Molecular docking, potentiometric and thermodynamic studies of azo rhodanines

Article abstract of DOI:10.1016/j.molliq.2016.05.058

Molecular docking was used to predict the binding between azo rhodanine derivatives (HL_n) with the receptor prostate cancer 2Q7K hormone. The values of dissociation constant (pK^H) of azo rhodanine derivatives (HL_n) are correlated with Hammett's constant (σ^R). The proton-ligand dissociation constant of azo rhodanine derivatives (HL_n) and metal-ligand stability constants of their complexes with metal ions (Mn²⁺, Co²⁺, Ni²⁺ and Cu²⁺) have been determined potentiometrically in 0.1 M KCl and 40% (by volume) ethanol-water mixture and at 298, 308 and 318 K. The stability constants of the formed complexes increase with the order Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺. The effect of temperature was studied and the corresponding thermodynamic parameters (ΔG, ΔH and ΔS) were derived and discussed. The dissociation process of the ligands is non-spontaneous, endothermic and entropically unfavorable. The formation of the metal complexes has been found to be spontaneous, endothermic and entropically favorable.

Full text of DOI:10.1016/j.molliq.2016.05.058

Journal of Molecular Liquids 221 (2016) 51–60
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
Molecular docking, potentiometric and thermodynamic studies of
azo rhodanines
A.Z. El-Sonbati a, I.M. El-Deen b, M.A. El-Bindary c,
⁎
a
Chemistry Department, Faculty of Science, University of Damietta, Damietta 34517, Egypt
b
c
Chemistry Department, Faculty of Science, University of Port Said, Port Said, Egypt
Engineering Chemistry Department, Higher Institute for Engineering and Technology, Damietta, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 May 2016
Received in revised form 18 May 2016
Accepted 19 May 2016
Available online 21 May 2016
Molecular docking was used to predict the binding between azo rhodanine derivatives (HLn) with the receptor
prostate cancer 2Q7K hormone. The values of dissociation constant (pKH) of azo rhodanine derivatives (HLn)
are correlated with Hammett's constant (σR). The proton-ligand dissociation constant of azo rhodanine deriva-
tives (HLn) and metal-ligand stability constants of their complexes with metal ions (Mn2+, Co2+, Ni2+ and
Cu2+) have been determined potentiometrically in 0.1 M KCl and 40% (by volume) ethanol–water mixture
and at 298, 308 and 318 K. The stability constants of the formed complexes increase with the order Mn2+ b Co2+-
b Ni2+ b Cu2+. The effect of temperature was studied and the corresponding thermodynamic parameters (ΔG,
ΔH and ΔS) were derived and discussed. The dissociation process of the ligands is non-spontaneous, endothermic
and entropically unfavorable. The formation of the metal complexes has been found to be spontaneous, endo-
thermic and entropically favorable.
Keywords:
Azo rhodanine
Molecular docking
Potentiometry
Thermodynamics
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
rate of the breast cancer in India is expected to be more than 90,000
in the coming years and over 50,000 women die each year.
Rhodanine is one of the privileged scaffolds in drug discovery. Bio-
logical effects of various rhodanine derivatives have been reviewed by
Tomasic and Masic [1,2]. Our research group has studied derivatives of
rhodanine as potential antifungal and antimycobacterial agents [3,4]. Ef-
forts have been made to carry out detailed studies to synthesize and elu-
cidate the structural and electronic properties of novel families of
complexes with rhodanine derivatives as a novel chelating bidentate
azodye models [5]. The high stable potential of rhodanine derivative
complexes in different oxidation states increased the application of
these compounds in a wide range [6]. Azodyes play an important role
in inorganic chemistry and form stable complexes with most transition
metal ions [7]. The behavior of azodye complexes has attracted the at-
tention of the bioinorganic chemists, since a number of these complexes
are recognized to serve as models for biologically important species [8].
Breast cancer now represents the most common female malignancy in
both the developing and developed world, and is the primary cause of
death among women globally [9]. Cancer can be described as the uncon-
trolled growth of abnormal cells [10]. At global level, it accounted for
more than 1.6 million new cases in 2010. The incidence or prevalence
In the present paper, we discuss the binding ability of azo rhodanine
derivatives (HLn) with the receptor prostate cancer 2Q7K hormone. The
dissociation constant of azo rhodanine derivatives (HLn) and the stabil-
ity constants for their complexes with Mn2+, Co2+, Ni2+ and Cu2+ were
obtained by potentiometric studies. Furthermore, the corresponding
thermodynamic functions of dissociation and stability constants are de-
rived and discussed.
2. Experimental
2.1. Measurements
Elemental microanalyses of the separated ligands for C, H, and N
were determined on Automatic Analyzer CHNS Vario ELIII, Germany.
IR spectra (KBr discs, 4000–400 cm−1) by Jasco-4100 spectrophotome-
ter. The pH measurements were carried out using VWR Scientific Instru-
ments Model 8000 pH-meter accurate to 0.01 units. The pH–meter
readings in the non–aqueous medium were corrected [11]. The elec-
trode system was calibrated according to the method of Irving et al.
[12]. The temperature was controlled to within 0.05 K by circulating
thermostated water (Neslab 2 RTE 220) through the outer jacket of
the vessel. All titrations have been carried out between pH 3.5–12.0
and under nitrogen atmosphere.
⁎
Corresponding author.
E-mail address: m.a_bindary@yahoo.com (M.A. El-Bindary).
http://dx.doi.org/10.1016/j.molliq.2016.05.058
0167-7322/© 2016 Elsevier B.V. All rights reserved.

52
A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
In the study simulates the actual docking process in which the li-
2.4. pH metric titration
gand–protein pair-wise interaction energies are calculated using
Docking Server [13]. The MMFF94 Force field was for used energy min-
imization of ligand molecule using Docking Server. Gasteiger partial
charges were added to the ligand atoms. Non-polar hydrogen atoms
were merged and rotatable bonds were defined. Docking calculations
were carried out on 2Q7K hormone protein model. Essential hydrogen
atoms, Kollman united atom type charges and solvation parameters
were added with the aid of AutoDock tools [14]. Affinity (grid) maps
of 20 × 20 × 20 Å grid points and 0.375 Å spacing were generated
using the Autogrid program [15]. AutoDock parameter set- and dis-
tance-dependent dielectric functions were used in the calculation of
the van der Waals and the electrostatic terms, respectively.
The experimental procedure involved the titration of the following
solutions (total volume = 50 ml) against a standard CO2-free
(0.002 M) NaOH solution. The following mixtures (i)–(iii) were pre-
pared and titrated potentiometrically at 298 K against standard
0.002 M NaOH in a 40% (by volume) ethanol–water mixture:
i) 5 cm3 0.001 M HCl + 5 cm3 1 M KCl + 20 cm3 ethanol.
ii) 5 cm3 0.001 M HCl + 5 cm3 1 M KCl + 15 cm3 ethanol + 5 cm3
0.00 l M ligand.
iii) 5 cm3 0.001 M HCl + 5 cm3 l M KCl + 15 cm3 ethanol + 5 cm3
0.001 M ligand + 10 cm3 0.0001 M metal chloride.
2.2. Materials
For each mixture, the volume was made up to 50 cm3 with bidistilled
water before the titration. These titrations were repeated for tempera-
tures of 308 K and 318 K.
The ligands solutions (0.001 M) were prepared by dissolving an ac-
curately weighed amount of the solid in ethanol. Metal ion solutions
(0.0001 M) were prepared from analar metal chlorides in bidistilled
water and standardized with EDTA [16]. Solutions of 0.001 M HCl and
1 M KCl were also prepared in bidistilled water. A carbonate-free sodi-
um hydroxide solution in 40% (by volume) ethanol–water mixture
was used as titrant and standardized against analar oxalic acid [17].
All chemicals used in this investigation were chemically pure grade
derived from BDH. They include chlorides of Mn2+, Co2+, Ni2+ and
Cu2+, sodium hydroxide (NaOH) (97%), sodium nitrite (NaNO2)
(97%), hydrochloric acid (HCl) (37%); purchased from BDH. The stan-
dard chemicals aniline (99%) and 4-alkylanilines (alkyl: OCH3 (99%)
and NO2 (98%)) purchased from Aldrich, Fluka and Merck and were
used without any further purification. Water used was bidistilled
water; distillation process was carried out using both of condensation
process and ion exchange technique.
2.3. Preparation of azo rhodanines (HL1−3
)
3. Results and discussion
The ligands (HL1–3) were prepared previously [3,5] by coupling of 2-
thioxo-4-thiazolidinone with aniline or its derivatives. 25 cm3 of dis-
tilled water containing 0.01 mol concentrated hydrochloric acid was
added to aniline (0.01 mol) or p-derivatives (–OCH3 and –NO2). To the
resulting mixture was cooled to 0 °C, a solution of 0.01 mol of sodium
nitrite in 20 ml of water was added dropwise. The formed diazonium
chloride was consecutively coupled with an alkaline solution of
0.01 mol 2-thioxo-4-thiazolidinone, in 10 ml of pyridine. The colored
precipitate, which formed immediately, was filtered through sintered
glass crucible, washed several times with water. The crude products
were purified by recrystallization from hot ethanol and then dried in a
vacuum desiccator over CaCl2. The purity of the compounds was
checked by elemental analyses [3].
3.1. Molecular docking
Molecular docking aims to achieve an optimized conformation for
both the protein and drug with relative orientation between them
such that the free energy of the overall system is minimized [18,19].
The data of molecular docking between ligands (HL1–3) and receptor
prostate cancer 2Q7K hormone showed a possible arrangement be-
tween ligands (HL1–3) and receptor (2Q7K). On a docking study show-
ing a favorable interaction between ligands (HL1–3) and the receptor
prostate cancer 2Q7K hormone and the calculated of energy are listed
in Table 1 and Fig. 1. 2D plot curves of docking with ligands (HL1–3
)
are shown in Fig. 2. This interaction could activate apoptosis in cancer
cells energy of interactions with ligands (HL1–3). Binding energies are
most widely used mode of measuring binding affinity of ligands. Thus,
decrease in binding energy due to mutation will increase the binding af-
finity of the ligands (HL1–3) towards the receptor. The characteristic fea-
ture of ligands (HL1–3) represent in presence of several active sites
available for hydrogen bonding.
The resulting formed ligands are:
HL1: 4-hydroxy-5-(4-methoxyphenylazo)thiazole-2(3H)-thione.
HL2: 4-hydroxy-5-(phenylazo)thiazole-2(3H)-thione.
3.2. Potentiometric studies
The interaction of a metal with an electron donor atom of li-
gands (HLn) is usually followed by the release of H+. Alkaline po-
tentiometric titrations are based on the detection of the protons
released upon complexation. The main advantage of this technique,
compared to other methods is that from the titration curves it is
possible to follow complexation continuously as a function of pH
and to detect exactly at which pH complexation takes place. Fur-
thermore, it is possible to calculate the dissociation constants and
HL3: 4-hydroxy-5-(4-nitrophenylazo)thiazole-2(3H)-thione.
Table 1
Energy values obtained in docking calculations of ligands (HL1−3) with the receptor of prostate cancer 2Q7K hormone.
Compound Est. free energy of binding
(kCal/mol)
Est. inhibition constant
(Ki) (μM)
vdW + bond + desolv energy
(kCal/mol)
Electrostatic energy
(kCal/mol)
Total intercooled energy
(kCal/mol)
Interact
surface
HL1
HL2
HL3
−6.90
−6.33
−5.69
67.98
22.93
8.73
−7.67
−7.25
−6.72
−0.10
−0.06
−0.06
−7.76
−7.31
−6.78
490.428
479.373
445.858

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
53
Fig. 1. The ligands (HLn) (green in (A) and blue in (B)) in interaction with the receptor of prostate cancer 2Q7K hormone. (For interpretation of the references to color in this figure legend,
the reader is referred to the web version of this article). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
the stability constants of its complexes from the potentiometric ti-
tration. The average number of the protons associated with ligands
(HLn) at different pH values, nA, was calculated from the titration
curves of the acid in the absence and presence of ligands (HLn).
Applying Eq. (1):
ðV1−V2ÞðNꢁ þ EꢁÞ
nA ¼ Y ꢀ
ð1Þ
ðVꢁ−V1ÞTCꢁ
L

54
A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
Fig. 2. 2D plot of interaction between ligands (HL1–3) and the receptor of prostate cancer 2Q7K hormone.

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
55
Table 2
Thermodynamic functions for the dissociation of (HL1−3) in 40% (by volume) ethanol-water mixture and 0.1 M KCl at different temperatures.
Compound
Temperature
(K)
Dissociation constant
Gibbs energy
Enthalpy change
Entropy change
(kJ mol−1
)
(kJ mol−1
)
(J mol−1 K−1
)
pKH
ΔG
ΔH
−ΔS
HL1
HL2
HL3
298
308
318
298
308
318
298
308
318
8.36
8.22
8.09
8.06
7.91
7.75
7.48
7.34
7.21
47.70
48.48
49.26
45.99
46.65
47.19
42.68
43.29
43.90
77.87
77.86
77.87
60.02
60.21
60.01
61.02
61.01
61.02
24.50
28.10
24.50
Table 3
Stepwise stability constants for complexes of (HL1−3) in 40% (by volume) ethanol-water mixtures and 0.1 M KCl at different temperatures.
Compound
Mn+
298 K
logK1
308 K
logK1
318 K
logK1
logK2
logK2
logK2
HL1
Mn2+
Co2+
Ni2+
Cu2+
Mn2+
Co2+
Ni2+
Cu2+
Mn2+
Co2+
Ni2+
Cu2+
7.53
7.71
7.80
8.07
7.35
7.49
7.60
7.84
6.93
7.10
7.19
7.42
5.45
5.63
5.73
5.98
5.22
5.39
5.52
5.77
4.92
5.05
5.14
5.38
7.68
7.86
7.94
8.22
7.48
7.62
7.74
7.99
7.08
7.26
7.34
7.60
5.60
5.78
5.87
6.12
5.36
5.54
5.66
5.92
5.06
5.21
5.29
5.53
7.83
8.01
8.10
8.37
7.63
7.76
7.89
8.15
7.23
7.41
7.49
7.75
5.75
5.93
6.03
6.25
5.50
5.69
5.80
6.08
5.19
5.35
5.43
5.68
HL2
HL3
Table 4
Thermodynamic functions for ML and ML2 complexes of (HL1−3) in 40% (by volume) ethanol-water mixture and 0.1 M KCl.
Comp.
Mn+
T/K
Gibbs energy
Enthalpy change
Entropy change
(kJ mol−1
)
(kJ mol−1
)
(J mol−1 K−1
)
−ΔG1
−ΔG2
ΔH1
ΔH2
ΔS1
ΔS2
HL1
Mn2+
Co2+
Ni2+
Cu2+
Mn2+
Co2+
Ni2+
Cu2+
Mn2+
Co2+
Ni2+
Cu2+
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
298
308
318
42.97
45.29
47.68
43.99
46.35
48.77
44.51
46.82
49.32
46.05
48.48
50.96
41.94
44.11
46.46
42.74
44.94
47.25
43.36
45.65
48.04
44.73
47.12
49.62
39.54
41.75
44.02
40.51
42.81
45.12
41.03
43.29
45.61
42.34
44.82
47.19
31.10
33.02
35.01
32.12
34.09
36.11
32.69
34.62
36.72
34.12
36.09
38.05
29.78
31.61
33.49
30.75
32.67
34.65
31.50
33.38
35.31
32.92
34.91
37.02
28.07
29.84
31.60
28.81
30.73
32.58
29.33
31.20
33.06
30.70
32.61
34.58
235.48
235.39
235.48
238.92
238.83
238.93
240.58
240.30
240.59
245.82
245.73
245.82
225.88
225.60
225.88
225.55
225.37
225.55
233.74
233.56
233.75
244.42
244.23
244.43
223.99
223.90
223.99
230.32
230.32
230.32
228.97
228.88
228.97
242.60
242.78
242.60
195.65
195.56
195.65
199.10
199.01
199.10
200.95
200.67
200.95
196.70
196.71
196.70
185.16
185.08
185.16
194.50
194.41
194.50
190.91
190.82
190.91
204.79
204.60
204.79
176.41
176.42
176.41
188.06
188.16
188.06
186.71
186.71
186.71
194.31
194.22
194.31
27.21
27.21
27.19
27.21
25.37
24.48
26.29
28.10
27.21
28.12
27.21
29.96
27.21
27.21
27.19
24.50
25.39
27.21
25.39
28.10
24.50
27.23
26.31
27.21
HL2
HL3

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A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
Fig. 3. The relation between stability constants (log K1 and log K2) and atomic number of
metal complexes at 298 K for ligands (HL1–3).
Fig. 4. The relation between stability constants (log K1 and log K2) and atomic number of
metal complexes at 308 K for ligands (HL1–3).
where Y is the number of available protons in ligands (HLn) (Y =
1) and V1 and V2 are the volumes of alkali required to reach the
same pH on the titration curve of hydrochloric acid and reagent, re-
spectively, V° is the initial volume (50 cm3) of the mixture, TC°L is
the total concentration of the reagent, N° is the normality of so-
dium hydroxide solution and E° is the initial concentration of the
free acid. Thus, the formation curves (nA vs. pH) for the proton-
ligand systems were constructed and found to extend between
0 and 1 in the nA scale. This means that ligands (HLn) have ion-
izable proton (the enolized hydrogen ion of –OH group of the
rhodanine moiety, pKH). Different computational methods were
applied to evaluate the dissociation constant [20]. Three replicate
titrations were performed; the average values obtained are listed
in Table 2. The completely protonated form of the ligands (HLn)
has dissociable proton, that dissociates in the measurable pH
range. The deprotonation of the o-hydroxy group most probably
results in the formation of stable intramolecular H–bonding
with the nitrogen of the azo group. Such an interaction decreases
the dissociation process of ligands (HLn), i.e. increases the pKH
value [21,22].
The formation curves for the metal complexes were obtained by
plotting the average number of ligands attached per metal ion (nA) vs.
the free ligands exponent (pL), according to Irving and Rossotti [23].

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
57
where TC°M is the total concentration of the metal ion present in the so-
lution, βHn is the overall proton-reagent stability constant. V1, V2 and V3
are the volumes of alkali required to reach the same pH on the titration
curves of hydrochloric acid, organic ligand and complex, respectively.
These curves were analyzed and the successive metal-ligand stability
constants were determined using different computational methods
[24,25]. The values of the stability constants (log K1 and log K2) are
given in Table 3. The following general remarks can be pointed out:
(i) The maximum value of nA was ~2 indicating the formation of 1:1
and 1:2 (metal:ligand) complexes [3].
(ii) The metal ion solution used in the present study was very dilute
(2 × 10−5 M), hence there was no possibility of formation of
polynuclear complexes [26,27].
(iii) The metal titration curves were displaced to the right-hand side
of the ligand titration curves along the volume axis, indicating
proton release upon complex formation of the metal ion with
the ligand. The large decrease in pH for the metal titration curves
relative to ligand titration curves point to the formation of strong
metal complexes [28].
(iv) For the same ligand at constant temperature, the stability of the
chelates increases in the order: Mn2+ b Co2+ b Ni2+ b Cu2+
[29]. This order largely reflects that the stability of Cu2+ com-
plexes is considerably larger than those of other metals of the
3d series. Under the influence of both the polarizing ability of
the metal ion and the ligand field [30,31] Cu2+ will receive
some extra stabilization due to tetragonal distortion of octahe-
dral symmetry in its complexes. The greater stability of Cu2+
complexes is produced by the well known Jahn–Teller effect [32].
3.3. Effect of temperature
Stepwise dissociation constants for the ligand (HL) and the stepwise
stability constants of their complexes with Mn2+, Co2+, Ni2+ and Cu2+
have been calculated at 298, 308 and 318 K. The corresponding thermo-
dynamic parameters (ΔG, ΔH and ΔS) were evaluated. The dissociation
constant (pKH) for ligands (HLn) as well as the stability constants of
their complexes with Mn2+, Co2+, Ni2+ and Cu2+ have been evaluated
at 298, 308 and 318 K, and given in Tables 2 and 4, respectively. The en-
thalpy (ΔH) for the dissociation and complexation process was calculat-
ed from the slope of the plot pKH or log K vs. 1/T using the graphical
representation of van't Hoff Eqs. (4) and (5):
ΔG ¼ −2:303RT logK ¼ ΔH–TΔS
ð4Þ
or
logK ¼ ð−ΔH=2:303 RÞð1=TÞ þ ðΔS=2:303 RÞ
ð5Þ
where R is the gas constant = 8.314 J mol−1 K−1, K is the dissociation
constant for the ligand stability and T is the temperature (K). From the
values of free energy change (ΔG) and enthalpy (ΔH), can deduce the
entropy ΔS using the well known Eqs. 4 and 6:
Fig. 5. The relation between stability constants (log K1 and log K2) and atomic number of
metal complexes at 318 K for ligands (HL1–3).
The average number of the reagent molecules attached per metal ion,nA
, and free ligands exponent, pL, can be calculated using Eqs. (2) and (3):
ΔS ¼ ðΔH−GÞ=T
ð6Þ
ðV3−V2ÞðNꢁ þ EꢁÞ
All thermodynamic parameters of the dissociation process of ligands
(HLn) are recorded in Table 2. From these results the following conclu-
sions can be made:
n ¼
ð2Þ
ð3Þ
ðVꢁ−V2Þ ꢂ nA ꢂ TCꢁ
M
and
(i) The pKH values decrease with increasing temperature, i.e. the
acidity of the ligand increases.
(ii) A positive value of ΔH indicates that the process is endothermic.
(iii) A large positive value of ΔG indicates that the dissociation pro-
cess is not spontaneous [33].
!
n
n¼J
X
1
βnH
ꢀ
ꢁ
Hþ
VꢁþV3
n¼o
pL ¼ log10
ꢂ
TCꢁL−n ꢂ TCꢁ
Vꢁ
M

58
A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
(iv) A negative value of ΔS is obtained due to the increased order as a
(ii) The stability constants (log K1 and log K2) of Mn2+, Co2+, Ni2+
and Cu2+ complexes were increased with increasing atomic
number in the order Cu2+ N Ni2+ N Co2+ N Mn2+ at different
temperatures (298, 308 and 318 K) as shown in Figs. 3–5.
(iii) The negative value of ΔG for the complexation process suggests
the spontaneous nature of such processes.
(iv) The values of free energy change (ΔG1 and ΔG2) of formed com-
plexes were increased with increasing atomic number at differ-
ent temperatures (298, 308 and 318 K) as shown in Figs. 6–8.
(v) The ΔH values are positive, meaning that these processes are en-
dothermic and favorable at higher temperature.
result of the solvation process.
All the thermodynamic parameters of the stepwise stability con-
stants of complexes of the ligands are recorded in Table 4. It is known
that the divalent metal ions exist in solution as octahedral hydrated spe-
cies [25] and the obtained values of ΔH and ΔS can then be considered
as the sum of two contributions: (a) release of H2O molecules, and (b)
metal-ligand bond formation. Examination of these values shows that:
(i) The stability constants (log K1 and log K2) for HLn complexes in-
crease with increasing temperature, i.e. its stability constants in-
crease with increasing temperature [4].
Fig. 6. The relation between free energy change (ΔG1 and ΔG2) and atomic number of
metal complexes at 298 K for ligands (HL1–3).
Fig. 7. The relation between free energy change (ΔG1 and ΔG2) and atomic number of
metal complexes at 308 K for ligands (HL1–3).

A.Z. El-Sonbati et al. / Journal of Molecular Liquids 221 (2016) 51–60
59
Fig. 9. Correlation of pKH with Hammett's substituent constant values (σR) at 298, 308 and
318 K for ligands (HL1–3).
phenyl moiety have a direct influence on the pKH values of the in-
vestigated compounds affording a maximum resonance via delo-
calization of its π-system.
4. Conclusion
Molecular docking was used to predict the binding between azo
rhodanine ligands with the receptor of prostate cancer 2Q7K hormone.
The proton-ligand dissociation constant of HLn and metal-ligand stabil-
ity constants of its complexes with metal ions (Mn2+, Co2+, Ni2+ and
Cu2+) at different temperatures were determined. The stability con-
stants of theformed complexes are increases in the order of Cu2+ N Ni2+-
N Co2+ N Mn2+. The dissociation process is non-spontaneous,
endothermic and entropically unfavorable. The formation of the metal
complexes has been found to be spontaneous, endothermic and entro-
pically favorable.
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