Flowers of the plant genusHypericumas versatile photoredox catalysts

Article abstract of DOI:10.1039/d0gc03281f

Photoredox catalysis is a powerful and modern strategy for the synthesis of complex organic molecules. So far, this field has relied on the use of a limited range of metal-based chromophores or artificial organic dyes. Here, we show that the ubiquitous plant genusHypericumcan be used as an efficient photoredox catalyst. The dried flowers efficiently catalyze two typical photoredox reactions, a photoreduction and a photooxidation reaction, with a versatile substrate scope. Constitution analysis of the worldwide available plant genus indicated that naphthodianthrones, namely the compounds of the hypericin family, are crucial for the photocatalytic activity of the dried plant material.In situUV-vis spectroelectrochemical methods provide insights into the mechanism of the photoreduction reaction where the radical dianion of hypericin (Hyp˙^2?) is the catalytically active species. Our strategy provides a sustainable, efficient and an easy to handle alternative for a variety of visible light induced photocatalytic reactions.

Full text of DOI:10.1039/d0gc03281f

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DOI: 10.1039/D0GC03281F
ARTICLE
Blossoms of the plant genus Hypericum as versatile photoredox
catalyst†
Jun-jie Wang,a Kai Schwedtmann,a Kun Liu,a Stephen Schulz,a, Jan Haberstroh,a Gerrit Schaper,a Anja
Received 00th January 20xx,
Accepted 00th January 20xx
Wenke,b Julia Naumann,b Torsten Wenke,b Stefan Wanke,b Jan J. Weiganda*
DOI: 10.1039/x0xx00000x
Photoredox catalysis is a powerful and modern strategy for the synthesis of complex organic molecules. So far, this field has
relied on the use on a limited range of metal-based chromophores or artificial organic dyes. Here, we show that the
ubiquitous plant genus Hypericum can be used as efficient photoredox catalyst. The dried blossoms efficiently catalyze two
typical photoredox reactions, a photoreduction and a photooxidation reaction, with a versatile substrate scope. Constitution
analysis of the worldwide available plant genus indicated that naphthodianthrones, namely compounds of the hypericin
family, are crucial for the photocatalytic activity of the dried plant material. In situ UV-vis spectroelectrochemical methods
provide insights into the mechanism of the photoreduction reaction where the radical dianion of hypericin (Hyp•2–) is the
catalytically active species. Our strategy provides a sustainable, efficient and an easy to handle alternative for a variety of
visible light induced photocatalytic reactions.
alternative photoredox catalysts still remains urgent and
desirable.
The plant genus Hypericum L. (Hypericaceae) comprising of 460
Introduction
The trend in modern synthetic chemistry more and more
endeavors to incorporate sustainable aspects which is highly
desirable but also extremely challenging. Sustainable chemistry
includes the design of efficient, safe and more environmentally
benign chemical processes and products. In this regard, the
renaissance of catalytic photochemistry, using light as natural
energy source, provides powerful solutions for various difficult
and seemingly insurmountable problems in organic synthesis.1,2
Among all the categories of photocatalysts, transition metal
chromophores such as Ruthenium and Iridium complexes stand
at the forefront due to their excellent photophysical properties,
which are the basis for numerous versatile applications in
inorganic and organic synthesis.3-5 However, transition metal
chromophores suffer from low availability, high expense and
toxicity resulting in environmental contamination. In order to
overcome the disadvantages brought by transition metal
complexes, synthetic organic photocatalysts, inter alia
Rhodamine B, Rhodamine 6G and Eosin Y were lately
introduced into photoredox catalytic processes.6-8 This results
in many excellent works demonstrating that synthetic organic
catalysts reach comparable or even better catalytic efficiency
compared to transition metal chromophores.2,9 However, those
artificial organic catalysts are often toxic and must be generated
by laborious multi-step syntheses.10,11 Therefore, finding a
sustainable - renewable and environmentally friendly - and
herbal species can be found in temperate to tropical regions of
the world.12 Hypericum perforatum (also known as St. John’s
Wort) is among the best known and the most frequently used
medicinal herb since second century B.C,13 covering a wide
application such as treatment of burns, skin injuries, neuralgia,
fibrosis, sciatica and depression.13-15 Furthermore, anti-
depressive,16,17 anti-viral,18 anti-oxidant,19 and anti-bacterial
effects of the plant extracts have been responsible for the
traditional use of Hypericum perforatum.20 Most recently, the
anticancer activity of hypericin ‒ the most active compound
from the plant extracts ‒ attracted much interest due to the
remarkable photophysical properties of hypericin making it an
ideal photosensitizer for phototherapy.21 In this regard,
hypericin and its homologues have long been recognized as an
excellent photosensitizer to produce reactive oxygen species
(ROSs).21 These ROSs generated by photo-excited hypericin are
considered as source of hypericin’s phototoxicity towards
bacteria and cancer cells.
The naphthodianthrones hypericin and pseudohypericin as well
as their biosynthetic precursor protohypericin, and
protopseudohypericin are present in fresh plant material.20,22
The
unstable
protoforms
(protohypericin
and
protopseudohypericin) are efficiently converted into the stable
products hypericin and pseudohypericin by the influence of
light.14,20 These are the major components for Hypericum’s
medicinal value, although other biologically active metabolites,
e.g. flavonoids and tannins, are also present.22 It was found that
these compounds are localized and probably also synthesized
a. Faculty of Chemistry and Food Chemistry, Technische Universität Dresden,
Dresden, Germany. Email: jan.weigand@tu-dresden.de
b. Faculty of Biology, Technische Universität Dresden, Dresden, Germany
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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with an increasing amount of hypericin analogues (hypericin,
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DOI: 10.1039/D0GC03281F
pseudohypericin, protohypericin and protopseudohypericin)
the catalytic yield improved simultaneously. It is worth noting
that although Hypericum spruneri and Hypericum rochelli
exhibit higher contents of hypericin analogues, neither of them
demonstrated superior catalytic performance compared to
Hypericum vesiculosum, which suggests a different catalytic
activity between these hypericin analogues. Moreover, some
species in which the concentration of hypericin analogues is
comparatively low, such as Hypericum cerastioides, also gave a
reaction yield of more than 30 % (Table 1, Entry 1), indicating
that further plant ingredients might also be catalytically active
in the model reaction.
Fig. 1 Schematic representation using blossoms of plant genus Hypericum as
catalyst in photooxidation and photoreduction reactions.
Table 1 Different Hypericum species as photo sensitizer in the catalytic
photoreduction reaction of 2-bromobenzonitrile as substrate and pyrrole as
radical trap under blue light irradiationa.
in the dark glands which are dispersed over the entire above-
ground plant parts (flowers, capsules, leaves, stems) but not in
the roots.23,24 The amount of hypericin produced depends on
the number and size of the dark glands but not on their
location.24 Nevertheless, the amount of hypericin and
pseudohypericin in flowers is higher than in leaves.25,26
Br
N
CN
Hypericum blossom, DIPEA, DMSO
N
+
CN
blue LED, N2, 25 oC, 24 h
Considering the wide availability of the plant and the excellent
photophysical properties of hypericin, we investigated the plant
genus Hypericum as a novel and versatile photoredox catalyst.
Two kinds of important model reactions, the reductive coupling
reactions of aryl halides9 and the oxidative coupling reactions of
N-aryl tetrahydroisoquinolines10 were selected to investigate
the photocatalytic properties of the Hypericum plants. The
results demonstrate that the dried blossoms of the plant
material efficiently catalyze the model reactions under mild
Entry
Hypericum
Hypericin
Analogues b
(w%)
0.016
0.018
0.25
condition
Yield c
Species
(%)
1
2
H. cerastioides
H. empetrifolium
H. hirsutum
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
470 nm, 48 h
470 nm, 24 h
470 nm, 24 h
530 nm, 24 h
470 nm, 24 h
Dark, 24 h
31
51
38
40
36
42
37
68
58
63
70
53
67
48
56
29
0
3
4
H. olympicum
H. maculatum
H. perfoliatum
H. perforatum
H. vesiculosum
H. spruneri
0.53
5
0.98
conditions. Furthermore, besides
a
standard column
6
1.11
chromatography, no additional purification procedure is
needed to isolate the desired coupling products.
7
1.25
8
1.86
9
1.97
10
11d
12e
13
14f
15g
16
17
18
H. rochelii
2.00
Results and discussion
H. vesiculosum
H. vesiculosum
H. vesiculosum
H. vesiculosum
H. vesiculosum
H. vesiculosum
-
1.86
The photocatalytic reduction of aryl halides in the presence of a
radical trap is an important strategy to form C‒C and C‒P bonds
and to build up larger molecules. Using perylene diimides as
catalyst, König and co-workers developed a method to activate
aryl bromides or chlorides through a consecutive visible light
induced electron transfer process.27 Inspired by their strategy,
we started our investigation using 2-bromobenzonitrile as
1.86
1.86
1.86
1.86
1.86
-
substrate,
N-methyl-pyrrole
as
radical
trap,
H. vesiculosum
1.86
0
diisopropylethylamine (DIPEA) as electron donor and dried
blossoms of different Hypericum species as catalyst. In order to
investigate the catalytic performance between different
Hypericum species, ten species collected from Germany, Austria
and Greece were tested. The plant materials were dried for 24 h
aReactions were performed using 0.1 mmol 2-bromobenzonitrile, 2.0 mmol N-
methylpyrrole, 50 mg of plant materials and 0.1 mmol DIPEA in 1.0 ml DMSO under
nitrogen with a blue LED (470 nm). bQuantifications of hypericin homologues
including protopseudohypericin, pseudohypericin, protohypericin and hypericin
were based on external standard methods (see the supporting information for
details). cCalculated from UPLC analysis by the external standard method. d100 mg
o
at 40 C in a drying chamber under exclusion of light and the
blossoms were separated from the dried plant. Prior to the
reaction the blossoms were grinded to a fine powder which was
directly added to the reaction without further purification (for
details, see SI 2.1†). To our delight, all Hypericum species
demonstrated a catalytic activity towards our benchmark
reaction in yields up to 68 % (Table 1, Entry 1-10). In general,
f
plant materials. e25 mg plant materials. 0.5 mmol DIPEA was used. g1.5 mmol
DIPEA was used.
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0GC03281F
a
b
c
e
OH
OH
HO
O
O
OR
OH
R = H
Quercetin
Hyperoside
Quercitrin
R = -D-galactosyl
R = -L-rhamnosyl
1
O
OH
R2
O
O
R1
d
f
R1 = H R2 = CH2CH3
Adhyperfirin
4
6
7
R1 = 3-methylbut-2-enyl R2 = CH3 Hyperforin
R1 = 3-methylbut-2-enyl R2 = CH3 Adhyperforin
OH
O
OH
R
OH
OH
H. cerastioides
H. empetrifolium
H. hirsutum
Hypericin
Protohypericin
Pseudohypericin
Protopseudohypericin
OH
R = CH2OH Protopseudohypericin
R = CH3 Protohypericin
O
OH
2
5
H. olympicum
H. maculatum
H. perfoliatum
H. perforatum
H. vesiculosum
H. spruneri
OH
O
OH
R
OH
OH
OH
R = CH2OH Pseudohypericin
R = CH3 Hypericin
O
OH
H. rochelii
3
0.0
0.5
1.0
1.5
2.0
8
w/w %
Fig. 2 UPLC-PDA/MS analysis of a typical Hypericum plant extract of H. perforatum (a and b) and H. vesiculosum (c and d); (a) and (c) detected by the tandem
quadrupole detector in the ESI‒ mode; (b) and (d) detected by the photodiode array detector at 588 nm; (e) assigned compounds of the plant extracts; (f) contents of
hypericin analogues in different Hypericum species.
In order to elucidate the catalytically active component, the plant to decompose under light irradiation within a short period of
material was investigated by means of UPLC-MS. In agreement with time.33,34 The flavonol glycosides, are structurally similar and differ
28-32
the literature
three classes of compounds have been found in only in the glycosyl groups linked to the hydroxy group (Fig. 2e),
the plant extracts, which were identified as flavonol glycosides therefore, quercetin was selected representatively in order to
(hyperoside, rutin and quercetin), naphthodianthrines elucidate the catalytic activity of this substance class. When2 mol%
(protopseudohypericin, pseudohypericn, protohypericin and of quercetin is inserted as catalyst in the benchmark reaction, a yield
hypericin) and polycyclic polyprenylated acylphloroglucinols of 28% was obtained from the optimized condition (Table 2). This
(hyperforin, adhyperforin, hyperfirin and adhyperfirin) (Fig. 2a-d). explains that Hypericum species having
a low amount of
The latter substance class can be excluded to be catalytically active naphthodianthrines, such as Hypericum cerastioides, show indeed a
as (a) a π-conjugated system is necessary for π‒π* electron excitation catalytic activity.
and subsequent electron transportation within the photoredox
procedure and (b) polycyclic polyprenylated acylphloroglucinols tend
photosensitizer in the benchmark reaction, yields from 40% to
Surprisingly, when 2 mol% of the naphthodianthrines are inserted as
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Table 2 Reactions using the pure compounds (quercetin, protopseudohypericin, COCH3 in combination with N-methyl-pyrrole and pyrrole. In
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pseudohypericin, protohypericin and hypericin) which are detected in the plant contrast, substrates bearing electron donatiDnOg Is:u10b.s1t0it3u9e/Dn0tsG,Cs0u3c2h8a1Fs
extract as photoredox catalystsa.
-CH3 and -OtBu, gave the corresponding products only in very low
yields which is attributed to the high reduction potential (Fig. 3A).27
Notably, the reaction with bromopentaflurobenzene as substrate
gives a mixture of two isomers where the pyrrole moiety is bonded
via the  C atom or the  C atom (Fig. 3A).35 Different kinds of radical
traps such as 3-methyl-indole, trimethoxybenzene and
trimethylphosphite were also applied to the protocol, giving yields of
23% to 59% depending on the activity of the traps. Most importantly,
the product can readily be separated from the plant catalysts by
simple column purification, demonstrating the ease in the
application of the plant materials as active catalyst.
Entry
Hypericum
Hypericin
condition
Yield c
(%)
Species
Analogues
(mmol%)
1
2
Quercetin
2
2
470 nm, 24 h
470 nm, 24 h
28
57
Protopseudohyp
ericin
3
4
5
Pseudohypericin
Protohypericin
Hypericinb
2
2
2
470 nm, 24 h
470 nm, 24 h
470 nm, 24 h
40
58
37
aReactions were performed using 0.1 mmol 2-bromobenzonitrile, 2.0 mmol N-
methylpyrrole, 2 mol% of corresponding catalyst and 0.1 mmol DIPEA in 1.0 ml
DMSO under nitrogen with a blue LED (470 nm). bHypericin was in situ synthesized
from protohypericin. cCalculated from UPLC analysis using an external standard.
As we found that hypericin is the most efficient photosensitizer in
the plant material, in situ prepared hypericin was applied as catalyst
in order to compare the catalytic activity with the dried plant
material of H. vesiculosum. The in situ preparation of hypericin from
protohypericin via light irradiation is necessary to increase the
solubility of the active catalyst hypericin.36-38 The condition
optimization (see Table S3†) demonstrates that with 2 mol% of
hypericin catalyst and 1.0 equivalent DIPEA, the best conversion can
be achieved under blue light irradiation for 48 hours. Although
hypericin reveals an absorption maximum at 555 nm and 599 nm
(Fig. S5†), blue light is necessary for the further stimulation of the
active species (Hyp•2–) in this process (vide infra).27,39 Using the
optimized conditions, moderate to good yields from 42% to 76% can
be obtained in the reaction of aryl bromides featuring different
substituents including ‒CN, ‒CHO, and ‒COCH3 in combination with
N-methyl-pyrrole or pyrrole and hypericin as catalyst (Fig. 3A). With
a few exceptions, the results reveal that hypericin provides generally
higher yields compared to the plant material. However, considering
the simplicity of the reactions by adding the blossoms of the plant as
active catalyst, it appears as sustainable and convenient alternative
since this method is beneficial regarding time, costs and chemical
waste.
73% are obtained (Table 2), from which hypericin displays the highest
catalytic activity among all the naphthodianthrines (73%). The
concentration of naphthodianthrines in the well investigated species
H. perforatum extract has been derived from the UV-vis absorption
spectra at 588 nm (Fig. 2b), revealing an amount of 1.8 mg/g for
protopseudohypericin, 3.7 mg/g for pseudohypericn, 1.0 mg/g for
protohypericin and 5.9 mg/g for hypericin, respectively. In contrast,
the extract of H. vesiculosum shows a reduced amount of flavonol
glycosides and polycyclic polyprenylated acylphloroglucinols and at
the same time more naphthodianthrines (Fig. 2c). The concentration
of the latter substance class is higher in the H. vesiculosum extract
(1.6 mg/g for protopseudohypericin, 3.9 mg/g for pseudohypericn,
1.7 mg/g for protohypericin and 11.4 mg/g for hypericin (Fig. 2d), and
in addition contains the highest amount of hypericin (Fig. 2f).
Therefore, this plant material has been chosen as catalyst for
subsequent reactions.
Since H. vesiculosum revealed the highest catalytic activity (68%
yield) among all the species, we optimized the photoredox reaction
conditions using H. vesiculosum as catalyst. As expected, reducing
the catalyst loading caused a lower yield of 53% (Table 1, entry 12 vs
entry 8). However, increasing the catalyst loading or extending the
reaction time only led to a comparable or slightly higher yield
compared to the standard condition, respectively (Table 1, entry 11
and 13 vs entry 8). Additionally, the concentration of the electron
donor (DIPEA) has no significant influence on the reaction yield
(Table 1, entry 14 and 15 vs entry 8). No reaction is observed in
absence of plant materials or visible light irradiation, indicating the
involvement of a photoredox process in the reaction. Summarizing,
the best condition for this reaction was determined as 0.1 mmol of
aryl halide, 2.0 mmol of a suitable radical trap and 50 mg of H.
vesiculosum as catalyst in DMSO under blue LED irradiation for 24
hours.
Motivated by our successful application of the H. vesiculosum plant
in a catalytic photoreductive process, the coupling reaction of N-aryl-
tetrahydroisoquinoline with nitromethane was selected as another
model reaction to explore the potential application in
photooxidation reactions (Fig. 3b). Please note that this reaction is
reported
to
proceed
without
catalyst,
however,
bromotrichloromethane (BrCCl3) is necessary and the conversion
using green light is comparatively low (Table S5†). 40 Considering the
highest UV-vis absorption of hypericin at 555 nm and 599 nm (see
Fig. S5†), green LED resource (535 nm) was chosen as it may provide
sufficient energy to stimulate the ground state of hypericin. To our
delight, when using Hypericum plant as catalyst in the initial
photooxidative
coupling
reaction
of
N-phenyl-
tetrahydroisoquinoline with nitromethane and green light irradiation
the desired coupling product was obtained in good yield (79%; Fig.
3b). Moreover, moderate to very good yields from 30% to 85% can
be observed depending on the inserted substrates under the
optimized condition (Fig. 3; for details see Table S4†). The use of
dialkyl phosphite ((RO)2P(O)H; R = Me, Et) in the reaction with N-
With the best condition in hand, we expanded the reaction to
different substrates and radical traps in order to elucidate the
influence of functional groups. Moderate to good yields (33%-65%)
were obtained with aryl bromide substrates featuring different
electron withdrawing substituents including -CN, -CHO, -CF3 and -
phenyl-tetrahydroisoquinoline
similarly
generates
the
corresponding dialkyl phosphonates in good yields (62%, 68%).
4 | J. Name., 2012, 00, 1-3
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Consistent with the aforementioned photoreduction reaction, the → Hyp– + H+) as it has been discussed in the literatures based on
View Article Online
use of in situ prepared hypericin as catalyst generally gives higher NMR41,42 and electrochemical studies (Fig. 4).43
DOI: 10.1039/DT0hGuCs0,32t8h1eF
yields (70% to 92%) after optimization (Fig. 3b; for details see Table monoanionic Hyp–, being considered as catalyst, is stimulated under
S5†). However, also in this case these results reveal the versatile light irradiation to its excited state [Hyp–]*. In the photoreduction
applicability of the Hypericum plant as efficient photocatalyst in process [Hyp–]* is subsequently reduced by the electron donor DIPEA
photooxidation reactions.
to give the radical dianion Hyp•2– along with oxidized DIPEA•+. Under
further light irradiation radical dianion Hyp•2– is again stimulated to
its excited state [Hyp•2–]* which enables the electron transfer to the
inserted aryl halide causing a homolytic halogen-carbon bond
A
Br
Hypericum vesiculosuma or Hypericinb
Trap
CN
blue LED
Trap
+
CN
DIPEA, DMSO, N2, 25 o
C
[Hyp-]*
[Hyp-]*
DIPEA
hv
hv
O
DIPEA +
N
N
O
N
O
R
R
R
photo-oxidation
photo-reduction
N
O
P
Ar
CN
HN
O
O
O
O
Hyp-
2-
CN
CN
Hyp
CN
Br
[O]
N
R = H
R= CH3 65%a
50%a
R = H
R= CH3 54%a
52%a
R = H
R= CH3 42%a
38%a
23%a
42%b
33%a
49%b
59%a
49%b
Ar
Blue
[O]
Ligh
[O]
Hyp
2-
R = H
62%b
R= CH3 76%b
R = H
56%b
R= CH3 73%b
R = H
33%b
R= CH3 60%b
t
R
[Hyp2-]*
[OH]
DIPEA +
Br
Trap
N
Ar
H-DIPEA+
R
N
Nu
N
N
N
N
N
Trap
F
F
F
F
N
O
Ar
R
Nu
CF3
CF3
F
O
CN
 :  = 4 : 1
Fig. 4 Proposed reaction mechanism of the photo-reduction (left) and the photo-
41%a; 64%b
39%a; 51%b
33%a; 46%b
4%a; 12%b
9%a; 15%b
47%a; 61%b
oxidation (right) process using hypercin as photo-catalyst.
a
B
Hypericum vesiculosuma or Hypericinb
green LED
N
N
Nu
+
NuH
air, solvent, 25 o
C
R
R
O
N
N
N
N
NO2
R
NO2
NO2
O
NO2
69%a; 76%b
R = H
79%a; 92%b
67%a; 81%b
54%a; 84%b
R = Me 66%a; 87%b
R = Cl 85%a; 81%b
R = F
30%a; 78%b
N
N
CN
N
O
O
O
R
P
O
O
O
O
R
b
62%a; 57%b
R = CH3 62%a; 70%b
R = C2H5 68%a; 77%b
86%a; 90%b
Fig. 3 (A) Photoreduction reactions using blossoms of Hypericum vesiculosuma or
hypericinb as catalyst. Reactions were performed using 0.2 mmol 2-
bromobenzonitrile, 4.0 mmol N-methylpyrrole, and 0.2 mmol DIPEA in 1.0 mL
DMSO under nitrogen with a blue LED (470 nm). aUsing 100 mg of plant materials
(containing 1.8 mmol% naphthodianthrines) for 24 hours. busing 4 µmol (2 mol%)
hypericin for 48 hours; (B) Hypericum vesiculosum plant or hypericin as photoredox
catalyst in photooxidative coupling reactions of N-aryl-tetra-hydroisoquinolines
with nitromethane or dialkylphosphites ((OR)2P(O)H) under green light irradiation.
Reactions were performed using 0.2 mmol N-aryl-tetra-hydroisoquinolines and
10.0 mmol nucleophile under ambient atmosphere with a green LED (530 nm).
aUsing 50 mg Hypericum plant as catalyst in 2.0 ml methanol. bUsing 2 µmol (1
mmol%) hypericin in 2.0 ml DMF.
Fig. 5 (a) Cyclic voltammetry (CV) curve and square wave voltammogram (SWV)
of hypericin (1.0 mM) in DMSO with 0.1 M [nBu4N][BF4] at a 1.6 mm platinum disk
electrode. (b) Three cycles of the CV measurement of hypericin (1.0 mM) in
acetonitrile with 0.1 M [nBu4N][BF4] at a 1.6 mm platinum disk electrode.
Mechanistically, we propose that under the given reaction
conditions, hypericin (HypH) is dissociated in DMSO solution (HypH
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cleavage to give the aryl radical along with the formed halide and the
inserted catalyst Hyp–. The highly reactive aryl radical subsequently
reacts with the corresponding radical trap (e.g. pyrroles) to form the
product radical, which is converted to the desired product upon
quenching with the DIPEA•+ radical cation. In order to justify, the
proposed mechanism including the intermediately formed active
species of hypericin we performed in depth spectroscopic and in situ
UV-vis spectroelectrochemical (SEC) investigations. The dissolved
Hyperin shows in DMSO absorption maxima 555 nm and 599 nm
consistent with the reported values of Na+Hyp–.44,45 No change of the
absorption maxima is observed upon addition of an excess amount
of base (e.g. DIPEA) indicating the presence of dissociated Hyp– in
DMSO which is in agreement with previous reports.43
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DOI: 10.1039/D0GC03281F
a
b
Similar to the catalysis, the hypericin for the SEC measurements was
prepared in situ from protohypericin in order to increase the
solubility (vide supra) in e.g. acetonitrile. The CV of hypericin
supports the assumption of the dissociation into Hyp– in DMSO in
comparison to acetonitrile. While the CV measurement of hypericin
in DMSO shows explicitly two reversible peaks at potentials of E1/2 (1)
= –1.39 V and E1/2 (2) = –1.74 V (vs E1/2(Cp2Fe/Cp2Fe+); Fig. 5a), the CV
curve of the first cycle in acetonitrile reveals a non-reversible peak at
Ep = –1.30 V followed by two reversible peaks at E1/2 (1) = –1.46 V and
E1/2 (2) = –1.75 V (vs E1/2(Cp2Fe/Cp2Fe+); Fig. 5b). The non-reversible
peak is attributed to the electrochemical deprotonation of HypH to
Hyp– + ½ H2 and the two reversible processes are assigned to the
subsequent redox steps of Hyp– to Hyp•2– and Hyp•2– to Hyp3–,
respectively.43, 44
Fig. 6 (a) In-situ UV-vis spectrum of the reaction of Hyp to Hyp•2– (0.5 mM) with an
excess of DIPEA (50 equiv.) in DMSO under constant blue light irradiation (470 nm;
top). (b) In-situ UV-vis spectrum of the electrolysis of Hyp to Hyp•2– (0.5 mM) at a
constant potential of –1.55 V in DMSO with 0.1 M [nBu4N][BF4] at a platinum grid
electrode (bottom).
species [Hyp–]* while the substrate 2-bromobenyonitrile has no
quenching effect (see Fig. S11†). The in-situ UV-vis spectroscopy of
hypericin with an excess DIPEA under constant blue light (470 nm)
irradiation congruently reveals a change of the absorption maxima
of Hyp– (Fig. 6a, red line, 554 nm and 598 nm) while four new
absorption peaks at 493 nm, 570 nm, 678 nm and 745 nm are formed
(Fig. 6a, red → blue line) which are attributed to the radical dianion
We continued to investigate the base induced formation of Hyp•2–
upon blue light irradiation from Hyp- in DMSO. The Stern-Volmer
quenching experiments reveal that the fluorescence emission of the
proposed active species [Hyp–]* gradually decreases upon
consecutive addition of the electron donor DIPEA, suggesting a single
electron transfer from the electron donor (DIPEA) to the excited
Hyp•2–
.
Fig. 7 In situ UV-vis-CV SEC measurement of hypericin (0.5 mM) in DMSO with 0.1 M [nBu4N] [BF4] at a platinum grid electrode in a double compartment cuvette cell
(d = 0.5 mm); left: 2D plot of UV-vis spectra during the CV measurement with the UV-vis spectra of Hyp (red) and Hyp•2– (blue); upper right: 2 cycles of CV; lower right:
potential dependent absorbance at 591 nm (red) for Hyp- and 493 nm (blue) for Hyp•2–
.
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In addition, the formation of the radical dianion Hyp•2– is confirmed contribute to the design of efficient, safe anDdOmI:o1r0e.1e0n39vi/rDo0nGmCe0n3t2a8l1lFy
by the electrolysis of Hyp– to Hyp•2– at a constant potential of –1.55 V benign chemical processes and future developments.
coupled with in situ UV-vis spectroscopy (Fig. 6b, red → blue line)
revealing the formation of the corresponding absorption maxima of
Hyp•2– during the reduction process. Furthermore, repetitive
chronoamperometric switching between Hyp– and Hyp2– proves that
Conflicts of interest
The authors declare no competing interests.
the reduction of Hyp– to Hyp•2– is a one-electron process (see Fig. S15
and S16†). Further in situ UV-vis SEC experiments in a double
compartment cuvette cell over two cycles of CV demonstrate the
reversible redox process between Hyp– and Hyp•2– (Fig. 7). The
reductive formation of Hyp•2– is coupled with the increased
Acknowledgements
We thank the Sächsische AufbauBank (SAB; HyperiPhen project
100315829 in TG70 Bioleben), European Regional Development
Fond, the Free State of Saxony (ERDF-InfraPro, GEPARD-
100326379) and the German Federal Ministry of Education and
Research (BMBF; Fenabium project 02NUK046A). We also thank
Prof. Xinliang Feng for providing access to the fluorescence
spectrometer.
absorbance at 493 nm (Fig. 7, 2D plot and blue absorption line)
whereby the re-oxidation to Hyp– is accompanied with the decrease
of the absorbance at 493 nm and the concomitant formation of the
absorbance at 591 nm (Fig. 7, 2D plot and red absorption line). The
CV curve based on the UV-vis absorbance changes for the starting
material Hyp– (Fig. 7, right, red line) as well as for the reduction
product Hyp•2– (Fig. 7, right, blue line) are in accordance with the in
situ CV (Fig. 7, right, top).
Ultimately, these results confirm the formation of Hyp•2– and thus its
excited state [Hyp•2–]* during the photo-redox process under the
given reaction conditions and furthermore justify the utilization of
the blue LED (470 nm) as the absorption maximum of the active
species (Hyp•2–) is at 493 nm.
Notes and references
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