Page 3 of 3
ChemComm
Fig. 4 Photodecomposition of 5 (100 µM) was monitored by HPLC. (a) 5
without photoirradiation, (b) 5 with photoirradiation for 400 seconds.
Notes and references
50 aGraduate School of Pharmaceutical Sciences, Nagoya City
University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-
8603, Japan. E-mail: deco@phar.nagoya-cu.ac.jp; Fax: +81 052
836 3407; Tel: +81 052 836 3407
DOI: 10.1039/C3CC47421F
To establish the potential utility of 5 for H2S generation in
biological samples, we evaluated photo-induced H2S release from
5 in commercially available fetal bovine serum. In this study, a
500 µM solution of 5 in the serum (1% DMSO as a co-solvent)
was prepared. The solution was then subjected to UV irradiation
at 300–350 nm, and H2S generation was detected by
methyleneblue assay. As shown in Figure 5, we observed
10 photoirradiation-dependent H2S release from 5. Therefore, we
concluded that 5 should be suitable for spatially and temporally
controlled H2S release in complex biological systems.
5
bGraduate School of Pharmaceutical Sciences, The University of
55 Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
cGraduate School of Medical Science Kyoto Prefectural
University of Medicine, 13 Nishitakatsukasa-cho Taishogun
Kita-ku, Kyoto 603-8334, Japan
dPRESTO, Japan Science and Technology Agency (JST), 4-1-8
60 Honcho Kawaguchi, Saitama 332-0012, Japan
† Electronic Supplementary Information (ESI) available:
experimental details and supplemental data.
DOI: 10.1039/b000000x/
See
1
(a) C. Szabo, Nat. Rev. Drug Discovery. 2007, 6, 917; (b) L.
65
70
75
80
85
Li, P. Rose and P. K. Moore, Annu. Rev. Pharmacol. Toxicol.
2011, 51, 169; (c) G. Caliendo, G. Cirino, V. Santagada and
L. J. Wallace, J. Med. Chem. 2010, 53, 6275.
2
(a) W. Zhao, J. Zhang, Y. Lu and R. Wang, The EMBO
Journal 2001, 20, 6008; (b) G. Yang, L. Wu, B. Jiang, W.
Yang, J. Qi, K. Cao, Q. Meng, A. K. Mustafa, W. Mu, S.
Zhang, S. H. Snyder and R. Wang, Science 2008, 322, 587.
K. Abe and H. Kimura, J. Neurosci. 1996, 16, 1066.
R. C. O. Zanardo, V. Brancaleone, E. Distrutti, S. Fiorucci, G.
Cirino and J. L. Wallace, FASEB J., 2006, 20, 2118.
S. Singh, D. Padovani, R. A. Leslie, T. Chiku and R.
Banerjee, J. Biol. Chem., 2009, 284, 22457.
T. Chiku, D. Padovani, W. Zhu, S. Singh, V. Vitvitsky and R.
Banerjee, J. Biol. Chem., 2009, 284, 11601.
N. Shibuya, M. Tanaka, M. Yoshida, Y. Ogasawara, T.
Togawa, K. Ishii and H. Kimura, Antioxid. Redox Signaling,
2009, 11, 703.
Fig. 5 Release of H2S from 5 (500 µM) in bovine serum as detected by
15 the methyleneblue method. Absorbance of formed methyleneblue after
irradiation of 5 was determined at 670 nm. (A) Detection of released H2S
from 5. (a) solution without 5 incubated in the absence of light; (b)
solution containing 5 incubated in the absence of light; (c) solution
without 5 incubated after irradiation; (d) solution containing 5 after
20 irradiation. (B) Solution containing 5 irradiated for 200, 400 and 600
seconds. The data represents the average of three experiments with
standard deviations.
3
4
5
6
7
Finally, we examined the photochemical properties of
compound 5. The quantum yield of 5 was determined with a
25 potassium ferrioxalate actinometer based on decomposition of
5.15 The value of φ at 313 nm was 0.42 ± 0.08. Compound 5
showed an absorption peak at 313 nm (ε = 2.35 × 103 M-1cm-1).
The efficiency of use of the incident uncaging light was
calculated to be 987, expressed as ε × φ. A solution of 5 (10 mM)
30 in DMSO was stable when stored for five months at −30 °C in the
dark, as determined by means of HPLC. Compound 5 is thus
sufficiently stable for biological applications as a H2S donor.
In conclusion, we have developed a directly photocontrollable
H2S donor that generates H2S proportionally to irradiation time
35 and intensity, with release of a benign photoproduct. The release
of H2S from 5 was confirmed by methylene blue assay and by the
use of fluorescent probe HSip-1. Photorelease of H2S from 5 was
also confirmed to proceed in bovine serum. These results indicate
that 5 has the potential to serve as a tool for elucidating the
40 poorly understood physiological roles of H2S.
This work was supported by the JST PRESTO program (H.N.)
from Japan Science and Technology Agency, as well as by a
Grant-in-Aid for Scientific Research on Innovative Areas
(Research in Proposed Research Area) (No. 21117514 to H.N.)
45 and a Grant-in-Aid for Scientific Research (No. 22590103 to
H.N.) from the Ministry of Education, Culture, Sports Science
and Technology Japan, and a Sasakawa Scientific Research Grant
from The Japan Scientific Society (No. 25-311, N.F.).
8
9
N. O. Devarie-Baez, P. E. Bagdon, B. Peng, Y. Zhao, C. Park
and M. Xian, Org. Lett., 2013, 15, 2786.
Y. V. Il’ichev, M. A. Schwörer and J. Wirz, J. Am. Chem.
Soc., 2004, 126, 4581.
10 K. Sasakura, K. Hanaoka, N. Shibuya, Y. Mikami, Y. Kimura,
T. Komatsu, T. Ueno, T. Terai, H. Kimura and T. Nagano, J.
Am. Chem. Soc., 2011, 133, 18003.
11 P. Zuman and B. Shah, Chem. Rev. 1994, 94, 1621.
90 12 M. Lukeman and J. C. Scaiano, J. Am. Chem. Soc., 2005, 127,
7698.
13 (a) L. M. Siegel, Anal. Biochem. 1965, 11, 126; (b) Y. Zhao,
H. Wang and M. Xian, J. Am. Chem. Soc., 2011, 133, 15.
14 E. R. DeLeon, G. F. Stoy and K. R. Olson, Anal. Biochem.
95
2012, 421, 203.
15 S. L. Murov, Handbook of Photochemistry; Marcel Dekker,
Inc.: New York, 1973; pp 119−123.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3