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A review of the applications of Schiff bases as optical chemical sensors

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 Trends in Analytical Chemistry 116 (2019) 74e91

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Trends in Analytical Chemistry

journal homepage: www.elsevier.com/locate/trac

A review of the applications of Schiff bases as optical chemical sensors

Asnake Lealem Berhanu a, Gaurav b, Irshad Mohiuddin a, Ashok Kumar Malik a,
Jatinder Singh Aulakh a, **, Vanish Kumar c, Ki-Hyun Kim d, *
a
Department of Chemistry, Punjabi University, Patiala, 147002, Punjab, India
b
Constituent College, Punjabi University, Ghannaur, Patiala, Punjab, India
c
National Agri-Food Biotechnology Institute (NABI), S.A.S. Nagar, Punjab, 140306, India
d
Department of Civil and Environmental Engineering, Hanyang University, Seoul, 04763, South Korea

a r t i c l e i n f o a b s t r a c t

Article history: Schiff bases and their metal complexes have become well-known for catalytic (e.g., in various synthetic
Available online 6 May 2019 processes) and biological properties (e.g., antifungal, antibacterial, anti-malarial, and antiviral charac-
teristics) since their discovery by Hugo Schiff in 1864. As synthetic compounds, they are employed as
Keywords: versatile tools in numerous applications such as fluorescent turn-on/turn-off sensors for the determi-
Azomethine nation of diverse analytes (e.g., metallic components). As such, they can offer a way to identify toxic ions
Chemosensors
and/or to provide their speciation in environmental media. This review covers a broad range of Schiff
Fluorescent probe
bases that are used in sensing applications for metallic cations and anions in various kinds of environ-
Ligand
Schiff base
mental and biological media.
© 2019 Elsevier B.V. All rights reserved.

1. Introduction Schiff bases are generally known as imines or azomethines and

The need for specific and sensitive identification of pollutant
species (e.g., toxins and metal ions) is in high demand, particularly
in health and environmental applications. The release of cations
and anionic pollutants due to industrial and farming practices has
increased threats to human health and the environment. Currently,
different methods, e.g., flame atomic absorption spectroscopy,
inductively coupled plasma optical emission spectroscopy, strip-
ping voltammetry, X-ray fluorescence spectrometry, and induc-
tively coupled plasma mass spectrometry are used to detect metal
ions [1,2]. However, most of these methods are costly, time
consuming (especially during sample preparation), and exhibit low
sensitivity. Different optical chemosensors have been explored for
the determination of metal ions to overcome the previously
mentioned limitations of these methods [3]. To this end, Schiff
base-based structures demonstrate excellent performance for the
determination of metal ions. Schiff base ligands have received great
attention from researchers because of their ease of synthesis and
their ability to form complexes with almost all metals [4].
* Corresponding author.
** Corresponding author.
E-mail addresses: chemiaulakh@gmail.com (J.S. Aulakh), kkim61@hanyang.ac.kr
(K.-H. Kim).
act as ligands in various metal complexes. They are formed as
condensation products from primary amines and aldehydes or
ketones. However, aldehydes react faster than ketones in conden-
sation reactions due to steric and electronic effects [5]. Hugo Schiff,
a German chemist, was the first to synthesize Schiff bases (in 1864)
by condensing primary amines with carbonyl compounds [6]. Later,
he synthesized complexes of metal-salicylaldehyde with primary
amines [7]. A Schiff base was also derived from condensing sali-
cylaldehyde and a primary amine, which exhibited a 2:1 stoichi-
ometry on complexation with the metal [8]. Likewise, an inclusive
and systematic study was carried out for preparing a series of
complexes derived from Schiff bases of salicylaldehyde and its
substituents [9,10]. Later on, several binuclear and multinuclear
Schiff base-transition metal complexes were synthesized having
broad areas of application (e.g., material science, catalysis, magneto
chemistry, bioinorganic chemistry, bioinorganic modeling studies,
multi electron redox chemistry, and super conductivity) [11e13].
The trinuclear Schiff base complexes of transition metals, e.g., Zn2þ
and Cd2þ, were also developed to study the crystal structures of
complexes [14]. Moreover, these complexes served as a simulator in
bimetallic bio-sites in many proteins and enzymes [15]. Schiff bases
have been successfully used in several studies as highly efficient
and selective sensing materials for diverse ion sensors such as
optical, electrochemical [16e18] and membrane sensors [19].
Depending upon the type of Schiff base, these structures displayed

https://doi.org/10.1016/j.trac.2019.04.025
0165-9936/© 2019 Elsevier B.V. All rights reserved.
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91 75

2.1. Detection of trivalent cations

Abbreviations:
Trivalent cations are involved in several biological processes in
AIEE Aggregation induced emission enhancement the human body (e.g., cell functions). Al3þ is the most abundant
APHA American public health association trivalent cation found in nature [22]. These cations can result in
13
CNMR Carbon-13 nuclear magnetic resonance water contamination and exhibit toxic effects on humans, if they
DL Detection limit are present in excess. For example, Al3þ toxicity (above the
DMF Dimethyl formaldehyde permissible level) can cause Alzheimer's disease and osteoporosis.
DMSO Dimethyl sulfoxide (Refer to Table 2 for permissible levels of common cations and
DNA Deoxyribonucleic acid anions). Cr3þ is another trivalent cation which can pollute the
EDTA Ethylenediaminetetraacetic acid environment. Cr3þ deficiencies in humans can disturb glucose
FT-IR Fourier transform infrared levels and lipid metabolism. In general, altered levels of these
HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic compounds in humans can significantly affect the normal function
acid) of a human body. Thus, rapid and accurate determination of these
1
H NMR Proton nuclear magnetic resonance cations in different fluids is necessary to avoid any harm.
HR-MS High resolution mass spectrometry
ISI Indian Standard Institution 2.1.1. Detection of aluminum
MS-ESI Mass spectrometry electron spray ionization Aluminum is the third most abundant metallic element present
RNA Ribonucleic acid on the earth [24]. Al3þ is also found in natural water and can enter
TOF-MS Time of flight mass spectrometry the human body via food and drinking water. The presence of Al3þ
UVeVis Ultravioletevisible spectroscopy above the allowable limit (refer to Table 2) can affect pulmonary
V/V Volume by volume systems and may pose severe health hazards like Alzheimer's and
Parkinson's disease, renal failure, and bone softening. The problems
associated with the existence of Al3þ beyond the requisite limit in
environmental and biological systems led many researchers to look
selectivity towards specific metal ions over the others due to the for easy, fast, sensitive, and selective detection methods. To this
unique size of the ion, the electron configuration of both the ligand end, a number of Schiff bases have been tested for the determina-
and the metal, the charge on the metal ion, the hard-soft acid base tion of Al3þ.
nature of both the metal and donor atom from the Schiff base, and For instance, the Schiff base 7-methoxychromone-3-
size of the cavity of the Schiff base [20]. carbaldehyde-(indole-2-formyl) hydrazone derived from 1H-
In this article, various Schiff bases have been reviewed as indole-2-carboxylic acid hydrazide and 7-methoxy chromone-3-
sensing materials for the detection of metal ions in environmental carbaldehyde was used as a selective fluorescent and colorimetric
matrices like water. This review provides deep insights into the chemosensor for Al3þion in an ethanol system [25]. The Schiff base
optical sensors developed by Schiff bases for the determination of was colorless in solution, while the colorless solution turns yellow-
cations and anions. The next section of this review will cover green upon complexing with Al3þ. The Al3þ derived coloration in a
different Schiff base-based optical sensors for the determination of Schiff base solution led to “offeon” type sensing of Al3þ by forming
metallic species in aqueous systems. Section 2 was divided on the 1:2 stoichiometry. Moreover, the interactions of metal ions with the
basis of the type of analyte ion, e.g., divalent/trivalent cations and Schiff base resulted in a 500-fold enhancement in the fluorescence
anionic species. Further, the synthesis approaches and sensing signals of the Schiff base. The formation of a complex between the
performances of different Schiff base sensors have been discussed Schiff base and Al3þ was suggested to increase the fluorescence
in detail. Finally, the merits and disadvantages of Schiff base sen- intensity of the sensing platform. The complex formation between
sors are discussed with their future prospects. Schiff base and Al3þ led to a reduction in photo induced electron
transfer, which enhanced the fluorescence intensity of the Schiff
2. Schiff bases as ionic sensors base. The fluorescence enhancement of metal complexation was
further confirmed by adding Na2EDTA into the testing solution. The
Schiff bases have been explored successfully for the determi- addition of Na2EDTA led to the removal of Al3þ from complexes
nation of diverse metal ions (Table 1). The chemical interactions (e.g., Schiff base and Al3þ metal complexes), which caused a
between Schiff bases and metal ions are critical for generating decrease in the fluorescence intensity of the sensing platform. This
sensing signals [21]. Chemosensors can be classified into different Schiff base-based Al3þ sensor was able to achieve a 50 nM detection
categories such as colorimetric sensors, fluorogenic sensors, and limit (DL).
electrochemical sensors based on the nature of the signal emitted The Al3þ derived aggregation of a few Schiff bases, e.g., (4Z,4E)-
by the sensing materials. In the case of Schiff base-based chemo- 4-(2-(2-hydroxy benzylidene)hydrazon)-2-phenyl-4H-chromen-3-
sensors, the change in their electronic properties via different ol 3 in an aqueous solution can induce fluorescence emission cor-
charge transfer processes (e.g., ligand-to-metal charge transfer and responding to the Al3þ concentration [26]. (Refer to Fig. 1(a) for
metal-to-ligand charge transfer) produces the sensing signal. To synthesis of (4Z,4E)-4-(2-(2-hydroxybenzylidene)hydrazono)-2-
date, Schiff bases have been primarily explored as optical metal ion phenyl-4H-chromen-3-ol.) from 1 and 2. The DL for the determi-
sensors. The signals of these sensors exhibited strong dependency nation of Al3þ was 290 nM by this Schiff base-system. The fluo-
upon the interactions between metal ions and Schiff bases. For rescence enhancement reached a maximum at 5.0 pH when tested
instance, the signals of the fluorescent sensor are affected by on a 3.0e12.0 pH range. Additionally, test papers were developed
various processes such as fluorescence resonance charge transfer, from this Schiff base for on-site sensing of Al3þ ions. The presence
excimer-exciplex formation, fluorescence resonance energy trans- of Al3þ changed the color of this Schiff base from yellow to colorless.
fer, excited state intramolecular proton transfer, and photo induced This Schiff base is also effective for imaging Al3þ in living cells.
electron transfer. Likewise, the sensing signals of an electro- Likewise, aggregation induced emission properties were
chemical sensor depend upon the change in redox potential explored for the sensing of Al3þ using another Schiff base i.e., N, N0 -
[22,23]. bis (salicylidene)-1, 4-diaminobenzene 6 [27] (refer to Fig. 1b) for
Table 1

76
Basic quality assurance and analytical parameters for the analysis of cations and anions using Schiff bases.

Order Methods Schiff base or amine and aldehyde Color change Sensor M:L ratio pH Wavelength Binding Detection Matrixes Reference
type constant (/M) limits (mM)
Excitation Emission
(nm) (nm)

A. Al3þ
i Fluorescent and 7-methoxychromone-3-carbaldehyde- Colorless to yellow- off-on 1:2 e 423 507 7.8  103 0.05 e [25]
colorimetric (indole-2-formyl) hydrazone green
ii Fluorescence spectroscopy N, N0 -bis(salicylidene)-1, 4-diaminobenzen off-on 2:1 7.0 365 e e 0.39 e [27]
iii Fluorescence spectroscopy (3, 5-dichloro-2-hydroxybenzylidene) turn-on 1:1 6.0 393 493 8.44  104 0.012 e [28]
quinolone-2-carbohydrazide
iv Fluorescence spectroscopy 6-ethoxychromone-3-carbaldehyde-(3- Black to pale yellow off-on 1:2 5.0 420 508 9.24  103 0.182 e [29]
hydroxy-2-naphthalene acyl) hydrazone
v Fluorescence spectroscopy (E)-1-((2-aminophenylimino)methyl) turn-on 1:1 e 273 473 6.53  103 0.108 Distilled, lake, and [30]
naphthalen-2-ol river water
vi Fluorescence spectroscopy 2-((9H-fluoren-2-yilimino)methyl)phenol e e 1:2 8.5 333 536 5.44  104 0.31 e [32]
vii Fluorescence spectroscopy 4-(diethylamino)salicylaldehyde and 6- e turn-on 1:1 e 448 488 e 2.4 e [34]
amino-7-hydroxycoumarin

A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

viii Ratio metric fluorescent (4Z,4E)-4-(2-(2-hydroxybenzylidene) Yellow to white e 1:1 7.0 370 537 e 0.29 Cell imaging [26]
chemosensor hydrazono)-2-phenyl-4H-chromen-3-ol
ix Colorimetric chemosensor 2,3-dimethyl-4-(3-oxo-1,3- Yellow to colorless e 1:1 e 256 428 e 0.49 Tap water, canal [31]
diphenylpropylideneamino)-1-phenyl-1,2- water, industrial
dihydropyrazol-5-one water
2,3-dimethyl-4-(2-oxo-1,2- e 1:1 e 321 455 e 0.73 e
diphenylethylideneamino)-1-phenyl-1,2-
dihydropyrazol-5-one
x Colorimetric chemosensor 4-((2, 4-dichlorophenyl) diazenyl)-2-(3- e e 1:2 e e e 1.8  104 e e [33]
hydroxy propylimino) methyl)phenol
B. Cu2þ
i Fluorescence spectroscopy diaminomaleonitrile and 1-pyrenealdehyde Yellow to colorless turn-on 1:2 5.5e7.5 350 417 5.55  103 100 e [47]
ii Fluorescence spectroscopy (1E,2E)-1,2-diphenyl-1,2-bis((E)-(pyridine- Colorless to reddish e 1:1 7.0 425 e 1.92  104 2.5 Distilled water, [49]
2-ylmethylene) hydrazono) ethane yellow copper gluconate
iii Fluorescence spectroscopy benzildihydrazone- N,N0 -bis(2-hydroxy-4- Yellow to light red turn-off 1:1 7.0 560 e e 0.00073 Drinking, tap and [52]
diethylamino-1-formyl benzene) sea water
iv Colorimetric chemosensor (4-diethylamino)-salicylaldehyde-azine Pale yellow to e 1:1 e 425 479 e 0.98 e [40]
purple
v Colorimetric chemosensor diarylethene- 1, 8-naphthalimide Greenish to e 1:1 e 525 542 3.13  104 2.4 e [46]
colorless
6
vi Colorimetric chemosensor 2-((1Z,3Z)-3-(2-hydroxyphenylimino)-1, 3- Colorless to e 1:1 7.0e10 426 e 1.0  10 100 e [48]
diphenylprop-1-enylamino) phenol yellowish brown
vii Colorimetric chemosensor 2,20 -((1E,10 E)-(((hexylazanediyl)bis (4,1- Yellow to dark pink e 1:1 5.5 450 e 1.65  106 0.0189 e [50]
phenylene)) bis(methanylylidene))
bis(azanylylidene))bis (4-methylphenol)
C. Zn2þ
i Fluorescence spectroscopy 7-(40 -(diethylamino)-20 - e e 1:2 e 380 500 1.09  106 2.59 e [61]
hydroxybenzylideneimino)-4-methyl
coumarin
ii Fluorescence spectroscopy tris (3-(2-hydroxyacetophenone)propyl) Light yellow to turn-on 2:1 7.2 350 365 3.0  106 0.088 Tap & river water [62]
amine lightless
iii Fluorescence spectroscopy N,N0 -bis(p-chlorosallicylidene)-1,2- e e 2:1 6.8 370 500 6.17  109 3.21 e [63]
etheylenediamine
iv Fluorescence spectroscopy N,N0 -bis(Salicylidene)-1,2- e 1:1 8.0e11.0 320 450 1.31  10 5
e e [64]
phenylenediamine
v Fluorescence spectroscopy furfuraldehyde and 4,5-dimethyl-1,2- e 1:1 e 308 361 e e e [65]
phenylendiamine
vi Fluorescence spectroscopy 1-amino-2-propanol and 2- e e e e e [66]
hydroxybanzaldehyde
vii Fluorescence spectroscopy e 1:2 7.4 356 0.452 Cell imaging [67]
 1-[(2-pyridin-2-yl-ethylimino)-methyl]- Yellow to opaque
naphthalen-2-ol blue
viii Colorimetric & fluorescence 2-hydroxynaphthalene-1-carboxaldehyde Colorless to blue off-on 1:1 2.0e10.0 308 450 1.23  107 0.489 e [68]
spectroscopy and tris(2-aminoethyl)amine
3þ
D. Fe
i Fluorescence spectroscopy 4-(diethylamino)salicylaldehyde and 6- e turn-on 1:1 e 448 488 e 4.3 e [34]
amino-7-hydroxycoumarin
ii Fluorescence spectroscopy 40 -hydroxy-30 -{[(2-phenyl-1,3-thiazol-4-yl) e on-off-on 1:1 7.4 420 580 9.8  104 0.109 Running water [36]
imino]methyl}biphenyl-4-carbonitrile
iii Fluorescence spectroscopy 2-(N-methylpiperaziinylimino) e e 1:1 6e7.5 564 588 6.9  103 2.2 Cell imaging [37]
acetaldehyde and rhodamine B hydrazine
4
iv Fluorescence spectroscopy 1-(3-(2-hydroxynaphthalen-1-ylamino) e 1:1 e e 351 (2.7 ± 0.3) x10 35.3 e [39]
naphthalene-2-ylamino)naphthalene-2-ol
v Fluorescence spectroscopy 8-hydroxyjulolidinal-azine Pale yellow to e 1:1 e 445 497 e 9.5 e [40]
violet
E. Hg2þ
i Fluorescence spectroscopy acenaptho [1,2-b]quinoxaline-based Colorless to yellow e 2:1 6.0e8.0. 365 2.51  105 0.907 Lake, tap & [54]
thiosemicarbazone drinking water
5
ii Fluorescence spectroscopy 1,10-phenanthroline-2,9-dicarbaldehyde Colorless to yellow on-off 2:1 4.0e12.0 540 1.77  10 21.72 ppb Deionized, Tap, [55]

A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

and 1H-indole-2-carbohydrazide drinking, lake,
ground & ditch
water
iii Fluorescence spectroscopy 2-(Diphenylmethyleneamino) e turn-on e 5.0e10.0 394 415 e 0.0226 [56]
benzenethiol)
F. Cr3þ
i Fluorescence spectroscopy 2,3-dimethyl-4-(3-oxo-1,3- Yellow to colorless e 1:1 e 258 463 e 0.96 Tap, canal & [31]
diphenylpropylideneamino)-1-phenyl-1,2- industrial water
dihydropyrazol-5-one
2,3-dimethyl-4-(2-oxo-1,2- e 1:1 e 338 484 0.121 e
diphenylethylideneamino)-1-phenyl-1,2-
dihydropyrazol-5-one
ii Fluorescence spectroscopy 2-((9H-fluoren-2-yilimino)methyl)phenol e e 1:2 8.5 333 536 8.33  104 0.25 e [32]
iii Fluorescence spectroscopy (6E)-6-((thiophene-2-yl)-2H-chromen-2- e Turn on 1:1 7.4 e e 8  104 1 Cell imaging [43]
one
G. Ni2þ
i Fluorescence spectroscopy 2-((E)-(2-(2-((E)-5-chloro-2- e e 1:1 e 428 542 4.18  105 0.00867 River, tap & bottled [70]
hydroxybenzylideneamino) phenylthio) water
phenylimino)methyl)-4-chlorophenol
ii UVevis spectroscopy 4-chloro-2-[(3-(4-(dimethyllamino) Yellow to deep e 1:1 5.5e8 480 e 1.29  105 10 e [ 71]
phenyl) allyli-dene)amino] orange
iii UVevis spectroscopy N,N0 -bis(3-methylsalicylidene)-ortho- e e 1:1 8 430 e e 0.0136 Starch sugar black [72]
phenylenediamine tea leaves tobacco
rice flour
H. Pd2þ
i Fluorescence spectroscopy 5,50 -Methylenebis (2- e turn-on 2:2 3.0e12.0 327 520 2.10  104 0.38 e [56]
hydroxybenzaldehyde) and 2-
aminoethanethiol
ii Fluorescence spectroscopy 2-hydroxy-1-naphthaldehydene-8- e e e e 298 355 e 0.083 e [75]
aminoquinoline
I. Co2þ
i Fluorescence spectroscopy 2-((4-(2-hydroxybenzylideneamino) e e 1:1 298 350 e 0.782 Lake & tap water [58]
phenylimino)methyl)phenol
ii UVevis spectroscopy (E)-benzyl-2-((7-(diethylamino)-2-oxo-2H- Yellow to red e 1:2 7.4 e e e 0.31 e [38]
chromen-3-yl)methylene)hydrazine
¡
J. F
i Fluorescence spectroscopy 4-((2, 4-dichlorophenyl) diazenyl)-2-(3- Yellow to Red e 2:1 e 400 515 1.5  104 1.66 e [33]
hydroxypropylimino)methyl)phenol
ii Fluorescence spectroscopy diarylethene- 1, 8-naphthalimide e x e 579 e e e [46]
(continued on next page)

77
 78 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

the synthesis of N, N0 -bis (salicylidene)-1, 4-diaminobenzene). The

Reference

DL for Al3þ with this Schiff base at physiological pH was 390 nM.
The Schiff base 3, 5-dichloro-2-hydroxybenzylidene) quinolone-2-
[ 89]

[52]

[86]

[33]

[36]

[39]

[63]
carbohydrazide 11 demonstrated excellent results as a selective
and sensitive turn-on probe for Al3þ sensing in an ethanol-water
mixture 10:90 (v/v) at pH 6.0 with a DL of 12 nM [28] (Refer to
simulated urine
Tap, rain water,

Running water
Matrixes

Fig. 1c) for steps involved in the synthesis of this Schiff base from
sample 7e10). The Schiff base formed a 1:1 complex with metals and was
employed for the fluorescence imaging of Al3þ HeLa cells and the
determination of Al3þ levels in human serum and tap water. A DL of
e

e
18.2 mM was achieved by 6-ethoxychromone-3-carbaldehyde-(3-
limits (mM)
Detection

hydroxy-2-naphthaleneacyl) hydrazine Schiff base for Al3þ at pH

0.186

(4.5 ± 0.3) x 103 0.425

7 in a 3:1 (v/v) ethanol: water mixture [28]. It was suspected that
0.15

1.03

1.24

65
Al3þ interaction with the Schiff base led to the restriction of photo
e

induced electron transfer and geometrical changes in the Schiff

constant (/M)

base to yield sensing signals [29]. This Schiff base exhibited binding
Binding

1.02  104

1.53  102

6.25  106
with Al3þ in a 1:2 stoichiometric ratio. Moreover, a binding con-
stant value of 9.24  103 M1 was calculated for binding between 6-
ethoxychromone-3-carbaldehyde-(3-hydroxy-2-naphthalene acyl)
e

hydrazine and Al3þ (Refer to Fig. 2 for absorption spectral change in

Excitation Emission
(nm)

the presence of the Schiff base.).

Wavelength

420

505

500

The Schiff base (E)-1-((2-aminophenylimino)methyl)naph-

e

thalen-2-ol is also very selective for the analysis of Al3þ when

(nm)

tested in the presence of water and other metal ions, e.g., Cr3þ, Fe3þ,
Hg2þ, and Agþ [27]. The 6-ethoxychromone-3-carbaldehyde-(3-
357

560

400

370
e

7.0 ± 0.1 e

hydroxy-2-naphthalene acyl) hydrazine 14 was synthesized by

condensation of 2-hydroxy-1-naphthalaldehyde 12 and benzene-
pH

1,2-diamine 13 in ethanol (Fig. 1d) and was employed as a turn-on

7.4

6.8
10

e
7

fluorescence probe for the determination of Al3þ. The DL, binding

M:L ratio

constant, and stoichiometry of the ligand to metal were 10.8 mM,

6.53  103 M1, and 1:1, respectively [30]. Likewise, Schiff bases
1:1

1:1

1:1

2:1

on-off-on 1:1

1:1

2:1

2,3-dimethyl-4-(3-oxo-1,3-diphenylpropylideneamino)-1-phenyl-
Sensor

1,2-dihydro pyrazol-5-one (derived from condensation of 4-

turn-off
turn on
type

aminoantipyrine and benzil) and 2,3-dimethyl-4-(2-oxo-1,2-

e

diphenylethylideneamino)-1-phenyl-1,2-dihydropyrazol-5-one
Greenish yellow to

(derived from 4-aminoantipyrine and 1,3-diphenylpropane-1,3-

Yellow to orange
Yellow to purple
Color change

dione) were synthesized and tested as chemosensors for the

reddish orange
Pale yellow to

determination of Al3þ [31]. These chemosensors displayed both

chromo and fluoro-genic sensing (e.g., fluorescence quenching)
responses. In contrast, insignificant changes in fluorescence signals
blue

4 -hydroxy-3 -{[(2-phenyl-1,3-thiazol-4-yl) e

were observed in the presence of other metal ions at wavelengths

of 428 and 445 nm for the first and second Schiff bases mentioned
naphthalene-2-ylamino)naphthalene-2-ol
benzildihydrazone-N,N0 -bis(2-hydroxy-4-

4-((2, 4-dichlorophenyl) diazenyl)-2-(3-

1-(3-(2-hydroxynaphthalen-1-ylamino)

above, respectively. The metal ions interacted with the previously

Schiff base or amine and aldehyde

4-((2,4-dichlorophenyl)diarenyl)-2-(3-

imino]methyl}biphenyl-4-carbonitrile
hydroxypropylimino)methyl)phenol

mentioned Schiff bases via the oxygen of the keto group (located in
1-((1H-indol-3-yl)methylene)-2-(4-

ydroxypropylimino) methyl)phenol

N,N0 -bis(p-chlorosallicylidene)-1,2-
diethylamino-1-formyl benzene)

Table 2
nitrophenyl)hydrazine

Summary of permissible concentration levels of metals in drinking water and bodily

fluid.
etheylenediamine

Order Cation/anion Permissible amount In bodily fluid (/kg) References

0

(mg/l) in drinking
water (WHO)

1 Iron 0.3 3e4 g [109,110]

0

2 Manganese 0.1 12 mg [109,110]

3 Copper 1.0 150 mg [109,110]
Fluorescence spectroscopy

Fluorescence spectroscopy

Fluorescence spectroscopy
Fluorescence spectroscopy

Colorimetric chemosensor

Colorimetric chemosensor

4 Mercury 0.001 [110]

5 Cadmium 0.005 0.5 mg [110,111]
UVevis spectroscopy

6 Lead 0.05 [110]

Methods

7 Zinc 5.0 2.5 g [ [109,110]

& colorimetric

8 Aluminum 0.03 3e10 mg [24]

9 Chromium 0.05 [110]
Table 1 (continued )

10 Cobalt 0.001 [110]

11 Nickel 0.0008 [110]
12 Palladium 0.00001 [110]
N. HSO¡
3
L. PO3¡
K. CN¡

13 Chloride 200 [110]

4
Order

M. I¡

14 Fluoride 1.5 [110]

iii

ii

ii

15 Cyanide 0.05 [110]

i

i
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91 79

Fig. 1. Synthesis of diverse Schiff bases: (a) (4Z, 4E)-4-(2-(2-hydroxybenzylidene)hydrazine)-2-phenyl-4H-chromen-3-ol [26]; (b) 2-((E)-4-((E)-(2-hydroxyphenylimino)methyl-
phenylimino)methyl)phenol [27]; (c) (E)-N0 -(3,5-dichloro-2-hydroxybenzylidene)quinolone-2-carbohydrazide [28]; (d) (E)-1-((2-aminophenylimino)methyl)naphthalene-2-ol
[30]; (e) (1E),2E) 1,2-diphenylbis ((E)(pyridine-2-ylmethylene (hydrazono)ethane [49], (f) 2-(diphenylmethyleneamino) benzenethiol Schiff base [56], (g) (Z)-2-((4-(2-
hydroxybenzylidene amino)phenylimino) methyl) phenol [58], (h) (N1E, N2E)-N1,N2-bis(furan-2-ylmethylene)-4,5-dimethylbenzene-1,2-diamine [104], (i) 1-((E)-(2-(bis(2-((E)-
(2-hydroxynaphthalen-1-yl)methyleneamino)ethyl)amino)ethyl imino)methyl)naphthalene-2-ol [68], and (j) 3-(benzo[d]thiol-2-yl)-7-hydroxy-2H-chromen-2-one and 3(benzo
[d]oxazol-2-yl)-7-hydroxy-2H-chromen-2-one [77].
80 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

Fig. 1. (continued).

antipyrine ring) and nitrogen located in the imine group and
antipyrine ring of the Schiff bases. There was a transfer of electrons
from imine to antipyrine moieties, which resulted in quenching of
fluorescence. Al3þ interacted with both the imine group and the
oxygen of the antipyrine moiety to form stable complexes with the
Schiff base, resulting in a fluorescence switch on [31]. Al3þ
exhibited greater affinity to form a complex with this Schiff base
due to its higher electron accepting nature as compared to other
metal ions such as Cr3þ. It was observed that these Schiff bases
displayed the best sensing response in alcoholic solvents, e.g.,
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91
Fig. 2. Fluorescence responses of L (50.0 mM) in ethanol and water (3:1, v/v) with 1
equiv of Naþ, Kþ, Agþ, Mg2þ, Ba2þ, Ca2þ, Cd2þ, Co2þ, Cu2þ, Zn2þ, Mn2þ, Hg2þ, Pb2þ, Ni2þ,
Fe3þ, Cr3þ and Al3þ (lex ¼ 420 nm) [29].
methanol and ethanol, at acidic and neutral pH, when tested in
methanol, ethanol, acetonitrile, dimethyl sulfoxide, dimethyl
formaldehyde, and tetrahydrofuran.
A fluorescence-based Schiff base sensor, i.e., 2-((9H-fluoren-2-
yilimino)methyl)phenol, derived from a 9H-fluoren-2-amine and
2-hydroxy benzaldehyde displayed selective fluorescent signals for
the detection of Al3þ [32]. The sensor exhibited a DL of 310 nM at
pH 8.5. In the absence of Al3þ, the Schiff base exhibited weak
fluorescence emission for two reasons: (1) isomerization of the
-C¼N- bond and (2) excited state intramolecular proton transfer. In
contrast, both the factors were restricted in the presence of Al3þ,
which led to enhancements in the fluorescence intensity of the
Schiff base.
The phenoliceazomethine (CH¼N) groups present in a Schiff
base, e.g., in 4-((2, 4-dichlorophenyl)diazenyl)-2-(3-
hydroxypropylimino)methyl)phenol serve as binding groups for
Al3þ [33]. Al3þ ions form a complex with Schiff bases in a 1:2 stoi-
chiometry with binding constant of 1.86  104 M1. A DL of 3.02 mM
was observed for the sensing of Al3þ ions by the previously
mentioned Schiff base sensor. In another study, a Schiff base derived
from 4-(diethyl amino) salicylaldehyde and 6-amino-7-
hydroxycoumarin was used as a selective chemosensor for Al3þ
with a DL of 4.3 mM in methanol [34]. The Schiff base exhibited two
types of isomers (E and Z) due to intramolecular O-H…N¼CH in-
teractions. The (E) isomer 15 is non-fluorescent, and the (Z) isomer is
fluorescent. Al3þ favors the (Z) isomer 16 (refer to Fig. 3). As a result,
the Schiff base was an effective off-on fluorescence Al3þ sensor.
2.1.2. Detection of iron
Iron is an important part of blood hemoglobin, which is used for
transportation of oxygen to cells and tissue [35]. It can also act as a
cofactor in several enzymatic electron transfer and oxidation
Fig. 3. Approach of metal ions toward the coordination sites of both isomers [34].
81
reactions, DNA synthesis, and in the normal functioning of the
central nervous system. Brain iron is important for normal myeli-
nation [35]. Myelination is defined as a process of forming a myelin
sheath around a nerve to allow nerve impulses to move more
quickly. Excess iron in a human body can initiate lipid peroxidation,
leading to an imbalance between oxidation and anti-oxidation
processes. When this unbalance happens, DNA damage will occur.
A man and woman need an average iron intake of 7 and 11 mg per
day, respectively. If iron is absorbed in excess and remains in the
tissue, then iron can cause conjunctivitis, choroiditis, and retinitis
[36]. Moreover, iron deficiency can cause low oxygen supply to cells
(which results in anemia), decrease body immunity, and lower
blood pressure [37].
Several Schiff base sensors have been synthesized for the
detection of small concentrations of iron in water and in vivo
studies. For instance, a Schiff base derived from 4-(diethylamino)
salicylaldehyde and 6-amino-7-hydroxycoumarin was used as a
selective off-on fluorescent chemosensor for Fe3þ with a DL of
4.3 mM in methanol [34]. This Schiff base exhibited two structural
isomers, e.g., a fluorescent Z-isomer and a non-fluorescent E-iso-
mer. The E-Z structural change was controlled by intramolecular
interactions between O-H…N¼CH groups. The interactions be-
tween Fe3þ and the Z isomer of a Schiff base led to an enhancement
in the structural rigidity and fluorescence of the Schiff base [34].
The color of another Schiff base 18 (e.g., synthesized from 2-(N-
methylpiperaziinylimino) acetaldehyde and rhodamine B hydra-
zine) switched from colorless to pink in the presence of Fe3þ [38].
This color change arose from the ring opening of rhodamine upon
coordination of Fe3þ (Fig. 4a). The Schiff base colorimetric sensor
displayed a DL of 2.2 mM for Fe3þ with a binding constant of
6.9  103 M1 at pH ¼ 6e7.5.
The color change and absorption spectral shift in the presence of
Fe3þ are shown in Fig. 4b and c. Likewise, the Schiff base 1-(3-(2-
hydroxynaphthalen-1-ylamino)naphthalene-2-ylamino) naphtha-
lene-2-ol was used as a fluorescent sensor for the determination of
Fe3þ [39]. This Fe3þ sensor exhibited a DL of 35.3 mM with a binding
constant of 2.7  104 M1 at pH ¼ 7. Schiff base 40 -hydroxy-30 -{[(2-
phenyl-1, 3-thiazol-4-yl)imino]methyl} biphenyl-4-carbonitrile
showed on-off-on behavior and was also an efficient fluorescence
probe for the determination of Fe3þ [36]. The previously mentioned
Schiff base displayed strong fluorescence in the absence of iron, and
the fluorescence was quenched in the presence of iron. The fluo-
rescence was regained in the presence of PO3 3 3þ
4 . PO4 dragged Fe
from the Schiff base, forming FePO4 to make the Schiff base free.
This Schiff base was employed for the detection of Fe3þ with a DL of
109 nM. In another study, Schiff base 8-hydroxyjulolidinal-azine
was used for the sensitive detection of Fe3þ with a DL of 9.5 mM and
a color change from pale yellow to violet [40].
2.1.3. Detection of chromium
Chromium influences the metabolism of different foods like
protein, carbohydrate, fat, and nucleic acids [41]. A deficiency of
82 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

Fig. 4. Development of chemosensor of Feþ3 with Schiff base: (a) Formation of Fe3þ complex with Schiff base. (b) Color (top) and fluorescence (bottom) changes of Chemosensor 1
(50 mM) after addition of various metal ions (200 mM) in wateremethanol (v/v ¼ 9/1, 2 mM TriseHCl, pH ¼ 7.4) solution. (c) Fluorescence response of 1 (50 mM) to different metal
ions (200 mM) in a wateremethanol (v/v ¼ 9/1, 2 mM TriseHCl, pH ¼ 7.4) solution. The excitation wavelength was 564 nm [37].

chromium can cause cardiovascular disease and enhance the risk of
diabetes. Moreover, excess chromium in the body may affect
cellular structure and functions [42]. In general, anthropogenic
release of chromium is in hexavalent form, which is classified as a
human carcinogen by many agencies. The severity of hazards
associated with chromium are determined by its solubility and
oxidation state, which ranges from low toxicity trivalent metal (e.g.,
Cr3þ) to highly toxic hexavalent form [41]. There is no clear
mechanism related to how chromium is toxic to humans. However,
it was assumed that the smaller size of Cr6þ may indicate that it can
cross the cell membrane and participate in different subsequent
intra-molecular reactions. Therefore, quantitative analysis of
chromium ion is very important in environmental as well as in
fluidic biological samples.
In light of such recognitions, a Schiff base derived from 6-
aminocoumarin and thiophene-2-carboxaldehyde, i.e., (6E)-6-
((thiophene-2-yl)-2H-chromen-2-one, was used for the identifica-
tion of Cr3þ in methanol [43]. The previously mentioned Schiff base
displayed a fluorescence enhancement in the presence of Cr3þ at
pH ¼ 7.4 in 4:6 (v/v) acetonitrile: HEPES buffer mixture with a DL of
1 mM. The interaction of Cr3þ with Schiff base led to reduced
electron transfer from the electron rich center (N-S) to the electron
poor center (coumarin) during photo induced electron transfer
processes. This Schiff base exhibited a more selective fluorescence
response for Cr3þ than Cr6þ. Therefore, it can be used for efficient
metal speciation. The molar concentration of Cr6þ can be calculated
by reducing it to Cr3þ followed by a subsequent enhancement in
fluorescence intensity upon treatment with Schiff base. In another
report, a Schiff base (9-{(E)-[2-(7-nitro-2,1,3-benzoxadiazol-4-yl)
hydrazinylidene] methyl}-2,3,6,7-tetra hydro-1H,5H-pyrido [3,2,1-
ij]quinolin-8-ol) colorimetric chemosensor was developed with a
DL of 0.159 mM for Cr3þ [42]. The color of the Schiff base was
changed from violet to blue in the presence of Cr3þ. Schiff bases 2,3-
dimethyl-4-(3-oxo-1,3-diphenylpropylideneamino)-1-phenyl-1,2-
dihydropyrazol-5-one (derived from condensation of 4-
aminoantipyrine and benzil) and 2,3-dimethyl-4-(2-oxo-1,2-
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91
diphenylethylideneamino)-1-phenyl-1,2-dihydro pyrazol-5-one
(derived from 4-aminoantipyrine and 1,3-diphenylpropane-1,3-
dione) were synthesized and tested as chemosensors for the
determination of Cr3þ [31]. The DLs of these Schiff bases were
0.96 mM and 1.21 mM, respectively. The binding constant calculated
for the two Schiff bases and their Cr3þ complexes were
1.13  104 M1 and 1.01  104 M1, respectively, in the pH range of
2.0e7.0. Likewise, a Schiff base 2-((9H-fluoren-2-yilimino)methyl)
phenol colorimetric chemosensor was employed for the determi-
nation of Cr3þ with a DL of 0.25 mM (binding constant
8.33  104 M1) at pH ¼ 8.5 [32].
2.2. Detection of divalent cations
2.2.1. Detection of copper
Copper is the third most abundant transition metal found in the
human body. Copper participates in various reactions in the human
body such as initiating formation of hemoglobin and participation
in the usage of iron by the body. A deficiency of copper in the hu-
man body can cause heart disease. In contrast, if present in excess
levels, it can cause Alzheimer's, Menkes, Parkinson's, and Wilson's
diseases [42,44]. These adverse effects of copper make its detection
both in vivo and in the environment critical.
Schiff base 9-{(E)-[2-(7-nitro-2,1,3-benzoxadiazol-4-yl)hydrazi-
nylidene]methyl}-2,3,6,7-tetra hydro-1H,5H-pyrido [3,2,1-ij]qui-
nolin-8-ol has been synthesized to detect Cu2þ from tap water,
drinking water and a water sample from a water purifier with a DL
of 0.36 mM by analyzing a color change from violet to yellow [42].
The Cu2þ exhibited photochromism and fluorescent switching ef-
fects (i.e., a reduction in fluorescence intensity) in a few Schiff ba-
ses, e.g., 1-(3,5-dimethyl-4-isoxazolyl)-2-{2-methyl-5-[4-hydroxyl-
3-(N-butyl-4-hydrazino-1,8-naphthal imide)-phenyl]-3-Thienyl}
perfluorocyclopentene [45]. Note that photochromism is a revers-
ible photo transformation of a chemical processes between two
forms of a molecule with different absorption spectra. The greenish
yellow color of the Schiff base changed to colorless in the presence
of Cu2þ ions due to the previously mentioned effect. A DL of 2.4 mM
was obtained with a binding constant 3.13  104 M1 and a 1:1
stoichiometry of metal to Schiff base [46]. The Schiff base synthe-
sized by condensation of diaminomaleonitrile and 1-
pyrenealdehyde was used for the detection of Cu2þ with selective
turn-on fluorescence for Cu2þ. Moreover, the color of the Schiff base
changed from visible yellow to colorless. The binding constant and
DL were 5.55  103 M1 and 100 mM, respectively [47]. Likewise,
Schiff base 2-((1Z, 3Z)-3-(2-hydroxyphenylimino)-1, 3-
diphenylprop-1-enyl amino) was used to make a phenol-based
colorimetric detection probe for the detection of Cu2þ ions [48].
In a stoichiometry of 1:1 with Cu2þ, this Schiff base showed a color
transition from colorless to yellowish brown that was visible to the
naked eye due to binding of Cu2þ to the Schiff base. This Schiff base
demonstrated a DL of 18.9 nM in a wide pH range for the deter-
mination of Cu2þ.
A highly selective benzildihydrazone-based Schiff base (1E, 2E)-
1,2-diphenyl-1,2-bis((E)-(pyridine-2-ylmethylene)hydrazono)
ethane 21 (Fig. 1e) chromogenic chemosensor was developed for
rapid detection of Cu2þ in an aqueous solution [49]. This Schiff base
was employed to identify Cu2þ in the physiological pH range.
Spectroscopic methods showed that the color changed from
colorless to reddish yellow, while colorimetric changes can be
observed by the naked eye at a concentration of 2.5 mM. A novel
Schiff base 2,20 -((1E,10 E)-(((hexylazanediyl)bis (4,1-phenylene))bis
(methanyl-ylidene))bis (azanylylidene))bis (4-methyl phenol) has
shown highly selective color transition from yellow to pink for Cu2þ
ions at concentrations of 1.89  108 M within the detection range
of 1.0  108 to 5.7  104 M [50]. Schiff base (4-diethylamino)-
83
salicylaldehyde-azine has shown selectivity and sensitivity toward
Cu2þ by displaying a color change from pale yellow to purple [40].
In another report, a Schiff base (E)-2-((2-(5-nitropyridin-2-
ylamino)ethylimino)methyl)-5-(pentan-3-yl)phenol derived from
N-(5-nitro-2-pyridyl)-1,2-ethanediamine and 4-(diethylamino)-2-
hydroxybenzalde-hyde has been used for the detection of Cu2þ
by color switching from colorless to yellow with a DL of 0.88 mM
[51]. The on-off-on fluorescence sensing signals on a benzildihy-
drazone-N,N0 -bis(2-hydroxy-4-diethylamino-1-formylbenzene)
Schiff base were identified for the detection of Cu2þ in environ-
mental samples (e.g., tap water, rain water, and simulated urine
samples) with a DL of 0.73 nM for Cu2þ determination at pH ¼ 7.0
[52]. The Schiff base showed a color change from yellow to red in
the presence of Cu2þ. This fluorescent sensor is one of the best
sensors in terms of DL among the Cu2þ sensors discussed in this
review.
2.2.2. Detection of mercury
Mercury has adverse effects on the environment as well as on
human health due to its toxic nature. Excessive exposure to mer-
cury and its derivatives can cause serious heart problems, brain
dysfunction, kidney diseases, and diseases associated with the
central nervous system [53]. These effects of mercury have helped
focus efforts on developing a specific, sensitive, and cost-effective
sensor. Schiff bases are promising candidates to develop mercury
sensors. An acenaptho [1,2-b]quinoxaline-based thio-
semicarbazone displayed aggregation-induced emission enhance-
ment (AIEE) properties for the detection of Hg2þ with an “on-off”
fluorescent response [54]. The Schiff base was characterized by FT-
IR, 1H NMR, 13CNMR and HR-MS (TOF-MS). This Schiff base was
selective and sensitive to Hg2þ in DMSO/H2O (v/v ¼ 9/1). The
response time of the sensor was only 10 s and showed color change.
Under natural light, the color of the Schiff base changed from yel-
low to yellow green, while it changed from yellow to light red under
UV irradiation. Likewise, a new phenanthroline-based Schiff base
24 (Fig. 5a) was synthesized by condensing 1,10-phenanthroline-
2,9-dicarbaldehyde 22 with 1H-indole-2-carbohydrazide 23 [55].
This Schiff base selectively identified Hg2þ in different water
sources (e.g., tap, drinking, deionized, ditch, lake, and ground wa-
ter) by a fluorescence ‘on-off’ response. The sensor exhibited a DL
value of 21.71 ppb in the 4.0e12.0 pH range and a binding constant
of 1.77  105 M1. The reported sensor was able to detect Hg2þ in
the presence of other competing ions by showing a transition from
colorless to yellow, which indicates the Schiff base was selective for
mercury. The changes in absorption spectrum and the color in the
presence of Hg2þ are shown in Fig. 5b and c. In another study, Schiff
base 2-(diphenyl methylene amino)benzenethiol 27 was derived by
condensing benzophenone 25 and 2-aminobenzenethiol 26 (Fig. 1f)
and was used for the detection of Hg2þ with a DL 0.0226 mM [56].
The sensor displayed good performance over a wide pH range of
5.0e10.0.
2.2.3. Detection of cobalt
Cobalt is classified as a trace element in the human body and is
part of vitamin B12, which plays a role in the metabolism of iron and
synthesis of hemoglobin. The presence of cobalt above allowable
levels can cause vasodilatation, flushing and cardiomyopathy,
serious kidney problems, and malfunctions in the respiratory/
central nervous system [57]. In contrast, the absence of cobalt in the
human body can cause various problems such as growth retarda-
tion, anemia and weight loss. A variety of Schiff bases have been
explored for the development of efficient sensors to detect cobalt
cations. For instance, Schiff base 2-((4-(2-
hydroxybenzylideneamino) phenylimino) methyl)phenol 30 was
utilized to sense Co2þ ions with a DL 0.782 mM in ethanol in the
84 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

Fig. 5. Development of 1,10-Phenanthroline based Schiff base sensor: (a) Synthesis of phenanthroline based Schiff base. (b) UV/vis spectra of phenanthroline based Schiff base
(30 mM) recorded in H2O (0.5% DMSO) after addition of 5 equiv of various metal ions. (c) The color changes observed by the naked eye for a phenanthroline based Schiff base (30 mM)
upon the addition of 5 equiv. of various metal ions in H2O (0.5% DMSO) [55].

range of 8.0  107 to 2  106 M [58]. The previously mentioned
Schiff base showed an enhanced fluorescence response at 350 nm
for Co2þ in an ethanol medium. The interference of other ions, e.g.,
Cu2þ and Fe3þ was nullified by reducing them with ascorbic acid
and citric acid, respectively. The coordination of Co2þ with OH
groups was likely responsible for the enhanced fluorescence signals
of the Schiff base. The coordination of Co2þ to this Schiff base
strengthened the hydrogen bonds between the hydrogen of OH
from salicylaldehyde moieties and the nitrogen of p-phenylenedi-
amine moieties, which resulted in the restriction of rotation of the
molecule and enhance fluorescence intensity (Fig. 1g).
In another report, (E)-benzyl-2-((7-(diethylamino)-2-oxo-2H-
chromen-3-yl)methylene)hydra-zine was synthesized and used for
ratio metric and selective colorimetric chemosensing of Co2þ dur-
ing which a color change could be identified using the naked eye in
an acetonitrile:water in 1:1 (v/v) medium with a DL of 0.13 mM at
pH ¼ 7.4 over the concentration range of 0.2e1 mg/ml [38]. The
stoichiometric ratio of metal to ligand was determined to 2:1 by
Job's method (refer to Fig. 6a and b for absorption spectrum and
color change).
2.2.4. Detection of zinc
Zinc is the second most abundant transition metal ion next to
iron in the human body [59]. Biologically, it plays many important
roles in enzymes systems, gene transcription, and regulation of
metallo-enzyme signal transmission in the nervous system. If its
level increases beyond the body's requirement, then it shows
many adverse effects such as Alzheimer's, Parkinson's, and
Menkes diseases, and familial amyotrophic lateral sclerosis [60].
The development of effective and efficient sensors is crucial for
zinc determination and estimation in various matrices as part of a
strategy to manage the health problem associated with excess
zinc. To this end, a Schiff base 7-(40 -(diethylamino)-20 -hydrox-
ybenzylideneimino)-4-methylcoumarin 36 was derived by
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91 85

Fig. 6. Development of colorimetric cobalt (II) chemosensor based on coumarin: (a) UVevis absorption spectra of HL (40 mM) upon addition of various metal ions (1.0 equiv) in
CH3CNewater (1/1, v/v, 10 mM HEPES buffer, pH ¼ 7.4) solution. (b) Color changes of (E)-benzyl-2-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene) hydrazine (40 mM) in
CH3CNewater (1/1, v/v, 10 mM HEPES buffer, pH ¼ 7.4) solution in the presence of 1.0 equiv. of various metal ions) [38].

reacting 7-amino-4-methylcomarin 34 and 4-diethylamino sali-
cylaldehyde 35. It was then employed for the selective
fluorescent-based detection of Zn2þ (Fig. 7a and b: synthesis of
the Schiff base and absorption spectrum change) [61]. In an
uncomplexed state, the free Schiff base underwent isomerization
by the free rotation of eC¼N bonds due to photo induced electron
transfer to make it non fluorescent. Nonetheless, the free rotation
is hindered upon binding with metal ions, which makes the
complex fluorescent.
Likewise, tris(3-(2-hydroxyacetophenone)propyl)amine derived
from tris(3-aminopropyl) amine and three equivalents of 2-
hydroxyacetophenone were employed as selective turn on fluo-
rescent sensors for Zn2þ in environmental samples with a DL, linear
detection range, and a binding constant of 88 nM, 1.6  107 to
5  105 M, 3.08  108 M1, respectively [62]. A Schiff base N, N0 -bis
(p-chlorosalicylidene)-1,2-etheylenediamine derived from p-
chlorosalicylaldehyde and 1,2-ethylenediamine has shown fluoro-
genic signaling toward Zn2þ with a DL of 3.21 mM [63]. This che-
mosensor showed the direct influence of a solvent on the optical
properties of light absorbing molecules. In another report, a Schiff
base, i.e., N, N0 -bis (salicylidene)-1,2-phenylenediamine was syn-
thesized from the condensation of salicylaldehyde and 1,2-
phenylenediamine in ethanol [64]. This Schiff base 39 served as a
selective fluorescent chemosensor for Zn2þ. Schiff base derived
from 4,5-dimethyl-1,2-phenylendiamine 37 and furfuraldehyde 38
(Fig. 1h) was also used as a selective fluorescence probe for Zn2þ
[65]. The complex showed stronger fluorescence than the ligand as
the Zn2þ ion is not simply oxidized or reduced since it has a closed
shell electronic configuration.
The complex derived from Zn2þ and 1-amino-2-propanol and 2-
hydroxybanzaldehyde showed strong fluorescence. Two different
products can be obtained from this complex by varying the reaction
conditions [66]. If a Schiff base is mixed with Zn2þ salt and a simple
Zn complex was formed after slow evaporation. Secondly, nano-
particles of a Zn complex were formed using a solvothermal
method, which were further converted to ZnO nanoparticles.
Likewise, a Schiff base ligand 1-[(2-pyridin-2-yl-ethylimino)-
methyl]-naphthalen-2-ol was used for selective detection of Zn2þ
and showed a color change from yellow to transparent blue under
UV irradiation [67]. The free ligands remained non-fluorescent due
to the excited state intramolecular proton transfer between
phenolic eOH and imine nitrogen eC¼N- rotation. Fluorescence
intensity was enhanced by removing these two effects through
complexation with Zn2þ (Fig. 8a and b). This indicates that the
Schiff base under study could be used as colorimetry and fluores-
cent sensors for Zn2þ.
The on-off behavior of another Schiff base 42 (derived from
reacting 2-hydroxynaphthalene-1-carboxaldehyde 40 and tris (2-
aminoethyl)amine) 41 was used for the selective determination of
Zn2þ [68] (Fig. 1i). Upon complexation, the ligand showed a drastic
color change from colorless to fluorescent blue with a DL of 48.9 nM
and a binding constant of 1.23  107 M1. The color change
confirmed that Zn2þ was selectively bound with the Schiff base. The
non-fluorescent Schiff base showed fluorescence properties upon
complexing with Zn2þ, which can be explained in terms of the
formation of a rigid complex. The presence of Zn2þ enhanced the
fluorescence of a Schiff base by chelation and blocking of photo
induced electron transfer.
86 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91

Fig. 7. Development of Schiff base (36) sensor for Znþ2: (a) Synthesis of (E)-7-(4-(diethylamino)-2-hydroxybenzylideneamino)-4-methyl-2H-chromen-one. (b) Fluorescence spectra
of HL (50 mM) upon the addition of metal salts (50 mM) of Naþ, Kþ, Agþ, Mg2þ, Ca2þ, Pb2þ, Cr3þ, Mn2þ, Fe2þ, Ni2þ, Co2þ, Fe3þ, Cu2þ, Ba2þ, Cd2þ, Al3þ, and Zn2þin DMF-H2O (v/v, 9:1)
(lex ¼ 380 nm, slit widths: 3 nm/3 nm) [61].

2.2.5. Detection of nickel
Nickel is considered to be toxic and carcinogenic. It can damage
the respiratory system, kidneys, and liver or decrease body immunity
[69]. A Schiff base synthesized from the condensation of 2-
aminophenylsulfide and 5-chlorosalicylaldehyde was effectively
and selectively applied for the detection of Ni2þ using fluorescence
spectrophotometry. In the presence of a 60 mM Ni2þ ion in water
sample, the fluorescence intensity of the Schiff base increased due to
chelation of Ni2þ with the Schiff base. The DL and binding constant
(i.e., for the metal ion and Schiff base) for Ni2þ sensing were 8.67 nM
and 4.18  105 M1, respectively [70]. Schiff bases were also
employed for the optical determination of Ni2þ. For instance, 4-
chloro-2-[(3-(4-(dimethylamino)phenyl) allyli-dene)amino] Schiff
base was synthesized by condensing 2-amino-4-chlorophenol and 4-
dimethylaminocinnamaldehyde and was used as a selective and
effective colorimetric sensor of Ni2þ [71]. The color of this Schiff base
changed from yellow to orange in the presence of Ni2þ. In aqueous
samples, the operating pH range for Ni2þ determination was 5.5e8.
DL values of 0.1 and 1 mM were achieved when measurements were
done by spectroscopy and the naked eye, respectively. Another
chromogenic Schiff base, i.e., N,N0 -bis(3-methylsalicylidene)-ortho-
phenylenediamine was also synthesized for the spectrophotometric
determination of Ni2þ from natural food samples (e.g., starch, sugar,
black tea leaves, tobacco, and rice flour) [72]. The obtained sensing
results were comparable with those obtained by using atomic
absorption spectroscopy (AAS). The DL of the sensor was 13.6 nM
with a linear range of detection from 0 to 0.1  105 M (at a metal to
Schiff base stoichiometric ratio of 1:1).
2.2.6. Detection of other cations
2.2.6.1. Detection of lead. When found in abnormal concentrations
in the body, lead can cause mental retardation in children, head-
aches, poor attention, loss of memory, dullness, and irritability
[41,73].
Schiff base 4-((E)-4-hydroxy-3-((E)-(2-mercaptoethylimino)
methyl) benzyl)-2-((E)-(2-mercaptoethylimino)methyl)phenol was
derived for the detection of lead by reacting 5,50 -methylenebis (2-
hydroxybenzaldehyde) and 2-aminoethanethiol in ethanol [74].
This Schiff base was proven to be a sensitive fluorescence turn-on
sensor for the selective determination of Pb2þ in 95:5 (v/v) aceto-
nitrile:water. The free state of the Schiff base showed weak fluo-
rescence at a 508 nm emission wavelength. In contrast, the
emission of this Schiff base was enhanced at a 508 nm emission
wavelength upon complexing with Pb2þ. Note that the binding
constant value for the Schiff base and Pb2þ was 2.1  104 M1. This
fluorescent sensor can be applicable for a wide pH range of
3.0e13.0 with a DL of 0.38 mM. The sensor was specific for the Pb2þ
ions and displayed no interference in the presence of other metal
cations with free ligands. Likewise, a fluorescent substance, i.e., 2-
hydroxy-1-napthaldehydene-8-aminoquinoline, was synthesized
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91
Fig. 8. Development of fluorescence sensor for Zn2þ using HPEMN: (a) Proposed
mechanism for the fluorescence changes of Schiff base upon addition of Zn2þ. (b)
Fluorescence spectra of HPEMN (5  106 M) with addition of increasing amount of
Zn2þ (0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 mM) in H2O/acetonitrile (8:2, v/v) HEPES buffer
(pH ¼ 7.4) medium. Inset shows fluorescence emission intensity of HPEMN
(lex ¼ 398 nm, lem ¼ 452 nm, slit: 5 nm/5 nm) [67].
and modified to a sol-gel for selective identification of lead with a
DL of 0.083 mM over the linear detection range of 1.9  107 to
1.9  104 M [75]. When Pb2þ was bound to the previously
mentioned Schiff base, it restricted the rotation of the molecule of
the Schiff base to enhance the fluorescence signals. The selectivity
test confirmed that the sensor was selective for Pb2þ, while no
sensing signals were generated in the presence of other metal
cations (e.g., Fe3þ, Al3þ, Cr3þ, Mg2þ and Ni2þ). The selectivity may
be due to the soft acidity of Pb2þ and the borderline nature of ni-
trogen. Since nitrogen coordinate with both soft and hard metals, it
has a unique role in coordination chemistry.
2.2.6.2. Detection of palladium. Pd2þ can bind with proteins, RNA,
and DNA, making it cytotoxic and the cause of skin and eye irrita-
tion [76]. Two Schiff bases (e.g., Schiff base 46 and 47) (Fig. 1j)) were
synthesized to detect the presence of Pd2þ [77]. Note that both the
Schiff bases were characterized by 1HNMR, 13CNMR, and FT-IR
elemental analysis and MS-ESI. Schiff base 1,3-(benzo[d]thiol-2-
yl)-7-hydroxy-2H-chromen-2-one 46 was synthesized from 2,4-
dihydroxy benzaldehyde 43, O-aminothiophenol 44, ethyl-
cyanoacetate 45, and benzoic acid in DMF and was used for naked
eye-based color change (e.g., from colorless to sienna) detection of
Pd2þ with a DL of 29 mM. On the other hand, Schiff base, i.e., 3(benzo
[d]oxazol-2-yl)-7-hydroxy-2H-chromen-2-one 47, was derived
from 2, 4-dihydroxybenzaldehyde 43, O-aminophenol 44 ethyl-
cyanoacetate 45, and benzoic acid in DMF. Both the Schiff bases
were also employed for the fluorescence-based detection of Pd2þ.
The Pd2þ caused a higher level of fluorescence quenching in the
87
case Schiff base 1, as Pd2þ prefers interactions with the sulfur in
Schiff base 1 rather than with oxygen present in Schiff base 2. Note
that the Schiff base 1 showed color as well as absorption/emission
spectra changes due to stereo and electronic effects caused by the
sulfur atom present in its structure.
2.2.6.3. Detection of cadmium. Cadmium has been used in
rechargeable batteries, fertilizers, coloring agents, and electro-
plating industries. Exposure of Cd can cause renal dysfunction,
calcium metabolism disorders, and increased risk of cancer [78].
Another study confirmed that chronic intake of Cd2þ can alter
respiratory function, while decreasing olfactory function and bone
mineral density [79,80]. Schiff base cinnamaldehyde-4-
hydoroxybenzoylhydrazone has been synthesized for the selec-
tive identification of Cd2þ from biological and environmental
samples by giving a yellow color on complexation [81].
2.2.6.4. Detection of manganese. Although manganese was classi-
fied as having low acute toxicity for humans, neurotoxic effects
have been observed in animals taking high concentrations man-
ganese salts in food. High intake of manganese can cause anemia
because of iron sequestration [82]. A slane-type Schiff base was
derived from the condensation of ethyl-O-hydroxybenzene with
ethylene diamine and ethylenesalicylidine-bisethylenediamine for
the spectrophotometric detection of Mn2þ in pharmaceutical
products [83]. The complex showed a brown color at pH ¼ 6.0 upon
complexation of a Schiff base with this metal.
2.3. Detection of anions
Many of the receptors synthesized were used for the detection
of cations, while only a few Schiff base detectors were developed
for anion identification [84].
This is explained in terms of the different properties of anions.
Anions are larger in size, and the compounds formed are not so
stable. As different anions exhibit different geometries (e.g., SO2
4 if
different in geometry from PO3 4 ), the presence of a large number of
lone pairs of electrons results in significant repulsion. As such, they
are highly hydrated and stable under a narrow pH range. Most of
the mechanisms employed for sensing anion species were based on
sequential detection, i.e., formation of metal complexes of a Schiff
base followed by reacting with anions [52], hydrogen bonding [85],
and induced charge transfer. In this section, fluorescence and
chemosensor techniques developed for the sensing of anions by
employing Schiff bases are discussed.
2.3.1. Detection of cyanide
Cyanide is highly poisonous due to its ability to bind to Fe pre-
sent in cytochrome c-oxidase, resulting in disruption of electron
transportation [52]. Despite its toxicity, cyanide is used in large
amounts in chemical industries such as the fiber and polymer in-
dustry, gold mining, and in electroplating processes. To control the
amount of cyanide in environmental samples, sensors are neces-
sary to identify its presence in extremely low concentrations [51].
Chemosensor 4-((2,4-dichlorophenyl)diazenyl)-2-(3-hydro
xypropylimino)methyl)phenol 48 (Fig. 9aec: color and absorption
spectral change) was investigated for CN detection based on color
changes from yellow to reddish orange [86]. The color change was
explained in terms of CN interactions with the Schiff base. The CN
interacted with the functionality of the Schiff base in two ways: (1)
through hydrogen bonding with phenolic groups and (2) covalent
interactions with imine double bonds. The DL for this sensor was
1.03 mM with a binding constant of 2.71  104 M1 between the
Schiff base and ions under basic conditions.
88 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91
Fig. 9. Development of a chemosensor by interaction of CN with Schiff base (48): (a)
Reaction scheme (b) Color changes. (c) UVevis absorption spectra of Schiff base 4-((2,
4-dichlorophenyl)diazenyl)-2-(3-hydroxypropyl imino) methyl) phenol
(5  105 mol L1) in DMSO/H2O (95:5) in the presence of 10 equiv. of diverse anions
[86].
Schiff base N,N0 -bis(2-hydroxy-4-diethylamino-1-
formylbenzene) showed an improved DL of 0.15 mM at pH ¼ 7.0 and
was used to identify CN in the environment by sequential displace-
ment of Cu2þ from Schiff base Cu2þ complexes [52]. The fluorescence
of a Schiff base was quenched in complexed form with Cu2þ. When
CN was added to the Cu2þ complexes of the Schiff base, the fluo-
rescence of the free Schiff base was regenerated due to strong in-
teractions between CN and Cu2þ. The interactions between CN and
Cu2þ led to the formation of cuprous cyanide, which resulted in
fluorescence.
Likewise, Schiff base 3-(2-butyl-1H-benzo [d]imidazole-1-yl)-
N0 -((2-hydroxynapthalen-1-yl) methylene) propanehydrazide was
employed for colorimetric and fluorometric detection of CN with
DLs of 2.0 nM and 97 mM, respectively [87]. The colorless Schiff base
changed to yellow under white light and showed blue fluorescence
under UV light. The change in fluorescence and UV/vis properties of
the Schiff base was expected due to the nucleophilic attack of CN
on carbonyl groups of the Schiff base, which was followed by
proton transfer of the hydrazone hydrogen to the alkoxide anion. At
the same time, proton transfer from O-H to the hydrazone nitrogen
took place, which induced changes in spectrum properties.
2.3.2. Detection of fluoride
Although there has been great improvements in the oral health
of the population, problems still exist. Water fluoridation can result
in elevated concentrations of fluoride, increasing the risk of
unaesthetic dental fluorosis [88]. For this reason, research is still
going on to identify fluoride in the environment using a simple
method of sensor application. Schiff base 1-((1H-indol-3-yl)
methylene)-2-(4-nitrophenyl) hydrazine was synthesized for the
colorimetric and turn-on fluorescence identification of F. The
binding constant and stoichiometry between the metal and the
Schiff base was calculated [89]. The Schiff base exhibited a color
change from yellow to purple in the presence of this ion regardless
of the presence of other anions and cations. The spectral change
may be due to the charge transfer induced by fluoride between the
electron rich and electron deficient center of the Schiff base.
Another Schiff base, i.e., 1-(3, 5-dimethyl-4-isoxazolyl)-2-{2-
methyl-5-[4-hydroxyl-3-(N-butyl-4-hydrazino-1, 8-
naphthalimide)-phenyl]-3-thienyl}perfluorocyclopentene was
explored for the identification of F [46]. This Schiff base displayed
color change from greenish yellow to blue upon binding of fluoride
to the Schiff base. The binding of F led to the deprotonation of both
NH2 and OH of the Schiff base, which enhanced the electron density
on nitrogen to induce charge transfer to the Schiff base. This is the
reason for the change in color.
2.3.3. Detection of iodide
Iodine is classified as an essential ingredient in thyroid hor-
mones. Both low and high iodine intake may cause thyroid disease
[90,91]. The effects of iodine are a major problem globally. Schiff
base 1-(3-(2-hydroxynaphthalen-1-ylamino) naphthalene-2-
ylamino) naphthalene-2-ol was synthesized for the detection of
iodide anions from the condensation of naphthalene-2, 3-diamine
with 2-hydroxy naphthalene-1-carbaldehyde using a catalytic
amount of Zn(ClO4)2. A DL of 0.425 mM was achieved using UV/vis
spectroscopy, and the binding constant value was 4.5  103 M1 at
pH ¼ 7.0 [39].
2.3.4. Detection of phosphate
Schiff base 4-((2,4-dichloro phenyl)diazenyl)-2-(3-
hydroxypropylimino) methyl)phenol was synthesized for the
detection of H2PO 4 in the presence of other ions by the conden-
sation of 3-amino-1-propanol and 1-(3-formyl-4-
hydroxyphenylazo)-2,4-dichlorobenzene in ethanol. The phenolic
OH served as the binding sight for anions to induce color changes
from yellow to orange for H2PO 4 with a DL of 1.24 mM [33].
3. Performance evaluation
Different methods for the analysis of cations and anions using a
variety of Schiff bases were discussed in this review. The literature
shows that some cations are well detected with one particular
Schiff base as opposed to others when the analysis is made using a
particular technique. In this subsection, the performance of Schiff
bases for sensing diverse metals is discussed.
As a simple means of assessing the best performing Schiff base
for a given target, DL values were compared as a main criterion, and
the best performing Schiff base is recommended for the analysis of
target ionic species. From a total of 10 Schiff bases studied for the
detection of Al3þ, (3, 5-dichloro-2-hydroxybenzylidene) quinolone-
2-carbohydrazide using fluorescence spectroscopy was seen to be
most sensitive with a DL of 12 nM [28]. Seven Schiff bases were
discussed for the detection of Cu2þ, and benzildihydrazone- N,N0 -
bis(2-hydroxy-4-diethylamino-1-formyl benzene) recorded the
best DL of 0.73 nM by a colorimetric and fluorescence spectroscopy
technique [52]. In a similar way, Schiff base tris(3-(2-
hydroxyacetophenone) propyl)amine showed good performance
for Zn2þ with a DL of 88 nM using fluorescence spectroscopy and
colorimetry from eight Schiff bases examined [62]. In the case of
Fe3þ, a 40 -hydroxy-30 -{[(2-phenyl-1, 3-thiazol-4-yl)imino]methyl}
 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91 89

biphenyl-4-carbo nitrile-based fluorescence spectroscopy tech-
nique exhibited the best DL of 109 nM from the five discussed Schiff
bases [36].
For the detection of Hg2þ, fluorescence spectroscopy and
colorimetry were applied using a Schiff base made by condensation
of 1, 10-phenanthroline-2, 9-dicarbaldehyde with 1H-indole-2-
carbohydrazide [55] out of the three discussed Schiff bases.
Accordingly, this approach yielded a DL of 21.71 ppb. Likewise,
colorimetric detection was developed based on Schiff base for the
analysis of Cr3þ using 2,3-dimethyl-4-(2-oxo-1,2-diphenyl ethyl-
ideneamino)-1-phenyl-1,2-dihydropyrazol-5-one recorded DL of
0.12 mM (Kumawat et al., 2016) from the three Schiff bases dis-
cussed. Out of the discussed Schiff bases, Schiff base 2-((E)-(2-(2-
((E)-5-chloro-2-hydroxybenzylideneamino) phenylthio)phenyl-
imino)methyl)-4-chlorophenol was recommended for the analysis
of Ni2þ using fluorescence spectroscopy with a DL of 8.67 nM [70].
From the limited discussion on the sensing of Pd2þ, the Schiff
base synthesized from the condensation of 2-hydroxy-1-
naphthaldehydene-8-aminoquinoline yielded a DL of 0.038 mM
based on fluorescence spectroscopy (Guo et al., 2008). For Co2þ, (E)-
benzyl-2-((7-(diethylamino)-2-oxo-2H-chromen-3-yl) methylene)
hydrazine yielded a DL of 0.31 mM using UVevis spectroscopy
techniques [38].
Ligands other than Schiff bases were also studied. These are
referred to here as non-Schiff base ligands. The DL values for some
non-Schiff base ligands are discussed here to allow a simple com-
parison with the sensitivities of Schiff bases. Non-Schiff base li-
gands were utilized for the detection of different metal ions in the
environmental and biological samples. A non-Schiff base ligand 1-
((8-hydroxyquinolin-5-yl) methyl)indolline-2,3-dione was used for
enhanced fluorescent sensors for Al3þ with a DL of 7.3 mM [92].
Fluorescent gold nanoclusters were synthesized and used for the
detection of Fe3þ with a DL of 0.2 mM by fluorescence quenching
[93]. N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-7-
hydroxy-2-oxo-2H-chromen-3-carbox amide was synthesized and
used for the detection of Fe3þ with a detection limit of 0.3 mM by
fluorescence quenching [94]. Hemicyanine dye for the colorimetric
and fluorometric detection of Hg2þ was synthesized and showed a
DL of 50 nM [95]. Ligand (E)-4-methyl-2-((1-methyl-1H-benzo [d]
imidazole-2-yl)phenol was synthesized for colorimetric detection
of Ni2þ with a DL of 2.79  103 M [96]. For the detection of Zn2þ, 5-
(2-(allyloxy)phenyl)-3-(2-hydroxy-5-methylphenyl)-4,5-
dihydropyrazole-1-carbothio amide showed a DL of 0.61 mM with
enhanced fluorescence [97]. The ligands 2-(pyridine-2-yl-methyl-
amino)-N-(quinol-8-yl)acetamide showed fluorescence quenching
upon complexing with Zn2þ, resulting in a DL of 885 mM [98]. [2-
(20 -aminophenyl)benzoxazole-amide-2-picolylamine] showed
fluorescence enhancement upon coordination with Zn2þ, which
yielded a DL of 0.0366 mM [99]. Glycine on hydrazine adsorbed gold
nanoparticles was used for the detection of Cu2þ from environ-
mental samples [100]. Detection of Cu2þ was made using Raman
spectroscopic techniques and DLs of 500 nM and 1 mM were
observed in distilled water and river water, respectively.
For selective and sensitive detection of Pb2þ, Pb2þ-driven DNA
molecular devices were constructed based on a DNA duplex-
quadruplex exchange with a DL of 20 nM. This was used for
detecting Pb2þ using fluorescence turn on [101]. Gold nanoparticles
functionalized with a dithiocarbamate-modified N-benzyl-4-(pyr-
idin-4-ylmethyl)aniline ligand were also used for colorimetric
detection of Cr3þ in an aqueous solution with a DL of 31 ppb; the
ligand showed color change upon complexing with Cr3þ and
changed from wine red to blue [102]. For detection of Co2þ, a simple
method based on the analyte-induced fluorescence quenching of
carbon dots was developed with DL of 0.45 mM [103].
The performance of Schiff bases for the detection of several
metal ions was compared with non-Schiff base ligands in terms
their DL (refer Table 3). The Schiff base sensors are advantageous
(over non-Schiff base sensors) in terms of the simplicity of their
synthesis, high sensitivity, and selectivity [104e106]. The Schiff
bases are effective off-on sensors; for instance, 4-(diethyl amino)
salicylaldehyde and 6-amino-7-hydroxycoumarin exist in two
types of isomers (E and Z) due to intramolecular O-H…N¼CH in-
teractions. The E isomer 15 is non-fluorescent. In contrast, the Z
isomer 16 is fluorescent to make the detection of this isomer

Table 3
Performance comparison of some Schiff base and non-Schiff base sensors in terms of detection limits (DL).

Order Detected ions Schiff base Methods DL Non-Schiff base DL method

1 Al3þ (3,5-dichloro-2-hydroxybenzylidene) fluorescence spectroscopy 12 nM gold nanocluster 0.3 mM enhanced

quinolone-2-carbohydrazide fluorescence
2 Cu2þ (benzildihydrazone- N,N0 -bis(2- colorimetric and 0.73 mM gold nanoparticles 1 mM Raman
hydroxy-4-diethylamino-1-formyl fluorescence spectroscopic
benzene))
3 Zn2þ tris (3-(2-hydroxyacetophenone) fluorescence spectroscopy 88 nM [2-(20 -aminophenyl) 36.6 nM fluorescence
propyl)amine and colorimetric benzoxazole-amide-2- chemosensor
picolylamine]
4 Fe3þ base 40 -hydroxy-30 -{[(2-phenyl-1,3- fluorescence spectroscopy 109 nM gold nanocluster 0.2 mM fluorescence
thiazol-4-yl)imino]methyl}biphenyl-4- quenching
carbo nitrile
5 Hg2þ Schiff base synthesized from fluorescence spectroscopy 22.2 nM Hemicyanine dye 50 nM colorimetric and
condensation of 1, 10-phenanthroline- and colorimetry fluorometric
2, 9-dicarbaldehyde with 1H-indole-2-
carbohydrazide
6 Cr3þ 2,3-dimethyl-4-(2-oxo-1,2-diphenyl colorimetric 0.12 mM AuNPs functionalized with 31 ppb colorimetric
ethylideneamino)-1-phenyl-1,2- a dithiocarbamate-
dihydropyrazol-5-one modified N-benzyl-4-
(pyridin-4-ylmethyl)aniline
7 Ni2þ 2-((E)-(2-(2-((E)-5-chloro-2- fluorescence spectroscopy 8.67 nM (E)-4-methyl-2-((1- 2.79  103 M colorimetric
hydroxybenzylideneamino) methyl-1H-benzo [d]
phenylthio)phenylimino)methyl)-4- imidazole-2-yl)phenol
chlorophenol
8 Pb2þ 2-hydroxy-1-naphthaldehydene-8- fluorescence spectroscopy 0.038 mM Pb2þ-driven DNA molecular 20 nM Turn-On
aminoquinoline device Fluorescence
9 Co2þ (E)-benzyl-2-((7-(diethylamino)-2- UVevis spectroscopy 0.31 mM carbon dots 0.45 mM fluorescence
oxo-2H-chromen-3-yl)methylene) quenching
hydrazine
90 A.L. Berhanu et al. / Trends in Analytical Chemistry 116 (2019) 74e91
through complex formation with aluminum (refer to Fig. 6). Simi-
larly, the performance (e.g., DL, sensitivity, and selectivity) of Schiff
base (16) sensor is much better in case of Cuþ2 than other Schiff
base (or non-Schiff base) sensors because the electron in its C¼N
group can have enhanced chelation with most metal ions [42]. In
addition to sensing, Schiff base has versatile applications in various
fields such as anti-fungal, anti-inflammatory, anti-oxidant, and
anti-cancer agents due to their strong chelating nature [4].
Transition-metal complexes of Schiff bases have also been found to
be useful as antibacterial agent [4,107], excellent catalysts [4], and
efficient drugs in the field of pharmacology [108]. Evidence from all
the available literature indicates that Schiff bases are easy to syn-
thesize with high purity products compared to non-Schiff bases.
4. Conclusion
Schiff base ligands play important roles in multiple areas of
application. As highlighted in this review, Schiff bases incorporated
as chelating agents are effective in sensing and the detection of
various ions with the aid of diverse analytical techniques (such as
UVevis and spectrofluorometry). On complexation with Schiff base
ligands, toxic and poisonous ions can quickly be identified under
ultraviolet radiation or by the naked eye by showing fluorescence
turn-on or turn-off mechanisms. Comparative analysis of the
sensitivity (e.g., detection limit) clearly demonstrated that Schiff
bases offer high sensitivity for particular ions in various kinds of
matrices. A single Schiff base can be used as a sensor for more than
one ion at a time under the same condition. The rapid change in
color from uncomplexed to complexed form can exhibit photo-
chromism with a particular ion. As explained above, Schiff bases
undergo a color change from yellow to purple in the presence of
fluoride ions, regardless of the interferences. The characteristic
complexing ability of Schiff bases makes them highly specific and
sensitive in detecting various targets in nature. Note that many
Schiff bases have been synthesized for the detection of toxic
chemicals. Nonetheless, there is still a growing need to explore the
optical sensing properties of these already synthesized Schiff base
metal complexes and to synthesize new ones with enhanced
sensing properties.
As discussed in this work, many works have been done on the
detection of toxic chemicals from the environment and biological
samples using a Schiff base as optical sensors. Among various
detection options, online detection is a challenging issue which
should be worked on. This can be done by devising electronics
probes using chemosensors and integrating the signals with
internet for online mapping of various environmental samples in
real time. This will help in detecting pollution and the related
problems at the very onset of a problem so that the proper control
measures can be taken at the right time. Schiff bases can also be
applied for the speciation of toxic metal ions like Cr(III)/Cr(VI). As
such, Schiff base plays a great role in diverse fields including optical
sensors and many other applications (e.g., antibiotics, antibacterial,
anticancer, antioxidants, and catalysts). The facile synthesis of
Schiff bases within one or two steps makes them preferably chosen
for highly versatile applications in various fields.
Acknowledgements
We acknowledge support made by the R&D Center for Green
Patrol Technologies through the R&D for Global Top Environmental
Technologies program funded by the Ministry of the Environment
(Grant No: 2018001850001) as well as by a grant from the National
Research Foundation of Korea funded by the Ministry of Science,
ICT & Future Planning (Grant No: 2016R1E1A1A01940995). This
work was also supported by “Cooperative Research Program for
Agriculture Science & Technology Development (Project No.
PJ014297)” Rural Development Administration, Republic of Korea.
VK acknowledges support from the Department of Science and
Technology, New Delhi, India in the form of an INSPIRE Faculty
Award and we also acknowledges support from the Department of
Chemistry Punjabi University, Patiala and the Ethiopian ministry of
Education for providing financial assistance.
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