Porphodilactones as synthetic chlorophylls: Relative orientation of ?-substituents on a Pyrrolic ring tunes NIR absorption

Article abstract of DOI:10.1021/ja502729x

Porphodilactones represent the porphyrin analogues, in which the peripheral bonds of two pyrrole rings are replaced by lactone moieties. They provide an opportunity to investigate how ?-substituent orientation of porphyrinoids modulates the electronic structures and optical properties, in a manner similar to what is observed with naturally occurring chlorophylls. In this work, a comprehensive description of the synthesis, characterization, and optical properties of meso-tetrakispentafluorophenylporphodilactone isomers is first reported. The ?-dilactone moieties are found to lie at opposite pyrrole positions (trans- and cis-configurations are defined by the relative orientations of the carbonyl group when one lactone moiety is fixed), in accordance with earlier computational predictions (Gouterman, M. J. Am. Chem. Soc. 1989, 111, 3702). The relative orientation of the ?-dilactone moieties has a significant influence on the electronic structures and photophysical properties. For example, the Q_y band of trans-porphodilactone is red-shifted by 19 nm relative to that of the cis-isomer, and there is a 2-fold increase in the absorption intensity, which resembles the similar trends that have been reported for natural chlorophyll f and d. An in depth analysis of magnetic circular dichroism spectral data and TD-DFT calculations at the B3LYP/6-31G(d) level of theory demonstrates that the trans- and cis-orientations of the dilactone moieties have a significant effect on the relative energies of the frontier π-molecular orbitals. Importantly, the biological behaviors of the isomers reveal their different photocytotoxicity in NIR region (>650 nm). The influence of the relative orientation of the ?-substituents on the optical properties in this context provides new insights into the electronic structures of porphyrinoids which could prove useful during the development of near-infrared absorbing photosensitizers.

Full text of DOI:10.1021/ja502729x

Article
pubs.acs.org/JACS
Porphodilactones as Synthetic Chlorophylls: Relative Orientation of
β‑Substituents on a Pyrrolic Ring Tunes NIR Absorption
Xian-Sheng Ke,† Yi Chang,‡ Jia-Zhen Chen,† Jiangwei Tian,‡ John Mack,§ Xin Cheng,† Zhen Shen,*,‡
and Jun-Long Zhang*,†,‡
†Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P.R. China
‡State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing
210093 P.R. China
§Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa
S
* Supporting Information
ABSTRACT: Porphodilactones represent the porphyrin ana-
logues, in which the peripheral bonds of two pyrrole rings are
replaced by lactone moieties. They provide an opportunity to
investigate how β-substituent orientation of porphyrinoids
modulates the electronic structures and optical properties, in a
manner similar to what is observed with naturally occurring
chlorophylls. In this work, a comprehensive description of the
synthesis, characterization, and optical properties of meso-
tetrakispentafluorophenylporphodilactone isomers is first re-
ported. The β-dilactone moieties are found to lie at opposite
pyrrole positions (trans- and cis-configurations are defined by
the relative orientations of the carbonyl group when one lactone
moiety is fixed), in accordance with earlier computational predictions (Gouterman, M. J. Am. Chem. Soc. 1989, 111, 3702). The
relative orientation of the β-dilactone moieties has a significant influence on the electronic structures and photophysical
properties. For example, the Qy band of trans-porphodilactone is red-shifted by 19 nm relative to that of the cis-isomer, and there
is a 2-fold increase in the absorption intensity, which resembles the similar trends that have been reported for natural chlorophyll
f and d. An in depth analysis of magnetic circular dichroism spectral data and TD-DFT calculations at the B3LYP/6-31G(d) level
of theory demonstrates that the trans- and cis-orientations of the dilactone moieties have a significant effect on the relative
energies of the frontier π-molecular orbitals. Importantly, the biological behaviors of the isomers reveal their different
photocytotoxicity in NIR region (>650 nm). The influence of the relative orientation of the β-substituents on the optical
properties in this context provides new insights into the electronic structures of porphyrinoids which could prove useful during
the development of near-infrared absorbing photosensitizers.
1). Although this demonstrates that modulating the orientation
of the β-substituents is a viable strategy for fine-tuning the
optical properties of natural pigments, the use of a similar
approach has yet to emerge in synthetic porphyrin chemistry.
Herein, we report the synthesis and characterization of
porphodilactones, in which the two peripheral lactone moieties
lie at opposite pyrrole positions (shown in Figure 1), and
investigate the effect of the relative orientation of the β-
dilactone moieties (trans- and cis-configurations are defined
based on the relative orientations of the carbonyl groups) on
the electronic structures and optical and biological properties.
Porpholactones, in which at least one pyrrole ring of the
porphyrin ligand is replaced by an oxazolone moiety, have
attracted increasing attention in recent years.4 The incorpo-
INTRODUCTION
■
The β-position substituents of naturally occurring tetrapyrrole
pigments have been found to play an important role in shaping
the optical properties in the near-infrared (NIR) region.1 In
contrast, traditional synthetic approaches for modulating the
properties of porphyrin ligands have tended to involve an
extension of the π-system or the size of the macrocycle.2 The
successful design of NIR absorbing porphyrinoids, which more
closely mimic the properties of naturally occurring tetrapyr-
roles, would provide new insights into the electronic structures
of these molecules, in a manner that should facilitate the
development of applications in optical materials and biological
studies. The recently discovered chlorophyll f (Qy(0,0) = 706
nm)3 has a formyl group located at the C2 position (Figure 1)
and a dramatically red-shifted Qy band compared to chlorophyll
b (Qy(0,0) = 648 nm)1b and d (Qy(0,0) = 688 nm)1d which have
formyl groups at the C7 and C3 positions, respectively (Figure
Received: March 26, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
orientations of the β-substituents have a significant effect on the
photophysical properties. Magnetic circular dichroism (MCD)
spectral data and theoretical calculations have been carried out
to analyze the influence of the relative orientation of β-
dilactone moieties on the relative energies of the frontier π-
MOs and hence on the optical properties. The photophysical
properties of the porphodilactones and their photocytotoxicity
toward cancer cells upon excitation at NIR regions (>650 nm)
have also been investigated. The insights achieved on this basis
should assist the future rational design of NIR region PDT
photosensitizers.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of the Opposite trans-
and cis-Porphodilactones and Their Zinc Complexes.
Reactions of tetrakispentafluorophenylporphyrin (H2F20TPP)
and tetrapentakisfluorophenylporpholatone (H2F20TPPL) with
an excess of Oxone (H2F20TPP: 12 equiv and H2F20TPPL: 4
equiv), in the presence of catalytic amounts of RuCl3 and 2,2′-
bipyridine, resulted in the formation of porphodilactone
isomers (H2F20TPPDL, Scheme 1) in 45 and 53% yield,
Scheme 1. Synthetic Procedure for Porphodilactone
a
Isomers
Figure 1. Chemical structures (a) Chl f, (b) d, (c) b and (d) the
orientation of β-formyl groups (purple: Chl f; green: Chl d; yellow:
Chl b); (e) stick models of the single crystal X-ray structures of cis-
Zn(py2)F20TPPDL and trans-Zn(py2)F20TPPDL, axial pyrindines,
meso-phenyl group, and protons omitted for clarity.).
ration of the oxazolone group results in optical properties that
lie between those of porphyrins and chlorins,4b,d due to their
lower molecular symmetry and the partial saturation of the
porphyrin periphery. Porpholactones provide attractive plat-
forms for designing catalysts for atom transfer reactions, novel
optical materials, and photodynamic therapy (PDT) photo-
sensitizers.5 The obvious next step is to explore the properties
of porphyrin analogues with two lactone moieties. In a seminal
paper on the subject by Gouterman and co-workers,4b
porphodilactones were tentatively identified, and their
structures were assigned using computational calculations as
shown in Figure S1. Given the wide range of possible
orientations for the dilactone moieties, the definitive character-
ization of these isomers became a bottleneck hindering further
progress, and this has impeded the emergence of a definitive
understanding of the relationship between the structures and
electronic properties of porphodilactones.
In this work, we found that the β-dilactone moieties were
located at the opposite pyrrole positions in tetrakispentafluor-
ophenylporphodilactones (H2F20TPPDL), which is consistent
with Gouterman’s earlier assignments based on the prediction
that the total energies of these structures are significantly lower
than those of the adjacent isomers (>0.84 eV).4b The Qy(0,0)
transition of trans-porphodilactone is red-shifted by 19 nm
compared to that of the cis-isomer, and there is a 2-fold increase
in the absorption intensity. Similar trends have been reported
for natural chlorophyll f and d, indicating that the relative
a
(a) 20% RuCl3, 20% 2,2′-bipyridine, 4−12 equiv oxone, H2O/1,2-
dichloroethane (1:1), 70 °C; (b) Zn(OAc)2, CHCl3/CH3OH (v/v =
7:3), reflux; (c) HCl solution (36−38%), acetone.
respectively. However, several attempts to separate the
porphodilactone isomers using silica gel chromatography,
HPLC, TLC, recrystallization, and even supercritical fluid
chromatography all failed (Figures S2−5). To isolate the
porphodilactone isomers, we metalized the porphodilactone
isomers with Zn(OAc)2 so that the trans- and cis-ZnF20TPPDL
isomers could be separated by silica gel chromatography (18
and 8% yields, respectively) (Figure S6). Subsequent
demetallization of the ZnF20TPPDL isomers by HCl solution
(36−38%) afforded pure porphodilactone free base isomers in
quantitative yield.
The characterization of trans- and cis-H2F20TPPDL and their
zinc complexes was carried out by 1H-, 13C- and 19F-NMR and
IR spectroscopy and by HR-ESI MS (Figure S19−35). As
shown in Figure 2, an analysis of the 1H NMR spectra
demonstrates that the mixture of porphodilactones contains
B
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
1
Figure 2. H NMR spectra (500 MHz) of mixture (a) the mixture of
trans- and cis-H2F20TPPDL (blue line), (b) trans-H2F20TPPDL (green
line), and (c) cis-H2F20TPPDL (red line) in CDCl3.
only the opposite forms, which have been termed the trans- and
cis-isomers in the context of this study. It should be noted that
similar results were obtained by using both Gouterman’s and
our experimental procedures.4b,f In the H NMR spectrum of
1
trans-H2F20TPPDL (Figure 2), one proton signal lies at δ =
8.86 (d, J = 1.7 Hz, 4H) (β-H) and another lies at −2.12 (s,
2H) (N−H) ppm. This simple pattern reflects the symmetry of
the structure. In contrast, the spectrum of cis-H2F20TPPDL is
more complicated with two peaks observed at δ = 8.53(d, J =
2.0 Hz, 2H) and 8.70 (d, J = 1.4 Hz, 2H) (β-H) ppm and
another two peaks at δ = −0.32 (s, 1H) and −0.94 (s, 1H) (N−
H) ppm, due to the change in the alignment of the main C2
symmetry axis. The IR spectra (Figure S31−34) also differ
based on the orientation of the β-dilactone moieties. CO
vibration bands are observed at 1769 cm−1 for trans-
H2F20TPPDL and 1771 and 1790 cm−1 for cis-H2F20TPPDL.
Similar spectral features are observed for trans- and cis-
ZnF20TPPDL.
Recrystallization of ZnF20TPPDL isomers in dichloro-
methane (DCM) (in the presence of 1% pyridine and benzene)
gave single crystals appropriate for X-ray diffraction analysis.
The unit cells of both trans- (CCDC: 987687) and cis-
ZnF20TPPDL (CCDC: 987686) contain two independent
molecules. The details are provided as Tables S1−2. The X-ray
structures in Figure 3 reveal the differing lactone moiety
arrangements of trans- and cis-ZnF20TPPDL. The two lactone
rings of trans-ZnF20TPPDL are correlated to one another by a
C2 axis perpendicular to the porphyrinoid plane, while the C2
axis of cis-ZnF20TPPDL lies in the plane. The porphyrinoid
plane of trans-ZnF20TPPDL is much less distorted from
planarity than that of cis-ZnF20TPPDL (Figure 3c,d). The
CO bond distances are 1.208 and 1.184 Å for trans- and cis-
ZnF20TPPDL, respectively. In each case, the Zn centers are
octahedrally coordinated by four pyrrole nitrogen atoms with
Zn−N bond distances ranging from 2.019 to 2.053 Å and those
of the two axial pyridine ligands with Zn−N bond distances
ranging from 2.344 to 2.443 Å. Interestingly, the axial pyridyl
N−Zn bonds of trans-ZnF20TPPDL (2.344 Å) are shorter than
those of cis-ZnF20TPPDL (2.443 Å). This might be due to a
slight deviation (4.5°) of the axial Zn−N4 (pyridine) bond
relative to the normal line of the porphyrinoid plane (N1, N1A,
N2, N3, and Zn1) in the case of cis-ZnF20TPPDL (Figure 3d).
The angle between the two axially coordinated pyridine ligand
planes of cis-ZnF20TPPDL is 17.6°. In contrast, the two axial
pyridines of trans-ZnF20TPPDL are coplanar. These results
suggest that the relative orientation of the dilactone moieties on
Figure 3. Stick models of the single crystal X-ray structures of (a)
trans-Zn(py2)F20TPPDL and (b) cis-Zn(py2)F20TPPDL. The align-
ment of the C2 symmetry axis for (c) trans-Zn(py2)F20TPPDL is
orthogonal to the porphodilactone π-system and (d) the cis-isomer lies
in the plane of the porphodilactone π-system.
the β-periphery influences the coordination of the central metal
ion.
Optical Spectra of trans- and cis-H2F20TPPDLs and
Their Zinc Complexes. The electronic absorption spectra
were measured in DCM (Figure 4) to investigate the effects of
β-dilactone orientation on optical properties. When compared
with the spectrum of H2F20TPPL, trans- and cis-H2F20TPPDL
have broad B (or Soret) bands centered at 410 and 408 nm,
respectively, with pronounced shoulders of intensity to the
blue. There is remarked red-shift of the Q bands between 500−
700 nm. The most likely explanation for this is that there is
strong electronic coupling between the lactone moieties and
the main porphyrin chromophores. Interestingly, trans-
H2F20TPPDL has a red-shifted (ca. 19 nm when compared to
cis-isomer) phyllo-type Q-band region in which the εmax value
of the lowest energy Q-band is twice that of the cis-isomer
(Figure 4). This suggests that the relative orientation of the
dilactone moieties plays a significant role in determining the
energies of the frontier π-MOs. Metalation with zinc(II) leads
to red-shifted and largely unresolved B bands (ca. 15 and 17
nm, respectively) and blue-shifted Qy bands (ca. 13 and 22
nm). This is the pattern normally observed for metal-
loporphyrinoids upon coordination of the free base compound
by Zn(II) ion.6 It is noteworthy that trans-ZnF20TPPDL has a
chlorin-type UV−vis absorption spectrum with a very intense
Qy band (εB/εQ@663= 1.8).
The fluorescence spectra of trans- and cis-H2F20TPPDLs and
their zinc complexes exhibit well-resolved vibronic progressions
upon excitation in the B band region. As shown in Figure 5,
each emission spectrum contains one intense dominant band
(I0−0) centered in the 644−678 nm region and a shoulder
(I0−1) slightly to the red. Small Stokes shifts are observed
relative to the lowest energy Q bands, as is characteristic of
most porphyrinoids.6 When compared to the spectrum of
H2F20TPPL, the main emission bands of trans- and cis-
H2F20TPPDL are red-shifted by ca. 35 and 23 nm, respectively,
C
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Figure 5. Emission spectra of (a) H2F20TPPL, trans- and cis-
H2F20TPPDL (excited at B band region); (b) ZnF20TPPL, trans-
and cis-ZnF20TPPDL (excited at B band region) in DCM.
Figure 4. UV−vis absorption spectra of (a) H2F20TPPL, trans- and cis-
H2F20TPPDL and (b) ZnF20TPPL, trans- and cis-ZnF20TPPDL in
DCM.
data reveal that the relative orientations of the lactone moieties
play a significant role in shaping the electronic structures and
the optical properties in the Q-band region.
and the fluorescence quantum yields (ΦF) are slightly lower
(0.10 and 0.09 vs 0.13 for H2F20TPPL). For the zinc
complexes, the fluorescence emission bands are shifted to the
blue by 12 and 18 nm compared to those of free bases with a 3-
to 4-fold decrease in the ΦF values (0.025 for trans-
ZnF20TPPDL and 0.028 for cis-ZnF20TPPDL). Shortened
lifetimes (from 3.49 to 0.65 ns for trans-F20TPPDL, and from
3.49 to 0.81 ns for cis-F20TPPDL) are also observed (Table S3).
These trends are probably related to an increase in intersystem
crossing due to the heavy atom effect. The excitation spectra for
the free bases and zinc complexes were identical with the
absorption spectra when monitored at their maximum emission
bands (I0−0). This demonstrates that the emission originated
from the lowest lying π−π* transition (Figure S7−10).
The redox potentials for the porphodilactones provide an
insight into their electronic structures. Cyclic voltammograms
(CV) were measured, and the data are listed in Table 1. Both
free base porphodilactone isomers have two quasi-reversible
reduction waves at ∼ −0.4 and −0.9 V and a quasi-reversible
oxidation wave at ∼ +1.60 V (Figure S11). The HOMO−
LUMO gaps obtained from the first-oxidation and -reduction
potentials of trans-H2F20TPPDL (1.98 eV) is narrower than
that of cis-H2F20TPPDL (2.10 eV). As would normally be
anticipated, the HOMO−LUMO gaps calculated from the
electrochemical data are consistent with those obtained from
the optical data (1.80 and 1.84 eV). Similar trends are observed
in the CV of trans-ZnF20TPPDL relative to cis-ZnF20TPPDL.
Compared to H2F20TPP, H2F20TPPL, and their zinc com-
plexes, the experimental and calculated HOMO−LUMO gaps
of porphodilactones are consistent to their absorptions. These
Electronic Structures of trans- and cis-H2F20TPPDLs
and Their Zinc Complexes. A series of MCD measurements
were made and B3LYP optimizations and TD-DFT calculations
were carried out to analyze the effect of dilactone orientation
on the optical properties and electronic structures. MCD
spectroscopy is based on intensity mechanisms described by the
Faraday
(
1, )0, and *0 terms.10 TD-DFT calculations were
carried out on a series of B3LYP-optimized geometries using
the Coulomb-attenuated B3LYP functional (CAM-B3LYP)
functional with 6-31G(d) basis sets, since the results of TD-
DFT calculations with the B3LYP functional of the Gaussian 09
software package11 are known to be problematic when
significant charge transfer character is involved.12 The CAM-
B3LYP functional includes a long-range correction of the
exchange potential, which incorporates an increasing fraction of
Hartree−Fock (HF) exchange as the interelectronic separation
increases. Moffitt13 and Michl14 demonstrated that the relative
intensities of the major electronic absorption bands of aromatic
π-systems can be successfully described in terms of
perturbations to the structure of a high-symmetry parent
2−
hydrocarbon (C16H16 in the case of metal tetrapyrrole
porphyrinoid complexes or C18H18 for free base compounds).
The nodal patterns of the π-system MOs are retained even
when the symmetry of the cyclic perimeter is modified. As a
consequence of this, there is an ML = 0, 1, 2, 3, 4, 5,
6, 7, 8 sequence in ascending energy terms in the π-MOs
of metal porphyrinoids. Within the band nomenclature of
D
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Table 1. CV Data (V vs SCE) for H2F20TPP, H2F20TPPL, trans and cis-H2F20TPPDLs and Their Zinc Complexes in CH2Cl2
Containing 0.1 M NBu4PF6
oxidation
reduction
second
a
b
compounds
second
first
first
third
HOMO−LUMO gap (V)
HOMO−LUMO gap (eV)
trans-H2F20TPPDL
cis-H2F20TPPDL
trans-ZnF20TPPDL
cis-ZnF20TPPDL
H2F20TPP
+1.61
+1.66
+1.25
+1.31
+1.55
+1.77
+1.20
+1.29
−0.37
−0.44
−0.75
−0.86
−0.76
−0.58
−1.05
−0.76
−0.87
−0.85
−1.28
−1.06
−1.17
−1.04
−1.47
−1.20
1.98
2.10
2.00
2.17
2.31
2.35
2.25
2.05
2.34
2.45
2.24
2.41
2.80
2.64
2.94
2.62
+1.54
+1.77
−1.28
H2F20TPPL
ZnF20TPP
+1.36
+1.57
ZnF20TPPL
a
b
The potential difference between the first oxidation and first reduction. Calculation results with the B3LYP functional.
Gouterman’s 4-orbital model,6 there is an electronically allowed
B transition and a forbidden Q transition linking the frontier
ML = 4, 5 π-MOs based, respectively, on ΔML = 1 and
9 transitions. When a structural perturbation results in a
marked lifting of the degeneracy of the MOs derived from the
HOMO and/or LUMO of the parent perimeter (referred to as
the ΔHOMO and ΔLUMO values within Michl’s terminol-
ogy14) there is a mixing of the allowed and forbidden properties
of the Q and B bands and a marked intensification of the Q-
band.15 When ΔHOMO ≈ ΔLUMO the Q bands remain
relatively weak, since the orbital angular momentum properties
of the parent hydrocarbon perimeter are retained.16
Michl14 introduced an a, s, −a and −s terminology for the
four MOs derived from the HOMO and LUMO of the parent
perimeter so that π-systems of porphyrinoids with differing
molecular symmetry and with different relative orderings of the
four frontier π-MOs in energy terms can be readily compared
(Figure 6). One MO derived from the HOMO of the parent
perimeter and another derived from the LUMO have nodal
planes which coincide with the yz-plane and are referred to,
respectively, as the a and −a MOs, while the corresponding
MOs with antinodes on the yz-plane are referred to as the s and
−s MOs. The D4h symmetry of porphyrin ligand dianions
dictates that the −a and −s MOs are degenerate since the ML =
5 nodal patterns differ along the x- and y-axes only by being
rotated by 90° with respect to each other (Figure 6). Both
H2F20TPP and ZnF20TPP are predicted to have very small
ΔHOMO and ΔLUMO values (Figure 6). When lactone
moieties are introduced to form porpholactones and -dilactones
(Figure 7), the s and −a MOs, which lack significant MO
coefficients on these moieties, are predicted to be significantly
stabilized in the free base compounds and zinc complexes
relative to the corresponding TPP compounds, due to the
inductive effects associated with the structural modification. In
contrast, there is a smaller stabilization of the a and −s MOs,
which have larger MO coefficients on the lactone moieties,
probably due to the mesomeric interaction between the
peripheral carbonyl bond and the π-system MOs. The
orientation of the carbonyl bonds has a more significant effect
on the relative energies of the −a and −s MOs of the cis- and
trans-dilactone isomers (Figure 7), since the nodal patterns of
the MOs derived from the LUMO of the parent perimeter are
not radially symmetric. This results in large ΔLUMO values for
trans-H2 and trans-ZnF20TPPDL (Figures 6 and 7) and
accounts for the intensification of the Q bands that is observed
in Figure 4, since the ΔLUMO values are significantly greater
than the ΔHOMO values (Figure 6).
Figure 6. Nodal patterns and energies of the frontier π-MOs of
H2F20TPP, H2F20TPPL and trans- and cis-H2F20TPPDL and of
ZnF20TPP, ZnF20TPPL and trans- and cis-ZnF20TPPDL in TD-DFT
calculations with the B3LYP functional.
E
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Figure 7. Energies of the a and −a MOs of H2F20TPP, H2F20TPPL cis-
and trans-H2F20TPPDL, ZnF20TPP, ZnF20TPPL, and cis- and trans-
ZnF20TPPDL in the TD-DFT calculations carried out with the B3LYP
functional are denoted with red diamonds, while those of the s and −s
MOs are denoted with blue diamonds. Gray squares are used to plot
the average HOMO−LUMO gap taking all four MOs of Michl’s
perimeter model into account against a secondary axis.
The main electronic Q and B bands of the cis and trans
isomers can be readily assigned, since the
(
1 terms that would
be anticipated in the MCD spectra of metal porphyrin
complexes are replaced by coupled pairs of oppositely signed
)0 terms due to the absence of a 3-fold or higher axis of
symmetry (Figure 7 and Table S4). Michl14 has demonstrated
that in the context of aromatic π-systems such as porphyrinoids,
the differential absorbance of left and right polarized light by
the excited states is related to the alignments of the induced
magnetic moments with and against the axis of light
propagation, and the applied field (and hence the ordering of
the MCD signs for the Qx, Qy, Bx, By bands) is determined
primarily by the relative magnitudes of the ΔHOMO and
ΔLUMO values. When a structural perturbation introduces a
large ΔHOMO or ΔLUMO value, circulation of charge on the
perimeter is hindered. The relative magnitudes of the ΔHOMO
and ΔLUMO values, therefore, determine whether the
circulation of the excited electron in the LUMO level or that
of the hole left in the HOMO level is the dominant factor in
conserving the quantum of orbital angular momentum provided
by the incident photon of left or right circularly polarized light.
When ΔHOMO > ΔLUMO and electronic charge circulation
in the LUMO predominates, the ordering of the MCD intensity
signs for the )0 terms associated with the Q and B bands is −,
+, −, + in ascending energy terms. In contrast, when ΔLUMO
> ΔHOMO and the circulation of the positive charge
associated with the hole left in the HOMO is the dominant
factor, the sequence reverses to +, −, +, −. Djerassi and co-
workers17 demonstrated in the context of chlorin compounds
where |ΔHOMO − ΔLUMO| ≈ 0, that the sign sequence of
the forbidden Q bands often changes before that of the allowed
B bands when ΔHOMO > ΔLUMO, so that a +, −, −, + sign
sequence is observed in the MCD spectrum. This is the pattern
that is observed for trans-H2 and trans-ZnF20TPPDL. In
contrast, a −, +, −, + sign sequence is observed for both cis-
H2 and cis-ZnF20TPPDL (Figure 8). Although this would only
be anticipated for cis-ZnF20TPPDL based on the predicted MO
energies (Figure 6), it should be noted that the differences
between the predicted ΔHOMO and ΔLUMO values are
relatively small in this context and there is more scope for
conformational flexibility with the free base compounds. The
sign sequences observed in the MCD spectra for the )0 terms
Figure 8. Absorption and MCD spectra of cis-H2F20TPPDL (H2 cis)
and cis-ZnF20TPPDL (Zn cis) (bottom) and of trans-H2F20TPPDL
(H2 trans) and trans-ZnF20TPPDL (Zn trans) (top) in CHCl3. TD-
DFT spectra calculated with the CAM-B3LYP functional were plotted
against a secondary axis. Large red diamonds and wavelength label are
used to highlight the main electronic Q and B bands. The details of the
TD-DFT spectra and a comparison of the calculated and observed
intensities of the main spectral bands are provided as Table S4.
associated with the Q and B bands are broadly consistent with
the trends that would be anticipated based on the MO energies
predicted in the B3LYP geometry optimizations and hence help
to validate the theoretical descriptions of the electronic
structures.
Photosensitizing Properties of the Porphodilactones
in the NIR Region. Although the use of porphyrins and their
derivatives in PDT is well-known,7 their major shortcoming in
this regard is their relatively weak absorption at the red end of
the visible region. Since the absorption intensities of the trans-
and cis-H2F20TPPDLs and their zinc complexes are 66, 22, 179,
and 53 times greater than that of H2F20TPP when the
extinction coefficient ratio of Q(0,0) band and B band (εQ(0,0)
/
εB) is taken into consideration, the obvious next step was to
investigate their 1O2 photosensitizing properties upon
excitation at NIR region.
Singlet oxygen quantum yields (ΦΔ) of trans- and cis-
H2F20TPPDLs and their zinc complexes were calculated using
1,3-diphenyl isobenzofuran (DPBF) as a singlet oxygen
scavenger.8 When trans-H2F20TPPDL and its zinc complex
were analyzed, mixed solutions of the sensitizer and DPBF were
F
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Table 2. Singlet Oxygen Quantum Yields (ΦΔ) of H2F20TPP,
H2F20TPPL, trans- and cis-H2F20TPPDLs and their zinc
complexes in DCM
a
compounds
ΦΔ
b
b
trans-H2F20TPPDL
trans-ZnF20TPPDL
cis-H2F20TPPDL
cis-ZnF20TPPDL
H2F20TPP
0.53
0.66
c
<0.05
c
0.87
d
d
c
n.d.
n.d.
ZnF20TPP
H2F20TPPL
0.84
d
ZnF20TPPL
n.d.
a
b
Methylene blue (MB) as standard (ΦΔ = 0.57 in DCM). Excited by
c
d
a 671 nm laser beam. Excited by a 635 nm laser beam. Not
determined due to too weak absorption at 635 and 671 nm.
irradiated with a 671 nm laser beam. The slope of the graph
obtained by plotting the changes in absorbance of DPBF at 411
nm against irradiation time was used to calculate the ΦΔ value
(Figures S12−18). Values of 0.53 and 0.66 were obtained for
trans-H2F20TPPDL and trans-ZnF20TPPDL in DCM refers to
methylene blue (MB) (ΦΔ = 0.57 in DCM). ΦΔ values of cis-
H2F20TPPDL and its zinc complex were analyzed by using
similar method. A value of 0.87 was obtained for cis-
ZnF20TPPDL when irradiated with a 635 nm laser beam. As
the control experiments, we chose H2F20TPP, H2F20TPPL and
their zinc derivatives and found that their singlet oxygen
quantum yields, except for H2F20TPPL (0.84), could not be
measured due to the extremely low absorption at 635 and 671
nm. To our surprise, cis-H2F20TPPDL showed no singlet
oxygen production at all after irradiation by a 635 nm laser
beam. Although the reasons for the unexpected behavior of cis-
H2F20TPPDL, the results showed that the orientation of
dilactone moieties affects the singlet oxygen production.
Figure 9. Dark toxicity and phototoxicity of (a) trans-H2F20TPPDL,
(b) trans-ZnF20TPPDL, (c) cis-H2F20TPPDL, (d) cis-ZnF20TPPDL-
loaded PLGA NPs in HeLa cells. Irradiated after a 671 nm laser at a
power of 20 mW cm−2 for 60 s and then analyzed by MTT assay.
The photocytoxicity of trans- and cis-H2F20TPPDL and their
zinc complexes in HeLa cells was investigated to explore their
potential utility for use as photosensitizes in PDT. We used the
modified solvent extraction/evaporation single-emulsion meth-
od9 to prepare porphodilactones-loaded poly(lactide-co-glyco-
lide) nanoparticles (PLGA NPs) to make the four porphodi-
lactones water-soluble. MTT assays were carried out to
investigate the dark toxicity and phototoxicity of the NPs in
HeLa cells. Both compounds showed no dark toxicity after
incubation for 24 h in HeLa cells (Figure 9). After irradiation
with a 671 nm laser at a power of 20 mW cm−2 for 60 s, trans-
H2F20TPPDL and its zinc complex-loaded PLGA NPs exhibited
good phototoxicity with a half-maximal inhibitory concen-
tration (IC50) value of 51 and 44 μg·mL−1, respectively.
However, the IC50 value of cis-ZnF20TPPDL-loaded PLGA NPs
was significantly larger (94 μg·mL−1), despite having a larger
ΦΔ value, which may be related to its low red light (671 nm)
absorption ability. The Propidium iodide (PI) staining
experiment (Figure 10) showed that most of the cells were
dead after incubation with 60 μg·mL−1 trans-H2F20TPPDL and
its zinc complex-loaded PLGA NPs for 24h and then irradiated
by using a 671 nm laser at a power of 20 mW cm−2 for 60 s,
while less cell death was observed for the cis-ZnF20TPPDL-
loaded PLGA NPs under identical condition. As expected, cis-
H2F20TPPDL-loaded PLGA NPs showed nearly no photo-
cytoxicity toward Hela cells, which was consistent with the zero
singlet oxygen production and the MTT results.
Figure 10. Confocal fluorescence images of PI stained HeLa cells
treated with 60 μg·mL−1 (a) trans-H2F20TPPDL, (b) trans-
H2F20TPPDL, (c) cis-H2F20TPPDL, (d) cis-ZnF20TPPDL-loaded
PLGA NPs incubation combined with irradiation. Scale bar: 75 μm
(DIC: differential interference contrast).
CONCLUSIONS
■
The free base cis and trans opp-porphodilactone isomers and
their zinc complexes have been successfully isolated and
characterized. A detailed analysis of their optical spectra and
TD-DFT calculations has demonstrated that the electronic
structures are similar to those of bacteriochlorins. The relative
orientation of the carbonyl bonds plays a significant role in
determining the optical properties in the Q-band region, since
it has a significant impact on the relative energies of the frontier
π-MOs. Moreover, an investigation of the photophysical
properties and in-depth photocytotoxicity studies has demon-
G
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
1
ZnF20TPPDL: H NMR (400 MHz, CDCl3) δ 8.57 (s, 2H), 8.43 (s,
2H). 13C NMR (126 MHz, CDCl3) δ 164.38, 155.58, 153.15, 148.33,
147.96, 146.87, 145.82, 145.16, 143.69, 141.65, 139.17, 137.15, 133.69,
133.07, 129.16, 123.44, 111.92, 110.96, 109.01, 88.72. HRMS (ESI+)
m/z [M + H]+: calcd for C42H5F20N4O4Zn 1072.9283, found:
1072.9275.
strated the potential utility of these compounds as PDT
photosensitizers for use in the biological window between 650
and 1000 nm. The novel strategy reported here should open
the door to design of more novel NIR absorbing porphyrinoids.
EXPERIMENTAL SECTION
Synthesis of trans-H2F20TPPDL. Concentrated HCl solution
(36−38%) (0.3 mL) were added to 5 mL acetone solution of trans-
ZnF20TPPDL (100 mg, 0.09 mmol) at room temperature, and after
several minutes the color of the solution changed from green to
purple. trans-H2F20TPPDL was obtained in quantitative yield. 1H
NMR (500 MHz, CDCl3) δ 8.86 (d, J = 1.7 Hz, 4H), −2.12 (s, 2H).
13C NMR (126 MHz, CDCl3) δ 165.09, 153.70, 147.27, 145.32,
144.02, 142.00, 139.31, 138.84, 137.29, 133.10, 128.21, 127.91, 110.77,
103.42, 91.80. HRMS (ESI+) m/z [M + H]+: calcd for C42H7F20N4O4
1011.0148, found: 1011.0139.
■
Unless otherwise stated, all reactions were performed under an inert
nitrogen atmosphere. UV−vis spectra were recorded on an Agilent
8453 UV−vis spectrometer equipped with an Agilent 89090A
thermostat ( 0.1 °C) at 25.0 °C. The emission spectra and lifetimes
were recorded on an Edinburgh Analytical Instruments FLS920
lifetime and steady state spectrometer (450 W Xe lamp, PMT R928).
Mass spectra were measured on a Bruker APEX IV FT-ICR Mass
Spectrometer (ESI-MS). IR spectra were recorded on a Bruker
1
Vector22 FT-IR spectrometer as KBr pellets. H NMR spectra were
Synthesis of cis-H2F20TPPDL. was obtained through a process
similar to that described for trans-H2F20TPPDL. 1H NMR (500 MHz,
CDCl3) δ 8.70 (d, J = 1.4 Hz, 2H), 8.53 (d, J = 2.0 Hz, 2H), −0.32 (s,
1H), −0.94 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 165.06, 155.95,
147.12, 145.29, 144.06, 142.76, 141.87, 139.27, 137.38, 136.58, 130.27,
130.20, 125.63, 110.77, 109.89, 107.94, 90.41. HRMS (ESI+) m/z [M
+ H]+ calcd for C42H7F20N4O4 1011.0148, found: 1011.0173.
Singlet Oxygen Quantum Yield Determination. Singlet
oxygen quantum yields (ΦΔ) of H2F20TPP, H2F20TPPL, trans- and
cis-H2F20TPPDLs and their zinc complexes were calculated using
DPBF as a singlet oxygen scavenger19 with MB as standard (ΦΔ = 0.57
in DCM).20 The ΦΔ values were calculated according to the following
equation:
measured on a Bruker ARX400 (400 MHz) or AVANCE III (500
MHz) spectrophotometer; 19FNMR (CF3COOH as external stand-
ard) and 13C NMR spectra were recorded on a Bruker AVANCE III
spectrophotometer (471 MHz for 19F, 126 MHz for 13C).
Spectroscopic-grade DCM was used as purchased from Alfa-Aesar,
for the various optical measurements. MCD spectra were recorded on
a Jasco J-725 spectrodichrometer with a Jasco electromagnet that
produced a magnetic field of up to 1.09 T. CHCl3 that was stabilized
by 0.5% EtOH (Nacalai Tesque) was used as the solvent. The
modified conventions of Piepho and Schatz18 are adopted for the three
Faraday terms, so in contrast with many earlier studies by authors such
as Michl,14 the sign of Faraday )0 terms matches that of the spectral
measurements.
Synthesis of 5,10,15,20-Tetra(pentafluorophenyl)-
porphodilactone (mixture of two isomers). Method 1.
5,10,15,20-tetra(pentafluorophenyl)porphyrin (0.1 mmol 100 mg)
was dissolved in 1,2-dichloroethane (DCE) (45 mL). The DCE
solution and 15 mL of water were mixed and stirred at room
temperature, and an aqueous RuCl3 solution (4.3 mg 0.02 mmol) and
a DCE solution of 2,2′-bipyridine (3.2 mg, 0.02 mol) were added to
the system. The solution was then heated to 70 °C, and a mixture of
Oxone and NaOH solution (12 equiv) was added by dropping funnel.
The reaction was monitored by TLC and quenched with an aqueous
solution of Na2S2O3. The organic phase was separated by separating
funnels, the aqueous phase was washed twice with DCM, and the
combined organic phase was evaporated by rotary evaporation. A
mixture of two 5,10,15,20-tetra(pentafluorophenyl)porphodilactone
isomers was obtained by column chromatography as a purple solid in
the yield of 45%. The trans-H2F20TPPDL:cis-H2F20TPPDL ratio was
SporFMB
Φ (1O2)por = Φ (1O2)MB
Δ
Δ
SMBFpor
Where ΦΔ(1O2) is the quantum yield of singlet oxygen, superscripts
por and MB represent mentioned porphyrinoids and methylene blue,
respectively. S is the slope of a plot of difference in change in
absorbance of DPBF (at 411 nm) with the irradiation time, and F is
the absorption correction factor, which is given by F = 1−10−OD (OD
at the irradiation wavelength).
Synthesis of Porphodilactones Loaded PLGA-NPs. The trans-
and cis-H2F20TPPDLs and their zinc complexes loaded PLGA NPs
were prepared using a modified solvent extraction/evaporation single-
emulsion method.9 10 mg of poly(lactide-co-glycolide) (PLGA,
Daigang Biomaterial Co., Ltd., Jinan, China) and 5 μmol trans-
H2F20TPPDL, trans-ZnF20TPPDL, cis-H2F20TPPDL or cis-
ZnF20TPPDL were dissolved into 1 mL DCM. The organic solution
was added dropwise to 10 mL of aqueous solution rotating at 5000
rpm containing poly(vinyl alcohol) (PVA, 2.5 wt % in ultrapure water;
MW = 30,000−70,000 Da from Sigma−Aldrich) as a surfactant,
sonicated for 2 min at 4 °C and then stirred overnight to evaporate the
organic solvent, forming porphyrin-loaded PLGA NPs. After removing
large particles by centrifugation at 3000 g for 25 min, the PLGA NPs
were collected by ultracentrifugation at 21,000 g for 25 min and
washed three times to remove excess PVA. In between the washing
steps, PLGA NPs were redispersed into ultrapure water by sonication.
The washed PLGA NPs were filtered with a 0.45 μm membrane filter
and stored at 4 °C until use.
MTT Assay. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
bromide) (MTT) assay was carried out to investigate the dark toxicity
and phototoxicity of the trans- and cis-H2F20TPPDLs and their zinc
complexes loaded PLGA NPs. HeLa cells were first seeded in two 96-
well plates at a seeding density of 1 × 104 cells per well in 200 μL
complete medium, which was incubated at 37 °C for 24 h. After
rinsing with PBS, HeLa cells were incubated with 200 μL culture
media containing serial concentrations of porphodilactone loaded
PLGA NPs for 24 h. One plate was kept in the dark to study the dark
toxicity, and another plate was irradiated using a 671 nm laser at a
power of 20 mW cm−2 for 60 s. Afterward, the cells were grown for
another 24 h. Then, 20 μL of 5 mg mL−1 MTT solution in pH 7.4 PBS
was added to each well. After 4h incubation, the medium containing
1
determined to be 3:2 from the integration of the H NMR data.
Method 2. 5,10,15,20-tetra(pentafluorophenyl)porpholactone, was
used as the starting material, and the synthesis procedure was similar
to Method 1, but the amount of oxidant (Oxone:NaOH = 1:1
solution) was (4 equiv). 5,10,15,20-tetra(pentafluorophenyl) porpho-
dilactone was obtained in 53% yield as a mixture of two isomers.
Synthesis of trans- and cis-ZnF20TPPDL. A 5,10,15,20-tetra-
(pentafluorophenyl)porphodilactone (1.0 g, 1 mmol) and Zn(AcO)2·
2H2O (2.2 g, 10 mmol) mixture was dissolved in CHCl3/MeOH (v/v
= 7:3) and was refluxed for 4h. The product (mixture of two isomers)
was isolated by column chromatography as a green solid in
quantitative yield. In a typical isolation run, the zinc 5,10,15,20-
tetrakispentafluorophenylporphodilactones (600 mg) were carefully
separated by column chromatography using petroleum ether/ethyl
acetate (v/v = 15:1) as the eluent. trans-ZnF20TPPDL (110 mg) can
be isolated from the first chromatography fraction, and cis-
ZnF20TPPDL (45 mg) can be accumulated by repeating the column
chromatography process another two times. The separation process
was monitored by UV−vis spectroscopy by monitoring differences in
1
the Qy(0,0) bands. The purity of the product was checked by H NMR
spectroscopy. trans-ZnF20TPPDL: 1H NMR (400 MHz, CDCl3) δ
8.70 (s, 4H). 13C NMR (126 MHz, CDCl3) δ 164.46, 159.99, 151.27,
150.41, 147.24, 145.24, 143.68, 141.68, 139.15, 137.14, 131.88, 131.34,
126.54, 111.92, 111.33, 104.18, 90.95. HRMS (ESI+) m/z [M + H]+:
calcd for C42H5F20N4O4Zn 1072.9283, found: 1072.9248; cis-
H
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
unreacted MTT was carefully removed, and 200 μL of DMSO was
added to each well to dissolve any blue formazan that had been
produced. After 1 h the optical density (OD) at a wavelength of 490
nm was measured with a Bio-Rad microplate reader. The cell viability
was determined by the following equation: Cell viability (%) = (mean
of OD value of treatment group/mean OD value of control) × 100%.
Confocal Imaging (PI Staining). HeLa cells were seeded in 35
mm confocal dishes (Glass Bottom Dish) at a density of 1 × 104 per
dish and incubated in complete medium for 24 h at 37 °C. The
medium was then replaced with fresh culture medium containing 60
μg mL−1 porphodilactone loaded PLGA NPs to incubate for 24 h at 37
°C. The cells were irradiated with a 671 nm laser at a power of 20 mW
cm−2 for 60 s and were then stained with 2 μM PI for 15 min so that
cell death can be visualized by confocal laser scanning microscope
(CLSM; TCS SP5, Leica, Germany). The PI solution was excited at
543 nm with an argon ion laser, and the emission was collected from
600 to 630 nm.
Theoretical Calculations. The density functional theory (DFT)
method was used to carry out geometry optimizations for
porphodilactones by using the B3LYP functional with 6-31G(d)
basis sets. The CAM-B3LYP functional was used with 6-31G(d) basis
sets to calculate the UV−vis absorption properties based on the time-
dependent (TD-DFT) method. The calculations were performed with
the Gaussian09 program package.
Fukuda, T. Chem.Eur. J. 2004, 10, 6294. (c) Sankar, J.; Mori, S.;
Saito, S.; Rath, H.; Suzuki, M.; Inokuma, Y.; Shinokubo, H.; Suk Kim,
K.; Yoon, Z. S.; Shin, J.-Y.; Lim, J. M.; Matsuzaki, Y.; Matsushita, O.;
Muranaka, A.; Kobayashi, N.; Kim, D.; Osuka, A. J. Am. Chem. Soc.
2008, 130, 13568. (d) Wu, D.; Descalzo, A. B.; Weik, F.; Emmerling,
F.; Shen, Z.; You, X. Z.; Rurack, K. Angew. Chem., Int. Ed. 2008, 47,
193. (e) Toganoh, M.; Furuta, H. Chem. Commun. 2012, 48, 937.
(f) Matsushita, O.; Derkacheva, V. M.; Muranaka, A.; Shimizu, S.;
Uchiyama, M.; Luk’yanets, E. A.; Kobayashi, N. J. Am. Chem. Soc.
2012, 134, 3411.
(3) Chen, M.; Schliep, M.; Willows, R. D.; Cai, Z.-L.; Neilan, B. A.;
Scheer, H. Science 2010, 329, 1318.
(4) (a) Crossley, M. J.; King, L. G. J. Chem. Soc., Chem. Commun.
1984, 920. (b) Gouterman, M.; Hall, R. J.; Khalil, G. E.; Martin, P. C.;
Shankland, E. G.; Cerny, R. L. J. Am. Chem. Soc. 1989, 111, 3702.
(c) McCarthy, J. R.; Jenkins, H. A.; Bruckner, C. Org. Lett. 2003, 5, 19.
̈
(d) Bruckner, C.; Ogikubo, J.; McCarthy, J. R.; Akhigbe, J.; Hyland, M.
̈
A.; Daddario, P.; Worlinsky, J. L.; Zeller, M.; Engle, J. T.; Ziegler, C. J.;
Ranaghan, M. J.; Sandberg, M. N.; Birge, R. R. J. Org. Chem. 2012, 77,
6480. (e) Lv, H. B.; Yang, B. Y.; Jing, J.; Yu, Y.; Zhang, J.; Zhang, J. L.
Dalton Trans. 2012, 41, 3116. (f) Yu, Y.; Lv, H. B.; Ke, X. S.; Yang, B.
Y.; Zhang, J. L. Adv. Syn. Catal. 2012, 354, 3509.
(5) (a) Zelelow, B.; Khalil, G. E.; Phelan, G.; Carlson, B.; Gouterman,
M.; Callis, J. B.; Dalton, L. R. Sens. Actuators, B. 2003, 96, 304.
(b) Khalil, G. E.; Costin, C.; Crafton, J.; Jones, G.; Grenoble, S.;
Gouterman, M.; Callis, J. B.; Dalton, L. R. Sens. Actuators, B. 2004, 97,
13. (c) Gouterman, M.; Callis, J.; Dalton, L.; Khalil, G.; Mebarki, Y.;
Cooper, K. R.; Grenier, M. Meas. Sci. Technol. 2004, 15, 1986.
(d) Waskitoaji, W.; Hyakutake, T.; Kato, J.; Watanabe, M.; Nishide, H.
Chem. Lett. 2009, 38, 1164. (e) Waskitoaji, W.; Hyakutake, T.;
Watanabe, M.; Nishide, H. React. Funct. Polym. 2010, 70, 669.
(f) Khalil, G. E.; Daddario, P.; Lau, K. S. F.; Imtiaz, S.; King, M.;
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Detailed isolation, photophysical and crystallographic data; H,
13C NMR and 19F NMR, UV−vis absorption, IR, and ESI-MS
spectra; the details of the TD-DFT calculations; and complete
ref 11. These materials are available free of charge via the
Internet at http://pubs.acs.org.
Gouterman, M.; Sidelev, A.; Puran, N.; Ghandehari, M.; Bruckner, C.
̈
Analyst 2010, 135, 2125. (g) Yu, Y.; Czepukojc, B.; Jacob, C.; Jiang, Y.;
AUTHOR INFORMATION
Zeller, M.; Bruckner, C.; Zhang, J.-L. Org. Biomol. Chem. 2013, 11,
■
̈
Corresponding Authors
zhangjunlong@pku.edu.cn
zshen@nju.edu.cn
4613. (h) Tang, J.; Chen, J.-J.; Jing, J.; Chen, J.-Z.; Lv, H.; Yu, Y.; Xu,
P.; Zhang, J.-L. Chem. Sci. 2014, 5, 558.
(6) Gouterman, M. The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. 3, Part A, pp 1−165.
(7) Ethirajan, M.; Chen, Y. H.; Joshi, P.; Pandey, R. K. Chem. Soc.
Rev. 2011, 40, 340.
Notes
The authors declare no competing financial interest.
(8) Cakmak, Y.; Kolemen, S.; Duman, S.; Dede, Y.; Dolen, Y.; Kilic,
B.; Kostereli, Z.; Yildirim, L. T.; Dogan, A. L.; Guc, D.; Akkaya, E. U.
Angew. Chem., Int. Ed. 2011, 50, 11937.
ACKNOWLEDGMENTS
■
Support from the National Key Basic Research Support
Foundation of China (NKBRSFC) (2010CB912302), NSFC
(grant no. 20971007, 21271013 to J.L.Z. and 21371090 to Z.S.)
and the National Fund for Fostering Talents of Basic Sciences
(J1030413) to J.Z.C. is gratefully acknowledged. Theoretical
calculations were carried out at the Centre for High
Performance Computing in Cape Town.
(9) (a) Li, K.; Pan, J.; Feng, S.-S.; Wu, A. W.; Pu, K.-Y.; Liu, Y.; Liu,
B. Adv. Funct. Mater. 2009, 19, 3535. (b) Zhang, Z. P.; Tongchusak, S.;
Mizukami, Y.; Kang, Y. J.; Ioji, T.; Touma, M.; Reinhold, B.; Keskin, D.
B.; Reinherz, E. L.; Sasada, T. Biomaterials 2011, 32, 3666.
(10) (a) Mack, J.; Stillman, M. J.; Kobayashi, N. Coord. Chem. Rev.
2007, 251, 429. (b) Kobayashi, N.; Muranaka, A.; Mack, J. Circular
Dichroism and Magnetic Circular Dichroism Spectroscopy for Organic
Chemists; Royal Society of Chemistry: London, 2011.
(11) Frisch, M. J., et al. Gaussian 09, revision A.02; Gaussian, Inc.,
Wallingford, CT, 2009. Complete reference is in Supporting
Information.
REFERENCES
■
(1) (a) Advances in Photosynthesis and Respiration; Grimm, B., Porra,
R., Rudiger, W., Scheer, H., Eds.; Springer: Dordrecht, 2006; Vol. 25:
̈
(12) Cai, Z.-L.; Crossley, M. J.; Reimers, J. R.; Kobayashi, R.; Amos,
R. D. J. Phys. Chem. B 2006, 110, 15624.
Chlorophylls and Bacteriochlorophylls. (b) Rudiger, W. In Advances in
̈
Photosynthesis and Respiration; Grimm, B., Porra, R., Rudiger, W.,
Scheer, H., Eds.; Springer: Dordrecht, 2006; Vol. 25: Chlorophylls and
Bacteriochlorophylls, pp 189−200. (c) Larkum, A. W. D. In Advances
in Photosynthesis and Respiration; Grimm, B., Porra, R., Rudiger, W.,
Scheer, H., Eds.; Springer: Dordrecht, 2006; Vol. 25: Chlorophylls and
Bacteriochlorophylls, pp 261−282. (d) Scheer, H. In Advances in
Photosynthesis and Respiration; Grimm, B., Porra, R., Rudiger, W.,
Scheer, H., Eds.; Springer: Dordrecht, 2006; Vol. 25: Chlorophylls and
Bacteriochlorophylls, pp 1−26. (e) Krautler, B. Angew. Chem., Int. Ed.
2011, 50, 2439.
̈
(13) (a) Moffitt, W. J. Chem. Phys. 1954, 22, 320. (b) Moffitt, W. J.
Chem. Phys. 1954, 22, 1820.
(14) (a) Michl, J. J. Am. Chem. Soc. 1978, 100, 6801. (b) Michl, J.
Pure Appl. Chem. 1980, 52, 1549. (c) Michl, J. Tetrahedron 1984, 40,
3845.
(15) (a) Mack, J.; Stillman, M. J. Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: New York, 2003; Vol.
16, Ch. 103, pp 43−116. (b) Mack, J.; Stillman, M. J. Coord. Chem.
Rev. 2001, 219, 993.
̈
̈
̈
(2) (a) Neves, M.; Martins, R. M.; Tome, A. C.; Silvestre, A. J. D.;
Silva, A. M. S.; Felix, V.; Drew, M. G. B.; Cavaleiro, J. A. S. Chem.
Commun. 1999, 385. (b) Kobayashi, N.; Nakajima, S.; Ogata, H.;
(16) Perrin, M. H. J. Chem. Phys. 1973, 59, 2090.
(17) (a) Keegan, J. D.; Stolzenberg, A. M.; Lu, Y. C.; Linder, R. E.;
Barth, G.; Moscowitz, A.; Bunnenberg, E.; Djerassi, C. J. Am. Chem.
I
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Soc. 1982, 104, 4317. (b) Keegan, J. D.; Stolzenberg, A. M.; Lu, Y. C.;
Linder, R. E.; Barth, G.; Moscowitz, A.; Bunnenberg, E.; Djerassi, C. J.
Am. Chem. Soc. 1982, 104, 4305. (c) Djerassi, C.; Lu, Y.; Waleh, A.;
Shu, A. Y. L.; Goldbeck, R. A.; Kehres, L. A.; Crandell, C. W.; Wee, A.
G. H.; Knierzinger, A.; Gaeteholmes, R.; Loew, G. H.; Clezy, P. S.;
Bunnenberg, E. J. Am. Chem. Soc. 1984, 106, 4241.
(18) Piepho, S. B.; Schatz, P. N. In Group Theory in Spectroscopy with
Applications to Magnetic Circular Dichroism; Wiley: New York, 1983.
(19) (a) Morone, M.; Beverina, L.; Abbotto, A.; Silvestri, F.; Collini,
E.; Ferrante, C.; Bozio, R.; Pagani, G. A. Org. Lett. 2006, 8, 2719.
(b) Rossi, L. M.; Silva, P. R.; Vono, L. L. R.; Fernandes, A. U.; Tada,
D. B.; Baptista, M. c. S. Langmuir 2008, 24, 12534.
(20) (a) Mirenda, M.; Strassert, C. A.; Dicelio, L. E.; Roman, E. S.
ACS Appl. Mater. Interfaces 2010, 2, 1556. (b) Thomas, A. P.; Saneesh
Babu, P. S.; Asha Nair, S.; Ramakrishnan, S.; Ramaiah, D.;
Chandrashekar, T. K.; Srinivasan, A.; Radhakrishna Pillai, M. J. Med.
Chem. 2012, 55, 5110.
J
dx.doi.org/10.1021/ja502729x | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX