Polymeric complexes - LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds

Journal of Molecular Liquids 215 (2016) 711–739

Contents lists available at ScienceDirect

Journal of Molecular Liquids

journal homepage: w ww.elsevier.com/locate/molliq

Polymeric complexes — LXI. Supramolecular structure, thermal

properties, SS-DNA binding activity and antimicrobial activities of

polymeric complexes of rhodanine hydrazone compounds

b

c

a

A.Z. El-Sonbati ^a, M.A. Diab ^a, A.A. El-Bindary ^a,, M.M. Ghoneim , M.T. Mohesien , M.K. Abd El-Kader

⁎

a

Chemistry Department, Faculty of Science, Damietta University, Damietta 34517, Egypt

b

Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt

c

Botany Department, Faculty of Science, Damietta University, Damietta 34517, Egypt

a r t i c l e i n f o

a b s t r a c t

Article history:

A series of new ligands 5-(4′-alkylphenylazo)-3-phenylamino-2-thioxothiazolidin-4-one (HL_n) were synthe-

sized from the coupling of 3-phenylamino-2-thioxothiazolidin-4-one with aniline and its p-derivatives. These

ligands and their Co(II) polymeric complexes of the [(Co)₂(L_n)₂(HL_n)(CH₃COO)₂(H₂O)₂]_nhave been deduced

from elemental analyses, IR, ¹H-NMR, X-ray diffraction and mass spectra as well as magnetic and thermal

measurements. IR and ¹H NMR studies reveal that the ligands (HL_n) exist in the tautomeric enol/hydrazo form

in both states with intramolecular hydrogen bonding. The important infrared (IR) spectral bands imply that

HL_nis coordinated to the metal ion in a monobasic tetradentate via NH (hydrazone), oxygen of the carbonyl

group (CO), nitrogen of the NH (3-phenylamine) and thion sulfur (CS) group. The complexes are polymeric,

non-electrolytes, paramagnetic and octahedral six-coordinated. The molecular and electronic structures of the

investigated compounds (HL_n) were also studied using quantum chemical calculations. The salmon sperm

DNA (SS-DNA) binding activity of the ligands (HL_n) was studied by absorption spectra. The interaction between

ligands (HL_n) and SS-DNA shows hypochromism effect coupled with obvious bathochromism. The values of

binding constant are correlated with Hammett's constant (σ^R). The cytotoxic activity of ligands (HL_n) and their

Co(II) complexes were tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast

cancer). The antioxidant activities of ligands (HL_n) and their Co(II) complexes were performed by ABTS method.

The antimicrobial activity of ligands HL_nand their Co(II) complexes were tested against Gram negative bacteria

(Escherichia coli), Gram positive bacteria (Staphylococcus aureus) and yeast (Candida albicans).

Received 21 October 2015

Received in revised form 8 November 2015

Accepted 2 December 2015

Available online xxxx

Keywords:

Co(II) complexes

SS-DNA binding

Molecular structure

Antimicrobial activities

1. Introduction

keto–enol tautomers. Hydrazone compounds of rhodanine usually

react as chelating with transition metal ions by bonding through the

In recent past, a variety of molecules based on rhodanine have been

synthesized and evaluated with improved pharmacological activities

due to their wide range of pharmacological and clinical utilization

[1–8]. Rhodanine compounds and their complexes play an important

role in biological reactions [9,10]. These molecules are considered

as good antimycobacterial, antifungal, antidiabetic, antihepatitis C

virus (HCV), anticancer, antioxidant, pesticidal, antihypertensive and

antineoplastic agents. These molecules attracted much attention and

encouraged the chemists and biologists to extensive investigations or

molecular manipulations [5,11]. Chemical properties of rhodanine and

its derivatives are of interest due to coordination capacity and their

use as metal extracting agents; these molecules are capable of having

oxygen and hydrazinic nitrogen atoms [1,8], as they form a stable six-

membered characterization of 5-(4′-alkylphenylazo)-3-phenylamino-

2-thioxothiazolidin-4-one (HL_n) and their polymer complexes with

cobalt(II). HL_nact as monobasic tetradentate reacting with Co(II)

through the CO (rhodanine moiety), hydrazinic N with displacement

of hydrogen atom, CS (rhodanine moiety) and amidic N.

DNA is one of the most important biomacromolecules in life

processes because it carries inheritance information and instructs

the biological synthesis of proteins and enzyme through the process

of replication and transcription of genetic information. DNA plays an

important role in the process of storing, copying and transmitting

gene messages. DNA is also a major target for drugs and some harm-

ful chemicals, and the studies on the binding nature of these small

molecules to DNA are important and fundamental issues on life sci-

ence because these drugs and chemicals can signiﬁcantly inﬂuence

the genetic information expression and result in some diseases

⁎

Corresponding author.

E-mail address: abindary@yahoo.com (A.A. El-Bindary).

http://dx.doi.org/10.1016/j.molliq.2015.12.010

712

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Fig. 1. Structure of ligands (HL_n).

Table 1

Physical properties and elemental analyses data of the ligands (HL_n) and their Co(II) complexes (1–5).

% Exp. (calc.)

Compound

M.P. (°C)

Composition

C

H

N

M

HL₁

131

–

53.60

(53.63)

46.22

(46.43)

56.00

(56.14)

48.03

(48.15)

54.90

(54.88)

46.77

(46.89)

49.70

(49.66)

43.14

4.00

(3.91)

3.56

(3.72)

4.10

(4.09)

3.66

(3.86)

3.70

(3.66)

3.35

(3.51)

3.10

(3.03)

2.89

15.60

(15.64)

12.12

(12.50)

16.40

(16.37)

12.74

(12.96)

17.10

(17.07)

12.04

(13.40)

15.50

(15.45)

12.03

–

8.37

(8.77)

–

(1)

HL₂

(2)

HL₃

(3)

HL₄

[(Co)₂(HL₁)(L₁)₂(CH₃COO)₂(H₂O)₂]_n

[(Co)₂(HL₂)(L₂)₂(CH₃COO)₂(H₂O)₂]_n

[(Co)₂(HL₃)(L₃)₂(CH₃COO)₂(H₂O)₂]_n

[(Co)₂(HL₄)(L₄)₂(CH₃COO)₂(H₂O)₂]_n

[(Co)₂(HL₅)(L₅)₂(CH₃COO)₂(H₂O)₂]_n

161

–

8.78

(9.10)

–

164

–

(9.40)

–

164

–

8.47

(8.68)

–

(4)

(43.32)

48.30

(48.26)

42.12

(3.02)

3.00

(2.95)

2.87

(12.38)

18.80

(18.77)

14.86

HL₅

178

–

8.15

(8.49)

(5)

(42.34)

(2.95)

(15.12)

^aMicroanalytical data as well as metal estimations are in good agreement with the stoichiometry of the proposed complexes.

^bThe excellent agreement between calculated and experimental data supports the assignment suggested in the present work.

^cHL₁–HL₅are the ligands and L₁–L₅are the anions.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

713

the complexes of these ligands with cobalt acetate [7]. The Co(II)

complexes attracted attention in coordination chemistry, thermal

stability and biological function of some bimetallic complexes for

which structural information was obtained by spectrochemical and

magnetochemical means; due to the Co(II) in d⁷is known, in four co-

ordinate as tetrahedral and six coordinate as octahedral stereochem-

istries [14–18].

The aim of this work is to, synthesis and characterize of Co(II) com-

plexes of 5-(4′-alkylphenylazo)-3-phenylamino-2-thioxothiazolidin-4-

one (HL_n) by elemental analyses, IR, ¹H & ¹³C NMR, UV–Vis, X-ray

diffractometer, magnetic moment, molar conductance, and thermal

analysis. Molecular and electronic structures of the ligands (HL_n) have

been discussed. Mass spectra and X-ray diffraction analysis of ligands

(HL₁, HL₃and HL₄) were discussed. The activation thermodynamic

Fig. 2. Proposed structure of Co(II) complexes.

⁎

parameters, such as activation energy (E_a), enthalpy (ΔH ), entropy

related to the cell proliferation and differentiation [12,13]. In our

laboratories, we have initiated a series of studies of the effects of sub-

stituents at p-position of the aromatic amine on the stoichiometries of

⁎

(ΔS ), and Gibbs free energy change of the decomposition (ΔG ) were

calculated using Coats–Redfern and Horowitz–Metzger methods. The

Fig. 3. The molecular structures for HL_n.

714

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Table 2

The selected geometric parameters for HL₁.

Bond lengths (Å)

Bond angles (°)

C(25)–H(38)

C(25)–H(37)

C(25)–H(36)

C(21)–H(35)

C(20)–H(34)

C(18)–H(33)

C(17)–H(32)

C(11)–H(31)

C(10)–H(30)

C(9)–H(29)

C(8)–H(28)

C(7)–H(27)

N(6)–H(26)

C(17)–C(22)

C(21)–C(22)

C(20)–C(21)

C(19)–C(20)

C(18)–C(19)

C(17)–C(18)

C(7)–C(12)

C(11)–C(12)

C(10)–C(11)

C(9)–C(10)

C(8)–C(9)

1.113

1.104

1.102

1.104

1.103

1.104

1.103

1.051

1.345

1.343

1.348

1.347

1.342

1.346

1.345

1.342

1.003

1.037

1.273

1.249

1.272

1.351

1.375

1.281

1.575

1.221

1.377

1.479

1.794

1.374

1.409

H(38)–C(25)–H(37)

H(38)–C(25)–H(36)

H(38)–C(25)–O(24)

H(37)–C(25)–H(36)

H(37)–C(25)–O(24)

H(36)–C(25)–O(24)

C(19)–O(24)–C(25)

H(34)–C(20)–C(21)

H(34)–C(20)–C(19)

C(21)–C(20)–C(19)

C(20)–C(19)–C(18)

C(20)–C(19)–O(24)

C(18)–C(19)–O(24)

H(33)–C(18)–C(19)

H(33)–C(18)–C(17)

C(19)–C(18)–C(17)

H(35)–C(21)–C(22)

H(35)–C(21)–C(20)

C(22)–C(21)–C(20)

H(32)–C(17)–C(22)

H(32)–C(17)–C(18)

C(22)–C(17)–C(18)

C(17)–C(22)–C(21)

C(17)–C(22)–N(16)

C(21)–C(22)–N(16)

H(23)–N(16)–C(22)

H(23)–N(16)–N(15)

C(22)–N(16)–N(15)

C(5)–S(4)–C(3)

N(16)–N(15)–C(5)

H(30)–C(10)–C(11)

H(30)–C(10)–C(9)

C(11)–C(10)–C(9)

H(29)–C(9)–C(10)

H(29)–C(9)–C(8)

C(10)–C(9)–C(8)

H(28)–C(8)–C(9)

H(28)–C(8)–C(7)

C(9)–C(8)–C(7)

H(31)–C(11)–C(12)

H(31)–C(11)–C(10)

C(12)–C(11)–C(10)

H(27)–C(7)–C(12)

H(27)–C(7)–C(8)

C(12)–C(7)–C(8)

C(7)–C(12)–C(11)

C(7)–C(12)–N(6)

111.887

108.169

110.347

108.167

110.354

107.776

118.767

116.943

120.926

122.131

115.683

125.543

118.775

118.575

118.627

122.798

120.437

118.181

121.382

121.128

118.067

120.805

117.202

122.386

120.412

122.189

108.605

129.206

96.437

116.122

120.035

119.886

120.079

120.144

120.146

119.709

119.865

120.019

120.116

120.723

118.691

120.586

121.023

118.446

120.531

118.978

122.597

C(11)–C(12)–N(6)

H(26)–N(6)–C(12)

H(26)–N(6)–N(2)

C(12)–N(6)–)–N(2)

S(14)–C(3)–S(4)

S(14)–C(3)–N(2)

S(4)–C(3)–N(2)

O(13)–H(23)–N(16)

N(6)–N(2)–C(3)

N(6)–N(2)–C(1)

C(3)–N(2)–C(1)

H(23)–O(13)–C(1)

N(15)–C(5)–C(1)

N(15)–C(5)–S(4)

C(1)–C(5)–S(4)

O(13)–C(1)–C(5)

O(13)–C(1)–N(2)

C(5)–C(1)–N(2)

Dihedral angle (°)

C(18)–C(17)–C(22)–N(16)

C(20)–C(21)–C(22)–N(16)

C(8)–C(7)–C(12)–N(6)

C(10)–C(11)–C(12)–N(6)

C(7)–C(12)–N(6)–N(2)

N(15)–C(5)–C(1)–N(2)

118.424

114.354

116.442

122.051

125.084

129.758

105.156

154.903

125.249

123.904

110.84

108.968

116.374

131.246

112.38

115.027

129.783

115.187

179.997

-179.99

179.986

-179.988

-32.896

-179.655

C(7)–C(8)

H(23)–O(13)

N(16)–H(23)

C(22)–N(16)

N(15)–N(16)

C(12)–N(6)

N(2)–N(6)

C(19)–O(24)

C(5)–N(15)

C(3)–S(14)

C(1)–O(13)

C(5)–C(1)

S(4)–C(5)

C(3)–S(4)

N(2)–C(3)

C(1)–N(2)

O(24)–C(25)

Table 3

The selected geometric parameters for HL₂.

Bond lengths (Å)

Bond angles (°)

C(23)–H(37)

C(23)–H(36)

C(23)–H(35)

C(21)–H(34)

C(20)–H(33)

C(18)–H(32)

C(17)–H(31)

C(11)–H(30)

C(10)–H(29)

C(9)–H(28)

C(8)–H(27)

C(7)–H(26)

N(6)–H(25)

C(17)–C(22)

C(21)–C(22)

C(20)–C(21)

C(19)–C(20)

C(18)–C(19)

C(17)–C(18)

C(7)–C(12)

1.114

1.113

1.104

1.103

1.104

1.103

1.051

1.346

1.342

1.344

1.343

1.346

1.345

H(37)–C(23)–H(36)

H(37)–C(23)–H(35)

H(37)–C(23)–C(19)

H(36)–C(23)–H(35)

H(36)–C(23)–C(19)

H(35)–C(23)–C(19)

H(33)–C(20)–C(21)

H(33)–C(20)–C(19)

C(21)–C(20)–C(19)

C(20)–C(19)–C(18)

C(20)–C(19)–C(23)

C(18)–C(19)–C(23)

H(32)–C(18)–C(19)

H(32)–C(18)–C(17)

C(19)–C(18)–C(17)

H(34)–C(21)–C(22)

H(34)–C(21)–C(20)

C(22)–C(21)–C(20)

H(31)–C(17)–C(22)

H(31)–C(17)–C(18)

C(22)–C(17)–C(18)

108.481

107.466

110.299

107.519

110.261

112.668

119.462

119.492

121.045

118.008

120.302

121.69

119.877

119.118

121.006

120.811

118.114

121.075

121.077

117.833

121.09

H(25)–N(6)–C(12)

H(25)–N(6)–N(2)

C(12)–N(6)–N(2)

S(14)–C(3)–S(4)

S(14)–C(3)–N(2)

S(4)–C(3)–N(2)

O(13)–H(24)–N(16)

N(6)–N(2)–C(3)

N(6)–N(2)–C(1)

114.364

116.46

122.051

125.08

129.763

105.156

154.915

125.252

123.907

110.834

108.969

116.371

131.248

112.381

115.024

129.783

115.191

C(3)–N(2)–C(1)

H(24)–O(13)–C(1)

N(15)–C(5)–C(1)

N(15)–C(5)–S(4)

C(1)–C(5)–S(4)

O(13)–C(1)–C(5)

O(13)–C(1)–N(2)

C(5)–C(1)–N(2)

Dihedral angle (°)

C(18)–C(17)–C(22)–N(16)

C(20)–C(21)–C(22)–N(16)

C(8)–C(7)–C(12)–N(6)

−179.998

179.979

C(11)–C(12)

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

715

Table 3 (continued)

Bond lengths (Å)

Bond angles (°)

C(10)–C(11)

C(9)–C(10)

C(8)–C(9)

1.342

1.004

1.037

1.274

1.249

1.272

1.351

1.51

1.281

1.575

1.221

1.377

1.479

1.794

1.374

C(17)–C(22)–C(21)

C(17)–C(22)–N(16)

C(21)–C(22)–N(16)

H(24)–N(16)–C(22)

H(24)–N(16)–N(15)

C(22)–N(16)–N(15)

C(5)–S(4)–C(3)

N(16)–N(15)–C(5)

H(29)–C(10)–C(11)

H(29)–C(10)–C(9)

C(11)–C(10)–C(9)

H(28)–C(9)–C(10)

H(28)–C(9)–C(8)

C(10)–C(9)–C(8)

H(27)–C(8)–C(9)

H(27)–C(8)–C(7)

C(9)–C(8)–C(7)

H(30)–C(11)–C(12)

H(30)–C(11)–C(10)

C(12)–C(11)–C(10)

H(26)–C(7)–C(12)

H(26)–C(7)–C(8)

C(12)–C(7)–C(8)

C(7)–C(12)–C(11)

C(7)–C(12)–N(6)

C(11)–C(12)–N(6)

117.775

122.127

120.097

122.19

108.581

129.228

96.438

116.139

120.036

119.883

120.081

120.147

120.145

119.708

119.867

120.016

120.117

120.723

118.695

120.581

121.026

118.444

120.53

C(10)–C(11)–C(12)–N(6)

C(7)–C(12)–N(6)–N(2)

N(15)–C(5)–C(1)–N(2)

−179.979

−32.812

−179.688

C(7)–C(8)

H(24)–O(13)

N(16)–H(24)

C(22)–N(16)

N(15)–N(16)

C(12)–N(6)

N(2)–N(6)

C(19)–C(23)

C(5)–N(15)

C(3)–S(14)

C(1)–O(13)

C(5)–C(1)

S(4)–C(5)

C(3)–S(4)

N(2)–C(3)

C(1)–N(2)

118.981

122.586

118.431

Table 4

The selected geometric parameters for HL₃.

Bond lengths (Å)

Bond angles (°)

C(21)–H(34)

C(20)–H(33)

C(19)–H(32)

C(18)–H(31)

C(17)–H(30)

C(11)–H(29)

C(10)–H(28)

C(9)–H(27)

C(8)–H(26)

C(7)–H(25)

N(6)–H(24)

C(17)–C(22)

C(21)–C(22)

C(20)–C(21)

C(19)–C(20)

C(18)–C(19)

C(17)–C(18)

C(7)–C(12)

C(11)–C(12)

C(10)–C(11)

C(9)–C(10)

C(8)–C(9)

1.104

1.103

1.104

1.103

1.051

1.347

1.342

1.341

1.343

1.346

1.345

1.342

1.003

1.037

1.274

1.249

1.272

1.351

1.281

1.575

1.221

1.377

1.479

1.794

1.374

H(33)–C(20)–C(21)

H(33)–C(20)–C(19)

C(21)–C(20)–C(19)

H(32)–C(19)–C(20)

H(32)–C(19)–C(18)

C(20)–C(19)–C(18)

H(31)–C(18)–C(19)

H(31)–C(18)–C(17)

C(19)–C(18)–C(17)

H(34)–C(21)–C(22)

H(34)–C(21)–C(20)

C(22)–C(21)–C(20)

H(30)–C(17)–C(22)

H(30)–C(17)–C(18)

C(22)–C(17)–C(18)

C(17)–C(22)–C(21)

C(17)–C(22)–N(16)

C(21)–C(22)–N(16)

H(23)–N(16)–C(22)

H(23)–N(16)–N(15)

C(22)–N(16)–N(15)

C(5)–S(4)–C(3)

N(16)–N(15)–C(5)

H(28)–C(10)–C(11)

H(28)–C(10)–C(9)

C(11)–C(10)–C(9)

H(27)–C(9)–C(10)

H(27)–C(9)–C(8)

C(10)–C(9)–C(8)

H(26)–C(8)–C(9)

H(26)–C(8)–C(7)

C(9)–C(8)–C(7)

120.073

119.833

120.094

120.261

120.264

119.475

119.779

120.051

120.17

O(13)–H(23)–N(16)

N(6)–N(2)–C(3)

N(6)–N(2)–C(1)

C(3)–N(2)–C(1)

H(23)–O(13)–C(1)

N(15)–C(5)–C(1)

N(15)–C(5)–S(4)

C(1)–C(5)–S(4)

O(13)–C(1)–C(5)

O(13)–C(1)–N(2)

154.932

125.247

123.915

110.831

108.97

116.365

131.255

112.381

115.021

129.784

115.192

120.84

118.03

121.13

C(5)–C(1)–N(2)

Dihedral angle (°)

C(18)–C(17)–C(22)–N(16)

C(20)–C(21)–C(22)–N(16)

C(8)–C(7)–C(12)–N(6)

C(10)–C(11)–C(12)–N(6)

C(7)–C(12)–N(6)–N(2)

N(15)–C(5)–C(1)–N(2)

121.177

117.779

121.044

118.088

121.969

119.943

122.183

108.56

179.985

−179.985

179.987

−179.978

−32.818

−179.634

129.257

96.436

C(7)–C(8)

116.153

120.033

119.886

120.081

120.146

120.15

119.704

119.864

120.017

120.119

120.724

118.692

120.584

121.023

118.448

120.529

118.98

H(23)–O(13)

N(16)–H(23)

C(22)–N(16)

N(15)–N(16)

C(12)–N(6)

N(2)–N(6)

C(5)–N(15)

C(3)–S(14)

C(1)–O(13)

C(5)–C(1)

H(29)–C(11)–C(12)

H(29)–C(11)–C(10)

C(12)–C(11)–C(10)

H(25)–C(7)–C(12)

H(25)–C(7)–C(8)

C(12)–C(7)–C(8)

C(7)–C(12)–C(11)

C(7)–C(12)–N(6)

C(11)–C(12)–N(6)

S(4)–C(5)

C(3)–S(4)

N(2)–C(3)

C(1)–N(2)

122.597

118.422

(continued on next page)

716

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Table 4 (continued)

Bond lengths (Å)

Bond angles (°)

H(24)–N(6)–C(12)

H(24)–N(6)–N(2)

C(12)–N(6)–N(2)

S(14)–C(3)–S(4)

S(14)–C(3)–N(2)

S(4)–C(3)–N(2)

114.354

116.459

122.069

125.08

129.76

105.159

salmon sperm DNA binding activity of the ligands (HL_n) was studied by

absorption spectra measurements.

sperm DNA (SS-DNA) was purchased from SRL (India). Double distilled

water was used to prepare all buffer solutions.

2.2. Preparation of azodye ligands

2. Experimental

Preparation

of

5-(4′-alkylphenylazo)-3-phenylamino-2-

2.1. Materials

thioxothiazolidin-4-one (HL_n) (Fig. 1); 25 ml of distilled water contain-

ing hydrochloric acid was added to aniline or a 4-alkyl-aniline. To the

resulting mixture stirred and cooled to 0 °C, a solution of sodium nitrite

0.01 mol in 20 ml of water was added dropwise. The formed diazonium

chloride was consecutively coupled with an alkaline solution of 3-

phenylamino-2-thioxothiazolidin-4-one 0.01 mol in 10 ml of pyridine.

3-Phenylamino-2-thioxtiazolidin-4-one was prepared previously

[1,8,13]. The standard chemical cobalt acetate, aniline and 4-

alkylanilines (alkyl: CH₃, OCH₃, Cl and NO₂) were purchased from

Sigma and Aldrich and used without any further puriﬁcation. Salmon

Table 5

The selected geometric parameters for HL₄.

Bond lengths (Å)

Bond angles (°)

C(21)–H(34)

C(20)–H(33)

C(18)–H(32)

C(17)–H(31)

C(11)–H(30)

C(10)–H(29)

C(9)–H(28)

C(8)–H(27)

C(7)–H(26)

N(6)–H(25)

C(17)–C(22)

C(21)–C(22)

C(20)–C(21)

C(19)–C(20)

C(18)–C(19)

C(17)–C(18)

C(7)–C(12)

C(11)–C(12)

C(10)–C(11)

C(9)–C(10)

C(8)–C(9)

1.104

1.103

1.104

1.103

1.051

1.347

1.343

1.342

1.343

1.346

1.345

1.342

1.003

1.037

1.274

1.249

1.272

1.351

1.727

1.281

1.575

1.221

1.377

1.479

1.794

1.374

H(33)–C(20)–C(21)

H(33)–C(20)–C(19)

C(21)–C(20)–C(19)

C(20)–C(19)–C(18)

C(20)–C(19)–Cl(23)

C(18)–C(19)–Cl(23)

H(32)–C(18)–C(19)

H(32)–C(18)–C(17)

C(19)–C(18)–C(17)

H(34)–C(21)–C(22)

H(34)–C(21)–C(20)

C(22)–C(21)–C(20)

H(31)–C(17)–C(22)

H(31)–C(17)–C(18)

C(22)–C(17)–C(18)

C(17)–C(22)–C(21)

C(17)–C(22)–N(16)

C(21)–C(22)–N(16)

H(24)–N(16)–C(22)

H(24)–N(16)–N(15)

C(22)–N(16)–N(15)

C(5)–S(4)–C(3)

N(16)–N(15)–C(5)

H(29)–C(10)–C(11)

H(29)–C(10)–C(9)

C(11)–C(10)–C(9)

H(28)–C(9)–C(10)

H(28)–C(9)–C(8)

C(10)–C(9)–C(8)

H(27)–C(8)–C(9)

H(27)–C(8)–C(7)

C(9)–C(8)–C(7)

H(30)–C(11)–C(12)

H(30)–C(11)–C(10)

C(12)–C(11)–C(10)

H(26)–C(7)–C(12)

H(26)–C(7)–C(8)

C(12)–C(7)–C(8)

C(7)–C(12)–C(11)

C(7)–C(12)–N(6)

C(11)–C(12)–N(6)

H(25)–N(6)–C(12)

H(25)–N(6)–N(2)

C(12)–N(6)–N(2)

S(14)–C(3)–S(4)

119.374

120.663

119.962

119.575

120.223

120.201

120.612

119.34

O(13)–H(24)–N(16)

N(6)–N(2)–C(3)

N(6)–N(2)–C(1)

C(3)–N(2)–C(1)

H(24)–O(13)–C(1)

N(15)–C(5)–C(1)

N(15)–C(5)–S(4)

C(1)–C(5)–S(4)

O(13)–C(1)–C(5)

O(13)–C(1)–N(2)

154.955

125.246

123.92

110.827

108.971

116.366

131.251

112.383

115.007

129.797

115.194

120.048

120.75

118.006

121.244

121.082

117.768

121.149

118.021

122.004

119.975

122.169

108.541

129.289

96.431

C(5)–C(1)–N(2)

Dihedral angle (°)

C(18)–C(17)–C(22)–N(16)

C(20)–C(21)–C(22)–N(16)

C(8)–C(7)–C(12)–N(6)

C(10)–C(11)–C(12)–N(6)

C(7)–C(12)–N(6)–N(2)

N(15)–C(5)–C(1)–N(2)

−179.999

180

179.984

−179.986

−32.136

−179.659

C(7)–C(8)

H(24)–O(13)

N(16)–H(24)

C(22)–N(16)

N(15)–N(16)

C(12)–N(6)

N(2)–N(6)

C(19)–Cl(23)

C(5)–N(15)

C(3)–S(14)

C(1)–O(13)

C(5)–C(1)

116.159

120.04

119.885

120.075

120.144

120.152

119.705

119.863

120.012

120.125

120.723

118.682

120.594

121.032

118.439

120.528

118.971

122.624

118.403

114.435

116.559

122.197

125.075

129.759

105.166

S(4)–C(5)

C(3)–S(4)

N(2)–C(3)

C(1)–N(2)

S(14)–C(3)–N(2)

S(4)–C(3)–N(2)

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

717

The colored precipitate, which formed immediately, was ﬁltered and

washed several times with water. The crude product was puriﬁed by

recrystallization from hot ethanol [7]. The analytical data conﬁrmed

the expected compositions (Table 1). The ligands (Fig. 1) were also

characterized by ¹H NMR and IR spectroscopy.

(0.03 mol) in EtOH (20 cm³) was added dropwise to a hot EtOH solution

(20 cm³) of Co(CH₃COO)₂·4H₂O (0.02 mol) with stirring and the reac-

tion mixture was reﬂuxed for 3 h. The solution was concentrated to

half of its original volume by evaporation and allowed to cool at room

temperature. During this, a polycrystalline solid was separated, which

was isolated by ﬁltration, washed with EtOH, ether and dried in vacuo

over anhydrous CaCl₂. Formation of the polymer complexes (Fig. 2)

can be obtainable in the following reaction:

The resulting formed ligands are:

HL1

=

5-(4′-methoxyphenylazo)-3-phenylamino-2-

thioxothiazolidin-4-one.

2Co(CH₃COO)₂. 4H₂O + 3HL_n→ [(Co)₂(L_n)₂(HL_n)(CH₃COO)₂(H₂O)₂]

HL2 = 5-(4′-methylphenylazo)-3-phenylamino-2-thioxothiazolidin-

4-one.

HL3 = 5-(phenylazo)-3-phenylamino-2-thioxothiazolidin-4-one.

HL4 = 5-(4′-chlorophenylazo)-3-phenylamino-2-thioxothiazolidin-

2.4. Measurements

4-one.

Microanalytical data (C, H and N) were collected on Automatic

Analyzer CHNS Vario ELIII, Germany. Spectroscopic data were obtained

using the following instruments: FT-IR spectra (KBr disks, 4000–

400 cm⁻¹) by Jasco FTIR-4100 spectrophotometer; the ¹H-NMR spectra

by Bruker WP 300 MHz using DMSO-d₆as a solvent containing TMS as

the internal standard. X-ray diffraction analysis of compounds in pow-

der forms was recorded on X-ray diffractometer in the range of diffrac-

tion angle 2θ = 4–80^°. This analysis was carried out using CuKα

HL5 = 5-(4′-nitrophenylazo)-3-phenylamino-2-thioxothiazolidin-

4-one.

2.3. Preparation of Co(II) complexes

All Co(II) polymer complexes were synthesized according to the

general procedure [7]: a stoichiometric amount of the desired ligand

Table 6

The selected geometric parameters for HL₅.

Bond lengths (Å)

Bond angles (°)

C(21)–H(36)

C(20)–H(35)

C(18)–H(34)

C(17)–H(33)

C(11)–H(32)

C(10)–H(31)

C(9)–H(30)

C(8)–H(29)

C(7)–H(28)

N(6)–H(27)

C(17)–C(22)

C(21)–C(22)

C(20)–C(21)

C(19)–C(20)

C(18)–C(19)

C(17)–C(18)

C(7)–C(12)

C(11)–C(12)

C(10)–C(11)

C(9)–C(10)

C(8)–C(9)

1.104

1.103

1.051

1.346

1.345

1.344

1.348

1.347

1.343

1.346

1.345

1.342

1.005

1.038

1.275

1.25

1.272

1.351

1.259

1.28

1.575

1.221

1.376

1.479

1.794

1.374

1.375

1.316

1.315

C(19)–N(24)–O(26)

C(19)–N(24)–O(25)

O(26)–N(24)–O(25)

H(35)–C(20)–C(21)

H(35)–C(20)–C(19)

C(21)–C(20)–C(19)

C(20)–C(19)–C(18)

C(20)–C(19)–N(24)

C(18)–C(19)–N(24)

H(34)–C(18)–C(19)

H(34)–C(18)–C(17)

C(19)–C(18)–C(17)

H(36)–C(21)–C(22)

H(36)–C(21)–C(20)

C(22)–C(21)–C(20)

H(33)–C(17)–C(22)

H(33)–C(17)–C(18)

C(22)–C(17)–C(18)

C(17)–C(22)–C(21)

C(17)–C(22)–N(16)

C(21)–C(22)–N(16)

H(23)–N(16)–C(22)

H(23)–N(16)–N(15)

C(22)–N(16)–N(15)

C(5)–S(4)–C(3)

N(16)–N(15)–C(5)

H(31)–C(10)–C(11)

H(31)–C(10)–C(9)

C(11)–C(10)–C(9)

H(30)–C(9)–C(10)

H(30)–C(9)–C(8)

C(10)–C(9)–C(8)

H(29)–C(8)–C(9)

H(29)–C(8)–C(7)

C(9)–C(8)–C(7)

H(32)–C(11)–C(12)

H(32)–C(11)–C(10)

C(12)–C(11)–C(10)

H(28)–C(7)–C(12)

H(28)–C(7)–C(8)

C(12)–C(7)–C(8)

C(7)–C(12)–C(11)

C(7)–C(12)–N(6)

C(11)–C(12)–N(6)

H(27)–N(6)–C(12)

H(27)–N(6)–N(2)

C(12)–N(6)–N(2)

123.194

123.277

113.529

117.229

120.927

121.844

116.528

122.139

121.333

121.134

117.124

121.742

120.232

118.425

121.342

121.014

117.472

121.514

117.03

S(14)–C(3)–S(4)

S(14)–C(3)–N(2)

S(4)–C(3)–N(2)

O(13)–H(23)–N(16)

N(6)–N(2)–C(3)

N(6)–N(2)–)–C(1)

C(3)–N(2)–C(1)

H(23)–O(13)–C(1)

N(15)–C(5)–C(1)

N(15)–C(5)–S(4)

C(1)–C(5)–S(4)

O(13)–C(1)–C(5)

O(13)–C(1)–N(2)

C(5)–C(1)–N(2)

Dihedral angle (°)

C(18)–C(17)–C(22)–N(16)

C(20)–C(21)–C(22)–N(16)

C(8)–C(7)–C(12)–N(6)

C(10)–C(11)–C(12)–N(6)

C(7)–C(12)–N(6)–N(2)

N(15)–C(5)–C(1)–N(2)

125.137

129.758

105.104

154.405

125.155

123.876

110.964

108.934

116.031

131.371

112.597

115.476

129.532

114.989

−179.933

179.94

179.976

−179.978

−33.186

−179.523

121.919

121.05

123.452

108.738

127.808

96.346

C(7)–C(8)

H(23)–O(13)

N(16)–H(23)

C(22)–N(16)

N(15)–N(16)

C(12)–N(6)

N(2)–N(6)

C(19)–N(24)

C(5)–N(15)

C(3)–S(14)

C(1)–O(13)

C(5)–C(1)

S(4)–C(5)

C(3)–S(4)

N(2)–C(3)

C(1)–N(2)

N(24)–O(26)

N(24)–O(25)

116.416

120.034

119.885

120.082

120.148

120.143

119.71

119.872

120.012

120.116

120.726

118.697

120.577

121.017

118.457

120.526

118.988

122.567

118.445

114.324

116.416

121.983

718

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Fig. 4. The molecular structures (HOMO &LUMO) for HL_n.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

719

Table 7

The calculated quantum chemical parameters for the ligands (HL_n).

E_HOMO

(eV)

E_LUMO

(eV)

ΔE

(eV)

χ

(eV)

η

(eV)

σ

Pi

(eV)

S

ω

(eV)

Comp.

ΔN_max

(eV)⁻¹

HL₁

HL₂

HL₃

HL₄

HL₅

−1.671

−1.907

−2.035

−1.614

−4.249

−0.333

−0.332

−0.333

−0.004

1.338

1.575

1.703

1.281

4.245

1.002

0.669

1.49476831

1.26984127

1.17439812

1.56128025

0.47114252

−1.002

0.74738416

0.63492063

0.58719906

0.78064012

0.23557126

0.75037668

0.79573349

0.82247343

0.7398144

1.06525377

1.49775785

1.4215873

1.38990018

1.51990632

1.00188457

1.1195

1.1835

0.9735

2.1265

0.7875

0.8515

0.6405

2.1225

−1.1195

−1.1835

−0.9735

−2.1265

radiation (λ = 1.540598 Ả). The applied voltage and the tube current

are 40 KV and 30 mA, respectively. Mass spectra were recorded by the

EI technique at 70 eV using MS-5988 GS-MS Hewlett-Packard. UV–

Visible spectra by Perkin-Elmer AA800 spectrophotometer Model AAS.

Thermal analysis of the ligands and their Co (II) complexes was carried

out using a Shimadzu thermogravimetric analyzer under a nitrogen

atmosphere with heating rate of 10 °C/min over a temperature range

from 30 °C up to 800 °C. Magnetic susceptibility measurements were

determined at room temperature on a Johnson Matthey magnetic

susceptibility balance using Hg[Co(SCN)₄] as calibrate. Conductivity

buffer solution to eliminate the absorbance of SS-DNA itself. The intrin-

sic binding constant K_bof the compound with SS-DNA was determined

using the following Eq. (1) [23]:

ꢀ

ꢁ

ꢀ

ꢁ

ꢀ

ꢁ

½DNAꢀ= є_a–є_f¼ ½DNAꢀ= є_b–є_fþ 1=K_bє_a–є_f

ð1Þ

where [DNA] is the concentration of SS-DNA in base pairs, є_ais the

extinction coefﬁcient observed for the A_obs/[compound] at the given

DNA concentration, є_fis the extinction coefﬁcient of the free compound

in solution and є_bis the extinction coefﬁcient of the compound when

fully bond to DNA. In plots of [DNA] / (є_a− є_f) vs. [DNA], K_bis given

by the ratio of the slope to the intercept.

measurements of the complexes at 25

1 °C were determined in

DMF (10⁻³M) using conductivity/TDS meter model Lutron YK-22CT.

The molecular structures of the investigated compounds were

optimized by HF method with 3-21G basis set. The molecules were

built with the Perkin Elmer ChemBio Draw and optimized using Perkin

Elmer ChemBio3D software [18,19].

2.6. Cytotoxicity investigation

2.6.1. Cell lines and chemical reagents

Hepatocellular carcinoma (HePG-2) and mammary gland breast

cancer (MCF-7) cell lines were obtained from ATCC via Holding compa-

ny for biological products and vaccines (VACSERA), Cairo, Egypt.

Chemical reagents; RPMI-1640 medium, MTT, DMSO and 5-ﬂuorouracil

were purchased from Sigma chemicals (St. Louis, USA), Fetal Bovine

serum (FBS) was purchased from (GIBCO, UK). 5-ﬂuorouracil (5-FU)

was used as a standard anticancer drug for comparison.

2.5. DNA binding experiments

The binding properties of the ligands and their complexes to SS-DNA

have been studied using electronic absorption spectroscopy. SS-DNA

(50 mg) was dissolved by stirring overnight in double deionized

water (pH = 7.0) and kept at 4 °C. Doubly distilled water was used to

prepare buffers (20 mM phosphate buffer (NaH₂PO₄–Na₂HPO₄),

pH = 7.2). A solution of (SS-DNA) in the buffer gave a ratio of UV absor-

bance at 260 and 280 nm (A₂₆₀/A₂₈₀) of ca. 1.8, indicating that the DNA

was sufﬁciently free of protein [20]. The DNA concentration was deter-

mined by UV absorbance spectroscopy using the molar absorption coef-

ﬁcient of 6600 M⁻¹cm⁻¹at 260 nm for SS-DNA [21,22] and was found

to be 1.4 × 10⁻⁴. Electronic absorption spectra (200–900 nm) were car-

ried out using 1 cm quartz cuvette at 25 °C by ﬁxing the concentration of

ligand (1.00 × 10⁻³mol.L⁻¹)_,while gradually increasing the concentra-

tion of SS-DNA (0.00 to 1.30 × 10⁻⁴mol.L⁻¹). An equal amount of

SS-DNA was added to both the compound solutions and the references

2.6.2. MTT assay

The cell lines mentioned above were used to determine the inhibito-

ry effects of ligands and their Co(II) complexes on cell growth using the

MTT assay [24]. This colorimetric assay is based on the conversion of the

yellow tetrazolium bromide (MTT) to a purple formazan derivative by

mitochondrial succinate dehydrogenase in viable cells. Cell lines were

cultured in RPMI-1640 medium with 10% fetal bovine serum. Antibi-

otics added were 100 units/ml penicillin and 100 μg/ml streptomycin

at 37 °C in a 5% CO₂incubator. The cell lines were seeded in a 96-well

plate at a density of 1.0 × 10⁴cells/well at 37 °C for 48 h under 5% Co₂,

followed by 24 h incubation with the indicated drug doses [25]. In the

end of the drug treatment, 20 μl of MTT solution at 5 mg/ml was

added and incubated for 4 h. Dimethyl sulfoxide (DMSO) in volume of

100 μl is added into each well to dissolve the purple formazan formed.

The colorimetric assay is measured and recorded as absorbance at

570 nm using a plate reader (EXL 800). Cytotoxicity was expressed as

Table 8

IR data (cm⁻¹) of free ligands (HL_n) and their Co(II) complexes (1–5).

Compound

υ(NH)

υ(C = O)

υ(C = S)

υ(Co-O)

υ(Co-N)

υ(Co-S)

HL₁

(1)

HL₂

(2)

HL₃

(3)

HL₄

(4)

HL₅

(5)

3207

–

3205

–

3209

–

3207

–

1751

1722

1754

1718

1727

1725

1751

1724

1735

1716

881

825

882

815

842

815

823

819

846

844

–

680

–

684

–

690

–

690

–

680

–

528

–

590

–

598

–

580

–

590

–

485

–

488

–

499

–

498

–

480

3210

–

Fig. 5. The relation between Hammett's substitution coefﬁcients (σ^R) vs. energy gap (ΔE).

^aNumbers as given in Table 1.

720

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

IC₅₀(μg/mL) which indicates the concentration of the compound that

inhibited proliferation rate of the tumor cells by 50% as compared to

the control untreated cells. IC₅₀values were determined from the plot:

% relative cell viability (% inhibition concentration) vs. compound con-

centration. The relative cell viability values were calculated as follows:

sample was run without ABTS and using MeOH/phosphate buffer

(1:1) instead of tested compounds. ^L-ascorbic acid was used as standard

antioxidant (positive control) and the negative control was run with

ABTS and MeOH/phosphate buffer (1:1) only.

A ðcontrolÞ−A ðtestÞ

A ð570 nmÞ of treated samples

%Inhibition ¼

ꢁ 100

%The relative cell viability ¼

ꢁ 100

A ðcontrolÞ

A ð570 nmÞ of untreated sample

2.8. Antimicrobial investigation

2.7. Antioxidant investigation

Rhodanine compounds were individually tested against Gram nega-

tive (Escherichia coli) bacteria, Gram positive (Staphylococcus aureus)

and yeast (Candida albicans). Each of the compounds was dissolved in

DMSO and solutions of the concentration 1 mg/ml were prepared sepa-

rately and paper disks of Whatman ﬁlter paper were prepared with

standard size (5 cm) and sterilized in an autoclave. The paper disks

were soaked in the desired concentration of the complex solution and

were placed aseptically in the petri dishes containing nutrient agar

media (agar 20 g, beef extract 3 g and peptone 5 g) seeded with

Staphylococcus aureus, E. coli and Candida albicans. The petri dishes

were incubated at 36 °C and the inhibition zones were recorded after

24 h of incubation. Each treatment was replicated three times. The

antibacterial activity of a common standard antibiotic ampicillin and

Antioxidant activity screening assay ABTS method [26–28] used for

determination of scavenging activity of ligands (HL_n) and their Co(II)

complexes (1–5). For each of the investigated compounds (2 mL) of

ABTS (2,2′-azinobis-(3-ethyl-benzothiazoline-6-sulphonic acid)

solution (60 μM) was added to 3 mL MnO₂solution (25 mg/mL), all

prepared in (5 mL) aqueous phosphate buffer solution (pH 7, 0.1 M).

The mixture was shaken, centrifuged, ﬁltered and the absorbance of

the resulting green blue solution (ABTS free radical solution) at

734 nm was adjusted to approx. ca. 0.5. Then, 50 μl of (2 mM) solution

of the tested compound in spectroscopic grade MeOH/phosphate buffer

(1:1) was added. The absorbance was measured and the reduction in

color intensity was expressed as inhibition percentage (I %). Blank

Fig. 6. X-ray diffraction patterns for ligands (HL₁, HL₃and HL₄) and the complex (1) in powder forms.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

721

Fig. 7. a. Mass spectrum of HL_1.b. Mass spectrum of HL_3.c. Mass spectrum of HL₄.

722

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

antifungal colitrimazole was also recorded using the same procedure as

above using the same concentration and solvents. The % activity index

for the complex was calculated by the formula:

structures (HOMO &LUMO) for HL_nare presented in Fig. 4. The HOMO–

LUMO energy gap, ΔE, which is an important stability index, is applied

to develop theoretical models for explaining the structure and confor-

mation barriers in many molecular systems. The smaller the value of

ΔE is, the more the stability the compound has [3,18]. The calculated

quantum chemical parameters are given in Table 7. Additional parame-

ters such as separation energies, ΔE, absolute electronegativities, χ,

chemical potentials, Pi, absolute hardness, η, absolute softness, σ, global

electrophilicity, ω [29], global softness, S, and additional electronic charge,

ΔN_max, have been calculated according to the following Eqs. (2–9):

Zone of inhibition by test compound ðdiameterÞ

%Activity Index ¼

ꢁ 100

Zone of inhibition by standard ðdiameterÞ

3. Results and discussion

3.1. Molecular structure

The molecular structures of the ligands (HL_n) were optimized by HF

method with 3-21G basis set. The molecules were built with the Perkin

Elmer ChemBioDraw and optimized using Perkin Elmer ChemBio3D

software. The geometrical parameters bond lengths and bond angles

of HL_nare calculated and presented in Fig. 3 and Tables 2–6. Molecular

ΔE ¼ E_LUMO−E_HOMO

ð2Þ

ð3Þ

−ðE_HOMOþ E_LUMO

Þ

χ ¼

2

a)

b)

c)

Scheme 1. a. Fragmentation patterns of HL₁. b. Fragmentation patterns of HL₃. c. Fragmentation patterns of HL₄.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

723

Fig. 9. TGA curves of complexes (1–5).

Fig. 8. TGA curves of ligands HL

Table 10

Thermal analysis data of the complexes (1–5).

E_LUMO−E_HOMO

η ¼

ð4Þ

Complex^aTemp. range (°C) Found mass loss (calc.) % Assignment

2

(1)

(2)

(3)

(4)

(5)

0–140

11.4 (11.45)

50.49 (50.75)

26.41(26.64)

11.7 (11.15)

11.19 (11.88)

50.95 (50.15)

25.9 (26.39)

11.96 (11. 56)

11.97 (12.27)

49.73 (49.6)

25.8(26.15)

12.8 (11.95)

11.42 (11.34)

50.36 (50.9)

26.4(26.7)

11.82 (11.04)

11.03 (11.08)

51.33 (51.26)

26.28(26.85)

10.36 (10.7)

Loss of C₄H₁₀O₆.

σ ¼ 1=η

Pi ¼ −χ

ð5Þ

ð6Þ

140–510

510–800

N800

Loss of C₃₂H₂₆N₈O₂S₄.

Loss of C₁₆H₁₄N₄O₂S₂.

Loss of 2CoO

0–145

Loss of C₄H₁₀O₆.

145–505

505–800

N800

Loss of C₃₂H₂₆N₈S₄.

Loss of C₁₆H₁₄N₄OS₂.

Loss of 2CoO

1

S ¼

ð7Þ

2η

0–160

Loss of C₄H₁₀O₆.

ω ¼ Pi²=2η

ð8Þ

ð9Þ

160–550

550–800

N800

Loss of C₃₀H₂₂N₈S₄.

Loss of C₁₅H₁₂N₄OS₂.

Loss of 2CoO

ΔN _max¼ −Pi=η

0–155

Loss of C₄H₁₀O₆.

155–515

515–800

N800

Loss of C₃₀H₂₀N₈S₄Cl₂.

Loss of C₁₅H₁₁N₄OS₂Cl.

Loss of 2CoO

The value of ΔE for ligands HL₁, HL₂, HL₃, HL₄and HL₅was found

1.338, 1.575, 1.703, 1.281 and 4.245 eV, respectively. The calculations

indicated that the HL₄is more stable form than the other ligands

[3].The relation between Hammett's substitution coefﬁcients (σ^R) vs.

energy gap (ΔE) is shown in Fig. 5. It is clear that that the values increase

with increasing σ^R.

0–155

Loss of C₄H₁₀O₆.

155–525

525–800

N800

Loss of C₃₀H₂₀N₁₀O₄S₄.

Loss of C₁₅H₁₁N₅O₃S₂.

Loss of 2CoO

a

Numbers as given in Table 1.

3.2. Metal complexes

The interaction of hydrazone ligands (HL_n) with [Co(CH₃COO)₂].4H₂O

in a molar ratio 2:3 [Co:HL_n] under reﬂux conditions gave the polymeric

products presented in Table 1. The polymeric Co(II) complexes are stable

in air and soluble in DMF and DMSO. The molar conductance values for

the cobalt (II) complexes (10⁻³M) are measured in DMF at 25 °C and

these values are in the range of 4–12 Ω⁻¹cm²mol⁻¹indicating a non-

electrolytic nature [23]. The no electrolytic nature of the Co(II) polymeric

complexes implies the contribution of acetate ions to the coordination

sphere in the complexes under investigation.

Table 9

Thermal analysis data of the ligands (HL_n).

Compound

Temp. range (°C)

Found mass loss (calc.) %

Assignment

30–260

260–570

570–800

30–265

265–700

700–800

30–330

330–800

30–350

350–800

30–400

62 (61.9)

30 (29.6)

8 (8.6)

65 (64.9)

30 (30.9)

5 (4.3)

68 (67.7)

32 (32.3)

71 (71.3)

29 (28.9)

59 (59.5)

28 (28.4)

13 (12.3)

Decomposition of a part of the ligand (C₉H₆N₂S₂O).

Further decomposition of a part of the ligand (C₆H₆N₂).

Further decomposition of a part of the ligand (OCH₃).

Decomposition of a part of the ligand (C₉H₆N₂S₂O).

Further decomposition of a part of the ligand (C₆H₆N₂).

Further decomposition of a part of the ligand (CH₃).

Decomposition of a part of the ligand (C₉H₆N₂S₂O).

Further decomposition of a part of the ligand (C₆H₆N₂).

Decomposition of a part of the ligand (C₉H₇N₂S₂OCl).

Further decomposition of a part of the ligand (C₆H₅N₂).

Decomposition of a part of the ligand (C₉H₆N₂S₂O).

Further decomposition of a part of the ligand (C₆H₆N₂).

Further decomposition of a part of the ligand (NO₂).

HL₁

HL₂

HL₃

HL₄

HL₅

400–600

600–800

724

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Evidence for all polymeric nature comes from its solubility proper-

3.3. Infrared spectra and nature of coordination

ties and the metal polymer complex to ligand stoichiometry which is

shown to be 2:3 from the elemental analysis. IR spectroscopy provides

partial evidence that the ligand is acting as a bridge, and that bridging

occurs through both the S and NH from side and through O and N

(hydrazone) from the other side.

The three bands around 823–882, 3205–3210 and 1727–1754 cm⁻¹

in the ligands assigned to υ(CS), –NH(3-phenylamine) and υ(CO)

groups, respectively, were shifted to lower frequencies and –NH(3-

phenylamine) disappearance in all polymer complexes. This indicates

Fig. 10. Coats–Redfern (CR) of ligands (HL_n), Stages (I, II).

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

725

Fig. 10 (continued).

the participation of the thione sulfur, NH(3-phenylamine) and carbonyl

oxygen groups, in the chelation (Table 8) [30]. The splitting of υ(N=N)

band into two bands in the ranges 1435–1520 and ~1230 cm⁻¹due to

υ(HC=N) and υ(=N–NH) hydrazone, respectively, for ligands provides

an evidence that the hydrazone N participate in the chelation after depro-

tonation leading to a covalent linkage. This is more rather conﬁrmed from

the observation of Karabatoses et al. [31] and El-Sonbati et al. [32] where

the hydrazone form is more than the azo structure for similar compounds

(Fig. 1D). In all polymer complexes, CN group remained intact, indicating

the non-participation of the azomethine nitrogen in the chelation [33].

The strong observed at ~1111–1123 cm⁻¹may be assigned to υ(N–N)

vibration mode [34] is affected on complexation. It is blue shifted and ap-

pearance as a weak band. In all polymer complexes, there are two bands

υ_as(1427–1444) and υ_s(1230–1243) cm⁻¹stretching vibration of acetate

group. The correlation between the positions of the antisymmetric and

symmetric stretching vibration of this group was earlier studied [35]. It

was concluded from these studies that the frequency difference between

the two carbonyl stretches of ionic acetate groups is usually in the interval

~160 cm⁻¹, longer values were found for monodentate and lower values

for bidentate groups [36]. Correspondingly, the split of 195–201 cm⁻¹in

polymer complexes indicates monodentate acetate. This is supported by

results of Ryde [37].

The above interpretation is further supported by the appearance

of the non-ligand bands at: 680–690 cm⁻¹; υ(Co–O), 528–598 cm⁻¹

;

υ(Co–N) [38] and 480–500 cm⁻¹; υ(Co–S) [39]. Such class of

compounds is with different types of hydrogen bonding [2–6]:

1. H-bonding of the type NH⋯O between the –NH (hydrazone) group

and C=O group.

2. Intermolecular hydrogen bonding of the NH⋯O type of one molecule

to another one.

3. The case is more favored. This is due to the presence of a broad band

located at 870–965 cm⁻¹which could be taken as a good evidence

for the intermolecular hydrogen bonding.

In all polymer complexes ~3500–3200 cm⁻¹is observed, such

region is attributed to different probabilities: (i) it is due to either free

OH or NH, (ii) bonded –OH group or –NH group or (iii) due to the

presence of coordinated water molecules.

3.4. ¹H NMR spectra

The ¹H NMR spectra of the ligands are recorded in dimethylsulfoxide

(DMSO-d₆) solution using tetramethylsilane (TMS) as internal stan-

dard. The broad signal exhibited by the ligands can be assigned to

726

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

intramolecular hydrogen bonded proton of NH (hydrazone) at

∼11.5 ppm and NH(3-phenylamine) at ∼9.0 ppm were not affected by

dilution and disappear in the presence of D₂O. The chemical shifts of

the different types of protons in the ¹H NMR spectra of the ligands

(HL₁and HL₂) display sharp signals at 3.7 and 2.3 ppm with an integra-

tion equivalent to three hydrogens corresponding to the O–CH₃and C–

CH₃groups, respectively. The aromatic rings give a group of multi sig-

nals at 6.5–8.0 ppm.

Fig. 11. Coats–Redfern (CR) of Co(II) complexes (1–5), Stages (I, II).

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

727

Fig. 11 (continued).

The ¹³C NMR of ligands exhibited signals at 170 ^_172 ppm

corresponding to the carbon of (C=N) groups, signals appear at 160–

163 ppm corresponding to (C=O) groups and signals around

~200 ppm corresponding to the carbon of (C=S). Ligands have different

chemical shift due to aromatic ring substituent. Therefore, it is clear

from these results that the data obtained from the elemental analyses;

IR and ¹H NMR spectra measurements are in agreement with each

other.

fragmentation mode of ligand (HL₁) shows the exact mass of 358 corre-

sponding to the formula C₁₆H₁₄N₄O₂S₂(Fig. 7a). The ion of m/z = 358

undergoes fragmentation to a stable peak at m/z = 224 by losing

C₇H₇N₂O atoms (structure I) as shown in Scheme (1a). A breakdown

of the backbone of HL₁ligand gives the fragment (structure II) with

m/z = 77 by losing of C₃H₂N₂OS₂.

The mass spectrum fragmentation mode of ligand (HL₃) shows the

exact mass of 328 corresponding to the formula C₁₅H₁₂N₄OS₂

(Fig. 7b). The ion of m/z = 328 undergoes fragmentation to a stable

peak at m/z = 224 by losing C₆H₅N₂atoms (structure I) as shown in

Scheme (1b). A breakdown of the backbone of HL₃ligand gives the frag-

ment (structure II) with m/z = 77 by losing of C₃H₂N₂OS₂.

The mass spectrum fragmentation mode of ligand (HL₄) shows the

exact mass of 362.5 corresponding to the formula C₁₅H₁₁N₄OS₂Cl

(Fig. 7c). The ion of m/z = 362 undergoes fragmentation to a stable

peak at m/z = 224 by losing C₆H₄N₂Cl atoms (structure I) as shown in

Scheme (1c). A breakdown of the backbone of HL₄ligand gives the

fragment (structure II) with m/z = 77 by losing of C₃H₂N₂OS₂.

3.5. X-ray diffraction analysis

The X-ray diffraction (XRD) patterns of HL₁, HL₃and HL₄ligands and

complex (1) in powder forms are shown in Fig 6. The XRD patterns of

HL₁, HL₃and HL₄ligands show many sharp diffraction peaks in addition

to a broad hump at 2θ = 8°. This behavior indicates that the powder is a

mixture of amorphous and polycrystalline nature. The XRD pattern of

complex (1) shows amorphous nature.

3.6. Mass spectra

3.7. Electronic spectra and magnetic measurements

The mass spectra of ligands (HL₁, HL₃and HL₄) are recorded and in-

vestigated at 70 eV of electron energy. It is obvious that, the molecular

ion peaks are in good agreement with their suggested empirical formula

as indicated from elemental analyses (Table 1). The mass spectrum

The electronic absorption spectra of the two ligands (HL_n) exhibits

bands at 26,350–26,150 cm⁻¹(CS) (n → π*), 30,460–30,250 cm⁻¹

(CO) (n → π*), 32,980–33,100 cm⁻¹(H-bonding and association),

728

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

40,240–39,890 cm⁻¹(phenyl) (ph-ph*, π–π*) [40] and 29,610–

29,350 cm⁻¹transition of phenyl rings overlapped by composite

broad π–π* of azo/CH=N structure. In the Co(II) complexes, the (CS

and CO) (n–π*) transition shifts to lower energy. These shifts or the

disappearance of the bands are indicative of coordination of the ligands

are indicative of coordination of the ligands to Co(II).

Based on magnetic moment values, the cobalt(II) compounds fall

into two classes. In the ﬁrst, the so called ionic complexes are with μ_eff

Fig. 12. Horowitz–Metzger (HM) of ligands (HL_n), stages (I, II).

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

729

Fig. 12 (continued).

values lying in the ﬁrst range 4.3–5.6 B.M., while the second is with

much smaller values (1.7–2.9 B.M.) and are of covalent properties.

From such scope of representation, the ﬁrst class of cobalt(II) com-

plexes. (i) may be associated with low spin octahedral ﬁeld, while the

second class (ii) is of square planar environment around cobalt(II).

The spectra of our data exhibited bands located at 9200–2210 and

43,320–4400 cm⁻¹. Such ﬁnding is a strong indicative of octahedral

spatial conﬁguration. It is of interest to mention that the low magnetic

moments of Co(II) complexes (μ_eff. = 1.15–1.24 B.M./atom) could be

referred to occur through a ligand bridge as shown in Fig. 2. Another

reason for the lowering magnetic moments may be due to the admix-

ture of cobalt(II) and cobalt(III) ions in the same molecule.

(C₆H₆N₂) (Found 30.0%, calc. 29.6%). The third stage in the temperature

range 570–800 °C corresponds to loss of a part of the ligand (OCH₃)

(Found 8.0%, calc. 8.6%).

HL₂ligand shows three decomposition steps, the ﬁrst stage that oc-

curs in the temperature range 30–265 °C is attributed to loss of

(C₉H₆N₂S₂O) (found 65.0% and calc. 64.9%). The second stage in the

temperature range 265–700 °C corresponds to loss of a part of the ligand

(C₆H₆N₂) (found 30.0%, calc. 30.9%). The third stage in the temperature

range 700–800 °C corresponds to loss of a part of the ligand (CH₃)

(Found 5.0%, calc. 4.3%).

HL₃ligand shows two decomposition steps, the ﬁrst stage that

occurs in the temperature range 30–330 °C is attributed to loss of

(C₉H₆N₂S₂O) (found 68.0% and calc. 67.7%). The second stage in the

temperature range 330–800 °C corresponds to loss of a part of the ligand

(C₆H₅N₂) (found 32.0%, calc. 32.3%).

3.8. Thermal analysis

HL₄ligand shows two decomposition steps, the ﬁrst stage that

occurs in the temperature range 30–350 °C is attributed to Loss of

(C₉H₇N₂S₂OCl) (found 71.0% and calc. 71.3%). The second stage in the

temperature range 350–800 °C corresponds to loss of a part of the ligand

(C₆H₅N₂) (found 29.0%, calc. 28.9%).

HL₅ligand shows three decomposition steps, the ﬁrst stage that

occurs in the temperature range 30–400 °C is attributed to Loss of

(C₉H₆N₂S₂O) (found 59.0% and calc. 59.5%). The second stage in the

The TGA curves for the ligands (HL_n) are shown in Fig. 8. It is clear

that the change of substituent affects the thermal properties of the

ligands. The temperature intervals and the percentage of loss of masses

are listed in Table 9.

HL₁ligand shows three decomposition steps, the ﬁrst stage that

occurs in the temperature range 30–260 °C is attributed to loss of

C₉H₆N₂S₂O (found 62.0% and calc. 61.9%). The second stage in the tem-

perature range 260–570 °C corresponds to loss of a part of the ligand

730

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

temperature range 400–600 °C corresponds to loss of a part of the ligand

(C₆H₆N₂) (found 28.0%, calc. 28.4%). The third stage in the temperature

range 700–800 °C corresponds to loss of a part of the ligand (NO₂)

(found 13.0%, calc. 12.3%).

The TGA curves for Co(II) complexes (1–5) are shown in Fig. 9. The

temperature intervals and the percentage of loss of masses are listed

in Table 10. The TG curves of all Co (II) complexes (1–5) showed the

loss of C₄H₁₀O₆in the temperature range ~30–150 °C. The ﬁrst stage is

Fig. 13. Horowitz–Metzger (HM) of Co(II) complexes (1–5), stages (I, II).

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

731

Fig. 13 (continued).

Table 11

Thermodynamic data of the thermal decomposition of ligands (HL_n).

Parameter

E_a

Compound

Decomposition temperature (°C)

Method

R

⁎

ΔG

A

ΔS

ΔH

(kJ mol⁻¹

)

(s⁻¹

)

(J mol⁻¹K⁻¹

)

(kJ mol⁻¹

)

(kJ mol⁻¹

)

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

45.8

53.6

180

193

46.9

48.4

162

173

329

338

108

120

70.9

80.8

102

114

31.2

39.2

108

119

7.58 × 10¹

4.18 × 10²

4.43 × 10⁸

6.40 × 10⁹

7.11 × 10¹

1.17 × 10²

2.34 × 10⁷

2.50 × 10⁸

2.54 × 10³⁰

1.70 × 10³²

1.51 × 10⁴

2.05 × 10⁵

5.53 × 10⁵

1.40 × 10⁷

1.31 × 10⁶

2.10 × 10⁷

3.31 × 10⁰

3.59 × 10¹

1.59 × 10⁴

5.78 × 10⁴

−214

−200

−87.9

−65.8

−215

−210

−113

−92.2

333

41.2

49

159

247

241

161

160

250

245

151

142

242

236

131

129

181

179

152

150

254

255

0.99221

0.99398

0.99355

0.99169

0.99322

0.99788

0.98442

0.99156

0.99453

0.99452

0.99432

0.9939

0.99122

0.98595

0.99104

0.99064

0.99523

0.98744

0.98712

0.98669

211–346

498–624

158–401

502–643

225–271

443–630

142–240

301–418

127–372

496–715

HL₁

HL₂

HL₃

HL₄

HL₅

174

186

42.3

43.8

155

166

325

333

101

113

67.1

76.9

96.5

108

26.9

34.9

101

112

367

−173

−152

−139

−112

−134

−111

−240

−220

−173

−163

HM

CR

HM

CR

HM

732

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Table 12

Thermodynamic data of the thermal decomposition of Co(II) complexes (1–5).

Parameter

E_a

Compound^a

Decomposition temperature (°C)

Method

R

⁎

ΔG

A

ΔS

ΔH

(kJ mol⁻¹

)

(s⁻¹

)

(J mol⁻¹k⁻¹

)

(kJ mol⁻¹

)

(kJ mol⁻¹

)

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

HM

CR

10.6

19.4

722

734

11.4

21.7

691

726

14.8

25

412

430

6.76

18.6

744

740

8

6.31 × 10³

5.36 × 10²

2.20 × 10⁴⁵

1.88 × 10⁴⁶

6.47 × 10³

9.87 × 10²

4.44 × 10⁴³

1.14 × 10⁴⁶

1.43 × 10²

2.14 × 10¹

6.11 × 10²⁴

1.77 × 10²⁶

1.35 × 10³

3.95 × 10²

8.17 × 10⁴⁶

5.05 × 10⁴⁶

2.51 × 10³

3.83 × 10²

1.50 × 10²²

5.83 × 10²²

−293

−275

615

5.59

14.4

715

727

6.41

16.8

684

719

9.81

20

406

423

1.70

13.5

738

734

3.01

13.1

360

371

181

179

223

221

181

177

221

220

181

178

229

224

188

182

221

183

180

223

225

0.96357

0.94125

0.97664

0.99571

0.9262

140–510

510–545

140–505

505–540

150–500

500–550

155–515

515–540

155–500

500–550

(1)

(2)

(3)

(4)

633

−293

−270

583

0.9493

0.98464

0.98183

0.9478

629

−286

−264

221

0.93629

0.99286

0.99395

0.92499

0.90661

0.98471

0.97099

0.9166

249

−306

−278

645

HM

CR

HM

CR

641

−301

−278

171

18.1

367

377

0.93422

0.92419

0.93396

(5)

HM

183

a

Numbers as given in Table 1.

related to loss of the part of the deprotonated ligand. The second stage is

related to loss of HL_n. The ﬁnal weight losses are due to the decomposi-

tion of metal oxides residue (Table 10).

3.8.1.2. Horowitz–Metzger equation. The Horowitz–Metzger equation is

an illustrative of the approximation methods. These authors derived

the relation:

3.8.1. Calculation of activation thermodynamic parameters

The thermodynamic activation parameters of decomposition

processes of the ligands HL_nand their Co(II) complexes (1–5) namely

activation energy (Ea), enthalpy (ΔH*), entropy (ΔS*), and Gibbs free

energy change of the decomposition (ΔG*) are evaluated graphically

by employing the Coast–Redfern [41] and Horowitz–Metzger [42]

methods.

"

#

1−n

1−ð1−αÞ

1−n

E_aθ

2:303RT²_s

log

¼

; for n≠1

ð13Þ

when n = 1, the LHS of Eq. (13) would be log[−log(1-α)] (Figs. 12 and

13). For a ﬁrst order kinetic process, the Horowitz–Metzger equation

may write in the form:

3.8.1.1. Coast–Redfern equation. The Coast–Redfern equation, which is a

typical integral method, can represent as:

ꢄ

ꢂ

ꢃꢅ

W_α

Wγ

E_aθ

2:303RT²_s

log log

¼

− log2:303

ð14Þ

ꢂ

ꢃ

Z

α

T₂

dx

ð1−αÞ

A

ϕ

E_a

RT

¼

exp

−

dt

ð10Þ

n

0

T₁

where θ = T − T_s, w_γ= w_α− w, w_α= mass loss at the completion

reaction; w = mass loss up to time t. The plot of log [log (w_α/w_γ)] vs.

θ was drawn and found to be linear from the slope of which E_awas cal-

culated. The pre-exponential factor, A, is calculated from equation:

For convenience of integration, the lower limit T₁is usually taken as

zero. This equation on integration gives

ꢄ

ꢅ

ꢄ

ꢅ

lnð1−αÞ

E_a

RT

AR

ϕE_a

E_a

RT²_s

A

ln −

¼ −

þ ln

ð11Þ

T²

ꢄ

ꢂ

ꢃꢅ

¼

ð15Þ

E_a

RT_s

ϕ exp

−

A plot of left-hand side (LHS) against 1/T was drawn (Figs. 10 and

11). E_ais the energy of activation and calculated from the slope and A

⁎

The entropy of activation, ΔS , is calculated from Eq. (12). The en-

in (s⁻¹) from the intercept value. The entropy of activation (ΔS ) in

⁎

thalpy activation, ΔH , and Gibbs free energy, ΔG , is calculated from:

(Jmol⁻¹K⁻¹) is calculated by using the equation:

ΔH^ꢂ¼ E_a−RT

ð16Þ

ð17Þ

ꢄ

ꢂ

ꢃꢅ

Ah

k_BT_s

ΔS^ꢂ¼ 2:303 log

R

ð12Þ

ΔG^ꢂ¼ ΔH^ꢂ−TΔS^ꢂ

⁎

The calculated values of E_a, A, ΔS , ΔH and ΔG for the decomposi-

tion steps for ligands (HL_n) and cobalt(II) complexes (1–5) are summa-

rized in Tables 11 and 12.

Where k_Bis the Boltzmann constant, h is the Plank's constant and T_s

is the TG peak temperature.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

733

Fig. 14. Absorption spectra of ligands (HL_n) in buffer pH 7.2 at 25 °C in the presence of increasing amount of SS-DNA. Arrows indicate the changes in absorbance upon increasing the

SS-DNA concentration. Inset: plot of [DNA] / (ε_a− ε_f) M²cm vs. [DNA] M for titration of DNA with ligands (HL_n).

3.9. Stoichiometries of the cobalt(II) complexes

complexes reveal that three molecules of the ligand and two of the

anions are coordinated to the two metal atoms in all complexes.

The ligands present four donor sites: the azo nitrogen, the carbonyl

oxygen and the thionyl sulfur of rhodanine moiety and the NH

group of 3-phenylamino. However, it is clear that the utilization of

all the four bonding sites would introduce certain steric restrictions

and hence either both the azo nitrogen and the carbonyl group

Analytical data of the polymeric complexes (Table 1) were isolat-

ed in the general formulae [(Co)₂(L_n)₂(HL_n)(CH₃COO)₂(OH₂)₂]_nas

shown in Fig. 2. The 2:3 stoichiometries of the polymeric complexes

were calculated from their elemental analyses. The analytical

data and the molar conductance measurements of the polymeric

734

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

DNA interaction study by UV–Visible Spectroscopy Electronic ab-

sorption spectra was initially used to examine the interaction between

ligands (HL_n) and SS-DNA. After interaction with increasing amount

of DNA, all the peaks decreased gradually and the wavelengths have

minor red shift of 1–2 nm. Long and Barton [43] had pointed out that

the absorption peaks shift of the small molecules after they interacted

with DNA could be as the clues to judge the binding mode between

the small molecules and DNA: If the binding involves a typical

intercalative mode, a hypochromism effect coupled with obvious

bathochromism for the characteristic peaks of the small molecules will

be found due to the strong stacking between the chromophore and

the base pairs of DNA [44]. Therefore, based on this viewpoint, the inter-

action between ligands (HL_n) and SS-DNA could be noncovalent

intercalative binding. After intercalating the base pairs of DNA, the π*

orbital of the intercalated ligand could couple with π orbital of base

pairs, thus decreasing the π–π* transition energy, and further resulting

in the bathochromism. On the other hand, the coupling of a π orbital

with partially ﬁlled electrons decreases the transition probabilities

hence results hypochromic shift. Since hypochromism due to π–π*

stacking interactions may appear in the case of the intercalative binding

mode, while bathochromism (red-shift) may be observed when the

DNA duplex is stabilized [45,46].

Fig. 15. The relation between Hammett's substitution coefﬁcients (σ^R) vs. intrinsic binding

constants (K_b) of the ligands (HL_n).

would coordinate or the NH group and the carbonyl group

would coordinate. The coordination of NH group and carbonyl

group seems unlikely in view of the large size of the chelated ring.

Polymeric complexes do not have a sharp melting point and decom-

pose at higher temperature.

The intrinsic binding constants (K_b) of all the ligands (HL_n) with

SS-DNA were determined (Eq. 1) [47]. The K_bvalues obtained from

the absorption spectral technique for ligands (HL₁−HL₅) were calculat-

ed as 2.63 × 10⁵, 3.15 × 10⁵, 4.64 × 10⁵, 5.1 × 10⁵and 7.35 × 10⁵M⁻¹

,

respectively. The values of binding constant are related to the nature of

the p-substituent as they increase according to the following order

p-(NO₂N Cl N H N CH₃N OCH₃). This can be attributed to the fact that

the effective charge increased due to the electron withdrawing p-

substituent (HL₄and HL₅) while it decreased by the electrons donating

character of (HL₁and HL₂). This is in accordance with that expected

from Hammett's constant (σ^R) as shown in Fig. 15, correlate the binding

constant values with σ^Rit is clear that all these values increase with

increasing σ^R.

3.10. DNA binding studies

3.10.1. Electronic absorption measurements

Absorption titration is one of the most universally employed

methods to study the binding modes and binding extent of compounds

to DNA. Absorption titration experiments were performed with ﬁxed

concentrations of the ligands (HL_n) (30 μM) while gradually increasing

the concentration of DNA (10 mM) at 25 °C. While measuring the

absorption spectra, an equal amount of DNA was added to both the

compound solution and the reference solution to eliminate the absor-

bance of DNA itself. We have determined the intrinsic binding constant

to SS-DNA by monitoring the absorption intensity of the charge transfer

spectral bands near 470, 455, 437, 480 and 540 nm for the ligands

(HL₁−HL₅), respectively. The absorption spectra of these ligands with

increasing concentration of SS-DNA in the range 300–700 nm are

shown in Fig. 14.

3.11. Cytotoxic activity

The synthesized ligands (HL_n) and their Co(II) complexes (1–5)

have been evaluated for in vitro cytotoxic activity against two human

cancer cell lines; HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast

cancer). Inhibitory activity against HePG-2 and MCF-7 cell lines was de-

tected by using different concentrations (i.e., 50, 25, 12.5, 6.25, 3.125,

1.56, and 0 μg) of the tested compounds and viability cells (%) were de-

termined by the colorimetric method, data presented in Table 13. Also,

Table 13

Evaluation of cytotoxicity of ligands (HL_n) and their Co(II) complexes (1–5) against HePG-2 and MCF-7 cells.

Compound

cell lines

HePG-2

Sample conc.

5-FU

HL₁

8.3

HL₂

7.9

HL₃

7.5

HL₄

7.6

HL₅

13.1

(1)

30.4

(2)

13.4

(3)

51.2

(4)

31.9

(5)

30.4

100 μg/ml

50 μg/ml

25 μg/ml

12.5 μg/ml

6.25 μg/ml

3.125 μg/ml

1.56 μg/ml

0 μg/ml

8.6

17.1

24.0

33.1

56.8

70.6

88.7

100

15.6

21.9

36.7

55.4

74.3

92.6

15.6

24.3

38.4

56.7

78.1

95.5

14.2

20.8

34.6

47.1

58.3

76.4

14.3

22.0

35.3

54.7

73.5

90.5

18.8

26.4

37.2

67.5

75.9

96.9

42.8

53.9

66.2

87.5

99.1

100

48.1

60.0

72.8

85.3

98.2

22.1

31.8

45.6

63.7

83.5

100

44.0

56.2

67.3

79.1

95.4

65.9

79.3

93.7

42.8

55.7

68.3

89.5

100

42.0

53.7

65.3

78.5

98.4

100

39.6

100

58.6

77.3

94.1

100

MCF-7

100 μg/ml

50 μg/ml

25 μg/ml

12.5 μg/ml

6.25 μg/ml

3.125 μg/ml

1.56 μg/ml

0 μg/ml

5.8

24.0

30.8

42.7

54.9

69.3

88.1

34.6

46.5

59.2

68.4

83.3

98.5

7.9

13.4

20.0

31.5

50.3

61.7

74.6

20.1

27.2

39.5

51.3

72.8

93.4

28.3

39.1

52.0

63.7

77.2

96.3

50.8

10.3

16.2

28.5

48.4

62.8

81.6

100

64.5

76.2

92.3

54.7

70.3

91.2

100

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

735

inhibitory concentration 50 (IC₅₀) was calculated from Fig. 16 and

Table 13. The results clearly revealed that most of the compounds pos-

sessed cytotoxic activity as evidenced by the IC₅₀values, as reported

in Table 14. The results revealed that some tested compounds have

cytotoxic activity against the hepatocellular carcinoma (HePG-2) and

mammary gland breast cancer (MCF-7) cell lines with superiority of

HL₃(IC₅₀= 5.4 μg/mL and 5.6 μg/mL, respectively). All ligands HL_nex-

hibit highly signiﬁcant cytotoxic activity against HePG-2 cell line.

Fig. 16. Cytotoxic and antitumor activity of ligands (HL_n) and their Co(II) complexes (1–5) against HePG-2 and MCF-7 cells.

736

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Fig. 16 (continued).

Among all the ligands tested against MCF-7 cell line HL₃is exhibiting

very good cytotoxic activity, but ligands HL₁, HL₂, HL₄and HL₅are

exhibiting good to moderate cytotoxic activity as shown in Table 14.

All cobalt(II) complexes are exhibiting moderate to weak cytotoxic or

non-cytotoxic activity. Apparently, complexation reduces the cytotoxic

activity of ligands. Comparing results with 5-ﬂuorouracil (5-FU)

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

737

Table 14

Table 16

Inhibition of cell viability of ligands (HL_n) and their Co(II) complexes (1–5) against HePG-

2 and MCF-7 cells in comparison with standard drug 5-ﬂuorouracil.

Antibacterial and antifungal activities data of ligands (HL_n) and their Co(II) complexes

(1–5).

Cell lines [IC₅₀(μg/mL)]

Compound

(mg/ml)

E. coli

S. aureus

C. albicans

Compound

HePG-2

MCF-7

Diameter of

inhibition

zone (mm) index

%

Diameter of

activity inhibition

%

Diameter of

activity inhibition

%

activity

5-FU

HL₁

HL₂

HL₃

HL₄

HL₅

(1)

(2)

(3)

(4)

(5)

7.9 0.24

8.3 0.47

9.0 0.68

5.4 0.31

7.9 0.38

10.3 0.97

34.8 3.15

12.4 1.04

96.5 6.35

37.1 2.98

32.9 2.32

5.6 0.13

19.4 1.27

41.5 3.41

5.6 0.21

17.6 1.10

29.5 1.29

81.6 4.87

67.0 4.11

N100

zone (mm) index

HL₁

HL₂

HL₃

HL₄

HL₅

(1)

(2)

(3)

9

3

20

14

6

–

37.5

12.5

83.3

58.3

25.0

–

14

7

16

17

10

3

4

–

2

63.6

31.8

72.7

77.3

45.4

13.6

18.2

–

17

6

25

21

14

–

65.4

23.1

96.1

80.8

53.8

–

93.5 6.37

62.7 4.12

(4)

9.1

(5)

3

24

–

12.5

100

–

5

22

–

22.7

100

–

26

–

100

Data presented as mean SD. IC₅₀(μg/ml): 1–10 (very strong). 11–20 (strong). 21–50

(moderate). 51–100 (weak) and above 100 (non-cytotoxic). All the compounds and the

standard dissolved in DMSO, diluted with culture medium containing 0.1% DMSO. The

control cells were treated with culture medium containing 0.1% DMSO.

Ampicillin

Colitrimazole

response indicated that HL₃have higher cytotoxic activity than 5-FU.

The other compounds also showed cytotoxic activity but at higher IC₅₀

values. The results indicated the importance of different heterocyclic

rhodanine derivatives in enhancing the cytotoxic activity.

Co(II) complex of HL₃represented a lower antioxidant activity com-

pared to its un-complexed compound. In accordance with the cytotox-

icity testing results, the complexation decreases the biological activity

of the synthesized compound.

3.12. Antioxidant activity

3.13. Antimicrobial activity

Oxygen is vital for aerobic life process. However about 5% or more of

the inhaled O₂is converted to reactive oxygen species (ROS). A free rad-

ical (FR) can be deﬁned as a chemical species possessing an unpaired

electron. FR can be positively charged, negatively charged or electrically

neutral [48]. When generation of ROS overtakes the antioxidant defense

of the cells, the free radicals start attacking the cell proteins, lipids and

carbohydrates which leads to a number of physiological disorders

[49]. Free radicals have been implicated in the pathogenesis of diabetes,

liver damage, nephrotoxicity, inﬂammation, cancer, cardiovascular dis-

orders, neurological disorders and in the process of aging [50].

Antioxidants are chemical substances that donate an electron to the

free radical and convert it to a harmless molecule. They may reduce the

energy of the free radical or suppress radical formation or break chain

propagation or repair damage and reconstitute membranes.

Table 15 expressed results of radical scavenging ability and percent-

age of inhibition of each ligands (HL_n), their Co(II) complexes (1–5) and

standard ascorbic acid, as a reference compound by ABTS method. The

results showed that all ligands have high antioxidant activity and have

asymptotic effect of ascorbic acid. HL₃presented the better activity

among all other compounds and when compared with ascorbic acid.

There are poor antioxidant activity for Co(II) complexes (1–5). The

The antimicrobial activity of ligands (HL_n) and their Co(II) com-

plexes (1–5) were tested against bacteria and fungi (yeast) for detecting

their antimicrobial activities [9,51,52]. The used organisms in the pres-

ent investigations included Gram negative (E. coli) bacteria, Gram posi-

tive (Staphylococcus aureus) and yeast (Candida albicans). The results of

the antibacterial activities of the synthesized compounds are recorded

in Table 16. All HL_nwere found to have antibacterial activity against

Gram negative bacteria; namely; E. coli (inhibition zone =9 mm with

activity index 37.5% for HL₁, inhibition zone =3 mm with activity

index 12.5% for HL₂, inhibition zone = 20 mm with activity index

83.3% for HL₃, inhibition zone = 14 mm with activity index 58.3% for

HL₄and inhibition zone = 6 mm with activity index 25% for HL₅).

Only complex (5) has antibacterial activity against Gram negative

bacteria; namely; E. coli (inhibition zone =3 mm with activity index

12.5%).

All compounds under investigation have antibacterial activity

against Gram positive bacteria; namely S. aureus (inhibition zone =

14 mm with activity index 63.6% for HL₁, inhibition zone = 7 mm

with activity index 31.8% for HL₂, inhibition zone = 16 mm with activity

index 72.7% for HL₃, inhibition zone = 17 mm with activity index 77.3%

for HL₄, inhibition zone = 10 mm with activity index 45.4% for HL₅, in-

hibition zone = 3 mm with activity index 13.6% for complex (1), inhibi-

tion zone = 4 mm with activity index 18.2% for complex (2), inhibition

zone = 2 mm with activity index 9.1% for complex (4) and inhibition

zone = 5 mm with activity index 22.7% for complex (5)) while complex

(3) has no activity. Only ligands HL_nhave antifungal activity against

C. albicans (inhibition zone = 17 mm with activity index 65.4% for

HL₁, inhibition zone = 6 mm with activity index 23.1% for HL₂, inhibi-

tion zone = 25 mm with activity index 96.1% for HL₃, inhibition

zone = 21 mm with activity index 80.8% for HL₄and inhibition

zone = 14 mm with activity index 53.8% for HL₅). HL_nwere found to

have high antibacterial and antifungal activities than their complexes

(Fig. 17). HL₃was found to have high antibacterial activity against

E. coli (Fig. 17a) and antifungal activity against C. albicans (Fig. 18)

more than the other ligands. HL₄was found to have high antibacterial

activity against S. aureus as shown in Fig. 17(b) more than other ligands.

HL₃and HL₄are good antibacterial and antifungal agents.

Table 15

Results of radical scavenging activity and % of inhibition of each ligands (HL_n) and their

Co(II) complexes (1–5) by ABTS method.

Compounds

Absorbance

% inhibition

Control of ABTS

Ascorbic-acid

0.520

0.057

0.070

0.082

0.055

0.068

0.079

0.332

0.296

0.424

0.339

0.283

0

89.0

86.5

84.2

89.4

86.9

84.8

36.1

43.1

18.5

34.8

45.6

HL₁

HL₂

HL₃

HL₄

HL₅

(1)

(2)

(3)

(4)

(5)

738

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

Fig. 17. Antibacterial activity data of ligands (HL_n) and their Co(II) complexes against (a) Escherichia coli and (b) Staphylococcus aureus.

4. Conclusion

bonding sites are 3-NH, CS, CO and hydrazo groups. The XRD patterns

of ligands indicate that the powder is a mixture of amorphous and

polycrystals nature. The polymeric complexes exhibit amorphous na-

ture. The interaction between ligands (HL_n) and SS-DNA involves a

hypochromism effect coupled with bathochromism. There are straight

line relationships between energy gap (ΔE) and the SS-DNA binding

activity (K_b) of the ligands with Hammett's p-substitution coefﬁcients

(σ^R). It is clear that that the values of energy gap (ΔE) and the SS-

The IR, ¹H-NMR spectra show that ligands (HL_n) exist in tauto-

meric between both states enol/hydrazo form with intramolecular

hydrogen bonding. The ligands coordinate to cobalt(II) as monobasic

tetradentate. The cobalt(II) complexes are non-electrolytes, paramag-

netic and six-coordinated octahedral polymeric complexes of struc-

ture [(Co)₂(L_n)₂(HL_n)(CH₃COO)₂(H₂O)₂]_n. It is clear that, the four

Fig. 18. Antifungal activity data of ligands (HL_n) and their Co(II) complexes against Candida albicans.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 215 (2016) 711–739

739

DNA binding activity (K_b) increase with increasing σ^R. Rhodanine de-

rivatives have been evaluated to have biological and pharmacological

activities. HL₃has the highest cytotoxic, antioxidant and antimicrobial

activities.

[22] M. Sirajuddin, S. Ali, Synthesis and Characterization of Potential Bioactive

Organotins, LAP, Germany, 2013.

[23] A. Wolfe, G.H. Shimer, T. Meehan, Biochemistry 26 (1987) 6392 –6396.

[24] T. Mosmann, J. Immunol. Methods 65 (1983) 55 –63.

[25] F. Denizot, R. Lang, J. Immunol. Methods 22 (1986) 271 –277.

[26] E. Lissi, B. Modak, R. Torres, J. Escobar, A. Urza, Free Radic. Res. 30 (1999) 471 –477.

[27] A.B.A. El-Gazar, A.M.S. Youssef, M.M. Youssef, A.A. Abu-Hashem, F.A. Badria, Eur. J.

Med. Chem. 44 (2009) 609 –624.

References

[28] R. Aeschlach, J. Loliger, C.B. Scott, A. Murcia, J. Butler, B. Halliwell, I.O. Aruoma, Food

[1] A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, Sh.M. Morgan, Inorg. Chim. Acta 404

(2013) 175 –187.

[2] A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, Sh.M. Morgan, Spectrochim. Acta A 127

Chem. Toxicol. 32 (1994) 31 –36.

[29] A.F. Shoair, J. Coord. Chem. 60 (2007) 1101 –1109.

[30] A.Z. El-Sonbati, M.A. Diab, M.M. El-Halawany, N.E. Salem, Spectrochim. Acta A 77

(2014) 310 –328.

(2010) 735 –766.

[3] N.A. El-Ghamaz, A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, M.K. Awad, Sh.M.

Morgan, Mater. Sci. Semicond. Process. 19 (2014) 150 –162.

[4] A.Z. El-Sonbati, A.F. Shoair, A.A. El-Bindary, M.A. Diab, A.S. Mohamed, J. Mol. Liq. 209

(2015) 635 –647.

[31] G.J. Karabatores, B.L. Shapiro, E.M. Vane, J.S. Fleining, J. Ratka, J. Am. Chem. Soc. 85

(1963) 2784 –2788.

[32] A.Z. El-Sonbati, A.A. El-Bindary, A. El-Dissouky, T.M. El-Gogary, A.S. Hilali,

Spectrochim. Acta A 58 (2002) 1623 –1629.

[5] A.Z. El-Sonbati, A.A.M. Belal, M.S. El-Gharib, Sh.M. Morgan, Spectrochim. Acta A 95

[33] S. Sen, S. Shit, S. Mitra, S.R. Battren, J. Struct. Chem. 19 (2008) 137 –142.

[34] A.Z. El-Sonbati, A.A. El-Bindary, E.M. Mabrouk, R.M. Ahmed, Spectrochim. Acta A 57

(2001) 1751 –1757.

[35] K. Nakamoto, Infrared and Raman Spectra of Inorganic and Coordination Com-

pounds, Wiley Interscience Publication John Wiley & Sons. Inc., New York, 1986.

[36] K. Nakamoto, Infrared Spectra of Inorganic and Coordination Compounds, John

Wiley, New York, 1986.

(2012) 627 –636.

[6] A.Z. El-Sonbati, M.A. Diab, A.A.M. Belal, Sh.M. Morgan, Spectrochim. Acta A 99

(2012) 353 –360.

[7] A.A. Al-Sarawy, A.A. El-Bindary, D.N. El-Sonbati, Spectrochim. Acta A 61 (2005)

1847 –1851.

[8] N.A. El-Ghamaz, A.Z. El-Sonbati, Sh.M. Morgan, J. Mol. Struct. 1027 (2012) 92 –98.

[9] M.I. Abou-Dobara, A.Z. El-Sonbati, Sh.M. Morgan, World J. Microbiol. Biotechnol. 29

(2013) 119 –126.

[37] U. Ryde, Biophys. J. 77 (1999) 2777 –2787.

[38] W.H. Mahmoud, N.F. Mahmoud, G.G. Mohamed, A.Z. El-Sonbati, A.A. El-Bindary,

[10] A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, G.G. Mohamed, Sh.M. Morgan, Inorg.

Spectrochim. Acta A 150 (2015) 451 –460.

Chim. Acta 430 (2015) 96 –107.

[11] M.A. Diab, A.Z. El-Sonbati, A.A. El-Bindary, G.G. Mohamed, Sh.M. Morgan, Res. Chem.

Intermed. 41 (2015) 9029 –9066.

[39] K. Dakshayani, Y. Lingappa, M.S. Kumar, S. Rao, J. Chem. Pharm. Res. 3 (2011)

506 –513.

[40] F.C. Brown, C.K. Bradsher, B.F. Moser, S. Forrester, J. Organomet. Chem. 24 (1959)

[12] X.H. Zhang, L.Y. Wang, Z.X. Nan, S.H. Tan, Z.X. Zhang, Dyes Pigments 79 (2008)

1056 –1060.

205 –209.

[41] A.W. Coats, J.P. Redfern, Nat. J. 20 (1964) 68 –79.

[13] K.L. Reddy, K.R.Y. Harish, K.K. Ashwini, S.S.S. Vidhisha, Nucleosides Nucleotides

Nucleic Acids 28 (2009) 204 –219.

[14] A.A. El-Bindary, A.Z. El-Sonbati, R.M. Ahmed, Spectrochim. Acta A 58 (2002)

[42] H.W. Horowitz, G. Metzger, J. Anal. Chem. 35 (1963) 1464 –1468.

[43] E.C. Long, J.K. Barton, J. Chem. Res. 23 (1990) 271 –273.

[44] Q. Wang, X. Wang, Z. Yu, X. Yuan, K. Jiao, Int. J. Electrochem. Sci. 6 (2011)

5470 –5481.

333 –339.

[15] M. Maghami, F. Farzaneh, J. Simpson, M. Ghiasi, M. Azarkish, J. Mol. Struct. 1093

(2015) 24 –32.

[16] R.C. Maurya, B.A. Malik, J.M. Mir, P.K. Vishwakarma, D.K. Rajak, N. Jain, J. Mol. Struct.

[45] M. Sirajuddin, S. Ali, A. Badshah, J. Photochem. Photobiol. B Biol. 124 (2013) 1 –19.

[46] M. Tariq, N. Muhammad, M. Sirajuddin, S. Ali, N.A. Shah, M.R. Khan, M.N. Tahir, J.

Organomet. Chem. 723 (2013) 79 –89.

5 (2015) 266 –285.

[47] J.P. Costes, F. Dahan, J.P. Laurent, M. Drillon, Inorg. Chem. Acta 294 (1999) 8 –12.

[48] K.H. Cheseman, T.F. Slater, Br. Med. Bull. 49 (1993) 481 –493.

[49] R.S. Cotran, V. Kumar, T. Collins, Robbin's Pathological Basis of Diseases, sixth ed.

Thomson Press (I) Ltd., Noida and India, 1999.

[17] Z. Wang, L. Tang, Y. Zhang, S. Zhan, J. Ye, J. Power, Sources 287 (2015) 50 –57.

[18] A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, A.M. Eldesoky, Sh.M. Morgan,

Spectrochim. Acta A 135 (2015) 774 –791.

[19] N.A. El-Ghamaz, M.A. Diab, A.A. El-Bindary, A.Z. El-Sonbati, H.A. Seyam, J. Mater. Sci.

[50] S.K. Mondal, G. Chakraborty, M. Gupta, U.K. Mazumdar, Indian J. Exp. Biol. 44 (2006)

Semicond. Proc. 27 (2014) 521 –531.

39 –44.

[20] M. Sirajuddin, S. Ali, N.A. Shah, M.R. Khan, M.N. Tahir, Spectrochim. Acta A 94 (2012)

134 –142.

[51] N.H. Metwally, M.A. Abdalla, M.A.N. Mosselhi, E.A. El-Desoky, Carbohydr. Res. 345

(2010) 1135 –1141.

[21] S. Dey, S. Sarkar, H. Paul, E. Zangrando, P. Chattopadhyay, Polyhedron 29 (2010)

[52] Z.H. Chen, C.J. Zheng, L.P. Sun, H.R. Piao, Eur. J. Med. Chem. 45 (2010) 5739 –5743.

1583 –1587.

Article Doi

Polymeric complexes - LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds

DOI: 10.1016/j.molliq.2015.12.010

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