Synthesis, structure, spectroscopic characterization, and protein binding affinity of new water-soluble hetero- and homometallic tetranuclear [Cu II2ZnII2] and [CuII 4] clusters

Article abstract of DOI:10.1021/ic302099y

Two new water-soluble hetero- and homometallic tetranuclear clusters, Na₄[Cu₂Zn₂(ccdp)₂(μ-OH) ₂]·CH₃OH·6H₂O (1) and K ₃[Cu₄(ccdp)₂(μ-OH)(μ-OH ₂)]·14H₂O (2), have been synthesized in methanol-water at room temperature by exploiting the flexibility, chelating ability, and bridging potential of a carboxylate-rich dinucleating ligand, N,N′-bis(2-carboxybenzomethyl)-N,N′-bis(carboxymethyl)-1,3 diaminopropan-2-ol (H₅ccdp). Complex 1 is obtained through the self-assembly of two monoanionic [CuZn(ccdp)]^-fragments, which are, in turn, exclusively bridged by two μ-OH^-groups. Similarly, complex 2 is formed through the self-assembly of two monoanionic [Cu ₂(ccdp)]^- species exclusively bridged by one μ-OH ^- and one μ-OH₂ groups. Complexes 1 and 2 are fully characterized in the solid state as well as in solution using various analytical techniques including a single-crystal X-ray diffraction study. The X-ray crystal structure of 1 reveals that two Cu^II centers are in a distorted square-pyramidal geometry, whereas two Zn^II centers are in a distorted trigonal-bipyramidal geometry. The solid-state structure of 2 contains two dinuclear [Cu₂(ccdp)]^- units having one Cu^II center in a distorted square-pyramidal geometry and another Cu^II center in a distorted trigonal-bipyramidal geometry within each dinuclear unit. In the powder state, the high-field EPR spectrum of complex 1 indicates that two Cu^II ions are not spin-coupled, whereas that of complex 2 exhibits at least one noninteracting Cu^II center coordinated to a nitrogen atom of the ligand. Both complexes are investigated for their binding affinity with the protein bovine serum albumin (BSA) in an aqueous medium at pH ～7.2 using fluorescence spectroscopy. Synchronous fluorescence spectra clearly reveal that complexes 1 and 2 bind to the active sites in the protein, indicating that the effect is more pronounced toward tyrosine than tryptophan. Density functional theory calculations have been carried to find the Fukui functions at the metal sites in complexes 1 and 2 to predict the possible metal centers involved in the binding process with BSA protein.

Full text of DOI:10.1021/ic302099y

Article
pubs.acs.org/IC
Synthesis, Structure, Spectroscopic Characterization, and Protein
Binding Affinity of New Water-Soluble Hetero- and Homometallic
II
II
II
Tetranuclear [Cu Zn ] and [Cu ] Clusters
2
‡
2
4
†
§
,⊥
‡
§
Ayan Patra, Tamal K. Sen, Atanu Ghorai, Ghezai T. Musie,* Swadhin K. Mandal, Utpal Ghosh,
,†
and Manindranath Bera*
†
Department of Chemistry, University of Kalyani, Kalyani, West Bengal 741235, India
‡
Department of Chemical Sciences, Indian Institute of Science Education & Research Kolkata, Mohanpur, West Bengal 741252, India
Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, Nadia, West Bengal 741235, India
§
⊥Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States
*
S Supporting Information
ABSTRACT: Two new water-soluble hetero- and homome-
tallic tetranuclear clusters, Na [Cu Zn (ccdp) (μ-OH) ]·
4
2
2
2
2
CH OH·6H O (1) and K [Cu (ccdp) (μ-OH)(μ-OH )]·
3
2
3
4
2
2
1
4H O (2), have been synthesized in methanol−water at room
2
temperature by exploiting the flexibility, chelating ability, and
bridging potential of a carboxylate-rich dinucleating ligand,
N,N′-bis(2-carboxybenzomethyl)-N,N′-bis(carboxymethyl)-
1
,3 diaminopropan-2-ol (H ccdp). Complex 1 is obtained
5
−
through the self-assembly of two monoanionic [CuZn(ccdp)]
fragments, which are, in turn, exclusively bridged by two μ-OH−
−
groups. Similarly, complex 2 is formed through the self-assembly of two monoanionic [Cu (ccdp)] species exclusively bridged by
2
−
one μ-OH and one μ-OH groups. Complexes 1 and 2 are fully characterized in the solid state as well as in solution using various
analytical techniques including a single-crystal X-ray diffraction study. The X-ray crystal structure of 1 reveals that two Cu centers
are in a distorted square-pyramidal geometry, whereas two Zn centers are in a distorted trigonal-bipyramidal geometry. The solid-
state structure of 2 contains two dinuclear [Cu (ccdp)] units having one Cu center in a distorted square-pyramidal geometry and
another Cu center in a distorted trigonal-bipyramidal geometry within each dinuclear unit. In the powder state, the high-field EPR
spectrum of complex 1 indicates that two Cu ions are not spin-coupled, whereas that of complex 2 exhibits at least one
noninteracting Cu center coordinated to a nitrogen atom of the ligand. Both complexes are investigated for their binding affinity
2
II
II
−
II
2
II
II
II
with the protein bovine serum albumin (BSA) in an aqueous medium at pH ∼7.2 using fluorescence spectroscopy. Synchronous
fluorescence spectra clearly reveal that complexes 1 and 2 bind to the active sites in the protein, indicating that the effect is more
pronounced toward tyrosine than tryptophan. Density functional theory calculations have been carried to find the Fukui functions at
the metal sites in complexes 1 and 2 to predict the possible metal centers involved in the binding process with BSA protein.
INTRODUCTION
chemistry, enzyme-like catalytic systems, and functional molecular
sensors. Furthermore, heterodimetallic complexes offer an
■
9
Properly designed hetero- and homometallic multinuclear complex
systems not only present synthetic challenges but also can provide
novel reactivity patterns as well as physical properties. The
neighboring metal centers in multimetallic systems are expected to
cooperate in promoting reactions, and new electronic interactions
might lead to distinct physical properties. Cooperative interactions
have commonly been observed in biological systems, and nature has
constructed numerous multimetallic protein complexes that perform
enormous potential in the fields of homogeneous catalytic
10
processes. Recently, progress has been documented in the
application of M−O−M1-based heterometallic complexes in
11
homogeneous catalytic processes with the concept of dual catalysis.
Similarly, the field of molecular-based magnetic materials has shown
12
spectacular advances over the last 2 decades. The advances have
rekindled interest in the fields of synthesis and characterization of
hetero- and homometallic dinuclear complexes. As a result, a
number of hetero- and homometallic dinuclear complexes of copper
and zinc are well documented in the literature using both
1
−4
an extraordinary array of catalytic transformations.
This
biochemistry has encouraged inorganic chemists to develop the
area from an inorganic viewpoint. Furthermore, from the materials
viewpoint, the multimetallic complexes can exhibit a full spectrum of
new magnetic, optical, and redox properties as a result of a
synergetic effect between the different metals.
interactions have been applied in the fields of supramolecular
13−18
symmetrical and unsymmetrical dinucleating ligands.
However,
5−8
Cooperative
Received: September 27, 2012
Published: March 1, 2013
©
2013 American Chemical Society
2880
dx.doi.org/10.1021/ic302099y | Inorg. Chem. 2013, 52, 2880−2890

Inorganic Chemistry
Article
very little is known about structurally characterized heterometallic
binding modes of a similar amide- and carboxylate-rich dinucleating
ligand have been explored in a self-assembled heptanuclear zinc
II
II
19
tetranuclear [Cu Zn ] complexes. Finding such multinuclear
2
2
27
hetero- and homometallic complex systems in good yield is indeed a
synthetic challenge given the increased complexity of these
compounds. Hence, the synthesis and investigation of hetero- and
homometallic polynuclear complexes for any purpose warrant filling
the void.
complex. In this paper, we report the synthesis, structure, spectral
characterization, and bovine serum albumin (BSA) protein binding
II
2
II
2
affinity of new hetero- and homometallic tetranuclear Cu Zn and
II
Cu
clusters.
4
Serum proteins play an essential role in the transport and
EXPERIMENTAL SECTION
■
II
II
20,21
metabolism of Cu and Zn ions.
Moreover, selective
Materials and Methods. 2-Carboxybenzaldehyde, 1,3-diamino-2-
propanol, and iodoacetic acid were purchased from Sigma-Aldrich
Chemie GmbH, Germany. Zinc perchlorate hexahydrate and copper
perchlorate hexahydrate were prepared in our laboratory following the
usual process. Bovine serum albumin (BSA) was purchased from
Sigma Chemicals, USA. Calf thymus DNA (CT-DNA) was purchased
from SRL, India. All other chemicals and solvents were reagent-grade
materials and were used as received from commercial sources without
further purification. Microanalyses (C, H, and N) were performed
using a Perkin-Elmer 2400 CHNS/O series II elemental analyzer. Fourier
transform infrared (FTIR) spectra were obtained on a Perkin-Elmer
quantification of protein is of fundamental importance in basic
biochemical or biomedical research and disease treatment.
Currently, the available classical methods for protein detection
include enzyme-linked immunosorbent assay, Western blotting,
22
and two-dimensional gel electrophoresis, etc. Most of these
techniques need rather complicated and laborious assay
procedures and expensive materials. Recently, many reports
on metal complex−protein interactions have appeared in the
literature. However, the majority of the documented works are
based on the interactions of mononuclear metal complexes with
−1
1
13
L120-000A spectrometer (200−4000 cm ). H and C NMR spectra
2
3
proteins. Few studies, however, have demonstrated that some
multinuclear copper(II) complexes can efficiently promote the
binding and cleavage of biological macromolecules such as
were obtained in a D O solution on a Bruker AC 400 NMR spectrometer
2
using tetramethylsilane as the internal standard. Mass spectrometry (MS)
spectra were recorded in MALDI-TOF MS using a Perseptive Bio System
Voyager DE-STR mass spectrometer. UV−vis spectra were recorded on a
Shimadzu UV 1800 (190−1100 nm; 1 cm quartz cell) spectrophotometer.
The solution electrical conductivity was obtained with a Systronics 304
2
4
DNA. The three global pharmacological factors controlling
the activity of metal-based drugs are cellular uptake, the
frequency and structure of biomolecule adducts, and the extent
of metabolizing interactions. The presence of multimetals in the
coordination sphere in multinuclear complexes allows modu-
lation of such pharmacological factors and, in turn, may alter
the drug efficacy. Moreover, during interaction of a protein
substrate with the multinuclear complexes, the influence of the
neighboring metal ions cannot be ignored. Binding at one metal
center can be favored under the strong electrostatic influence of
the other metal ions in the multinuclear complexes. This is in
contrast to the mononuclear complexes. In this context, there is
a demanding need for multinuclear hetero- and homometallic
complexes with proportional variations in the metal ions
because of their potential applications in medicinal chemistry
such as the development of new metal-based drugs for the
−3
digital conductivity meter with a solute concentration of about 10 M. The
room temperature magnetic susceptibilities in the solid state were measured
using a home-built Gouy balance fitted with a polytronic direct-current
power supply. The experimental magnetic susceptibilities were corrected
for the diamagnetic response using Pascal’s constants. High-frequency
electron paramagnetic resonance (EPR) spectra were recorded on a home-
built spectrophotometer at the EMR facility of NHMFL. The instrument
was a transmission-type device in which microwaves are propagated in
cylindrical light pipes. The microwaves were generated by a phase-locked
Virginia Diodes source generating a frequency of 13 ± 1 GHz and
producing its harmonics, of which the 4th, 8th, 16th, 24th, and 32nd were
available. A superconducting magnet (Oxford Instruments) capable of
reaching a field of 17 T was employed.
31
32
Synthesis of N,N′-Bis(2-carboxybenzomethyl)-N,N′-bis-
(
carboxymethyl)-1,3-diaminopropan-2-ol (H ccdp). The ligand
5
28
25
has been prepared according to the previously reported procedure.
binding of different biological macromolecules.
The product was collected by filtration, washed with water and methanol,
and dried at 80 °C. The product was confirmed by elemental analysis,
The focus here is on a carboxylate-rich dinucleating ligand,
N,N′-bis(2-carboxybenzomethyl)-N,N′-bis(carboxymethyl)-1,3
1
13
FTIR, and H and C NMR spectroscopy. Anal. Calcd for
·2HCl: C, 50.47; H, 5.16; N, 5.12. Found: C, 50.35; H,
diaminopropan-2-ol (H ccdp), with two acetate and two benzoate
5
C H N O
23 26 2 9
−1
functionalities (Figure 1). The carboxylate-rich dinucleating ligands
5.47; N, 5.01. FTIR (cm ): ν 3505(b), 3032(b), 1665(s), 1590(vs),
1
1
562(s), 1440(s), 1392(s), 1264(s), 1160(s), 902(s), 846(s), 788(s). H
NMR for the sodium salt of the compound (400 MHz, D O, room
2
temperature): δ 7.52 (d, 2H, J = 7.5 Hz), 7.40 (m, 4H), 7.35 (t, 2H, J = 7.5
Hz), 3.92 (d, 2H, J = 13.5 Hz), 3.81 (d, 2H, J = 13.5 Hz), 3.82 (d, 1H),
3
.19 (d, 2H, J = 16.5 Hz), 3.10 (d, 2H, J = 16.5 Hz), 2.62 (d, 1H, J = 3.0 Hz),
2.60 (d, 1H, J = 3.0 Hz), 2.45 (d, 1H, J = 9.0 Hz), 2.40 (d, 1H, J = 9.0 Hz).
13
C NMR (400 MHz, D O, room temperature): δ 180.16, 178.81, 140.58,
2
1
34.40, 130.46, 128.51, 127.30, 126.39, 66.29, 58.70, 58.57, 56.72.
Synthesis of Na [Cu Zn (ccdp) (μ-OH) ]·CH OH·6H O (1). A
4
2
2
2
2
3
2
Figure 1. Chemical structure of the ligand H ccdp.
methanol solution (10 mL) of ligand H ccdp (0.250 g, 0.457 mmol) and
5
5
NaOH (0.128 g, 3.199 mmol) was slowly added at ambient temperature
to a magnetically stirred solution of Cu(ClO ) ·6H O (0.169 g, 0.457
4
2
2
have been used for some time as a way to assemble metal ions into
mmol) and Zn(ClO ) ·6H O (0.170 g, 0.457 mmol) in 15 mL of water
4 2 2
26,27
during a period of 15 min. The whole reaction mixture was stirred at
room temperature for 2 h. It was then filtered to discard any insoluble
precipitates. The X-ray-quality sky-blue plate-shaped single crystals were
obtained by slow ether diffusion into the clear filtrate after ∼15 days.
aggregates with relevance in the area of bioinorganic chemistry.
II
II
The ligand H ccdp is recently known to bind Zn and Co ions to
5
yield mono- and hexanuclear zinc(II) complexes and tetranuclear
cobalt(II) complexes, showing the bridging potential of carbox-
Yield: 0.257 g (85%). Anal. Calcd for C H N O Na Cu Zn : C, 41.75;
28,29
46 44
4
20
4
2
2
ylates.
Very recently, we have reported the synthesis, character-
H, 3.33; N, 4.24; Cu, 9.61; Zn, 9.89. Found: C, 41.60; H, 3.53; N, 4.15;
ization, and spectroscopic investigations correlating the diverse
−1
2
Cu, 9.71; Zn, 9.95. Molar conductance (MeOH): Λ = 392 Ω cm
M
−1
−1
binding modes of carboxylates of the ligand H ccdp in a tetranuclear
mol . FTIR (KBr, cm ): ν 3436(b), 1607(s), 1589(s), 1563(s),
5
30
zinc(II) complex. Recently, the unusual amide and carboxylate
1452(s), 1387(vs), 1222(s), 1157(s), 1122(s), 1028(s), 996(s), 914(s),
2
881
dx.doi.org/10.1021/ic302099y | Inorg. Chem. 2013, 52, 2880−2890

Inorganic Chemistry
Article
−
1
−1
−3
7
(
59(s), 671(s). UV−vis (H O): λ (ε, L mol cm ) = 760 (116), 270
the range +2.173 to −1.524 e Å . For 2, a total of 17120 data were
recorded with Miller indices h = −17, h = 17, k = −22, k = 22,
2
max
sh
−
5771) . MS (ESI): m/z 1265 (M = {[Cu Zn (ccdp) (μ-
OH ) ]·CH OH + H} ). μ (total): 2.44 μ . μ /Cu: 1.72 μ .
Synthesis of K [Cu (ccdp) (μ-OH)(μ-OH )]·14H O (2). To a
solution of H ccdp (0.250 g, 0.457 mmol) and KOH (0.179g, 3.199
mmol) in methnol (10 mL) was added Cu(ClO ) ·6H O (0.338 g,
.914 mmol) in water (15 mL) with magnetic stirring during a period
2 2 2
min
max
min
max
−
lmin = −23, and lmax = 23 in the range 1.24 < θ < 27.00° using ω oscillation
frames. The data were corrected for absorption by the multiscan method,
giving minimum and maximum transmission factors. The data were merged
to form a set of 11019 independent reflections with R = 0.0697. The
residual electron density is in the range +1.687 to −1.047 e Å . The
structures were solved by direct methods and refined by full-matrix least-
squares methods on F . Hydrogen-atom positions were initially
determined by geometry and refined by a riding model. Non-hydrogen
atoms were refined with anisotropic displacement parameters. All hydrogen
atoms were generated at ideal positions (C−H, 0.96 Å) and fixed with
isotropic thermal parameters. In complex 1, the solvent molecules, mainly
diethyl ether molecules, show some disorder, but they could not be modeled
to fit this space because some solvent molecules were lost during crystal
handling.
2
2
3
eff
B
eff
B
34
3
4
2
2
2
5
4
2
2
−3
0
of 15 min. The reaction mixture was then stirred for 1 h, resulting in a
greenish-blue solution. It was then filtered to discard any insoluble
precipitates. The X-ray-quality blue plate-shaped single crystals were
obtained by slow ether diffusion into the clear filtrate after ∼5 days.
Yield: 0.269 g (88%). Anal. Calcd for C H N O K Cu : C, 41.07;
2
35
46
45
4
20
3
4
H, 3.37; N, 4.16; Cu, 18.89. Found: C, 41.22; H, 3.80; N, 4.35; Cu, 18.97.
−1
2
−1
Molar conductance (MeOH): Λ = 290 Ω cm mol . FTIR (KBr,
M
−1
cm ): ν 3402(b), 1628(s), 1587(s), 1560(s), 1453(s), 1385(vs),
1
6
(
2
220(s), 1152(s), 1112(s), 1031(s), 983(s), 923(s), 767(s), 715(s),
70(s). UV−vis (H O): λ (ε, L mol cm ) = 763 (273), 266
10825) . MS (ESI): m/z 1294 (M = {[Cu (ccdp) (μ-OH ) ]·
−
1
−1
DNA Binding Study. To investigate the DNA binding properties
of complexes 1 and 2, we titrated a fixed concentration of each
2
max
sh
−
4 2 2 2
−6
−
complex (1 × 10 M) with varying concentrations of CT-DNA from
6
CH OH + H} ). μ (total): 3.36 μ . μ /Cu: 1.68 μ .
3 eff B eff B
−
0
to 0.3 × 10 M, and the optical density was measured at 275 nm
Caution! Perchlorate salts of metal complexes are potentially explosive
and should be handled in small quantities with great care.
X-ray Crystallography and Data Analysis. Crystal data as well
as data collection and refinement for complexes 1 and 2 are summarized in
Table 1. Selected bond distances and bond angles are given in Table 2.
using UV−vis spectrophotometer [Shimadzu UV 1800 (190−1100 nm;
1
cm quartz cell)].
Protein Binding Study. We have studied the binding interactions
of complexes 1 and 2 with BSA protein using standard Trp
fluorescence with excitation at 280 nm and the corresponding
emission at 339 nm, using a Perkin-Elmer-LS55 spectrofluorimeter
equipped with FLWINLAB software with a rectangular quartz cuvette
of 1 cm path length. A stock solution of BSA protein was prepared in
phosphate buffer (pH ∼7.2). Concentrated stock solutions of
complexes 1 and 2 were prepared by dissolving them separately in
doubly distilled water and diluted suitably with doubly distilled water
to get the required concentrations. An aqueous solution (2 mL) of
Table 1. Crystal Data and Structure Refinement for 1 and 2
1
2
empirical formula
fw
C H N O Na Cu Zn C H N O K Cu
47 60 4 27 4 2 2 46 73 4 34 3 4
1462.8
1597.6
cryst syst
space group
a, Å
triclinic
triclinic
−
6
P1
̅
P1
̅
BSA protein (0.375 × 10 M) was titrated by successive additions of
5
−
14.0024(9)
13.9984(9)
the respective complexes [(0−11.285) × 10 M].
Theoretical Calculations. Theoretical calculations regarding
b, Å
15.4647(9)
17.3764(12)
18.4280(12)
109.399(4)
103.984(4)
99.382(4)
3955.1(5)
1
+
k
structure optimization and the Fukui function (f ) of the metal
sites of the monomeric halves of complexes 1 and 2 were carried out
with Gaussian 03 software. The functions f were estimated from
single-point calculations using the B3LYP method and 6-311G basis
set at the optimized geometry, performed for N and N + 1 electron
systems, where N is the total number of electrons in the system. In a finite
c, Å
17.0062(10)
77.940(3)
68.504(3)
64.402(3)
3084.5(3)
3
α, deg
3
6
+
k
β, deg
37
38
γ, deg
volume, mm3
+
Z
difference approximation, fk of an atom k, in a molecule with N
3
+
density (calcd), Mg/m
wavelength, Å
temperature, K
F(000)
1.629
1.589
electrons, is expressed by the equation f = q (N) − q (N+1), where q
k
k
k
k
39
0.71073
296
0.71073
296
is the charge of atom k. The q values were calculated by Mulliken
k
population analysis.
1548
1857
−
1
abs coeff, mm
1.568
1.826
RESULTS AND DISCUSSION
■
θ range for data collection, deg 1.29−30.53
reflns collected
2.3−29.79
17120
Synthesis and General Characterization. The reaction
of H ccdp with Cu(ClO ) ·6H O and Zn(ClO ) ·6H O in a
1:1:1 molar ratio in the presence of NaOH at pH ∼9 in
methanol−water at room temperature in air led to the assembly of
sky-blue heterometallic tetranuclear cluster 1 (Figure 2). The
reaction of H ccdp with Cu(ClO ) ·6H O in a 1:2 molar ratio in
the presence of KOH at pH ∼9 in methanol−water at ambient
temperature in air afforded a blue compound that was easily
crystallized into a new tetranuclear cluster 2 (Figure 2). The
molecular structures of complexes 1 and 2 have been established
using a single-crystal X-ray diffraction study. Other analytical
techniques used in the characterization of the complexes include
elemental analysis, solution electrical conductivity, room temper-
ature magnetic moment measurement, FTIR, UV−vis, high-field
EPR, and MS techniques. The molar conductivity value of 1 in
17818
5
4 2
2
4 2
2
indep reflns
12181
11019
a
R1(F obsd data) [I > 2σ(I)] 0.0516
0.0697
2
b
wR2(F all data)
GOF on F2
0.1490
0.1949
1.035
0.997
largest diff peak and hole, e Å−3 +2.173 and −1.524
R1 = ∑||F | − |F ||/∑|F |. wR2 = {∑[w(F − F ) ]/∑[w(F ) ]}1/2.
5
4 2
2
+1.687 and −1.047
a
b
2
o
2
2
2 2
o
c
o
c
o
Clear sky-blue plate-shaped single crystals of complex 1 with approximate
3
dimensions of 0.33 × 0.22 × 0.12 mm and blue plate-shaped single crystals
3
of complex 2 with approximate dimensions 0.6 × 0.4 × 0.2 mm were
selected for structural analysis. Intensity data for these compounds were
33
collected using a diffractometer with a Bruker SMART CCD area detector
and graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). For 1, a
total of 17818 data were measured with Miller indices hmin = −19, h = 17,
max
−1
2
−1
MeOH is 392 Ω cm mol at room temperature, corresponding
to a 4:1 electrolyte. Complex 2 behaves as a 3:1 electrolyte in a
MeOH solution (Λ = 290 Ω cm mol ). The total room
temperature magnetic moment value for 1 is 2.44 μ and that per
kmin = −22, k = 21, lmin = −22, and l = 22 in the range 1.29 <
max
max
θ < 30.53° using ω oscillation frames. The data were corrected for
−1
2
−1
34
absorption by the multiscan method, giving minimum and maximum
transmission factors. The data were merged to form a set of 12181
independent reflections with R = 0.0516. The residual electron density is in
M
B
II
each copper is 1.72 μ , indicating the presence of two Cu ions
B
2
882
dx.doi.org/10.1021/ic302099y | Inorg. Chem. 2013, 52, 2880−2890

Inorganic Chemistry
Article
Table 2. Selected Bond Lengths [Å] and Angles [deg] in 1 and 2
Bond Lengths
Bond Angles
1
2
1
2
Zn1−O14
Zn1−O19
Zn1−O17
Zn1−O15
Zn1−N4
Zn2−O20
Zn2−O5
Zn2−O8
Zn2−O6
Zn2−N2
Cu1−O19
Cu1−O5
Cu1−O3
Cu1−N1
Cu1−O1
Cu2−O14
Cu2−O20
Cu2−O11
Cu2−N3
Cu2−O12
1.977(2)
1.981(2)
2.007(2)
2.044(2)
2.211(3)
1.911(2)
2.022(2)
2.062(2)
2.076(2)
2.096(3)
1.920(2)
1.978(2)
1.987(2)
2.038(3)
2.224(3)
1.938(2)
1.905(2)
1.981(3)
2.012(3)
2.261(3)
Cu1−O5
Cu1−O1
Cu1−N4
Cu1−O8
Cu1−O18
Cu2−O4
Cu2−O1
Cu2−O2
Cu2−N3
Cu2−O25
Cu3−O4
Cu3−O10
Cu3−N1
Cu3−O15
Cu3−O12
Cu4−O5
Cu4−O10
Cu4−N2
Cu4−O11
Cu4−O7
1.889(4)
1.987(4)
1.992(5)
2.069(4)
2.178(4)
1.926(4)
1.960(4)
1.996(4)
2.016(6)
2.237(4)
1.911(4)
1.982(4)
2.020(5)
2.069(4)
2.084(5)
1.885(4)
1.956(4)
1.991(5)
2.002(4)
2.259(4)
O15−Zn1−N4
O20−Zn2−O5
O20−Zn2−O8
O5−Zn2−O8
O20−Zn2−O6
O5−Zn2−O6
O8−Zn2−O6
O20−Zn2−N2
O5−Zn2−N2
O8−Zn2−N2
O6−Zn2−N2
O19−Cu1−O5
O19−Cu1−O3
O5−Cu1−O3
O19−Cu1−N1
O5−Cu1−N1
O3−Cu1−N1
O19−Cu1−O1
O5−Cu1−O1
O3−Cu1−O1
N1−Cu1−O1
O20−Cu2−O14
O20−Cu2−O11
O14−Cu2−O11
O20−Cu2−N3
O14−Cu2−N3
O11−Cu2−N3
O20−Cu2−O12
O14−Cu2−O12
O11−Cu2−O12
N3−Cu2−O12
80.23(10)
O8−Cu1−O18
O4−Cu2−O1
O4−Cu2−O2
O1−Cu2−O2
O4−Cu2−N3
O1−Cu2−N3
O2−Cu2−N3
O4−Cu2−O25
O1−Cu2−O25
O2−Cu2−O25
N3−Cu2−O25
O4−Cu3−O10
O4−Cu3−N1
O10−Cu3−N1
O4−Cu3−O15
O10−Cu3−O15
N1−Cu3−O15
O4−Cu3−O12
O10−Cu3−O12
N1−Cu3−O12
O15−Cu3−O12
O5−Cu4−O10
O5−Cu4−N2
O10−Cu4−N2
O5−Cu4−O11
O10−Cu4−O11
N2−Cu4−O11
O5−Cu4−O7
O10−Cu4−O7
N2−Cu4−O7
O11−Cu4−O7
104.93(16)
96.52(18)
93.39(18)
161.51(18)
175.11(18)
85.66(19)
83.4(2)
93.73(10)
100.26(10)
103.35(10)
94.06(10)
139.95(11)
113.73(10)
168.77(11)
83.83(10)
90.97(11)
81.05(10)
96.85(10)
91.10(10)
157.06(11)
173.51(10)
86.55(10)
83.73(11)
95.63(9)
91.05(17)
99.69(16)
95.68(16)
92.89(18)
96.74(17)
177.06(19)
85.30(19)
88.02(17)
117.00(17)
92.95(19)
95.63(18)
122.9(2)
97.23(10)
103.38(10)
89.40(10)
98.52(10)
89.67(11)
163.34(12)
172.73(11)
86.19(11)
84.40(12)
90.04(10)
105.53(11)
88.84(11)
94.05(11)
81.5(2)
Bond Angles
118.9(2)
95.19(18)
172.66(19)
86.5(2)
1
2
O14−Zn1−O19
O14−Zn1−O17
O19−Zn1−O17
O14−Zn1−O15
O19−Zn1−O15
O17−Zn1−O15
O14−Zn1−N4
O19−Zn1−N4
O17−Zn1−N4
98.67(9)
114.12(11)
93.55(10)
123.92(11)
93.90(10)
119.34(11)
82.03(10)
173.23(10)
92.29(10)
O5−Cu1−O1
O5−Cu1−N4
O1−Cu1−N4
O5−Cu1−O8
O1−Cu1−O8
N4−Cu1−O8
O5−Cu1−O18
O1−Cu1−O18
N4−Cu1−O18
92.81(17)
174.54(18)
86.75(19)
93.79(16)
137.42(18)
82.91(18)
93.60(17)
116.56(17)
91.46(19)
93.07(18)
165.80(17)
83.9(2)
91.96(17)
98.07(17)
94.90(19)
93.16(17)
oxygen atom of the other ccdp5 ligand. The observed bond
lengths for Cu1−O1 and Cu2−O12 are 2.224(3) and 2.261(3) Å,
respectively. The square base of the pyramid around the Cu1
center is defined by the O3, O19, O5, and N1 atoms, whereas that
around the Cu2 center is defined by the O11, O20, O14, and N3
atoms. The axial positions of a trigonal bipyramid around Zn1 are
−
having one unpaired electron in each. The room temperature
magnetic moment per copper for complex 2 is 1.68 μ , showing
B
II
the presence of one unpaired electron in each Cu ion.
Description of the X-ray Crystal Structure of Complex 1.
The crystal structure of complex 1 consists of a tetraanionic
4
−
+
species [Cu Zn (ccdp) (μ-OH) ] , four Na ions along with a
2
2
2
2
5−
methanol, and six water molecules of crystallization. A structural view
occupied by the tertiary amine nitrogen atom of the ccdp ligand
of the anion of complex 1 is shown in Figure 3. The tetraanionic
and a bridging hydroxo (μ -OH) group with bond distances of
2
II
II
5−
species contains two Cu ions, two Zn ions, two ccdp ligands,
Zn1−N4 = 2.211(3) Å and Zn1−O19 = 1.981(2) Å. Similarly, the
−
and two OH ions. The heterotetranuclear complex anion is formed
axial positions around Zn2 are occupied by a tertiary amine
−
5−
through the self-assembly of two [CuZn(ccdp)] units exclusively
nitrogen atom of the other ccdp ligand and the second bridging
−
−
bridged by two μ-OH groups. Each of the [CuZn(ccdp)] units,
hydroxo (μ -OH) with bond distances of Zn2−N2 = 2.096(3) Å
2
5−
II
contains a dinucleating ccdp ligand coordinated to the Cu and
Zn centers. Both heterodinuclear units of the complex take similar
and Zn2−O20 = 1.911(2) Å. The triangular plane around the Zn1
center is defined by the O14, O15, and O17 atoms, whereas that
around the Zn2 center is defined by the O5, O6, and O8 atoms.
II
structural arrangements with respect to the coordination mode of the
ccdp5 ligand. Two aliphatic carboxylate arms and two aromatic
−
The distortion from the regular geometry around the Cu centers
II
5−
II
carboxylate arms of the ccdp ligand in the complex are oriented in
a trans fashion (Figure 4).
is more pronounced than the distortions observed around the Zn
centers. This observation is consistent with the tendency that the
II
The respective metal centers in each of the heterodinuclear
units pose different coordination geometries, bond lengths, and
bond angles. For example, the coordination geometry around
the Cu1 and Cu2 centers exhibit distorted square-pyramidal
geometry, while the Zn1 and Zn2 centers exhibit distorted
trigonal-bipyramidal geometry (Figure 5). Whereas the axial
position of the square-pyramidal geometry around the Cu1
center is occupied by a benzoate oxygen atom of one ccdp5−
ligand, the axial position around Cu2 is taken by a benzoate
Zn ion favors the trigonal-bipyramidal coordination geometry
II
40
compared to the Cu ion.
The average Cu---Zn separation in a dinuclear unit is 3.628
13a,19a,41
Å.
The average Cu---Zn separation where the copper
and zinc centers are interligated to each other is 3.380 Å. The
longer metal carboxylate arms with the shorter metal alkoxo
arms provide the framework to support an average wide-
bridging angle, Cu−O−Zn of 132.96°. The two different
geometries observed within each heterodinuclear unit are due
2
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Figure 2. Synthetic procedure of complexes 1 and 2.
to the different coordination modes adopted between the
[Cu ] pairs. The metal ions within each [Cu ] pair are bridged
and chelated by one ccdp ligand. One hydroxyl group and
2
2
5−
5−
extremely flexible ccdp ligand and the metal ions in response to
steric constraints within the complex. This strain has yielded a
concave-shaped octagonal metal core defined by Zn1−O14−
Cu2−O20−Zn2−O5−Cu1−O19, illustrated as part of Figure 5.
Interestingly, the solid-state X-ray crystal structure of
complex 1 features a large number of ligand carboxylates and
one water molecule act as bridges between the two
−
monoanionic dinuclear [Cu (ccdp)] units through the Cu1−
2
HO5−Cu4 and Cu2−H O4−Cu3 links, respectively. The
2
Cu1−O5−Cu4 and Cu2−H O4−Cu3 bond angles of 122.33°
2
and 127.60°, respectively, are open enough to afford further
I
coordination by two oxygen atoms coming from one bridging OH−
Na ions susceptible to being involved in a three-dimensional
I
(
3D) coordination network (Figure 6). In this network, the Na
group and one bridging H O molecule in a syn−syn bidentate
2
II
ions with their well-defined coordination environments join the
fashion to the pair of Cu ions in each dinuclear unit. Within each
two heterotetranuclear Cu Zn units to form a heterooctanu-
dinuclear unit, the two aliphatic and two aromatic carboxylate arms
of the ccdp5 ligand are oriented in a trans fashion (Figure 8).
The two copper centers in each dinuclear unit exhibit different
coordination geometries, bond lengths, and bond angles. As shown
in Figure 9, the Cu1 and Cu3 centers adopt distorted trigonal-
bipyramidal geometry, whereas the Cu2 and Cu4 centers exhibit
distorted square-pyramidal geometry. One bridging alkoxo oxygen,
one monodentate aliphatic carboxylate oxygen, one monodentate
aromatic carboxylate oxygen, one tertiary amine nitrogen of the
ccdp ligand, and one bridging μ-OH− group make up the
coordination environment around the Cu1 and Cu4 centers.
2
2
−
clear Cu Zn cluster (Figure S1 in the Supporting Information,
4
4
SI). In this supramolecular arrangement, the repeating cluster
II
II
I
consists of four Cu , four Zn , and eight Na metal ions.
Description of the X-ray Crystal Structure of Complex 2.
II
A structural view of the tetranuclear Cu cluster anion of 2 is
depicted in Figure 7. The crystal structure of the tetranuclear
complex 2 consists of a trianionic species [Cu (ccdp) (μ-OH)-
4
2
3‑
+
(
μ-OH )] and three K ions as countercations along with 14
water molecules of crystallization. This tetranuclear Cu cluster
anion is formed through the self-assembly of two dinuclear
2
II
5−
2
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Figure 3. Molecular structure of complex 1 with an atom numbering scheme. Hydrogen atoms are omitted for clarity.
Figure 4. Molecular structure of the dinuclear unit of complex 1 with
an atom numbering scheme showing the trans fashion of two aliphatic
carboxylate arms and two aromatic carboxylate arms of the ligand.
Figure 7. Molecular structure of complex 2 with an atom numbering
scheme. Hydrogen atoms are omitted for clarity.
Similarly, one bridging alkoxo oxygen, one monodentate aliphatic
carboxylate oxygen, one monodentate aromatic carboxylate oxygen,
one tertiary amine nitrogen of the ccdp5 ligand, and one bridging
−
μ-OH molecule complete the coordination environment around
2
the Cu2 and Cu3 centers. The two different coordination
geometries observed within each dinuclear unit are due to the
Figure 5. Core structure of complex 1 with an atom numbering
scheme.
Figure 6. Stick representation of a 3D coordination network of 1.
2
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Figure 8. Molecular structure of the dinuclear unit of complex 2 with an atom numbering scheme showing the trans fashion of two aliphatic and two
aromatic carboxylate arms of the ligand.
Figure 9. Core structure of complex 2 with an atom numbering scheme.
Figure 10. High-field (406.4 GHz) EPR spectrum of complex 1 at ca. 6 K.
different coordination modes adopted between the extremely
flexible ccdp5 ligand and the Cu ions in response to steric
−
II
constraints within the complex. The coordination environment of
the countercations K may be best described by the distorted
the spectrum suggests the presence of magnetically isolated
Cu centers in complex 1. The spectrum shows the splitting
+
II
octahedral geometry, with either carboxylate and water/hydroxyl
between the lines in both the low- and high-field pairs scales
with the microwave frequency, which suggests that there are no
zero-field-splitting effects. This might be due to the broadening
of the ligand hyperfine splitting. The spectrum shows the
superposition of two spectra from two essentially isolated
oxygen atoms or only water oxygen atoms. The Cu−O
bond
alkoxo
distances are within the range of previously reported alkoxo-bridged
4
2,43
dinuclear copper systems.
The Cu−O
and Cu−N
carboxylate
amine
bond distances are in the range of those previously reported in the
42−46
II
literature.
The Cu−O
bond distances (Cu1−O5 = 1.889 Å
magnetically inequivalent sites for Cu ions. One copper center
hydroxyl
and Cu4−O5 = 1.886 Å) are quite shorter than the Cu−O
has g = g = 2.061, and g = 2.294, and the other copper center
water
x
y
z
bond distances (Cu2−O4 = 1.927 Å and Cu3−O4 = 1.910 Å).
The Cu−O bond distances are comparable with the values
has g = 2.085, g = 2.092, and g = 2.274. These parameters are
x y z
very weakly dependent on the temperature. Thus, no coupling
water
47,48
II
reported in the literature.
The average Cu---Cu separation in a
interactions in complex 1, where the two Cu centers occupy
dinuclear unit is 3.679 Å. The average Cu---Cu separation where
the two copper centers are interligated to each other is 3.375 Å.
These bond distances are also in agreement with those reported in
opposite corners of the core and are not directly bridged to
each other, are observed. The spectrum of complex 2 is very
weak at room temperature but becomes stronger at lower
temperature and persists as strong down to 6 K (Figure S2 in
the SI). The spectrum could be interpreted in terms of a
mononuclear copper(II) complex. Additionally, the presence
of the spectral features in the low field is due to hyperfine
49,50
the literature.
The crystal structures of complexes 1 and 2 exhibit a synergy
with respect to the supramolecular assemblies. In complex 1,
−
two heterodinuclear [CuZn(ccdp)] units are exclusively
−
II
bridged by two μ-OH groups to form the heterotetranuclear
splitting of the Cu signal by a coordinated nitrogen atom.
cluster, whereas in complex 2, two homodinuclear
The spectrum has resolved g values of g = g = 2.060 and
gz = 2.264, which are typical for copper(II) complexes, either
x
y
Cu (ccdp)] units are exclusively bridged by one μ-OH−
−
[
2
group and one μ-OH molecule to form the homotetranuclear
mono- or mulitinuclear with at least one noninteracting copper
atom.
2
5
1,52
cluster. The main difference in their supramolecular structures
is that complex 1 shows a 3D coordination network where the
In an attempt to further characterize complexes 1 and 2,
methanolic solutions (pH ∼7.5) were negative-ion electro-
sprayed into a quadrupole ion-trap mass spectrometer and
subjected to collision-induced dissociation to gain structural
information. The MS spectrum of complex 1 (Figure S3 in the SI)
shows a signal at m/z 1265, which corresponds to the {[Cu Zn -
I
two heterotetranuclear Cu Zn units are connected by the Na
2
2
ions to form a heterooctanuclear Cu Zn cluster, while complex
4
4
2
shows no 3D coordination network.
EPR and MS Studies. High-field (406.4 GHz) EPR spectra
for complexes 1 and 2 in the powder state are collected at 6 K.
The spectrum of complex 1 shows an isotropic signal consisting
2
2
−
(ccdp) (μ-OH ) ]·CH OH + H} species, reconfirming the
2
2 2
3
of hyperfine splitting patterns (Figure 10). The absence of
heterodimetallic nature of complex 1 even in solution. The MS
spectrum of complex 2 yields a signal at m/z 1294, which
3
seven hyperfine splitting lines (copper nuclear spin ICu = / ) in
2
2
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Inorganic Chemistry
Article
−
corresponds to the {[Cu (ccdp) (μ-OH ) ]·2CH OH + H}
4
2
2 2
3
species, confirming the homodimetallic nature of complex 2 in
solution. Therefore, the mass spectral analyses suggest that both
the hetero- and homodimetallic tetranuclear complexes are stable
in solution at physiological pH.
Binding Studies. Complexes 1 and 2 are highly water-
soluble and well-stable in solution at physiological pH. So,
considering that copper and zinc ions and their complexes in
biological systems may act as biological probes, we were
interested in investigating their DNA and protein binding
affinity in an aqueous medium. Accordingly, we have performed
UV−vis and fluorescence experiments to evaluate their binding
interactions with DNA and BSA protein.
Binding of Complexes 1 and 2 with DNA. We have
observed from UV−vis experiments that complexes 1 and 2 do
not interact with DNA because there are no changes of the
absorption maxima of the complexes upon the addition of
CT-DNA. The representative UV−vis spectra for complex 1 in
the absence of CT-DNA and in the presence of CT-DNA are
shown in Figure S4 in the SI.
Figure 12. Emission spectra of BSA protein in an aqueous medium
−6
(0.375 × 10 M; λexi = 280 nm; λemi = 339 nm) as a function of the
5
−
concentration of complex 2 [(0−11.285) × 10 M]. Inset: Stern−
Volmer plot of the fluorescence titration data. The arrow indicates the
change in the emission intensity with respect to various concentrations
of complex 2.
fluorophore−quencher complex formation, and the dynamic
quenching refers to a process in which the fluorophore and
quencher come into contact during the transient existence of the
excited state. The fluorescence quenching data have been analyzed
Binding of Complexes 1 and 2 with BSA Protein.
Because BSA constitutes ∼55% of the total protein in blood
plasma and it plays an important role in drug transport and
drug metabolism, the interactions of complexes 1 and 2 with
BSA have been studied from the binding experiments with BSA
as a model protein. The binding of complexes with BSA protein
in an aqueous medium has been investigated from the
concentration dependence of the change in the fluorescence
intensity of protein upon the addition of complexes. A BSA
molecule consists of three aromatic amino acids (phenylalanine,
tyrosine, and tryptophan), and its fluorescence can appear
by the Stern−Volmer relation I /I = 1 + K [Q], where I and I
0
SV
0
are the fluorescence intensities of the fluorophore in the absence
and presence of quencher, respectively, KSV is the Stern−Volmer
quenching constant, and [Q] is the quencher concentration. A plot
of I /I versus [Q] with respect to complexes 1 and 2 results in a
0
linear graph, and the KSV values are calculated from the slope. The
Stern−Volmer plots of the fluorescence titration data for
complexes 1 and 2 are shown in Figures 11 and 12, inset.
Because the lifetime of BSA protein is on the order of 10− s,
9
53
because of tryptophan and tyrosine residues. Figure 11 shows
the calculated bimolecular quenching rate constants (k ) using
q
the effect of complex 1 on the fluorescence intensity of BSA
KSV = k τ were found to be higher than the maximum collisional
q 0
quenching (k ) of various kinds of quenchers to biopolymers
q
10
−1 −1
(
2.0 × 10 M s ). Hence, fluorescence quenching results from
the formation of a Cu Zn -BSA complex/Cu -BSA complex.
2
2
4
At a certain point, when small molecules bind independently
to a set of equivalent sites on a macromolecule, some will be in
bound condition and some will be in unbound condition. So,
the equilibrium between the unbound and bound molecules is
5
5,56
represented by the Scatchard equation
log[(F − F)/F] =
0
log(K) + n log [Q], where K and n are the binding constant
and the number of binding sites, respectively, and F and F are
0
the fluorescence intensities in the absence and presence of the
quencher, respectively. Thus, a plot of log(F − F)/F versus log
0
Figure 11. Emission spectra of BSA protein in an aqueous medium
−6
(
0.375 × 10 M; λexi = 280 nm; λemi = 339 nm) as a function of the
5
−
concentration of complex 1 [(0−11.285) × 10 M]. Inset: Stern−
Volmer plot of the fluorescence titration data. The arrow indicates the
change in the emission intensity with respect to various concentrations
of complex 1.
protein in water. Upon increasing concentration of complex 1, a
gradual decrease in the fluorescence intensity accompanied by a
significant red shift has been observed. Following the same
procedure, the fluorescence titration experiments of BSA protein
with complex 2 have been executed. The fluorescence spectra
indicate that there is a progressive decrease in the fluorescence
intensity along with a significant red shift (Figure 12). This
quenching effect with an observed red shift indicates the
Figure 13. Synchronous fluorescence spectra of BSA (0.375 × 10−6 M)
−5
as a function of the concentration of complex 1 [(0−11.285) × 10 M]
23b,54
interaction of BSA protein with the title complexes.
The
with a wavelength difference of Δλ = 15 nm. The arrow indicates the
change in the emission intensity with respect to various concentrations of
complex 1.
mechanisms of quenching are usually classified by either dynamic
quenching or static quenching. Static quenching refers to
2
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Inorganic Chemistry
Q] (Figures S5 and S6 in the SI) can be used to determine the
Article
[
are tetranuclear clusters, their binding constant values could be
lesser attributed to the steric effects arising out of the number of
acetate and benzoate functionalities of the ligand. However,
surprisingly, the complexes show comparably high BSA binding
propensity in an aqueous medium at pH ∼7.2, possibly because of
the additional hydrogen-bonding ability of the acetate and
benzoate groups with the peptide backbone.
In synchronous fluorescence spectroscopy, according to
Miller, the difference between excitation and emission wave-
lengths (Δλ = λ − λ ) reflects the spectra of a different nature
value of the binding constants, and such values were calculated
4
5
−1
to be 4.669 × 10 and 3.562 × 10 M for complexes 1 and 2,
respectively. From the value of the binding constants, it can be
suggested that complex 2 interacts more strongly with BSA
protein compared to that of complex 1 under the physiological
condition. The difference in the binding strength between
II
complexes 1 and 2 is most likely due to variation of the Cu
60
II
and Zn ions in the respective complexes. The binding strengths
emi
exc
of complexes 1 and 2 are comparable to those of the reported
of chromophores. With large Δλ values such as 60 nm, the
synchronous fluorescence of BSA is characteristic of the tryptophan
residue, and with a small Δλ value, such as 15 nm, it is characteristic
mononuclear copper(II), nickel(II), cobalt(II), and gadolineum-
57−59
(III) complexes in the literature.
Because complexes 1 and 2
61
of tyrosine. To understand the structural changes of BSA protein
due to the addition of complexes 1 and 2, we have measured
synchronous fluorescence spectra of the former with respect to the
addition of test complexes. At Δλ = 15 nm, the intensity of
emission at 303 nm corresponding to tyrosine was found to
decrease significantly upon increasing concentrations of complexes
1
and 2 with a red shift of the emission wavelength (Figures 13 and
S7 in the SI). However, at Δλ = 60 nm, the tryptophan
fluorescence showed a significant decrease in the intensity of
emission (at 360 nm) without any change in the position of the
emission band (Figures 14 and S8 in the SI). The results indicate
that the microenvironments of both tyrosine and tryptophan
residues in BSA have been affected by the complexes during the
binding process, highlighing that the effect is more pronounced
toward tyrosine than tryptophan. Hence, the results clearly indicate
that complexes 1 and 2 bind to active sites in the protein, which
make them potential molecules for biological applications. These
Figure 14. Synchronous fluorescence spectra of BSA (0.375 × 10−6 M)
−5
as a function of the concentration of complex 1 [(0−11.285) × 10 M]
with a wavelength difference of Δλ = 60 nm. The arrow indicates the
change in the emission intensity with respect to various concentrations of
complex 1.
62
results are comparable with earlier literature reports.
Table 3. Fukui Functions of the Monomeric Analogues
Density Functional Theory (DFT) Calculations. In order
to gain a better understanding of where the complexes bind to
BSA protein, we have carried out DFT calculations. Calculations
(1m and 2m) of Complexes 1 and 2
1
m
2m
II
II
Cu
Zn
Cu
Cu
have been performed on the monomeric halves [Cu Zn (ccdp)-
(OH)2]3 (1m) and [Cu (ccdp)(OH)(OH )] (2m) of
−
II
2−
fk+
0.1539
0.0034
0.1276
0.0503
2 2
Figure 15. Representative HOMOs and LUMOs of monomeric analogues of complexes 1 and 2 calculated at the B3LYP/[6-311G] level of theory.
2
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Inorganic Chemistry
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representative complexes 1 and 2 and on the corresponding one-
electron-reduced analogues 1m and 2m at the B3LYP level
ASSOCIATED CONTENT
Supporting Information
■
−
−
*
S
using the Gaussian 03 software package. The structures of 1m and
X-ray crystallographic data in CIF format for complexes 1 and 2,
experimental details of the ligand and its synthetic scheme, MS
spectra of the complexes, EPR, electronic spectra, Scatchard plots,
synchronous fluorescence spectra, and HOMO and LUMO. This
material is available free of charge via the Internet at http://pubs.
acs.org.
1
2
m proved to be the doublet ground state (S = / ) and the
2
closed-shell singlet state, respectively, with optimized structural
parameters fully consistent with crystallographic data. The one-
−
−
electron-reduced species 1m and 2m display a closed-shell
1
singlet state and a doublet (S = / ) ground state, respectively. The
calculated condensed Fukui function values fk at the metal sites of
2
+
the monomeric halves are given in Table 3. According to the values
AUTHOR INFORMATION
Corresponding Author
*E-mail: mbera2009@klyuniv.ac.in (M.B.), ghezai.musie@utsa.
edu (G.T.M.). Fax: +91 33 25828282. Tel: +91 33 25828282
x306.
■
presented in Table 3, it can be anticipated that BSA protein binds
+
k
as a nucleophile to the copper centers (f = 0.1539) more
favorably than zinc centers (fk+ = 0.0034) in complex 1. In
complex 2, the Fukui function values of all of the copper centers
are fairly close in magnitude, and thereby it is presumed that the
BSA protein may interact with all of the copper centers with more
or less equal probability. The small difference in the Fukui function
values at the two copper sites is most likely due to the different
coordination geometries around the two copper centers in the
monomeric half of complex 2. In 1m, while the highest occupied
molecular orbital (HOMO) is located near the zinc center, the
lowest unoccupied molecular orbital (LUMO) is spread on and
around the copper center (Figure 15a,b). Therefore, the BSA
protein being a nucleophile will prefer to interact with the copper
center more preferably. This is in accordance with the findings
observed in Fukui function calculations. In the one-electron-
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors thank the Department of Science and Technology
DST; Grant SR/FT/CS-067/2009), New Delhi, for funding
and financial support. The authors acknowledge Prof. Andrew
Ozarowski, National High Magnetic Field Laboratory, Florida
State University, for measurement of the high-frequency EPR
spectra. The instrumental facilities provided by the DST-FIST,
DST-PURSE and UGC-SAP program in the Department of
Chemistry are greatly acknowledged. A.P. also thanks the
University of Kalyani for providing a university research
fellowship.
■
(
−
reduced analogue 1m , the HOMOs and LUMOs are spread
mostly on and around the copper center rather than the zinc
center (Figure S9a,b in the SI). The HOMOs and LUMOs in 2m
are spread on and around both copper centers, indicating the
involvement of all of the copper centers in the binding process
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CONCLUSIONS
■
(
(
2
In conclusion, we have described the preparation and character-
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