Efficient nuclease activity of dinuclear iron(III) complex with ligand having carboxamido nitrogen donors

Article abstract of DOI:10.1016/j.inoche.2012.02.042

A new dinucleating ligand N,N′-diphenyl-N,N′-di(pyridin-2-yl) oxalohydrazide (GampH₂) has been synthesized and GampH₂ gave rise to complex [Fe₂(Gamp)(DMF)₂Cl₄], 1 with FeCl₃ salt and 1 was isolated as shiny blue crystalline solid. The molecular structure of complex 1 was characterized by X-ray crystallography. In this dinuclear complex, Fe-Fe separation was found to be 5.49 ? and variable temperature magnetic moment was examined. Electrochemical investigation afforded a quasireversible redox couple with E_1/2 value of 0.144 V vs Ag/AgCl. Complex 1 was efficient in DNA cleavage activity and enhancement of DNA cleavage was observed in the presence of 2-mercaptoethanol and hydrogen peroxide. Investigation of mechanism indicated possible involvement of hydroxyl radical in nuclease activity.

Full text of DOI:10.1016/j.inoche.2012.02.042

Inorganic Chemistry Communications 20 (2012) 167–171
Contents lists available at SciVerse ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Efficient nuclease activity of dinuclear iron(III) complex with ligand having
carboxamido nitrogen donors
⁎
Kaushik Ghosh , Nidhi Tyagi, Pramod Kumar, Sweety Rathi, Udai P. Singh
Department of Chemistry, Indian Institute of Technology, Roorkee, Roorkee-247667, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new dinucleating ligand N,N′-diphenyl-N,N′-di(pyridin-2-yl)oxalohydrazide (GampH2) has been synthe-
sized and GampH2 gave rise to complex [Fe2(Gamp)(DMF)2Cl4], 1 with FeCl3 salt and 1 was isolated as
shiny blue crystalline solid. The molecular structure of complex 1 was characterized by X-ray crystallography.
In this dinuclear complex, Fe–Fe separation was found to be 5.49 Å and variable temperature magnetic mo-
ment was examined. Electrochemical investigation afforded a quasireversible redox couple with E1/2 value of
0.144 V vs Ag/AgCl. Complex 1 was efficient in DNA cleavage activity and enhancement of DNA cleavage was
observed in the presence of 2-mercaptoethanol and hydrogen peroxide. Investigation of mechanism indicat-
ed possible involvement of hydroxyl radical in nuclease activity.
Received 14 September 2011
Accepted 28 February 2012
Available online 12 March 2012
Keywords:
Dinucleating ligand
Dinuclear iron(III) complex
Carboxamido nitrogen
X-ray structure
© 2012 Elsevier B.V. All rights reserved.
Nuclease activity
There has been considerable current interest in the studies on in-
teraction of DNA with transition metal complexes because of their ap-
plications in the design and development of artificial nucleases, foot-
printing reagents, spectroscopic probes and chemotherapeutic agents
which demand applications in medicinal chemistry and nucleic acid
research [1–3]. Among the first row transition elements iron has got
special interest due to its versatile coordination chemistry [4] and
its redox properties [5]. In fact Fe-BLM causes DNA damage and it is
clinically used for cancer treatment [6]. It is reported in the literature
that deprotonated carboxamido nitrogen was bound to the iron cen-
ter in Fe-BLM [7,8]. Therefore, the peptide bond (carboxamido nitro-
gen (Nam)) linkage to metal center plays important role for inorganic
as well as biological chemists because of their biomimetic and phar-
maceutical relevances [9–13]. Indeed carboxamido nitrogen (Nam) is
very important for several applications. Mascharak and co-workers
reported the role of Nam for the coordination and photolability of
NO [14]. Coordination chemistry of carboxamido nitrogen is also im-
portant for catalytic activity [15], prion protein research [16] and
metal coordination in nitrile hydratase [17]. Recently, we have also
communicated the role of carboxamido nitrogen in nuclease activity
for manganese complexes [7]. We synthesized dinuclear iron com-
plex with ligand having carboxamido nitrogen donors. It has been
documented in the literature that dinuclear complexes exhibit higher nu-
clease activity compared to mononuclear complexes [18,19]. Recently,
Peng et al. [20–22] reported dinuclear iron complexes derived from li-
gands containing phenolato donors and the complexes exhibited
nuclease activity. In these reports the ligands were capable of binding
more than one metal centers. On the other hand several dinuclear iron
complexes were synthesized from bi, tri or tetradentate ligands and
their DNA interaction studies were investigated [20–28]. However to
the best of our knowledge there was no report on nuclease activity of
dinuclear iron complexes with a dinucleating ligand having carboxamido
nitrogen donor(s).
Herein we report the synthesis and characterization of a new
dinucleating ligand (GampH2) having two carboxamido nitrogen
(Nam) donors (Scheme 1). Iron complex of GampH2 was synthesized
and molecular structure of the complex was determined by X-ray
crystallography. Redox property was investigated. Nuclease activity
and possible mechanism of DNA cleavage activity will be scrutinized
in this report.
White solid of ligand (GampH2) has been synthesized by refluxing
2-(1-phenylhydrazinyl)pyridine [29] (2 equiv.) with oxalyl chloride
(1 equiv.) in dichloromethane, in the presence of the base triethyla-
mine (5 equivalent) for 4 h. The ligand was characterized by IR, IR
and NMR techniques and shown in supporting information (Fig. S1–
S3). Reaction of deprotonated ligand (by sodium hydride) GampH2
with (Et3N)[FeCl4] salt (metal to ligand ratio 1:1) in dimethylforma-
mide (DMF) and tetrahydrofuran (THF) solution afforded blue needle
like crystals of complex 1, [Fe2(Gamp)(DMF)2Cl4].
IR spectral studies of
1
shows νC
stretching frequency at
O
_
1606 cm−1. Coordination of deprotonated Gamp2- to iron metal center
was observed by shifting of νC
from 1674 cm−1 in free ligand to
O
_
1606 cm−1 in metal complex. The decrease in νC O frequency in com-
_
plex 1 clearly indicated that the binding of deprotonated ligand to the
metal center and the decrease of νC
partial double bond character in carbonyl moiety after complex
were due to the generation of
O
_
⁎
Corresponding author. Tel.: +91 1332 285547; fax: +91 1332 273560.
E-mail address: ghoshfcy@iitr.ernet.in (K. Ghosh).
1387-7003/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2012.02.042

168
K. Ghosh et al. / Inorganic Chemistry Communications 20 (2012) 167–171
reported for FeIII metal center by Wieghardt and coworkers [34]. The
equatorial Fe\Cl1 bond length (trans to carboxamido nitrogen was
2.2691(14)Å), however, the axial Fe\Cl2 bond length was 2.3209(14)
Å, which was longer than equatorial Fe\Cl1 distance. The short distance
of Fe\Cl1 may be due to the trans effect of carboxamido nitrogen [35].
The Fe\ODMF bond lengths was 2.112(4)Å which was quite large than
reported literature value [36]. The bond lengths Fe\Cl, Fe\N and
Fe\O were quite long which represented high-spin d5 configuration of
metal center [34,31]. The flexibility of the ligand was expressed by the
small chelated bite angles between the carboxamido and pyridine nitro-
gen atoms, with 72.88(15)° for N1\Fe1\N2 as well as carboxamido ni-
trogen and oxygen from \C O moiety with 78.41(15)° for N1\Fe1\O2.
_
The angles between the chloride ligands and solvent molecule (dimethyl-
formamide) were significantly larger than 90°, with values 94.81(5)° for
Cl1\Fe1\Cl2, 103.83(11)° and 97.83(11)° for O2\Fe1\Cl1 and
O2\Fe1\Cl2 respectively. These values expressed the distortion from
octahedral geometry and consistent with reported literature values
[31,32]. There are two types of non-covalent interactions observed in
packing diagram of complex 1. First, a hydrogen bonding between axial
chlorine atom and pyridyl hydrogen atom (distance — 2.865 Å ) and sec-
ond, non-covalent interaction between aromatic hydrogen and carbon
atom of dimethylformamide (distance — 2.857 Å) (Shown in supporting
information (Fig. S7)). We would like to mention here that the bond dis-
tances observed after structure calculation were similar to the distances
in high-spin Fe(III) complexes [34,31].
Magnetic property of dinuclear iron (magnitude of the intermole-
cular Fe\Fe separation was 5.49 Å) complex 1 has been studied by
SQUID magnetometer in the range 5–300 K at an external field of
5 T. The variable-temperature (5–300 K) magnetic susceptibility
(χm) of complex 1 and plot of χmT vs T is shown in Fig. S8. The mag-
netic moment of complex 1 at 300 K was about 7.8 BM and as the
temperature lowered magnetic moment decreases monotonically
from 7.8 BM to 1.4 BM (at 5 K). This decrease at low temperature
represented the spin of two ferric centers were weakly antiferromag-
netically coupled [34,37].
Scheme 1. Schematic representation of ligand GampH2.
formation. Similar red shift of νC
has been noted with other Fe(III)
O
_
complexes with coordinated carboxamido nitrogens [30]. This result
was further supported by disappearance of νN H (3242 cm−1) in com-
–
plex 1. UV–vis spectra of complex 1 was recorded in acetonitrile show-
ing peak at 238 nm (ε=24,600 M−1 cm−1) and shoulder at 270 nm
(ε=21,330 M−1 cm−1) which were assigned to be ligand based
π–π*, n–π* transitions [29]. Small humps near 320 nm (ε=
18,220 M−1 cm−1) and 350 nm (ε=14,680 M−1 cm−1) were due to
charge-transfer transitions from the coordinated chloride to the metal
center [31,32] and a broad band at 562 nm (ε=2346 M−1 cm−1
was also assigned as ligand to Fe(III) charge transfer transition. The
molar conductivity value (8.0 Λm/Ω−1cm2mol−1 in DMF) represents
neutral or non-electrolytic behavior of complex 1 [33].
)
Molecular structure of dinuclear iron complex [Fe2(Gamp)(DMF)2Cl4]
(1) depicted in Fig. 1. All the crystallographic parameters are tabulated in
Table S1. Needle shaped blue crystals of 1 were obtained by slow evapo-
ration of dimethylformamide:tetrahydrofuran (1:5) solution within a
week. The X-ray crystal structure of 1 revealed that both the iron centers
were octahedrally coordinated by two oxygen atoms from the carbonyl
group (Oox), two carboxamido nitrogens (Nam) and two pyridine nitro-
gens (Npy) from the ligand and the remaining terminal coordination
site was occupied by four chloride and two solvent molecules. In complex
1, Fe\Nam, Fe\Npy and Fe\Oox bond lengths were 2.071(4)Å, 2.152(4)
Å and 2.017(4)Å respectively and they are consistent with the values
The electrochemistry of the dinuclear complex was studied by
cyclic voltammetry. The neutral uncomplexed ligand does not
show any cyclic voltammogram over the range from −0.2 to 0.4 V;
hence the curve shown here attributed to the redox activity of com-
plex 1. Cyclic voltammetry of the complex 1 was recorded in aceto-
nitrile with TBAP as supporting electrolyte vs Ag/AgCl. Cyclic
voltammogram of complex 1 showed a quasireversible peak and
shown in Fig. 2. The E1/2 value of Fe(III)/Fe(II) couple for complex
1 was 0.144 V vs Ag/AgCl.
20
10
0
-10
Fig. 1. Ball and stick representation of [Fe2(Gamp)(DMF)2Cl4] (1). Selected bond
lengths (Å) and angles (°): Fe1\N1 2.071(4), Fe1\N2 2.152(4), Fe1\O2 2.017(4),
Fe1\Cl1 2.2691(14), Fe1\Cl2 2.3209(14), Fe1\O1 2.112(4), N1\Fe1\N2
72.88(15), N1\Fe1\O2 78.41(15), N1\Fe1\O1 84.34(15), N1\Fe1\Cl1
174.68(12), N1\Fe1\Cl2 89.63(11), N2\Fe1\Cl1104.24(12), N2\Fe1\Cl2
88.60(11), Cl1\Fe1\Cl2 94.81(5), O1\Fe1\N1 84.34(15), O1\Fe1\N2 85.90(15),
O1\Fe1\O2 84.81(15), O1\Fe1\Cl2 172.81(11), O1\Fe1\Cl1 91.03(11),
O2\Fe1\Cl1 103.83(11), O2\Fe1\Cl2 97.83(11), O2\Fe1\N2 150.53(15).
-0.15
0.00
0.15
0.30
V vs. Ag+/AgCl
Fig. 2. Cyclic voltammogram of 10−3 M solution of complex 1 using working electrode:
glassy-carbon, reference electrode: Ag/AgCl; auxiliary electrode: platinum wire, scan
rate 0.1 V/s.

K. Ghosh et al. / Inorganic Chemistry Communications 20 (2012) 167–171
169
Fig. 3. Gel electrophoresis separations showing the cleavage of supercoiled pBR322 DNA (60 ng) by complex 1 incubated at 37 °C for 3 h. (a) Key, lane 1: DNA, lanes 2–8: DNA+H2O2
(200 μM)+1=10, 15, 30, 40, 50, 60, 70 μM respectively, lane 9: DNA+H2O2 (200 μM). (b) Key, lane 1: DNA, lane 2: DNA+1 (50 μM), lane 3: DNA+1 (100 μM), lanes 4–7: DNA+1
(50 μM)+BME=50, 100, 150, 200 μM respectively, lanes 8–9: DNA+BME (200 μM)+1=10, 70 μM respectively, lane 10: DNA+BME (200 μM).
We have investigated the stability of our complex in phosphate
buffer at pH 7.2 and the complex was observed in buffer solution by
UV–vis spectral studies with repetitive scans for 5 h. It has been
found out that the complex is generating new species in the phos-
phate buffer solution as the spectra obtained after 5 h are different
to that of ligand. This is probably due to the coordination of H2O mol-
ecule and/or dissociation of Cl− ion. Electronic spectra for this study
were furnished in the Fig. S6 in the supporting information. We
were unable to find out the binding constant of the complex with
calf thymus DNA (CT DNA) because we did not observe appreciable
change in UV–vis spectra during our DNA titration experiment [29].
The DNA cleavage behavior of the complex 1 was studied under phys-
iological conditions (37 °C) and observed by the transformation of the
supercoiled form (SC) to the nicked (NC) and linear (LC) forms of
plasmid DNA (60 ng) in Tris–boric acid–EDTA buffer. The nuclease ac-
tivity of the complex 1 was examined by gel electrophoresis, which
allowed quantitative evaluation of different forms of the DNA by
plotting their integrated densities graphs [28]. The nuclease activity
was performed in 10% acetonitrile solution and no cleavage was
found in the presence of acetonitrile (Fig. S9, lane 6). Nuclease activ-
ities were performed in the absence as well as in the presence of re-
ducing (BME) and oxidizing (H2O2) agents. Complex
1 alone
cleaved pBR322 plasmid DNA without any oxidizing or reducing
agent at high concentrations (150–200 μM), however, no LC form
was observed (Fig. S9, lanes 3–5). Gel electrophoresis experiment
was investigated with the variation of incubation time in presence
of complex also. The electrophoresis data afforded enhancement of
nuclease with increase in incubation time (Fig. S9, lanes 8–10). Com-
plex 1 efficiently cleaved DNA in the presence of H2O2 shown in
Fig. 3(a). A 10–70 μM of complex is sufficient for production of LC
form of DNA in the presence of 200 μM of H2O2 (Fig. 3(a), lanes
2–8). Complex 1 also exhibited DNA cleavage in the presence of
BME with increasing amount of BME (50–200 μM) where integrated
density of NC form started increasing with incubation time
Fig. 4. Gel electrophoresis separations showing the cleavage of supercoiled pBR322 DNA (60 ng) by complex 1 (50 μM) and H2O2 (200 μM) incubated at 37 °C for 3 h. (a) Key, lane 1:
DNA, lane 2: DNA+1+H2O2, lanes 3–8: DNA+1+H2O2 +EtOH (20 mM), NaN3 (20 mM), urea (20 mM), D2O (20 mM), DMSO (20 mM), KI (20 mM) respectively. (b) Key, lane 1:
DNA, lane 2: DNA+1+BME, lanes 3–8: DNA+1+BME+DMSO (20 mM), NaN3 (20 mM), KI (20 mM), D2O (20 mM), urea (20 mM), EtOH (20 mM) respectively.

170
K. Ghosh et al. / Inorganic Chemistry Communications 20 (2012) 167–171
(Fig. 3(b), lanes 4–7). In Fig. 3, it is clear that at high concentration of
H2O2 and BME (200 μM) complex 1 showed efficient nuclease activi-
ty. In the control experiment, H2O2 and BME itself did not show DNA
cleavage (Fig. 3). The nuclease activity at the lower concentration of
the complex was not enough when only complex was utilized; how-
ever, the enhancement of the DNA cleavage activity with the addition
of H2O2 and BME is important and integral part of this study. For ex-
ample, the work reported by Borras and coworkers [37] described the
nuclease activity by the complex only as well as the complex in the
presence of H2O2/BME. The activity was found to be in the range
25–30 μM. Hence no enhancement was observed, however the activ-
ity for 1 in the presence of H2O2 and BME is similar to the work de-
scribed by Borras and coworkers. In a recent report by Chakravarty
and coworkers [38] Fig. 5 clearly showed the activity of the iron com-
plex at a concentration of 30 μM. Of course our molecule is not effi-
cient like the complexes described by Mandal and coworkers [39].
However to the best of our knowledge there was no report on nucle-
ase activity of dinuclear iron complexes with a dinucleating ligand
having carboxamido nitrogen donor(s).
thankful to UGC for financial assistance. UPS is thankful to IIT Roorkee
for single crystal X-ray facility.
Appendix A. Supplementary data
Supplementary data to this article can be found online at doi:10.
1016/j.inoche.2012.02.042.
References
[1] I. Bertini, H.B. Gray, S.J. Lippard, J.S. Valentine, Bioinorganic Chemistry University
Science Books: South Asian Edn, 1998.
[2] B.M. Zeglis, V.C. Pierre, J.K. Barton, Metallo-intercalators and metallo-insertor,
Chem. Commun. (2007) 4565–4579.
[3] G.C. Silver, W.C. Trogler, Efficient cleavage of DNA by iron(III) triazacyclononane
derivatives, J. Am. Chem. Soc. 117 (1995) 3983–3993.
[4] F.A. Cotton, G. Wilkinson, Advanced Inorganic Chemistry, 4th Edn Wiley, New
York, 1980.
[5] C.D. Kaplan, J. Kaplan, Iron acquisition and transcriptional regulation, Chem. Rev.
109 (2009) 4536–4552.
[6] G. Roelfes, M.E. Branum, L. Wang, L. Que Jr., B.L. Feringa, Efficient DNA cleavage
with an iron complex without added reductant, J. Am. Chem. Soc. 122 (2000)
11517–11518.
Investigation of mechanism of DNA cleavage was performed in the
presence of several quenchers eg. NaN3 (singlet oxygen quencher),
DMSO, urea, EtOH, KI and D2O (hydroxyl radical quenchers)
[7,29,33]. Addition of singlet oxygen quencher NaN3 did not show
any inhibition of DNA cleavage in the presence of oxidizing agent
H2O2. Addition of D2O significantly inhibited the cleavage of DNA in
the presence of H2O2 which ruled out the possible role of singlet ox-
ygen in cleavage pathway (Fig. 4(a)). However, hydroxyl radical scav-
engers such as DMSO and KI (Fig. 4(a), lanes 7, 8) inhibited the
nuclease activity and hence hydroxyl radical was probably responsi-
ble for nuclease activity. Similar observation was made during the in-
vestigation of mechanism of nuclease activity in the presence of
reducing agents BME (Fig. 4(b)). Moreover NaN3 did not inhibit and
D2O did not enhance the nuclease activity of 1 in the presence of
BME (Fig. 4(b)). These results indicated the involvement of hydroxyl
radicals as the reactive oxygen species in the nuclease activity of com-
plex 1 in the presence of H2O2 and BME [7,29]. For further confirma-
tion of role of hydroxyl radical we tried to do rhodamine B Assay [40].
We cannot predict with confirmation with the data obtained from the
assay, however we got some indication regarding the role of hydroxyl
radical. There are two important points we would like to mention
here. First, there was an increase in absorbance of 552 nm band of
rhodamine B due to the addition of our complex 1 which indicated
probable interaction of dye with metal complex. Second, we saw
the decrease in the absorbance of 552 nm band similar to the data
obtained by using iron salt and H2O2. These data support our observa-
tion during inhibition studies.
In conclusion, a novel dinuclear iron(III) complex was synthesized
and spectroscopically characterized. Molecular structure of this com-
plex was determined by X-ray crystallography. Redox property of the
metal center was investigated and variable temperature magnetic
moment measurement afforded weak antiferromagnetically coupled
iron centers. The complex itself was efficient in cleaving DNA at
high concentration, however, the efficiency was increased with the
increase in incubation time. Moreover, we have found out the en-
hancement of nuclease activity in the presence of H2O2 as well as
BME. Preliminary results on investigation of mechanism predicted
possible role of hydroxyl radicals in DNA cleavage activities. Detail
of the mechanism of such activity and biological applications are
under progress.
[7] K. Ghosh, N. Tyagi, P. Kumar, Role of carboxamido nitrogen in mononuclear man-
ganese complex: superoxide scavenging activity and nuclease activity, Inorg.
Chem. Commun. 13 (2010) 380–383.
[8] R.J. Guajardo, S.E. Hudson, S.J. Brown, P.K. Mascharak, [Fe(PMA)]n+ (n=1,2):
good models of iron-bleomycins and examples of mononuclear non-heme iron
complexes with significant oxygen-activation capabilities, J. Am. Chem. Soc. 115
(1993) 7971–7977.
[9] H. Sigel, R.B. Martin, Coordinating properties of the amide bond. Stability and
structure of metal ion complexes of peptides and related ligands, Chem. Rev. 82
(1982) 385–426.
[10] J.W. Peters, M.H.B. Stowell, S.M. Soltis, M.G. Finnegan, M.K. Johnson, D.C. Rees,
Redox-dependent structural changes in the nitrogenase P-cluster, Biochemistry
36 (1997) 1181–1187.
[11] D.S. Marlin, P.K. Mascharak, Coordination of carboxamido nitrogen to tervalent
iron: insight into a new chapter of iron chemistry, Chem. Soc. Rev. 29 (2000)
69–74.
[12] S. Hazra, S. Naskar, D. Mishra, S.I. Gorelsky, H.M. Figgie, W.S. Sheldrick, S.K.
Chattopadhyay, Synthesis, X-ray crystal structure and DFT calculations of bis(N-(2-
picolyl)picolinamido)Mn(III) hexafluorophosphate, Dalton Trans. (2007) 4143–4148.
[13] J. Zhang, Q. Liu, C. Duan, Y. Shao, J. Ding, Z. Miao, X.-Z. You, Z. Guo, Structural evidence
for the facile chelate-ring opening reactions of novel platinum(II)–pyridine carbox-
amide complexes, J. Chem. Soc., Dalton Trans. (2002) 591–597.
[14] A.K. Patra, J.M. Rowland, D.S. Marlin, E. Bill, M.M. Olmstead, P.K. Mascharak, Iron
nitrosyls of a pentadentate ligand containing a single carboxamide group: syn-
theses structures, electronic properties, and photolability of NO, Inorg. Chem.
42 (2003) 6812–6823.
[15] J.M. Workman, R.D. Powell, A.D. Procyk, T.J. Collins, D.F. Bocian, Vibrational and
electrochemical properties of a series of stable manganese(V)-oxo complexes,
Inorg. Chem. 31 (1992) 1548–1550.
[16] G.L. Millhauser, Copper binding in the prion protein, Acc. Chem. Res. 37 (2004) 79–85.
[17] T.C. Harrop, P.K. Mascharak, Fe(III) and Co(III) centers with carboxamido nitrogen
and modified sulfur coordination: lessons learned from nitrile hydratase, Acc.
Chem. Res. 37 (2004) 253–260.
[18] L.M.T. Schnaith, R.S. Hanson, L. Que Jr., Double-stranded cleavage of pBR322 by a
diiron complex via a “hydrolytic” mechanism, Proc. Natl. Acad. Sci. U. S. A. 91
(1994) 569–573.
[19] X.-Q. Chen, X.-J. Peng, J.-Y. Wang, Y. Wang, S. Wu, L.-Z. Zhang, T. Wu, Y.-K. Wu, Ef-
ficient increase of DNA cleavage activity of a diiron(III) complex by a conjugating
acridine group, Eur. J. Inorg. Chem. (2007) 5400–5407.
[20] X. Chen, J. Wang, S. Sun, J. Fan, S. Wu, J. Liu, S. Ma, L. Zhang, X. Peng, Efficient en-
hancement of DNA cleavage activity by introducing guanidinium groups into diir-
on(III) complex, Bioorg. Med. Chem. Lett. 18 (2008) 109–113.
[21] X. Chen, J. Fan, X. Peng, J. Wang, S. Sun, R. Zhang, T. Wu, F. Zhang, J. Liu, F. Wang, S.
Ma, Bisintercalator-containing dinuclear iron(III) complex: an efficient artificial
nuclease, Bioorg. Med. Chem. Lett. 19 (2009) 4139–4142.
[22] X.Q. Chen, J.Y. Wang, T.Y. Zhang, L.Z. Zhang, X.J. Peng, Synthesis and DNA cleavage ac-
tivity of diiron(III) complex bearing pyrene group, Chin. Chem. Lett. 19 (2008)
342–344.
[23] M. Roy, R. Santhanagopal, A.R. Chakravarty, DNA binding and oxidative DNA
cleavage activity of (μ-oxo)diiron(III) complexes in visible light, Dalton Trans.
(2009) 1024–1033 and references therein.
[24] C. Liu, S. Yu, D. Li, Z. Liao, X. Sun, H. Xu, DNA hydrolytic cleavage by the diiron(III)
complex Fe2(DTPB)(μ-O)(μ-Ac)Cl(BF4)2: comparison with other binuclear transi-
tion metal complexes, Inorg. Chem. 41 (2002) 913–922.
[25] H. Kurosaki, A. Maruyama, H. Koike, N. Kuroda, Y. Ishikawa, M. Goto, DNA cleav-
age by pentadentate iron(II) complexes containing fluoro-substituted phenyl
groups, Bioorg. Med. Chem. Lett. 12 (2002) 201–203.
[26] G.L. Parrilha, C. Fernandes, A.J. Bortoluzzi, B. Szpoganicz, M.D.S. Silva, C.T. Pich, H.
Terenzi, A. Horn Jr., A new μ-oxo di-iron complex with suitable features to mimic
metallohydrolase activity: X-ray molecular structure, aqua solution behavior and
Acknowledgments
KG is thankful to IITR for Faculty Initiation Grant (Scheme B) and
DST, New Delhi, India for SERC FAST Track project (SR/FTP/CS-44/
2006) support. NT and PK are thankful to CSIR, India and SR is

K. Ghosh et al. / Inorganic Chemistry Communications 20 (2012) 167–171
171
nuclease activity of the complex [Fe(HPClNOL)(SO4)]2-μ-oxo, Inorg. Chem. Com-
mun. 11 (2008) 643–647.
[27] A. Neves, H. Terenzi, R. Horner, A. Horn Jr., B. Szpoganicz, J. Sugai, Hydrolytic DNA
cleavage promoted by a dinuclear iron(III) complex, Inorg. Chem. Commun. 4
(2001) 388–391.
[28] R. Herchel, Z. Sindelar, Z. Travnicek, R. Zboril, J. Vanco, Novel 1D chain Fe(III)- salen-like
complexes involving anionic heterocyclic N-donor ligands. Synthesis, X-ray structure,
magnetic, 57Fe Mössbauer, and biological activity studies, Dalton Trans. (2009)
9870–9880 and references therein.
[29] K. Ghosh, N. Tyagi, P. Kumar, U.P. Singh, N. Goel, Stabilization of Mn(II) and
Mn(III) in mononuclear complexes derived from tridentate ligands with N2O do-
nors: synthesis, crystal structure, superoxide dismutase activity and DNA interac-
tion studies, J. Inorg. Biochem. 104 (2010) 9–18.
[34] U. Beckmann, E. Bill, T. Weyhermuller, K. Wieghardt, Exchange interactions and co-
valency in dinuclear complexes of iron(III) and gallium(III) containing the redox-
noninnocent ligand 1,2-Bis(3,5-di-tert-butyl-2-hydroxyphenyl)oxamide, Eur. J.
Inorg. Chem. (2003) 1768–1777.
[35] R.K. Afshar, A.K. Patra, E. Bill, M.M. Olmstead, P.K. Mascharak, Synthesis, structure,
and properties of an Fe(II) carbonyl [(PaPy3)Fe(CO)](ClO4): insight into the reac-
tivity of Fe(II)\CO and Fe(II)\NO moieties in non-heme iron chelates of N-donor
ligands, Inorg. Chem. 45 (2006) 3774–3781.
[36] A.K. Patra, M.J. Rose, M.M. Olmstead, P.K. Mascharak, Reactions of nitric oxide
with a low-spin Fe(III) center ligated to a tetradentate dicarboxamide N4 ligand:
parallels between heme and non-heme systems, J. Am. Chem. Soc. 126 (2004)
4780–4781.
[37] F.B.A.E. Amrani, L. Perelló, J.A. Real, M. González-Alvarez, G. Alzuet, J. Borrás, S.
García-Granda, J. Montejo-Bernardo, Oxidative DNA cleavage induced by an iro-
n(III) flavonoid complex: synthesis, crystal structure and characterization of
chlorobis (flavonolato)(methanol) iron(III) complex, J. Inorg. Biochem. 100
(2006) 1208–1218.
[30] R.K. Afshar, A.A. Eroy-Reveles, M.M. Olmstead, P.K. Mascharak, Stoichiometric and
catalytic secondary O-atom transfer by Fe(III)-NO2 complexes derived from a pla-
nar tetradentate non-heme ligand: reminiscence of heme chemistry, Inorg. Chem.
45 (2006) 10347–10354.
[31] D. Mandon, A. Nopper, T. Litrol, S. Goetz, Tridentate coordination of monosubstituted
derivatives of the tris(2-pyridylmethyl)amine ligand to FeCl3: structures and spectro-
scopic properties of ((2-bromopyridyl)methyl)bis- (2-pyridylmethyl)amine FeIIICl3
and (((2-p- methoxyphenyl)pyridyl)methyl)bis(2-pyridyl- methyl)]amine FeIIICl3
and comparison with the bis(2-pyridylmethyl)]amine FeIIICl3 complex, Inorg. Chem.
40 (2001) 4803–4806.
[38] A. Mukherjee, S. Dhar, M. Nethaji, A.R. Chakravarty, Ternary iron(II) complex with
an emissive imidazopyridine arm from Schiff base cyclizations and its oxidative
DNA cleavage activity, Dalton Trans. (2005) 349–353.
[39] K.I. Ansari, J.D. Grant, G.A. Woldemariam, S. Kasiri, S.S. Mandal, Iron(III)-salen
complexes with less DNA cleavage activity exhibit more efficient apoptosis in
MCF7 cells, Org. Biomol. Chem. 7 (2009) 926–932.
[32] T. Kojima, R.A. Leising, S. Yan, L. Que Jr., Alkane functionalization at nonheme iron
centers. Stoichiometric transfer of metal-bound ligands to alkane, J. Am. Chem.
Soc. 115 (1993) 11328–11335.
[40] S.S. Tonde, A.S. Kumbhar, S.B. Padhye, R.J. Butcher, Self-activating nuclease activ-
ity of copper (II) complexes of hydroxyl-rich ligands, J. Inorg. Biochem. 100
(2006) 51–57.
[33] K. Ghosh, P. Kumar, N. Tyagi, U.P. Singh, V. Aggarwal, M.C. Baratto, Synthesis and re-
activity studies on new copper(II) complexes: DNA binding, generation of phenoxyl
radical, SOD and nuclease activities, Eur. J. Med. Chem. 45 (2010) 3770–3779.