Investigation of the demetallation of 10-aryl substituted synthetic chlorins under acidic conditions

Article abstract of DOI:10.1016/j.jinorgbio.2019.110979

The acidic demetallation of a series of sparsely substituted Zn(II) chlorins is reported. The chlorins were functionalized in the 10-position with substituents ranging from strongly electron donating mesityl and p-methoxyphenyl to electron-withdrawing p-n

Full text of DOI:10.1016/j.jinorgbio.2019.110979

JournalofInorganicBiochemistry205(2020)110979
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Journal of Inorganic Biochemistry
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Investigation of the demetallation of 10-aryl substituted synthetic chlorins
under acidic conditions
Anna I. Arkhypchuk, Ruisheng Xiong, K. Eszter Borbas⁎
Department of Chemistry, Ångström Laboratory, Box 523, Uppsala University, 75120 Uppsala, Sweden
A B S T R A C T
The acidic demetallation of a series of sparsely substituted Zn(II) chlorins is reported. The chlorins were functionalized in the 10-position with substituents ranging
from strongly electron donating mesityl and p-methoxyphenyl to electron-withdrawing p-nitrophenyl and pentafluorophenyl groups. The demetallation kinetics were
investigated using UV–Visible absorption spectroscopy. Demetallation was carried out by exposing the metallochlorins dissolved in CH2Cl2 to an excess of tri-
fluoroacetic acid. Reasonable correlation was found between the Hammett constant of the 10-substituent and the rate constant of the loss of the metal ion. The largest
differences were observed between the p-methoxyphenyl and p-nitrophenyl-substituted Zn(II) chlorins, undergoing loss of Zn(II) with pseudo first order rate con-
stants of 0.0789 × 10–3 and 3.70 × 10–3 min–1, respectively. Taken together, these data establish the dramatic influence even subtle changes can have in altering the
electronic properties of chlorins, which in turn impacts metallochlorin function.
1. Introduction
effects of peripheral substituent on chelate stability, and the quantifi-
cation of the effect individual substituents exert.
Chlorins are 18 π-electron cyclic tetrapyrroles with a porphyrin-like
carbon framework but with one less peripheral double bond compared
to porphyrins [1–3]. Discovered in 1817, chlorins remain a topic of
interest due to their natural abundance. Chlorophylls a, b, d and f are
chlorins, and as such are central to supporting life on Earth [3].
Chlorins are extensively used as photosensitizers [4–9] and as imaging
agents [10–13], and they are versatile components of light-harvesting
polymers in artificial photosynthesis [14–17]. The tetrapyrrolic mac-
rocycle provides a tetradentate square planar metal coordination site
that can bind a large variety of metal ions [18,19]. Chelation of a metal
ion can impart new functionality to the chlorin. Examples include the
catalytic activities of cobalt chlorins for proton reduction to H2 [20]
and for the reduction of O2 to H2O2 [21,22]. Chlorins in Nature are
found as their metal (Mg(II)) chelates, the stabilities of which are of
profound interest for a number of reasons [3]. Free base and metallo-
chlorins have very different properties, including differences in po-
larity, spectroscopic properties, redox potentials, macrocycle geometry
and reactivity [23–26]. The loss of the central metal ion is typically the
first step of the chlorophyll degradation [27]. Extensive studies on
naturally-occurring or naturally-derived metallochlorins have revealed
dramatic differences in the chelate stabilities. In general, electron-
withdrawing substituents tend to decrease the sensitivity of metallo-
chlorins to acidic conditions due to a decrease in the basicity of the
nitrogen donors [28–31]. However, the complexity of the macrocycle
structures precludes the drawing of general conclusions about the
For the reasons listed above, a systematic investigation of chlorin
demetallation that goes beyond naturally-occurring magnesium chlor-
ophylls is desirable. Scattered evidence suggests a wide range of re-
activities, providing a motivation for this study. For example, Battersby
removed Cu(II) from an 2,3,7,8,12,13-hexaalkylchlorin using tri-
fluoroacetic acid (TFA) saturated with H2S (18 h, r.t., 71% isolated
yield) [32], while we observed quantitative demetallation of a Cu(II)
10-aryl chlorin under mild conditions (dilute TFA in CH2Cl2, r.t.) within
minutes [33]. Comparison of Zn(II) porphyrins and chlorins with
identical substitution patterns have shown that the metalloporphyrins
are more stable under acidic conditions than the chlorins [34]. The
effect of macrocycle saturation was relatively modest, with the por-
phyrin ligand conferring 1.3 to 1.7-fold increased stability to the che-
late compared to the chlorin. However, the effect of the substituents
was more dramatic. The introduction of electron-withdrawing 3-, 7- or
13-substituents increases the stabilities of both Mg(II) [35,36] and Zn
(II) chlorins [30,31]. The effect of such a substitution can be quite
dramatic, e.g. a 3-acetyl in the place of a 3-vinyl group slows down
acidic demetallation by up to 20-fold [28].
Here, we investigate the kinetics of the chlorin demetallation in a
library of stable, sparsely substituted chlorins. The library consists of Zn
(II) chlorins carrying only 10-aryl substituents in addition to 18,18-
gem-dimethyl substituents. The purpose of the latter is to lock-in the
hydroporphyrin oxidation level, while the aryl substituents modulate
the electronic properties of the macrocycle. The acidic demetallation
⁎ Corresponding author.
E-mail address: eszter.borbas@kemi.uu.se (K.E. Borbas).
https://doi.org/10.1016/j.jinorgbio.2019.110979
Received 30 September 2019; Received in revised form 11 December 2019; Accepted 24 December 2019
Availableonline03January2020
0162-0134/©2020ElsevierInc.Allrightsreserved.

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
kinetics were followed by UV–Vis absorption spectroscopy. The rates of
the demetallations were then analyzed in the context of macrocycle
electronic structure using a combination of 1H and 13C NMR spectro-
scopy and cyclic voltammetry. Taken together, these results represent
the first systematic investigation of single substituent effects on me-
tallochlorin stability, and provide an entry point for predicting chelate
robustness in future applications.
temperature in CH2Cl2 solution. Selected free base chlorins were then
metallated to obtain the Pd(II) and Cu(II) analogues [33,42]. Zn-1a, c
[39,43], Zn-1d [14], Zn-1f [44], Zn-1g [45], Zn-1h [14], Zn-1j [46],
Zn-1k [46], Zn-1l [33] are known compounds, as are Pd-1a,l [33] and
Cu-1a,l [33,39]. Details of the syntheses and standard characterization
data are provided in the Experimental section. The characterization
data for the known species were in accordance with reported values and
with the proposed structures. Selected NMR-spectroscopic, electro-
chemical and photophysical characterizations are presented below.
2. Results and discussion
To investigate the demetallation kinetics and the influence of per-
ipheral substituents, we designed a small library of 10-substituted
chlorins (Scheme 1). The 10-aryls include substituents with electron-
neutral (H, 1a), electron-withdrawing (I, F, NO2, Br, F5; M-1b,e,f,i,k),
3. UV–Vis absorption spectroscopy
In total, 12 free base chlorins were synthesized. These were used as
reference compounds for the demetallation products. Additionally, 12
Zn(II) chelates were prepared, along with 5 each of Cu(II) and Pd(II)
complexes. With these 34 compounds in hand, we performed a detailed
study of their absorption properties, the results of which are presented
in Table 1. Typical spectra are shown in Fig. 1. The UV–Vis absorption
spectra of the free base and the metallochlorins were recorded in
CH2Cl2. All chlorins had absorptions typical of this class of compounds
consisting of two sets of relatively sharp, high intensity bands. The
Soret (B) band was located at ~400 nm and the Q bands at ~500 nm
(Qx) and ~600 nm (Qy). The position of the latter is very sensitive to the
t
electron-donating (2,4,6-tri-Me, 2,6-di-OMe, 4-OMe, 4-OCH2CO2 Bu,
M-1c,g,j,l), sterically demanding (2,4,6-tri-Me, 2,6-di-OMe, M-1c,g)
properties, as well as heterocyclic groups (thienyl and furanyl, M-1d,h).
The chlorins were prepared following a standard two-step proce-
dure developed by Lindsey (Scheme 1) [37–39]. Condensation of 1-
bromo-9-formyldipyrromethanes (Eastern half) [40] with
a tetra-
hydrodipyrrin (Western half) [41] yielded Zn(II) chlorins in isolated
yields ranging from 4% to 41%. The corresponding free base chlorins
were obtained by treating the Zn(II) chlorins with TFA at room
Scheme 1. The synthetic chlorins studied here, and a general scheme for their preparation.
2

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Table 1
Summary of UV–Vis data. Spectra were recorded in CH2Cl2, [Chlorin] = ⁓8 × 10–6 M.
Free base
Zn
Pd
Cu
λB (nm)
λQ (nm)
IB/IQ
λB (nm)
λQ (nm)
IB/IQ
λB (nm)
393
λQ (nm)
587
IB/IQ
2.66
2.63
λB (nm)
399
λQ (nm)
599
IB/IQ
5.77
6.10
a
c
e
i
403
404
403
404
404
404
405
404
404
406
406
405
634
635
634
634
634
636
634
635
635
638
640
634
4.21
3.74
3.96
4.47
4.46
3.69
4.38
3.96
3.67
4.08
4.32
4.41
402
402
402
403
403
402
403
403
404
405
407
403
604
604
604
604
604
607
604
607
608
609
610
604
5.72
5.81
5.85
5.85
5.76
4.51
5.84
5.60
4.73
5.33
4.82
5.60
394
587
399
599
b
f
j
395
395
586
588
2.68
2.55
400
400
599
601
5.79
5.76
g
k
d
h
l
394
587
2.73
400
600
5.94
macrocycle substitution, albeit the variation induced by alterations of a
single meso-substituent is modest. Most of the free base compounds
displayed Qy bands at λmax = 634–636 nm. The only exceptions were
the slightly red-shifted absorptions (638 and 640 nm, respectively) of
the thienyl- (1d) and furylchlorins (1h). This may be caused by the
small five-membered heterocycle being more co-planar with the mac-
rocycle than the phenyl-based substituents [47].
Table 2
Cyclic voltammetry data for free base chlorins.
Chlorin
Reduction, Epc [V]
Oxidation, Epa [V]
1a
1c
1e
1i
−2.13
−2.16
−2.12
−2.11
−2.15
−2.23
−2.19
−2.20
−2.04
−2.11a
−2.14a
−2.14
−1.71
−1.75
−1.71
−1.70
−1.69
−1.82
−1.72
−1.78
−1.60
−1.67a
−1.67a
−1.74
0.43
0.39
0.46
0.47
0.44
0.49
0.40
0.38
0.53
0.43a
0.43a
0.42
0.99
0.95
0.98
0.98
0.98
0.97
0.93
0.91
0.99
0.94a
0.83a
0.98
Metalation hypsochromically shifts the Qy-band by ~30 nm for
M = Zn(II), 35–40 nm for M = Cu(II) and 45–50 nm for Pd(II), com-
pared to the analogous free base chlorins. The Soret band is much less
sensitive towards the metalation; only for Cu(II) (5 nm) and Pd(II)
(10 nm) chelates was a slight hypsochromic shift observed. The ratio of
the intensities of the B and Q bands (IB/IQ) is also changed upon
macrocycle metalation. Introduction of Zn(II) and Cu(II) results in an
increased IB/IQ ratio from 4:1 in free base compounds to 6:1 in the
metallochlorins. Palladation has the opposite effect, decreasing the
ratio to 2.5:1. These changes are accompanied by dramatic changes in
color observable with the naked eye: free base chlorins are deep green,
Zn(II) chelates are bright blue-violet, Pd(II) chelates are pink and Cu(II)
species are navy blue in solution (at ~10−5 M).
1b
1f
−1.69
−1.53
1j
1g
1k
1d
1h
1l
1.21
1.05a
Measured for 1 mM solutions of the analyte in CH2Cl2 (0.1 M NBu4PF6), glassy
C-electrode, n = 100 mV s–1. All potentials are given versus Fc+/0
.
a
From reference [14].
All free base chlorins with electrochemically inert substituents (1a-
e, g, i, j and l) show two oxidation and two reduction peaks, of which
only the first reduction peak is reversible (Table 2). The macrocycle-
based redox processes were assigned based on the similarities between
the compounds. For example, phenyl-substituted 1a had two oxidation
and two reduction peaks, at 0.43 and 0.99 eV, and –1.71 and –2.13 eV,
respectively. These values are almost identical to those obtained for the
regioisomeric 15-phenyl chlorin [48]. The first oxidation potentials are
somewhat substituent-dependent, and are in the 0.39–0.51 eV range.
The separation between the first and the second oxidations are essen-
tially constant in this series of chlorins, with a value of ~0.52 eV. The
majority of the other chlorins studied here had similar peaks in the
4. Cyclic voltammetry
To evaluate the influence of the central metal on the electronic
structure of the macrocycle we decided to perform cyclic voltammetry
on the Zn(II), Cu(II) and Pd(II) chlorins and compare them to their free
base analogues. Results are summarized in Tables 2–4. Typical vol-
tammograms are shown in Fig. 2, and all voltammograms are provided
in the Supporting information. Voltammograms of the free base 10-
furanyl and 10-thienyl-chlorins have been reported before [14].
Fig. 1. Typical UV–Vis spectra of free base, Zn, Pd and Cu chlorins (M-1e (left) and M-1j (right)).
3

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Table 3
explanation for this result, however, it may reflect an increased mac-
rocycle rigidity caused by metal ion coordination. This, in combination
with the fact that the bulky 2,6-dimethoxyphenyl substituent is forced
to be perpendicular to the macrocycle results in a diminished sub-
stituent-macrocycle communication compared to what is possible in the
free base species. Further studies are required to understand the redox
behavior of M-1g.
Cyclic voltammetry data for Zn chlorins.
Chlorin
Reduction, Epc [V]
Oxidation, Epa [V]
Zn-1a
Zn-1c
Zn-1e
Zn-1i
Zn-1b
Zn-1f
Zn-1j
Zn-1g
Zn-1k
Zn-1d
Zn-1h
Zn-1l
−2.27
−2.32
−2.26
−2.25
−2.28
−2.28
−1.87
−1.89
−1.85
−1.84
−1.84
−1.98
0.148
0.132
0.173
0.173
0.183
0.220
0.605
0.581
0.606
0.616
0.616
0.66
−1.55
5. NMR spectroscopy
a
a
a
a
a
a
–
–
–
–
–
–
−2.33
−2.15
−2.24
−2.26
−2.27
−1.87
−1.75
−1.81
−1.86
−1.90
−1.53
−1.08
0.138
0.243
0.183
0.223
0.148
0.56
The electron density of the macrocycle is a known factor in de-
termining metallochlorin stabilities. We investigated whether a mean-
ingful correlation could be detected between chelate stability and the
shielding of the macrocycle protons as observed in the 1H NMR spec-
trum. If confirmed, this would provide a simple tool for the preliminary
assessment of metallochlorin robustness. Therefore, the 1H and 13C
NMR spectra of all the diamagnetic chlorins were fully assigned using a
combination of literature data, and 1H-1H correlation spectroscopy
(COSY), attached proton test (APT) and heteronuclear single-quantum
correlation spectroscopy (HSQC) experiments. Results are summarized
in Figs. 3 and 4. Full spectra are provided in the Supporting Informa-
tion. The aromatic regions of representative 1H NMR spectra for the
diamagnetic free base 1j and Zn(II)- and Pd(II)-1j chlorins are shown in
Fig. 3. These values are similar to those reported by Lindsey and co-
workers [45,50,51] and Ptaszek et al. [7,11]. The Cu(II) chelates were
paramagnetic, as expected [33,52].
0.787
0.621
0.675
0.60
Measured for 1 mM solutions of the analyte in CH2Cl2 (0.1 M NBu4PF6), glassy
C-electrode, n = 100 mV s−1. All potentials are given vs Fc+/0
.
a
Could not be determined due to instrument problems.
same region. There were a handful of exceptions to this pattern. Ni-
trophenyl-substituted 1f showed additional reductions. These could
tentatively be assigned to the stepwise reduction of the NO2 group.
Arylnitro compounds are known to undergo multielectron reductions
via the nitroso species to the amine [49].
The voltammograms of the Zn(II) complexes were similar in shape
to those of the free base substances, however all peaks except for the
one corresponding to the second reduction became reversible. Both
oxidations are happening at lower potentials, as expected for formally
dianionic ligands (0.13–0.24 eV for first oxidation and 0.58–0.79 eV for
the second). The oxidation potentials are correlated with the electronic
properties of the substituent. Reductions are taking place at slightly
(~0.1 eV) lower potentials than in the free base compounds, in line
with the increased electron density of the macrocycle (Table 3). The
reduction of nitrophenylchlorin Zn-1f was complicated, similarly to
that of its free base analogue 1f. 2,6-Dimethoxyphenyl-substituted Zn-
1g showed two additional fully reversible reductions at −1.53 and
–1.08 eV, the source of which is unclear at this point.
Macrocycle resonances are in the range 8.5–10 ppm for deshielded
β-pyrrolic C-H and meso C-H protons, and –1.8 ppm to −2.5 ppm for
the shielded N-H protons. No obvious correlation between the nature of
the 10-substituent and size of the chemical shift changes for the nearest
8-H and 12-H were found. This may be because the shift is due to a
combination of electronic effects and a shielding by the 10-position
aromatic ring in semi-perpendicular orientation. The N-pyrrolic protons
in the free base chlorins were on the other hand very sensitive to 10-
substitution. Their chemical shifts correlate strongly with electronic
properties of the substituent expressed by the Hammett constant (Fig.
S1).
Pd(II) chlorins show two oxidation peaks appearing at almost the
same potentials as the free base compounds, the first of these is re-
versible. Two reductions take place at −1.8 eV and –2.35 eV. The first
one is located at a potential ~0.20 eV lower than the potential of the
corresponding free base chlorin, and second is shifted by ~0.3 eV.
The oxidations of the Cu(II)-chlorins contained an additional, pre-
sumably metal-based oxidation peak. Of the three oxidation peaks only
the first one was reversible. The first oxidation takes place at ~0.22 eV,
which is located at ~0.20 eV lower potential than for the corresponding
free base chlorins. Reduction potentials were almost identical to those
of the analogous Pd(II) complexes, with electron transfers occurring
between −1.86 and –2.40 eV for all 5 compounds tested. The effects of
the 10-substituents on the macrocycle-based oxidation and reduction
potentials follow the trends expected based on their electronic prop-
erties (vide infra). Interestingly, 2,6-dimethoxyphenyl-substituted Cu-
1g and Pd-1g displayed reduction waves that were similar to those of
Pd and Cu chelates carrying other substituents. We do not have an
Metalation influences the 1H NMR signature [53]. Metal ion co-
ordination shifts all macrocyclic signals upfield, with Δδ the largest for
the meso protons (~0.4 ppm) and ~0.2 ppm for the β-pyrrolic protons.
The size of the shift is metal ion dependent. On average, the largest
upfield shifts were observed for Zn(II) complexes and moderate ones for
Pd(II) (Table S3). This is in line with both the cyclic voltammetry data
and the larger electronegativity of Pd. Substituent effects on the shifts
of 1H and 13C resonances of the meso-protons in the Pd chlorins was
very small, < 0.4 ppm (Table S3).
6. Demetallation kinetics
With the full characterization in hand, the demetallation kinetics
under acidic conditions was studied. Reactions were followed by
UV–Vis absorption spectroscopy. Representative spectral changes in the
red region of the spectrum for metallochlorins in CH2Cl2
Table 4
Cyclic voltammetry data for copper and palladium chlorins.
Cu chlorins
Pd chlorins
10-substituent
Reduction, Epc [V]
Oxidation, Epa [V]
Reduction, Epc [V]
Oxidation, Epa [V]
Ph
−1.86
0.22
0.24
0.22
0.18
0.23
0.81
0.83
0.83
0.77
0.82
1.14
1.17
1.11
1.06
1.08
−2.34
−2.32
−2.36
−1.80
0.39
0.40
0.38
0.34
0.32
1.03
1.04
1.03
1.04
0.93
p-F-C6H4
−2.38
−2.39
−2.43
−2.38
−1.84
−1.86
−1.89
−1.85
−1.77
−1.79
−1.86
−1.82
p-OCH3-C6H4
2,6-(OMe)2-C6H3
p-OCH2C(O)OtBu-C6H4
−2.35
1.19
Measured for 1 mM solutions of the analyte in CH2Cl2 (0.1 M NBu4PF6), glassy C-electrode, n = 100 mV s−1. All potentials are given versus Fc+/0
.
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A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Fig. 2. Representative cyclic voltammograms for M-1e chlorins. All cyclic voltammograms are provided in the Supporting Information.
Fig. 3. Representative aromatic region of the 1H NMR spectrum of M-1j chlorin in CDCl3.
([Chlorin] ~ 8 × 10−6 M) upon TFA addition ([TFA] ~ 3 × 10−2 M)
chlorins facilitated the investigation of their demetallation kinetics.
Investigations began with the Zn(II) chelates, as these are known to
undergo quantitative demetallation upon TFA-treatment on time scales
ranging from minutes to hours. In the presence of a large excess of acid
(pseudo first order conditions) the Soret band of the Zn(II) chlorin
gradually disappeared, and a new, bathochromically shifted band
are shown in Fig. 5. Similar spectra for the other metallochlorins are
given in the Supporting Information (Figs. S70–78). It is important to
note that the Zn(II) chelates were stable in solution in the absence of
acid, and they could even be purified by column chromatography on
mildly acidic silica gel. This increased stability compared to Mg(II)
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A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Fig. 4. Summary of 1H NMR resonances of the free based and metallochlorins in CDCl3.
emerged. Similar trends are seen for the Qy band at 604 nm, however,
the change here is less pronounced as the bands overlap. Complexes Zn-
1a-e and Zn-1g-j lost the Zn(II) within minutes. For compound Zn-1k,
several hours were required for the same result, while the demetallation
of Zn-1f was incomplete even after 12 h.
This lends support to the process delineated in Scheme 2, ending in the
monoprotonated free base chlorin. The free base chlorin and the
monoprotonated free base chlorin are both downstream of the rate
determining step (k1). The absorption spectrum of the free base chlorin
could be observed in the reaction mixture, however with a very low
intensity. The rate constant of the free base chlorin protonation (k2)
could not be determined under these conditions.
The reaction intermediates and products were identified by com-
parisons of the absorption maxima with those of well-characterized
reference compounds. We have recently isolated and fully characterized
three mono- and diprotonated free base chlorins (10-substituents: Ph,
pentafluorophenyl, p-C6H4-OMe) [46]. With the help of these data we
could identify the starting Zn(II) chlorin (λ = 604 nm for Ph), the
charge-neutral free base chlorin (λ = 633 nm), the monoprotonated
free base chlorin intermediates (λ = 613 nm). The overlaid UV–Vis
traces of the reaction mixture during the demetallation and in-
dependently obtained reference compounds are presented in Fig. 5.
The mechanism of acidic demetallation of porphyrins and chlorins
has been studied before [54–57]. Based on previous reports, as well as
the species we could identify in the reaction mixtures, we have adopted
the two-step sequence shown in Scheme 2 as the putative mechanism.
The first step is demetallation of the starting metallochlorin (reaction
rate k1) to form free base chlorin. Most probably this step includes
multiple steps, such as the coordination of the proton to the metallo-
chlorin and expulsion of the metal (here: Zn2+) cation upon the arrival
of the second proton. Based on the UV–Vis data reported herein we
could not identify any of those intermediates and so assume them to be
very short lived and not to be present in the reaction mixture in high
enough concentration to be detected. Fukuzumi et al. have character-
ized several protonated Co(II) chlorins; however, protonation in these
pyropheophorbide-derived chelates took place on the E-ring carbonyl
oxygen [21,22]. It is worth noting that even at this remote site, basicity
was greatly influenced by the electronic properties of the 3-susbtituents
in the A-ring [21]. Subsequent protonation of free base chlorin leads to
the formation of the singly N-protonated chlorin (reaction rate k2). We
have recently isolated and fully characterized such a species, and have
shown that it is surprisingly stable under a range of conditions [46].
Therefore, it is reasonable to postulate the formation of a mono-
protonated intermediate under these acidic solutions. The second step
of the sequence presented in Scheme 2 was studied in detail. The values
of k2 correlated with the para-Hammett constants of the substituent in
10-position of the chlorin [46].
The calculated rate constants for the formation of the free base
chlorins (k1) are summarized in Table 5. Initial protonation of the
starting Zn(II) complexes is very fast, and is instantaneous under con-
ditions that feature a large excess of the acid. The reaction rate for the
first step is in the 1.0 × 10−3 to 1.29 × 10−3 min−1 range, with the
exception of the least basic p-nitrophenyl and pentafluorophenyl-sub-
stituted complexes (k1 = 7.89 × 10−5 and 1.92 × 10−4 min−1 re-
spectively). This translates to a demetallation 47 times faster for Zn(II)
chlorin with a p-methoxyphenyl substituent than with a p-nitrophenyl.
In practice, the reaction mixture containing p-OMe contains < 1% of
the starting Zn(II) complex after 10 min, while for the p-nitrophenyl
compound after the same time 88% of the starting material remains
(Table 6).
The pKa values of the first protonation of the free base chlorin were
estimated for the chlorins shown in Table 5. These values are similar to
the ones determined previously for the 1a, 1j and 1k chlorins. The
macrocycle basicities vary with the electron-donating or withdrawing
ability of the 10-substituent. The range of pKa values is relatively
modest, the most basic macrocycle (1j) has pKa = 5.39, while the least
basic (1k) pKa = 4.79. Previously, we have noted good correlation
between the Hammett constant of the 10-substituent and the pKa of the
first protonation of the free base chlorin [46], here, we relied on this
observation to estimate the pKa values in order to be able to extract the
rate constants. The fastest demetallation was seen for the most basic
macrocycle, while the slowest kinetics was noted in those carrying
strongly electron-withdrawing groups (1f, 1k). However, basicity cor-
relates only loosely with the demetallation rate, and it appears that
there are additional factors also in play, such as the different macro-
cycle distortions during protonation and metallation. The flexibility of
the chlorin ligand conferred stability on the Co chelate of a pheo-
phorbide under acidic conditions, while under the same conditions the
Co complex of octaethylporphyrin was quantitatively demetalated [22].
Therefore, structural and electronic considerations are likely both im-
portant.
Since key intermediates (Zn chelate, free base and monoprotonated
free base chlorin) have characteristic absorptions, quantitative analysis
of the demetallation could be performed by following the absorbance
changes. The concentrations of the intermediates were calculated from
the absorption spectrum of the reaction mixture and the individual
absorption spectra using a least square root method. After the com-
pletion of the reaction the UV–Vis absorption of the mixture resembled
the spectrum of the monoprotonated free base chlorin (Fig. 5, middle).
To see if the electronic properties of the macrocycle substituent
correlate with the reaction rate, k1 was plotted vs Hammett constants
for the entire substituent on the macrocycle (Fig. 6). While slower ki-
netics was observed for the less electron-rich ligands, no linear de-
pendence was obtained. This further suggests that the reaction is more
complex and the demetallation is influenced by more than just electron-
withdrawing/donating properties of the substituent present in the 10-
6

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Table 5
Calculated reaction rates for demetallation of Zn chlorins.
σ, 4-Ph-R
k1 × 103, min−1
pK1
1
Zn-1a
Zn-1c
Zn-1e
Zn-1i
Zn-1b
Zn-1f
Zn-1j
Zn-1g
Zn-1k
Zn-1d
Zn-1h
−0.01
1
5.27
a
a
a
2
–
–
–
3
0.06
0.12
0.1
1.06
1.08
1.29
0.0789
3.7
5.15
5.05
5.08
4.81
5.39
4
5
6
0.26
−0.08
8
a
a
a
9
-
-
-
10
11
12
0.27
0.05
0.02
0.192
1.15
1.13
4.79
5.17
5.22
a
Not determined because Hammett constants were not available for sub-
stituent.
Table 6
Proportion of Zn(II) complexes carrying different 10-substituents in the reaction
mixtures at the different time points.
Zn-1j
Zn-1a
Zn-1f
10 min
30 min
5 h
< 1%
27%
< 1%
–
88%
–
–
73%
< 4%
Fig. 6. Correlation of the Hammett constants vs. calculated demetallation rate
k1.
are, with one possible exception, unhelpful in predicting Zn(II) chlorin
stability. The exceptions are the N-H resonances, which showed good
correlation for the set of free base chlorins analyzed with the meso-
substituent's Hammett constants, and with sufficiently large differences.
As the demetallation rates loosely correlated with the substituent
Hammett constants, the inner N-H resonance could be a good initial
guide to stability. Calculations by Holten, Bocian and Lindsey on Zn
chlorins carrying 0–4 meso-substituents showed that the highest occu-
pied molecular orbital-1 (HOMO-1) orbital has large coefficients on the
meso-positions, the nitrogens and the central Zn, suggesting the pre-
sence of high electron density on these positions. Helaja et al. have
calculated electron density maps for a series of chlorin tautomers. They
found that in the most stable trans-N21-H,N23 tautomer electron den-
sity is highest in the meso-positions and on the nitrogen atoms [58]. In
the absence of blocking substituents chlorins react with electrophiles in
the meso-positions [59–61]. These data are all consistent with the ob-
servation that the meso-substituent strongly impacts the electronic
Fig. 5. Top: example of the experimental absorption changes during the de-
metallation reaction for Zn-1a to 1a. Initial UV–Vis trace shown in black, the
final spectrum after the reaction in dark grey. Middle: initial and final spectra of
the reaction mixture overlaid with the UV–Vis traces of reference compounds.
Bottom: Change of UV–Vis spectra during course of the demetallation reaction
of Zn-1a (30 min). All data were normalized to simplify the figure.
Scheme 2. Demetallation mechanism used in the analysis of the data.
position of the macrocycle.
Finally, with the rate constants in hand, we note that the 1H and 13
C
NMR chemical shifts and the macrocycle oxidation and redox potentials
7

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
Fig. 7. HOMO-1 and HOMO of Zn-1j.
properties of the macrocycle. The HOMO on the other hand had no
contributions from the meso-carbons [62]. This is analogous to what
has been seen in free base chlorins. The 10-p-methoxyphenyl-sub-
stituent also has a small contribution to the HOMO-1, seen both in the
free base and the Zn chelate (Fig. 7) [46].
proved suitable for accurate calculation of large π-conjugated systems.
Structures were determined to be true minima by performing a vibra-
tional analysis. Geometries and electron densities were analyzed and
visualized using Molden [64].
General procedure for preparation of Zn-chlorins: Chlorins were
prepared following the general procedure developed by Lindsey
[37,39]. Compounds Zn-1a, c [39,43], Zn-1d [14], Zn-1f [44], Zn-1g
[45], Zn-1h [14], Zn-1j [46], Zn-1k [46], Zn-1l [33], Pd-1a,l [33] and
Cu-1a,l [33,39] were synthesized following literature procedures. Their
characterization data were in accordance with reported values. Synth-
esis of macrocycles consists of two steps – bromination of the corre-
sponding formyldipyrromethane and macrocyclisation itself. Due to
low solubility of the 1-bromo-9-formyldipyrromethane, bromination
was usually performed directly before cyclisation, and the product was
used in the subsequent steps without further purification.
The analysis of the Pd(II) and Cu(II) chlorin demetallation kinetics
will be the subject of subsequent investigations. However, the current
work was prompted by the high acid sensitivity of Cu-1l, and we note
that the Zn analogue of the electronically similar 1j displayed very fast
demetallation kinetics. Therefore, we expect that for Cu(II) and Pd(II)
the findings on Zn(II) chlorins will be mirrored.
7. Conclusion
A library of synthetic metallochlorins varying only in their 10-
substituent was demetallated under acidic conditions. The rate of the
loss of the metal was analyzed using UV–Vis absorption spectroscopy.
By comparison of the absorption spectra of the reaction mixtures with
authentic samples of free base and metallochlorins, as well as those of
monoprotonated chlorins obtained under controlled conditions we
were able to extract pseudo first-order rate constants. The rate of de-
metallation was faster for more basic chlorins, which is expected. This
observation is also in line with previous literature reports.
Step 1. Bromination.
A sample of 1-formyldipyrromethane (1
equiv.) dissolved in dry THF was cooled to −78 °C. The solution was
treated dropwise with a THF-solution containing 1 equiv. of NBS. The
reaction mixture was stirred for 30 min, during which time it was al-
lowed to slowly warm up to approximately −50 °C. The reaction was
quenched by the addition of 30 mL brine, and the mixture was allowed
to warm up to room temperature. After this two phases are separated
and aqueous layer extracted with 2 × 50 mL of diethyl ether. Combined
organic layers are washed with 50 mL of brine and dried over MgSO4.
Removing of the solvent under reduced pressure (Caution! temperature
of the water bath should not be > 25 °C) gives crude product which is
directly used in the next step without additional purification.
Somewhat more surprisingly, we measured rate constants that
varied by orders of magnitude in chlorins that differed only in a single
substituent in the p-position of a 10-phenyl group. Currently, it is not
known whether groups in all other peripheral positions provide similar
levels of control over the properties of the macrocycle. Previously, Saga
and co-workers have noted a 20-fold acceleration upon replacement of
the 3-vinyl group with an acetyl. These groups were directly attached to
the macrocycle, so the effect seems smaller than in the systems in-
vestigated herein. However, the difference in reaction conditions (sol-
vents) precludes the direct comparison of the data [28]. Out results
suggest that the stabilities of the increasingly utilized metallochlorins
could be readily tuned by the judicious choice of quite remote func-
tionalities.
Step 2. Macrocyclisation. Manipulations should be performed with
the exclusion of light. To the solution of bromoformyldipyrromethane
(1 equiv.) and Western half (1 equiv.) in dry CH2Cl2 solution of 5 equiv.
of p-toluenesulfonic acid monohydrate in MeOH was added. The reac-
tion mixture was stirred for 30 min, and the reaction was then quen-
ched by the addition of 10 equiv. of TMPP. Solvents were removed
under reduced pressure. The temperature of the water bath should not
exceed 25 °C. The solid residue was dissolved in dry acetonitrile. TMPP
(25 equiv.), Zn(OAc)2 (15 equiv.) and AgOTf (3 equiv.) were added,
and the reaction mixture was heated at reflux for 16–24 h in the dark
and open to the air. During this time a dark gray to black suspension
formed. Filtration through a silica pad and thorough washing with
CH2Cl2, followed by the evaporation of the solvents from the filtrate
gave dark green to black crude products. Column chromatography on
silica gel using 50% CH2Cl2 in hexane gave spectroscopically clean
products as dark green solids after solvent evaporation.
8. Experimental
8.1. General
All reactions were performed under and Ar atmosphere using
Schlenk techniques unless stated otherwise. Diethyl ether and THF were
freshly distilled from Na/benzophenone prior to use. CH2Cl2 was dis-
tilled from CaH2. 1H and 13C spectra were recorded on a 400 MHz
spectrometer. Chemical shifts (ppm) are reported and referenced to the
internal signal of residual solvent protons. High resolution mass spec-
tral analyses (HRMS) were performed at the Organisch Chemisches
Institut of the University of Münster on a high resolution FTMS+pNSI
mass spectrometer (OrbitrapXL).
8.2. Zn-1b
Bromination was performed starting from 80 mg (0.21 mmol) of the
required dipyrromethane and 38 mg (0.21 mmol) of NBS. During
macrocyclization 39 mg (0.21 mmol) of Western half, 200 mg
(1.05 mmol) of p-toluenesulfonic acid monohydrate, 296 mg
(2.10 mmol) and 740 mg (5.25 mmol) of TMPP, 576 mg (3.15 mmol) of
Zn(OAc)2 and 162 mg (0.63 mmol) of AgOTf were used. Rf (50%
CH2Cl2 in hexane) = 0.48. Yield: 19%, 24 mg.
Calculations. All calculations were performed with the Gaussian suit
of programs (G09 Rev. C.01) [63]. All structures were fully optimized
using the MO6-2X functional with a 6-311++G** basis set which
8

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
1H NMR (400 MHz, CDCl3): δ = 9.58 (s, 1H), 9.06 (d, J = 4 Hz,
1H), 8.84 (d, J = 4 Hz, 1H), 8.77 (d, J = 4 Hz, 1H), 8.69 (s, 1H), 8.65
(d, J = 5 Hz, 1H), 8.63 (d, J = 5 Hz, 1H), 8.62 (s, 1H), 8.47 (d,
J = 4 Hz, 1H), 8.47 (d, J = 4 Hz, 1H), 8.04 (d, J = 8 Hz, 2H), 7.81 (d,
J = 8 Hz, 2H), 4.52 (s, 2H), 2.04 (s, 6H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 171.2, 159.4, 154.1, 153.2, 146.8, 146.5, 146.1, 145.5,
142.0, 135.8, 135.4, 133.1, 132.8, 128.8, 128.2, 127.5, 127.0, 122.0,
109.5, 97.1, 94.4, 93.6, 50.3, 45.4, 31.0 ppm. HRMS: calc. C28H21IN4Zn
[M]+ 604.0097, obsd. 604.0075.
123.3, 119.8, 107.3, 97.0, 94.4, 93.9, 52.0, 46.5, 31.2 ppm. HRMS:
calc. C28H24IN4 [M + H]+ 543.1040, obsd. 543.1034.
8.6. 1e
Reaction was performed using 15.7 mg (0.032 mmol) of Zn chlorin.
Rf (50% CH2Cl2 in hexane) = 0.45. Yield: 94%, 13.1 mg.
1H NMR (400 MHz, CDCl3): δ = 9.88 (s, 1H), 9.26 (d, J = 5 Hz,
1H), 9.06 (s, 1H), 8.99 (d, J = 4 Hz, 1H), 8.97 (d, J = 5 Hz, 1H), 8.93
(s, 1H), 8.85 (d, J = 5 Hz, 1H), 8.79 (d, J = 5 Hz, 1H), 8.62 (d,
J = 4 Hz, 1H), 8.12 (dd, J = 9, JHF = 6 Hz, 2H), 7.44 (dd, J = 9,
JHF = 9 Hz, 2H), 4.66 (s, 2H), 2.08 (s, 6H), −1.97 (s, 1H), −2.35 (s,
1H). 13C NMR (101 MHz, CDCl3): δ = 175.4 (s), 164.0 (s), 162.9 (s),
152. 5 (s), 150.9 (s), 141.0 (s), 139.5 (s), 137.7 (d, J = 3 Hz), 135.3 (d,
J = 8 Hz), 135.2 (d, J = 1 Hz), 134.2 (s), 132.4 (s), 131.8 (s), 128.4 (s),
128.0 (s), 123.6 (s), 123.3 (s), 120.1 (s), 113.8 (d, J = 21.4 Hz), 107.2
(s), 96.9 (s), 94.3 (s), 52.0 (s), 46.5 (s), 31.2 (s) ppm. HRMS: calc.
8.3. Zn-1e
Bromination was performed using 343 mg (1.30 mmol) of the re-
quired dipyrromethane and 228 mg (1.30 mmol) of NBS. During mac-
rocyclisation 244 mg (1.30 mmol) of Western half, 1.24 g (6.50 mmol)
of p-toluenesulfonic acid monohydrate, 1.83 g (13.0 mmol) and 4.58 g
(32.5 mmol) of TMPP, 3.57 g (19.5 mmol) of Zn(OAc)2 and 1.002 g
(3.9 mmol) of AgOTf were used. Rf (50% CH2Cl2 in hexane) = 0.49.
Yield: 16.8%, 110 mg. 1H NMR (400 MHz, CDCl3): δ = 9.58 (s, 1H),
9.06 (d, J = 4 Hz, 1H), 8.84 (d, J = 4 Hz, 1H), 8.77 (d, J = 4 Hz, 1H),
8.69 (s, 1H), 8.64 (d, J = 5 Hz, 2H), 8.62 (s, 1H), 8.47 (d, J = 4 Hz,
1H), 8.03 (dd, J = 9, JHF = 6 Hz, 2H), 7.40 (dd, J = 9, JHF = 9 Hz,
2H), 4.52 (s, 2H), 2.04 (s, 6H) ppm. 13C NMR (101 MHz, CDCl3): δ
=171.2 (s), 163.9 (s), 161.4 (s), 159.3 (s), 154.1 (s), 153.1 (s), 147.2
(s), 146.5 (s), 146.0 (s), 138.3 (d, J = 3 Hz), 134.9 (d, J = 8 Hz), 133.0
(s), 132.9 (s), 128.8 (s), 128.2 (s), 127.4 (s), 126.8 (s), 122.30 (s), 113.6
(d, J = 21 Hz), 109.4 (s), 97.0 (s), 94.4 (d, J = 17 Hz), 50.3 (s), 45.4
(s), 30.9 (s) ppm. HRMS: calc. C28H21FN4Zn [M]+ 496.1036, obsd.
496.1022.
C
28H24FN4 [M + H]+ 435.1980, obsd. 435.1975.
8.7. 1i
Reaction was performed using 26 mg (0.046 mmol) of Zn chlorin. Rf
(50% CH2Cl2 in hexane) = 0.53. Yield: 91%, 21 mg.
1H NMR (400 MHz, CDCl3): δ = 9.88 (s, 1H), 9.25 (d, J = 4 Hz,
1H), 9.06 (s, 1H), 9.00–8.95 (m, 2H), 8.94 (s, 1H), 8.85 (d, J = 5 Hz,
1H), 8.79 (d, J = 5 Hz, 1H), 8.61 (d, J = 4 Hz, 1H), 8.02 (d, J = 8 Hz,
2H), 7.87 (d, J = 8 Hz, 2H), 4.65 (s, 2H), 2.06 (s, 6H), −2.05 (s, 1H),
−2.36 (s, 1H) ppm.
13C NMR (101 MHz, CDCl3): δ = 175.4, 163.0, 152.1, 150.9, 141.0,
140.7, 139.5, 135.5, 134.9, 134.9, 134.2, 134.2, 132.5, 131.7, 130.0,
128.4, 127.9, 123.7, 123.4, 122.2, 122.2, 119.7, 119.7, 107.3, 97.0,
94.4, 52.0, 46.5, 31.2. HRMS: calc. C28H24BrN4 [M + H]+ 495.1179,
obsd. 495.1167.
8.4. Zn-1i
Bromination was performed starting from 33 mg of the required,
18 mg of NBS. During macrocyclisation 19 mg of Western half, 95 mg of
p-toluenesulfonic acid monohydrate, 141 mg and 352 mg of TMPP,
274 mg of Zn(OAc)2 and 77 mg of AgOTf were used. Rf (50% CH2Cl2 in
hexane) = 0.37. Yield: 21%, 12 mg.
General procedure for the preparation of Pd chlorins: To the solu-
tion of 1 equiv. of free base chlorin in 5 mL of pyridine, 5 equiv. of Pd
(acac)2 was added. The reaction mixture was irradiated in microwave
reactor for 30 min at 180 °C. After the completion of the reaction the
solvent was removed under reduced pressure, and the solid residue was
extracted with CH2Cl2. Column chromatography on silica gel using 50%
CH2Cl2 in hexane gave spectroscopically clean products as bright pink
solids after solvent removal.
1H NMR (400 MHz, CDCl3): δ = 9.62 (s, 1H), 9.09 (d, J = 4 Hz,
1H), 8.86 (d, J = 4 Hz, 1H), 8.78 (d, J = 4 Hz, 1H), 8.71 (s, 1H), 8.65
(s, 1H), 8.65 (s, 1H), 8.63 (s, 1H), 8.48 (d, J = 4 Hz, 1H), 7.94 (d,
J = 8 Hz, 2H), 7.82 (d, J = 8 Hz, 2H), 4.53 (s, 2H), 2.03 (s, 6H) ppm.
13C NMR (101 MHz, CDCl3): δ = 171.3, 159.6, 154.2, 153.3, 146.7,
146.2, 141.5, 135.1, 133.2, 132.9, 129. 9, 128.9, 128.4, 127.6, 127.1,
122.0, 109.5, 97.2, 94.4, 50.4, 45.5, 31.0 ppm. HRMS: calc.
8.8. Pd-1e
C
28H21BrN4Zn [M]+ 558.0215, obsd. 558.0227.
Reaction was performed using 15 mg (0.035 mmol) of free base
chlorin. Rf (50% CH2Cl2 in hexane) = 0.58. Yield: 71%, 13.3 mg.
1H NMR (400 MHz, CDCl3): δ = 9.68 (s, 1H), 8.96 (d, J = 5 Hz, 1H),
8.84 (d, J = 5 Hz, 1H), 8.74 (s, 1H), 8.72 (d, J = 5 Hz, 1H), 8.69 (s, 1H),
8.57 (d, J = 5 Hz, 1H), 8.53 (d, J = 5 Hz, 1H), 8.49 (d, J = 5 Hz, 1H),
8.01 (dd, J = 8, JHF = 6 Hz, 2H), 7.40 (dd, J = 8, JHF = 9 Hz, 2H), 4.57
(s, 2H), 2.01 (s, 6H) ppm. 13C NMR (101 MHz, CDCl3): δ = 164.0 (s),
161.6 (s), 150.0 (s), 145.5 (s), 144.6 (s), 138.7 (d, J = 0.4 Hz), 138.4 (s),
137.6 (s), 137.4 (d, J = 3 Hz), 137.3 (s), 134.7 (d, J = 8 Hz), 132.0 (s),
131.8 (s), 127.5 (d, J = 16 Hz), 127.1 (s), 126.5 (s), 113.9 (s), 113.7 (s),
110.0 (s), 97.8 (s), 95.5 (s), 50.1 (s), 45.5 (s), 30.8 (s) ppm. HRMS: calc.
General procedure for the preparation of free base chlorins from Zn
chlorins: To the solution of the Zn chlorin in 50 mL of dry CH2Cl2 ca.
0.25 mL of TFA was added in one portion. The reaction mixture was
stirred at room temperature for 20 min. The reaction was and quenched
with 1 mL of triethylamine. The resulting dark green to black solution
was then directly applied onto a silica gel column. The product was
eluted with 50% CH2Cl2 in hexane mixture. Removal of the solvent
under reduced pressure gave spectroscopically clean products as dark
green solids.
8.5. 1b
C
28H21FN4Pd [M]+ 538.0790, obsd. 538.0770.
Reaction was performed using 13 mg (0.021 mmol) of Zn chlorin. Rf
(50% CH2Cl2 in hexane) = 0.47. Yield: 64%, 7.3 mg.
8.9. Pd-1g
1H NMR (400 MHz, CDCl3): δ = 9.88 (s, 1H), 9.26 (d, J = 5 Hz,
1H), 9.06 (s, 1H), 8.99 (d, J = 4 Hz, 1H), 8.97 (s, 1H), 8.94 (s, 1H),
8.85 (d, J = 5 Hz, 1H), 8.80 (d, J = 5 Hz, 1H), 8.63 (d, J = 4 Hz, 1H),
4.66 (s, 2H), 2.08 (s, 6H), −2.00 (s, 1H), −2.37 (s, 1H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 175.4, 163.0, 152.0, 150.9, 141.3, 141.0,
139.5, 136.0, 135.8, 134.8, 134.3, 132.5, 131.7, 128.4, 127. 9, 123.7,
Reaction was performed using 15 mg (0.031 mmol) of free base
chlorin. Rf (50% CH2Cl2 in hexane) = 0.51. Yield: 69%, 12.4 mg.
1H NMR (400 MHz, CDCl3): δ = 9.66 (s, 1H), 8.94 (d, J = 5 Hz,
1H), 8.81 (d, J = 5 Hz, 1H), 8.72 (s, 1H), 8.69 (d, J = 5 Hz, 1H), 8.66
(s, 1H), 8.54 (s, 2H), 8.49 (d, J = 5 Hz, 1H), 7.67 (t, J = 8 Hz, 1H),
6.96 (d, J = 9 Hz, 2H), 4.57 (s, 2H), 3.52 (s, 6H), 2.01 (s, 6H) ppm. 13
C
9

A.I. Arkhypchuk, et al.
JournalofInorganicBiochemistry205(2020)110979
NMR (101 MHz, CDCl3): δ = 160.8, 160.2, 149.5, 145.0, 144.5, 139.3,
138.0, 137. 9, 137.0, 131.4, 130.0, 127.5, 126.8, 126.5, 126.3, 119.1,
116.4, 109.9, 104.3, 97.4, 95.2, 56.1, 50.2, 45.4, 30.7 ppm. HRMS:
calc. C30H26N4O2Pd [M]+ 580.1096, obsd. 580.1091.
Acknowledgments
This work was supported by the Swedish Research Council (project
grant 2013-4655 to KEB), and Stiftelsen Olle Engkvist Byggmästare
(post doc fellowship to A.I.A.).
8.10. Pd-1j
Synthesis and characterization data for all new compounds. Cyclic
voltammograms, 1H and 13C NMR data and UV–Vis absorption spectra
for new chlorins. UV–Vis absorptions of acidic demetallations.
Supplementary data to this article can be found online at doi: https://
doi.org/10.1016/j.jinorgbio.2019.110979.
Reaction was performed using 21 mg (0.047 mmol) of free base
chlorin. Rf (50% CH2Cl2 in hexane) = 0.57. Yield: 67%, 17 mg.
1H NMR (400 MHz, CDCl3): δ = 9.68 (s, 1H), 8.96 (d, J = 5 Hz,
1H), 8.84 (d, J = 5 Hz, 1H), 8.75 (s, 1H), 8.71 (d, J = 5 Hz, 1H), 8.68
(s, 1H), 8.61 (d, J = 5 Hz, 1H), 8.57 (d, J = 5 Hz, 2H), 8.57 (d,
J = 5 Hz, 2H), 7.97 (d, J = 9 Hz, 2H), 7.23 (d, J = 9 Hz, 2H), 4.58 (s,
2H), 4.07 (s, 3H), 2.01 (s, 6H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 161.5, 159.3, 149.8, 145. 5, 144.6, 139.1, 138.4, 137.6, 137.5,
134.4, 133.8, 132.1, 131.9, 127. 9, 127.3, 126.9, 126.2, 123.9, 112.3,
110.0, 97.7, 95.3, 55.5, 50.1, 45.5, 30.8 ppm. HRMS: calc.
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[4] S.K. Pandey, X. Zheng, J. Morgan, J.R. Missert, T.-H. Liu, M. Shibata, D.A. Bellnier,
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C
29H24N4OPd [M]+ 550.0990, obsd. 550.1018.
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tion of 1 equiv. of free base chlorin in 15 mL of CH2Cl2 5 equiv. of Cu
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acac
APT
COSY
Epa
Acetylacetonate
Attached proton test
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Anodic potential
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Ferrocene
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HOMO Highest occupied molecular orbital
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HRMS
HSQC
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NBS
High resolution mass spectrometry
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N-bromosuccinimide
Rf
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TFA
Trifluoroacetic acid
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Declaration of competing interest
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11