Coumarin based chemosensors for the detection of CN- IONS

DSE B-4: Dissertation ; B.sc Honours Chemistry(CEMA); Semester-

VI

Presentation prepared by

Satadal Sengupta
C.U. Roll: 183224-21-0011 C.U. Reg.: 224-1111-0385-18

Department of Chemistry,
Seth Anandram Jaipuria College
10, Raja Naba Krishna St, Raja Nabakrishna Street,
Sovabazar, Shobhabazar, Kolkata, West Bengal 700005

Introduction to the topic & Abstract:
R1
In modern day, chemistry governs the very essence of life, from
a simple toothpaste to the lifesaving drugs we depend on.
Therefore, the detection and study of these chemicals becomes
an absolute necessity, because of the toxicity & the notorious
side effects of the very same chemicals. Thus, comes the
usefulness of certain compounds called “Chemo-sensors”
which specialise in trapping the target chemical entities and
could be separated later or can create specific fluorescent
lights, making it visible for the naked eye. One of such type of
“fluorescent chemo-sensors” are the family of chemicals called
Coumarins. They consist of 1-benzopyran-2-one motif which
can be traced even around 200 years back.
H CN
R2 R2
CN
O O R1 O O
The very large family of compounds containing 1-benzopyran-
2-one motif called the Coumarins have proven to be the best of
these chemosensors, majorly due to its variety of unique
biological and photophysical properties. Among which the
high quantum yielding fluorescent properties have gained
much attention due to its exceptional stability and biological
compatibility.
Various cations and anions are responsible for the life of
organisms, so much so that the slightest change in the ratio of
these elements can lead to serious complications to the
organism. Such a chemical compound is Cyanide ion (CN-)
with a permissible limit of 0.07 mg/l i.e. 2.7 μM in drinking
water, it is considered to be the most lethal compund. From
electro plating, resin industries, metallurgy to gold mining4.
Nevertheless, its highly toxic and harmful nature is not
something to be taken lightly as it adversely effects both flora
and fauna of the environment and perhaps the most intriguing
compound with an absolute necessity for detection. The
mechanism being mainly dependant on the nucleophilic
addition on coumarins5 at specified positions or by
displacement reactions by Cu ions, resulting in the optical
behaviour of a simple intramolecular charge transfer probe
 Types of chemosensing methods
via Coumarin compounds

Copper
Fluorescent based
on nucleophilic
Nucleophilic
addition to
Nucleophilic
addition to C=N/C-
exchang
Other sensing
addition to 4-
position of the
C=C/C=N bonds
in conjugated
N of heterocyclic
pendants conjugate
e mechanisms
Coumarin group bridge to the Coumarin mechani
sm
 Fluorescent based on nucleophilic addition to 4-position of the Coumarin group
&
Some major examples

O HN
Possessing a strong electronic partial NH TBACN N

charge, the 4-position of coumarin and its H2N O

O

derivatives acts like a good electrophile thus O

O O
1
resulting in a strong Michael type 1-CN
COOH
nucleophilic addition reaction with CN-;
O
Which leads to the decrease in planarity of O O NH HN
N
the moity and disrupts the intramolecular O TBACN
O
charge transfer(ICT) through the coumarin NH2
O
2 O O
backbone, thus causing a spectral blue-shift 2-CN
as well as a considerable decrease in the
fluorescent intensity Cao et al. (2012) synthesized the above compounds 1
and 2 which are doubly activated Michael acceptors
purposed to sensitively and sensitively select CN -.
NMR of the original compounds explain that they undergo a nucleophilic addition (mechanism given in the diagram)
with cyanide ion and then internal cyclization regaining aromaticity. The final
intramolecular cyclization occurs through a proton transfer thus completing the
reaction. Which results in ratiometric absorbance and a blue-shift from 332 to 298 nm
for compound 1 and 292 to 270 nm for compound 2
 Fluorescent based on nucleophilic addition to 4-position of the Coumarin group
&
CO Et Some major examples
2
N
CN
S O CN O
Et2N O O
N N
Et2N O O Et2N O O

CN O
Kim’s group independently reported a H

coumarin-thiazole compound 3 (above) as Et2N O O

N

a chemoreceptor for cyanide ion with

similar mechanism
Long et al. reported two compounds 4&5(below)
to detect endogenous cyanide with the help of
similar transient 4-position coumarin
CO2Et CO2Et intermediates. They exhibit low fluorescent due to
Ha N
Hc Hb CN N ICT17 process occurring from coumarin ring to
HC
S NaCN S
pyridyl vinyl ketone.
Et2N O O Et2N O O
Strong fluorescence Weak fluorescence
O O
N

N Et2N
Et2N O O O O
 Nucleophilic addition of CN- to C=C/C=N in conjugated bridge
CHO
n

Li et al. developed a highly reactive Et2N O O

and selective chemodosimetric probe O O

as a novel cyanide detecting site O

Piperdium
O
acetate
which is basically a coumarin- O O
PhH ref l.
O
malonitrile compound 8. O O
O

(synthesis provided to the right & Et2N O O O O

Et2N O O
spectral results below)
CN O

Et2N O O O O

Coumarin derivatives possessing

polarized C=C or C=N are highly
susceptible to nucleophilic attacks
Fluorescence spectra of probe 8 (20μM) in the presence of (a)
various concentrations of NaCN (0–5 equiv.) and (b) 5 equiv. of which may induce the disruption of
various anions. Inset of (b): Fluorescent color change of 1 ([1] = elongated π-conjugations and thus
20μM, CN- concentration= 100μM). λex= 451 nm and the splits
were 5 nm.
letting the exhibits to only show the
core coumarin properties.
 Nucleophilic addition of CN- to C=C/C=N in conjugated bridge

Yin et al. independently discovered a similar

Ha Hb CN
coumarin-Meldrum derivative CN
CN
CN

This probe has 3 distinct sites for

CN
CN Et2N O O
Et2N O O

chemodosimetric selective detection of CN

(a) Sensing process of chemosensor 19

Zhang et al. discovered another for CN-.
CHO O O CHO coumarin derivative as a means of (b) Fluorescent microscopic imaging
POCl3
Piperdine ratiometric cyanide detection. of 19 for the detection of CN- in
Et2N OH O O EtOH DMF Et N O O HeLa cells.
Et2N O O 2

CH2PPh3Cl NO2
NO2
NO2 CN
CHO
tBOK CN
THF
Et2N O O Et2N O O Et2N O O
Et2N O O
NO2
 Nucleophilic addition of CN- to C=N/C-N bond of heterocyclic pendants conjugated to coumarin.
H

Liu et al. developed a coumarin-hemicyanin

1. diethylmalonate,
CHO piperdine,ethanol reflux
POCl3/DMF O
2. HCl/AcOH, ref lux 330K
probe for ratiometric as well as S CN S
N OH Et2N O O Et2N O O

colourimetric detection of cyanide ion Br

N
O CN
N
O
S S 1. piperdine
S
Et2N O O ethyl-2-bromoacetate N
(synthesis & spectra provided)
Et2N O O EtOH, reflux
OH OH
413K, 8h
O
N N Et2N O O Br
Br
OH
O
HO

The C=N/C-N bonds conjugate to the benzothiazolium and

indolium29 salts bear heavy positive partial charges and are
rather susceptible to nucleophilic addition through Michael
addition by CN- ion. A transformation of charged compounds to
neutral compounds occur causing a blue shift due to ICT
reduction.

1 non-fluroscent 1 (ts) non-fluroscent

O
O
Shiarashi’s group33 studied about the varied influences of additional electron O UV

withdrawing and electron donating to the indolium moity of the coumarin-indolium N O Vis N O

complexes. Each showed a varied affinity for cyanide ion in basic medium with 30% O
O

ACN, as spirogyran34 based dyes facilitate selective and sensitive flurometric detection of O

cyanide ion under UV irradiation. 1-CN

flurosent
N CN O
 Nucleophilic addition of CN- to C=N/C-N bond of heterocyclic pendants conjugated to coumarin.

Yin et al. synthesized

julolidine type analogues
which shows identical
photophysical behaviour N
I
N O O

A “turn-on” green fluorescent probe with hybrid coumarin-

hemicyanine CN- functionality has been synthesized for sensing.
The detection of cyanide was performed via the nucleophilic
attack toward the polarized C=N bond of the probe. The sensor
achieved rapid detection of cyanide anion in 100 20
 Copper exchange mechanism
OR
Lee’s group reported a coumarin fluorophore
Click Reaction
O decorated peptoid based Cu2+ complex probe
CuSO4,5H2O
O
N
O H
N
RO O O NaAsc
H2O:t-BuOH (1:1)
N
N O which exhibits clear fluorescence quenching
H2N N N3
O 323K, 15h O
N
O H response to Cu2+ in aprotic solvents such as
O 50% N N
H2N
O
N
DMSO and DMF and to a lesser extent in
O methanol

Cyanide ion shows high binding affinity towards transition metal complex like of
Cu2+37, which originally are non-emissive due to high PET effect. Therefore, by
performing displacement reaction high fluorescence38 can be observed which
becomes the basis of several chemosensors.

Jose et al.9employed copper complex of natural product

aesculetin (6,7-dihydroxycoumarin) as a cyanide sensor in 1%
DMSO solution as well as mouse serum. The probe showed high
efficiency phospho fluorescence in presence of various cations
like Zn2+, Fe3+ and Pb2+. But Cu2+ was the highest with 13-fold
increase in fluorescence at 495nm
 Other sensing mechanisms
Kim et al. proposed detection of cyanide ion H transfer R O
R OH
via the use of CN- catalysed 2-
hydroxycinnamate to coumarin reaction in a CO2Et
5% ACN buffer CH2O2Et
CN
cat. CN Et2N O O
CN
Et2N OH
EtOH Strong Fluroscence
Weak Fluroscence
CO2Et

18
NH2 (ii)
Ghosh’s group reported three coumarin-based urea-amide scaffold
NH2 NH2
20
(v) (iv) (i) compounds. Among these three compounds, compound 20 exhibits a
NH NH2
NH bright yellow fluorescence turn-on response to CN- with high
O O
NH selectivity. The proposed mechanism consists of several
(iii)
deprotonation steps, followed by a nucleophilic addition and ring-
opening of the coumarin lactone
19
Synthesis mechanism NO2
H
N
H
N
H
N
H
N
H
N
H
N

O O O
O O NH O O NH O O
NH
O O O
(i) p-nitroaniline, triphosgene, Et3N, dry CH2Cl2 stirring 7 h (ii) 6-amino NH NH
coumarin, triphosgene, Et3N, dry CH2Cl2, stirring 8 h (iii) 3-aminocoumarin,
18 19 20
triphosgene, Et3N, dry CH2Cl2, stirring 10 h (iv) butyryl chloride, dry Et3N, dry
CH2Cl2, stirring for 6 h (v) 3-amino coumarin, triphosgene, Et3N, dry CH2Cl2,
O2N O2N
stirring 8 h.
 Conclusion

Coumarins have been extensively employed as chemosensors targeting different analytes, ranging from
inorganic anions, metal cations, reactive oxygen, sulfur, or nitrogen species to small biologically active
molecules to deadly poisonous cyanides. In most cases, the coumarin acts as a fluorescent molecule,
attached to a recognition unit, but several examples of the sensing mechanisms where the coumarin
skeleton itself is key in the reactivity or selectivity through various mechanisms which are outlined in this
review as well. Over the course of the last years, coumarin has emerged as a strong and highly adaptable
platform, and we expect a bright future for this fluorophore in the field of fluorescent sensing.
 Acknowledgement

This work was guided and supported by the highly capable professors of
the department of Chemistry, Seth Anandram Jaipuria College.
Prof. Nilasish Pal (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Dinesh Ch. Ghosh (H.O.D., Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Dipanwita Guha Bose (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Monirul Islam (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Sudeshna Sawoo (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Manisha Ukil (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)
Prof. Annwesha Bhattacharya (senior professor, Dept. of Chemistry, Seth Anandram Jaipuria College)