A highly selective phosphorescent chemodosimeter for cysteine and homocysteine based on platinum(II) complexes

Article abstract of DOI:10.1016/j.ica.2008.11.026

A platinum(II) complex Pt(phen)C{triple bond, long}CC₆H₄CHO has been demonstrated as a highly selective phosphorescent chemodosimeter for cysteine and homocysteine. Upon addition of homocysteine or cysteine to its acetonitrile-water

Full text of DOI:10.1016/j.ica.2008.11.026

Inorganica Chimica Acta 362 (2009) 2577–2580
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Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
A highly selective phosphorescent chemodosimeter for cysteine
and homocysteine based on platinum(II) complexes
*
*
Kewei Huang, Hong Yang, Zhiguo Zhou , Huili Chen, Fuyou Li , Tao Yi, Chunhui Huang
Department of Chemistry and Laboratory of Advanced Materials, Fudan University, 220 Handan Road, Shanghai 200433, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 August 2008
Received in revised form 24 November 2008
Accepted 26 November 2008
Available online 9 December 2008
A platinum(II) complex Pt(phen)C„CC6H4CHO has been demonstrated as a highly selective phosphores-
cent chemodosimeter for cysteine and homocysteine. Upon addition of homocysteine or cysteine to its
acetonitrile–water solution, an evident luminescent color variation from green to orange was observed.
This red-shift of phosphorescence emission could be attributed to formation of a thiazinane through a
selective reaction of aldehyde group of Pt(phen)C„CC6H4CHO with cysteine/homocysteine, which was
confirmed by 1H NMR investigation and density functional theory (DFT) calculations. The further selec-
tivity investigation indicates that it displays high selectivity for homocysteine and cysteine, and therefore
can be utilized as cysteine/homocysteine phosphorescent chemodosimeter.
Keywords:
Phosphorescence
Chemodosimeter
Platinum complex
Cysteine
Ó 2008 Elsevier B.V. All rights reserved.
Homocysteine
1. Introduction
would lead to many diseases, such as hematopoiesis decrease,
leucocyte loss, and psoriasis [9], while Hcy is a risk factor for
The design of highly selective and sensitive receptors for ana-
lytes has attracted much attention in the past several decades
[1]. Especially, there have been an expanding number of reports
on the utilization of transition-metal complexes as chemosensors
with increasing awareness of the interesting photophysical proper-
ties associated with the metal-to-ligand charge-transfer (MLCT)
excited state. Among them, iridium (III), rhenium (I) and ruthe-
nium (II) complexes have successfully been explored as phospho-
rescent chemosensors for anion [2], oxygen concentration [3] and
metal ions [4].
cardiovascular [10] and Alzheimer’s disease [11]. However, only
one transition-metal iridium (III) complexes with advantageous
photophysical properties has been applied as Cys/Hcy probes
[12].
In this study, we extended to develop a platinum(II) complex
Pt(phen)(C„CC6H5CHO)2 (1) [13] (Scheme 1) as a phosphorescent
probe for Cys and Hcy. In addition, a platinum (II) complex without
aldehyde group (2) (Scheme 1) was also investigated as a contrast
compound of 1.
Due to the excellent photophysical properties such as relatively
long-lifetime phosphorescence resulting in separated from fluores-
cent backgrounds easily, some platinum(II) complexes were used
as chemsensors. Che et al. have explored diiminoplatinum (II)
complex as luminescent sensor for metal ions [5] and cyclometa-
lated platinum (II) complexes as pH sensor [6]. And recently,
Yam and coworkers synthesized a novel luminescence chemosen-
sor of metal ions based on platinum (II) complex [7] containing
crown groups. There are still large improving room in terms of
molecules of biological interests, such as amino acids, amines
and thiols.
2. Results and discussion
2.1. Synthesis of Compounds 1 and 2
Synthesis of Pt(phen)(C„CC6H5CHO)2 (1).
Complex 1 was synthesized according to the previous litera-
tures [14]. A 450 mg (1.01 mmol) sample of Pt(phen)Cl2, 50 mg
of CuI, 8 mL of diethylamine and 40 mL of dichloromethane were
stirred for 10 minutes. After addition of 286 mg (2.20 mmol) of
4-ethynylbenzaldehyde, the mixture was stirred at room tempera-
ture for 18 h. The yellow mixture was evaporated to dryness, dis-
solved in dichloromethane, and loaded on the silica column with
dichloromethane as eluents. Yield: 90%. 1H NMR (500 MHz,
DMSO-d6, TMS): d = 9.98 (2H, s), 9.69 (2H, d, J = 5.5 Hz), 9.02 (2H,
d, J = 8 Hz), 8.27 (2H, s), 8.22 (dd, 2H, J = 5.0 Hz, J = 5.5 Hz), 7.85
As the merely two thiol-containing natural amino acids in hu-
man body, cysteine (Cys) and homocysteine (Hcy) are crucial to
the physiological balance in living system [8]. Deficiency of Cys
(4H, d, J = 8 Hz), 7.62 (4H, d, J = 8.5 Hz). FT-IR:
m mC„C).
/cmÀ1 2107 (
* Corresponding authors. Tel./fax: +86 21 55664185.
E-mail addresses: zgzhou@fudan.edu.cn (Z. Zhou), fyli@fudan.edu.cn (F. Li).
MS (MALDI-TOF): m/z 634 [M+H]+.
0020-1693/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2008.11.026

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K. Huang et al. / Inorganica Chimica Acta 362 (2009) 2577–2580
S
2.3. Optical response of 1 to Cys/Hcy
COOH
N
H
H2N
HS
COOH
The photophysical investigation indicates that the existence of
an aldehyde group as an electron-withdrawing group significantly
affects the luminescence of 1 compared with that of 2. Besides,
N
N
HS
Pt
CHO
CHO
H
COOH
COOH
N
N
N
selective reaction of the aldehyde moiety with b- and
c-amin-
Pt
S
oalkylthiol groups to form thiazolidines has been extensively ap-
plied in Cys and Hcy detection. Inspired by these results, we
surmised that the platinum (II) complex 1 with an aldehyde group
could be used as a luminescent probe for Cys and Hcy.
The recognition of Cys/Hcy with 1 was determined by spectro-
photometric method. The solution of 1 with various concentrations
NH2
COOH
1
S
N
H
N
N
Pt
N
H
N
Pt
COOH
N
of Cys/Hcy in acetonitrile–water (40 lM, pH 7.2, 4:1 v/v) were kept
S
at 37 °C, and then UV–VIS absorption and other spectra test were
carried out. As shown in Fig. 2, agradual increase of Hcy in the solu-
tion of 1 leads to clear changes in its absorption spectrum. The
high-energy band at ꢀ330 nm assigned to n ? p* transition due
to the presence of an aldehyde group decreased gradually upon
addition of Hcy, at the same time, the increase of the band centred
2
Scheme 1. The chemical structures of compounds 1 and 2 and the probable sensing
mechanism of 1 towards Hcy and Cys.
Synthesis of Pt(phen)(C„CC6H5)2 (2)
at 270 nm was observed corresponding to
p ? p
* transition of dii-
The procedure followed for 1 was used except that 1 mL
(1.01 mmol) of freshly distilled phenlacetylene was used. Yield:
75%. 1H NMR (500 MHz, DMSO-d6, TMS): d = 9.81 (2H, d,
J = 6.5 Hz), 9.04 (2H, d, J = 10.0 Hz), 8.30 (2H, s), 8.24 (2H, dd,
J = 10.0 Hz, J = 6.5 Hz), 7.41 (4H, d, J = 8.5 Hz), 7.30 (4H, pseudo-t,
mie and acetylide-based intra-ligand transitions. The same phe-
nomena were observed with the addition of Cys (Supporting
Information Figure S1). These results implied that the reaction of
the aldehyde group of 1 and Cys/Hcy occurred.
Due to its sensitivity to small change, emission spectroscopy is
widely applied for sensors. Here, the recognition of 1 towards Cys
and Hcy was also investigated by photoluminescence technique
and the spectra of 1 upon addition of Hcy are shown in Fig. 3. Upon
addition of Hcy, the emission band was red-shifted from 510 nm to
J = 8.0 Hz, J = 9.5 Hz), 7.19 (2H, pseudo-t, J = 7.0 Hz, J = 9.0 Hz). m/
cmÀ1 2104 (
[M+H]+.
mC„C); 1683 (mC@O). MS (MALDI-TOF): m/z 578
2.2. Photophysical properties of 1 and 2
The absorption and room-temperature photoluminescence (PL)
spectra of 1 and 2 in acetonitrile–water (40 M, pH 7.2, 4:1 v/v) are
l
shown in Fig. 1. In this case, 1 and 2 exhibit a wide band centred at
ꢀ400 nm, which has been previously assigned as the charge-trans-
fer transition corresponding to excitation from a filled Pt (d) orbital
*
to an unoccupied
p diimine orbital (MLCT) [15,16]. In addition,
the absorbance less than 400 nm of 1 should be attributed to dii-
mine and acetylide-based intra-ligand transitions, whereas the
absorption band of 2 was located at 270 nm.
Meanwhile, the photoluminescent properties of the two com-
plexes 1 and 2 were also investigated (Fig. 1). Complex 2 exhibited
an intense orange emission band centered at 560 nm, while the
maximum emission wavelength of 1 was blue-shifted to 510 nm,
corresponding to the green luminescence. This blue shift could
be ascribed to an increase of the electron-withdrawing ability of
the aldehyde group in 1. In addition, the luminescent quantum
Fig. 2. Changes in UV–VIS absorption spectra of 1 in acetonitrile–water solution
(40 lM, pH 7.2, 4:1 v/v) with various amounts of Hcy (0–4 mM).
yield of 1 in such air-equilibrated acetonitrile–water (40 lM, pH
7.2, 4:1 v/v) solution was measured to be 1.4% [17].
Fig. 3. Changes in the phosphorescence emission spectra of 1 in acetonitrile–water
solution (40 M, pH 7.2, 4:1 v/v) with various amounts of Hcy (0–4 mM)
l
Fig. 1. The absorption and emission spectra of 1 and 2 in CH3CN–H2O solution
(40 M, pH 7.2, 4:1 v/v).
(kex = 365 nm). Inset: images of 1 in acetonitrile–water solution in the presence
and absence of 4 mM Hcy.
l

K. Huang et al. / Inorganica Chimica Acta 362 (2009) 2577–2580
2579
555 nm, corresponding to a luminescence color change from green
to orange. These changes are supported by the fact that the acety-
lide is varied as the donor of the ligand increases, so the metal-
based HOMO rises in energy leading to a shift of the emission to
longer wavelengths.
Furthermore, the time dependence of the response of 1 to Cys/
Hcy was monitored by means of photoluminescence spectroscopy.
The results revealed that the reaction of 1 and Cys/Hcy in acetoni-
trile–water solution (40 lM, pH 7.2, 4:1 v/v), reached completion
well within 120 minutes (Supporting Information Figure S2).
Therefore, this system is well suitable for the use of Cys/Hcy
detection.
Fig. 5. 1H NMR spectra of 1, 1-Cys, 1-Hcy in DMSO-d6. The resonances centered at
9.98 is assigned to the aldehyde of 1.
The apparent disappearance of the aldehyde resonance
(9.98 ppm) of 1 upon addition of Cys/Hcy indicated the interaction
of aldehyde moiety with Cys/Hcy, accompanied with a signal up-
shift of ortho-H of the phenyl group, from 7.40 ppm to 7.85 ppm.
The up-shift of the proton signal basically results from the electron
density increases.
2.4. Selective luminescence response of 1 to Cys/Hcy
As an excellent luminescent probe, high selectivity is essential.
To validate the selectivity of 1 in practice, besides Cys/Hcy, various
other natural amino acids including
(Leu), -asparagine (Asp), -arginine (Arg),
nine (Thr), -proline (Pro), -isoleucine (IsoLeu),
-methionine (Met), -valine (Val), -alanine (Ala),
-glutamine (Glu-ine), -glutamic acid (Glu),
-lysine (Lys), and -glycine (Gly) were
L
-histidine (His),
-tyrosine (Tyr),
-tryptophan (Try),
-phenylalanine
-serine (Ser),
L
-leucine
L
L
L
L
-threo-
To further understand the effect of the aldehyde group on the
photophysical properties, calculations based on DFT for 1, 1-Hcy
and 1-Cys were performed. Orbital analysis revealed that, for 1,
1-Hcy and 1-Cys, no obvious change was observed for the lowest
unoccupied molecular orbital (LUMO) distributions (Table 1). For
1, the HOMO distribution was localized averagely on the anionic li-
gands including aldehyde substituent. In contrast, the HOMO dis-
tributions of 1-Hcy and 1-Cys were also located on the anionic
ligands but not located on the thiazoliding (thiazinane). As a result,
the HOMO energy level of 1-Hcy and 1-Cys were higher. The
HOMO–LUMO energy gaps were calculated as 2.53, 2.15 and
2.20 eV for 1, 1-Hcy and 1-Cys, respectively, which are in agree-
ment with the remarkable red-shift in the luminescence spectra
of 1-Hcy and 1-Cys compared to that of 1. With reference to previ-
ous electrochemical studies of related platinum (II) complexes, the
irreversible oxidation wave is ascribed to a Pt(II) to Pt(III) oxidation
process. In general, the oxidation wave was found to occur at more
positive potential for the complexes with less electron-rich alkynyl
ligands, so 1, 1-Hcy and 1-Cys exhibit an irreversible oxidation
wave at 0.94, 0.58 and 0.50 V, respectively, resulting in the energy
L
L
L
L
L
L
L
(Phe),
L
L
L
L-hydroxyproline (Hyd),
L
L
added into the acetonitrile–water solution of 1 (pH 7.2, 4:1 v/v).
Under the same condition, no obvious changes were measured in
the emission spectra of 1 in the presence of these amino acids.
Even the structurally related thiol peptide (such as reduced gluta-
thione, GSH) was served likewise, and its no response was also ob-
served (Fig. 4). In addition, the variation of the emission spectra of
1 induced by Hcy was not influenced when simultaneous addition
of 100 equiv. of other amino acids or GSH, respectively. Similar
observation was obtained for the selectivity and competition
experiments of the response of 1 to Cys (supporting information
Figure S5 and Figure S6). These results indicate that 1 displays a
high selectivity for Cys/Hcy.
2.5. Recognition mechanism of 1 towards Cys/Hcy
To testify the recognization mechanism for 1 as Cys/Hcy probe,
the adducts of 1 with Cys/Hcy were characterized by 1H NMR
(Fig. 5).
of the d
p(Pt) orbital in the order 1-Hcy (1-Cys) < 1.
Table 1
HOMO and LUMO distributions of 1, 1-HCy and 1-Cys.
HOMO LUMO
1
1-HCy
Fig. 4. Changes of the luminescence intensity at 555 nm (L555) over the intensity at
510 nm (L510) of 1 (40 lM) upon the addition of various amino acids and GSH
(4 mM) in acetonitrile/water (4:1, v/v, pH 7.2). White bars represent the lumines-
cence response of 1 to the amino acid of interest, and the black bars represent the
simultaneous addition of Hcy to 4 mM in above solutions. Other amino acids
1-Cys
include
tyrosine (Tyr),
(Try), -methionine (Met),
glutamine (Glu-ine), -glutamic acid (Glu),
glycine (Gly) and glutathione (GSH). Excitation was provide at 365 nm.
L
-histidine (His),
-threonine (Thr),
-valine (Val),
L
-leucine (Leu),
-proline (Pro),
-alanine (Ala),
-serine (Ser),
L
-asparagine (Asp),
L
-arginine (Arg),
L
-
L
L
L
-isoleucine (IsoLeu),
L
-tryptophan
L
L
L
L
-phenylalanine (Phe),
L
-
-
L
L
L-hydroxyproline (Hyd),
L

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K. Huang et al. / Inorganica Chimica Acta 362 (2009) 2577–2580
[4] W.S. Tang, X.X. Lu, K.M.C. Wong, V.W.W. Yam, J. Mater. Chem. 15 (2005)
In conclusion, we have presented a highly selective chemodos-
2714.
imeter for Hcy and Cys with an evident luminescent color variation
from green to orange. The red-shift of phosphorescence emission
upon addition of homocysteine or cysteine could be attributed to
formation of a thiazinane through the reaction of aldehyde group
with cysteine/homocysteine. It is very useful to expand the appli-
cation of phosphorescent complexes.
[5] P.K.M. Siu, S.W. Lai, W. Lu, N.Y. Zhu, C.M. Che, Eur. J. Inorg. Chem. 15 (2003)
2749.
[6] (a) K.H. Wong, M.C.W. Chan, C.M. Che, Chem. Eur. J. 5 (1999) 2845;
(b) K.M. Phyllis, S.W. Lai, W. Lu, N.Y. Zhu, C.M. Che, Eur. J. Inorg. Chem. 24
(2003) 2749.
[7] (a) H.S. Lo, S.K. Yip, K.M.C. Wong, N.Y. Zhu, V.W.W. Yam, Organometallics 25
(2006) 3537;
(b) V.W.W. Yam, R.P.L. Tang, K.M.C. Wong, C.C. Ko, K.K. Cheung, Inorg. Chem.
40 (2001) 571;
(c) V.W.W. Yam, R.P.L. Tang, K.M.C. Wong, C.C. Ko, K.K. Cheung,
Organometallics 20 (2001) 4476.
Acknowledgments
[8] N. Shao, J.Y. Jin, S.M. Cheung, R.H. Yan, W.H. Chan, T. Mo, Angew. Chem., Int. Ed.
45 (2006) 4944.
The authors thank the financial supports of National Natural
Science Foundation of China (20501006, 20775017 and
20801015), NCET-06-0353, Shanghai Leading Academic Discipline
Project (B108) and Huo Yingdong Education Foundation (104012)
for financial support.
[9] M. Zhang, M.X. Yu, F.Y. Li, M.W. Zhu, M.Y. Li, Y.H. Gao, L. Li, Z.Q. Liu, J.P. Zhang,
D.Q. Zhang, T. Yi, C.H. Huang, J. Am. Chem. Soc. 129 (2007) 10322.
[10] H. Refsum, P.M. Ueland, O. Nygard, S.E. Vollset, Annu. Rev. Med. 49 (1989) 31.
[11] 11.S. Seshadri, A. Beiser, J. Selhub, P.F. Jacques, I.H. Rosenberg, R.B. D’Agostino,
P.W.F. Wilson, New Engl. J. Med. 346 (2002) 476.
[12] H.L. Chen, Q. Zhao, Y.B. Wu, F.Y. Li, H. Yang, T. Yi, C.H. Huang, Inorg. Chem. 46
(2007) 11075.
[13] (a) S. Chakraborty, T.J. Wadas, H. Hester, C. Flaschenreim, R. Schmehl, R.
Eisenberg, Inorg. Chem. 44 (2005) 6284;
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.ica.2008.11.026.
(b) P.W. Du, J. Schneider, F. Li, W. Zhao, U. Patel, F.N. Castellano, R. Eisenberg, J.
Am. Chem. Soc. 130 (2008) 5056;
(c) P.W. Du, J. Schneider, P. Jarosz, J. Zhang, W.W. Brennessel, R. Eisenberg, J.
Phys. Chem. B 111 (2007) 6887.
References
[14] (a) M. Hissler, W.B. Connick, D.K. Geiger, J.E. McGarrah, D. Lipa, R.J. Lachicotte,
R. Eisenberg, Inorg. Chem. 39 (2000) 447;
(b) S.C. Chan, M.C.W. Chan, Y. Wang, C.M. Che, K.K. Cheung, N.Y. Zhu, Chem.
Eur. J. 7 (2001) 4180.
[15] T.J. Wadas, R.J. Lachicotte, R. Eisenberg, Inorg. Chem. 42 (2003) 3772.
[16] C.E. Whittle, J.A. Weinstein, M.W. George, K.S. Schanze, Inorg. Chem. 40 (2001)
4053.
[1] (a) R. Martinez-Manez, F. Sancenon, Chem. Rev. 103 (2003) 4419;
(b) C. Suksai, T. Tuntulani, Chem. Soc. Rev. 32 (2003) 192;
(c) P.D. Beer, P.A. Gale, Angew. Chem., Int. Ed. 40 (2001) 486.
[2] Z.H. Lin, Y.G. Zhao, C.Y. Duan, B.G. Zhang, Z.P. Bai, Dalton Trans. (2006) 3678.
[3] R.P. Brinas, T. Troxler, R.M. Hochstrasser, S.A. Vinogradov, J. Am. Chem. Soc. 127
(2005) 11851.
[17] K. Nakamura, Bull. Chem. Soc. Jpn. 55 (1982) 2697.