Design, synthesis, characterization, DNA binding, acetyl and butyryl cholinesterase activities of metal chelates with 1,10-Phenanthroline derivative

Article abstract of DOI:10.1016/j.inoche.2020.108232

Metal chelates comprised of highly conjugated planar 1,10-Phenanthroline derivative, [ML] where L is ligand (1,10-Phenanthroline derivative); M = Cu²⁺, Co²⁺, Ni²⁺ & Zn²⁺, were prepared. They were subjected to the composition measurement and different spectroscopic techniques for structural elucidation. Based on spectroscopic and analytical measurements confirmed that a distorted square planar arrangement for the Cu²⁺, Co²⁺, Ni²⁺ & Zn²⁺ chelates. The antimicrobial efficacy of prepared complexes were assessed against C. albicans, E. coli, B. subtilis, A. flavus, S. aureus, and A. niger. The anti-mycobacterial efficacy of ligand title chelates was evaluated against H₃₇Rv and related to standard with the aid of MABA assay. The acetylcholinesterase (AChE) inhibitory effect of the ligand was examined to find out the beneficial efficiency of compound in the management of neurodegenerative syndromes. The synthesized ligand exhibited selective inhibition (AChE & BuChE), IC₅₀ values of 0.20 and 3.20 μM as compared to standard, Rivastigmine and Galantamine. Further, the in vitro anti-inflammatory efficiency of metal chelates were performed with the help of egg albumin method. The α-glucosidase inhibition activity was also carried out for the prepared metal chelates. The inherent binding constants of metal chelates with DNA was calculated based molar extinction coefficient (K_b), 4.11, 3.62, 3.85 and 2.9 × 10⁵ mol^?1 for Cu²⁺, Co²⁺, Ni²⁺ & Zn²⁺ chelates, respectively, demonstrating that the metal chelates intensely bound to DNA. Studies of DNA cleavage were also conducted on pUC 18 DNA.

Full text of DOI:10.1016/j.inoche.2020.108232

Inorganic Chemistry Communications 122 (2020) 108232
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Short communication
Design, synthesis, characterization, DNA binding, acetyl and butyryl
cholinesterase activities of metal chelates with 1,10-Phenanthroline
derivative
a,b
c,⁎
b
E.H. Edinsha Gladis , K. Nagashri , J. Joseph
b
c
a
Research Scholar, Dept. of Chemistry, Manonmaniam Sundaranar University, Tirunelveli 627012, Tamil Nadu, India
Dept. of Chemistry, Noorul Islam Centre for Higher Education, Kumaracoil 629180, Tamil Nadu, India
Dept. of Chemistry, Manonmaniam Sundaranar University, Tirunelveli 627012, Tamil Nadu, India
G R A P H I C A L A B S T R A C T
The prepared ligand and its metal complexes constitute the ligand framework, the 1,10-Phenanthroline derivative (planarity and conjugation) makes structure-based
ligand architecture manifest higher pharmacological activities as compared to standards.
A R T I C L E I N F O
A B S T R A C T
Keywords:
Metal chelates comprised of highly conjugated planar 1,10-Phenanthroline derivative, [ML] where L is ligand
2
+
2+
2+
2+
Complexes
(1,10-Phenanthroline derivative); M = Cu , Co , Ni
& Zn , were prepared. They were subjected to the
Biomimetic
composition measurement and different spectroscopic techniques for structural elucidation. Based on spectro-
Antimicrobial
2+
2+
scopic and analytical measurements confirmed that a distorted square planar arrangement for the Cu , Co
,
Acetylcholinesterase
Butyrylcholinesterase
2+
2+
Ni & Zn chelates. The antimicrobial efficacy of prepared complexes were assessed against C. albicans, E. coli,
B. subtilis, A. flavus, S. aureus, and A. niger. The anti-mycobacterial efficacy of ligand title chelates was evaluated
against H37Rv and related to standard with the aid of MABA assay. The acetylcholinesterase (AChE) inhibitory
effect of the ligand was examined to find out the beneficial efficiency of compound in the management of
neurodegenerative syndromes. The synthesized ligand exhibited selective inhibition (AChE & BuChE), IC50 va-
lues of 0.20 and 3.20 µM as compared to standard, Rivastigmine and Galantamine. Further, the in vitro anti-
inflammatory efficiency of metal chelates were performed with the help of egg albumin method. The α-gluco-
sidase inhibition activity was also carried out for the prepared metal chelates. The inherent binding constants of
⁎
Corresponding author.
E-mail address: shrik1810@gmail.com (K. Nagashri).
https://doi.org/10.1016/j.inoche.2020.108232
Received 13 August 2020; Received in revised form 7 September 2020; Accepted 7 September 2020
Available online 23 September 2020
1387-7003/ © 2020 Elsevier B.V. All rights reserved.

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
5
metal chelates with DNA was calculated based molar extinction coefficient (K
mol for Cu , Co , Ni & Zn
bound to DNA. Studies of DNA cleavage were also conducted on pUC 18 DNA.
b
), 4.11, 3.62, 3.85 and 2.9 × 10
−
1
2+
2+
2+
2+
chelates, respectively, demonstrating that the metal chelates intensely
1
. Introduction
utilized for separation. The chemical composition like CHN analysis
was recorded with the assistance of Elemental Analyzer (Carlo Erba-
EA1108). The proportions of metal content were measured using
gravimetric approach; copper, nickel, cobalt and zinc as cuprous thio-
cyanate, nickel dimethylglyoximate, cobalt pyridine thiocyanate and
zinc ammonium phosphate, respectively. The FTIR spectra were re-
corded using Shimadzu Affinity-1 Spectrophotometer. The absorption
spectra of ligand and chelates were measured using Systronics
UV–Visible spectrophotometer (200–1000 nm region). The nature
Schiff bases are potential group of substances and chelation with
redox active transition metal ions through rCH]Ne or AreOe atoms
[
[
1–3]. They have extensive range of applications in pharmaceutical
4–7], catalyst [8–10], polymer synthesis, energy sector [11], industrial
chemistry [12], etc. Among the transition metals, the complexes of
copper, cobalt, nickel and zinc are more promising due to their redox
behavior, low toxicity and present in the biological molecules [13].
Chemical structural modifications of recognized therapeutic molecules
are significant approach to drug development process. Heterocyclic
moieties, which are present in several compounds, play a significant
role in many biological processes [14,15]. These compounds' biological
activity depends essentially on their molecular structures. In existing
drug molecules, nitrogen containing scaffold containing phenanthroline
core is a potent pharmacophoric moiety [16–18].
1
proton and anionic coordination sites were ascertained using H NMR
spectrum of ligand and zinc complex with the help of BRUKER 400 MHz
spectrometer. The FAB mass were recorded and predicted the molecular
mass & fragmentation of mode of ligand and metal chelates using JEOL
SX 102/DA-6000. The systronics conductivity bridge was utilized to
measure the molar conductance and magnetic moment also calculated
using Guoy’s electronic balance. The electrochemical features of metal
A progressive illness describes that a deterioration in cognitive ca-
pacity, memory loss and other mental issues are termed as Alzheimers
disease. In the current scenario, the 6th rank of deadly disease in
worldwide and distresses nearly 50 million people worldwide. Changes
in the activities of AChE and BuChE was observed in cerebral cortex &
hippocampus and causative to the progression of the disease [19,20].
Many AChE inhibitors have been investigated and researchers are
continuing their work to create some new pharmacologically profiled
drug molecules [21,22]. In AD, AChE and BuChe levels are irregularly
shifting in the brain due to the neurotransmitter acetylcholine defi-
ciency in the brain. AD can be easily tracked and handled with better
understanding of the relationship between the AChE and BuChE levels.
The loss of cholinergic neurotransmission in the brain especially pay the
attention to the significant mental and behavioural indications of AD.
Cholinesterase inhibitors (Galantamine, Donepezil, Rivastigmine) are
the majority of medications accessible on the market for suggestive
treatment of AD. Then, inhibitors of cholinesterase inhibiting both
AChE and BuChE as well as highly selective BuChE inhibitors may have
potential therapeutic benefits in treating AD and other related de-
mentias. Both enzymes remain valuable targets in drug discovery stu-
dies performed against AD challenging task is always to synthesize the
redox active and conjugated planar molecule with improved bioactiv-
ities against a particular target. Our research was focused on novel
cholinesterase inhibitors as prospective anti-Alzheimer 's multi-
functional agents. In this study, synthesis and spectroscopic elucidation
of metal chelates were performed and presented. The prepared com-
plexes characterized using various spectroscopic techniques. The 1,10-
Phenanthroline derivative and metal chelates were accessed for anti-
oxidant, antimicrobial, DNA binding & cleavage, cytotoxicity, anti-in-
flammatory and α-Glucosidase inhibitory activities. The AChE and
BuChE inhibition of ligand was screened using modified Ellman’s
method.
chelate were examined using CHI 604D and n-Bu
4
NClO
4
as supp.
electrolyte. The thermal analysis (Perkin Elmer instrument) of com-
plexes was executed under N atm.
2
2.1. Synthesis of 1,10-Phenanthroline derivative
The ethanolic solutions of 1,10-Phenanthroline-2,9-dicarbaldehyde,
3-amino-7-nitronaphthalen-2-ol (20 mM) (10 mM) were thoroughly
mixed in RB flask. Then, it was refluxed for 3 hrs. TLC plate has utilize
to monitor the progress of the reaction. The solid residue was separated
and dried in vacuum desiccator (Scheme 1).
Ligand (H L): Mol. Formula: C
2
36 20
H
N O , Mass: 600. Productivity:
6
6
70%; Elemental composition: Calcd for; Nitrogen 13.81, Carbon 67.10,
Hydrogen 3.31; Found: Nitrogen 13.68, Carbon 67.02, Hydrogen 3.20,
−1
UV (nm): 330, 248 nm. FT-IR (cm ): 3320 υ(Aromatic OeH);
3080–3078 υ(AreH); 2960, 2886 υ(CeH); 1650 υ(azomethine, C]N);
1
1232 (Aromatic CeOH). H NMR (ppm): 8.8 (HC]N, 2H, s), 11.2
1
3
(eOH, 2H, s), 6.8–7.9 (16H, m). FAB-MS: 601. C NMR (ppm)
(DMSO‑d )
6
=
108.36, 125.5, 128.6, 130.06, 135.58, 152.18,
160.40 ppm.
2.2. Preparation of copper chelate
Equimolar hot methanolic proportion of 1,10-Phenanthroline ana-
logue and metal acetate(s) (0,05 M) in 50 mL was taken in RB flask. It
was refluxed up to the solid residue obtained at the bottom of reaction
vessel. The product was filtered, separated using petroleum ether and
dried. Similar experimental protocol followed for all other metal che-
lates.
2
+
Cu chelate: Molecular Formula: C36
H N O Cu. Mass. 669. Yield:
18
6 6
70%; elemental composition: Theoretical: Carbon 67.25, Hydrogen
3.52, Nitrogen 12.66, Copper 10.90; Experimental: Carbon 67.15,
Hydrogen 3.39, Nitrogen 12.52, Copper 10.84. UV: 346, 248 & 510 nm.
FT-IR (KBr): 1170 υ(CeN), 1632 υ(C]N), 550 υ(MeN). mass (Mole.
2
. Experimental: Materials and methods
2
−1
Ion): 670 m/z. Magnetic moment = 1.93 BM. Λm (Scm mol ) = 16.
2
+
All chemicals were procured from Merck, Sigma and utilized in the
Ni
chelate: Formulae: C36H18N6O6Ni. Mass. 667. Yield: 68%;
chemical reactions without further purification. The solvents used in
this work like ethanol, methanol, hexane, petroleum ether were pur-
ified according to the procedures mentioned in Vogel procedure. The
solvents used in electrochemical studies like acetonitrile, dimethyl
Elemental composition: Theoretical: Carbon 70.99, Hydrogen 3.50,
Nitrogen 9.74, Nickel 10.20; Experimental: Carbon 70.85, Hydrogen
3.38, Nitrogen 9.62, Nickel 10.06. UV–Vis.: 352, 250, 612, 730 nm. FT-
−1
IR (KBr,cm ): 1164 υ(CeN), 1622 υ(C]N), 540 υ(MeN). Mass (Mole.
o
2
−1
1
sulfoxide, etc. were purified stored under inert atmosphere in 3 A
ion): m/z: 668. µeff(BM) = 3.40. Λm (Scm mol ) = 18. H NMR
2+
molecular sieve. TLC tracked the path of the chemical cycle with the aid
of pretreated, silica gel-coated plates. Using column chromatography
approach, the proper choice mesh and size (60–120) of silica was
(ppm): 8.2 (HC]N, 2H, s), 6.4–7.8 (16H, m). Co chelate: Formulae:
C36H18N6O6Co. Mass. 667. Productivity: 66%; Elemental composi-
tion: Theoretical: C 69.90, H 3.50, N 9.74, Cobalt 10.24. Experimental:
2

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
Scheme 1. Schematic outline for the preparation of title metal chelates.
Carbon 69.78, Hydrogen 3.36, Nitrogen 9.60, Cobalt 10.18. UV–Vis.,
%denaturation of egg albumin inhibition = [(At Ac)/At] × 100
−
1
(
nm): 350, 260, 568, 750 nm. FT-IR (KBr,cm ): 1150 υ(CeN), 1620
where A
t
and A are absorbance of sample and standard, respectively
c
υ(C]N), 540 υ(MeN). FAB mass (mol.ion): 668 m/z. µeff(BM) = 4.32.
[
23].
2
−1
2+
Λm (Scm mol
)
=
10. Zn
chelate: Mol. Formulae:
C36H18N6O6Zn. Mass. 671. Productivity: 70%; Elemental composi-
tion: Theoretical; Carbon 70.17, Hydrogen 3.46, Nitrogen 9.63, Zinc
3
. Results and discussion
1
1
5
1.24; Experimental: Carbon 70.00, Hydrogen 3.35, Nitrogen 9.58, Zinc
−1
3.1. Structural characterization
1.14. UV–Vis.: 268, 380 nm. FT-IR (cm ): 1156 (C–N), 1614 (C]N),
1
56 (MeN). H NMR (ppm): 8.1 (HC]N, 2H, s), 6.5–7.8 (16H, m). FAB
In the present investigations were concentrated on the preparation
2
−1
mass: 672 m/z[M + 1]. µeff(BM) = 0. Λm (Scm mol ) = 12.
of 1,10-phenanthroline derivative as ligand. Further, the metal acetate
(
s) were reacted with ligand to arrive the desired metal chelates for
2.3. Pharmacological studies
catalytic applications. The composition of different elements, mass and
molar conductivity values were presented in experimental section gave
information about the structural features of title complexes. The ob-
served values are excellent agreement with theoretical calculations
within the limit. Structural interpretation was endeavored with spectral
measurements, magnetic behaviour with the proposed formulae. The
complexes are soluble in dimethyl sulphoxide, acetonitrile and in-
soluble in other organic solvents. Numerous attempts are made for the
development of crystal with the help of crystallization using solvent
mixtures and low temperatures but the end result could not be
achieved. The formation of ligand (L) and its metal chelates were as-
certained based on elemental composition and also indicative 1:1
stoichiometric radio of ligand and metal. Using molar conductivity
measurements of metal chelates (0.001 M) in DMSO the electrolytic
2
.3.1. Anti-inflammatory study
The prepared ligand and their metal chelates were reacted with
diclofenac at various amounts of 10 μM, 50 μM, 100 μM, 250 μM and
5
00 μM mixed in double distilled water and phosphate buffer. The re-
action admixture 2 mL and 1% egg albumin solution of 1 mL in buffer
was kept at 37 °C for 20 min at incubator. The denaturation of egg
albumin was convinced in the admixture at 65 °C in water bath for
1
5 min. The prepared chelates were assessed for anti-inflammatory
efficiency with the help of denaturation of egg albumin protocol. In this
assay, the denaturation induces the change of absorbance at 660 nm
were noticed with the help of UV–Vis double beam spectrophotometer.
The diclofenac was utilized as standard. The observed outcomes were
compared with standard drug / literature resources at different con-
centrations (10, 50, 100, 250, 500 μM/mL). The inhibition percentage
-
1
2
activity was calculated and found to be 10–18 mho mol cm [24].
The FTIR spectrum of 1,10-phenanthroline derivative and title
chelates were measured. The formation of ligand was established based
(
IC50) was arrived using the formula as follows:
3

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
on the peak at 1654 cm−1 owing to υC]N stretching vibration. On
chelates [31]. The thermogravimetric profile of metal complexes was
recorded upto 750 °C under nitrogen atm at the heating rate of 10 °C/
min. In the copper complex, no decomposition below 200 °C indicated
that no water molecules present in the complex. Then, the decom-
position was detected in the temp range 260–400 °C which corresponds
to the partial decomposition of ligand system. Further, the deviation
was noticed in the range 340–468 °C indicate the complete decom-
position of ligand leads to copper oxide (CuO) as residue along with
minimal quantity of ash. A similar thermogravimetric characteristics
were observed for all metal chelates. Thermal stability is a notable
structural feature in catalytic applications. Therefore, it is concluded
that the observed mode of decomposition with respect to temperature
and excellent agreement with the proposed structural formulae of the
metal chelates as depicted in Scheme 1.
complexation with metal ion, the above peak was moved to lower
−
1
wavenumber (1635–1620 cm ) which authenticates the chelation
through azomethine nitrogen [25–27]. The band was appeared at
−
1
1
270 cm , which is attributed to phenolic CeO stretching frequency
in the 1,10-Phenanthroline derivative and shifted to higher frequencies
−
1
(
1281–94 cm ) due to chelation. Furthermore, the new medium in-
−1
tensity vibrational peak in the region 468–476 and 532–556 cm
which was assigned to ʋ(MeN) & ʋ(MeO) formation of complexes
[
26,27]. These observations highlighted that ligand coordinates
through phenolic oxygen and azomethine moieties to respective metal
ions.
FAB mass approach authenticated the molecular weight of ligand
and its metal chelates. These complex molecular ions were confirmed as
[
ML] stoichiometric form of metal chelates. The ligand mass spectrum
The ligand's X-ray diffractogram and complexes were reported in
the range of values from 5° to 80° 2 theta values. The PXRD pattern of
ligand and its chelates have shown well-defined crystalline patterns
with different crystallinity. Additional peaks were present in the che-
lates compared with ligand due to metal complex formation. The PXRD
spectrum of copper chelate was given in supplementary information
(Fig. S2).
confirms with the suggested formula (molecular ion m/z 609). The
molecular mass peak in the copper complex was observed at 672 which
endorses that metal chelate as monomeric. Additionally, the mass
spectra show various peaks reflecting successive degradation of the
complexes with intensity gives an indication of fragment stability.
Therefore, the molecular weight and conductivity values of complexes
are authenticated the molecular stoichiometry as [ML].
The absorption spectrum of ligand displayed peaks at 250 & 348 nm
which corresponds to the transitions (π-π*(cyclic aromatic scaffold) and
n- π*(azomethine moiety)). The prepared zinc(II) complex is diamag-
netic with completely filled d orbitals. The UV absorption spectrum of
3
.2. Antimicrobial activity
The World Health Organization (WHO) is monitoring infections
1
caused by micro-organisms, such as bacteria and fungi, with concerns
due to increased antimicrobial resistance. Metal-based pharmaceuticals
represent a promising approach to new drugs with various action me-
chanisms. The goal of destroying hydrophobic interactions of bacterial
plasma membranes, consisting of a phospholipid bilayer similar to that
of eukaryotic cells, takes us to amphiphilic metal complexes once again.
The synthesized 1,10-Phenanthroline derivative and metal complexes
were accessed in the present investigations against microbial species, C.
albicans E. Coli, A. flavus, S. aureus, A. niger and B. subtilis. Microbial
species growth inhibition is expressed in terms of minimum inhibitory
concentration (MIC) and summarized in Table 1. The experimental
findings suggested that the prepared copper chelate is more inhibitory
of microbial growth than other chelates, ligand and standards under the
similar conditions due to chelation [29] and overtone concept [32] via
the series of biochemical action, inhibitions of protein, RNA & DNA.
The experimental findings suggested better efficiency of the prepared
metal chelates against Gram +ve strain than Gram −ve due to their
difference in the composition of the cell membranes.
nickel chelate showed a peak at 652 nm which corresponds to
A
Ig
1
→
BIg consistent with square planar arrangements. There is a broad
2 2
band was observed at 510 nm ( BIg→ AIg) which assigned to Cu(II)
complex with square planar geometrical arrangements. The other metal
chelates showed an peak at around 330–399 nm which corresponds to
n → π* transition. The observed electronic absorption peaks 560 and
7
52 nm which are in excellent agreement with the bands reported for
cobalt(II) square planar complex [28].
UV–visible spectrophotometer with the aid of stability of prepared
metal chelates in DMSO was monitored. The chelates of metal(II) are
unchanging, preserving spectral appearance and minor deviations after
2
4 hrs. The stability of metal chelates in organic solvent in PBS buffer
was also assessed under biological conditions. Similar spectral behavior
is the activity of chelates in aqueous solvent and in buffer solutions. All
complexes are stable up to 24 h and express only minor variations in
spectral appearance after a long period (after 24 h) due to ligand under
physiological conditions undergoing hydrolysis.
The proton NMR spectra were documented for prepared ligand, zinc
A number of factors consider the biological activity of a given mo-
lecule to be affected. Such considerations include lipophilia, resonance,
chemical structure and thermodynamic stability [33–35]. Many Schiff
bases and their metal chelates typically demonstrates extensive array of
cytotoxic behaviours, with minor variations in chemical composition
often resulting in large differences in selectivity and behaviour. Schiff
bases complexation with metal ions decreases the polarity of metal ions
by partially sharing positive charge on chelation with the donor atoms
and π-electron delocalisation. The findings showed a greater behaviour
&
nickel complexes. In the case of ligand, the peaks were observed at
8
.4 and 6.8–7.9 ppm, respectively corresponding to the eHC]N and
aromatic protons. Because of the nitrogen chelation to the metal ion by
contributing electron pair, the azomethine peak was marginally moved
from 8.4 ppm to 8.2 ppm. Aromatic proton signals do not show any
appreciable shift. Two peaks corresponding to aromatic carbon atoms
1
3
and azomethine carbon were seen in the C NMR spectrum of prepared
ligand in the range of 90–135 ppm and 162.5 ppm, respectively.
The EPR spectrum of copper chelate was recorded at 77 K in DMSO
solution (Fig. S1, Supplementary file). The observed g|| value for
copper chelate 2.265 was calculated which suggested that both ionic
and covalent character in the metal–ligand bond (Budagumpi et al.,
Table 1
MIC values of ligand and its copper complex against different microbial species
(
µg/mL).
2
010). The planar distortion from regular geometrical arrangements
(
f = g||/A||) of copper(II) chelate was calculated and is found to be
Compound/
E. coli S. aureus B. subtilis C. albicans A. niger A. flavus
Standard
1
46.4. The observed values [29] indicated that the distortion from
regular square planar geometry around the copper center and enabling
the biomolecular mechanism for biological reactions [30].
Ligand, H
2
L
90
30
42
36
34
8
84
26
38
40
38
12
–
88
22
46
44
36
6
96
20
40
38
35
–
80
18
44
42
28
–
78
25
36
36
30
–
[CuL]
TGA offers important structural evidence regarding the thermal
stability of metal chelates. Based on the thermogravimetric profile gave
information about the different structural moieties like lattice water or
coordinated water molecules, anions, molecular fragments after de-
composition of ligand and metal oxide as residue present in the metal
[CoL]
[
[
NiL]
ZnL]
Sreptomycin
Nystatin
–
–
14
10
15
4

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
of the prepared compounds against Gram +ve bacteria than towards
Gram −ve bacteria. This explanation may possibly be attributed to the
variance in the composition of the cell membrane, where Gram-nega-
tive bacteria's outer membrane will minimize the damage from the
synthesized compounds.
(CNS) targeting drug will have a logP value of about 2 (ideal value is
1.35–1.8)
3.4. Antioxidant activity
Results showed that ligand with imine, planar moiety and metal ion
making them suitable for the anti-TB agents as the lead molecule. It
may also serve as modulators to disrupt bacterial metabolism by in-
hibiting main enzymes and inhibiting the DNA function by commend-
ably binding with the active DNA sites through hydrogen bonding,
hydrophobic interaction, and electrostatic interactions. Further, there is
no toxic nature of metal complexes as compared to metal salts owing to
its liphophilic 1,10-Phenanthroline and naphthalene moieties and en-
hances the efficacy.
Schiff bases comprises of active pharmacophore (hydroxy moiety) in
the bioactive molecule and then induces the conversion of harmful free
radicals into neutral molecule (namely antioxidants). Antioxidant has
the potency of transferring electrons into reactive radicals and effec-
tively scavenging radical species making them stable and unreactive. In
the present analysis the ligand 's radical antioxidant scavenging po-
tential, metal chelates, and FRAP assay standards. Reducing the ferric
ions is an example of the ability of a material to suppress antioxidants.
The Schiff base ligand's antioxidant potency, metal complexes have
been investigated and compared with known standards, BHA, ascorbic
acid, respectively. As seen from the Fig. 1, the standards have higher
absorbance as compared metal chelates and ligand. In the BHA and
metal chelates, the copper complex showed higher absorbance indicates
that higher antioxidant potency. The above deliberations were ac-
counted for the redox characteristics of copper chelate. The reducing
efficiency of ligand and metal complexes displayed similar antioxidant
potency.
3.3. Anti-tubercular activity
The anti-tuberculosis efficiency of metal chelates with 1,10-
Phenanthroline derivative was accessed with the aid of MABA protocol.
The metal complexes displayed improved in-vitro anti-tuberculosis ef-
ficiency against H37Rv as compared to 1,10-Phenanthroline derivative
and standard (INH). Comparing the effectiveness of antituberculosis,
the synthesised Cu(II) chelate was appeared a higher potency (MIC
value: 5.40 mg / mL) while other metal complexes exhibited lower
The yellow color of the test solution has been converted into various
shades of colors in this assay method depends on the reduction power of
each complex. A compound which reduces the ability to serve as an
important measure of its antioxidant activity. The complex reduction
capacity increased with concentration increasing. Metal complexes
demonstrated much greater behavior than the precursors to ligand and
metal. The values of antioxidants are expressed in values IC50. The
antioxidant efficiency of tested samples is 7 ± 0.02 (Copper complex),
28 ± 0.10 (Nickel complex), 26 ± 0.20 (Cobalt complex), 18 ± 0.30
(Zinc complex), 52 ± 0.25 (ligand) and 8 ± 0.05 (BHT), respectively.
Among the metal complexes studied, the copper chelate exhibited
higher antioxidant power due to its redox potential and organic moi-
eties (1,10-Phenanthroline and naphthalene).
2
+
2+
2+
efficiency (12.4 (Zn ), 22.6 (Ni ) and 32.0 (Co ) mg/mL). The
derivative 1,10-Phenanthroline (ligand) for the formation of metal
chelate with enriched lipophilicity against M. tuberculosis, which in-
duces cell permeation. The experimental findings above highlighted the
ligand with imine, fused aromatic ring structure, planarity and metal
ion showing robust anti-TB activity making them suitable as the lead
compound for the development of new TB drugs.
In the pharmaceutical laboratories / industries LogP is used to ar-
rive at the characteristic activity of chemotherapy agents in the human
body. For drug molecule selection and optimization, based on the logP
values. Lipophilia is a significant factor that affects absorption, dis-
tribution, penetration across membranes, metabolism and excretion.
The logP of a compound intended for oral administration should
be < 5, based on the 'Lipinski 's Rule of 5′ (developed at Pfizer). In the
3.5. DNA interaction studies
2
+
2+
present case, the chelate log P was observed (1.20 (Cu ), 1.86 (Zn ),
The interaction of metal chelates with DNA (along with a host of
other targets that occur in living cells) is one of the potential me-
chanisms responsible for their cytotoxic capacity. In theory, there are
two types of binding of the metal complexes to DNA: covalent [36] and
non-covalent — (including electrostatic interactions, groove binding,
and base pair intercalation) [37]. Relationship between intrinsic
2
+
2+
2
.12 (Ni ) and 2.30 (Co )). Good lipophilic character imparted to
cisplatin with a strongly negative log(P) factor (−2.21) and its ability
to spread to the BBB. The copper chelate prepared is hoped to have
presented itself as an outstanding candidate for therapeutic applica-
tions. The literature resources indicated that a central nervous system
Fig. 1. Ferric reducing potentials of the ligand and its metal complexes and standards.
5

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
binding DNA mode and biochemical activity provides crucial indication
to promote the creation of new therapeutic drug targets with improved
potency.
smaller quantities. Ethidium bromide, a well-known DNA intercalator,
significantly increases relative viscosity by intercalating the double
helix of the DNA. Addition of DNA to the metal complexes (Fig. S3,
supplementary file), there is a significant rise in viscosity. The observed
viscosity increase suggested that the complexes bind through inter-
calation binding mode that is consistent with electronic spectral details.
The experimental findings above showed that the copper complex has
the higher affinity to binding DNA than other metal complexes. The
interaction of these complexes with DNA occurs primarily through the
intercalation of the planar 1,10-phenanthroline ligand into the base
pairs of DNA, resulting in the intense π- π stacking interaction.
3
.5.1. Electrochemical studies
Cyclic voltammetric investigations on Cu(II) complex with 1,10-
Phenanthroline derivative displayed (Fig. 2) one-electron redox char-
2
+
+
acteristics, Cu /Cu couple at Epa = 0.05 and Epc = − 0.20 V. A
significant decline in both anodic and cathodic current and shift in
electrode potential has been observed with the adding of CT-DNA to the
metal chelate (Fig. 2). The progressive change in potential and current
indicated that due to the binding of copper chelate to the electrode
surface by partial intercalation (fused aromatic rings) and partial
electrostatic interactions (between the -ve charged phosphate back
bone and + ve charged copper ion [38]. Metal complex displayed
considerable cytotoxicity activity against the HeLa cell line, and further
clarified the DNA binding studies.
3.5.2. DNA melting studies
It is understood that the binding attraction of metal chelates with
DNA (double helical form) impressively raises the melting temperature
of DNA and converts double helix into single helix DNA. On the basis of
melting temperature, the bonding chelates with CT-DNA was calculated
and also identify the nature affinity mode. The denaturation tempera-
ture of metal chelates with CT-DNA was measured at 260 nm in the
ranges from 30 to 90 °C. The denaturation curves of CT-DNA in the
absence and presence of the copper(II) complex are illustrated in Fig. S4
(supplementary file). The DNA alone and bound copper chelate with
(
a) 3.5.2 Electronic absorption titration
Generally, the metal chelates were effectively interact with DNA
and imparts changes in absorption with the aid of electronic absorption
spectroscopy. The DNA purity was determined by measuring the UV
absorbance at 260 and 280 nm. Their absorbance ratio at 1.8–1.9 in-
dicates that there is no protein contamination in the DNA. DNA is a
therapeutic target molecule outstanding interaction between planar
aromatic core and base pairs of DNA, bound with metal complex via
intercalation mode. In the absence and presence of DNA, the electronic
absorption spectra of the copper complex were recorded. In the absence
of DNA, a band at 344 nm was seen in the copper complex which
corresponds to the transition from π-π*. Due to the addition of DNA,
this absorption band encountered both hypochromic and bathochromic,
suggesting that the chelate bound with CT-DNA via intercalation mode
DNA showed T value are 65 and 75 °C, respectively. A small increase
m
in temperature of DNA denaturation was witnessed when the chelate
bound with DNA. The extinction coefficient contributes to find out the
denaturation (double helical form (ε is smaller) into single stranded
form (ε is high)) and indicate the increase in absorption at 260 nm.
Thus, transition temperature was calculated by drawing the plot of
absorbance as a function vs temperature. Due to the π-stacking inter-
action between complex and DNA base pairs, the destabilization of the
DNA structure was occurring. The composition, conformation, stability
and affinity of nucleic acids can be greatly affected by metal co-
ordination and organic structural core (1,10-Phenanthroline & naph-
thalene). It is understood that the intercalation of complexes into the
double helix raises the helix melting temperature greatly, after which
the double helix denatures into single stranded DNA. Of all other metal
complexes, a similar pattern has also been observed (Fig. S4).
[
39–42]. Depending on the absorbance and molar extinction coefficient
the inherent binding constant (K ) of the copper complex with DNA was
calculated. The K obtained for the copper, nickel, cobalt and zinc
b
b
5
−1
chelates were 4.11, 3.62, 3.85 and 2.9 respectively 10
M
. These
observations demonstrated that power of binding strengths of metal
complexes with CT-DNA due to π → π* sandwich like stacking between
the complex and DNA. It is suggested that copper chelate has greater
binding affinity with DNA than that of ethidium bromide (EB)
3.6. DNA cleavage studies
Experiments on Gel electrophoresis were carried out using CT-DNA
5
−1
(
K = 3.3 × 10 mol ) due to distorted square planar geometrical
b
arrangements. Copper complex also exhibits greater effectiveness
against cancer cells derives from its ability to inhibit the enzyme that
binds to the nitro genic DNA bases and reinforce the conclusion drawn
from DNA binding studies. Based on the observations, the interaction of
title metal chelates with DNA was occurred as follow (Scheme 2, sup-
plementary file): first, the interaction of Cu(II), Ni(II), Co(II) and Zn(II)
chelate with phosphate backbone of DNA, and second, insertion of the
flat part (planar scaffold) of the metal chelate among the base pairs and
then coordination of metal(II) with specific base pairs of DNA.
(
b) 3.5.3 Viscosity measurements
Optical tests alone are inadequate to infer the method of binding
small molecules with DNA. The experiment on viscosity is an important
tool for assessing the binding of metal complexes to DNA. Viscosity
measurements were performed via intercalation or electrostatic or
groove binding mode to determine the interactions between the com-
plex and the DNA. Hydrodynamic measurements, based on changes in
length (viscosity and sedimentation) are considered the most significant
binding information in the absence of crystallographic structural data.
The relative changes in viscosity suggested that complexes have a
binding affinity to DNA. A classic intercalation mode means the DNA
helix must be lengthened and the DNA viscosity must be increased.
Either of electrostatic or groove surface binding the viscosity varies
Fig. 2. Cyclic voltammetric behaviour of copper complex in the presence and
absence of DNA.
6

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
with ligand, complexes in the presence and absence of H
2
O
2
. The title
modulate the conformation changes to make it easier to inhibit alpha-
glucosidase. Hence, the redox properties and molecular scaffolds make
copper complex as an efficient inhibitor in the inhibition of α-Gluco-
sidase.
chelates exhibited low concentration (20 μM) DNA cleavage capability
(
Table 2 & Fig. 3). Under the presence of oxidant, the ligand has no
noticeable activity. Of the complexes the activity was much higher in
the presence of H . When electrophoresis occurs with calf-thymus
O
2 2
DNA, the DNA movements were observed faster for the intact supercoil
form (Form I). If cleavage or denaturation occurs in the presence of
metal chelates and oxidant, the coiled form is divided into open circular
shape (Form II) and DNA movements are reduced. When the coiled
form is cleaved or denatured completely, a linear shape (Shape III) was
observed with slow movements. During the electrophoresis method,
because of the hydroxyl radical reaction with DNA, the metal chelates
displayed higher cleavage efficiency in the presence of oxidants. Both
hydroxyl-free radicals engage in the dexoyribose moiety oxidation fol-
3
.8. Anti-inflammatory efficiency
The purchase and utility of animals for pharmacological research
work is more complicated process due to some ethical issues. Keep
these aspects in mind, in the present work was concentrated on protein
denaturation methodology for in vitro anti-inflammatory efficiency of
metal chelates with the help of egg albumin method. The chemical
molecules those may inhibit protein denaturation and thereby im-
proving the anti-inflammatory process. Among the prepared metal
complexes, copper chelates (IC50 40 µg/mL) exhibited greater in-
hibitory efficacy than other chelates (IC50 78–90 µg/mL) due to the
existence of redox and chemical molecular moiety as compared to
Diclofenac (IC50 50 µg/mL). The upward rising of absorbance of che-
lates with respect to control showed the stabilization of protein and
thereby inhibiting the denaturation process. Among the chelates, the
copper chelate is active at lower concentration as compared to stan-
dard. Therefore, the biochemical interpretations suggested that the
synthesised metal chelates possessed manifested in anti-inflammatory
efficiency. Further, clinical trials are essential to ascertain the me-
chanism of anti-inflammatory actions.
lowed by sugar phosphate backbone hydroxyl cleavage. The H
2
2
O is
coordinated with the complex's copper ions, which include peroxo-di-
copper cells. This coordinated peroxide ion attacks the phosphate bond
of DNA via a nucleophilic mechanism, and hydrolyses the bond of P –
O.
3.7. Cytotoxicity activity
After 24 h of incubation the cytotoxicity of metal chelates and li-
gand on HeLa was assessed. It depends on their ability to bind the DNA
and damage its structure resulting in degradation of their function
followed by obstruction of the replication and transcription process,
and ultimately cell death. The results have been analyzed using cell
viability curves and given IC50 values. The values for IC50 were calcu-
lated using the MTT assay, which tests mitochondrial dehydrogenase
activity in living cells. The copper complexes had greater activity than
cisplatin at 24 hrs incubation. The study findings therefore suggested
that there is a significant increase in anti-proliferative activity due to
the synergetic effect of combining Cu(II) with a conjugated ligand
scheme, which is further confirmed by the coordinated addition of Phen
to the metal core. While the concentration of the compound increases,
the viability of the cells decreases (Fig. S5), the viability of incubated
cells without any compound is considered to be 100%. Increasing
complex concentration increases the adsorption of the complex on cell
membranes, leading to increased penetration, facilitates binding to the
DNA bases, and induces effective activity to kill cells. The copper
complexes showed a cytotoxic profile based on concentration in cell
line HeLa. The complex of Cu(II) (IC50 = 0.20 µM) showed greater
cytotoxicity than its parent ligand (0.90 µM) and other complexes
3.9. Cholinesterase inhibitory activity
Cholinesterase inhibitors (ChEIs) are type of perspective agents that
can improved cholinergic activity to boost memory, efficiency, mini-
mize psychiatric and behavioural disorders. The AChE and BuChE in-
hibitory activities of prepared 1,10-Phenanthroline derivative were
determined and compared with Galantamine & Rivastigmine as stan-
dard using modified Ellman approach. Some inhibitors of acet-
ylcholinesterase (Donepezil, Galantamine and Rivastigmine) were uti-
lized and treat AD problems. The IC50 values for inhibitions of AChE
and BuChE are summarized in Table 4. Similar to the regular Ga-
lantamine (IC50 = 2.41 μM), the strongly conjugated 1,10-Phenan-
throline derivative displayed the best inhibition against AChE with an
IC value of 0.20 μM and Rivastigmine (IC50 = 3.01 μM). The IC50 va-
lues obtained against BuChE demonstrated that 1,10-Phenanthroline
derivatives act as a selective inhibitor of AChE as opposed to Galanta-
mine. Phenolic compounds interact with residues of amino acids that
characterize the active site of AChE through a hydrogen bond, hydro-
phobic interaction, and an interaction between π–π interactions. Be-
cause of greater binding ability, several hydroxyl groups in the phenolic
compound are thought to improve AChE inhibitory action. The aro-
matic centre (conjugation) illuminates the fused aromatic nuclei with
higher inhibitory AChE potencies than their corresponding molecules
with just one or two fused ring systems. The best inhibitor to behave as
potent inhibitors of AChE with fused aromatic characteristics. The
+
2+
2+
(
(
IC50 = 0.32 µM(Zn2 ), 0.38 µM(Ni ), 0.44 µM(Co )).
c) 3.8 α-Glucosidase inhibition
The study on α-glucosidase inhibition for metal(II)-1,10-
Phenanthroline derivative complexes was described in Table 3, re-
flecting the IC50 values. The chelation of various metal acetate with
inactive produced a perceptible increase in the inhibitory potential of
ligand α-glucosidase and demonstrated the vital function of metal (II)
centre during enzyme inhibition. This research predicts the con-
centration-dependent inhibition of α-glucosidase induced by the metal
complexes (II)-1,10-Phenanthroline derivative. Among the complexes
tested, the copper (II) complex was highly potent α-glucosidase in-
hibitors (IC50 = 0.20 μM) and was approximately 200 times more ac-
tive than the DNJ (IC50 = 300 μM) standard α-glucosidase inhibitor.
The active site residues of α-glucosidases (imidazole and carboxy
groups) were interactions with metal (II) ion by soft electron donors
such as imidazole nitrogen, and impart enzyme inhibition. The α-glu-
cosidase inhibition is modulated by the existence and location of the
substituents in the Cu(II) complexes. The inhibitory values suggest that
the 1,10-Phenanthroline derivative copper complex occupies the active
α-glucosidase sites more easily than the normal DNJ. The copper
complex can also undergo hydrogen bonding with the enzyme, and
Table 2
DNA fragmentation using metal chelates in the presence of hydrogen peroxide
(
HP) for the incubation of 3 hrs.
Sl.No
Reaction mixture
% form
SC
NC
L
1
2
3
4
5
6
7
DNA alone
DNA + HP
96
96
96
0
4
0
4
0
DNA + Cu(OAc)
2
+ HP
4
0
DNA + CuL + HP
DNA + CoL + HP
DNA + NiL + HP
DNA + ZnL + HP
35
30
35
35
65
55
45
55
15
20
10
7

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
azomethine moiety also promotes tight binds to the active site of the
AChE and commendably inhibits hydrolysis of choline substrates.
Consequently, the main requirement for anti-AChE activity may be the
azomethine, naphthyl and phenolic moiety or lipophilic moieties on
conjugated aromatic centre. This research finding may provide oppor-
tunities for researchers to develop new effective inhibitors of ChEs by
adequately modulating the pattern of substitution and also some
pharmacophores from the perspective of multifunctional anti-AD
agents. More clinical trials, however, are required to clarify the effec-
tiveness of the 1,10-Phenanthroline derivative in AD management. The
experimental observations highlighted that the conjugated fused aro-
matic core and naphthalene moieties were involved in the inhibitory
actions.
Kinetic studies with AChE and BuChE along with ligand were per-
formed to understand the nature of binding manner between them. The
plot (Lineweaver–Burk reciprocal plot) representation was applied and
arrive the ligand kinetic properties and inhibitory features. The ob-
Fig. 3. Agarose gel (1%) showing the results of electrophoresis of pUC18 DNA
served K
and Vmax values of ligand at different concentrations with
m
with metal(II) complexes. Lane 1: 1Kb ladder; Lane 2: pUC18 alone; Lane 3:
AChE and BuChE are noted. As seen in Fig. 4, It is evident that both
slopes (decreased Vm) and intercepts (higher K) varied by increasing
concentration (0.2, 0.4, 0.6 and 1.0 mM). This observed activity has
indicated that ligand inhibit AChE. As seen in Fig. 5, it is confirmed that
ligand demonstrated BuChE inhibition and a dose-dependent reduction
in the enzymatic velocity of catalytic BuChE-substrate response. Such
experimental responses revealed that when interacting with the ther-
apeutic targets, the ligand could be bound to the catalytic active site
and peripheral anionic site (PAS).
pUC18
+
CoL
+
H
2
O
2
;
Lane 4: pUC18
+
ZnL
).
+
H
2
O ; Lane 5:
2
pUC18 + NiL + H
2
O
2
; Lane 6: pUC18 + CuL + H
2
O
2
Table 3
α-Glucosidase inhibition activity of metal(II) complexes.
Sl.No
Complex/standard
IC50 (µM)
2
1
1
1
1
5
Ligand
0.50 ± 0.4
0.20 ± 0.02
0.32 ± 0.02
0.36 ± 0.02
0.25 ± 0.02
0.3 ± 0.5
Copper complex
Cobalt complex
Nickel complex
Zinc complex
DNJ
3
.9.1. Aggregation studies
Using absorption spectroscopy, the aggregation properties of the
,10-Phenanthroline derivative were investigated. The ligand ag-
1
gregation property has been investigated in mixtures of DMSO-PBS.
Aggregates displayed bands wider and weak than monomers. The ab-
sorption spectra of the 1,10-Phenanthroline derivative that thus differ
according to the ratio of PBS / DMSO. Alternatively, the absorption
peak may be changed to blue or red, depending on the geometric ar-
rangement of aggregated material. 1,10-Phenanthroline derivative with
addition of PBS showed a blue shifted aggregation.
Table 4
In vitro inhibition IC50 values (μM) and selectivity index of compound and
standards for AChE and BuChe.
Compound
Inhibitory values IC50 (µM)
Selectivity index = IC50
BuChE)/IC50 (AChE).
(
AChE
BuChE
Ligand (H
2
L)
0.32 ± 0.16
2.41 ± 0.10
3.01 ± 0.2
3.2 ± 0.20
17.30 ± 0.15
0.30 ± 0.1
16
3
.10. Comparative study
Galantamine
Rivastigmine
7.21
0.10
Scientists synthesized different metal(II) complexes and im-
plemented numerous biochemical experiments to express as
Fig. 4. Plot of AChE initial velocity with increasing substrate concentrations.
8

E.H. Edinsha Gladis, et al.
Inorganic Chemistry Communications 122 (2020) 108232
Fig. 5. Plot of BuChE initial velocity with increasing substrate concentrations.
2+
2+
2+
chemotherapeutic agents. The experimental observations revealed that
the copper complex showed higher activity with square planar geo-
metry. The structural features, metal ion, geometrical arrangements
had influenced the biological efficiency. Researchers motivated from
the literature resources, the different biological activities of metal
chelate with highly conjugated ligand system comprised on 1,10-phe-
nanthroline and naphathalene moieties was performed in the present
investigations.
distorted square planar arrangement for the Cu2+, Co , Ni & Zn
chelates. The antimicrobial efficacy of copper complex is higher in-
hibition activity as compared to other chelates, ligand and standard.
The derivative 1,10-Phenanthroline demonstrated the highest inhibi-
tion of AChE (IC50 = 0.20 μM), which was 10 times higher than
Galantamine & Rivastigmine (IC50 = 2.41, 3.01 μM). The 1,10-
Phenanthroline SI (selectivity index) against AChE is 16-fold higher
than Galantamine, and Rivastigmine, respectively. The synthesised Cu
(II) complex displayed an effective inhibition activity of α-glucosidase
compared to the standard inhibitor (DNJ) and may be significant in
future for antidiabetic and other related disorders.
Some of the related literature information were presented as fol-
2
+
2+
2+
2+
lows: Imran Ali et al [43] have synthesised Co , Cu , Ni and Zn
chelates with Schiff base (o-hydroxyl & nitrogen donor atoms). The zinc
chelate demonstrated 83.60 and 88.52 percent inhibitions of celllines
A549 and H1299 at 20 mM among the complexes. Narendra Kumar
Singh et al [44] indicated that copper(II) chelates that denature DNA
via oxidation process, cell death through inherent ROS induced mi-
tochondrial pathways and are therefore initiate reactivity than com-
plexes of Ni and Pt. Moamen S.Refat et al.[45] have studied the TSC
ligand and its complexes for their possible biological activity including
antibacterial and antifungal activity. José M.Méndez-Arriaga et al [46]
have synthesised a sequence of triazolopyrimidine transition metals
CRediT authorship contribution statement
E.H. Edinsha Gladis: Conceptualization, Data curation, Formal
analysis. K. Nagashri: Supervision, Validation, Visualization, Writing -
original draft, Writing - review & editing. J. Joseph: Investigation,
Methodology, Project administration, Resources, Software.
Declaration of Competing Interest
2
+
2+
2+
complexes (dmtp with M(NO
3
)
2
··H
2
O (M = Co , Cu , Ni
and
2
+
Zn ). The toxicity and antiparasitic efficiency of chelates have been
studied. Researchers have concluded that metal ion along with phar-
maphore are responsible for the pharmacological activities.
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
In the present investigations, there are three essential structural
moieties present in the molecular system (Scheme 1). First, the naph-
thalene moiety is essential building block for novel drug molecules with
unique or selective target and induces therapeutic efficiency. Second,
the metal ion is essential for redox characteristics and modulates
pharmacological activities. Third, the whole designed ligand system,
Acknowledgment
We thank the Head, Department of chemistry, Manonmaniam
Sundaranar University for providing the necessary facilities and the
Chancellor, Noorul Islam Centre for Higher Education. This research
did not receive any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.
1
,10-Phenanthroline derivative includes planarity and conjugation
makes structure based ligand architecture manifested higher pharma-
cological activities as compared to standards. The distorted geometry of
chelates, the structural ligand core and the copper atom have improved
biological activities as compared to literature data.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.inoche.2020.108232.
4
. Conclusion
Metal chelates comprised of highly conjugated planar 1,10-
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