also exist in the CPL measurements. CPL
measurements for (SAP)EuL3 were conducted in different
solvents: 0.1 M HEPES, MeOH and DMSO. In HEPES and MeOH,
the CPL spectra of (SAP)EuL3 displayed similar spectral shapes.
There were, however, some differences observed in DMSO,
where more spectral splitting were observed. For example, the
studies,[48] our design strategy required 8 chiral centers in order
to create a chiral environment to give an optimised glum (-0.23 at
the transition 5D0 → 7F1), but it has simultaneously increased the
synthetic difficulties. Here, in this simpler design of EuL2-7, we
show that comparable glum values (Table 2) are possible even by
reducing the number of chiral centers to only 4 chiral centers by
incorporating a more rigid chromophore. To obtain a more rigid
chromophore, the phosphate group was modified to a carboxyl
group and an increased glum values was achieved as expected.[11]
From our CPL studies, the largest dissymmetry factor among
EuL2-7, 0.240, was observed in the 5D0 → 7F1 transition of EuL5.
To the best of our knowledge, this is one of the highest glum values
observed in such classes of Eu(III) macrocyclic complexes. We
hypothesis that the asymmetric nature of the DO3A structure with
a chromophore in these Eu(III) complexes may also assist in
generating such high glum values as the non-symmetric structure
deviates the twist angles of the SAP and TSAP geometries from
40° and 29° to around ±22.5°, which is similar to previous values
for a maximal glum reported by Bruce et al.[10]
7
peak of 5D0 → F1 transition in (SAP)EuL3 splits into 2 in DMSO
(Figure 3A). The glum values of (SAP)EuL3 in DMSO, MeOH and
0.1 M HEPES buffer were calculated as -0.138, -0.203 and -0.222
respectively. Interestingly, the glum values enhanced with an
increase in solvent polarity. Comparing the least polar solvent
(DMSO with relative polarity = 0.444) to the most polar solvent
(0.1 M HEPES with relative polarity = 1),[49] the glum value of
(SAP)EuL3 increased around 61% (|0.138| to |0.222|). One of the
possible explanations is the Pfeiffer effect between (SAP)EuL3
and the solvent molecules, in which the solvation sheath created
around the complex generates a second source of chirality
affecting the glum value. [46]
The effects of the steric hindrance from the chiral
substituents were also examined in this study. The asymmetry
ratio, R, is calculated to reveal the geometric difference in EuL1-
Upon examination of the (S)(SAP)EuL3 and (R)(SAP)EuL3
which are of opposite handedness, these exhibited mirror images
in the CPL spectra with opposite signals and glum (Figure 2). This
reflects the results as expected from the isomeric nature from
these two enantiomers.
7
7
7, according to the equation: I(5D0 → F2)/I (5D0 → F1), which is
the ratio between the integrated intensity of the peaks ∆J = 2 and
∆J = 1.[20] The luminescent intensity of 5D0 → 7F1 transition, which
is magnetic dipole-allowed, but spin and orbit forbidden, can act
as a reference as it is relatively independent of site symmetry and
5
7
coordination environment of Eu(III) ion, whereas the D0 → F2
transition, the forced electric dipole transition, is hypersensitive to
the environment and the coordination symmetry.[31] The R value
thus can give an insight to whether the substituents affected the
local symmetry of the Eu(III) center. When the bulkiness of R
groups was increased from methyl to isopropyl, similar R ratios
were obtained, implying that the R groups had minimal effect on
the local symmetries of the Eu(III) centers of EuL1-7. Examination
of the quantum yields also shows no apparent influences from the
peripheral chiral groups. However, analysis of the glum values
shows an uphill trend which can be correlated to the increased
steric bulkiness of the chiral groups. This is important as it shows
the sensitivity of CPL, as even peripheral or distant structural
deviations can have an impact on the CPL but not the PL
properties.
Figure 2. CPL spectra (upper curves) and total luminescence (lower curves) of
(SAP)EuL3 isomers in 0.1 M HEPES, pH 7.3, λexc = 340 nm.
4
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Altering the inner coordination sphere of Eu(III) ion will also
affect the CPL properties. However, in our nine coordinated
complexes, EuL1-7 is expected to have minimal changes as the
Eu(III) ion’s coordination site within these complexes are fully
saturated, shielding the cation from the surrounding environment.
To confirm this hypothesis, (SAP)EuL3 was titrated in a pH
ranged from 4-9 with various small molecules, L-glutamic acid, L-
histidine, L-threonine, sodium L-ascorbate and human serum
albumin (HSA) in aqueous media and the CPL spectra were
compared. From Figures 3B & 3C, there was no change among
these CPL spectra; moreover, the glum values remained the same.
These indicated the coordination of (SAP)EuL3 did not changed
during different titrations. Stable CPL signals and glum values were
obtained even when subjected to different environments.
This was further supported by examining EuL1-6 under a
“physiological environment” mimicked by an anion cocktail (0.9
mM HPO42-, 100 mM chloride, 2.3 mM lactate, 0.13 mM citrate
-
and 15 mM HCO3 ),[50] and also at various pH conditions (Figures
S16-S29). All these europium complexes showed no significant
changes in luminescence intensity or in spectral splitting upon
addition of the anion cocktail. The pH titrations also showed no
changes in the luminescence from the range of pH 5-10. Hence,
it can be concluded that no apparent decomplexation occured
even in extreme pH ranges. These Eu(III) complexes show a high
tolerance to the changes of pH under physiological conditions.
Based on the excellent quantum yields and high glum values,
we further studied the magnetic responses of our complexes,
EuL2-7. Although EuL2-7 have intrinsic CPL signals, we
hypothesised that the CPL or glum would be influenced under
magnetic fields. Hence, these Eu(III) complexes were placed in
static magnetic fields to test for MCPL responses. In MCPL
measurements, magnets from 0 T to 1.4 T were applied to EuL2-
6 in a specific direction: S to N for complexes in S configuration,
N to S for (R)(SAP)EuL3. From the glum spectra (Figure 4), the
Δglum values displayed a linear relationship with the applied
magnetic field strengths. The |glum| obtained from the magnetic
dipole allowed 5D0
→
7F1 transition increased with increasing
applied magnetic field strength and the |glum| value at this
transition for (SAP)EuL3 was enhanced by 20% from 0.222 to
0.267 from 0 T to 1.4 T at room temperature.
Figure 3. A) CPL spectra of (SAP)EuL3 in 0.1 M HEPES (purple), MeOH (cyan)
and DMSO (red), λex = 340 nm. B) CPL spectra & C) glum spectra of (SAP)EuL3
titrated with L-threonine (purple), L-histidine (blue), L-glutamic acid (cyan), L-
ascorbate (yellow) and HSA (red) in 0.1 M HEPES, pH 7.3.
5
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10.1002/anie.202012133
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RESEARCH ARTICLE
Figure 4. A) Magnetic field dependent glum spectra of (R)&(S)(SAP)EuL3 in 0.1 M HEPES buffer, pH 7.3, excited at 350 nm at room temperature, arrows indicate
the trends of glum changes, inserted diagrams show the direction of applied magnetic field; B) glum and C) Δglum as a function of magnetic field strength at 5D0 → 7F1
transition.
Polytechnic University ((a) University Research Facility in
Chemical and Environmental Analysis (UCEA); (b) University
Research Facility in Life Sciences (ULS)) and the National Natural
Science Foundation of China (NSFC, 21875201). We also wish to
thank the Engineering and Physical Sciences Research Council
(EPSRC) for financial support (AMW, Department of Chemistry
EPSRC DTG, [EP/L504762/1].
Conclusion
In summary, a series of nine-coordinated chiral macrocyclic
Eu(III) complexes were synthesized by introducing chiral
substituents onto the macrocyclic backbone. A highly rigid and
bioconjugatable chromophore was designed to optimise the
luminescence properties. With a fully coordinated inner sphere,
EuL2-7 shows high stability and excellent luminescent quantum
yields and glum values under various biological conditions, making
these Eu(III) complexes ideal as chiroptical probes and sensors
Among these complexes, the highest quantum yield, 31.3%, was
determined in (R)EuL7 and the largest glum value of 0.240 was
obtained for EuL5. More importantly, to the best of our knowledge,
this is amongst the first series of Eu(III) chiral DO3A derivatives
to show enhanced MCPL response, with 20% glum enhancement
(from 0 T to 1.4 T), which we believe can be further optimised by
higher magnetic field strengths to provide an alternative way to
increase the image contrast in chiroptics. We demonstrated that
these highly biocompatible complexes, EuL2-7, offers insights to
the design criteria of CPL probes and simultaneously expands the
choices of CPL materials used in biological studies with the
additional value of MCPL.
Conflict of interest
The authors declare no conflict of interest.
Keywords: chiral cyclen
• chirality • circularly polarized
luminescence • lanthanide • magnetic properties
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10.1002/anie.202012133
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RESEARCH ARTICLE
Entry for the Table of Contents
A series of chiral, water-soluble, DO3A-based Eu(III) complexes was designed and synthesized. The chiral substituents introduced
onto the macrocyclic scaffolds enhanced the photophysical properties with quantum yield up to 31% and |glum| up to 0.240. The |glum
value increased by 20% from 0.222 to 0.267 under external magnetic field showing a linear response.
|
8
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