1O2 Generating Luminescent Lanthanide Complexes with 1,8-Naphthalimide-Based Sensitizers

Article abstract of DOI:10.1021/acs.inorgchem.9b02431

Lanthanide ion (Ln^III) complexes with two new 1,8-naphthalimide-based ligands, Nap-dpe and Nap-cbx, were isolated, and their photophysical properties were explored. Upon excitation at 335 nm, Nap-dpe and Nap-cbx sensitize visible and near-infra

Full text of DOI:10.1021/acs.inorgchem.9b02431

Article
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
pubs.acs.org/IC
1
O Generating Luminescent Lanthanide Complexes with 1,8-
2
Naphthalimide-Based Sensitizers
Katherine R. Johnson and Ana de Bettencourt-Dias*
Department of Chemistry, University of Nevada, Reno, Nevada 89557, United States
*
S Supporting Information
III
ABSTRACT: Lanthanide ion (Ln ) complexes with two
new 1,8-naphthalimide-based ligands, Nap-dpe and Nap-cbx,
were isolated, and their photophysical properties were
explored. Upon excitation at 335 nm, Nap-dpe and Nap-
III
III
cbx sensitize visible and near-infrared emitting Ln ions (Ln
III
III
III
1
=
Eu , Nd , and Yb ) and generate singlet oxygen ( O ).
The quantum yields of Eu luminescence for [Eu(Nap-
cbx)3] and [Eu(Nap-dpe) ] are 16.7% and 8.3%,
respectively, with O generation efficiencies of 41% and
9%, respectively. The efficiencies of O generation for the
NIR emitting complexes [Ln(Nap-dpe)3] are 59% and 56%,
respectively, and those for [Ln(Nap-cbx) ] (Ln = Nd ,
Yb ) are 64% and 61%, respectively. In an oxygen-free environment, the quantum yields of Eu luminescence for [Eu(Nap-
2
III
3
+
3+
3
1
2
1
5
2
3
+
3+
III
III
3
III
III
3
+
3+
cbx)3] and [Eu(Nap-dpe)3] increase to 20% and 18%, respectively.
1
INTRODUCTION
III
high as 24% and O generation efficiencies (ϕ1O2) as high as
2
■
12
III
12%. Although the complexes are good Tb sensitizers, their
O generation efficiencies fall well below the efficiencies of
organic photosensitizers. More recently, Maury and co-
workers described a tris-picolinato-1,4-7-triazacyclononane
macrocycle with ϕ1O2 = 80% when complexed to Gd .
However, when the Gd ion was exchanged for Yb , only
luminescence was observed, due to the competition between the
two energy transfer pathways. This group also recently
described helicenic complexes of Ln , and in this case, good
efficiencies of both metal-centered emission and O generation
were observed. As shown in Figure 1, the T state is
responsible for generation of both O and Ln luminescence,
and competing nonradiative processes lead to quenching of the
excited states. A good understanding of the interplay between
the two properties is important to enable researchers to use
compounds with phototoxic properties for therapeutic applica-
tions and to track them in situ through Ln -centered
luminescence. Thus, we aimed to isolate Ln complexes that
display efficient luminescence and, in addition, efficiently
generate O . We chose naphthalimide as the O generating
Ln ion luminescence is based on 4f-4f transitions. Due to
shielding of the 4f orbitals by the filled 5s and 5p orbitals, these
transitions are not significantly altered by the ion’s environment.
This leads to characteristic emission with high color purity
1
2
13
III
III
making luminescent Ln complexes great candidates for
III
III
1
,2
3
application as imaging agents, as sensors, as anti-counter-
4
5,6
III
feiting inks, and in optics. However, direct excitation of Ln
1
4
ions is inefficient due to the parity-forbidden nature of the f−f
transitions, which leads to low extinction coefficients. A
sensitizer (or antenna) is coordinated to the metal ion to
III
1
2
1
5
3
III
promote Ln -centered emission, in a process called the antenna
1
III
7
effect. As illustrated in Figure 1, a photon is absorbed by the
2
1
antenna and generates a ligand-based singlet ( S) excited state.
After intersystem crossing (ISC), a triplet ( T) excited state is
populated, which then transfers energy to the Ln excited state.
This excited state decays by luminescence. Using an organic
ligand as a sensitizer is advantageous because it can be tailored to
a specific application or property. For example, our group has
isolated several functionalized pybox (pyridine-bis(oxazoline))
3
III
III
III
1
1
III
ligands that lead to highly luminescent visible Ln emitters in
2
2
8
functional group.
organic solvents. When para-functionalized with a glycol tail,
9
1,8-Naphthalimide is known for its near unit quantum yield of
ISC and high ϕ1O2 in acetonitrile. 1,8-Naphthalimide-based
compounds are also efficient photosensitizers of O , with
reported ϕ1O2 in the range 5−82%,
biological sensing,
anticancer therapeutics.
the new complexes display efficient luminescence in water,
which is valuable for imaging in biological systems.
Our group is now interested in luminescent Ln complexes
with additional properties. As illustrated in Figure 1, the T
state of the ligand can be used to also generate singlet oxygen
16
1
III
2
1
6−19
1
0
3
and are proposed for
20−23
24
as anti-inflammatory drugs, and as
2
5−28
1
11
III
For example, the derivatives
(
O ), a cytotoxic species. Examples of luminescent Ln
2
1
III
compounds capable of generating O are Tb DOTA-based
2
complexes functionalized with either naphthyl or azaxanthonyl
pendants. These complexes display Tb emission efficiencies as
Received: August 12, 2019
III
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.9b02431
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
1
To expand our knowledge of compounds that generate O
2
III
and that simultaneously display Ln -centered luminescence, we
isolated two new 1,8-naphthalimide-based compounds, Nap-
III
dpe and Nap-cbx, shown in Scheme 1, in which a Ln chelator
Scheme 1. Compounds Nap-dpe and Nap-cbx Studied Here
is present at the imide nitrogen atom. These ligands are easily
synthesized, as discussed below, with direct communication of
the two functional groups involved in the sensitization process;
Figure 1. Energy level diagram showing the energy transfer (ET)
III
1
pathways for both Ln ion sensitization and O generation. Energy hν
2
1
is absorbed by the ligand to populate a singlet excited state ( S).
this synthetic strategy has proven successful in our group for
Intersystem crossing (ISC) leads to population of a triplet excited state
55−57
other families of sensitizers.
We report here their ability to
3
(
T). This state can then transfer energy to populate the emissive *f
III
sensitize Ln luminescence in the visible and NIR and
excited state, which decays by luminescence (L) to the ground state, f.
Alternatively, the energy transfer leads to O generation, which decays
to triplet oxygen O by emitting at 1270 nm. Nonradiative (NR)
1
1
concurrently generate O .
2
2
3
2
RESULTS AND DISCUSSION
(
dash-dot lines) pathways lead to quenching of excited states.
■
Competing radiative processes are fluorescence (F) and phosphor-
Nap-dpe and Nap-cbx were synthesized through condensation
of 4-aminopyridine-2,6-diethyl ester or 4-aminopyridine-2,6-
dicarboxamide with 1,8-naphthalic anhydride in 34% and 46%
yields, respectively (Figure S1; details of synthesis can be found
in the Supporting Information). We confirmed their isolation by
NMR and FT-IR spectroscopy and mass spectrometry (Figures
S2−S8). Both compounds display broad absorption in the
ultraviolet (UV) region with maxima at 334 nm. Exciting at
∼330 nm results in fluorescence bands with maxima at 380 nm
escence (P). Energy levels are not drawn to scale.
amonafide and mitonafide were tested in clinical trials as
2
9,30
anticancer agents.
1,8-Naphthalimide and its derivatives
intercalate between DNA base pairs and form strong van der
31
32
Waals interactions, resulting in reduced gene expression.
Selected derivatives are reported to bind and disable
topoisomerase II (the enzyme responsible for DNA pack-
3
3
34
35
F
aging) or tubulin, or nitroreductase, considerably
hindering cell function. Naphthalimide derivatives are often
(Figures S9 and S10). Quantum yields of fluorescence (ϕ ) are 2
and 5% for Nap-cbx and Nap-dpe (Table 1), respectively, and
17,24,26,36,37
18,58−60
used as fluorescent reporters.
Hideg and co-workers
are similar to other naphthalimide derivatives.
Upon
III
described an example used to infiltrate chlorophyll-containing
complexation to Gd , which cannot be sensitized by these
1
3
mesophyll cells of tobacco leaves and to detect O in vitro by
ligands due to its high lying emissive state ( P at 32,200
2
7/2
38
−1 61
luminescence in the range 500−600 nm.
,8-Naphthalimide is easily functionalized, and many
groups have investigated ways to increase its potency by adding
cm ), the emission spectra do not change appreciably
3
9
1
(Figures S11 and S12). Instead, a slight red-shift of the emission
maxima and an increase in emission efficiency to 6% for
4
0,41
18
3+
3+
heavy atoms,
extending conjugation, or incorporating
[Gd(Nap-dpe) ] and 7% for [Gd(Nap-cbx) ] are observed,
3 3
62
42
multiple cytotoxic motifs. Some of these methods do increase
consistent with planarization of the ligand upon coordination
the efficiency of ISC, but can result in shortening the lifetime of
and some phosphorescence contribution, due to improved ISC.
1
the S excited states. This leads to decreased fluorescence
In degassed solutions, fluorescence efficiencies increase slightly
1
8,40,43
44
F
efficiency,
and thus decreased signal-to-noise ratio,
to ϕ = 7% for both Nap-based compounds and to 9% for both
III
preventing in situ and in vivo bioimaging. The long-lived
Gd complexes, confirming that fluorescence decreases because
III
1
luminescence of Ln ions, which is a result of the forbidden
of the simultaneous generation of O in aerated solution (vide
2
nature of the f-f transitions, circumvents these two barriers
inherent to organic fluorophores.
Luminescent Ln complexes with 1,8-naphthalimide-based
infra).
To assess the adequacy of Nap-dpe and Nap-cbx as sensitizers
III
III
1
for Ln emission, the energies of their singlet ( S) and triplet
1
3
ligands have been reported, but their O generating properties
( T) excited states were determined through fluorescence and
2
6
,45−52
III
have not been explicitly explored.
Ward and co-workers
phosphorescence spectroscopy of the Gd complexes (Table 1,
Figures S13 − S18). The S and T states are located at 25,700
and 18,300 cm , respectively, for [Gd(Nap-dpe) ] and
26,500 and 21,200 cm , respectively, for [Gd(Nap-cbx) ] . As
expected, the T excited state for both complexes is lower than
what is reported for the T state for chelators diethylpyridine-
III
63
1
3
studied a Eu DOTA-based complex featuring a 1,8-
naphthalimide pendant that in solution displays concurrent
ligand- and Eu -centered emission as a white light emitter, and
they determined a Eu emission efficiency (ϕ ) of 12%.
Pischel and co-workers discussed a polyamine-derivatized
naphthalimide chromophore for Eu luminescence with ϕ
−1 3+
3
III
−1
3+
3
III
Eu
53
3
3
III
Eu
−1 64
=
2,6-dicarboxylate (23,260 cm ) and N,N,N′,N′-tetraethyl-
5
4
−1 65
1
1%. More recently, two 1,8-naphthalimidopyridine-N-oxides
were shown to sensitize Eu luminescence, with ϕ of 42% and
pyridine-2,6-dicarboxamide (20,600 cm ). Using the INDO/
III
Eu
66
67
S-CIS method and ORCA, as implemented within
LUMPAC, we modeled the ground state geometry of the
6
68
2
9%.
B
DOI: 10.1021/acs.inorgchem.9b02431
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Inorganic Chemistry
Article
F
III
Table 1. Quantum Yields of Fluorescence (ϕ ) for Nap-cbx and Nap-dpe and Their Gd Complexes and Experimental and
1
3
Calculated Singlet ( S) and Triplet ( T) State Energies
b
c
Experimental
Calculated
ϕF [%]
a
1S [cm−1
]
3T [cm−1
]
1S [cm−1]
31,840
3T [cm−1
]
Compound
Nap-cbx
Nap-dpe
d
d
d
d
2 ± 07 ± 1
5 ± 17 ± 2
7 ± 09 ± 1
6 ± 09 ± 0
[
[
Gd(Nap-cbx) ]3+
26,500 ± 60
25,700 ± 150
21,200 ± 50
18,300 ± 10
21,115
18,035
3
Gd(Nap-dpe) ]3
+
26,231
3
a
b
c
Measured at 25.0 ± 0.1 °C. Measured at 77 K in 1:1 dichloromethane:acetonitrile, reported as the 0−0 transition. Calculated using the INDO/
S-CIS method and ORCA, as implemented within LUMPAC.
66
67
68 d
Degassed solutions of 1:1 dichloromethane:acetonitrile.
Figure 2. Ground state geometries of (a) [Gd(Nap-cbx)3]3+ and (b) [Gd(Nap-dpe) ] . Hydrogen atoms are omitted for clarity. Insets show a
3+
3
III
tricapped trigonal prismatic coordination geometry around the Gd .
1
complexes (vide infra), as shown in Figure 2. The calculated S
species at the appropriate conditions. The formation of the 3:1
complexes was further assessed through speciation studies using
H NMR spectroscopy with the diamagnetic La analogs
3
−1
−1
and T excited state energies are 26,231 cm and 18,035 cm
3+
−1
−1
1
III
for [Gd(Nap-dpe) ] and 31,840 cm and 21,115 cm for
Gd(Nap-cbx)3] (Table 1), respectively, which compare
3
3
+
[
(Figures S22 and S23). It is noteworthy that while the speciation
diagrams (Figure S21) indicate the possible presence of a small
amount of the 2:1 ligand-to-metal ion complex in solution, as
discussed below, emission lifetime measurements of the Eu
analogs show that the decay curves can be fit to a single
favorably with the experimental values. These energies indicate
III
that both ligands are capable of sensitizing Eu , which has its
−
1
III
III
III
emissive state at 17,300 cm , in addition to Yb and Nd , with
−
1
−1
their emissive states at 11,500 cm and 11,600 cm ,
6
9,70
respectively.
exponential, which is consistent with the presence of one
72−74
The stoichiometry of the complexes in solution was
determined through emission titrations of Eu(NO ) with
emissive species in solution.
3
3
Attempts to isolate X-ray quality single crystals to confirm
structure are ongoing. Nonetheless, the ground state geometry
of each complex (Figure 2) was modeled using SPARKLE/
aliquots of either ligand (Figures S19 and S20). The stability
constants for the 1:1, 2:1, and 3:1 ligand-to-metal species for the
7
5
76
Nap-dpe complexes are 8.02 ± 0.07 (log β ), 14.01 ± 0.24 (log
PM3 implemented in MOPAC2016. In both cases, each
1
III
β ), and 19.00 ± 0.20 (log β ) and are comparable to the values
Gd ion is bound to three ligands through the nitrogen atom of
2
3
reported for diethylpyridine-2,6-dicarboxylate coordinating to
the pyridine rings and the carbonyl oxygen atoms of the
carboxamide or ester, respectively, resulting in a coordination
number of 9. The coordination polyhedra (insets, Figure 2) are,
in both cases, distorted tricapped trigonal prisms. To validate the
calculated geometry, we compared calculated bond lengths and
dihedral angles in these structures with known complexes for
which crystallographic data is available. We obtained Gd−N and
Gd−O bond distances around 2.5 and 2.6 Å, respectively, for
both complexes, similar to what is observed for related
III
Ln , which are in the range 6.8−7.0 for log β , 12.8−14.0 for log
1
71
β , and 16.3−18.0 for log β . The stability constants for the
2
3
Nap-cbx complexes are 8.64 ± 0.12 (log β ), 14.67 ± 0.11 (log
1
β ), and 19.80 ± 0.24 (log β ) (Table S1). These values are
2
3
similar to the values reported for N,N,N′,N′-tetraethylpyridine-
III
2
,6-dicarboxamide coordinating to Ln , which are in the range
of 7.3−8.5 for log β , 13.8−16.0 for log β , and 21.0−22.9 for log
1
2
65
β . Speciation diagrams for both systems (Figure S21) confirm
3
7
7,78
the presence of the 3:1 complex as the main metal-containing
dipicolinato-based complexes.
We calculated dihedral
C
DOI: 10.1021/acs.inorgchem.9b02431
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Inorganic Chemistry
Article
Figure 3. Normalized emission spectra of the (a) [Ln(Nap-cbx) ] complexes [Ln = EuIII (blue), NdIII (light blue), or Yb (navy)] and of the (b)
3
+
III
3
Ln(Nap-dpe)3]3+ complexes [Ln = Eu (red), Nd (pink), or Yb (dark red)] in 1:1 dichloromethane:acetonitrile measured at 25.0 ± 0.1 °C (λ
III
III
III
=
[
exc
3
35 nm).
3
5
III
III
Eu
Table 2. Difference in Energy (ΔE) between T and D of Eu , Quantum Yield of Eu Luminescence (ϕ ), Observed Lifetime
0
III
(
τ), Intrinsic Quantum Yield (ϕ EuEu), and Sensitization Efficiency (η ) for the Eu Complexes in Aerated and Degassed
sens
Solutions
ΔE ( T − D ) [cm−1]
3
5
ϕEu [%]a
τ [ms]
0.51 ± 0.01;
a
ϕ Eu [%]
ηsens [%]
Compound
Eu(Nap-dpe) ]3
0
Eu
+
[
[
∼1,000
8.3 ± 0.0
7.7 ± 0.2
22
35
38
51
3
b
b
c
c
1
0.81 ± 0.02
.08 ± 0.08
0.68 ± 0.01;
0.85 ± 0.03
d
1
Eu(Nap-cbx) ]3+
∼4,000
16.7 ± 0.1
32
39
52
53
3
b
b
c
c
2
0.4 ± 0.5
d
1
.10 ± 0.04
a
b
c
Measured at 25.0 ± 0.1 °C in 1:1 dichloromethane:acetonitrile. Degassed 1:1 dichloromethane:acetonitrile Calculated from data collected in
d
degassed solutions. Degassed 1:1 dichloromethane:acetonitrile at 77 K.
angles between the naphthalimide and pyridyl groups of about
To characterize the photophysical properties of the
complexes, [Ln(Nap-dpe)3] and [Ln(Nap-cbx)3] were
isolated by reacting Nap-dpe or Nap-cbx with Ln(NO3)3
3
+
3+
∼
51°, which are comparable to experimental values in similar
6
compounds.
D
DOI: 10.1021/acs.inorgchem.9b02431
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Inorganic Chemistry
Article
III
III
III
III
III
(
Ln = Nd , Eu , Gd , and Yb ) in 1:1 dichloromethane:a-
Table 3. Quantum Yields of Singlet Oxygen Generation
(ϕ1O2) at 25.0 ± 0.1 °C in 1:1 Dichloromethane:Acetonitrile
cetonitrile. After filtration and subsequent solvent evaporation,
the salts [Ln(Nap-dpe) ](NO ) or [Ln(Nap-cbx) ](NO )
3 3
3
3 3
3
Compound
Nap-cbx
ϕ 1O2 [%]
Compound
Nap-dpe
ϕ 1O2 [%]
precipitated as white powders in 91−98% yield (details in
Supporting Information). Their isolation was confirmed
through high resolution mass spectrometry (Figures S24 −
S31). After redissolving them in 1:1 dichloromethane:acetoni-
trile, the complexes display the characteristic metal-based
emission colors upon excitation. The emission spectra of
Eu(Nap-cbx) ] and [Eu(Nap-dpe)3] (Figure 3) show the
D → F (J = 0−4) transitions of Eu luminescence. The
presence of the D → F band for both complexes suggests a
low symmetry environment around the metal ion. The
emission spectra of [Yb(Nap-cbx) ] , [Yb(Nap-dpe) ] ,
Nd(Nap-cbx) ] , and [Nd(Nap-dpe) ] display the charac-
teristic NIR emission bands for Yb ( F → F7/2) and Nd
60 ± 1
68 ± 4
41 ± 5
64 ± 1
61 ± 3
56 ± 2
72 ± 2
59 ± 2
59 ± 5
56 ± 2
3
+
3+
[Gd(Nap-dpe)3]
3+
[Eu(Nap-dpe)3]
[
[
[
[
Gd(Nap-cbx)3]
Eu(Nap-cbx) ]3
+
3
3
+
3+
Nd(Nap-cbx)3]
[Nd(Nap-dpe)3]
[Yb(Nap-dpe)3]3+
Yb(Nap-cbx) ]3
+
3
3
+
3+
[
3
5
7
III
0
J
III
14,15
Gd complexes, reported by Maury and co-workers,
and to
photosensitizers, such as
81
5
7
0
0
1
2
a variety of naturally occurring O
2
clorin-e (64% in phosphate buffer), chlorophyll a (44% in
ethanol), riboflavin (48% in methanol), porfimer sodium
89% in phosphate buffer), and lutetium texaphyrin (23% in
3
+
3+
6
3
3
82
83
3
+
3+
[
81
3
3
(
III
2
2
III
5
/2
84
methanol).
4
4
(
F3/2 → I (J = 9/2, 11/2, and 13/2)).
As mentioned, all LnIII complexes generate 1O , while
J
III
Eu
2
Quantum efficiencies of sensitized Eu emission (ϕ ) are
concurrently displaying metal-centered emission. While not
.3% for [Eu(Nap-dpe)3]3 and 16.7% for [Eu(Nap-cbx) ]
+
3+
8
(
3
demonstrated here, this should facilitate luminescence imaging.
Eu
Table 2) and are comparable to reported ϕ for
naphthalimide-based complexes (vide supra).
the lower emission efficiency of [Eu(Nap-dpe) ] to the
1
To further characterize the concurrent processes of O
53,54
2
We attribute
generation and metal-centered luminescence, the emission of
3
+
3
III
III
III
Eu , Nd , and Yb in the complexes was evaluated in degassed
solutions. For all complexes, luminescence emission intensity
3
5
narrower gap between the T excited state and the D emissive
0
7
9
state, which results in a low sensitization efficiency (ηsens) of
15,54
increased under anaerobic conditions (Figures S37−S42).
3+
3
8% (Table 2) compared to 52% for [Eu(Nap-cbx) ] and also
Eu
3
In the absence of O , we observed an increase of ϕ to 17.7% for
Eu(Nap-dpe) ] and 20% for [Eu(Nap-cbx) ] (Table 2), as
the T state is only involved in sensitization of Eu emission but
The increased emission intensity also
leads to an increase in both Eu lifetimes to 0.81 and 0.85 ms for
Eu(Nap-dpe) ] and [Eu(Nap-cbx) ] , respectively (Figures
2
explains the residual ligand band seen in the region 500−550 nm
in the emission spectrum of the former complex (Figure 3b,
S32).
The luminescence lifetimes (τ) for both Eu complexes are
.51 ms for [Eu(Nap-dpe) ] and 0.68 ms for [Eu(Nap-
3+
3+
[
3
3
3
III
1
15,54
not in O generation.
III
2
III
3+
0
3+
3+
3
[
3
+
3
3
cbx)3] in aerated solution at 298 K. Both τ could be fit as
single-exponential decays (Figures S33 and S34, Table S2),
indicating one unique coordination environment around the
Eu
3+
S43 and S44), higher ϕ
of 39% for [Eu(Nap-cbx)3] and
5% for [Eu(Nap-dpe) ] , and higher η of 53% and 51% for
Eu
3+
3
[
3
sens
3+
3+
Eu(Nap-cbx)3] and [Eu(Nap-dpe) ] , respectively.
III
72−74
3+
3
Eu ions.
The slightly longer lifetime of [Eu(Nap-cbx) ]
3
Despite the expectation that efficiencies of NIR emission
Eu
is consistent with a higher intrinsic quantum yield (ϕ Eu= 32%)
III
would be larger in degassed solutions, quantum yields of Yb
compared to [Eu(Nap-dpe)3]3 (ϕ
+
Eu
Eu
= 22%) and indicates
80
III
and Nd luminescence emission and emission lifetimes under
slightly better shielding from vibrational quenching. Nap-dpe
shows slightly lower sensitization efficiency, consistent with the
lower energy gap between the T state and the D level of Eu .
Finally, this lower gap leads to a certain degree of back-energy
transfer from D to T, as can be seen by the small increase in
the emission lifetimes when the solutions of the complexes are
cooled to 77 K (Table 2 and Figures S45 and S46, Table S3).
This repopulation of the T and lower sensitization efficiency are
advantageous for a more efficient O generation for the
Eu(Nap-dpe)3] complex, as discussed below.
these conditions are still too weak to be determined reliably.
3
5
III
0
CONCLUSIONS
■
5
3
We isolated two new sensitizing ligands based on 1,8-
naphthalimide, Nap-dpe and Nap-cbx, and their lanthanide
compounds then demonstrated their ability to concurrently
0
III
3
display Ln -centered emission in the visible and NIR and
1
1
generate O
2
in solution upon excitation at 335 nm. The
2
1
3
+
compounds with the largest O generation efficiencies while
2
[
III
3+
III
III
sensitizing Ln luminescence are [Nd(Nap-cbx)
3
] (64%) and
Quantum yields of Yb and Nd luminescence emission and
emission lifetimes could not be determined reliably due to weak
emission.
3
+
[
Eu(Nap-dpe)3] (59%). We identified that the complexes’
1
ability to generate O efficiently impacts the luminescence
2
3
efficiency, as is expected, due to the involvement of the T
1
All compounds discussed here generate O . Its formation was
2
excited state of the ligand in both processes. While their lack of
solubility in water prevents them from being used for bioimaging
and therapy purposes, the work presented here expands our
knowledge of compounds displaying the superior properties of
evaluated by monitoring the phosphorescence at 1270 nm from
1
3
1
the O → O transition (Figures S35 and S36). The O
2
2
2
generation efficiencies (ϕ1O2) for Nap-cbx and Nap-dpe are
0% and 56% (Table 3), respectively, comparable to values
reported for other naphthalimide derivatives.
complexes generate O with efficiencies comparable to Nap-
6
III
16,18
emissive Ln complexes, while simultaneously generating a
All metal
cytotoxic species.
1
2
cbx and Nap-dpe, as summarized in Table 3. They are 41% for
EXPERIMENTAL SECTION
3
+
3+
■
[
Eu(Nap-cbx) ] , 59% for [Eu(Nap-dpe) ] , 59% and 56%
3
3
3+
3+
All commercially obtained reagents were of analytical grade and were
used as received. Solvents were dried and purified by standard methods
unless otherwise noted. All synthetic steps were completed under N2
unless otherwise specified. The detailed synthetic procedures of the
for [Nd(Nap-dpe) ] and [Yb(Nap-dpe) ] , respectively, and
6
respectively. The largest ϕ1O2 are observed for the Gd
complexes, which are 72% for [Gd(Nap-dpe) ] and 68% for
3
3
3+
3+
4% and 61% for [Nd(Nap-cbx)3] and [Yb(Nap-cbx) ] ,
3
III
3+
III
3
ligands and their Ln complexes are provided in the Supporting
3
+
[
Gd(Nap-cbx) ] . These values are similar to values of ϕ for
Information.
3
1O2
E
DOI: 10.1021/acs.inorgchem.9b02431
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
2
Preparation of Ln(NO3)3 Solutions. The stock solutions of
gradx
n
Istd
x
III
III
III
III
ϕx =
× n2 × I
ϕ
std
lanthanide(III) nitrate (Ln = Eu , Gd , Nd , or Yb ) nitrate were
prepared by dissolving the nitrate salt in spectroscopic grade 1:1
dichloromethane:acetonitrile. The concentration of the metal was
determined by complexometric titration with EDTA (0.01 M) using
gradstd
std
x
(1)
Grad is the slope of the plot of the emission area as a function of the
absorbance, n is the refractive index of the solvent (n = 1.3870 was
determined experimentally for the acetonitrile/dichloromethane
mixture; see below), I is the intensity of the excitation source at the
excitation wavelength used, and ϕ is the quantum yield for sample, x,
and standard, std. All data are the average of at least three independent
measurements.
Standards for emission quantum yield measurements were quinine
sulfate (ϕ = 55%, 5 × 10 M in aqueous 0.5 M H SO ),
Cs [Eu(dpa) ] (ϕ = 24%, 7.5 × 10 M in aqueous TRIS/HCl buffer
3 3
90,91 92
85
xylenol orange as indicator.
NMR Spectroscopy. All NMR spectra were recorded on Varian
00 and 500 MHz spectrometers with chemical shifts reported (δ,
4
ppm) in deuterated chloroform (CDCl ) against tetramethylsilane
3
(
TMS, 0.00 ppm) at 25.0 ± 0.1 °C.
Infrared Spectroscopy. All FT-IR spectra were measured on a
−
6
89
Nicolet 6700 FT-IR in ATIR mode. The IR data for each sample were
2 4
−
1
−1
−5
collected in the range 4000−590 cm , with 32 scans at 4 cm
resolution per spectrum. A background correction for CO and H O
(0.1 M, pH ∼7.4)),
and 2,2′:5′,2″-terthiophene (ϕ = 74%, 1 ×
2
2
−
4
III
was conducted.
10 M in air-saturated acetonitrile) for ligand and Gd complex
III
1
Mass Spectrometry. Electrospray ionization mass spectra (ESI-
MS) were collected in positive ion mode on a Waters Micromass ZQ
quadrupole in the low-resolution mode for the ligands and on an
Agilent model G6230A with a QTOF analyzer in the high-resolution
mode for the metal complexes. The samples were prepared by diluting
acetonitrile solutions to a concentration of ∼1 mg/mL and passing
through a 0.2 mm microfilter.
Absorption Spectroscopy. Absorption spectra were measured on
a PerkinElmer Lambda 35 spectrometer equipped with deuterium and
tungsten halogen lamps (PerkinElmer) and a concave grating with 1053
lines/mm. The absorption spectra were collected using a scan speed of
fluorescence, Eu emission, and O2 emission, respectively. The
excitation wavelengths for both sample and quantum yield standard
were chosen to ensure a linear relationship between the intensity of
emitted light and the concentration of the absorbing/emitting species
emission efficiencies should be determined with both
sample and standard in the same solvent, due to different oxygen
1
(A ≤ 0.05). O
2
1
92,93
contents and O
the two slightly different solvent systems due to solubility issues.
However, the mol fractions of O are not very different, at 0.662 in
acetonitrile and 0.709 in dichloromethane. In addition, the O
lifetimes, yet this is not always the case.
We used
2
2
9
4
1
2
−5
lifetimes are also very similar, with values of 5.4 × 10 s in
95
−5
94
acetonitrile and 5.5 × 10 s in dichloromethane. Determination of
the emission efficiency of 2,2′:5′,2″-terthiophene in 1:1 acetonitrile:di-
chloromethane yielded a value of 77 ± 3%, which is experimentally
equivalent to the value we used for the standard in acetonitrile and
within the range 65−81% reported by different authors for this standard
4
80 nm/min in the range 225−600 nm with a photodiode detector. All
spectra were background corrected, using solvent as the blank. Spectra
of the ligands and their complexes were collected using concentrations
between 9.0 × 10−5 M and 1.25 × 10−4 M.
Speciation Studies. For speciation studies using emission
spectroscopy, spectra were measured in 1:1 dichloromethane:acetoni-
trile at 25.0 ± 0.1 °C using a constant concentration of Eu(NO ) (1 ×
9
2,93,96,97
in a variety of solvents.
The intrinsic quantum yield (ϕ ) was determined using eq 2.
Eu
Eu
98
3
3
−
4
1
0
M). Solutions of the ligand and Eu(NO ) were prepared with
stoichiometries between 1:0.25 and 1:3.5 (Eu :ligand), and their
emission spectra were measured under the same experimental
conditions. The concentration of Eu in solution remained constant,
× 10 M. Fitting and refinement of the data were performed using
HypSpec2014. The speciation diagrams were generated using
Arad
Atot
3
3
Eu
III
ϕ
=
Eu
(2)
III
Atot is the total emission rate (Atot = k + k = 1/τexp), where k is the
R
NR
R
−
4
1
radiative rate constant, kNR is the nonradiative decay constant, τexp is the
observed excited state lifetime, and Arad is the radiative emission rate,
determined using eq 3.
8
6
87
HySS.
For speciation studies using NMR spectroscopy, solutions of Nap-
i I
y
dpe and Nap-cbx were prepared in a deuterated solvent mixture (1:1
3j tot z
Arad = AMD,0 × n j
z
III
j
j
z
z
CDCl :CD CN) with ratios of 0:1, 1:1, 2:1, and 3:1 (La :Nap-dpe or
I
3
3
MD
(3)
k
{
III
La :Nap-cbx). The concentration of ligand, Nap-dpe or Nap-cbx, was
kept constant at 1 × 10−3 M. All NMR spectra were recorded on a
Itot and IMD are the total integrated emission spectrum and the area of
F1 transition, respectively, and A
coefficient of spontaneous emission (A
5
7
the D0
→
is the Einstein
MD,0
99
Varian 400 spectrometer with chemical shifts reported (δ, ppm) against
tetramethylsilane (TMS, 0.00 ppm) at 25.0 ± 0.1 °C.
−
1
= 14.65 s ).
MD,0
98
The sensitization efficiency (ηsens) was determined using eq 4.
Excitation and Emission Spectroscopy. Emission and excitation
III
spectra of Nap-dpe and Nap-cbx and their Ln complexes were
Eu
ϕ
ϕ
obtained on a Fluorolog-3 fluorimeter (Horiba FL3-22-iHR550), with
200 grooves/mm excitation monochromator gratings blazed at 330
ηsens =
Eu
Eu
(
4)
1
nm and 1200 grooves/mm or 600 grooves/mm emission mono-
chromator gratings blazed at 500 or 1000 nm for UV−vis or NIR range,
respectively. An ozone-free xenon lamp of 450 W (Ushio) was used as
the radiation source. The excitation spectra were corrected for
instrumental function and measured between 250 and 600 nm. The
emission spectra were measured in the range 350−800 nm using a
Hamamatsu 928P detector and in the range 800−1600 nm using a
ϕEu is the efficiency or quantum yield of sensitized emission.
Refractive Index Measurements. Refractive indices were
measured on a Leica MARK II ABBE refractometer with a built-in
light source for the measuring prism with an accuracy of ±0.0001 in nD
mode at 25.0 ± 0.2 °C. The average value of three independent
measurements (1.3870 ± 0.0004) was used in determining the
quantum yield as the refractive index for a 1:1 acetonitrile:dichloro-
methane solution. This value is in agreement with the value reported by
Hamamatsu 5509−73 detector cooled with liquid N . All emission
2
1
100
spectra were also corrected for instrumental function. The ligands’ S
Tsierkezos.
and 3T energies were obtained at ∼77 K by deconvoluting the
fluorescence and phosphorescence spectra of the analogous gadolinium
complexes into their Franck−Condon progression and are reported as
Ground-State Geometries and Excited State Calculations.
The Sparkle/PM3 model was used to determine the complexes’ ground
75
state geometries. In this model the lanthanide ion is replaced by a +3e
63
101
the 0−0 transition. Spectra of the ligands and their complexes were
collected using solution concentrations of 9.5 × 10 M to 1.25 × 10
point charge. The RHF wave functions were optimized using the
−
5
−4
Broyden−Fletcher−Goldfarc−Shanno (BFGS) procedure with a
M.
convergence criterion of 0.15 kcal/mol·Å and the semiempirical PM3
Emission Efficiency Measurements. The emission and 1O2
−6
with a convergence criterion of 10 kcal/mol for the SCF. In the
76
generation quantum yields of the samples were determined by the
MOPAC2016 package the keywords GNORM = 0.25, PRECISE,
GEO-OK, XYZ, T = 10D, and ALLVEC were used. The excited state
88
dilution method using eq 1.
F
DOI: 10.1021/acs.inorgchem.9b02431
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
6
7
calculations were preformed using ORCA software using the INDO/
S-CIS method.
(12) Law, G.-L.; Pal, R.; Palsson, L. O.; Parker, D.; Wong, K.-L.
Responsive and reactive terbium complexes with an azaxanthone
sensitiser and one naphthyl group: applications in ratiometric oxygen
sensing in vitro and in regioselective cell killing. Chem. Commun. 2009,
66
ASSOCIATED CONTENT
* Supporting Information
■
7
321−7323.
13) Redmond, R. W.; Gamlin, J. N. A Compilation of Singlet Oxygen
Yields from Biologically Relevant Molecules. Photochem. Photobiol.
999, 70, 391−475.
14) Galland, M.; Le Bahers, T.; Banyasz, A.; Lascoux, N.; Duperray,
S
(
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b02431.
1
(
A.; Grichine, A.; Tripier, R.; Guyot, Y.; Maynadier, M.; Nguyen, C.;
Gary-Bobo, M.; Andraud, C.; Monnereau, C.; Maury, O. A “Multi-
Heavy-Atom” Approach toward Biphotonic Photosensitizers with
Improved Singlet-Oxygen Generation Properties. Chem.Eur. J.
Synthesis details, NMR spectra, FT-IR spectra, mass
spectra, absorption, excitation, and emission spectra,
fluorescence and phoporescnece spectra, (PDF)
2019, 25, 9026
AUTHOR INFORMATION
Corresponding Author
E-mail: abd@unr.edu.
(15) Galland, M.; Riobe, F.; Ouyang, J.; Saleh, N.; Pointillart, F.;
́
■
Dorcet, V.; Le Guennic, B.; Cador, O.; Crassous, J.; Andraud, C.;
Monnereau, C.; Maury, O. Helicenic Complexes of Lanthanides:
Influence of the f-Element on the Intersystem Crossing Efficiency and
Competition between Luminescence and Oxygen Sensitization. Eur. J.
Inorg. Chem. 2019, 2019, 118−125.
*
ORCID
Katherine R. Johnson: 0000-0002-1323-0222
Ana de Bettencourt-Dias: 0000-0001-5162-2393
Notes
(16) Aveline, B. M.; Matsugo, S.; Redmond, R. W. Photochemical
Mechanisms Responsible for the Versatile Application of Naphthali-
mides and Naphthaldiimides in Biological Systems. J. Am. Chem. Soc.
The authors declare no competing financial interest.
1
(
997, 119, 11785−11795.
17) Liu, X.; Qiao, Q.; Tian, W.; Liu, W.; Chen, J.; Lang, M. J.; Xu, Z.
ACKNOWLEDGMENTS
Financial support of this work through the National Science
Foundation is gratefully acknowledged (Grant CHE 1800392).
Aziridinyl Fluorophores Demonstrate Bright Fluorescence and
Superior Photostability by Effectively Inhibiting Twisted Intra-
molecular Charge Transfer. J. Am. Chem. Soc. 2016, 138, 6960−6963.
■
(18) Zhang, L.; Huang, Z.; Dai, D.; Xiao, Y.; Lei, K.; Tan, S.; Cheng, J.;
Xu, Y.; Liu, J.; Qian, X. Thio-bisnaphthalimides as Heavy-Atom-Free
Photosensitizers with Efficient Singlet Oxygen Generation and Large
Stokes Shifts: Synthesis and Properties. Org. Lett. 2016, 18, 5664−
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