Technological University Dublin Technological University Dublin
ARROW@TU Dublin ARROW@TU Dublin
Articles
School of Chemical and Pharmaceutical
Sciences
2019-11-19
Heavy-Atom-Free BODIPY Photosensitizers with Intersystem Heavy-Atom-Free BODIPY Photosensitizers with Intersystem
Crossing Mediated by Intramolecular Photoinduced Electron Crossing Mediated by Intramolecular Photoinduced Electron
Transfer Transfer
Mikhail Filatov
Technological University Dublin
, mikhail.<latov@tudublin.ie
Follow this and additional works at: https://arrow.tudublin.ie/scschcpsart
Part of the Life Sciences Commons
Recommended Citation Recommended Citation
Filatov, M. (2019) Heavy-atom-free BODIPY Photosensitizers with Intersystem Crossing Mediated by
Intramolecular Photoinduced Electron Transfer,
Org. Biomol. Chem.,
2020, 18, 10. DOI: 10.1039/
C9OB02170A
This Article is brought to you for free and open access by
the School of Chemical and Pharmaceutical Sciences at
ARROW@TU Dublin. It has been accepted for inclusion in
Articles by an authorized administrator of ARROW@TU
Dublin. For more information, please contact
arrow.admin@tudublin.ie, aisling.coyne@tudublin.ie.
This work is licensed under a Creative Commons
Attribution-Noncommercial-Share Alike 4.0 License
Funder: European Commission
Heavy-atom-free BODIPY Photosensitizers with Intersystem Crossing Mediated by
Intramolecular Photoinduced Electron Transfer
Mikhail A. Filatov
School of Chemical and Pharmaceutical Sciences, Technological University Dublin, City Campus, Kevin Street, Dublin 8, Ireland
Abstract
Organic photosensitizers possessing efficient intersystem crossing (ISC) and forming long-living triplet excited states, play a crucial role in a
number of applications. A common approach in the design of such dyes relies on the introduction of heavy atoms (e.g. transition metals or
halogens) into the structure, which promote ISC via spin-orbit coupling interaction. In recent years, alternative methods to enhance ISC have
been actively studied. Among those, the generation of triplet excited states through photoinduced electron transfer (PET) in heavy-atom-free
molecules has attracted particular attention because it allows for the development of photosensitizers with programmed triplet state and
fluorescence quantum yields. Due to their synthetic accessibility and tunability of optical properties, boron dipyrromethenes (BODIPYs) are so
far the most perspective class of photosensitizers operating via this mechanism. This article reviews recently reported heavy-atom-free BODIPY
donor-acceptor dyads and dimers which produce long-living triplet excited states and generate singlet oxygen. Structural factors which affect
PET and concomitant triplet state formation in these molecules are discussed and the reported data on triplet state yields and singlet oxygen
generation quantum yields in various solvents are summarized. Finally, examples of recent applications of these systems are highlighted.
1. Introduction
The development of innovative photonic technologies critically
depends on the availability of photoactive materials with strong
absorption across the visible spectrum and tunable excited state
properties. In this context, organic dyes have an important
advantage compared to common inorganic photocatalysts: their
excited state energies and lifetimes can be finely tuned by rational
design of molecular structures to match the desired range.
Normally, excitation of a chromophore, leads to the lowest singlet
excited state S
1
, which possesses rather short lifetimes
(nanoseconds or less) and rapidly relaxes back to the ground state.
1
Alternatively, lower-lying triplet excited states T
n
can be populated
from S
1
state via a spin-forbidden intersystem crossing (ISC)
process. Due to their long lifetimes (up to seconds), triplet excited
states can efficiently transfer energy to other molecules and
mediate chemical transformations. Dyes possessing efficient ISC,
referred to as triplet sensitizers, are used to harvest light energy
and found applications in various fields of technology, e.g. in solar
fuel generation,
2
photovoltaics,
3
photoredox catalysis for organic
synthesis,
4
photooxidation of organic pollutants,
5
photoinitiated
polymerization,
6
triplet-triplet annihilation upconversion (TTA-UC)
7
and photodynamic therapy (PDT).
8
Triplet photosensitizers are commonly obtained through
complexation of organic chromophores with transition metals (e.g.
Ru, Pd or Pt) or introduction of halogens (Br or I) into the structure.
9
ISC in such derivatives is usually efficient due to spin-orbital
interaction - a relativistic effect pronounced in atoms with large
nuclei (heavy atoms). This mechanism is known as a spin-orbit
coupling intersystem crossing (SO-ISC). The effect of heavy atoms
on photophysical properties is illustrated in Figure 1 on an example
of boron dipyrromethenes (BODIPYs)
10
1 and its 2,6-diiodo
derivative 2. Compound 1 possesses intense fluorescence, while its
ISC is inefficient due to a weak spin-orbit coupling, giving a triplet
state yield (
T
) of less than 1%. On the other hand, enhanced spin-
orbit coupling in BODIPY 2 results in a triplet excited state yield of
> 80%, making it suitable for use as a triplet sensitizer.
11
Although this approach for enhancing triplet state yields in organic
molecules seems convenient, the introduction of heavy atoms
often results in issues such as tedious synthesis, increased cost, low
solubility and other unwanted side effects. For instance, in
photoredox catalysis much effort is currently focused on replacing
costly transition metal-based photosensitizers with heavy-atom-
free organic dyes,
12
because on an industrial scale their application
is expected to be more economical and will reduce environmental
impact.
13
For this reasons, alternative methods to promote ISC, e.g.
using a spin converter,
14
introduction of carbonyl groups,
15
radical‐
enhanced ISC
16
and twist-induced ISC
17
have been actively studied
in recent years. However, it is still difficult to design heavy-atom-
free sensitizers due to the lack of established relationships between
ISC and molecular structure.
The formation of triplet excited states by way of intramolecular
photoinduced electron transfer (PET) was studied for the first time
by Okada and co-workers on a series of aminopyrenes.
18
Recently,
unexpectedly efficient ISC has been reported for various heavy-
atom-free BODIPYs
19
and other difluoroboron complexes,
20
metal
dipyrrins,
21
phenoxazines,
22
biphenyls,
23
naphthalene and perylene
imides.
24
For many of these systems, very high triplet state yields (>
90%) and long triplet lifetimes (up to a few hundreds of
microseconds) have been observed. Notably, triplet state and
fluorescence quantum yields in these systems strongly depend on
molecular geometry and polarity of the media, providing
outstanding possibilities for “programming” excited state behavior
via rational design of the structures.
Figure 1. a) Structures of BODIPYs 1 and 2. IUPAC numbering system is
shown in the structure of 1.
fl
– fluorescence quantum yield,
T
– triplet
state yield. b) Jablonski diagram illustrating excited state transitions in 2. S
0
– ground state, S
1
– lowest singlet excited state, T
1
– lowest triplet excited
state. SO-ISC – spin-orbit coupling intersystem crossing, IC – internal
conversion. Solid arrow: most likely process; dashed arrow: less likely
process.
Figure 2. a) Schematic frontier molecular orbital diagram for the PET process in electron donor-acceptor dyads. b) Energy level diagram of PET in polar solvent. c)
Structure of BODIPY-anthracene dyad 3 and its fluorescence spectra in non-polar (hexane) and polar (ethanol) solvents.
Polarity-controlled triplet states generation is particularly
advantageous for applications involving reactive oxygen species
(ROS). In PDT, interaction of the sensitizer triplet states with
molecular oxygen (
3
O
2
), results in the formation of highly reactive
singlet oxygen (
1
O
2
) which causes oxidative stress and ultimately
cell death.
25
Formation of
1
O
2
in selected sites of the cell via
polarity-controlled PET in diiodo-substituted BODIPY derivatives
was demonstrated for deactivation of specific proteins by the
Nagano group.
26
Activatable photosensitizers based on transition
metal complexes were reported in a number of works.
27
However,
the use of this methodology in photomedicine is still limited,
because molecules containing heavy atoms often possess rather
high dark cytotoxicity,
28
i.e. can be harmful to the tissue in the
absence of light. On the other hand, the scope of available heavy-
atom-free photosensitizers which selectively generate singlet
oxygen in polar/non-polar environments or in response to
activation stimuli is still quite narrow and principles for their design
are not sufficiently elaborated.
In this review, the progress in the development of heavy-atom-free
BODIPY photosensitizers achieved over the past several years is
discussed. The paper is structured as follows. Background
information on photoinduced electron transfer and triplet state
formation from charge transfer states (CT) is presented in Section
2. In Sections 3 and 4, data on electron transfer, triplet state and
singlet oxygen quantum yields for the reported BODIPY donor-
acceptor dyads and dimers are summarized. Correlations between
molecular structures and the observed photophysical properties in
different solvents are discussed. On the basis of this information,
criteria for the design of efficient photosensitizers operating via PET
are highlighted in Section 5. Examples of recent applications of such
photosensitizers in photon upconversion and PDT are presented in
Section 6.
2. Photoinduced electron transfer and triplet
states formation from charge transfer states
Photoinduced electron transfer in donor-acceptor dyads, i.e.
molecules in which electron donor (D) and acceptor (A) subunits are
chemically connected, is a very general and well-studied
phenomenon.
29
A schematic frontier molecular orbital diagram for
the PET process, outlining the requirements towards HOMO and
LUMO energy levels of the subunits, is shown in Figure 2a. Upon
light absorption, electron transfer within the dyad results in the
formation of a highly polar excited state, usually called a charge-
transfer state (CT), or a charge-separated state (CSS).
30
This state
can be described as a radical ion-pair, in which a radical cation is
localized on the donor subunit (D
+·
) and a radical anion is localized
on the acceptor subunit (A
-·
).
The thermodynamic feasibility of PET in dyad molecules can be
estimated from spectroscopic and electrochemical data by
calculating the free energy change using the Rehm-Weller equation
(1):
31
(1)
where E
Ox(D)
and E
Red(A)
are one-electron oxidation and reduction
potentials of the donor and acceptor, respectively, E* is the energy
of the excited state (S
1
) and C represents is the coulombic
interaction between two ions produced at a distance r
DA
in a solvent
with a dielectric constant
r
(Figure 2b).
Efficient PET in donor-acceptor dyads is usually manifested by the
profound effect of solvent on the emission properties. A
progressive red-shift in the emission maxima, accompanied by a
concomitant broadening and decrease in emission quantum yields,
is observed for such compounds with increasing solvent polarity.
32
This effect is illustrated in Figure 2c for dyad 3, composed of a
tetramethyl-substituted BODIPY (electron acceptor) and 9-
methylanthracene (electron donor) subunits. The intense emission
observed in hexane (
r
= 4.81) corresponds to the fluorescence
from a local excited (LE) state of the BODIPY subunit. It is strongly
quenched in ethanol (
r
= 24.5) due to the PET process leading to a
poorly emissive CT state.
19a
Solvent dependence in dyad emission can be rationalized by taking
into account the dipolar nature of the CT state being formed. While
the energy of the LE state is virtually unchanged in various solvents,
the CT state energy level is strongly dependent on the possibility of
dipole-dipole interactions with solvent molecules.
33
In non-polar
solvents, such as hexane, the CT state does not get stabilized,
resulting in a situation where it resides in a higher energy state than
the LE state. In this case the electron transfer process is
thermodynamically unfavorable (G
PET
> 0) and the dyad exhibits
intense LE emission. More polar solvents render the energy level of
the CT state lower than LE state, making the electron transfer
process thermodynamically allowed (G
PET
< 0).
Charge-transfer states undergo a non-radiative charge
recombination (CR), also known as a back electron transfer (BET),
to restore the ground state of the dyad.
30a
The free energy change
associated with the recombination process can have rather large
negative values due to a large energy gap between the CT state and
the ground state (e.g. > 1.5 eV). Under these circumstances,
thermodynamics of the process falls into the so-called Marcus
“inverted” region, where the activation energy is substantially
increased, consequently decreasing the CR rate. Because of slow
charge recombination, CT states can have rather long lifetimes,
often reaching the microsecond range.
34
Over the past decades, a number of efforts have been devoted to
the design of electron donor-acceptor systems which efficiently
produce long-living CT states.
35
For many of these systems an
alternative charge recombination process is observed, namely the
recombination into local triplet excited states.
36
This process is
recognized as one of the most serious bottlenecks in the design of
artificial photosynthetic systems.
37
Two general pathways for the formation of triplets from CT states
have been investigated and are schematically presented in Figure
3a. The mechanism involving the formation of an intermediate
triplet charge-transfer state (
3
CT) is known as a radical-pair
intersystem crossing (RP-ISC).
38
This process was found to occur in
natural photosynthetic reaction centers
39
and various electron
donor-acceptor dyads which exhibit a weak electronic coupling
between the donor and acceptor subunits due to long separation
distances (e.g. > 15 Å).
40
ISC in the initially formed singlet charge-
transfer state (
1
CT) happens via hyperfine interaction (HFI) – an
interaction between an electron spin and a nuclear spin. ISC is
followed by a fast charge recombination populating the lowest
triplet excited state of either donor or acceptor subunit. The rate of
RP-ISC is very sensitive to external magnetic fields and can be
studied with several spectroscopic methods, e.g. time-resolved EPR
and chemically induced dynamic nuclear polarization (CIDNP).
41
Figure 3. a) Jablonski diagram showing possible mechanisms of triplet state
formation in electron donor-acceptor dyads. PET – photoinduced electron
transfer,
1
CT – singlet charge-transfer state,
3
CT – triplet charge-transfer
state. RP-ISC – radical pair intersystem crossing, SOCT-ISC – spin-orbit
charge transfer intersystem crossing. b) Schematic representation of
conditions required for efficient SOCT-ISC in a closely-spaced donor-
acceptor dyad. CR
T
and CR
s
- charge recombination into the local triplet state
and into the ground state, respectively.
For donor-acceptor systems with stronger electronic couplings, ISC
via HFI is less probable, since the energy splitting between
1
CT and
3
CT states becomes larger than the HFI energy. An alternative ISC
pathway which can take place in such molecules is a direct
conversion of
1
CT into T
1
state, involving a back electron transfer
and a spin inversion. This process is referred to as a spin-orbit
charge transfer intersystem crossing (SOCT-ISC). It is enhanced if
the subunits are in a near perpendicular orientation, which allows
to compensate electron spin angular momentum changes during
ISC by molecular orbit angular momentum changes.
42
This
mechanism is similar to the ISC in aromatic carbonyl compounds,
where the S
1
(n,π*)→T
2
(n,π*) transition can be regarded as a
transfer of an electron from the lone pair of the oxygen atom to the
π* orbital located on the carbon atom.
43
SOCT-ISC was recognized as a major mechanism responsible for the
formation of triplets in closely-spaced dyads, i.e. those in which the
donor and the acceptor are directly linked through a single C-C
bond. Steric hindrance between the subunits in such dyads leads to
their orthogonal arrangement, which induces a large variation of
the orbital magnetic momentum during electron transfer. This
compensates the change of spin magnetic momentum, essential for
the occurrence of ISC. The probability of SOCT-ISC is substantially
reduced for dyads with dihedral angles between the subunits of less
than 70°, leading to reduced triplet state yields. Nevertheless,
triplet states formation in non-orthogonal BODIPY dyads was noted
in several works, which are discussed in sections 3.2 and 3.3.
As was demonstrated for various dyads and dimers, the triplet state
yield from
1
CT state depends on the rates of two competitive
relaxation pathways: charge recombination into the local triplet
state (CR
T
) and recombination into the ground singlet state (CR
S
),
k
CRT
and k
CRS
, respectively (Figure 3b).
44
High triplet state yields can
be achieved if k
CRS
is substantially lower than k
CRT
. This condition is
met, for example, if the driving force of the CR
S
process (G
CRS
) has
large negative values and falls within the Marcus inverted region.
In
this case, charge recombination into the lowest triplet excited state
can be considerably faster because the corresponding Gibbs free
energy change (G
CRT
) is smaller due to a smaller
1
CT-T
1
energy gap.
BODIPYs have been employed both as electron donors and
acceptors in a number of dyads undergoing PET.
45
Surprisingly, the
development of triplet sensitizers operating via SOCT-ISC has
attracted attention only recently. The formation of triplets upon CT
state recombination in the absence of heavy atoms was studied for
the first time in BODIPYs covalently attached to
buckminsterfullerene, C
60
.
46
Applications of these systems as triplet
sensitizers in photocatalysis
47
and photon upconversion,
48
have
been demonstrated and are discussed in a recent review by Zhao.
14
However, preparation of such compounds costs a considerable
synthetic effort, limiting the opportunities for their practical use.
For this reason, compact dyad molecules capable of triplet state
formation, discussed in the following section, are particularly
interesting.
3. BODIPY donor-acceptor dyads
3.1 Meso-phenyl, naphthyl- and pyridyl BODIPYs
The presence of aryl substituents in the BODIPY core is known to
have a strong influence on its excited state dynamics and
luminescent properties.
49
As reported by the groups of Daub
50
and
Nagano,
51
various BODIPYs bearing an electron donating meso-aryl
group undergo PET and form charge-transfer excited states. Zhang
and co-workers systematically studied singlet oxygen generation
for a series of molecules 5-12, in which the aryl group plays the role
of electron donor (Figure 4a). Compared to the reference meso-
phenyl BODIPY 4 possessing intense fluorescence and low singlet
oxygen quantum yields (
) in all solvents, dyad 5 bearing a 2-
methoxyphenyl group exhibited a progressive quenching of the
fluorescence and singlet oxygen quantum yield values, which
increased with solvent polarity (Table 1). By changing the number
and the position of methoxy substituents in meso-phenyl group
(compounds 5-9), singlet oxygen generation was optimized to
reach 46% yield.
52
,54a
Characteristic charge-transfer emission bands
were observed for compounds 6 and 9, having substituents in ortho
positions of the aryl group, which hinder its rotation and secure
orthogonal arrangement with respect to the BODIPY subunit.
Formation of BODIPY triplets upon CT state recombination was
confirmed by transient absorption (TA) experiments for 9, with a
lifetime estimated to be 6.4 s.
Introduction of electron donating substituents was found to
activate PET and singlet oxygen generation in meso-naphthyl
BODIPYs.
53
,
54
For dyad 10, electron transfer is thermodynamically
unfavourable (G
PET
> 0.2 eV) and it exhibits strong fluorescence
even in polar solvents. On the other hand, dyads 11 and 12 with
Figure 4. Structures of the BODIPYs incorporating electron donating (a) and electron accepting (b) meso-aryl groups and reference compounds (4 and 13).
Table 1. Absorption/emission peaks, fluorescence quantum yields (Φ
fl
) and singlet oxygen generation quantum yields (Φ
) of meso-phenyl and naphthyl BODIPYs
and reference compounds in solvents of different polarities.
Compound
Solvent (
r
)
a
λ
abs
(nm)
b
λ
fl
(nm)
Φ
fl
Φ
c
Reference
4
hexane (1.89)
CH
3
CN (37.5)
501
497
511
508
0.56
0.52
0.05
0.017
53
53
5
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
504
503
499
516
516
512
0.98
0.87
0.57
0.029
0.061
0.18
52
52
52
6
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
507
506
500
519
520
513
0.71
0.64
0.54
0.04
0.051
0.18
52
52
52
7
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
504
503
499
517
514
510
0.971
0.457
0.01
0.026
0.462
0.125
54a
54a
54a
8
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
504
503
500
518
514
510
0.863
0.004
0.001
0.11
0.357
0.033
54a
54a
54a
9
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
505
506
501
520
517
513
0.95
0.78
0.55
0.02
0.06
0.31
52
52
52
10
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
503
505
500
513
514
510
0.87
0.85
0.83
0.05
0.13
0.057
53
53
53
11
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
503
503
499
515
516
512
0.906
0.438
0.123
0.011
0.232
0.872
54a
54a
54a
12
hexane (1.89)
THF (7.58)
CH
3
CN (37.5)
500
500
498
511
513
508
0.637
0.581
0.118
0.047
0.442
0.081
54a
54a
54a
13
hexane (1.89)
EtOH (24.5)
498
498
513
514
0.031
0.025
d
0.03
55
55
14
hexane (1.89)
EtOH (24.5)
500
496
519
513
0.61
0.66
d
0.04
55
55
15
hexane (1.89)
EtOH (24.5)
499
496
516
513
0.69
0.66
d
0.06
55
55
16
hexane (1.89)
EtOH (24.5)
e
500
e
523
e
0.47
e
0.07
55
55
17
hexane (1.89)
EtOH (24.5)
505
502
527
522
0.35
0.08
d
0.16
55
55
18
hexane (1.89)
MeOH (32.7)
516
514
526
528
0.49
0.75
d
0.45
55
55
19-o
hexane (1.89)
MeOH (32.7)
505
501
521
512
0.027
0.023
0.018
0.0083
56
56
19-m
hexane (1.89)
MeOH (32.7)
505
501
521
512
0.42
0.14
0.0062
0.01
56
56
19-p
hexane (1.89)
MeOH (32.7)
505
501
521
512
0.19
0.03
0.0067
0.0036
56
56
20
hexane (1.89)
MeOH (32.7)
514
510
510
508
0.033
0.045
0.021
0.0055
56
56
21
hexane (1.89)
MeOH (32.7)
505
503
515
513
0.059
0.071
0.0052
0.013
56
56
22
hexane (1.89)
MeOH (32.7)
503
501
517
517
0.25
0.12
0.0091
0.012
56
56
a
ε
r
– dielectric constant of the solvent.
b
Low energy band corresponding to the BODIPY chromophore.
c
Determined using singlet oxygen trapping with
diphenylisobenzofuran (DPIBF).
d
Not reported.
e
Not soluble.
