Aspartic Acid-Promoted Highly Selective and Sensitive Colorimetric

Article pubs.acs.org/ac

Aspartic Acid-Promoted Highly Selective and Sensitive Colorimetric Sensing of Cysteine in Rat Brain Qin Qian, Jingjing Deng, Dalei Wang, Lifen Yang, Ping Yu,* and Lanqun Mao* Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China S Supporting Information *

ABSTRACT: Direct selective determination of cysteine in the cerebral system is of great importance because of the crucial roles of cysteine in physiological and pathological processes. In this study, we report a sensitive and selective colorimetric assay for cysteine in the rat brain with gold nanoparticles (Au-NPs) as the signal readout. Initially, Au-NPs synthesized with citrate as the stabilizer are red in color and exhibit absorption at 520 nm. The addition of an aqueous solution (20 μL) of cysteine or aspartic acid alone to a 200 μL Au-NP dispersion causes no aggregation, while the addition of an aqueous solution of cysteine into a Au-NP dispersion containing aspartic acid (1.8 mM) causes the aggregation of Au-NPs and thus results in the color change of the colloid from wine red to blue. These changes are ascribed to the ion pair interaction between aspartic acid and cysteine on the interface between Au-NPs and solution. The concentration of cysteine can be visualized with the naked eye and determined by UV−vis spectroscopy. The signal output shows a linear relationship for cysteine within the concentration range from 0.166 to 1.67 μM with a detection limit of 100 nM. The assay demonstrated here is highly selective and is free from the interference of other natural amino acids and other thiolcontaining species as well as the species commonly existing in the brain such as lactate, ascorbic acid, and glucose. The basal dialysate level of cysteine in the microdialysate from the striatum of adult male Sprague−Dawley rats is determined to be around 9.6 ± 2.1 μM. The method demonstrated here is facile but reliable and durable and is envisaged to be applicable to understanding the chemical essence involved in physiological and pathological events associated with cysteine.

H

functional nanostructures that can be used to achieve the selectivity for cysteine detection. In this study, we demonstrate a novel method for highly selective and sensitive sensing of cerebral cysteine. The rationale for the sensing essentially stems from the intrinsic structure of the cysteine molecule. First, cysteine bears a thiol group, which can interact with gold through the formation of a Au−S bond. This property essentially forms a straightforward basis for developing a new principle for simple colorimetric sensing of cysteine through aggregation-induced changes in the color and UV−vis spectrum of a gold nanoparticle (Au-NP) dispersion. As reported recently, Au-NP-based colorimetric assays have been particularly attractive for simple detection of various kinds of analytes, even physiologically important species, and have been of great concern recently because of their technical simplicity and mechanistic designability.4 Second, in physiological pH, cysteine bears a negatively charged carboxyl group (pKa = 1.71) and a positively charged amino group (pKa = 10.78). This intrinsic structural property

ighly selective and sensitive detection of physiologically important species involved in brain functions is of great importance for understanding chemical essences involved in the physiological and pathological events.1 As one kind of thiolcontaining amino acid, cysteine plays important roles in the cerebral system. For instance, cysteine-induced hypoglycemic brain damage has been proposed as an alternative mechanism to excitotoxicity and is related with the pathogenesis of several neurological disorders such as Parkinson’s and Alzheimer’s disease.2 Although some methods such as high-performance liquid chromatography, voltammetry, and fluorescence spectroscopy have been demonstrated for in vitro cysteine detection,2c,3 the high complexity of the cerebral system substantially makes direct selective detection of cerebral cysteine a long-standing challenge. This is the case because, on one hand, the coexistence of cysteine analogues including thiol-containing species (e.g., cystine, homocysteine, and glutathione) and other kinds of amino acids in the cerebral system, unfortunately, invalidates existing methods for the direct detection of cerebral cysteine. On the other hand, the mechanisms employed so far for electrochemically and optically probing brain chemistry cannot be explored for selective detection of cysteine since there are neither enzymes nor © 2012 American Chemical Society

Received: August 26, 2012 Accepted: October 2, 2012 Published: October 2, 2012 9579

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584

Analytical Chemistry

Article

continuously boiled for 30 min until a red mixture was obtained. The mixture was cooled to room temperature and then filtrated through a Millipore syringe (0.45 μm) to remove the precipitate, and the filtrate was then stored in a refrigerator at 4 °C for use. The size of the synthetic nanoparticles was about 13 nm, which was confirmed by TEM image and UV−vis spectroscopy (TU-1900 spectrophotometer, Beijing Purkinje General Instrument Co. Ltd., China) with an absorption peak at around 520 nm (data not given). Colorimetric Sensing of Cysteine in aCSF. The samples were all prepared by dissolving cysteine directly into the aCSF. However, the concentration of salt in aCSF was about 160 mM, and such a high concentration of salt can directly induce the aggregation of Au-NPs, which may affect the assay demonstrated in this study. In order to eliminate the interference from the highly concentrated salts in aCSF, the aCSF was 2-fold diluted with Milli-Q water to prepare cysteine solutions with different concentrations prior to each measurement. For the colorimetric detection of cysteine in aCSF, a reaction mixture was first prepared by mixing the aqueous solution of 20 mM aspartic acid (20 μL) into 5 nM Au-NPs (200 μL) in a vial. After 2 min, 20.0 μL of different concentrations of cysteine in 2-fold-diluted aCSF was added into 220 μL of Au-NP dispersions containing 1.8 mM aspartic acid, and the resulting mixtures were then incubated for 10 min at 37 °C. The initial concentrations of cysteine in 20 μL of 2-fold-diluted aCSF were 2, 4, 8, 12, and 20 μM. In Vivo Microdialysis. Animal surgery and in vivo microdialysis were carried out with the procedures reported in our earlier works.7 Briefly, adult male Sprague−Dawley rats (250−300 g) purchased from Health Science Center, Peking University, were housed with a 12:12 h light−dark schedule with food and water ad libitum. The microdialysis guide cannula (BAS/MD-2250, BAS) was implanted into the striatum using standard stereotaxic procedures. Throughout the surgery, the body temperature of the animals was maintained at 37 °C with a heating pad. After the rats were allowed to recover for at least 24 h, a microdialysis probe was first implanted into the rat striatum and then perfused with aCSF at 3.0 μL/min. After continuously perfusing the probe for at least 90 min for equilibration, the microdialysate was collected for the colorimetric analysis. Colorimetric Sensing of Cerebral Cysteine. For colorimetric detection of cysteine in the brain microdialysate, the microdialysate sampled from striatum was first 2-fold diluted with Milli-Q water, and 20 μL of the diluted brain microdialysate was added into 220 μL of the Au-NP dispersion containing aspartic acid (1.8 mM). The mixture was then photographed with a digital camera (Canon IXUS951S, Japan). For the quantitative assay of cysteine in the striatum microdialysate, the resulting mixture was then diluted to 600 μL with Milli-Q water for UV−vis spectrometric measurements.

provides an opportunity to achieve the selectivity for cysteine sensing through an ion pair interaction. The ion pair interaction is mainly a Coulombic interaction, and its strength is directly related to the molecular structure and the charged groups.5c Moreover, compared with the simple Coulombic interaction, an ion pair interaction can be directional especially when structured organic ions are involved, which can be employed to establish highly selective analytical methods through rationally tailoring the strength of the interactions.5 A previous attempt has revealed that a positively charged amino group and a negatively charged carboxyl group could form an intermolecular ion pair, and such ion pair interaction has been widely used in supramolecular chemistry.5c By rationally designing the surface chemistry of Au-NPs and tuning the strength of the intermolecular ion pair interaction between a positively charged amino group and a negatively charged carboxyl group, we demonstrate here a highly selective colorimetric method for direct sensing of cysteine in the cerebral system, through a combination with in vivo microdialysis for dialysate sampling (Scheme 1). As far as we know, Scheme 1. Aspartic Acid-Promoted Colorimetric Sensing of Cerebral Cysteine Coupled with in Vivo Microdialysis

this is the first report on the direct selective sensing of cerebral cysteine, which is envisaged to pave a new pathway to monitoring brain chemistry in a simple fashion.

■

EXPERIMENTAL SECTION Chemicals and Reagents. Cysteine, dopamine (DA), ascorbate acid (AA), uric acid (UA), 3,4-dihydroxyphenylacetic acid (DOPAC), homocysteine, and glutathione were purchased from Sigma-Aldrich and used as supplied. L(+)-Lactate acid (90%) was obtained from Acros Organics. Chloroauric acid (HAuCl4·4H2O), trisodium citrate, and other chemicals of at least analytical reagents were obtained from Beijing Chemical Corporation (Beijing, China) and used without further purification. Artificial cerebrospinal fluid (aCSF) was prepared by mixing NaCl (126 mM), KCl (2.4 mM), KH2PO4 (0.5 mM), MgCl2 (0.85 mM), NaHCO3 (27.5 mM), Na2SO4 (0.5 mM), and CaCl2 (1.1 mM) into Milli-Q water. Aqueous solutions of DA, AA, UA, DOPAC, lactate, glutathione, cystine, and homocysteine were freshly prepared with aCSF prior to experiments. All aqueous solutions were prepared with Milli-Q water (18.2 MΩ cm−1). Synthesis of Au-NPs. Au-NPs with a diameter of about 13 nm were synthesized as reported previously.6 Briefly, 10 mL of 38.8 mM trisodium citrate was added into 100 mL of 1 mM HAuCl4 boiling solution, and the resulting solution was then

■

RESULTS AND DISCUSSION Mechanstic Investigation on Colorimetric Sensing of Cysteine. To accomplish the direct colorimetric sensing of cysteine through aggregation-induced changes in the color and UV−vis spectrum of the Au-NP dispersion based on ion pair interaction, various kinds of compounds with at least one charged moiety at each end were added into the aqueous dispersion of Au-NPs to investigate their capability to act as cross-linkers to selectively trigger the aggregation of Au-NPs 9580

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584

Analytical Chemistry

Article

with only two terminal carboxyl groups such as malonate and succinic acid were found to be able to trigger the aggregation of Au-NPs by subsequent addition of the alkaline amino acids including lysine, histidine, and arginine into the dispersion of Au-NPs (Figure S-2, vials 2, 3, and 4). These alkaline amino acids have one end terminated with at least one nitrogencontaining moiety that can possibly interact with Au-NPs through electrostatic interaction and/or formation of a Au−N bond. Thus, the alkaline amino acids-triggered Au-NP aggregation with the copresence of malonate or succinic acid could presumably be explained in terms of the ion pair interaction between the carboxyl groups in the cross-linkers and the amino groups in the alkaline amino acids. The results demonstrated above, unfortunately, invalidate the uses of molecules with only terminal carboxyl groups at each end as the cross-linkers for the selective sensing of cysteine. Interestingly, we found that the copresence of the amino group with the terminal carboxyl group at one end of the molecules such as aspartic acid and glutamic acid substantially induces the aggregation of Au-NPs to be triggered only by cysteine, as depicted in Figure 1b, vials 4 and 5, and Figure 1c, purple and blue curves, suggesting both kinds of amino acids could be used as the cross-linkers for selective detection of cysteine. This property could be elucidated by the intermolecular ion pair interactions between cysteine self-assembled onto the surface of Au-NPs and the cross-linkers employed. A close comparison of the UV−vis spectra displayed in Figure 1c (purple and blue curves) indicates that aspartic acid produces a higher signal intensity (i.e., the ratio of A650/A520; A650 and A520 represent the absorption at 650 and 520 nm, respectively) as compared with glutamic acid. Aspartic acid was thus used as the cross-linker for the colorimetric cysteine sensing in the following studies. We should note that, while meso-2,3diaminosuccinic acid may also be used as a potential crosslinker for this study in terms of its molecular structure, it is not easily commercially available. Selectivity and Sensitivity. By using aspartic acid as the cross-linker, we next studied the selectivity of the colorimetric method for cysteine sensing. Among all species that may potentially interfere with selective cysteine sensing, thiolcontaining small molecules such as cystine, homocysteine, and glutathione were first taken into account because they have a high structural similarity to cysteine and are endogenously present in the cerebral system. The selectivity of the colorimetric sensing was investigated by testing the responses of the assay toward these thiol-containing compounds. In this case, aqueous solutions of cysteine, cystine, glutathione, and homocysteine were freshly prepared with 2-fold-diluted aCSF and then added to the Au-NP dispersion containing aspartic acid. As shown in Figure 2, only cysteine causes an aggregation of the Au-NPs, which was verified by the naked eye and UV− vis spectroscopy. These results substantially demonstrate that the present method has a high selectivity against these thiolcontaining analogues. This high selectivity may be considered to arise from the specific ion pair interaction between cysteine and aspartic acid, as demonstrated in Scheme 1. Although homocysteine bears a very similar structure to cysteine, the longer carbon chain increases the structural flexibility, which may decrease the possibility of ion pair formation with cysteine. Moreover, in the cerebral system, homocysteine is present in a much lower concentration than cysteine.9 Besides, as could be seen from Figure 2c (blue and wine curves), the presence of 100 μM

caused by subsequent addition of cysteine. Among the crosslinkers studied, the sole addition of diamines (i.e., 1, 2diaminoethane and 1,3-diaminopropane, structures shown in Figure 1a) into the aqueous dispersion of Au-NPs leads to the

Figure 1. (a) Molecular structures of the compounds studied in terms of their capability as cross-linkers to trigger the aggregation of Au-NPs. (b) Photographs and (c) UV−vis spectra of aqueous dispersions of Au-NPs containing different compounds with the addition of cysteine. The mixtures were prepared by adding 20 μL of cysteine (20 μM) into 220 μL of Au-NP dispersions containing 1.8 mM of different compounds indicated in the figure. After being incubated for 10 min at 37 °C, each of the resulting mixtures was diluted to 600 μL with Milli-Q water for UV/vis spectroscopic detection.

obvious aggregation of Au-NPs (Figure S-1, vials 6 and 7). This may arise from the electrostatic interaction between the negatively charged Au-NPs and the positively charged amino group and/or the Au−N interaction as reported previously.8 This result rules out the possibility of using this kind of compound as cross-linkers to enable cysteine-triggered aggregation of Au-NPs for subsequent sensing. Different from the phenomena observed with diamines, the sole addition of compounds with a negatively charged carboxyl group at each end (i.e., malonate and succinic acid) does not result in the aggregation of Au-NPs (Figure S1, vials 1, 2, 3, 4, and 5), whereas the further addition of cysteine into these mixtures containing malonate or succinic acid clearly leads to the aggregation of Au-NPs, as could be clearly seen from the changes in the color (Figure 1b, vials 2 and 3) and UV−vis spectra of the dispersions (Figure 1c, green and red curves). This result essentially indicates that the presence of negatively charged carboxyl groups in the cross-linkers remains essential to induce aggregation of the Au-NPs in this study through ion pair interactions between amino groups in cysteine and carboxyl groups in the cross-linkers. However, the cross-linkers 9581

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584

Analytical Chemistry

Article

exploration of the intrinsic structural property of cysteine and on the rational design of the surface chemistry of Au-NPs through tailoring the strength of the ion pair interaction is very specific for cerebral cysteine sensing. To evaluate the sensitivity of the assay, different concentrations of cysteine in aCSF were added into the aqueous dispersion of Au-NPs containing aspartic acid to trigger the aggregation of Au-NPs and further evoke the obvious changes in the Au-NP dispersion, both in color (from red to purpleblue) and in the UV−vis spectrum (a decreased absorption at 520 nm (A520) and an increased absorption at 650 nm (A650)). These changes eventually form a straightforward basis for visualization and colorimetric sensing of cysteine. The ratio of A650/A520 increases with the concentration of cysteine in aCSF and shows a linear response toward cysteine in Au-NP dispersions (240 μL) within a concentration range from 0.166 to 1.67 μM (A650/A520 = 0.60 C/μM + 0.09, R2 = 0.99, Figure 3). The detection limit was 100 nM, calculated from S/ N = 3.

Figure 2. (a) Molecular structures of analogues of cysteine. (b) Photographs and (c) UV−vis spectra of aqueous dispersions of AuNPs containing aspartic acid with the addition of different compounds. The mixtures were prepared by adding 20 μL of different compounds into 220 μL of Au-NP dispersions containing 1.8 mM aspartic acid. After being incubated for 10 min at 37 °C, each of the resulting mixtures was diluted to 600 μL with Milli-Q water for UV/vis detection. The initial concentrations of analogous solutions added into Au-NP dispersions were 15 μM cysteine, 100 μM glutathione, 100 μM cystine, and 5 μM homocysteine.

glutathione or 100 μM cystine does not lead to the aggregation of Au-NPs with aspartic acid as the cross-linker. This selectivity may be understood by the structural diversities of these molecules and thereby different interaction capabilities with AuNPs and/or with aspartic acid cross-linker. These results essentially suggest that the exploitation of the specific ion pair interaction between aspartic acid and cysteine could offer a direct colorimetric assay of cysteine against others kinds of thiol-containing species. We next investigated the selectivity against other natural amino acids that have similar structures to cysteine, containing negatively charged carboxyl and positively charged amino groups. With the addition of each kind of amino acid into the aqueous dispersion of Au-NPs containing aspartic acid, only that of cysteine produces significant signal output (Figure S-3), demonstrating the high selectivity of this method against these amino acids. This selectivity may result from the thiol group on the cysteine, since other amino acids do not have a thiol group and consequently may not induce the aggregation of Au-NPs. In addition, the selectivity against physiologically important species such as DOPAC, DA, UA, AA, glucose, and lactate coexisting with cysteine in the cerebral system was also investigated (Figure S4). The addition of each of these species does not trigger the aggregation of Au-NPs with aspartic acid as the cross-linker. It is worthy to note that the selectivity against the thiol-containing proteins was not considered since there are no concentrated proteins in the cerebral microdialysis due to the use of microdialysis for in vivo sampling. All these results substantially demonstrate that the present method based on the

Figure 3. (a) Photographs and (b) UV−vis spectra of Au-NP dispersions prepared by the addition of various concentrations of cysteine to Au-NP dispersions containing 1.8 mM aspartic acid. The final concentrations of cysteine in the resulting Au-NP dispersions (240 μL) were 166, 333, 666, 1000, and 1666 nM. After being incubated for 10 min at 37 °C, each of the resulting mixtures was diluted to 600 μL with Milli-Q water for UV/vis detection. Inset: Plot of A650/A520 against CCys. Each point is the average of four independent experiments. Error bars indicate standard deviations.

Colorimetric Sensing of Cysteine in Rat Brain. To demonstrate the application of the as-established Au-NP-based assay for selectively sensing cysteine in the rat brain, the 2-folddiluted brain microdialysate (20 μL) was added into 220 μL of an aqueous dispersion of Au-NPs containing 1.8 mM aspartic acid. After being incubating for 10 min at 37 °C, the resulting mixture was diluted to 600 μL for UV−vis detection. As shown in Figure 4a, the addition of the brain microdialysate into the Au-NP dispersion containing aspartic acid cross-linker leads to a slight change in the color of the Au-NP dispersion from red to somewhat purple (Figure 4a, vial 3). To verify that the aggregation of Au-NPs was induced by ion pair interaction between cysteine in the brain microdialysate and aspartic acid in the Au-NP dispersion, the diluted brain microdialysate was added into a pure Au-NP dispersion (i.e., without aspartic acid cross-linker). In this case, no color change was observed 9582

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584

Analytical Chemistry

Article

far as we know, this is the first demonstration of the direct sensing of cysteine in the rat brain. The successful determination of cysteine in the cerebral system is envisaged to be applicable to monitoring brain chemistry in a simple fashion and understanding the chemical essence involved in some physiological and pathological events. This study essentially paves the way to a new analytical platform to understand brain chemistry through a supramolecular route.

■

ASSOCIATED CONTENT

S Supporting Information *

Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*E-mails: Ping Yu, [email protected]; Lanqun Mao, lqmao@ iccas.ac.cn. Fax: +86-10-62559373. Notes

Figure 4. (a) Photographs and (b) UV−vis spectra of Au-NP dispersions (5 nM, 200 μL) with the additions of different solutions. Black curve and vial 1: with sole addition of aspartic acid solution (20 μL, 20 mM); red curve and vial 2: with sole addition of 2-fold-diluted brain microdialysate (20 μL); blue curve and vial 3: with addition of aspartic acid solution (20 μL, 20 mM) and 2-fold-diluted brain microdialysate (20 μL). After being incubated for 10 min at 37 °C, each of the resulting mixtures was diluted to 600 μL with Milli-Q water for UV/vis detection.

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This research was financially supported by the NSF of China (Grant Nos. 20975104, 20935005 21127901, and 21210007 for L.M. and 91132708 for P.Y.), the National Basic Research Program of China (973 program, 2010CB33502), and Chinese Academy of Sciences (KJCX2-YW-W25 and Y2010015).

■

(Figure 4a, vial 2). This control experiment virtually demonstrates that the tailor-made ion pair interaction between cysteine and aspartic acid cross-linker remains very essential for the direct selective sensing of cysteine. We note that aspartic acid endogenously existing in the cerebral system does not interfere with the detection because of its lower concentration than that (e.g., 1.8 mM) added into the Au-NP dispersion.10 Moreover, the addition of brain microdialysate into the Au-NP dispersion containing aspartic acid results in a similar change in the UV−vis spectrum (Figure 4b) to that with the addition of standard cysteine, further demonstrating the presence of cysteine in the microdialysate, which was consistent with the color change induced by the brain microdialysate. According to the calibration curve described above (A650/A520 = 0.60 C/μM + 0.09, R2 = 0.99, Figure 3), the initial value of the basal level of cysteine in rat brain microdialysates was determined to be 9.6 ± 2.1 μM (n = 3), which was almost consistent with the reported values.11 These properties substantially demonstrate that the colorimetric assay developed in this study by exploring the intrinsic structural property of cysteine and tailor-making the ion pair interaction between cysteine would offer an effective way to direct selective sensing of cysteine in the cerebral system.

REFERENCES

(1) (a) Zhang, M.; Yu, P.; Mao, L. Acc. Chem. Res. 2012, 45, 533− 543. (b) Robinson, D. L.; Hermans, A.; Seipel, A. T.; Wightman, R. M. Chem. Rev. 2008, 108, 2554−2584. (c) Khan, A. S.; Michael, A. C. Trends Anal. Chem. 2003, 22, 503−508. (d) Watson, C. J.; Venton, B. J.; Kennedy, R. T. Anal. Chem. 2006, 78, 1391−1399. (e) Zhang, M.; Mao, L. Front. Biosci. 2005, 10, 345−352. (2) (a) Go, Y. M.; Jones, D. P. Free Radical Biol. Med. 2011, 50, 495− 509. (b) Sawamoto, O.; Hagiwara, R.; Kurisu, K. Exp. Toxicol. Pathol. 2004, 56, 45−52. (c) Wang, W.; Rusin, O.; Xu, X.; Kim, K. K.; Escobedo, J. O.; Fakayode, S. O.; Fletcher, K. A.; Lowry, M.; Schowalter, C. M.; Lawrence, C. M.; Fronczek, F. R.; Warner, I. M.; Strongin, R. M. J. Am. Chem. Soc. 2005, 127, 15949−1595. (d) Quig, D. Altern. Med. Rev. 1998, 3, 262−270. (e) Spencer, J. P. E.; Jenner, P.; Daniel, S. E.; Lees, A. J.; Marsden, D. C.; Halliwell, B. J. Neurochem. 1998, 71, 2112−2122. (f) Zhang, F.; Dryhurst, G. J. Med. Chem. 1994, 37, 1084−1098. (g) Canet-Avilés, R. M.; Wilson, M. A.; Miller, D. W.; Ahmad, R.; McLendon, C.; Bandyopadhyay, S.; Baptista, M. J.; Ringe, D.; Petsko, G. A.; Cookson, M. R. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 9103−9108. (h) Puka-Sundvall, M.; Sandberg, M.; Hagberg, H. Brain Res. 1998, 797, 328−332. (3) (a) Xu, H.; Hepel, M. Anal. Chem. 2011, 83, 813−819. (b) Shao, N.; Jin, J. Y.; Cheung, S. M.; Yang, R. H.; Chan, W. H.; Mo, T. Angew. Chem., Int. Ed. 2006, 45, 4944−4948. (c) Feng, D.; Liu, G.; Zheng, W.; Liu, J.; Chen, T.; Li, D. Chem. Commun. 2011, 47, 8557−8559. (d) Rusin, O.; Luce, N. N., St.; Agbaria, R. A.; Escobedo, J. O.; Jiang, S.; Warner, I. M.; Dawan, F. B.; Lian, K.; Strongin, R. M. J. Am. Chem. Soc. 2004, 126, 438−439. (e) Wang, W.; Rusin, O.; Xu, X.; Kim, K. K.; Escobedo, J. O.; Fakayode, S. O.; Fletcher, K. A.; Lowry, M.; Schowalter, C. M.; Lawrence, C. M.; Fronczek, F. R.; Warner, I. M.; Strongin, R. M. J. Am. Chem. Soc. 2005, 127, 15949−15958. (f) Lee, J. S.; Ulmann, P. A.; Han, M. S.; Mirkin, C. A. Nano Lett. 2008, 8, 529− 533. (g) Shao, J.; Sun, H.; Guo, H.; Ji, S.; Zhao, J.; Wu, W.; Yuan, X.; Zhang, C.; James, T. D. Chem. Sci. 2012, 3, 1049−1061. (4) (a) Jiang, Y.; Zhao, H.; Zhu, N.; Lin, Y.; Yu, P.; Mao, L. Angew. Chem., Int. Ed. 2008, 47, 8601−8604. (b) Li, B.; Du, Y.; Dong, S. Anal. Chim. Acta 2009, 644, 78−82. (c) Jiang, Y.; Zhao, H.; Lin, Y.; Zhu, N.; Ma, Y.; Mao, L. Angew. Chem., Int. Ed. 2010, 49, 4800−4804. (d) Liu,

■

CONCLUSIONS In summary, by fully exploring the intrinsic structural property of cysteine and rationally tailoring the surface chemistry of AuNPs as well as carefully tuning the strength of the intermolecular ion pair interaction between a positively charged amino group and a negatively charged carboxyl group, we demonstrate a highly selective colorimetric method for direct sensing of cysteine in the cerebral system. The method bears advantages in theoretical simplicity, and low technical and instrumental demands and could thus be very attractive for the reliable detection of cysteine in the rat brain microdialysate. As 9583

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584

Analytical Chemistry

Article

D.; Chen, W.; Sun, K.; Deng, K.; Zhang, W.; Wang, Z.; Jiang, X. Angew. Chem., Int. Ed. 2011, 50, 4103−4107. (e) Kalluri, J. R.; Arbneshi, T.; Khan, S. A.; Neely, A.; Candice, P.; Varisli, B.; Washington, M.; McAfee, S.; Robinson, B.; Banerjee, S.; Singh, A. K.; Senapati, D.; Ray, P. C. Angew. Chem., Int. Ed. 2009, 48, 9668− 9671. (f) Kong, B.; Zhu, A.; Luo, Y.; Tian, Y.; Yu, Y.; Shi, G. Angew. Chem., Int. Ed. 2011, 50, 1837−1840. (g) Liu, D.; Chen, W.; Wei, J.; Li, X.; Wang, Z.; Jiang, X. Anal. Chem. 2012, 84, 4185−4191. (h) Zhu, K.; Zhang, Y.; He, S.; Chen, W.; Shen, J.; Wang, Z.; Jiang, X. Anal. Chem. 2012, 84, 4267−4270. (i) Li, J.; Fu, H.; Wu, L.; Zheng, A.; Chen, G.; Yang, H. Anal. Chem. 2012, 84, 5309−5315. (j) Derbyshire, N.; White, S. J.; Bunka, D. H. J.; Song, L.; Stead, S.; Tarbin, J.; Sharman, M.; Zhou, D.; Stockley, P. G. Anal. Chem. 2012, 84, 6595− 6602. (5) (a) Corbellini, F.; Di Costanzo, L.; Crego-Calama, M.; Geremia, S.; Reinhoudt, D. N. J. Am. Chem. Soc. 2003, 125, 9946−9947. (b) Ikeda, M.; Tanaka, Y.; Hasegawa, T.; Furusho, Y.; Yashima, E. J. Am. Chem. Soc. 2006, 128, 6806−6807. (c) Rehm, T. H.; Schmuck, C. Chem. Soc. Rev. 2010, 39, 3597−3611. (d) Willerich, I.; Gröhn, F. Chem.Eur. J. 2008, 14, 9112. (e) Schmuck, C. Chem.Eur. J. 2000, 6, 709−718. (f) Gröger, G.; Stepanenko, V.; Würthner, F.; Schmuck, C. Chem. Commun. 2009, 698−700. (6) Grabar, K. G.; Freeman, R. G.; Hommer, M. B.; Natan, M. J. Anal. Chem. 1995, 67, 735−743. (7) (a) Lin, Y.; Liu, K.; Yu, P.; Xiang, L.; Li, X.; Mao, L. Anal. Chem. 2007, 79, 9577−9583. (b) Lin, Y.; Zhu, N.; Yu, P.; Su, L.; Mao, L. Anal. Chem. 2009, 81, 2067−2074. (8) (a) Thomas, K. G.; Kamat, P. V. J. Am. Chem. Soc. 2000, 122, 2655−2656. (b) Niemeyer, C. M. Angew. Chem., Int. Ed. 2001, 40, 4128−4158. (c) Zhao, W.; Brook, M. A.; Li, Y. ChemBioChem 2008, 9, 2363−2371. (9) (a) Ganguly, P. K.; Maddaford, T. G.; Edel, A. L.; O, K.; Smeda, J. S.; Pierce, G. N. Brain Res. 2008, 1226, 192−198. (b) Li, Y.; Vijayanathan, V.; Gulinello, M.; Cole, P. D. Pharmacol., Biochem. Behav. 2010, 95, 428−433. (10) (a) Lada, M. W.; Vickroy, T. W.; Kennedy, R. T. Anal. Chem. 1997, 69, 4560−4565. (b) Zhou, S. Y.; Zuo, H.; Stobaugh, J. F.; Lunte, C. E.; Lunte, S. M. Anal. Chem. 1995, 67, 594−599. (11) Xu, F.; Wang, L.; Gao, M.; Jin, L.; Jin, J. Anal. Bioanal. Chem. 2002, 372, 791−794.

9584

dx.doi.org/10.1021/ac3024608 | Anal. Chem. 2012, 84, 9579−9584