C O M M U N I C A T I O N S
The ESI-MS spectra (Figure 4 bottom) of the reaction solutions
revealed some similarity but marked the difference of the reactions
among the ROS with [Fe(DTCS)3]3-. Nitric oxide reacted with
[Fe(DTCS)3]3- cleanly to give [Fe(I)(NO)(DTCS)2]2- (considering
NO as NO+,10 the angle of Fe-N-O is 172°11) and an oxidatively
dimerized ligand (thiuram disulfide).6,12 In contrast, the reaction
with hydrogen peroxide swiftly generated thiuram disulfide, N-
(dithioperoxocarboxy)sarcosine, and uncharacterized iron species.
Similar to H2O2, the reaction with hypochlorite also produced
thiuram disulfide, N-(dithioperoxocarboxy)sarcosine, and an iron(III)
complex [Fe(III)(DTCS)2]2- at m/z ) 381.9. The results suggested
that H2O2 and ClO- acted merely as oxidants to decompose
[Fe(III)(DTCS)3]3- with a slight alternation of the absorbance at
595 nm. In sharp contrast, NO acted not only as a one-electron
reductant but also as a strong field ligand (in its oxidized form,
NO+) that caused a dramatic blue shift of the UV-vis spectrum.
Therefore it could switch on the fluorescence of the QD by shutting
down the energy transfer pathway. The oxidation of the lost ligand
did not require the presence of oxygen because, under air-free
conditions, the reaction still occurred readily. The oxidation of the
DTCS to its dimer was likely caused by iron(III), which decreased
the oxidation state by two as it apparently received one electron
each from NO and DTCS, respectively. The resulting DTCS radical
then dimerized to form thiuram disulfide.6,12
nitric oxide in living cells.15 Uncoated CdSe QDs were known to
be highly sensitive in the quantification of hydrogen peroxides
through the fluorescence quenching mechanism.16 Yet, there was
no report on sensing ROS by the fluorescence “switch-on”
mechanism, which is preferred as it has low background interference
and higher sensitivity. Our Fe(III)-QD-nanoprobe described herein
can be easily assembled and can be further fine-tuned to achieve
even greater sensitivity and compatibility with different settings
such as cell line or gaseous nitric oxide measurement in a highly
selective and sensitive manner.
In conclusion, we demonstrated here the first example of a
fluorescent probe consisting of a transition metal complex and QD
in sensing nitric oxide with good sensitivity and excellent selectivity
by taking advantage of the strong ligand field property and reducing
property of nitric oxide. It is apparent that the combination of the
rich optical property of a vast number of transition metal complexes
and the desirable fluorescent property of semiconductor QDs may
lead to novel probes for sensing reactive oxygen species and small
molecule ligands.
Acknowledgment. The authors are grateful for the financial
support of the Science and Engineering Research Council (SERC)
of the Agency for Science, Technology and Research (A*Star) of
Singapore. Grant Number: 072-101-0015. D.H. thanks Ken Caulton
for critical comments and suggestions on the manuscript.
Supporting Information Available: Synthesis methods for the
nanoprobe and characterization procedures; different ROS sensing
procedure with the nanoprobe; UV-vis spectra and absorbance changes
at 595 nm upon reaction with different ROS additions; photolumines-
cence quenching behaviors of QDs by surface bound and free iron
dithiocarbamates. This material is available free of charge via the
References
(1) (a) Culotta, E.; Koshland, D. E., Jr. Science 1992, 258, 1862–1864. (b)
Isenberg, J. S.; Martin-Manso, G.; Maxhimer, J. B.; Roberts, D. D. Nat.
ReV. Cancer 2009, 9, 182–194.
(2) (a) Nagano, T.; Yoshimura, T. Chem. ReV. 2002, 102, 235–1269. (b) Lim,
M. H.; Lippard, S. J. Acc. Chem. Res. 2007, 40, 41–51. (c) Miles, A. M.;
Wink, D. A.; Cook, J. C.; Grisham, M. B. Method Enzymol. 1996, 268,
105–120.
(3) Zhang, C. Y.; Yeh, H. C.; Kuroki, M. T.; Wang, T. H. Nat. Mater. 2005,
4, 826–831.
(4) Yoshimura, T.; Yokoyama, H.; Fujii, S.; Takayama, F.; Oikawa, K.;
Kamada, H. Nat. Biotechnol. 1996, 14, 992–994.
(5) Fujii, S.; Yoshimura, T.; Kamada, H. Chem. Lett. 1996, 785–786.
(6) Fujii, S.; Kobayashi, K.; Tagawa, S.; Yoshimura, T. J. Chem. Soc., Dalton
Trans. 2000, 3310–3315.
(7) (a) Jansson, M.; Stilbs, P. J. Phys. Chem. 1987, 91, 113–116. (b) Anacker,
E. W.; Underwood, A. J. J. Phys. Chem. 1981, 85, 2463–2466. (c) Toullec,
J.; Couderc, S. Langmuir 1997, 13, 1918–1924.
(8) Keefer, L. K.; Nims, R. W.; Davies, K. M.; Wink, D. A. Methods Enzymol.
1996, 268, 281–293.
Figure 4. Reaction scheme of Fe(III)(DTCS)3 with nitric oxide, hydrogen
peroxide, and sodium hypochlorite and the corresponding ESI-MS spectra
of the resulting solution 5 min after the addition of ROS.
(9) (a) Furlani, C.; Luciani, M. L. Inorg. Chem. 1968, 7, 1586–1592. (b)
Coucouvanis, D. In Progress in Inorganic Chemistry; Lippard, S. J., Ed.;
John Wiley & Sons: New York, 1979; Vol. 26, pp 301-470.
(10) Ogasawara, M.; Huang, D.; Streib, W. E.; Huffman, J. C.; Gallego-Planas,
N.; Maseras, F.; Eisenstein, O.; Caulton, K. G. J. Am. Chem. Soc. 1997,
119, 8642–8651.
A fluorometric method for NO detection is preferred because it
is convenient and has potential for in situ spatial and temporal
monitoring of NO generation and bioactivity. Nagano and co-
workers developed a series NO probes containing o-phenylenedi-
amine derived fluorophores.13 The fluorescence of the probe was
switched on upon oxidation by dinitrogen trioxide (N2O3) which
was formed from the NO oxidation in the presence of oxygen.
Lippard and co-workers developed an interesting fluorescein-based
Cu(II) complex probe.14 The fluorescence of the probe was switched
on upon reaction with NO by converting the aliphatic amine into
nitrosoamine accompanied by the dissociation of the reduced
cuprous ion from the complex. The probe was applied in imaging
(11) Davies, G. R.; Jarvis, J. A. J.; Kilbourn, B. T.; Mais, R. H. B.; Owston,
P. G. J. Chem. Soc. A 1970, 8, 1275–1283.
(12) Fujii, S.; Yoshimura, T. Coord. Chem. ReV. 2000, 198, 89–99.
(13) Sasaki, E.; Kojima, H.; Nishimatsu, H.; Urano, Y.; Kikuchi, K.; Hirata,
Y.; Nagano, T. J. Am. Chem. Soc. 2005, 127, 3684–3685.
(14) Lim, M. H.; Wong, B. A.; Pitcock, W. H.; Mokshagundam, D.; Baik, M.;
Lippard, S. J. J. Am. Chem. Soc. 2006, 128, 14364–14373.
(15) Lim, M. H.; Xu, D.; Lippard, S. J. Nat. Chem. Biol. 2006, 2, 375–380.
(16) Hay, K. X.; Waisundara, V. Y.; Zong, Y.; Han, M.; Huang, D. J. Small
2007, 3, 290–293.
JA904824W
9
11694 J. AM. CHEM. SOC. VOL. 131, NO. 33, 2009