Appraisal of DNA obligatory, DNA cleavage and in vitro anti-biogram efficiency of 9,10-phenanthrenequinone based metal complexes

Article abstract of DOI:10.1016/j.inoche.2014.06.011

This work presents the synthesis and characterization of four new metal(II) complexes of 9,10-phenanthrenequinone based Schiff base precursor. From UV-vis, FT-IR, ¹H NMR, EPR and Raman spectral data, an octahedral geometry has been assigned to

Full text of DOI:10.1016/j.inoche.2014.06.011

Appraisal of DNA obligatory, DNA cleavage and in vitro anti-biogram
efficiency of 9,10-phenanthrenequinone based metal complexes
Natarajan Raman, Thesingu Rajan Arun, Rajkumar Mahalakshmi, Seemon
Packianathan, Rajendran Antony
PII:
DOI:
Reference:
S1387-7003(14)00266-4
doi: 10.1016/j.inoche.2014.06.011
INOCHE 5627
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Inorganic Chemistry Communications
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Accepted date:
6 May 2014
7 June 2014
13 June 2014
Please cite this article as: Natarajan Raman, Thesingu Rajan Arun, Rajkumar Maha-
lakshmi, Seemon Packianathan, Rajendran Antony, Appraisal of DNA obligatory, DNA
cleavage and in vitro anti-biogram efficiency of 9,10-phenanthrenequinone based metal
complexes, Inorganic Chemistry Communications (2014), doi: 10.1016/j.inoche.2014.06.011
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ACCEPTED MANUSCRIPT
Appraisal of DNA obligatory, DNA cleavage and in vitro anti-biogram efficiency of 9,10-
phenanthrenequinone based metal complexes
Natarajan Raman* Thesingu Rajan Aruna, Rajkumar Mahalakshmia, Seemon Packianathana,
Rajendran Antonyb
aResearch Department of Chemistry, VHNSN College, Virudhunagar-626 001, Tamilnadu, India
bCentre for Scientific and Applied Research, PSN College of Engineering and Technology,
Tirunelveli-627152, Tamilnadu, India
Email: ramchem1964@gmail.com; Tel.: +91-9245165958
List of Abbreviations Used
DNA= Deoxyribonucleic acid
CT DNA= Calf thymus deoxyribonucleic acid
pBR322 DNA = plasmid Bolivar and Rodriguez 322 deoxyribonucleic acid
Tris-HCl = Tris(hydroxymethyl)aminomethane hydrochloride
L= Ligand
M = Metal
OC = Open circular
SC= Supercoiled
DMF= Dimethylformamide
DMSO= Dimethylsulfoxide
IIT = Indian Institute of Technology
CDRI= Central Drug Research Institute
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Appraisal of DNA obligatory, DNA cleavage and in vitro anti-biogram efficiency of 9,10-
phenanthrenequinone based metal complexes
Natarajan Raman* Thesingu Rajan Aruna, Rajkumar Mahalakshmia, Seemon Packianathana,
Rajendran Antonyb
aResearch Department of Chemistry, VHNSN College, Virudhunagar-626 001, Tamilnadu, India.
bCentre for Scientific and Applied Research, PSN College of Engineering and Technology
(Autonomous), Tirunelveli-627152, Tamilnadu, India.
Email: ramchem1964@gmail.com; Tel.: +91-9245165958
ABSTRACT
_________________________________________________________________________________
This work presents the synthesis and characterization of four new metal(II) complexes of
1
9,10-phenanthrenequinone based Schiff base precursor. From UV-Vis, FT-IR, H NMR, EPR
and Raman spectral data, an octahedral geometry has been assigned to the complexes. The molar
conductivity and magnetic moment measurements indicate the non-electrolytic and monomeric
nature of the complexes. DNA binding ability of these complexes has been explored using
diverse techniques viz UV-Vis. absorption, cyclic voltammetry, fluorescence spectroscopy and
viscometry. Comparative DNA oxidative cleavage ability of the complexes has been
accomplished under UV photo radiation on pBR322 DNA. These studies reveal that they are
good metallointercalators and chemical nucleases. In addition, the biocidal action of the
complexes is investigated against few pathogenic bacteria and fungi by well diffusion method.
The screening data reveal that the complexes exhibit more efficient antimicrobial activity than
the free ligand. These findings may lead to develop novel metal based drugs.
______________________________________________________________________________
Keywords: Schiff base• Metal complexes• Metallointercalators• DNA cleavage• Methionine•.
______________________________________________________________________________
*Corresponding author: Tel.: +91-9245165958; fax: +91-4562281338
Email : ramchem1964@gmail.com (N.Raman)
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Medicinal inorganic chemistry is one of the rapidly intensifying curiosities in the intend of
small novel molecules that can interact with DNA since the interaction of small molecules with
DNA helps us to recognize how biomolecules function in biological systems [1]. The interaction
of small molecules with DNA is also interested due to its involvement in the development of
artificial endonucleases and anticancer drug therapies. DNA offers several potential binding sites
for transition metals including the anionic phosphate backbone, electron-rich nitrogenous bases,
and the major or minor grooves [2]. The bio-interested transition metal complexes can interact
with such DNA binding sites either by covalent or non-covalent binding (intercalation, groove
binding, electrostatic forces and hydrogen bonding) [3]. These kinds of interactions displayed by
metal complexes toward DNA are currently fascinated owing to the role of metal complexes as
DNA structural probes, DNA foot printers, sequence-specific cleavage agents and potential
anticancer drugs [4–5]. Intercalative mode has been reported as the predictable mode when metal
complexes are under operation with DNA [6].
In the field of inorganic chemistry, contribution of Schiff base metal complexes has been
extensive and inevitable because of their diverse functions as catalysts [7], fluorescent indicators,
and oxygen carriers [8]. Besides, the imine (-C=N) group of Schiff base ligands escorts to the
astounding biological activities including antitumor, antibacterial, antifungal and herbicidal
activities [9]. The transition metal complexes of amino acids are also important owing to their
functions as models for a number of imperative biological systems [10]. Furthermore, metal
complexes of amino acids or their derivatives based ligands are key intermediates in a variety of
metabolic reactions such as decarboxylation, transamination, recemization and C-C bond
cleavage, which are catalyzed by enzymes [11]. The over specifics put forward that structure of
such complexes of amino acid based ligands would be the prolific attitude both in structural and
biological aspects.
In this context, we are impelled to synthesize a new Schiff base derived from
9,10-phenanthrenequinone and p-nitroaniline and its Cu(II), Co(II), Ni(II) and Zn(II) complexes
using methionine as coligand. Methionine amino acid is well known to make coordination bonds
with metal ion through COOH and/or NH2 groups which have potential donor sites [12]. The
synthesized complexes have been characterized by physicochemical and various spectroscopic
techniques. Besides, their communal biological properties have been analyzed by antimicrobial,
DNA cleavage (using gel electrophoresis) and DNA binding (by UV-Vis., viscometry,
fluorescence and cyclic voltammetry) studies. The communal biological properties obtained
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from our study would be helpful in perceptive of DNA interaction exposed by metal complexes
and it also would be assisted in advancing potential probes of DNA structure and conformation
and forecasting new therapeutic reagents for some uncommon diseases.
The Schiff base ligand and its mixed ligand metal complexes were synthesized by following
the previously reported typical procedure [13-19]. Prior to demonstrate, the synthetic procedures
of all compounds and discussion of their characterization are provided as supplementary data
(S1 and S2). The ligand and complexes were found to be air stable at room temperature. The
ligand was soluble in common organic solvents but the complexes were soluble in DMF and
DMSO only. The schematic representation of the synthesis of ligand and the complexes is
illustrated in Scheme 1. The expected geometry and stoichiometry of complexes ([ML(met)2])
1
have been affirmed by various spectral techniques such as FT-IR, UV-Vis., H NMR, Raman
and EPR. A few physicochemical characterizations including elemental analysis, molar
conductance and magnetic susceptibility were also employed in the prediction of geometry and
stoichiometry.
(Kindly insert Scheme1 here)
Electronic absorption spectroscopy is a valuable technique to examine the binding modes of
metal complexes with DNA [20]. The absorption titration of the Cu(II) complex in the absence
and presence of CT DNA is illustrated in Fig.1. Upon increasing amounts of DNA, the
absorption bands of the complex are disturbed. In specific, hypochromism and red shift
(bathochromism) are observed in all the complexes after mounting DNA concentration. While
increasing DNA concentration, the observed hypochromisms are 11.4%, 7.3%, 4.5% and 8.1%
for Cu(II) (319 nm), Co(II) (327 nm), Ni(II) (338 nm) and Zn(II) (326 nm), respectively. These
bands are attributed to intra-ligand π–π* transition available in the corresponding complexes.
The intensities of hypochromism and bathochromism were suggested to occur due to the
interaction between the electronic state of aromatic chromophores of azomethine ligand and
those of the nitrogenous DNA bases [21, 22].
(Kindly insert Fig.1 here)
The intrinsic DNA binding constants (Kb) of complexes have been measured using Eq. (1) to
collect the details regarding binding affinity of complexes with CT-DNA. The calculated values
are given in Table 1. The determined intrinsic binding constants for [CuL(met)2], [CoL(met)2],
[NiL(met)2] and [ZnL(met)2] are 7.9 × 105 M-1, 3.4 × 105 M-1 , 4.6 × 105 M-1 and 5.2 × 105 M-1,
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respectively. These outcomes reveal that the complexes may bind with DNA through an
intercalation mode into the double helix structure of DNA.
(Kindly insert Table.1 here)
To further investigate the interaction mode of the complex with CT DNA, the emission
spectrum was studied. Fluorescence titrations were conducted by preset amount of metal
complexes which were titrated with escalating amount of CT DNA concentration. The emission
spectrum of Cu(II) complex with CT DNA is illustrated in Fig.2. The addition of
CT DNA into the complex causes the obvious raise in fluorescence intensity which clearly
delegates that binding of metal complexes with DNA might be intercalation [23]. Perhaps, the
fortification of fluorescence intensity is due to changes in metal center of complexes.
Subsequently it implies that the complex has strong interaction between the base pairs of the CT
DNA which is supposed to be one of the criteria for intercalative binding [24]. From Fig.2, it is
observed that there is an enrichment of the fluorescence intensity of metal complex in the
presence of CT DNA. During the Cu(II) complex formation, the florescence intensity is
increased and there is an extension of the π system of the intercalated ligand due to the
coordination of the Cu(II) ion. Since the metal complexes have greater planar area than that of
the ligand, the metal complexes penetrate more deeply into, and stacking more strongly with the
base pairs of the DNA [25].
(Kindly insert Fig.2 here)
The viscosity of DNA solution is sensitive to its length changes and its viscosity
measurement upon addition of complexes may give important support to clarify the interaction
mode of complexes with DNA [26]. Viscosity measurements were carried out on CT DNA
solutions by increasing the amount of the complexes. In classical intercalation, an insertion of the
complexes in between the DNA base pairs most probably leads to an increase in the separation of
base pairs (intercalation site) to accommodate the bound complexes which again results in the
augmentation of DNA viscosity. Conversely, a partial non-classical intercalation causes a bend
(or kink) in DNA helix and reduces its effective length and thereby its viscosity. Eventually, the
increase of DNA viscosity noted upon addition of complexes can confirm the existence of an
intercalative binding mode between DNA and each complex [27]. The understandings and
outcomes of this viscosity study are depicted in Fig.3. It apparently shows that the viscosity of
DNA is found to be increased when it interacts with metal complexes. The upshot of this study
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clearly proposes the intercalative mode of binding between the complexes with CT DNA as
evidenced by UV-Vis and fluorescence spectroscopic results.
(Kindly insert Fig.3 here)
Cyclic voltammetry is the widely handled technique to study the binding modes of metal
complexes with DNA which greatly withstands the results obtained from the methods viz UV
Vis spectroscopy, fluorescence titrations and viscosity measurements. In recent years, there is an
upward concern on the electrochemical investigation of interaction between metal complexes
0
and DNA [28]. The cyclic voltammograms of [CuL(met)2] in buffer (pH = 7.2) at 25 C in the
presence of increasing amount of DNA are illustrated in Fig.4.
(Kindly insert Fig.4 here)
In the absence of DNA, cyclic voltammogram of Cu(II) complex reveals four characteristic
peaks which are allotted to two anodic peaks Epa (-0.365 and -0.031 V) and two cathodic peaks
Epc (-0.556 and -0.259 V) at a scan rate of 0.1 V s-1. The first reduction and oxidation potentials
are noticed at Epc = -0.556 V and Epa = -0.365 V whereas the second reduction and oxidation
potentials are identified at Epc = -0.259 V and Epa = -0.031 V. In the same environment, Zn(II)
complex shows the redox couple with Epc =−0.804 V and Epa = -0.593 V; Co(II) complex shows
the redox couple with Epc = -1.037 V and Epa = -0.044 V; and Ni(II) complex shows redox
couple with Epc = -0.374 V and Epa = -0.244 V. The cyclic voltammograms of all studied
complexes show approximately unity peak current ratio which is credited that the reaction of the
complex on the glassy carbon is quasi-reversible redox process. The incremental addition of
CT DNA to the complex reduces the anodic and cathodic peak current of values of the
complexes. This consequence shows that complex stabilizes the duplex (GC pairs) by
intercalating way. The addition of CT DNA to the complex causes shift in the potential of peak
in cyclic voltammogram. Both cathodic and anodic peaks show positive or negative shift which
indicates the intercalation of complex with base pairs of DNA [29]. The electrochemical data for
all complexes in DMSO and the obtained shifts in cathodic (Epc V) and anodic (Epa V) potentials
as a result of DNA inclusion are shown in Table 2. It is concluded that cyclic voltammetry
studies here effectively suggest the intercalative mode of binding between metal complexes and
binding sites of CT DNA.
(Kindly insert Table 2. here)
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From differential pulse voltammogram of the complex ([CuL(met)2]), it is apparent that
current intensity gets decreased upon the incremental addition of DNA. The shift in potentials
both in presence and absence of DNA is related to the ratio of binding constant by the following
equation:
Eb - Ef = 0.0591 log (K[red]/K[oxd])
where Eb and Ef are peak potentials of complex in presence (bound) and absence (free form) of
DNA, respectively. The result of the present study is that all metal(II) complexes show one
electron transfer during the redox process. The ipc/ipa value of such redox process is less than
unity which peculiarly supports the quasi-reversible nature of redox process which occurs on the
surface of glassy carbon working electrode. The synthesized complexes give both the anodic and
cathodic peak potential shifts which are either positive or negative (Table 2). These shifts specify
the intercalating mode of DNA binding with metal(II) complexes.
(Kindly insert Fig.5 here)
As the metal(II) complexes showed maximum binding affinity with DNA, thus the DNA
cleavage activity was evaluated by agarose gel electrophoresis using supercoiled (SC) plasmid
pBR322 DNA in a medium of 5 mM Tris HCl/50 mM NaCl buffer solution (pH 7.2). The
reaction mixture was subjected to agarose gel electrophoresis with incubated for 45 min. The
agarose gel electrophoresis experiments were carried out in the presence of activating agent
(H2O2) under aerobic conditions and are illustrated in Fig. 6. When supercoiled (SC) plasmid
pBR322 DNA is conducted by electrophoresis, the fastest migration will be observed for the
super coiled form-I (SC). If one strand is cleaved, the SC form will relax to produce a
slow-moving open circular form-II (OC). If both strands are cleaved, a nicked form-III (NC) will
be generated in the presence of oxidizing agent H2O2 [30]. As seen from Fig.6, there is no
cleavage observed in the case of control DNA (lane 1). However, all the metal complexes expose
good DNA cleaving properties. In detail, Cu(II) and Ni(II) complexes have shown complete
DNA cleavage as confirmations identified from diminishing of lanes′ intensity. On the other
hand, other two complexes (Zn(II) and Co(II)) have shown only partial DNA cleavage. These
observations announced that a combination of metal(II) complexes and activating agent (H2O2)
are very essential to show effectual cleavage of plasmid DNA. The DNA cleavage activity of
metal complexes may be allocated to the liberation of metal ion to the DNA helix in the locality
of stimulated oxygen or hydroxide free radicals [31].
(Kindly insert Fig.6 here)
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The antimicrobial bustle of the ligand and its metal complexes was examined against certain
sensitive organisms such as two Gram-positive bacteria (N. asteroides and P. putida), two
Gram- negative bacteria (E. coli and L. lactis) and few fungi (A. niger, A. flavus and
C. albicans). The minimal inhibitory concentrations of tested complexes against chosen sensitive
bacteria and fungi are shown in Tables 3 and 4, respectively. From Tables 3 and 4, it is observed
that the ligand functioned feebly against both bacteria and fungi. But after metallation, the same
ligand was found to have higher activity in the form of complexes. The presence of imine group
may be one of the reasons for the biocidal action of both the ligand and metal complexes [32]. In
addition, it has been already proved that the electron-withdrawing substituent such as nitro group
on the benzene ring exhibited a comparable growth-inhibitory activity against micro-organisms.
The presence of nitro group in our complexes may also be the reasonable for the better
antimicrobial activity of metal complexes. The acquired consequences designate that the
complexes have higher activity than the ligand against the same microorganisms under
indistinguishable experimental conditions. This can be explained by Overtone’s concept and
Tweedy’s chelation theory [33]. Chelation considerably reduces the polarity of the metal ion
because of partial sharing of its positive charge with donor groups and possible electron
delocalization over the whole chelate ring. This fact could enhance the lipophilic character of the
central metal atom, which subsequently favors its permeation through the lipid layer of the cell
membrane. The variation in the effectiveness of different compounds against different organisms
depend either on the impermeability of the cells of microbes or on differences in ribosome of
microbial cells. From the data, it is observed that the Gram-positive bacteria are more sensitive
to metal complexes than Gram-negative bacteria. It is due to the presence of cell wall in
Gram-negative bacteria which is impermeable lipid based bacterial outer membrane.
(Kindly insert Tables 3 and 4 here)
In the present cram, we have attempted to synthesize and characterize few novel mixed
ligand Schiff base metal complexes of Cu(II), Co(II), Ni(II) and Zn(II) in the motive to reach
new bioinorganic agents with better biological properties. The complexes have been also
employed to bind CT DNA and such binding ability has been explored using diverse techniques
such as UV-Vis., viscosity, fluorescence and cyclic voltammetry. It is concluded that all these
studies proved the CT DNA binding of the complexes through intercalation mode. The
antimicrobial screening data reveal that complexes exhibit higher activity than the free ligand.
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The communal biological action of the complexes may be helpful for the designing of metal
based drugs.
Acknowledgments
The authors express their heartfelt thanks to the College Managing Board, Principal, and
Head of the Department of Chemistry, VHNSN College for providing necessary research
facilities to complete this work successfully. The characterization facilities afforded by IIT
Bombay and CDRI, Lucknow are gratefully acknowledged by all authors.
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1
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[16] [CuL(met)2]: Yield: 72%; brown colour; Anal.Calc.(%): C (53.7), H (4.7), N (10.7), S (8.2)
and Cu (8.1); Found (%): C (53.4), H (4.4), N (10.3), S (7.9) and Cu (7.9); FT-IR (KBr) (cm-1):
3372 (NH2), 1622 (C=N), 1447 (υasy(COO-)), 1365 (υsy(COO-)), 536 (M-O) and 424 (M-N);
m (Ω-1mol-1cm2) 16.21; μeff (BM) 1.81; UV-Vis. in DMSO, cm-1 (transition): 31,746 (LMCT)
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and Co (7.6); Found (%): C (53.7), H (4.5), N (10.4), S (7.9) and Co (8.2); FT-IR (KBr) (cm1):
3360 (NH2), 1623 (C=N), 1440 (υasy (COO-)), 1358 (υsy(COO-)), 532 (M-O) and 424 (M-N);
m (Ω-1mol-1cm2) 22.30; μeff (BM) 2.57; UV-Vis. in DMSO, cm-1 (transition): 33,493 (LMCT)
and 21,420 (d-d).
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[18] [NiL(met)2]: Yield: 71%; yellow colour; Anal.Calc (%): C (53.9), H (4.9), N (10.7), S (8.1), Ni
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and 17,456 (d-d).
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(cm-1): 3361 (NH2), 1621 (C=N), 1448 (υasy(COO-)), 1304 (υsy(COO-)), 534 (M-O) and 438
1
(M-N); H NMR (DMSO-d6) δppm: 6.5-7.8 (phenyl multiplet),3.4 (s, (−NH2)) 3.9–4.2 (C−H)
-1
(mn- H) δ; m (Ω mol-1cm2) 18.70; μeff (BM) diamagnetic; UV-Vis. in DMSO, cm-1
(transition): 30,674 (LMCT).
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Figure captions
Scheme 1. Schematic route for the synthesis of Schiff base ligand and its metal complexes.
0
Fig 1. Absorption spectrum of [CuL(met)2] in buffer pH = 7.2 at 25 C in the presence
of increasing amount of DNA. Arrow indicates the changes in absorbance upon increasing
the DNA concentration.
Fig 2. Emission enhancement spectrum of [CuL(met)2] in the absence and presence of
increasing amounts of CT-DNA. Arrow indicates the emission intensity changes of upon
the increasing CT-DNA concentration.
Fig 3. Effect of increasing amounts of [CuL(met)2] (▲), [CoL(met)2 (×), [NiL(met)2](),
[ZnL(met)2](■), on the relative viscosity of CT DNA vs [complex]/[DNA].
0
Fig 4. Cyclic voltammogram of [CuL(met)2] in buffer (pH = 7.2) at 25 C in the presence of
increasing amount of DNA. The changes in voltammetric current upon increasing the
DNA concentration.
0
Fig 5. Differential pulse voltammograms of [CuL(met)2] in buffer (pH = 7.2) at 25 C in the
presence of increasing amount of DNA. Arrow indicates the changes in voltammetric
currents upon increasing the DNA concentration.
Fig 6. The gel electrophoretic separation of plasmid pBR322 DNA treated with [ML(met)2]
complexes. Lane 1; DNA control ; Lane 2: DNA + ligand + H2O2; Lane 3: DNA +
[CuL(met)2] + H2O2; Lane 4: DNA + [CoL(met)2] + H2O2; Lane 5: DNA + [NiL(met)2]
+ H2O2; Lane 6: DNA + [ZnL(met)2] + H2O2.
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where M= Cu(II),Co(II),Ni(II) and Zn(II); R= -CH2-S-CH3
Scheme 1. Schematic route for the synthesis of Schiff base ligand and its metal complexes.
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0
Fig 1. Absorption spectrum of [CuL(met)2] in buffer pH = 7.2 at 25 C in the presence
of increasing amount of DNA. Arrow indicates the changes in absorbance upon increasing
the DNA concentration.
16

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Fig 2. Emission enhancement spectrum of [CuL(met)2] in the absence and presence of
increasing amounts of CT-DNA. Arrow indicates the emission intensity changes of upon
the increasing CT-DNA concentration.
17

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Fig 3. Effect of increasing amounts of [CuL(met)2] (▲), [CoL(met)2 (×)], [NiL(met)2](),
[ZnL(met)2](■) on the relative viscosity of CT DNA vs [complex]/[DNA].
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0
Fig 4. Cyclic voltammogram of [CuL(met)2] in buffer (pH = 7.2) at 25 C in the presence of
increasing amount of DNA. The changes in voltammetric current upon increasing the
DNA concentration.
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Fig 5. Differential pulse voltammograms of [CuL(met)2] in buffer (pH = 7.2) at 25 0C in the
presence of increasing amount of DNA. Arrow indicates the changes in voltammetric
currents upon increasing the DNA concentration.
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Form II
Form III
Form I
Fig 6. The gel electrophoretic separation of plasmid pUC19 DNA treated with [M(L)(met)2]
complexes. Lane 1; DNA control ; Lane 2: DNA + ligand + H2O2; Lane 3: DNA +
[CuL(met)2] + H2O2; Lane 4: DNA + [CoL(met)2] + H2O2; Lane 5: DNA + [NiL(met)2] +
H2O2; Lane 6: DNA + [ZnL(met)2] + H2O2.
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Graphical abstract
Synopsis
The synthesized 9,10-phenanthrenequinone based complexes have good in vitro DNA binding and
cleavage efficacy. They are efficient antimicrobial and metallointercalators. These findings may lead to
develop novel DNA targeting metallonucleases.
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Table Captions
Table 1. Electronic absorption parameters for the interaction of DNA with Cu(II), Co(II), Ni(II)
and Zn(II) complexes.
Table 2. Electrochemical parameters for the interaction of DNA with Cu(II), Co(II), Ni(II) and
Zn(II) complexes.
Table 3. Minimum inhibitory concentration of the synthesized compounds against the growth
of bacteria (μM).
Table 4. Minimum inhibitory concentration of the synthesized compounds against the growth
of bacteria (μM).
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Table 1. Electronic absorption parameters for the interaction of DNA with Cu(II), Co(II), Ni(II)
and Zn(II) complexes.
λ max
∆λ
(nm)
Kb×105 (M−1)
Compound
[CuL(met)2]
[CoL(met)2]
H%
11.4
7.3
Free
Bound
315.4
319.2
3.8
2.3
7.9
3.4
327.0
329.3
[NiL(met)2]
[ZnL(met)2]
338.5
326.2
340.6
328.1
2.1
1.9
4.5
8.1
4.6
5.2
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Table 2. Electrochemical parameters for the interaction of DNA with Cu(II), Co(II), Ni(II) and
Zn(II) complexes
E1/2(V)a
bEp(V)
Compound
Ipa/Ipc
K[red]/K[oxd]
Free
Bound
Free Bound
-0.460
-0.145
-0.466
-0.135
0.191 0.201
0.84
1.26
[CuL(met)2]
0.392
0.228
0.190
[CoL(met)2]
[NiL(met)2]
[ZnL(met)2]
0.346
0.123
0.458
-0.201
-0.663
-0.678
0.221
0.683
-0.680
0.065 0.672
-0.033 -0.039
1.12
0.89
0.81
0.211
0.165
Data from cyclic voltammetric measurements: aE1/2 is calculated as the average of anodic (EPa) and cathodic (Epc)
b
peak potentials; E1/2a = EPa + Epc / 2 ; Ep = Epa─Epc
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Table 3. Minimum inhibitory concentration of the synthesized compounds against the growth
of bacteria (μM).
Minimum inhibitory concentration (MIC) ( × 104 μM)
Compound
N.asteroide
P.putida
L.lactis
E.coli
[L]
18.2
7.6
18.9
8.2
19.5
8.9
19.8
9.2
[ CuL(met)2]
[CoL(met)2]
[NiL(met)2]
[ZnL(met)2]
Gentamicin
9.3
9.7
10.2
10.2
10.4
10.4
10.4
11.6
9.7
10.5
10.9
10.8
3.1
3..4
3.9
4.1
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Table 4. Minimum inhibitory concentration of the synthesized compounds against the growth
of fungi (μM).
Minimum inhibitory concentration (MIC) ( × 104 μM)
Compound
A. niger
A. flavus
C.albicans
[L]
19.7
7.5
17.1
6.9
18.8
5.8
[ CuL(met)2]
[CoL(met)2]
[NiL(met)2]
[ZnL(met)2]
Fluconazole
7.9
6.2
8.2
10.2
12.2
3.2
9.5
8.7
11.3
2.9
10.2
2.4
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Research Highlights
 The complexes exhibit admirable DNA binding and chemical nuclease activity.

They have efficient antimicrobial effect against various pathogens.
 They act as potential DNA targeting agents.
 Leading to develop designing and synthesis of novel metal based drugs.
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