achieve controllable H2S delivery which could have other
interesting applications. Such studies are undergoing in our
laboratory.
Acknowledgments
This work is supported by the National Institutes of Health
(R01HL116571) to MX and DJL and the Petroleum Research
Fund administrated by the American Chemical Society (ACS-
PRF 55140-UR4) to YL. BP was recipient of a Graduate
Fellowship provided by WSU Alcohol and Drug Abuse Research
Program.
Scheme 2 Structures of the additional polysulfides tested
Table 3 Reactions between HEH/BNAH and compounds 4-7 (reactions were
conducted in ethanol under dark. The concentrations of HEH or BNAH were
50 mM and the concentrations of 4-7 were 100 mM).
References
1.
Li, L.; Moore, P. K. Annu. Rev. Pharmacol. Toxicol.
2011, 51, 169.
Entry
Polysulfide Yield of 2
Yield of 3
95%
2.
3.
Wang, R. Physiol Rev, 2012, 92, 791.
94%
90%
94%
90%
1
2
3
4
4
5
6
7
98%
99%
75%
Fukuto, J. M.; Carrington, S. J.; Tantillo, D. J.;
Harrison, J. G.; Ignarro, L. J.; Freeman, B. A.; Chen,
A.; Wink, D. A. Chem. Res. Toxicol. 2012, 25, 769.
4.
Zhao, Y.; Biggs, T. D.; Xian, M. Chem. Commun. 2014,
50, 11788.
To further understand the reactions between NADH models
and polysulfides, we studied the kinetics of reaction of BNAH
with S8 in ethanol containing dichoromethane (3/1, v/v). S8 was
selected in this study because of its high purity. BNAH has a
characteristic UV absorption peak at 350 nm while S8 has a very
weak absorbance at this wavelength. Monitoring the decay of
BNAH’s UV absorption at 350 nm with time under pseudo-first-
order conditions allowed us to determine the pseudo-first-order
rate constants (kobs). In these experiments, BNAH (1 mM) was
treated with large excess of S8 (20, 30, 40 and 50 mM) at 37 °C.
The pseudo-first-order reaction rate constants were determined
by linear fits of -ln(At-A∞) plotted versus reaction time (t) (see
the supporting information). The effect of S8 concentration on the
pseudo-first-order rate constants gave rise to a linear plot with an
intercept close to zero, showing that the reaction is also first-
order in S8 (Figure 4). The second-order rate constant of this
reaction was calculated to be 0.074 M-1min-1.
5.
6.
Kimura, H. Amino Acids, 2011, 41, 113.
Predmore, B. L.; Lefer, D. J.; Gojon, G. Antioxid.
Redox Signaling, 2012, 17, 119.
7.
8.
Olson, K. R. Antioxid. Redox Signaling, 2012, 17, 32
Kolluru, G. K.; Shen, X.; Bir, S. C.; Kevil, C. G. Nitric
Oxide, 2013, 35, 5.
9.
Ono, K.; Akaike, T.; Sawa, T.; Kumagai, Y.; Wink, D.;
Tantillo, D. J.; Hobbs, A. J.; Nagy, P.; Xian, M.; Lin, J.;
Fukuto, J. M. Free Radical Biol. Med. 2014, 77, 82.
10.
11.
12.
Jacob, C.; Anwar, A.; Burkholz, T. Planta Med. 2008,
74, 1580.
Hughes, M. N.; Centelles, M. N.; Moore, P. K. Free.
Radic. Biol. Med. 2009, 47, 1346.
Ishigami, M.; Hiraki, K.; Umemura, K.; Ogasawara, Y.;
Ishii, K.; Kimura, H. Antioxid. Redox Signaling, 2009,
11, 205.
13.
14.
15.
16.
Pollak, N.; Dölle, C.; Ziegler, M. Biochem. J. 2007,
402, 205.
Nagel, Z. D.; Klinman, J. P. Chem. Rev. 2006, 106,
3095.
Wang, L.; Goodey, N. M.; Benkovic, S. J.; Kohen, A.
Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 15753.
Voet, D.; Voet, J. G.; Pratt, C. W. Fundamentals of
Biochemistry, 4th Edition, 2013, John Wiley & Sons,
New York.
Figure 4 Linear plot of the pseudo-first-order rate constant kobs(min-1) versus
the concentrations of S8. The slope is the second-order rate constant k(M-
1min-1) for this reaction.
17.
18.
19.
Filipovic, M. R. Handb Exp Pharmacol. 2015, 230, 29.
Yasui, S.; Ohno, A. Bioorg. Chem. 1986, 14, 70.
In conclusion, we report here the model studies of the
reactions between NADH models and sulfane sulfurs. HEH and
BNAH were used as NADH models and polysulfides were used
as sulfane sulfur models. We confirmed that such reactions could
lead to the oxidation of NADH models and the production of
H2S. This might be another source of H2S generation in cells. As
can be expected, the non-enzymatic H2S production process was
found to be slow, indicating its limited contribution to overall
H2S biosynthesis in cells. However, it provides a new way to
Maharjan, B.; Raghibi Boroujeni, M.; Lefton, J.; White,
O. R.; Razzaghi, M.; Hammann, B. A.; Derakhshani-
Molayousefi, M.; Eilers, J. E.; Lu, Y, J. Am. Chem. Soc.
2015, 137, 6653.
20.
Zhu, X. Q.; Deng, F. H.; Yang, J. D.; Li, X. T.; Chen,
Q.; Lei, N. P.; Meng, F. K.; Zhao, X. P.; Han, S. H.;