Visible to NIR Light Photoactivation of Hydrogen Sulfide for Biological Targeting

Article abstract of DOI:10.1021/acs.orglett.8b02043

The synthesis and photochemical properties of H₂S-releasing BODIPY thiocarbamate photocage scaffolds activatable by visible-to-NIR (up to 700 nm) light to release carbonyl sulfide (COS), which is transformed to H₂S using either isolated or natural carbonic anhydrase, is reported. The excellent uncaging cross section and high H₂S release yields in in vitro experiments, including live-cell imaging, suggest that these photocages can serve as a platform for the bio-orthogonal phototriggered release within the tissue-transparent window.

Full text of DOI:10.1021/acs.orglett.8b02043

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Visible to NIR Light Photoactivation of Hydrogen Sulfide for
Biological Targeting
Peter Stacko,* Lucie Muchova, Libor Vítek, and Petr Klan*
,†
‡
‡
,†
̌
́
́
†Department of Chemistry and RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic
‡
̌
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Na Bojisti 3, 121 08
Praha 2, Czech Republic
S
* Supporting Information
ABSTRACT: The synthesis and photochemical properties of H2S-releasing
BODIPY thiocarbamate photocage scaffolds activatable by visible-to-NIR (up to
700 nm) light to release carbonyl sulfide (COS), which is transformed to H2S
using either isolated or natural carbonic anhydrase, is reported. The excellent
uncaging cross section and high H2S release yields in in vitro experiments,
including live-cell imaging, suggest that these photocages can serve as a platform
for the bio-orthogonal phototriggered release within the tissue-transparent
window.
ydrogen sulfide (H2S), along with carbon monoxide
light (470 nm), reported by Chakrapani and co-workers, took
H(CO) and nitric oxide (NO), is a gasotransmitter advantage of photorelease of thiocarbamate from the boron
atom of a BODIPY scaffold to trigger H2S formation.27
Photoactivation within a so-called tissue-transparent or
phototherapeutic window, limited by the absorption of
hemoglobin below 600 nm and absorption of water over 900
nm,28,29 is crucial for biological and medical applications. The
current absence of H2S-photoreleasing systems activatable with
these wavelengths still remains a serious obstacle in H2S
therapeutic applications in living organisms.
The teams of Winter and Weinstein as well as our group
have recently demonstrated the advantages of a BODIPY
scaffold acting as a photoremovable protecting group (PPG,
Scheme 1) from its meso-position via a photosolvolysis
step.30−33 Subsequently, this concept was used by Szymanski
and co-workers to photorelease amines via a carbamate
linker.34
produced endogenously from cysteine and homocysteine,1
which acts as a signaling agent and mediator of important
cellular processes resulting in numerous beneficiary antiox-
idative, anti-inflammatory, vasorelaxant, and generally cytopro-
tective effects.2−4 For example, relaxation of blood vessels by
KATP channels activation5 and protection of cardiomyocytes
from reactive oxygen species (ROS)6,7 have been attributed to
both endogenous H2S presence and its exogenous admin-
istration. These effects are likely to provide important clinical
benefits, such as protection from atherosclerosis8 and
cardiovascular diseases,3 obesity, metabolic syndrome and
possibly diabetes,9 and aging and neurodegenerative diseases.10
Controlled modulation of the biological levels of H2S has
received considerable attention in recent years. A number of
H2S-releasing molecules have been developed utilizing various
triggers, such as pH,11 reaction with glutathione (GSH),12
esterase-activated release,13 redox-controlled release,14 or
light,15,16 which offers unparalleled advantages in terms of
availability, adjustability, very high spatial and temporal
precision, high release orthogonality toward biochemical
systems, and reducing side-product formations.
Scheme 1. Photorelease of a Leaving Group (LG) from the
BODIPY Photocage
The absorption of the reported photoactivatable H2S-
releasing systems, such as an o-nitrobenzyl photocage17 or
ketoprofenate18 and xanthone19 photocages, require bio-
logically adverse20 UV or near-UV (<420 nm) light. An
elegant approach utilizing the release of thiocarbamates via
either UV-light activation21 or nonphotochemical initia-
tions14,22,23 of caged thiocarbamates has been demonstrated
by Pluth and co-workers. In this concept, the released
thiocarbamate undergoes spontaneous fragmentation to release
carbonyl sulfide (COS) which is subsequently converted by
the enzyme carbonic anhydrase, ubiquitous in mammalian
tissues, into H2S.24−26 The only example employing visible
In this work, we incorporated thiocarbamate as a leaving
group into the meso-position of BODIPY systems 1 to facilitate
its release using visible and near-infrared light as an exogenous
trigger (Scheme 2). Because the parent derivative 1a was
subsequently found to lack the desired solubility in aqueous
Received: June 29, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02043
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
solubility in aqueous systems, the derivative 1a was studied
only in methanol, whereas the derivatives 1b and 1c were
investigated in a PBS buffer solution (pH 7.4, c = 100 mM).
The compounds 1a and 1b possess absorption maxima λmax at
509 and 513 nm in methanol and PBS buffer, respectively.
They exhibit bright fluorescence with quantum yields Φf of 58
and 55%, respectively. These values compare well with the data
previously reported for analogous BODIPY photocages.31 The
derivative 1c bearing the styryl groups displays a broad
absorption spectrum with a maximum at 690 nm in PBS buffer,
indicative of aggregation to some degree,36 which was reduced
by the addition of DMSO (10%).
Scheme 2. meso-Methyl-S-Thiocarbamate Photocages 1a−c
and Their Release of H2S
In the next step, we probed the compounds 1a−c for their
ability to undergo release of the thiocarbamate group upon
irradiation with visible and near-infrared light (Scheme 2).
Irradiation of 1a in methanol at 507 nm led to formation of a
meso-methoxy BODIPY photoproduct (Figure S37), analogous
to that shown in Scheme 1. Subsequently, the derivative 1a was
excluded from further studies due to its insolubility in aqueous
media. Irradiation of the compound 1b in PBS buffer (pH 7.4,
10 mM) at 507 nm resulted in the gradual disappearance of the
absorption band at 513 nm and formation of only UV-light
absorbing photoproducts (Figure S14), such as pyrrol
derivatives reported elsewhere.31 Simultaneously, formation
of Ph2NH was observed using HPLC (Figure S26), confirming
that the anticipated release of a thiocarbamate and its
subsequent fragmentation into COS and Ph2NH are taking
place. Upon exhaustive irradiation, the total chemical yield of
systems, the fluorine atoms of the BF2 group were substituted
by polyethylene glycol (PEG) chains (1b) to improve its
solubility. In the derivative 1c, PEG-substituted styryl units
were installed on the BODIPY core to extend the π-
conjugation and shift the absorption to the desired near-
infrared region.33,35 The release of H2S was then facilitated via
carbonic anhydrase catalysis in spectroscopic as well as in vitro
studies using mice liver homogenate and HepG2 cells.
The synthesis of the starting BODIPY thiocarbamates 1a−c
is described in the Supporting Information (SI, Scheme S1).
Their photophysical properties were evaluated using absorp-
tion and emission spectroscopy, and the results are
summarized in Figure 1 and Table 1. Due to its insufficient
Ph2NH was determined to be 64.5
1.0% (Table 2).
Exclusion of oxygen by purging the solution with argon
resulted in an increase of the yield to 85.9 0.5%.
Table 2. Photochemistry of the BODIPY Derivatives 1b and
1c
a
a
b
b
Φ
R(aer)/10−2
%
Φ
R(deg)/10−2
%
Y
(aer)/%
Y(deg)/%
1b
1c
8.4 0.8
3.5 0.6
15.1 1.1
9.7 1.2
64.5 1.0
58.0 1.3
85.9 0.5
68.8 1.2
a
Quantum yields ΦR of Ph2NH release in degassed (deg) or aerated
(aer) methanol determined using ferrioxalate as an actinometer44 at
λirr = 365 nm. The total maximum chemical yields Y of the released
b
Ph2NH in degassed (deg) and aerated (aer) methanol determined by
HPLC upon exhaustive irradiation at 507 and 700 nm for 1b and 1c,
respectively. Standard deviations of the mean from three independent
experiments are shown.
Similarly, irradiation of 1c in PBS buffer (pH 7.4, 10 mM,
containing 10% DMSO) at 700 nm led to complete
disappearance of the major absorption band at 690 nm,
accompanied by the concomitant emergence of a band with
λmax ≈ 590 nm (Figure 2; the spectra of irradiated 1c in
methanol are shown in Figure S16). This signal presumably
belongs to the side product(s), formed by oxidation of one of
the styryl moieties with singlet oxygen via sensitization of O2
by the triplet state of 1c, resulting in a partial disruption of the
π-conjugated system of the starting material.37,38 Fortunately,
this photoproduct does not interfere with the photouncaging
process as an internal filter when irradiation is performed at
700 nm (Figure 2). The total chemical yields of Ph2NH upon
exhaustive irradiation of aerated and degassed samples were
Figure 1. UV−vis absorption (solid lines; left axis) and normalized
emission (dotted lines; right axis) spectra of 1b (red) and 1c (blue) (c
≈ 1 × 10−5 M) in PBS buffer (pH 7.4, 10 mM).
Table 1. Photophysical Properties of the BODIPY
Derivatives 1a−c
c
d
d
λabs/nm
λem/nm
εmax
Φf/%
τ/ns
a
b
a
1a
1b
1c
509
519
524
779
57 200
59 200
55 400
58.0 0.8
55.0 0.2
4.2 0.1
6.2 0.1
513
688
b
a
c
c
n.d.
n.d.
a
b
Measured in methanol. Measured in PBS (pH 7.4, c = 100 mM).
c
d
εmax/mol−1 dm3 cm−1. The fluorescence quantum yields Φf and
58.0
1.3% and 68.8
1.2%, respectively (Table 2). The
singlet lifetimes τ.
difference between the chemical yields of Ph2NH formation in
aerated and degassed samples of both 1b and 1c can be
B
DOI: 10.1021/acs.orglett.8b02043
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
opted to use a commercial fluorogenic H2S probe (SF7-
AM).49 Irradiation of 1c (PBS pH 7.4, 10 mM) at 700 nm in
the presence of SF7-AM showed a time-dependent increase of
the fluorescence signal (λexc = 488 nm, λem = 500−640 nm)
with a plateau corresponding to the ∼48% total chemical yield
of H2S (Figures S31 and S32).
To probe the compatibility of our system further under
biologically relevant conditions, we performed the photolysis
of 1b in the presence of a crude mice liver homogenate
containing natural concentrations of carbonic anhydrase (CA).
A sample of 1b in PBS (pH 7.4, 10 mM; aerated) was
irradiated at λ = 507 nm in the presence of a liver homogenate
(see Supporting Information (SI) for details). The methylene
blue assay showed that H2S is formed in the course of the
photolysis (Figure S28) in 35−40% chemical yields, whereas
no H2S was detected in identical samples kept in the dark.
Such lower yields when compared to those of the experiments
with CA are explained by partial reduction of MB with NADH
and GSH present in the homogenate.50 This unavoidable
reduction process restricted further investigation of the effects
of endogenous levels of GSH on the oxidation of H2S; thus a
different detection method was used.
Irradiation of 1c (50 μM, 2% DMSO in culture media;
aerated) at 700 nm in the presence of HepG2 cells in a 48-well
plate and live-cell imaging using a fluorescence microscopy
(see experimental details in SI) resulted in a substantial
increase of the fluorescence intensity of SF7-AM in
comparison to that of the control sample kept in the dark or
a sample containing the SF7-AM probe only (exhibiting weak
background fluorescence, Figures 3 and S34). This observation
Figure 2. Irradiation of 1c (c ≈ 1.5 × 10−5 M) at 700 nm in aerated
PBS buffer (pH 7.4, 10 mM, 10% DMSO) followed by UV−vis
spectroscopy. The spectra prior (red line) and after (blue line) the
irradiation are highlighted.
explained by partial bleaching of the starting material with the
generated singlet oxygen as was also reported elsewhere.39,40
The formation of Ph2NH was not observed in the control
samples kept in the dark.
The quantum yields of Ph2NH formation in aerated
methanol upon irradiation at 365 nm (the second major
absorption band) were determined to be (7.9 0.8) × 10−4
and (3.5 0.6) × 10−4 for 1b and 1c, respectively (Table 2).
These values are comparable to those of the analogous
BODIPY photocages reported by us before.30,31 The adverse
influence of oxygen on the quantum yields of the photo-
reaction of both 1b and 1c (vide supra, Table 2) is related to
the quenching of the productive triplet excited state.41,42 The
quenching by oxygen was not complete; thus, the leaving
groups are probably liberated from both the singlet and triplet
excited states as observed in the case of analogous meso-methyl
BODIPY carboxylates.31 The lower quantum yields of the
release for 1c compared to those of 1b can be explained in
terms of the enhanced radiationless decay from a lower-lying
excited state.43 The excellent uncaging cross section ΦRεmax on
the order of 50−100 designates the compounds for subsequent
biological applications.15
In order to determine the amount of H2S produced upon
photolysis, we utilized a well-established methylene blue (MB)
assay.18,45,46 However, determination of the total chemical
yield of H2S was complicated by its oxidation, presumably with
singlet oxygen generated through the sensitization process.47,48
Such behavior has been reported in the case of an o-
nitrobenzyl system, where H2S release exhibited time-depend-
ent release with a peaking time.21 Therefore, the analysis was
performed using either degassed samples or in the presence of
zinc acetate which precipitates H2S from the solution in the
form of ZnS. We analyzed independent samples of 1b (c = 5 ×
10−5 M) in degassed PBS buffer (pH 7.4, 10 mM) at different
irradiation times to observe a time-dependent H2S release with
a plateau at the ∼70% total chemical yield (Figure S27). This
correlates well with the previously determined total chemical
yield of Ph2NH (Table 2, vide supra). In the presence of zinc
acetate and under an ambient atmosphere, the yield decreased
to 51.2 0.8%.
Figure 3. Fluorescence microscopy images of HepG2 cells and H2S-
probe in the presence (top) or absence (bottom) of 1c irradiated with
700 nm (from left to right 30, 60, 90, and 120 min) at fixed exposure
time. The scale bar represents 50 μm (see also Figure S34).
was further verified by analysis of the sample fluorescence
using a microplate reader (Figure S33). The observed
background fluorescence of SF7-AM has also been observed
before, and it most likely stems from the reaction with
endogenous H2S, cysteine, and GSH.51
The compound 1b displayed a certain degree of toxicity
above 25 μM in 24 h in vitro experiments on human
neuroblastoma SH-SY5Y cells (a surrogate cell line for studies
of neuronal cell metabolism); the photoproducts formed from
the BODIPY core upon irradiation were much less toxic at
these concentrations (Figure S30). On the contrary, the NIR-
absorbing 1c as well as the corresponding photoproducts
exhibited practically no toxicity within 4 h (SI). As the
endogenous concentrations of H2S in the brain of the
mammals are in the range of 10 nM to 3 μM,52,53 our results
are significantly below the toxicity levels observed for both 1b
and 1c.
In the case of 1c, the assay was complicated by the fact that
the absorption spectra of 1c (λmax = 690) and MB (λmax = 676
and 748 nm) partially overlap (Figure S24). We therefore
C
DOI: 10.1021/acs.orglett.8b02043
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(6) Predmore, B. L.; Lefer, D. J. Expert Rev. Clin. Pharmacol. 2011, 4,
83−96.
(7) Polhemus, D. J.; Li, Z.; Pattillo, C. B.; Gojon, G.; Gojon, G.;
Giordano, T.; Krum, H. Cardiovasc. Ther. 2015, 33, 216−226.
(8) Mani, S.; Untereiner, A.; Wu, L.; Wang, R. Antioxid. Redox
Signaling 2014, 20, 805−817.
We report the synthesis and photochemical behavior of
BODIPY-based molecules releasing H2S upon irradiation in
the presence of carbonic anhydrase. They represent the first
system, which can efficiently liberate H2S in a controllable way
using visible and near-infrared light (up to 700 nm) as an
exogenous trigger under biological conditions. Their phys-
icochemical and biocompatible properties designate the
molecules to be a promising platform for in vivo release of
H2S in a noninvasive fashion, providing a powerful tool for
harnessing its potential therapeutic properties. In addition, the
BODIPY scaffold allows for further tuning of its physical and
optical properties in a simple manner.
́
́
(9) Bełtowski, J.; Wojcicka, G.; Jamroz-Wisniewska, A. Biochem.
Pharmacol. 2018, 149, 60−76.
(10) Paul, B. D.; Snyder, S. H. Biochem. Pharmacol. 2018, 149, 101−
109.
(11) Kang, J.; Li, Z.; Organ, C. L.; Park, C. M.; Yang, C. T.; Pacheco,
A.; Wang, D.; Lefer, D. J.; Xian, M. J. Am. Chem. Soc. 2016, 138,
6336−6339.
(12) Benavides, G. A.; Squadrito, G. L.; Mills, R. W.; Patel, H. D.;
Isbell, T. S.; Patel, R. P.; Darley-Usmar, V. M.; Doeller, J. E.; Kraus, D.
W. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 17977−17982.
(13) Chauhan, P.; Bora, P.; Ravikumar, G.; Jos, S.; Chakrapani, H.
Org. Lett. 2017, 19, 62−65.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02043.
■
S
(14) Steiger, A. K.; Pardue, S.; Kevil, C. G.; Pluth, M. D. J. Am.
Chem. Soc. 2016, 138, 7256−7259.
̌
́
(15) Klan, P.; Solomek, T.; Bochet, C. G.; Blanc, A.; Givens, R.;
Rubina, M.; Popik, V.; Kostikov, A.; Wirz, J. Chem. Rev. 2013, 113,
119−191.
Materials and methods; Synthetic details; NMR and
absorption spectra; HPLC calibration; methylene blue
assay; live-cell imaging data; LEDs emission; toxicity
evaluation (PDF)
̌
́
(16) Solomek, T.; Wirz, J.; Klan, P. Acc. Chem. Res. 2015, 48, 3064−
3072.
(17) Devarie-Baez, N. O.; Bagdon, P. E.; Peng, B.; Zhao, Y.; Park, C.
M.; Xian, M. Org. Lett. 2013, 15, 2786−2789.
(18) Fukushima, N.; Ieda, N.; Sasakura, K.; Nagano, T.; Hanaoka,
K.; Suzuki, T.; Miyata, N.; Nakagawa, H. Chem. Commun. 2014, 50,
587−589.
(19) Fukushima, N.; Ieda, N.; Kawaguchi, M.; Sasakura, K.; Nagano,
T.; Hanaoka, K.; Miyata, N.; Nakagawa, H. Bioorg. Med. Chem. Lett.
2015, 25, 175−178.
(20) Brash, D. E.; Rudolph, J. A.; Simon, J. A.; Lin, A.; McKenna, G.
J.; Baden, H. P.; Halperin, A. J.; Ponten, J. Proc. Natl. Acad. Sci. U. S.
A. 1991, 88, 10124−10128.
(21) Zhao, Y.; Bolton, S. G.; Pluth, M. D. Org. Lett. 2017, 19, 2278−
2281.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: stacko.peter@gmail.com.
*E-mail: klan@sci.muni.cz.
ORCID
́
Petr Klan: 0000-0001-6287-2742
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(22) Zhao, Y.; Henthorn, H. A.; Pluth, M. D. J. Am. Chem. Soc. 2017,
This project has received funding from the European Union’s
Horizon 2020 Research and Innovation Program under the
Marie Skłodowska-Curie, and it is cofinanced by the South
Moravian Region under the Grant Agreement No. 665860
(SoMoPro III Program - Project VLAMBA, Nr. 6SA17811,
139, 16365−16376.
(23) Steiger, A. K.; Yang, Y.; Royzen, M.; Pluth, M. D. Chem.
Commun. 2017, 53, 1378−1380.
(24) Chengelis, C. P.; Neal, R. A. Toxicol. Appl. Pharmacol. 1980, 55,
198−202.
(25) Chengelis, C. P.; Neal, R. A. Biochem. Biophys. Res. Commun.
1979, 90, 993−999.
̌
P.S.). This publication only reflects the authors’ views and the
EU is not liable for any use that may be made of the
information contained herein. Support for this work was also
provided by the Czech Science Foundation (GA18-12477S,
P.K.) and the Czech Ministry of Health (RVO-VFN64165/
2018, L.V.). This research was supported by the RECETOX
Research Infrastructure (LM2015051 and CZ.02.1.01/0.0/
(26) Supuran, C. T.; Scozzafava, A. Bioorg. Med. Chem. 2007, 15,
4336−4350.
(27) Sharma, A. K.; Nair, M.; Chauhan, P.; Gupta, K.; Saini, D. K.;
Chakrapani, H. Org. Lett. 2017, 19, 4822−4825.
(28) Phan, T. G.; Bullen, A. Immunol. Cell Biol. 2010, 88, 438−444.
(29) Dąbrowski, J. M.; Arnaut, L. G. Photochem. Photobiol. Sci. 2015,
14, 1765−1780.
́
̌
0.0/16_013/0001761). We acknowledge Lukas Maier (Masar-
yk University) for assistance with NMR analysis, Miroslava
(30) Goswami, P. P.; Syed, A.; Beck, C. L.; Albright, T. R.;
Mahoney, K. M.; Unash, R.; Smith, E. A.; Winter, A. H. J. Am. Chem.
Soc. 2015, 137, 3783−3786.
́
Bittova (Masaryk University) for HRMS analysis, and Jana
̌
́
Jasprova (Charles University) for performing MTT assays.
(31) Slanina, T.; Shrestha, P.; Palao, E.; Kand, D.; Peterson, J. A.;
́
REFERENCES
Dutton, A. S.; Rubinstein, N.; Weinstain, R.; Winter, A. H.; Klan, P. J.
Am. Chem. Soc. 2017, 139, 15168−15175.
■
(1) Kabil, O.; Banerjee, R. Antioxid. Redox Signaling 2014, 20, 770−
(32) Rubinstein, N.; Liu, P.; Miller, E. W.; Weinstain, R. Chem.
Commun. 2015, 51, 6369−6372.
782.
(2) Wallace, J. L.; Wang, R. Nat. Rev. Drug Discovery 2015, 14, 329−
(33) Peterson, J. A.; Wijesooriya, C.; Gehrmann, E. J.; Mahoney, K.
M.; Goswami, P. P.; Albright, T. R.; Syed, A.; Dutton, A. S.; Smith, E.
A.; Winter, A. H. J. Am. Chem. Soc. 2018, 140, 7343−7346.
(34) Sitkowska, K.; Feringa, B. L.; Szymanski, W. J. Org. Chem. 2018,
83, 1819−1827.
345.
(3) Lefer, D. J. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 17907−
17908.
(4) Polhemus, D. J.; Lefer, D. J. Circ. Res. 2014, 114, 730−737.
(5) Wallace, J. L.; Vong, L.; McKnight, W.; Dicay, M.; Martin, G. R.
Gastroenterology 2009, 137, 569−578.
(35) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107, 4891−4932.
D
DOI: 10.1021/acs.orglett.8b02043
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(36) Allampally, N. K.; Florian, A.; Mayoral, M. J.; Rest, C.;
́
Stepanenko, V.; Fernandez, G. Chem. - Eur. J. 2014, 20, 10669−
10678.
(37) Rybina, A.; Lang, C.; Wirtz, M.; Grußmayer, K.; Kurz, A.;
Maier, F.; Schmitt, A.; Trapp, O.; Jung, G.; Herten, D. P. Angew.
Chem., Int. Ed. 2013, 52, 6322−6325.
(38) Harriman, A.; Stachelek, P.; Sutter, A.; Ziessel, R. Photochem.
Photobiol. Sci. 2015, 14, 1100−1109.
(39) Kamkaew, A.; Lim, S. H.; Lee, H. B.; Kiew, L. V.; Chung, L. Y.;
Burgess, K. Chem. Soc. Rev. 2013, 42, 77−88.
(40) Yogo, T.; Urano, Y.; Ishitsuka, Y.; Maniwa, F.; Nagano, T. J.
Am. Chem. Soc. 2005, 127, 12162−12163.
̌
́
(41) Palao, E.; Slanina, T.; Muchova, L.; Solomek, T.; Vítek, L.;
́
Klan, P. J. Am. Chem. Soc. 2016, 138, 126−133.
́
(42) Al Anshori, J.; Slanina, T.; Palao, E.; Klan, P. Photochem.
Photobiol. Sci. 2016, 15, 250−259.
(43) Ortiz, M. J.; Garcia-Moreno, I.; Agarrabeitia, A. R.; Duran-
́
Sampedro, G.; Costela, A.; Sastre, R.; Lopez Arbeloa, F.; Banuelos
̃
́
Prieto, J.; Lopez Arbeloa, I. Phys. Chem. Chem. Phys. 2010, 12, 7804.
(44) Hatchard, C. G.; Parker, C. A. Proc. R. Soc. London, Ser. A 1956,
235, 518−536.
(45) Moest, R. R. Anal. Chem. 1975, 47, 1204−1205.
(46) Powell, C. R.; Foster, J. C.; Okyere, B.; Theus, M. H.; Matson,
J. B. J. Am. Chem. Soc. 2016, 138, 13477−13480.
̈
(47) Spiller, W.; Wohrle, D.; Schulz-Ekloff, G.; Ford, W. T.;
Schneider, G.; Stark, J. J. Photochem. Photobiol., A 1996, 95, 161−173.
(48) Jensen, F.; Greer, A.; Clennan, E. L. J. Am. Chem. Soc. 1998,
120, 4439−4449.
(49) Lin, V. S.; Lippert, A. R.; Chang, C. J. Proc. Natl. Acad. Sci. U. S.
A. 2013, 110, 7131−7135.
(50) Buchholz, K.; Schirmer, R. H.; Eubel, J. K.; Akoachere, M. B.;
Dandekar, T.; Becker, K.; Gromer, S. Antimicrob. Agents Chemother.
2008, 52, 183−191.
(51) Lin, V. S.; Lippert, A. R.; Chang, C. J. Proc. Natl. Acad. Sci. U. S.
A. 2013, 110, 7131−7135.
(52) Levitt, M. D.; Abdel-Rehim, M. S.; Furne, J. Antioxid. Redox
Signaling 2011, 15, 373−378.
(53) Ishigami, M.; Hiraki, K.; Umemura, K.; Ogasawara, Y.; Ishii, K.;
Kimura, H. Antioxid. Redox Signaling 2009, 11, 205−214.
E
DOI: 10.1021/acs.orglett.8b02043
Org. Lett. XXXX, XXX, XXX−XXX