Colorimetric detection of histidine in aqueous solution by Ni2+ complex of a thiazolylazo dye based on indicator displacement mechanism

Article abstract of DOI:10.1016/j.tetlet.2018.09.052

A colorimetric naked-eye chemosensor for histidine (His) was established by mixing a thiazolylazo dye and Ni²⁺ in a 1:1 M ratio (TAMSMB-Ni²⁺). Due to the interaction of Ni²⁺ with His, TAMSMB was regenerated upon the addition of His to TAMSMB-Ni²⁺ to lead a significant hypsochromic shift in absorption spectra accompanied by a visual color change from red to yellow which can be directly observed by the naked eye. On the other hands, other amino acids did not trigger any significant changes in absorption properties and solution color. Moreover, it exhibited the selective recognition of His without obvious interference from other amino acids. Thus, TAMSMB-Ni²⁺ can act as a simple and efficient colorimetric chemosensor for His with sensitivity and selectivity in aqueous solution.

Full text of DOI:10.1016/j.tetlet.2018.09.052

Accepted Manuscript
Colorimetric detection of histidine in aqueous solution by Ni2+ complex of a
thiazolylazo dye based on indicator displacement mechanism
Tatsuya Nagae, Shunichi Aikawa, Koshiro Inoue, Yasumasa Fukushima
PII:
S0040-4039(18)31154-7
https://doi.org/10.1016/j.tetlet.2018.09.052
TETL 50291
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
31 July 2018
13 September 2018
20 September 2018
Please cite this article as: Nagae, T., Aikawa, S., Inoue, K., Fukushima, Y., Colorimetric detection of histidine in
aqueous solution by Ni2+ complex of a thiazolylazo dye based on indicator displacement mechanism, Tetrahedron
Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.09.052
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Colorimetric detection of histidine in aqueous solution by Ni2+ complex of a thiazolylazo dye based on
indicator displacement mechanism
Tatsuya Nagae1, Shunichi Aikawa2, Koshiro Inoue1, Yasumasa Fukushima1*
1 Faculty of Science and Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
2 Research Institute of Industrial Technology, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
* Corresponding author. Tel.: +81492391379; fax: +81492311031
E-mail address: fukusima_m@toyo.jp
Abstract
A colorimetric naked-eye chemosensor for histidine (His) was established by mixing a thiazolylazo dye and Ni2+ in a
1:1 molar ratio (TAMSMB-Ni2+). Due to the interaction of Ni2+ with His, TAMSMB was regenerated upon the addition
of His to TAMSMB-Ni2+ to lead a significant hypsochromic shift in absorption spectra accompanied by a visual color
change from red to yellow which can be directly observed by the naked eye. On the other hands, other amino acids did
not trigger any significant changes in absorption properties and solution color. Moreover, it exhibited the selective
recognition of His without obvious interference from other amino acids. Thus, TAMSMB-Ni2+ can act as a simple and
efficient colorimetric chemosensor for His with sensitivity and selectivity in aqueous solution.
Keywords: Colorimetric detection, Chemosensor, Histidine, Thiazolylazo dye, Nickel ion
1

1. Introduction
The selective and sensitive detection of environmentally and biologically relevant important analytes
including amino acids, anions, and metal ions has nowadays received considerable attention because of the involvement
in a wide variety of biological processes.1-20 Among amino acids, His is an indispensable constituent of proteins and
plays an important role in the growth and repair of tissue.21 His exists at the active site of many enzymes because its
imidazole group can act as the chelate ligand and be dissociated at almost a neutral pH range.22 Furthermore, it is a
precursor of histamines and works as neurotransmitter or neuromodulator in both the brain and the central nervous
systems.23 A deficiency of His causes chronic kidney disease, Friedreich ataxia, epilepsy, and Parkinson’s disease,
whereas an excess of His induces metabolic disorders or histidinemia.24-28 Thus, because abnormal levels of His in the
body are closely associated with a variety of diseases, the selective and sensitive quantification of His in biological
fluids can be of great interest and provide important information for clinical diagnosis.
Therefore, to date, several analytical methods including resonance light scattering,29 surface enhanced Raman
scattering,30 capillary electrophoresis,31 liquid chromatography,32 electrochemistry,33 fluorescence spectrometry,34,35 and
colorimetric assay36 have been explored to analyze His quantitatively. Among these techniques, the colorimetric method
has attracted much attention because of more advantages over the other techniques, such as the operational simplicity,
convenience, low cost, and naked-eye visualization. However, to the best of our knowledge, despite the existence of His
in aqueous media, not too much colorimetric chemosensors for the detection of His in pure aqueous solution have been
reported in the literature.37,38 Moreover, most of the reported chemosensors have been prepared by organic synthetic
methods, while commercially available compounds offer several advantages in terms of cost effectiveness, simplicity,
no need of organic synthesis process.
Compared with the colorimetric method based on the chromophore covalently bonded with the receptor, the
indicator displacement assay (IDA) method based on the indicator-metal complex is a successful strategy due to no
tedious organic synthesis by the simple combinations of indicators and metal ions in solution.39 Recently, although
many indicator-metal complexes have been utilized in sensing various anions and amino acids,40-42 there have been few
reports on chemosensors for the colorimetric detection of His by the IDA method.42
2

4-Methyl-5-(sulfomethylamino)-2-(2-thiazolylazo)benzoic acid (TAMSMB) has been utilized in clinical and
chemical fields for quantitative determination of Cu2+ in serum.43 It contains thiazolylazo and benzoic acid moieties as
shown in Scheme 1, which is a commercially available and water-soluble colorimetric indicator for several metal ions
such as Co3+ and Ni2+.44,45 Previous studies have reported that His acts as a ligand for Ni2+ in several proteins46 and
binds to Ni2+ to form the complex in aqueous solution.34,37,47 Herein, we describe a chemosensor based on the
TAMSMB-Ni2+ complex for selective and sensitive detection of His
in
by the IDA method. TAMSMB is well known as a colorimetric detection reagent for several
metal ions in aqueous solution. However, as far as we know, there is no report of a metal complex of TAMSMB which
can detect analytes such as anions and amino acids by the IDA method. Notably, TAMSMB-based Ni2+ complex is the
first example of a colorimetric probe for detecting His.
Scheme 1 Chemical structure of TAMSMB.
2. Results and discussions
The addition of Ni2+ or Cu2+ to TAMSMB resulted in the color change from yellow to red or blue,
respectively, suggesting that TAMSMB can form the complexes with Ni2+ and Cu2+, while other typical metal ions
including Cd2+, Co2+, Fe2+, Fe3+, Hg2+, Pb2+, and Zn2+ yielded no color change of TAMSMB solution. Both of the
TAMSMB-Ni2+ and TAMSMB-Cu2+ complexes were treated by His to return to an original yellow color, however,
TAMSMB-Cu2+ were restored to TAMSMB even by treatment with cysteine (Cys). Therefore, we chose
TAMSMB-Ni2+ for the selective colorimetric detection of His based on the IDA method.
Initially, to assess the optical properties of TAMSMB-Ni2+ complex formation, the absorption spectra were
measured when aqueous solution of TAMSMB was titrated with Ni2+ in 10 mM phosphate buffer solution (pH 6.5) at
room temperature (Fig. 1). The absorption spectrum of TAMSMB exhibited an absorption band centered at 475 nm in
the absence of Ni2+. As gradually increasing the concentration of Ni2+, the absorbance at 475 nm decreased, while a new
3

red-shift absorption band centered at 552 nm appeared, with a significant visible color change from yellow to red. Thus,
the absorption bathochromic shift of TAMSMB toward Ni2+ may be mainly attributed to the metal-to-ligand
charge-transfer.
The stoichiometric ratio between TAMSMB and Ni2+ was evaluated through a Job's plot experiment to
display the formation of the 1:1 stoichiometry complex between TAMSMB and Ni2+ (Fig. S1).48 The association
constant of Ni2+ to TAMSMB was found to be 4.39 × 104 M-1 (log Ka = 4.64) using the Benesi–Hildebrand method (Fig.
S2).49
Fig. 1 (a) Absorption spectra of TAMSMB (20 μM) as a function of Ni2+ concentration in 10 mM phosphate buffer solution at pH 6.5.
(b) The color changes of TAMSMB (20 μM) as a function of Ni2+ concentration in 10 mM phosphate buffer solution at pH 6.5.
His is predicted to be able to remove Ni2+ from TAMSMB-Ni2+ to reproduce TAMSMB in that there have
been some reports on the formation of a complex between His and Ni2+ in aqueous solution.34,37,47 To investigate
whether TAMSMB-Ni2+ can be utilized as a selective chemosensor toward His against other amino acids, the
absorption spectral studies of TAMSMB-Ni2+ (20 μM) were conducted upon addition of 20 various amino acids (40
4

μM) including Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val in
10 mM phosphate buffer solution at pH 6.5 (Fig. 2). The addition of His to TAMSMB-Ni2+ gave rise to a characteristic
colorimetric change as a decrease in the absorbance at 552 nm and an increase in the absorbance at 475 nm. Cys and
Asp also induced slight spectral changes, which were very insignificant compared to the change induced by His. Amino
acids other than His, Cys, and Asp yielded no dramatic changes in the absorption spectra of TAMSMB-Ni2+. Thus,
TAMSMB-Ni2+ can act as a selective colorimetric chemosensor for His through Ni2+ complex displacement mechanism.
Fig. 2 Absorption spectra of TAMSMB-Ni2+ (20 μM) in the presence of various amino acids (40 μM) in 10 mM phosphate buffer
solution at pH 6.5.
Moreover, to realize the Ni2+ displacement approach, the solution color and absorption spectral changes of
TAMSMB-Ni2+ in the presence of various concentrations of His were also monitored (Fig. 3). Upon gradual addition of
His into TAMSMB-Ni2+ (20 μM) significantly resulted in a gradual decrease in the absorbance at 552 nm with a
hypsochromic shift, whereas the absorbance at 475 nm steadily increased and reached saturation at 4 equiv. (80 μM) of
His (Fig. 3a). These spectral responses of TAMSMB-Ni2+ toward His were accompanied by a distinct visible color
change from red to yellow, leading to the detection of His by the naked eye (Fig. 3c). Thus, the results indicated that
TAMSMB-Ni2+ was recovered to TAMSMB by Ni2+ through a displacement mechanism with the formation of His and
Ni2+ complex during the detection procedure of His. To determine the detection limit, from Fig. S3, the slope (k) of
5

straight line between the absorbance at 552 nm and His concentration was calculated to be 1.41 × 10-2 μM-1 (R2
=0.9967). To estimate the S/N ratio, σ value was determined to be 2.29 × 10−3. The detection limit of TAMSMB-Ni2+
for His was calculated to be 0.49 μM, which was comparable to those (0.05-5 μM) of previously reported sensors for
His.37,38,50-53
Fig. 3c displays the color change of TAMSMB-Ni2+ with various concentrations of His. The solution color
gradually turned from red to orange then yellow with an increase in His concentration from 0 μM to 40 μM. The red
solution changed to orange color in the presence of 12 μM His, which meant that the detection limit by the naked eye
could be as low as 12 μM. These detection limits of TAMSMB-Ni2+ for His are lower than the normal levels of His
concentration (20 to 170 μM and 130 to 2100 μM in blood serum and urine, respectively).54,55 Thus, the TAMSMB-Ni2+
complex could serve as a potential chemosensor for His with the visual observation.
Fig. 3 (a) Absorption spectra of TAMSMB-Ni2+ (20 μM) as a function of His concentration in 10 mM phosphate buffer solution at
pH 6.5. (b) Absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) as a function of hisidine concentration in 10 mM phosphate buffer
solution at pH 6.5. (c) The color changes of TAMSMB-Ni2+ (20 μM) as a function of His concentration in 10 mM phosphate buffer
solution at pH 6.5.
6

To estimate the stoichiometry between His and Ni2+, a Job's plot experiment between His and TAMSMB-Ni2+
was carried out (Fig. S4). We can find when the molar fraction of His was 0.5, the absorbance difference (ΔA) at 552
nm reached a maximum, implying the formation of a 1:1 complex between His and Ni2+. The binding constant for the
formation of the His-Ni2+ complex was determined to be Kb = 2.28 × 105 M-1 (log Kb = 5.36) by non-linear least squares
fitting of the absorption titration data of TAMSMB-Ni2+ (552 nm) with His utilizing a 1:1 competitive binding
equilibrium model (Fig. S5).56,57 Since the binding constant (Kb) for the interaction of His and Ni2+ is approximately
5-fold higher than that (Ka) for the interaction of TAMSMB and Ni2+, the transfer of Ni2+ from TAMSMB to His can
thermodynamically favorably occur.
The response time is an important property for practical application. The time dependences of absorbance at
552 nm of TAMSMB-Ni2+ (20 μM) in the presence of different concentrations of His (10, 20, and 40 μM) were
investigated (Fig. 4). The absorbance began to decrease immediately after the addition of His and then remained
unchanged after about 60 s in each case, demonstrating fast response time of TAMSMB-Ni2+ toward His.
Fig. 4 Plots of the absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) as a function of hisidine concentration in 10 mM phosphate
buffer solution at pH 6.5 in the presence of His (10, 20, and 40 μM) as a function of time.
To verify practicality of TAMSMB-Ni2+ as a selective colorimetric chemosensor for His, competition
experiments with His and the other amino acids were conducted in 10 mM phosphate buffer at 6.5 (Fig. 5). Compared
7

to TAMSMB-Ni2+ containing only His, no obvious changes in the absorbance at 552 nm were observed with the other
amino acids. This result demonstrated that other amino acids did not interfere with the absorption change induced by
His, confirming the sensing ability of TAMSMB-Ni2+ for His could not be significantly affected by the coexistence of
other amino acids.
Fig. 5 Competitive selectivity of TAMSMB-Ni2+ (20 μM) toward His (40 μM)) in the presence of other amino acids (40 μM) in 10
mM phosphate buffer solution at pH 6.5.
The effects of pH on the absorption response in the presence of His or Cys were investigated in aqueous
solution with pH values ranging from 4 to 11 as shown in Fig 6. The presence of His gave rise to remarkable color
changes in the TAMSMB-Ni2+ solution from red to yellow between pH 6.5 and 9, while the colorimetric changes almost
disappeared below pH 5 and above pH 11. The addition of Cys to TAMSMB-Ni2+ resulted in the color changes from red
to yellow between pH 7 and 10. Therefore, pH 6.5 was selected as the optimal pH value in the light of an effective
colorimetric response and a selective detection of His.
8

Fig. 6 Absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) and in the presence of His (40 μM) or Cys (40 μM) as a function of pH
in 10 mM buffer solution.
The reversible responsive property of TAMSMB-Ni2+ to His in aqueous solution is very important for
practical application. In order to examine the reversibility of TAMSMB-Ni2+ toward His, when Ni2+ was added to the
solution of TAMSMB-Ni2+ in the presence of His, the absorption maximum shift from 475 to 552 nm with the color
change from yellow to red, which indicated the production of TAMSMB-Ni2+ (Fig. 7). Subsequently, upon addition of
His to the solution again, although TAMSMB was regenerated by the release of Ni2+, the absorbance at 552 nm
gradually increased with the number of addition, suggesting that the reversibility declined with an increase in the cycle.
9

Fig. 7 (a) Absorption spectra of TAMSMB-Ni2+ (20 μM) after the sequential addition of His (20 μM) and Ni2+ (20 μM) in10 mM
phosphate buffer solution at pH 6.5. (b) Reversible changes in absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) after the sequential
addition of His (20 μM) and Ni2+ (20 μM).
Upon addition of Ni2+, the absorption maximum of TAMSMB exhibited a red shift with color change from
yellow and red. TAMSMB could be combined with Ni2+ in aqueous solution with pH values ranging from 4 to 6.5 as
previously reported.45 Additionally, from the Job’s plot between TAMSMB and Ni2+ (Fig. S1), TAMSMB could form
the complex with Ni2+ in a 1:1 stoichiometric ratio (TAMSMB-Ni2+). Subsequently, although the addition of His to the
TAMSMB-Ni2+ solution resulted in the color change from red to yellow, the amino acids other than His caused no or
insignificant color changes. There have been some reports on the complex formation between His and Ni2+ in aqueous
solution. 34,37,47 The Job’s plot between TAMSMB-Ni2+ and His exhibited a 1:1 stoichiometry for the His-Ni2+ complex
10

formation (Fig. S4). It can be presumed from these findings that TAMSMB-Ni2+ was regenerated to TAMSMB by the
release of TAMSMB through a displacement mechanism with the 1:1 binding stoichiometry between interaction
between His and Ni2+ (Scheme 2).
Scheme 2 Possible proposed sensing mechanism of TAMSMB-Ni2+ toward His.
3. Conclusion
In summary, we have successfully developed the Ni2+ complex with a commercially available organic dye
TAMSMB as a colorimetric chemosensor for selective detection of His. TAMSMB bound to Ni2+ in a 1:1
stoichiometric ratio, resulting in a significant bathochromic shift with a remarkable color change from yellow to red.
The TAMSMB-Ni2+ complex could detect His selectively through the regeneration of original TAMSMB by the
interaction of Ni2+ with His. The detection could be done within 60 s with the detection limits of 0.49 μM and 12 μM by
absorption and naked-eye methods, respectively, which are lower than the normal levels of His. Moreover, interference
studies confirmed the high selectivity of the TAMSMB-Ni2+ colorimetric probe for His with little interference by other
amino acids.
References
1. Zhou Y, Yoon J. Chem. Soc. Rev. 2012; 41: 52-67.
2. Wang J, Liu H-B, Tong Z, Ha C-S. Coord. Chem. Rev. 2015; 303: 139-184.
3. Gupta VK, Nayak A, Agarwal S, Singhal B. Combinatorial Chemistry & High Throughput Screening 2011; 14:
284-302.
4. Gupta VK, Sethi B, Sharma RA, Agarwal S, Bharti A. J. Mol. Liq. 2013; 177: 114-118.
5. Gupta VK, Ganjali MR, Norouzi P, Khani H, Nayak A, Agarwal S. Crit. Rev. Anal. Chem. 2011; 41: 282-313.
11

6. Srivastava SK, Gupta VK, Jain S. Analyst 1995; 120: 495-498.
7. Srivastava SK, Gupta VK, Dwivedi MK, Jain S. Analytical Proceedings including Analytical Communications 1995;
32: 21-23.
8. Gupta VK, Karimi-Maleh H, Sadegh R. Int. J. Electrochem. Sci. 2015; 10: 303-316.
9. Gupta VK, Singh AK, Kumawat LK. Sens. Actuators B 2014; 195: 98-108.
10. Srivastava SK, Gupta VK, Jain S. Anal. Chem. 1996; 68: 1272-1275.
11. Gupta VK, Singh LP, Singh R, Upadhyay N, Kaur SP, Sethi B. J. Mol. Liq. 2012; 174: 11-16.
12. Gupta VK, Kumar S, Singh R, Singh LP, Shoora SK, Sethi B. J. Mol. Liq. 2014; 195: 65-68.
13. Karthikeyan S, GuptaVK, Boopathy R, Titus A, Sekaran G. J. Mol. Liq. 2012; 173: 153-163.
14. Dehghani MH, Sanaei D, Ali I, Bhatnagar A. J. Mol. Liq. 2016; 215: 671-679.
15. Asfaram A, Ghaedi M, Agarwal S, Tyagi I, Gupta VK. RSC Adv. 2015; 5: 18438-18450.
16. Gupta VK, Atar N, Yola ML, Üstündağ Z, Uzun L. Water Research 2014; 48: 210-217.
17. Yola ML, Vinod Kumar Gupta VK, Eren T, Sen AE, Atar N. Electrochimica Acta 2014; 120: 204-211.
18. Gupta VK, Mergu N, Kumawat LK, Singh AK. Sens. Actuators B 2015; 207: 216-223.
19. Gupta VK, Mergu N, Kumawat LK, Singh AK. Talanta 2015; 144: 80-89.
20. Karimi-Maleh H, Tahernejad-Javazmi F, Atar N, Yola ML, Gupta VK, Ensafi AA. Ind. Eng. Chem. Res. 2015; 54:
3634-3639.
21. Kopple JD, Swendseid ME. J. Clin. Investig. 1975; 55: 881-891.
22. Harding CR, Scott IR. J. Mol. Biol. 1983; 170: 651-673.
23. Kusakari Y, Nishikawa S, Ishiguro S, Tamai M. Curr. Eye Res. 1997; 16: 600-604.
24. Watanabe M, Suliman ME, Qureshi AR, Garcia-Lopez E, Barany P, Heimburger O, Stenvinkel P, Lindholm B. Am.
J. Clin. Nutr. 2008; 87: 1860-1866.
25. Verri C, Roz L, Conte D, Liloglou T, Livio A, Vesin A, Fabbri A, Andriani F, Brambilla C, Tavecchio L. Am. J.
Respir. Crit. Care Med. 2009; 179: 396-401.
26. Jones AL, Hulett MD, Parish CR. Immunol. Cell Biol. 2005; 83: 106-18.
27. Saito H, Goodnough LT, Boyle JM, Heimburger N. Am. J. Med. 1982; 73: 179-182.
12

28. Sullivan DJ, Gluzman IY, Goldberg DE. Science 1996; 271: 219-222.
29. Chen Z, Liu J, Han Y, Zhu L. Anal. Chim. Acta 2006; 570: 109-115.
30. Ye S, Guo Y, Xiao J, Zhang S. Chem. Commun. 2013; 49: 3643-3645.
31. Yu H, Xu L, You T. Luminescence 2013; 28: 217-221.
32. Wadud S, Or-Rashid MM, Onodera R. J. Chromatogr. B 2002; 767: 369-374.
33. Li LD, Chen ZB, Zhao HT, Guo L. Biosens. Bioelectron. 2011; 26: 2781-2785.
34. He Y, Wang X, Zhu J, Zhong S, Song G. Analyst 2012; 137: 4005-4009.
35. Du J, Yu S, Huang Z, Chen L, Xu Y, Zhang G,Chen Q, Yu X, Pu L. RSC Adv. 2016; 6: 25319-25329.
36. Kim YS, Park GJ, Lee SA, Kim C. RSC Adv. 2015; 5: 31179-31188.
37. Sun SK, Tu KX, Yan XP. Analyst 2012; 137: 2124-2128.
38. Gu P, Zhang G, Deng Z, Tang Z, Zhang H, Khusbu FY, Wu K, Chen M, Ma C. Spectrochim. Acta A 2018; 203:
195-200.
39. Nguyen BT, Anslyn EV. Coord. Chem. Rev. 2006; 250: 3118-3127.
40. Wu J, Kwon B, Liu W, Anslyn EV, Wang P, Kim JS. Chem. Rev. 2015; 115: 7893-7943.
41. Inoue K, Aikawa S, Fukushima Y. J. Incl. Phenom. Macrocycl. Chem. 2018; 90: 105-110.
42. Folmer-Andersen JF, Lynch VM, Anslyn EV. Chem.-A Eur. J. 2005; 11: 5319-5326.
43. Wada H, Ishizuki T, Nakagawa G. Mikrochim. Acta 1983; 3: 235-244.
44. Nomura Y, Imai K, Suzuki M, Okuda K. Clin. Chem. 1987; 33: 1565-1566.
45. Wada H, Ishizuki T, Nakagawa G. Bunseki Kagaku 1983; 32: E225-E230.
46. Rowinska-Zyrek M, Zakrzewska-Czerwinska J, Zawilak-Pawlik A, Kozlowsk H. Dalton Trans. 2014; 43:
8976-8989.
47. Qiao Y, Chen B, Yang Y, Wang X, Xu Y, Li H. Dalton Trans. 2016; 45: 1310-1314.
48. Job P. Ann. Chim. 1928; 9: 113-203.
49. Benesi AH, Hildebrand HJ. J. Am. Chem. Soc. 1949; 71:.2703-2707.
50. Elbaz J, Shlyahovsky B, Willner I. Chem. Commun. 2008; 13:.1569-1571.
51. Zhang Z, Wang L, Li G, Ye B. Analyst 2017; 142: 1821-1826.
13

52. Sun J, Yang F, Zhao D, Chen C, Yang X. ACS Appl. Mater. Interfaces 2015; 7:6860-6866.
53. Hosseini M, Ganjali MR, Jarrahi A, Vaezi Z, Mizani F, Faridbod F. Spectrochim. Acta A 2014; 132: 629-633.
54. Walters RR, Johnson PA, Buck RP. Anal. Chem. 1980; 52: 1684-1690.
55. Kovach PM, Meyerhoff E. Anal. Chem. 1982; 54:.217-220.
56. Hu M, Feng G. Chem. Commun. 2012; 48:.6951-6953.
57. Inoue K, Aikawa S, Fukushima Y. Luminescence 2018; 33: 277-281.
14

Figure captions
Scheme 1 Chemical structure of TAMSMB.
Scheme 2 Possible proposed sensing mechanism of TAMSMB-Ni2+ toward His.
Fig. 1 (a) Absorption spectra of TAMSMB (20 μM) as a function of Ni2+ concentration in 10 mM phosphate buffer
solution at pH 6.5. (b) The color changes of TAMSMB (20 μM) as a function of Ni2+ concentration in 10 mM
phosphate buffer solution at pH 6.5.
Fig. 2 Absorption spectra of TAMSMB-Ni2+ (20 μM) in the presence of various amino acids (40 μM) in 10 mM
phosphate buffer solution at pH 6.5.
Fig. 3 (a) Absorption spectra of TAMSMB-Ni2+ (20 μM) as a function of His concentration in 10 mM phosphate buffer
solution at pH 6.5. (b) Absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) as a function of hisidine concentration in 10
mM phosphate buffer solution at pH 6.5. (c) The color changes of TAMSMB-Ni2+ (20 μM) as a function of His
concentration in 10 mM phosphate buffer solution at pH 6.5.
Fig. 4 Plots of the absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) as a function of His concentration in 10 mM
phosphate buffer solution at pH 6.5 in the presence of His (10, 20, and 40 μM) as a function of time.
Fig. 5 Competitive selectivity of TAMSMB-Ni2+ (20 μM) toward His (40 μM) in the presence of other amino acids (40
μM) in 10 mM phosphate buffer solution at pH 6.5.
Fig. 6 Absorbance at 552 nm of TAMSMB-Ni2+ (20 μM) toward His (40 μM) or Cys (40 μM) as a function of pH in
10 mM buffer solution.
15

Fig. 7 (a) Absorption spectra of TAMSMB-Ni2+ (20 μM) after the sequential addition of His (20 μM) and Ni2+ (20 μM)
in10 mM phosphate buffer solution at pH 6.5. (b) Reversible changes in absorbance at 552 nm of TAMSMB-Ni2+ (20
μM) after the sequential addition of His (20 μM) and Ni2+ (20 μM).
16

Highlights
1) A colorimetric chemosensor for histidine was developed using a TAMSMB-based Ni2+ complex in aqueous solution.
2) It could selectively detect histidine by color change from red to yellow.
3) It showed a fast response toward histidine.
17

18