Quinoline appended pillar[5]arene (QPA) as Fe3+ sensor and complex of Fe3+ (FeQPA) as a selective sensor for F?, arginine and lysine in the aqueous medium

Article abstract of DOI:10.1016/j.saa.2019.117390

A quinoline functionalized pillar[5]arene, QPA has been prepared and its interaction with biologically relevant ions and molecules in aqueous solution has been demonstrated. The sensor molecule, QPA has shown selectivity towards Fe³⁺ among elev

Full text of DOI:10.1016/j.saa.2019.117390

Accepted Manuscript
Quinoline appended pillar[5]arene (QPA) as Fe3+ sensor and
complex of Fe3+ (FeQPA) as a selective sensor for F−, arginine
and lysine in the aqueous medium
Roymon Joseph, Adersh Asok, Kuruvilla Joseph
PII:
S1386-1425(19)30780-2
DOI:
https://doi.org/10.1016/j.saa.2019.117390
Article
Number:
Reference:
1
17390
SAA 117390
Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy
To appear in:
Received date:
Revised date:
Accepted date:
11 June 2019
7 July 2019
14 July 2019
Please cite this article as: R. Joseph, A. Asok and K. Joseph, Quinoline appended
pillar[5]arene (QPA) as Fe3+ sensor and complex of Fe3+ (FeQPA) as a selective sensor
for F−, arginine and lysine in the aqueous medium, Spectrochimica Acta Part A: Molecular
and Biomolecular Spectroscopy, https://doi.org/10.1016/j.saa.2019.117390
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ACCEPTED MANUSCRIPT
3
+
3+
Quinoline appended pillar[5]arene (QPA) as Fe sensor and complex of Fe (FeQPA)
-
as a selective sensor for F , arginine and lysine in the aqueous medium
1
2
1
Roymon Joseph* , Adersh Asok and Kuruvilla Joseph
1
Department of Chemistry, Indian Institute of Space Science and Technology (IIST),
Thiruvananthapuram, Kerala, India 695547.
2
Material Science and Technology Division, National Institute for Interdisciplinary Science and
Technology (NIIST) Thiruvananthapuram, India 695019.
Email: royj80@gmail.com. Tel: +918301871153.
Abstract
A quinoline functionalized pillar[5]arene, QPA has been prepared and its interaction
with biologically relevant ions and molecules in aqueous solution has been demonstrated.
3
+
The sensor molecule, QPA has shown selectivity towards Fe among eleven metal ions
3
+
-
studied. The Fe complex of QPA (FeQPA) selectively interacts with F among halides by
~
4 fold fluorescence enhancement. Further, FeQPA has shown selectivity towards arginine
3
+
and lysine among twenty naturally occurring amino acids. The binding of QPA with Fe has
1
been confirmed by MALDI-TOF and H NMR titrations.
Keywords
3
+
Fe sensor, fluoride sensor, Pillar[5]arene, amino acid detection, fluorescence
1
. Introduction
1

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Owing to the indispensable role in various biological processes, the detection and
quantification of ions and molecules are of fundamental importance [1-2]. To cite an
example; iron the most essential trace element in the human body plays an integral role in
many physiological processes such as oxygen transport, electron transfer, and enzyme
catalysis [3-8]. The optimum amount of iron present in men and women are 3 and 4 grams
respectively and the total iron is disseminated throughout the body in haemoglobin, bone
marrow, tissues, muscles, blood proteins, etc [9]. Iron deficiency or overload may impact
various biological processes in human body and this abnormal iron content may lead to
different diseases such as anemia, Parkinson’s syndrome, Alzheimer’s disease, and cancer
[10-11]. Consequently, the monitoring of iron levels in humans using fluorescent molecules
has been elevated to an intriguing area of research in recent years [12-14]. Also, due to the
relevance of anions in chemical, biological, and environmental processes several synthetic
receptors have been reported in the literature for the selective sensing of anions [15-16].
-
Among various anions, detection of F is of particular concern on account of its vital role in
treating osteoporosis and protecting dental health [17]. Nevertheless, excessive fluoride
-
ingestion may lead to urolithiasis and fluorosis [18]. Thus the detection of F is paramount in
human health.
In addition to cations and anions, amino acids are involved in several crucial functions
in cell regulations and metabolism, and they are essential in numerous cellular functions [19-
2
0]. For instance, the basic amino acids such as arginine and lysine play a vital role in the
proper functioning of biological systems. Arginine functions as a precursor for the synthesis
of agmatine, creatine, glutamate, urea, proline, nitric oxide and polyamines [21-22]. The
important biological processes associated with arginine are tissue integrity, reproduction,
hormone release, wound healing, etc [23-24]. The ability of arginine to lower blood pressure,
reduce blood clots and strokes and its application in the treatment of erectile dysfunction is
2

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well evident from the literature [25-26]. Arginine overdose may lead to life threating allergic
reactions, anaphylaxis and increase in the levels of stomach acid [22]. Similarly, lysine also
plays vital role in various biological processes. However, it acts as a precursor for protein
synthesis and in the biosynthesis of carnitine. Excess amount of lysine in plasma and urine
may cause congenital metabolic disorders such as cystinuria or hyperlysinemia [23, 27-28].
Therefore, the selective detection of ions and molecules are of necessity in biology to avert its
deficiency or overload and thereby head off several side effects in humans [23-24, 29-31].
Though there are several synthetic fluorescent receptors known for the selective
detection of ions and amino acids, a single system which recognizes all the three species;
cations, anions and amino acids are rather rare [32-33]. In the search for a suitable molecular
system which can function as a platform for functionalization, ease of synthesis, tuning
solubility, hydrophobic and hydrophilic cavity we have come across a relatively new
supramolecular system, pillar[5]arenes. Pillar[n]arenes are first reported by Ogoshi and co-
workers in 2008 and the functionalized pillar[n]arenes are known for various applications in
the areas of host-guest recognition, fluorescence sensing, supramolecular aggregates,
biomedical applications, etc [34-41]. Hence, in this paper we have demonstrated the synthesis
of a novel quinolone appended pillar[5]arene (QPA) through a triazole linkage and its
3
+
selective detection of Fe using fluorescence spectroscopy. Further, the iron complex of
-
QPA (FeQPA) has been used for the sensing of F among all the halides and arginine and
lysine among the twenty naturally occurring amino acids by fluorescence spectroscopy.
2
2
. Experimental Section
.1. Materials and physical methods
The salts used for the present study, viz., Mn(ClO4).6H2O, Fe(ClO4)2.xH2O,
Fe(ClO4)3.6H2O, Co(SO4)2.7H2O, Ni(ClO4)2.6H2O, Cu(ClO4)2.6H2O, Zn(ClO4)2.6H2O,
3

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NaClO4.H2O, KClO4, Ca(ClO4)2.4H2O and Mg(ClO4)2.6H2O, were procured from Sigma
Aldrich Chemical Company. Salts of anions, viz., Bu4NF and Me4NCl were procured from
Otto Chemie Pvt. Ltd. and Bu4NBr, Bu4NI were procured from Spectrochem Pvt. Ltd. India.
All the 20 naturally occurring amino acids, except lysine (TCI Chemicals (India) Pvt. Ltd.)
and histidine (Avra Synthesis Pvt. Ltd. India), were procured from Spectrochem Pvt. Ltd.
1
13
TM
India. H and C NMR spectra were measured on a Brucker Ascend
400 spectrometer
working at 400 MHz. The mass spectra were recorded on Bruker UltrafleXtreme MALDI-
TOF mass spectrometer. The absorption and steady-state fluorescence spectra were measured
on Varian Cary 100 Bio and Horiba Scientific FluoroMaz-4 respectively. The elemental
analysis was carried out using PerkinElmer 2400 SeriesII CHNS.
2
.2. General procedure for fluorescence experiments
All the fluorescence titrations were carried out in HPLC grade solvents. The bulk
-
4
solution of QPA (6 × 10 M) was prepared in DMSO and the salts of cations and anions, and
the amino acids were dissolved in water. During the fluorescence titration the final
concentration of QPA was kept at 10 µM and the concentration of metal salts was increased
n+
gradually to get requisite mole ratios of QPA:M . All the titrations were conducted in 1:1
H2O: CH3CN solvent. The limit of detection (LOD) was calculated from the fluorescence
titration of host and guest species. The standard deviation of the blank () was determined by
measuring the fluorescence intensity of the probe without analyte at least 10 times. Then, the
fluorescence intensity of the probe has been measured upon addition of increasing
concentrations of analyte (3 times). The slope of the linearity plot (m) has been obtained by
4

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plotting the average value of fluorescence intensity of the probe versus concentration of
analyte. Finally the LOD was calculated using the equation, LOD = 3/m.
2
.3. Synthesis of QPA and its precursors
Synthesis of 1a. A mixture of hydroquinone (5.0 g, 45 mmol), potassium carbonate
(28.2 g, 0.20 mol) and 1,6-dibromohexane (21 mL, 0.14 mol) in acetone (120 mL) were
refluxed for 24 h under nitrogen atmosphere. The reaction mixture was cooled to 25 C,
filtered and the filtrate was evaporated under vacuum. The product was purified by
chromatography (silica gel; petroleum ether/dichloromethane) followed by recrystallization
1
from ethyl acetate to afford 1a (8.2 g, 43%) as white solid. H NMR (CDCl3): δ = 6.81 (s,
4
H, ArH), 3.90 (t, J = 6.3 Hz, ArOCH2, 4H), 3.42 (t, J = 6.3 Hz, CH2Br, 4H), 1.92-1.85 (m,
1
3
CH2, 4H), 1.80-1.73 (m, CH2, 4H), 1.54-1.44 (m, CH2, 8H) ppm. C NMR (100 MHz): δ
1
53.2, 115.5, 68.4, 33.9, 32.8, 29.3, 28.0, 25.4 ppm. HRMS (ESI) calcd for C18H30Br2O2
+
(
[M+Na] ) 459.03332, found 459.03399.
Synthesis of 1b. To a solution of 1a (6.3 g, 14.4 mmol) and paraformaldehyde (1.37
g, 45.6 mmol) in dichloroethane (120 ml) was added BF .OEt (2.0 mL, 15.9 mmol) under
3
2
inert atmosphere and the reaction mixture was stirred at 25 C for 2 h. Water (200 ml) was
then added and the organic layer was separated. The solution was again extracted with
dichloromethane (2 × 50 mL) and the combined organic layers were washed with water (2 ×
1
00 mL), brine (2 × 100 mL) and dried with Na SO and the solvents evaporated. The
2 4
product
was
purified
by
column
chromatography
(silica
gel;
petroleum
1
ether/dichloromethane) to afford 1b (3.1 g, 48%) as white solid. H NMR (CDCl3): δ 6.87 (s,
ArH, 10H), 3.91 (br, OCH , 20H), 3.76 (s, ArCH Ar, 10H), 3.24 (br, CH N , 20H), 1.81-1.60
2
2
2
3
1
3
(
br, CH2, 40H), 1.44-1.28 (br, CH2, 40H) ppm. C NMR (100 MHz): δ 149.6, 128.2, 114.6,
5

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6
4
8.0, 33.9, 32.6, 29.8, 29.5, 28.1, 25.5 ppm. Anal. Calcd for C95H140Br10O10.12.7H2O: C,
6.2; H, 6.75. Found C, 45.96; H, 6.51.
Synthesis of 1c. Sodium azide (0.73 g, 11 mmol) was added to a solution of 1b (2.0
g, 0.89 mmol) in DMF (30 mL) under inert atmosphere and the reaction mixture was kept at
9
0 C for 12 h. After cooling to 25 C, water (150 mL) was added and the precipitate was
1
filtered and dried under vacuum to afford 1c as white solid (1.5 g, 87%). H NMR (400 MHz,
CDCl3): δ 6.86 (s, ArH, 10H), 3.89 (br, ArOCH2, 20H), 3.76 (s, ArCH2Ar, 10H), 3.10 (br,
1
3
CH2N3, 20H), 1.81 (br, CH2, 20H), 1.47-1.32 (m, CH2, 60H) ppm. C NMR (100 MHz): δ
49.7, 128.3, 114.7, 68.1, 51.4, 29.8, 29.5, 28.7, 26.6, 25.9 ppm. Anal. Calcd for
1
C95H140N30O10.5.6C3H7ON: C, 59.11; H, 7.95; N, 21.95. Found C, 58.58; H, 8.01; N, 22.48.
Synthesis of QPA. A mixture of 1c (0.25 g, 0.13 mmol), 8-(prop-2-ynyloxy)quinoline
[
42] (0.37 g, 2.0 mmol), CuSO4.5H2O (8.0 mg, 32 µmol) and ascorbic acid (42 mg, 0.21
mmol) in DMF (25 mL) were kept at 90 C for 24 h. The reaction mixture was cooled to 25
C and evaporated. The solid was treated with water and extracted with dichloromethane (2 ×
00 mL). The combined organic layers were washed with brine (2 × 20 mL) and dried with

1
Na2SO4 and the solvents evaporated. The product was purified by chromatography (silica gel;
1
dichloromethane/methanol) to afford QPA as brown solid (0.31 g, 63%). H NMR (400
MHz, CDCl3): δ 8.77 (br, ArH, 10H), 8.26 (m, ArH, 20H), 7.47-7.43 (m, ArH, 30H), 7.34-
7
2
.32 (m, ArH, 10H), 6.78 (s, ArH, 10H), 5.28 (s, OCH2, 20H), 4.35 (t, J = 6.8 Hz, OCH2,
0H), 3.95 (br, ArCH2Ar, 10H), 3.63 (br, NCH2, 20H), 1.83-1.69 (m, CH2, 40H), 1.49-1.46
1
3
(
m, CH2, 20H), 1.31-1.28 (m, CH2, 20H) ppm. C NMR (100 MHz): δ 154.3, 149.5, 149.3,
1
3
5
42.9, 140.2, 136.2, 129.5, 128.3, 127.1, 125.0, 122.3, 120.4, 114.4, 110.4, 68.2, 62.3, 49.8,
0.1, 29.5, 29.2, 26.3, 25.7 ppm. Anal. Calcd for C215H N O .10CH Cl .10C H ON: C,
230
40 20
2
2
3
7
8.07; H, 6.11; N, 13.28. Found C, 57.74; H, 6.47; N, 13.61.
6

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3
. Results and Discussion
The receptor molecule QPA has been synthesized by four known steps starting from
commercially available material hydroquinone as given in Scheme 1. Alkylation of
hydroquinone was carried out with 1,6-dibromohexane using potassium carbonate in acetone
to afford dibromo derivative, 1a. The cyclized derivative of pillar[5]arene, 1b was obtained
by the reaction of 1a with paraformaldehyde and boron trifluoride diethyletherate in
dichloroethane. Reaction of 1b with sodium azide resulted in the formation of azido
derivative of pillar[5]arene, 1c. Finally, the sensor molecule, QPA was synthesized by the
1
,3-dipolar cycloaddition reaction using 1c and the 8-(prop-2-ynyloxy)quinoline. QPA and
1
13
its precursor molecules were well characterized by H and C NMR, high-resolution mass
spectroscopy (HR-MS) and elemental analysis (Fig. S1-S4 in supplementary Data).
Scheme 1. Synthesis of quinolone derivative of pillar[5]arene, QPA.
7

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The pillar[5]arene derivative, QPA has been studied for its interaction with various
biologically relevant metal ions using fluorescence spectroscopy in aqueous acetonitrile (1:1).
The QPA has been excited at 320 nm and followed its emission band at 400 nm. Among the
eleven metal ions studied, QPA showed a significant decrease in fluorescence intensity upon
3
+
+
+
2+
2+
2+
interaction with Fe (Fig. 1a). None of the other metal ions, viz., Na , K , Ca , Mg , Mn ,
2
+
2+
2+
2+
2+
2+
Fe , Co , Ni , Cu , and Zn , showed fluorescence changes except Cu which shows
minimal changes (~7 fold) upon the titration with QPA (Fig. 1b). The amount of fluorescence
3
+
quenching observed during the titration of QPA with Fe is ~31 fold. Hence, QPA can be a
3
+
selective sensor for the detection of Fe among all the biologically relevant ions reported in
3
+
this paper. The lowest amount of QPA required to detect Fe in a sample using the current
fluorescence technique in aqueous acetonitrile solution is 157 ppm. The stoichiometry of the
3
+
complex between QPA and Fe were determined based on MALDI-TOF studies. The
3
+
5+
molecular ion peak observed at m/z = 781.32 {m/5 of 3906.60 of [QPA + 2Fe + ClO4] }
3
+
indicates the 1:2 complex formation between QPA and Fe (Fig. S5 in Supplementary Data).
The isotopic peak pattern observed is characteristic for the presence of iron in the complex.
3
+
The complex formation of QPA with Fe
has been further supported by UV-Vis
1
spectroscopy and H NMR experiments (Fig S6-S7 in Supplementary Data). Upon the
3
+
addition of Fe into a solution of QPA in DMSO-d6, the proton signals corresponding to
triazole ring and quinoline experience considerable broadening along with marginal chemical
1
3+
shift. The changes observed in the H NMR experiments supporting the binding of Fe with
QPA.
8

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1
1
600000
200000
1.0
30
20
10
0
0
0
0
0
.8
.6
.4
.2
(b)
(c)
(
a)
8
4
00000
00000
0
0.0
3
50 400 450 500 550 600
Wavelength, nm
0
10
20
30
40
50
3
+
[QPA]/[Fe
]
Na
K
Ca Mg Mn Fe2+ Fe3+ Co Ni Cu Zn
Fig. 1 (a) Fluorescence spectral traces obtained during the titration of QPA (10 µM) with
3
+
increasing concentrations of Fe , (b) plot of relative fluorescence intensity with mole ratio of
3
+
Fe , and (c) histogram representing relative fluorescence intensity of QPA upon the addition
of 50 equivalents of different metal ions.
A competitive metal ion titration has been carried out to demonstrate the efficiency of
3
+
QPA to detect Fe in the presence of other competing ions. An in-situ prepared mixture of
3
+
QPA with 10 equivalents of metal ions other than Fe
was titrated with various
3
+
concentrations of Fe
selectivity of QPA towards Fe over other ions (Fig. 2). During the competitive titration of
resulted in the fluorescence quenching of QPA indicating the
3
+
2
+
3+
{
QPA+Cu } with Fe , the initial fluorescence intensity of the receptor was quenched ~4.2
2
+
fold by the presence of Cu and as a result, the total quenching fold obtained after the
3
+
addition of Fe was only 7.4 fold.
30
25
20
15
10
5
0
Fig. 2 Relative fluorescence intensity of QPA obtained during the addition of 50 equivalents
3
+
n+
of Fe in the presence of 10 equivalents of M
9

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3
+
Since QPA showed selective quenching towards Fe
relevant ions, we further explored the utility of in-situ prepared QPA and Fe complex
FeQPA) as a secondary sensor for anions and amino acids. The FeQPA complex was
among other biologically
3
+
(
3
+
prepared by mixing QPA and Fe in a 1:10 ratio in aqueous acetonitrile solution. The
stability of FeQPA complex in acidic and alkaline environment has been monitored by
analysing the fluorescence spectral traces of FeQPA at different pH ranges. It has been found
that FeQPA is stable in the pH ranges 3.5 to 10 (Fig. S8 in Supplementary Data).
In the detection of anions, the ensemble FeQPA was titrated with varying
-
-
-
-
concentrations of halide ions, viz., F , Cl , Br & I . The initial fluorescence intensity of the
3
+
ensemble FeQPA has been quenched due to the presence of Fe . During the titration with
anions, the fluorescence band of FeQPA at 400 nm has been increased significantly upon the
-
interaction with F and no changes were observed with other anions (Fig. 3). The reversal of
-
fluorescence during the titration of FeQPA by the addition of F leads to the displacement of
3
+
3+
Fe from the binding core of FeQPA and leaving the sensor QPA alone. The free Fe forms
-
3-
a stable complex with F ([FeF6] ) and the fluorescence intensity of the QPA has been
restored [43-44]. The chemosensor ensemble FeQPA exhibited ~4 fold fluorescence
-
enhancement upon interaction with F . Therefore, it clearly demonstrates the ability of
-
-
FeQPA to detect F selectively among all the halide ions. The detection limit of F by FeQPA
has been found to be 289 ppm. Absorption titrations were also carried out to support the
-
secondary sensing of FeQPA with F and the corresponding results were summarised in the
-
Fig. S9 of supplementary data. The displacement mechanism of FeQPA in the sensing of F
1
-
has been further supported by H NMR titrations by adding 10 equivalents of F to an in-situ
prepared complex of FeQPA. During the titration, the proton signals of triazole ring and the
quinoline were marginally shifted and moved toward simple QPA (Fig. S10 in
10

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1
-
Supplementary Data). The regeneration of H NMR spectra of QPA upon the addition of F
3
+
supports the displacement of Fe from the binding core of FeQPA complex.
1
1
200000
000000
4
3
2
1
8
6
4
2
00000
00000
00000
00000
0
(a)
(b)
3
50 400 450 500 550 600
0
100
200
[A ]/[FeQPA]
300
400
-
Wavelength, nm
Fig. 3. (a) Fluorescence spectral traces obtained during the titration of in-situ prepared
-
FeQPA with increasing concentrations of F , and (b) plot of relative fluorescence intensity of
-
-
-
-
FeQPA with mole ratios of halides. Symbols corresponds to ● = F , ○ = Cl , ■ = Br , □ = I .
Selective detection of amino acids using FeQPA has been investigated by
fluorescence spectroscopy. The complex FeQPA has been titrated with increasing
concentration of twenty naturally occurring amino acids and the corresponding fluorescence
intensity was monitored. None of the amino acids, except arginine and lysine, have shown
any change in the fluorescence intensity of FeQPA during the titration (Fig. 4). It indicates
that FeQPA interacts selectively with arginine and lysine among all the amino acids reported
in this paper. The fluorescence enhancement observed for arginine and lysine were 3.9 and
4
.3 fold respectively (Fig. S11 in Supplementary Data). The FeQPA detects arginine and
3
lysine among the naturally occurring amino acids to the lowest concentration of 3.57 × 10
3
and 3.17 × 10 ppm respectively. Similar to the detection of anions, a displacement
mechanism is responsible for the fluorescence enhancement of the sensor molecule when it
interacts with basic amino acids. During the absorption titration of FeQPA with arginine and
lysine, the absorption band observed at 300 nm exhibited a marginal increase in the
absorbance while the absorption band at 250 nm showed marginal decrease in the absorbance
(Fig. S12-S13 in Supplementary Data). The displacement strategy for the detection of amino
11

ACCEPTED MANUSCRIPT
1
acids has been verified by H NMR titration. Upon the addition of 10 equivalents of lysine or
1
arginine to a solution of in-situ prepared FeQPA resulted in the formation of H NMR
spectra corresponds to free QPA (Fig. S14 in Supplementary Data). Therefore, FeQPA is a
secondary sensor for lysine and arginine among twenty naturally occurring amino acids.
1
1
200000
000000
1200000
1000000
800000
600000
400000
4
3
2
1
0
(a)
(b)
(c)
8
6
4
2
00000
00000
00000
00000
0
2
00000
0
3
50 400 450 500 550 600
Wavelength, nm
3
50 400 450 500 550 600
Wavelength, nm
Fig. 4. Fluorescence spectral traces obtained during the titration of in-situ prepared FeQPA
with increasing concentrations of (a) arginine, (b) lysine, and (c) histogram representing
relative fluorescence intensity of FeQPA upon the addition of 50 equivalents of different
amino acids.
4
. Conclusions
In conclusion, quinoline appended pillar[5]arene, QPA selectively detects Fe and its
3
+
3
+
-
in-situ prepared Fe complex, FeQPA exhibits secondary sensing towards F , and arginine
3
+
and lysine. The sensing of Fe has been monitored by the decrease in the fluorescence
-
emission band of QPA at 420 nm while the detection of F , lysine and arginine have been
observed by the fluorescence enhancement of FeQPA at 420 nm. The ion and molecular
interactions have been monitored by fluorescence spectroscopy and the complexation was
1
3+
further supported by H NMR titration and MALDI-TOF experiments. The QPA detects Fe
3
to the lowest concentration of 157 ppm and FeQPA’s detection limits are 289, 3.57 × 10 and
3
-
3
.17 × 10 ppm towards F , arginine and lysine respectively.
12

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Acknowledgements
R.J. thanks the Department of Science and Technology (DST)-SERB India for Young
Scientist Start-Up Research Grant (YSS/2015/001868). Thanks to Central Laboratory for
Instrumentation and Facilitation (CLIF) at Kerala University for NMR analysis. R.J.
acknowledge Jibin Raj R J (CLIF, Kerala University) for NMR data acquisitions.
13

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4
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Graphical abstract
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Highlights
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Selective sensing of Fe by novel pillar[5]arene derivative, QPA
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Fe complex of QPA (FeQPA) detects F among all halides
FeQPA selectively detects arginine and lysine among twenty amino acids
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