Biological and catalytic potential of sustainable low and high valent metal-Schiff base sulfonate salicylidene pincer complexes

Article abstract of DOI:10.1039/c9ra06816c

ONO-Pincer Schiff base salicylidene (HSaln ligand) complexes with VO²⁺, UO₂²⁺, MoO₂²⁺ and Mn²⁺ ions (MSaln complexes = VOSaln, UO₂Saln, MoO₂Saln and MnSaln, respectively) were synthesized and fully characterized by different physico-chemical tools. The VOSaln complex was further treated with 1,10-phenanthroline which afforded a new VO-complex (VOSaln-Ph). All complexes and their ligands, as eco-friendly reagents, were explored for their biological potential as antibacterial and antifungal agents. Reactivity of MSaln complexes against the tested pathogen strains exhibited a remarkable inhibitory effect compared to the coordinated ligand (HSaln) and applicable standard drugs. Moreover, the MSaln complex-DNA interaction was investigated by ultraviolet-visible spectroscopy, viscosity and gel electrophoresis techniques affording binding strengths in the order: UO₂Saln > MnSaln > MoO₂Saln > VOSaln-Ph > VOSaln. Additionally, the biological potential of the investigated compounds was further explored by molecular docking to illustrate the nature of the drug-DNA interactions. All MSaln complexes show respectable anti-proliferative potential as anticancer agents against selected human carcinoma cell lines. Aside from the biological activities these complexes (MSaln complexes) were also investigated for catalytic efficiency in the Suzuki-Miyaura cross-coupling system of phenylboronic acid with 2-bromopyridine in water, sustainably. The results indicated that the MnSaln catalyst performed well with high yield. The catalytic potential of MnSaln was compared in water, water-ionic liquid mixtures and ionic liquids.

Full text of DOI:10.1039/c9ra06816c

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Biological and catalytic potential of sustainable low
and high valent metal-Schiff base sulfonate
salicylidene pincer complexes†
Cite this: RSC Adv., 2019, 9, 34311
Mohamed Shaker S. Adam, *ab Omar M. El-Hady and Farman Ullahc
b
2+
2+
2+
2
2+
ONO-Pincer Schiff base salicylidene (HSaln ligand) complexes with VO , UO
2
, MoO
and Mn ions
(
MSaln complexes ¼ VOSaln, UO Saln, MoO Saln and MnSaln, respectively) were synthesized and fully
2
2
characterized by different physico-chemical tools. The VOSaln complex was further treated with 1,10-
phenanthroline which afforded a new VO-complex (VOSaln-Ph). All complexes and their ligands, as eco-
friendly reagents, were explored for their biological potential as antibacterial and antifungal agents.
Reactivity of MSaln complexes against the tested pathogen strains exhibited a remarkable inhibitory
effect compared to the coordinated ligand (HSaln) and applicable standard drugs. Moreover, the MSaln
complex-DNA interaction was investigated by ultraviolet-visible spectroscopy, viscosity and gel
2 2
electrophoresis techniques affording binding strengths in the order: UO Saln > MnSaln > MoO Saln >
VOSaln-Ph > VOSaln. Additionally, the biological potential of the investigated compounds was further
explored by molecular docking to illustrate the nature of the drug–DNA interactions. All MSaln
complexes show respectable anti-proliferative potential as anticancer agents against selected human
carcinoma cell lines. Aside from the biological activities these complexes (MSaln complexes) were also
investigated for catalytic efficiency in the Suzuki–Miyaura cross-coupling system of phenylboronic acid
with 2-bromopyridine in water, sustainably. The results indicated that the MnSaln catalyst performed well
with high yield. The catalytic potential of MnSaln was compared in water, water–ionic liquid mixtures
and ionic liquids.
Received 28th August 2019
Accepted 19th October 2019
DOI: 10.1039/c9ra06816c
rsc.li/rsc-advances
15,20
and DNA interacting reagents, as reported in the literature.
Some biological studies of vanadyl Schiff bases and other metal
Schiff bases, as azomethine or imine derivatives (–CH]N–), are Schiff base complexes have been reported recently by Rudbari
1
. Introduction
21
22
the most famous chelating ligands for complexation with et al. and by Shah et al., respectively.
transition metal ions of different oxidation states to afford
Cancer remains the main cause of death globally. The
1,2
highly stable metal pincer complexes. Wide applicability of M- International Agency for Research on Cancer (IARC) recently
Schiff base pincer chelates could be observed in many areas, e.g. reported that 7.6 million deaths globally were due to cancer
biological (antibacterial, antifungal, antiviral and anti- with millions of new cases per year being reported worldwide.
3
–5
6
7–11
inammatory effectiveness),
pharmaceutical, catalysts,
With continues growth of cancer patients globally pushing the
12
13
sensors, and organic photovoltaic materials. The indis- scientic community to discover new drugs with minimum side
pensable function of the metal ion and its charge in the Schiff effects. Many research groups are focused to overcome the
base complexes could help to measure their potential biologi- massive chemotherapeutic drugs side effects, as metal-complex
14,15
14,20
cally, e.g. with DNA cleavage.
or dioxy-vanadium Schiff base chelates
The structural features of oxy- drugs.
Hence, many reported works highlighted on the
16,17
are of interest bio- research for the development of various metal Schiff base
18
19
logically, as an inhibitor of protein-tyrosine phosphatase 1B
chelates as anticancer agents along with the study of their side
23
effects. DNA binding and the anticancer reactivity on transi-
tion metal Schiff base complexes have been evaluated recently
24,25
a
Department of Chemistry, College of Science, King Faisal University, P. O. Box 380, Al and reported in details, e.g. by Abdel-Rahman et al.
Hofuf, Al Ahsa 31982, Saudi Arabia. E-mail: madam@kfu.edu.sa; shakeradam61@
The high reactivity of M-Schiff base pincer chelates towards
yahoo.com
DNA play pivotal role for such progressing in nucleic acids
biochemically as foot-printing reagents, models for limited
b
Chemistry Department, Faculty of Science, Sohag University, Sohag-82534, Egypt
c
Department of Chemistry, Winnipeg University, 515 Portage Avenue, Winnipeg,
26
enzymes and therapeutic use as drugs. Currently, there are
many published literatures reporting the anticancer activities of
various transition metal Schiff base complexes, Abd El-Halim
Manitoba, R3B 2E9 Canada
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c9ra06816c
1
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34311

View Article Online
RSC Advances
Paper
2
7
2+
2+
2+
2+
2+
2+
2+
et al. studied the Cr , Fe , Mn , Cu , Cd , Co and Ni - protocol, which was obtained from the reaction of 1.0 equiva-
,10-phenanthroline–Schiff base complex as high antimicrobial lent of anthranilic acid in ethanol with 1.0 equivalent of 5-
1
41
and anticancer reagents. The antimicrobial and anticancer salicylaldehyde-sodium sulfonate sustainably. HSaln ligand
3
+
2+
3+
2+
2+
2+
2+
2+
2+
activity of Bi , Pb , Cr , Cu , Cd , Ba , Ni , Fe , Nd and was fully characterized by the most valuable spectroscopic
2
+
28
Sn –Schiff base complexes are studied by Sheng et al. and techniques (Tables 1 and 2, which are supported by attached
Sharaby et al. They investigated the microbial and anticancer les in the ESI†). Moreover, the coordination features of HSaln
potentials of sulfonamide imine and mixed coordinated ligand ligand were investigated by complexation with M ions in an
complexes with glycine spectroscopically. Mahmoud et al. aqueous media. Hence, a new series of complexes with metal
published many biological studies of bidentate Schiff base ions of high and low oxidation states, i.e. with VO , MoO
ferrocene metal complexes derived from amino acids.
29
2
+
41
2
+
2+
2
,
3
0–33
2+
2+
UO2 and Mn ions as MSaln complexes were synthesized. All
Manganese and some other metal chelates of polymeric Schiff MSaln complexes were prepared under sustainable conditions,
base ligand were studied as antimicrobial reagents by Rasool i.e. in H O, with 1 : 1 ligand metal ions ratio afforded VOSaln,
2
3
4
and Hasnain. Moreover, the coordination chemical behaviour MoO
2
Saln, UO
VOSaln in ethanol was further treated with 1,10-phenanthroline
towards ONO-tridentate imine ligand, i.e. 2-[(2-hydroxy- (1 : 1 ratio) provided a new complex (VOSaln-Ph) by substitution
2
Saln and MnSaln, respectively (Scheme 1).
2
+
2+
2+
2+
2+
and biological activity of Zn , Cu , Ni , Co and Mn
43
2
naphthalen-1-ylmethylene)-amino]-benzoic acid, as a non- of the two coordinated H O molecules as observed elsewhere.
water-soluble ligand was investigated and reported by Refat To avoid oxidation of Mn ions to Mn ion in the synthetic
et al. Zayed et al. presented the coordination chemistry, bio- pathway of MnSlan, the reaction carried out under N
logical efficiency and molecular docking studies of various atmosphere.
2
+
3+
35
2
46
36–39
1
13
transition metal complex.
All previous biological reported
All M-complexes (MSaln) were characterized H-NMR, C-
studies assigned important results for the high potential of M- NMR, infrared, electronic and mass spectra, elemental anal-
Schiff base pincer chelates towards bacteria, fungi and cancers, yses, thermogravimetric analyses (TGA), measurements of
as well as, high DNA-cleavages.
conductance, and magnetic susceptibilities were utilized to
C–C, C–O and C–N cross-coupling protocols are one of the estimate the complexation mode of those metal ions with HSaln
44
most famous catalytic organic approaches for various organic ligand. They are fairly soluble in water due to the presence of
40
+
ꢀ
syntheses. High oxidation state metal complexes are widely a polar group (Na SO –) and in DMSO as high coordinated
3
known as catalysts for oxidation and oxygenation processes, e.g. solvent. They are sparingly soluble in acetone, methanol and
2
+
2+
2+
2+
+
20,41–43
MoO2 , WO2 , UO2 , VO and VO species.
Low valent acetonitrile. C, H and N percentages values of the elemental
2
+
metal complexes, e.g. M ions, are highly active catalysts for analysis, as recorded in Table 1, are very close to the proposed
most of the cross couplings
4
4,45
0
in order to generate M active structure of all MSaln complexes, with very little difference up to
2
+
catalysts. For example, Mn -pincer chelates display an effective ꢁ0.4% referring to high purity of all MSaln complexes.
1
13
role as homogeneous catalysts for most versatile and prevalent
H and C NMR spectra of HSaln ligand are reported, pre-
46
41
recent synthetic devises under sustainable conditions. Sus- sented in the ESI† and compared to those complexes, i.e.
tainably, the incorporated sodium sulfonate group to the MoO Saln, and UO Saln. NMR spectra of MoO Saln and UO -
2
2
2
2
synthesized Schiff base ligand improves its reactivity and the Saln were measured in DMSO-d6 at room temperature and
41
corresponding metal complexes under green conditions. Ionic presented in Fig. S5–S9 in the ESI.†
1
liquids, as imidazolium- and pyridinium-based liquids are of
In H NMR spectra, the disappearance of a singlet at
for many C–C biaryls 10.26 ppm which belongs to –OH group of the HSaln ligand
syntheses, e.g. Suzuki–Miyaura cross-coupling protocols. in MoO Saln and UO Saln is the indication for the de-
In the present work, we present the synthesis, biological protonation of hydroxyl and formation of desired
47–50
51–54
interest as solvents
or co-catalysts
2
2
4
1
activities and catalytic performance of the polar chelate pincer complexes.
Similarly, the distinguished –OH of the
complexes, synthesized from the water-soluble Schiff base carboxylic group in HSaln ligand within deprotonation
2
+
2+
2+
pincer ligand with various metal ions, i.e. MoO , UO2 and coordinated to M ion. The characteristic broad singlet
2
2
+
2+
VO and Mn ions. Their biological reactivity was investigated signal of the Schiff base (–CH]N–) was shied from
as antimicrobial and anticancer agents. Moreover, DNA inter- 10.82 ppm (HSaln ligand) to 11.00 and 9.34 ppm in MoO Saln
action with the prepared complexes was explored and sup- and UO Saln respectively, by the coordination of nitrogen
ported by the molecular docking studies. We also report the lone pair in the Schiff base moiety, as observed elsewhere
2
2
5
5
1
3
catalytic behavior with the high valent metal ions in their Schiff (Scheme 1). From C NMR spectral scans, the signal of the
2
+
2+
2+
base complex catalysts, i.e. MoO
2
, UO
2
and VO ions, as well Schiff base group (–CH]N–) was clearly observed when
2
+
2+
2+
as, Mn -complex in Suzuki–Miyaura cross-coupling processes shied aer coordination to MoO2 and UO2 ions from
of arylboronic acid with different aryl halides, representatively. 192.20 ppm to 163.41 and 161.20 ppm in MoO Saln and
2
UO Saln, respectively. Moreover, the carboxylate C]O group
2
4
1
was little shied from 169.22 ppm
74.11 ppm in MoO Saln and UO Saln, respectively.
The electronic transitions in the aqueous solution of all
ONO-Tridentate polar pincer ligand (HSaln ligand) was MSaln complexes were recorded at lmax, nm, with calculating
to 169.92 and
2
. Results and discussion
1
2
2
2.1. Synthesis and structure estimation
ꢀ
1
ꢀ1
prepared according to the well-known condensation reaction the molar absorptivity, 3max, mol cm , in Table 1 (Fig. 1). It
34312 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Table 1 Distinctive elemental analysis, melting point, color, electronic and mass spectra (electrospray ionization mass spectra) HSaln ligand and
ꢀ5
ꢀ3
ꢃ
its MSaln complexes at [compound] ¼ 1 ꢂ 10 mol dm in H
2
O at 25 C
Elemental analysis
found%, (calc.%)
Electronic transition spectra
Mass spectra (m/z)
MW
Compound (g mol ) C
Mp
( C) (nm)
l
max
3
max
ꢀ1
ꢃ
ꢀ1
ꢀ1
+
+
H
N
Color
(mol cm ) Assign.
[M + Na ]
[M ꢀ Na ]
HSaln
ligand
VOSaln
343.29
444.24
49.25
(48.98)
38.11
3.08
3.81
Pale yellow 164 325, 256
5894, 12 436 n / p*, p
/ p*
5073, 8211, LM-CT,
(2.94) (4.08)
2.98 3.07
(2.72) (3.15)
Dark green 288 395, 310,
249
465, 467, 468,
469, 471
419, 420, 421,
422, 423
(37.85)
12 099
n / p*,
p / p*
LM-CT,
VOSaln-
606.43
629.31
51.76
(51.50)
27.10
3.02
7.36
Brownish >300 376, 322
4863, 8956
610, 611, 612
565, 566
Ph.$H
2
O
(2.99) (6.93) green
1.94 2.12 Deep
(1.60) (2.23) yellow
n / p*
UO Saln
2
304 388, 299,
271, 238
3418, 5874, LM-CT,
6693, 10 112 n / p*,
p / p*,
604, 605, 606,
607
651, 652, 653
(26.72)
p / p*
MnSaln
250.25
37.47
37.35)
3.44
(3.13) (3.11)
2.86
Brown
294 416, 329,
284
3015, 7488, LM-CT,
471, 473, 474
4645, 465
425, 427, 428
510, 511, 512
(
18 894
n / p*,
p / p*
MoO
2
Saln 287.24
34.66
34.51)
1.77
(2.07) (2.87)
2.53
Orange
>300 449, 320,
262
2322, 6152, LM-CT,
(
15 749
n / p*,
p / p*
was found some specic transitions of p / p* and n / p* in n / p* transition (Fig. 1). In the colored area of the visible
the UV region for HSaln ligand (256 and 325 nm, respectively) region, all MSaln complexes assign broad bands at 395, 376,
with little shi aer bonding to the metal ions, MSaln 388, 449 and 416 nm for probably the M-LCT transitions for
complexes, to be 249 and 310 nm for VOSaln, 262 and 320 for VOSaln, VOSaln-Ph, UO
2
Saln, MnSaln, MoO
Saln, respectively. tively. No detection for the d / d transition in any of the
VOSaln-Ph shows only one band at 322 nm for n / p* complexes could be observed even at higher concentration of
2
Saln, respec-
5
6
MnSaln and 284 and 329 nm for MoO
2
ꢀ
3
transition. UO Saln displays two high energy bands at 238 MSaln (1.0 ꢂ 10
mmol). This result suggested that the
2
and 271 nm for p / p* and an additional band at 299 nm for metal complexes are in high spin-state.
ꢀ
1
Table 2 Specific infrared spectral assignments ( nꢀ , cm ), distinguished magnetic moments (m) and molar conductivity values (L
m
) of HSaln ligand
ꢀ
3
ꢀ3
a
and its MSaln complexes ([compound] ¼ 1 ꢂ 10 mol dm ) in DMSO and DMF at ambient temperature
Compound
Group
HSaln ligand
VOSaln
VOSaln-Ph
3368(m br)
UO
2
Saln
MoO
2
Saln
MnSaln
O–H(water)
3420(m br),
3403(w),
3135(w br)
3352(w br),
3296(m br)
3308(m br),
3233(m br)
3342(m br)
O–H
C–Har
C]O
3401(w br)
3058(w)
1601(m)
1494(w)
1419(w)
1577(w)
1236(m)
1382(w)
1103(m)
3062(w)
1597(s)
1451(m)
1422(m)
1518(s)
1175(s)
1340(m)
1142(m)
962(m)
722(w)
608(m)
140
3080(w)
1585(s)
1455(m)
1410(w)
1531(s)
1154(m)
1372(m)
1108(m)
964(m)
743(w)
608(m)
130
3074(w br)
1589(m)
1470 (m)
1409 (w)
1559(m)
1159(m)
1362(m)
1099(m)
900(m)
723(m)
666(w)
117
3124(w)
1693(m)
1478(w)
1403(m)
1612(m)
1162(s)
1378(w)
1112(s)
919(w)
749(w)
583(m)
125
1643(m)
1455(m)
C–O(phenolic)
C–O(carboxylic)
C]N(azomethine)
C–N
1589(m)
1164(s)
1402(m)
1107(s)
ꢀ
S–O
S]O
M]O
M–O
M–N
751(w)
601(w)
142
ꢀ1
2
ꢀ1
L
m
(U cm mol
)
DMSO
DMF
139
158
—
154
149
142
151
163
m (B.M.)
2.79
2.24
—
—
5.74
a
br (broad), s (strong), m (moderate), w (weak), ar (aromatic CH), alph (aliphatic CH).
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34313

View Article Online
RSC Advances
Paper
Scheme 1 Diagrammatic scheme for the synthesis of MSaln complexes from HSaln ligand.
The distinct infrared spectral bands values for HSaln ligand in the ESI.† From Table 2, a broad spectral band of HSaln ligand
2
+
ꢀ1
are listed in Table 2, which also affected by the presence of M
at 3401 cm , which corresponded to the hydroxy-phenolic
ions. The IR spectrum of all compounds is given in Fig. S10–S15, group and/or the hydroxyl-carboxylic group, completely
Fig.
1 Electronic spectral scans of HSaln ligand and its MSaln Fig. 2 Continuous variation plots for the stoichiometric molar ratios in
ꢀ5
ꢀ3
ꢀ4
complexes, [compound] ¼ 1 ꢂ 10 mol dm in an aqueous medium MSaln complexes in an aqueous- medium at [MSaln] ¼ 1 ꢂ 10 mol
ꢀ3
ꢃ
at room temperature.
dm and 25 C.
34314 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Table 3 Stability constants and thermodynamic parameters of MSaln complexes [complex] ¼ 1 ꢂ 10ꢀ4 mol dmꢀ3
ꢃ
8
ꢀ1
ꢀ1
ꢀ1
ꢀ1 ꢀ1
Complex
VOSaln
T ( C)
K
f
ꢂ 10 (L mol
)
ꢀD
f
G (kJ mol
)
ꢀD
f
H (kJ mol
)
ꢀD
f
S (J mol
K
)
20
49.23
38.31
22.93
14.45
7.58
54.36
54.67
54.29
54.00
53.20
54.46
54.83
54.89
54.58
54.05
54.80
55.03
55.13
55.33
54.19
54.80
55.03
55.13
55.33
54.19
54.93
55.60
56.13
56.59
56.81
6.99
86.27
72.85
72.15
72.20
32.52
2
3
3
4
5
0
5
0
VOSaln
20
51.22
40.99
29.08
18.12
10.50
54.77
48.75
40.12
35.65
27.49
59.02
44.41
32.01
24.26
11.08
62.18
55.82
47.62
39.65
30.31
2.38
2
3
3
4
5
0
5
0
MoO
2
Saln
20
2.01
2
3
3
4
5
0
5
0
MnSaln
20
2.02
2
3
3
4
5
0
5
0
UO
2
Saln
20
11.50
2
3
3
4
5
0
5
0
4
1
disappeared in all MSaln complexes. Other broad vibrating
Mass spectra of HSaln ligand was reported previously,
ꢀ1
bands appeared at the same area at 3342 and 3420 cm for whereas, that measurement for VOSaln, VOSaln-Ph, UO
2
Saln,
MoO Saln and MnSaln was supported by Fig. S16–S20 in the
for MoO Saln, and 3233 and 3308 cm for MnSaln due to the ESI.† All MSaln complexes show characteristic base peaks for
ꢀ
1
ꢀ1
VOSaln, 3135 and 3403 cm for UO Saln, 3296 and 3352 cm
2
2
ꢀ1
2
+
presence of the coordinated H O ligands. The presence of the the complex as [M + Na ] and as complex anion without sodium
2
+
–
OH band of VOSaln-Ph is due to the H
2
1
O molecule in the cation [M ꢀ Na ]. Evaluation of H
2
O in the M-complexes as
ꢀ
crystal lattice of the complex at 3368 cm . The characteristic coordinated or crystalline molecules could be established by
band of Schiff base group –C]N– (1577 cm ) is also highly TGA. The TGA results as mass lose percentages of the repre-
shied aer bonding to M ions to be 1518, 1531, 1559, 1612 sented complexes are shown in Fig. S21 (ESI†), those all
ꢀ
1
2
+
ꢀ
1
and 1559 cm for VOSaln, VOSaln-Ph, UO
2 2
Saln, MoO Saln and
MnSaln, respectively. Particularly, the single bond of C–N at
ꢀ1
1
236 cm
complexation to be 1175, 1154, 1159, 1162 and 1164 cm for
VOSaln, VOSaln-Ph, UO Saln, MoO Saln and MnSaln, respec-
for HSaln ligand was also inuenced by the
ꢀ
1
2
2
tively. Moreover, the vibrational spectra of the C–O single bond
of the phenolic and carboxylic groups was shied due to the
ꢀ
ꢀ1
1
complexation from 1494 and 1419 cm
to be 1451 and
ꢀ
1
1
422 cm for VOSaln, 1455 and 1410 cm for VOSaln-Ph, 1470
ꢀ1
ꢀ1
and 1409 cm for UO Saln, 1478 and 1403 cm for MoO Saln,
and 1455 cm for MnSaln (Table 2). The coordination feature
of the carboxylate group was similar to that reported by Ziegler
2003). New stretching bands were explored in the infrared
spectra of the novel M-complexes at 962, 964, 900 and 919 cm
2
2
ꢀ1
55
(
ꢀ1
2 2
for VOSaln, VOSaln-Ph, UO Saln and MoO Saln, resulted from
the bond stretching of M]O. Furthermore, the coordination
bonds could be found for the M–O and M–N bonding at 722 and
ꢀ
1
6
6
08 for VOSaln, 743 and 608 cm for VOSaln-Ph, 723 and
ꢀ1
ꢀ1
66 cm for UO Saln, 749 and 583 cm for MoO Saln, and 751
and 601 cm for MnSaln, respectively.
2
2
ꢀ
1
55
Fig. 3 Dissociation plot of MSaln complexes in an aqueous media at
various pHs.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34315

View Article Online
RSC Advances
Paper
Table 4 Antimicrobial bioassay of HSaln ligand and MSaln complexes versus various strains of bacteria
Inhibition zone (mm)
Compound
Serratia marcescens (ꢀve)
Escherichia coli (ꢀve)
Staphylococcus aureus (+ve)
ꢀ1
Conc. (mg mL
)
10
20
10
20
10
20
HSaln ligand
VOSaln
VOSaln-Ph
MnSaln
7 ꢁ 0.23
10 ꢁ 0.33
34 ꢁ 0.16
30 ꢁ 0.27
36 ꢁ 0.24
33 ꢁ 0.12
38 ꢁ 0.27
40 ꢁ 0.33
5 ꢁ 0.21
14 ꢁ 0.43
12 ꢁ 0.24
15 ꢁ 0.14
13 ꢁ 0.04
16 ꢁ 0.07
17 ꢁ 0.15
8 ꢁ 0.15
9 ꢁ 0.18
14 ꢁ 0.24
40 ꢁ 0.12
36 ꢁ 0.17
42 ꢁ 0.19
38 ꢁ 0.17
44 ꢁ 0.25
46 ꢁ 0.11
15 ꢁ 0.17
13 ꢁ 0.21
16 ꢁ 0.18
14 ꢁ 0.11
17 ꢁ 0.05
19 ꢁ 0.71
33 ꢁ 0.13
29 ꢁ 0.21
34 ꢁ 0.27
32 ꢁ 0.19
35 ꢁ 0.19
37 ꢁ 0.72
18 ꢁ 0.14
16 ꢁ 0.11
19 ꢁ 0.16
17 ꢁ 0.05
20 ꢁ 0.11
22 ꢁ 0.93
MoO
UO Saln
Gentamycin
2
Saln
2
1
complexes have various numbers of diagnostic H
2
O molecules
For V(IV) ion with d electronic conguration, the expected
in the lattice or in the coordination sphere. VOSaln, MnSaln, magnetism is agreed with the derived value for VOSaln and
MoO Saln and UO Saln complexes have mass lose percentage VOSaln-Ph. The observed for manganese complex with oxida-
2
2
ꢃ
5
2+
only in the temperature range from 180 to 230 C (Dm
2.4, 3.2 and 2.5%), which are almost convenient with the unpaired electrons) due to the magnetic moment value. The
¼ 7.9, tion state of +2, a d ion of Mn could exist as high spin (5
exp.
1
2
calculated mass lose percentages of H O in the coordination reported magnetic values in Table 2 illustrate that there is no
sphere (Dmcal. ¼ 8.1, 12.0, 3.7 and 2.8%, respectively). Hence, possibility for interaction between the central metal ions in
20
2 2
VOSaln, MnSaln, MoO Saln and UO Saln have two, three, one their chelates.
and one coordinated water molecules, respectively. On the other
hand, VOSaln-Ph has no observed mass lose percentage in that
range, however, it has mass lose percentage in the temperature
range from 100 to 130 C, which is corresponded to the crystal
lattice molecules. The mass lose percentage is, Dmexp., 3.1%
2
.2. Stability and thermodynamic properties
ꢃ
The stability of all MSaln complexes was determined by spec-
trophotometric continuous variation with appreciation of the
stoichiometric molar ratios of MSaln complexes,
referred to that 1 equivalent of M ion formed a complex with 1
equivalent of HSaln ligand, as presented in Fig. 2. The stability
constants K
and tabulated in Table 3. K
MSaln complexes are quite stable in the aqueous media,
moreover, UO Saln is the most stable complex and VOSaln is
the less stable one. The stability order could be presented for all
MSaln as follow: MoO Saln > UO Saln > MnSaln > VOSaln-Ph >
VOSaln complex.
20,58
which
2
referring to the presence of one H O molecule in the lattice per
2
+
one molecule of VOSaln-Ph complex (Dmcal.
approximately).
¼
2.9%,
20,41
f
of MSaln complexes were deduced from eqn (1)
m
Conductance values, L , of all complexes in DMSO or DMF
f
magnitudes elucidated that all
were measured and listed in Table 2, which informed us about
the polar nature of studied compounds and the number of ions
57
in the solution. The high conductivity of HSaln ligand and all
MSaln complexes refers to that they are polar compounds with,
particularly, two counter ions in their solutions, because of the
2
2
2
ꢀ
+
presence of –SO
3
and Na ions. Magnetic features of the binary
Kf values could be applied to estimate the thermodynamic
MSaln complexes proposed that VOSaln, VOSaln-Ph and
MnSaln complexes have high spin via para-magnetic properties
as 2.79, 2.24 and 5.74 B.M., respectively.
parameters values for all MSaln complexes from eqn (2) (Gibb's–
Helmholtz equation as a function of the temperature reciprocal
in Kelvin, 1/T) (Fig. S22, ESI†). The thermodynamic parameters,
Table 5 Antimicrobial bioassay of HSaln ligand and MSaln complexes versus various strains of fungi
Inhibition zone (mm)
Compound
Candida albicans
Aspergillus avus
Trichophyton rubrum
ꢀ1
Conc. (mg mL
)
10
20
10
20
10
20
HSaln ligand
VOSaln
VOSaln-Ph
MnSaln
4 ꢁ 0.14
22 ꢁ 0.13
18 ꢁ 0.17
21 ꢁ 0.11
19 ꢁ 0.10
23 ꢁ 0.14
24 ꢁ 0.55
7 ꢁ 0.16
3 ꢁ 0.21
13 ꢁ 0.18
9 ꢁ 0.17
8 ꢁ 0.34
5 ꢁ 0.10
14 ꢁ 0.41
10 ꢁ 0.16
13 ꢁ 0.23
12 ꢁ 0.05
15 ꢁ 0.13
16 ꢁ 0.49
11 ꢁ 0.07
29 ꢁ 0.17
25 ꢁ 0.15
28 ꢁ 0.13
27 ꢁ 0.12
30 ꢁ 0.23
31 ꢁ 0.88
34 ꢁ 0.37
29 ꢁ 0.12
33 ꢁ 0.27
32 ꢁ 0.12
36 ꢁ 0.17
37 ꢁ 0.62
23 ꢁ 0.18
19 ꢁ 0.12
22 ꢁ 0.22
21 ꢁ 0.09
24 ꢁ 0.21
25 ꢁ 0.90
12 ꢁ 0.27
11 ꢁ 0.10
14 ꢁ 0.11
14 ꢁ 0.71
MoO
UO Saln
Fluconazole
2
Saln
2
34316 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Table 6 MIC, minimum inhibitory zone, for antimicrobial assay of HSaln ligand and MSaln complexes
ꢀ
1
Minimum inhibition concentration (MIC) mg mL
Compound
S. Marcescens
E. coli
S. aureus
C. albicans
A. avus
T. rubrum
HSaln ligand
VOSaln
VOSaln-Ph
MnSaln
6.25
3.25
4.75
3.75
4.50
2.75
7.50
2.75
4.25
3.25
3.75
2.50
5.50
2.25
3.75
2.75
3.25
1.75
5.75
4.25
3.00
2.75
4.00
2.25
8.50
5.25
3.75
4.25
4.75
3.50
6.75
5.00
3.50
4.00
4.50
3.00
2
MoO Saln
UO Saln
2
D
f
H and D
Gibb's free energy values (D
values. So, the spontaneous complexation between HSaln 5).
f
S, could be derived from eqn (2). Conclusively, the chelates MSaln complexes had higher antimicrobial potential
f
G) were determined as negative compared to their chelating agent, HSaln ligand (Tables 4 and
20,24
For the antibacterial action, the M-chelates with different
ligand and M ion under given conditions is the result of the central metal ions showed moderate to high potential when
negative D G. Moreover, the negative values of D H illustrate the compared with standard antibiotic (gentamycin). The strong
2
+
25
f
f
exothermic nature of the complexation reaction and the strong active Schiff base group (–CH]N–) improved the antimicrobial
bonding between HSaln ligand and the central metal ion in all potential of all studied reagents, furthermore, the addition of
57
MSaln complexes.
this group increased the potential of MSaln complexes relative
The high stability pH range (3.1–9.7) for the new MSaln to the HSaln ligand. One explanation for this comes from the
59,60
chelates and typical dissociation curves were displayed by pH- chelation theory effect.
The high positive charge and the
plot, i.e. absorbance values versus different pH at lmax of each strong coordination capability of the central metal ion are
M-chelate, as demonstrated in (Fig. 3). This explained that the considered to play an observable role in improving the anti-
consistency of the metal chelate could be greatly stabilized by microbial action of the HSaln ligand. This effect was seen in the
Schiff base ligands within complexation. Hence, proper pH current data as the highest antimicrobial potential was seen
extent for different applicability for the novel MSaln derives with UO Saln and MnSaln complexes. UO Saln could increase
2
2
61
from pH ¼ 3.1 to pH ¼ 10.0. The proposed formula for the metal its coordination number as a 4f element and also, MnSaln,
chelates is identied by correlation among the existence of which has the highest number of the labile coordinated solvent
62
magnetic measurements, molar conductance, elemental anal- molecules. Additionally, the p-electron delocalized rings over
ysis, electronic spectra and infrared spectra.
the antimicrobial reagents and their lipophilic character could
enhance their action and effect. The high solubility of the
current compounds resulted from the bonded p-sodium sulfo-
2.3. Biological studies
14
nate group and their conductivity could be the reason for their
2
.3.1. Antimicrobial potential. The results of the antimi- valuable antimicrobial action. The activity index percentages, A,
crobial potential of the HSaln ligand and all the MSaln of the antibacterial and antifungal potential of HSaln ligand
complexes are presented in Tables 4 and 5. As can be observed and MSaln complexes, which are calculated according to eqn (3)
in the resulted data, there was signicant antimicrobial and recorded in Tables S1 and S2 (ESI†). The antimicrobial
potential of the current compounds against three different capability of our studied compounds could also be measured by
strains of bacteria and against a strain of fungi. All metal pincer activity index percentages.
Fig. 4 Histogram showing MIC values for antimicrobial activity of HSaln ligand and MSaln complexes.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34317

View Article Online
RSC Advances
Paper
a
Table 7 UV-visible spectroscopic parameters for the DNA–MSaln complexes interaction
Chromism
%
5
s
ꢀ1
Compound
MnSaln
l
max free (nm)
l
max bound (nm)
Dn
Type
Hypo
Hypo
K
b
ꢂ 10
b
DG kJ mol
251
03
252
240
325
252
271
288
394
252
271
288
252
325
386
238
251
269
286
352
376
11
78
0
0
1
2
1
1
1
0
5
0
1
1
1
2
2
4.00
8.65
3.80
5.91
9.23
39.76
2.14
1.59
3.03
1.65
23.93
44.62
2.20
2.10
2.10
2.58
7.22
19.05
3.92
2.60
ꢀ31.20
ꢀ30.20
4
2
MoO Saln
2
2
3
251
2
2
252
3
3
71
89
96
VOSaln-Ph
Hypo
Hypo
Hypo
1.35
6.50
1.70
ꢀ29.27
ꢀ32.43
ꢀ29.18
72
89
UO
2
Saln
20
86
VOSaln
239
2
2
2
3
3
52
70
88
54
82
6
a
ꢀ1
3
b
K , mol dm .
Table 6 presents the minimum inhibitory concentration cell membrane permeability of these microbes. The lower
MIC) potential of HSaln ligand and MSaln complexes versus activity of complexes as compared to others may be attributed to
(
both the bacteria and fungi strains. The MIC values of the HSaln the low lipid solubility of these complexes. If this is the case, the
ligand and its MSaln complexes versus the chosen bacterial and metal ion may not be able to reach its site of action within the
fungi strains indicate that the HSaln ligand has the lowest cell. Chelation itself plays a signicant role in determining
antimicrobial potential compared to the metal pincer chelates antibacterial behavior of the MSaln complexes but concurrently
2
+
(
Fig. 4). This suggests that the central M ion plays an essential factors such as solubility, size, dipole moment, coordinating
24
role in the antimicrobial potential of the studied compounds.
sites, redox potential of metal ion, solubility, bond length
The variation in the activity of the metal complexes against between metal and the ligand, geometry of complexes, steric,
the different microbes possibly results from a difference in the pharmacokinetic, concentration and hydrophobicity also have
ribosomes of the various microbial cells or a difference in the substantial inuence on the antibacterial activity. Given that
the tested complexes were more active against Gram (+ve) than
Fig. 5 The UV-vis spectral scans of UO
absence and presence of DNA with interval time 15 min.
2
Saln in the buffer solution in Fig. 6 The UV-vis spectral scans of MnSaln complex in absence and
presence of DNA with interval time 15 min.
34318 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Fig. 7 The effect of MSaln complexes amounts on the CT-DNA
ꢃ
relative viscosity at [DNA] ¼ 0.5 mM and 25 C.
Gram (ꢀve) bacteria, it may be concluded that the antibacterial
activity of the compounds is related to the cell wall structure of
the bacteria.
Fig. 8 The interaction of the studied reagents with CT-DNA was
studied by agarose gel electrophoresis; where lane 1: DNA ladder; lane
2
.3.2. CT-DNA binding
.3.2.1. Electronic spectroscopy. The nature of bonding of
MSaln complexes with DNA was estimated with electronic spec-
2
2: CT-DNA + VOSaln-Ph; lane 3: CT- DNA + VOSaln; lane 4: CT-DNA
+
UO Saln; lane 5: CT-DNA + MnSaln; lane 6: CT-DNA + MoO Saln.
2
2
14,20,24,25
trophotometrically.
There are three reported types of
bonding with DNA; the rst is an interaction of two grooved DNA
double spiral, the second one is an intercalation of the arranged
native DNA base pairs, and the third one is an electrostatic
interaction with the nucleic sugar-phosphate negative charge
which is parallel to the external double spiral DNA without any
(
20,63
selectivity).
The DNA–MSaln complexes interaction was
2
Scheme 2 Type of interaction of DNA–UO Saln complex via intercalation and/or coordinated water replacement bindings.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34319

View Article Online
RSC Advances
Paper
Fig. 9 IC50 values of HSaln ligand and MSaln complexes against human colon carcinoma cells (HCT-116 cell line), hepatic cellular carcinoma
cells (HepG-2) and breast carcinoma cells (MCF-7) cell line.
conrmed in buffered solutions of DNA by the electronic tran- Both UO Saln and MnSaln complexes have the highest inter-
2
sition spectral values (Table 7), which provided the hypochromic action potential with DNA (Table 7). There are two additional
character of that interaction and increase of the high p / p* factors might account for their high DNA interaction. For the
interaction transition (Fig. 5). The nature of p / p* transition UO
could be a result of the nitrogenous DNA base pairs and the a higher coordination potential than transition metal ions (M )
2
Saln complex, the central metal ion as 4f element has
2
+
2
+
delocalized aromatic system in the coordinated ligand in MSaln in MSaln complexes. Usually the UO
2
ion can form complexes
14,64
complexes.
UO Saln complex shows observable enhancement with more than 6 coordination number, as observed else-
2
55
of the p / p* transition band, with increased energy due to the where. This could increase the strength of the bonding inter-
DNA and UO Saln complex interaction (Fig. 5). Hypochromism is action of the UO Saln complex with DNA more than the other
2
2
the consequence of interaction between the coordinated ligand MSaln complexes, via the intercalative mode (Fig. 5). Moreover,
orbital and the DNA base pairs orbitals via intercalation mode. MnSaln complex has the highest number of the labile coordi-
65
2
Hence, there is a red shi in the visible region of the transition nated solvent molecules, i.e. three H O, and could have pro-
band for the interaction of DNA and MnSaln complex (from the gressed reactivity towards DNA binding more than the other
maximum values at 449 to 368 nm; Fig. 6) with a hypochromatic MSaln complexes within replacement. This could be suggested
14
character due to the decreasing of the maximum absorption.
by the DNA interaction reactivity of VOSaln and VOSaln-Ph
The measured value of the DNA–MSaln complexes interac- complexes in which VOSaln is more reactive than VOSaln-Ph
tion is the binding constant. These spectrophotometric complex. The secondary coordinated ligand, liable solvent
parameters (K ) were derived from eqn (4) and are recorded in water in VOSaln and 1,10-phenanthroline in VOSaln-Ph
b
Table 7. Kb is a measure of the strength of the DNA–MSaln complex, increases the DNA interaction in case of water and
complexes binding interaction. The binding order of DNA with reduces in case of 1,10-phenanthroline. Particularly, 1,10-phe-
MSaln complexes is as follows: UO
MoO Saln > VOSaln-Ph complex. From Table 7, the chromism water, which would increase the VOSaln-Ph complex could be
type and values for the DNA–MSaln complexes interacting bound to DNA via interaction more than that of the coordinated
2
Saln > MnSaln > VOSaln > nanthroline is a stronger coordinated ligand compared to
2
2
7,66
s
binding and Dn, which points out to the characteristic absorp- water.
b
The conclusion of the DG values supports strongly
14
tion band shi for MSaln complexes due to its DNA-interaction. the replacement mechanism.
s
The Gibbs' free energy values DGb are presented as negative
values, which could be the measurement of the binding
strength of DNA–MSaln complexes (Table 7). The most negative
Table 8 The molecular docking values for HSaln ligand and its MSaln
complexes
s
ꢀ1
DG
b
is for UO
2
Saln as ꢀ32.43 kJ mol and ꢀ31.20, ꢀ30.20,
ꢀ
1
ꢀ
29.27 and ꢀ29.18 kJ mol for MnSaln, MoO
2
Saln, VOSaln
Compound
k
b
S
E
conf.
and VOSaln-Ph complexes, respectively. The variation in the
Gibbs' free energy values between the MSaln complexes is due
to the nature of the central metal ion.
HSaln ligand
VOSaln
VOSaln-Ph
1.09
2.67
2.05
4.33
3.91
4.76
ꢀ2.2441
ꢀ4.1794
ꢀ4.0727
ꢀ4.4996
ꢀ4.3615
ꢀ5.1609
ꢀ100.1223
ꢀ247.6790
ꢀ206.5358
ꢀ794.3703
ꢀ551.9431
ꢀ975.1266
Besides what is mentioned above about the nature of
binding between DNA and MSaln complexes, the structural MnSaln
feature of MSaln complexes could have an important impact on
the variation between the studied complexes in such binding.
2
MoO Saln
UO Saln
2
34320 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Fig. 10 Molecular docking results of HSaln ligand and its MSaln complexes.
2
.3.2.2. Viscosity measurements. The measured viscosities of complexes (calculated according to eqn (7) and (8); as reported
DNA with and without MSaln complexes can provide informa- previously for different transition metal-Schiff base
14,20,24
tion on the bonding features between DNA and MSaln complexes
). Ethidium bromide (EB) is known to bind to
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34321

View Article Online
RSC Advances
Paper
Scheme 3 C–C cross-coupling system of phenylboronic acid and 2-bromopyridine catalyzed by MSaln complexes.
65
DNA and cause an increase in the DNA viscosity (Fig. 7).
MSaln complexes are reported in Table S3.† The cytotoxicity
Similarly, the interaction of DNA with increasing concentra- data indicates that all MSaln complexes have remarkable anti-
ꢀ
1
tions of MSaln complexes in the reaction media can cause cancer potential, with IC50 values between 17.70–35.60 mg mL
ꢀ
1
increases in the DNA viscosity, i.e. increased DNA–MSaln for HCT-116 cell, from 9.60 to 24.90 mg mL for Hep-G2 cell and
67
ꢀ1
complexes binding to intercalation sites in DNA.
between 11.60–28.90 mg mL for MCF-7 cell (Fig. 9). MSaln
From Fig. 7, the distinction between the reacted MSaln chelates were found to be more potent anticancer reagents
2
+
complexes depends on the type of M ion. UO Saln complex compared to their coordinated ligand, HSaln, and compared to
2
shows the highest increase in the viscosity for a given increase the standard anticancer reagent, i.e. vinblastine drug. The bio-
in concentration. This means that UO Saln complex forms the logical effectiveness of MSaln complexes compared to HSaln
2
strongest complex with DNA in our studied series of MSaln ligand may be attributed to the presence of a central metal ion,
complexes. The order of the viscosity measurements of the the nature of which is considered in Tweed's chelation
2
5,68
studied MSaln complexes were: UO
2
Saln > MnSaln > MoO
2
2
Saln theory.
The Lewis acid character of the metal ions (with its
6
+
6+
>
VOSaln > VOSaln-Ph complex. This indicates that the UO
Saln positive charge, especially for the high valent metals, U , Mo ,
4
+
complex could be binding to DNA via intercalation and coor-
V
ions) enhances the acidic character of the coordinated Schiff
dinated water replacement binding, as shown in Scheme 2.
base ligand. Those strengths their hydrogen binding to DNA
2
.3.2.3. Gel electrophoresis. Another important tool to probe resulting in a remarkable enhancement of their biological
24
14,24
the DNA–MSaln complexes is the gel electrophoresis. When action towards cancers.
comparing the DNA gels before and aer mixing of DNA with cells, the UO Saln complex has the highest biological potential
MSaln complexes, it could be seen that the staining intensity of as an anticancer agent. This observation is supported by all the
the gel was slightly reduced for all instances when the DNA was above results involving the UO Saln–DNA interaction and the
mixed with the MSaln complexes. With UO Saln and MnSaln antimicrobial tests. It could be concluded that the uranyl Schiff
complexes, in particular, the DNA staining intensity dis- base complex is the best antimicrobial and anticancer reagent.
With all types of colon carcinoma
2
2
2
14
appeared, possibly due to strong DNA cleavage (Fig. 8).
2.3.4. Molecular docking. Molecular docking aids in
Therefore, it is possible that the effects of these complexes on understanding the nature of DNA–HSaln ligand and DNA–
69
the pathogenic organism growth could be attributed to the MSaln complex interactions, which are essential for medical
genomic interaction of the current MSaln complexes. proposes. The current compounds were investigated using
.3.3. Anticancer potential. The anticancer inuence of Molecular Operating Environment (MOE) package version
2
HSaln ligand and its M-complexes was examined on Hep-G2 cell 2018.01 to derive the potential binding mode and energy. The
line (hepatocellular carcinoma), MCF-7 cell line (breast carci-
noma) and HCT-116 cell line (colon carcinoma) within
ꢀ1
concentrations ranging from 0 to 120 mg mL . The anticancer Table 10 MnSaln complex catalyzed the Suzuki–Miyaura cross
coupling system of phenylboronic acid and 2-bromopyridine in
various ionic liquids
potential of the current compounds was measured by gener-
ating IC50 values (eqn (9)). The IC50 values for HSaln ligand and
a
b
Entry
Ionic liquid
Yield (%)
c
1
2
3
4
5
6
7
8
[bmim][Tf
[bmim][Tf
2
N]
90
94
87
91
84
89
88
90
Table 9 Suzuki–Miyaura cross coupling system of phenylboronic acid
N] : H
2
O (3 : 1)
a
2
and 2-bromopyridine catalyzed by MSaln complexes
d
[emim][Tf
[emim][Tf
2
N]
2
N] : H
2
O (3 : 1)
b
Catalyst
Yield (%)
e
[omim][Tf
[omim][Tf
2
N]
2
N] : H
2
O (3 : 1)
No catalyst
VOSaln
VOSaln-Ph
0
f
[bmim][PF
[bmim][PF
6
]
51
39
49
88
50
6
] : H
2
O (3 : 1)
a
MoO
2
Saln
Phenylboronic acid (1.0 mmol), 2-bromopyridine (1.1 mmol), base
CO , 2.0 mmol) and catalyst (0.10 mmol) in 10 mL solvent or
.7 mL solvent : 3.3 mL H
percentages of the C–C product analyzed by GC-MS. 1-Butyl-3-
MnSaln
UO Saln
2
(K
6
2
3
ꢃ
b
2
O (1 : 1), at 100 C for 6 hours. c The yield
a
d
Phenylboronic acid (1.0 mmol), 2-bromopyridine (1.1 mmol), base methylimidazolium bis(triuoromethylsulfonyl)imide.
1-Ethyl-3-
1-Octyl-3-
1-Butyl-3-
ꢃ
e
f
(K
2
CO
3
, 2.0 mmol) and catalyst (0.10 mmol) in 10 mL H
2
O, at 100
C
methylimidazolium bis(triuoromethylsulfonyl)imide.
b
for 6 hours. The yield percentages of the C–C product analyzed by methylimidazolium bis(triuoromethylsulfonyl)imide.
GC-MS. methylimidazolium hexauorophosphate.
34322 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
binding energy (Econf.) and the nal score function (S), obtained VOSaln-Ph complex, the p-hydrogen interaction could be
from the MOE for the docked compounds were listed in Table 8. observed due to the presence of coordinated 1,10-phenanthro-
Molecular docking showed the hydrogen bonding interactions line moiety, with lipophilic character.
between HSaln ligand and B-DNA, provides the binding energy
2.3.5. Catalytic potential in Suzuki–Miyaura cross-
value and hydrophobic character of the interaction. The couplings. From the literatures survey, it came to our notice that
molecular docking studies showed the hydrophobic character the catalytic efficiency of oxy- and dioxy-high oxidation state
2
+
2+
2+
and hydrogen bonding of HSaln ligand– and MSaln complexes– transition metal ions, e.g. MoO
2
, VO and UO
2
ions, are not
DNA, as displayed in Fig. 10. The docked highest binding score enough investigated in different cross-coupling reactions.
ꢀ
1
and binding energy were ꢀ5.1609 and ꢀ975.1266 kcal mol for Therefore, it gave us motivation to examine the catalytic suffi-
UO Saln complex, respectively, with p-hydrogen interaction ciency of MSaln chelates in standard Suzuki–Miyaura cross-
2
without remarking of hydrogen bonds presence with DNA.
coupling of phenylboronic acid with 2-bromopyridine
The molecular docking studies showed that the p-polar (Scheme 3). At the optimal reaction condition, i.e. 6 hours
ꢃ
substituent (p-sodium sulfonate group) of chelating ligand in heating at 100 C, the % yield of the cross-coupling product was
HSaln ligand had no feasibility in binding between DNA and monitored by GC-MS which displayed in Table 9. From the
HSaln ligand or MSaln complexes (Fig. 10), due to their lip- obtained results, it shows that the MnSaln complex offered
ophobic characters. Furthermore, the functional groups of the comparatively higher catalytic potential (provided 88% yield).
phenolic or carboxylic hydroxyl group in HSaln ligand are All other high valent metal complexes, i.e. UO Saln, MoO Saln,
2 2
seemed to be the most reactive in binding with the DNA. For the VOSaln and VOSaln-Ph complexes afforded moderate to low
Table 11 MnSaln complexes catalyzed the Suzuki–Miyaura C–C coupling reaction of phenylboronic acid and various aryl halides
a
b
Entry
Aryl halide
Product
Yield (%)
1
85
2
3
91
72
4
94
5
6
90
89
7
87
8
74
a
ꢃ
b
Phenylboronic acid (1.0 mmol), aryl halide (1.1 mmol), base (K
2
CO
3
, 2.0 mmol) and catalyst (0.10 mmol) in 10 mL H
2
O, at 100 C for 6 hours. The
yield percentages of the C–C product analyzed by GC-MS.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34323

View Article Online
RSC Advances
Paper
percentages amount of the C–C product under the same extended conjugation or electron-withdrawing substituent
sustainable conditions (50, 49, 61 and 39%, respectively), as (–NO ) on aryl halide reduced the % yield of the cross-coupling
2
shown in Table 9. Potassium carbonate is the most favored base product s (entries 7 and 8).
for the C–C catalytic process, due to the strong interaction
2
between the catalyst, solvent (H O) and the base to enhance the
catalytic potential. The solubility of organic substrates is
always an issue when only water is used as a solvent in the cross- The complexation of the high and low valent metal ions (VO ,
3
. Conclusions
70
2
+
2
+
2+
2+
coupling reactions, though it helps to dissolve the polar inor- UO
2
, MoO
2
and Mn ions) with ONO-tridentate pincer
ganic reagents. As a result, it reduces the catalytic performance Schiff base salicylidene sodium sulfonate (HSaln ligand) ligand
7
1,72
of the catalyst.
Therefore most of cross coupling processes provided water-soluble M-pincer chelates (MSaln complexes ¼
were processed in organic solvents or in mixture of organic VOSaln, VOSaln-Ph, UO Saln, MoO Saln and MnSaln
solvent with water. Water is the most favored solvent (green complexes, respectively), which was fully characterized by
solvent) for such catalytic systems, but not suitable for the various spectroscopic tools. Spectrophotometrically, the
solubility and miscibility of the organic substrates.
Aer optimizing the reaction condition, all catalysts were for MSaln complexes, UO
tested under the same reaction condition. When the metal- the most stable complexes. Biologically, the antibacterial and
complex catalyst was excluded from the reaction mixture no antifungal potentials of MSaln complexes showed that UO Saln
2
2
71
70
stability constants were derived by continuous variation method
2
Saln and MoO Saln are found to be
2
2
cross-coupling product was observed. The higher catalytic and MoO Saln complexes have the highest activity against some
2
activity of the MnSaln complex could be resulted from the easily bacterial and fungal strains and the rest showed reasonably
2
+
0
73
reduction of Mn to Mn in the catalytic cycle. The higher good potential. With selected human carcinoma cell lines, the
stability of high valent metal complexes could resist the anticancer effects of HSaln ligand and all MSaln complexes
reduction step in order to prepare the active catalyst of the low manifest high interaction. The interaction between MSaln
38,74
oxidation state in the catalytic cycle.
Although, Mn- complexes and CT-DNA with the type of binding was studied by
complexes presented in high oxidation state Mn(V)-Salen as an UV-vis spectroscopy, viscosities and gel electrophoresis. All
effective catalyst for polymerization of furan derivatives MSaln complexes exhibited good interaction with CT-DNA. The
75
awarding poly(silylether)s, the high valent M-complexes two complexes (UO Saln and MnSaln complexes) demonstrated
2
(
UO Saln, MoO Saln, VOSaln and VOSaln-Ph complexes) as strong interaction with CT-DNA. The biological potential of
2 2
catalysts for such coupling systems did not promote the cata- MSaln complexes was studied by the molecular docking to
lytic process. Most probably the low efficiency of UO Saln, illustrate the active site of the drug and the type of bonding
MoO Saln, VOSaln and VOSaln-Ph complexes could be due to between complex and DNA. As anticancer agents, all MSaln
the doubly bonded oxygen to the metal ion (Mo , U and V
2
2
6
+
6+
4+
complexes and ligand showed remarkable anti-proliferative
ion), forming the high stable oxidation state of those metal ions, potential. The catalytic efficiency of MSaln complexes was
preventing its reduction to lower oxidation state in such cross- studied in Suzuki–Miyaura cross-coupling reaction of phenyl-
40,76
coupling mechanisms.
boronic acid with 2-bromopyridine in sustainable conditions.
As shown in Table 10, by using ionic liquids, the yield of the The result showed that the MnSaln complex has the highest
desired product was signicantly improved in contrast to that in catalytic potential, providing the highest % yield of the cross-
water catalyzed by MnSaln complex catalyst (entries 1, 3, 5 and coupling product. Moreover, the catalytic potential of the
7, Table 9). Consequently, by using the mixture of ionic liquid MnSaln complex was further improved in ionic liquid–aqueous
with water also helped to increase the percentages yield of the mixtures (3 : 1). Generally, the biological and catalytic potential
C–C product (entries 2, 4, 6 and 8) due to the considered of the various MSaln complexes is following a similar trend.
47,77
acceleration effect on such cross-couplings,
by enhancing
the solubility of the polar inorganic compounds and the
4
. Experimental
substantial effect of the cations and anions on the ionic liquid,
47,54,77
4.1. Reagents, apparatus and methodology
as reported elsewhere.
Depending upon the nature of the substrates (electron- The starting materials were ordered from Acr ¨o s and Fluka,
donating, and electron-withdrawing group on the aryl halides) which was used as such for further work. The micro-elemental
the obtained product percentages yield showed variation from analyses of HSaln ligand and all MSaln complexes were done
moderate to high, (entries 1, 2 and 3, Table 11), with aryl by a CHNS machine GMBH VarioEl model V2.3. Electronic
bromide, the yield was promoted, as seen in entries 2, 4–7 transition spectroscopy was executed by a Jasco Ultra Violet-
(
Table 11), whereas, with the other aryl halides, i.e. chloride and Visible Spectrophotometer V-570 model with 1.0 cm quartz
ꢃ
iodide, the yield of C–C products was little reduced (entries 1, 3 cells in the thermostated holder at 25 C. NMR spectroscopy
and 8). When the electron-donating group on aryl bromides was was carried out by a FT-NMR multinuclear spectrometer model
ꢃ
1
attached, the yield was enhanced (entries 2, 4–6). The o-methyl Bruker ARX400 at 25 C with 400.1 MHz for H-nucleus and
1
3
group on bromobenzene slightly improved the percentage 100.6 MHz for C-nucleus. Mass spectroscopy was measured
amount to 94% (entry 4), whereas, the p-methyl group or the p- by the apparatus Agilent Technology 6310 (Ion Trap LC/MS –
47
methoxy group on bromobenzene showed slight reduction in 1200 Series). Thermogravimetric analysis was obtained by
78
the yield (90 or 89%) respectively. In contrast, the electronic using Shimadzu TGA-50H thermal analyzer under inert
34324 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
3
ꢀ1
nitrogen atmosphere (with rate 20 cm min ) as carrier gas with continues stirring. The color was changed slowly from
ꢃ
using rate of heating 10 C per min for the temperature range dark green to brownish-green. The solvent was evaporated in
ꢃ
from 30 to 400 C. IR vibrational spectroscopy was measured vacuum and the solid residue was washed with diethyl ether
ꢀ
1
ꢃ
in the region of 4000–400 cm as KBr pellet using Shimadzu and dried in an oven (50 C). The pure complexes were ob-
FTIR-8101 Fourier transform infrared spectrophotometer. tained by recrystallization with 1 : 1 mixture of methanol–
Conducting features were evaluated in
a Jenway con- water.
ductometer model 4320, supported by an epoxy bodied
conductivity cell (two electrodes, shiny) with cell constant
calibration from 0.01 to 19.99 at 25 C. Magnetic measure-
4
.3. Stability constants of the prepared MSaln complexes
ꢃ
All MSaln complexes were synthesized by the reaction of equi-
molar ratios of the metal ion and HSaln ligand. This could be
determined by the continuous variation method, which is
helpful to deduce the MSaln complexes stability constants K at
various applied temperatures (20, 25, 30, 35 and 40 C), by
using eqn (1):
ments were achieved by a Gouy's balance with diamagnetic
correction by Pascal's constants and mercury(II) hex-
20
ꢃ
acyanocobaltate, as a calibrating agent, at 25 C.
f
ꢃ
41
4.2. Synthesis
4
.2.1. Synthesis of HSaln ligand. HSaln ligand was
A=A
m
41
K
f
¼
(1)
prepared according to the previously reported procedure in an
aqueous media using 1 equivalent of sodium salicylaldehyde-5-
sulfonate with 1 equivalent of an ethanolic solution of anthra-
nilic acid. (NMR data are presented in Fig. S1–S4 in the ESI†).
2
ð1 ꢀ A=A
m
Þ C
The Gibb's free energy (D
calculated according to eqn (2), and the thermodynamic
parameters, D H and D S, were deduced from the Gibb's–
f
G) of all MSaln complexes was
2 2
4.2.2. Synthesis of VOSaln, MoO Saln, MnSaln and UO -
Saln complexes. Sustainably, an aqueous solution of vanadyl
acetylacetonate, molybdenyl acetylacetonate, manganese
acetate hexahydrate or uranyl acetate dihydrate (5 mmol, 30 mL)
was added slowly to an aqueous solution of HSaln ligand
f
f
Helmholtz equation as function reciprocal of T in kelvin:
D
f
G ¼ ꢀRT ln K
f
(2)
(
5 mmol, 30 mL) at room temperature. The obtained solution
where, K is the stability constant, R represents the gas constant
and T (K) represents the temperature.
f
ꢃ
was heated at 70 C for 3 hours with continuous stirring. The
color of the mixed solution was changed slowly to the color of
the corresponding complex. The solvent was evaporated in
vacuum and the solid residue was washed with diethyl ether 4.4. Antibacterial investigations
ꢃ
and dried in an oven (50 C). The pure complexes were obtained
HSaln ligand and its corresponding M-chelates were exam-
by recrystallization with 1 : 1 mixture of methanol–water
provided 69, 74, 76 and 72% yield of VOSaln, MoO Saln, MnSaln
and UO Saln complexes, respectively.
.2.3. NMR spectra of MoO Saln and UO
, 400 MHz): d 3.35 (s, 2H, H
ined as antibacterial reagents. Using DMSO (dimethylsulf-
oxide) as a solvent and the agar well dilution method, three
14
2
2
different bacterial strains, Serratia marcescens (ꢀve), Escher-
ichia coli (ꢀve) and Staphylococcus aureus (+ve) using were
evaluated. The various bacterial strains were grown on
nutrient agar in sterile Petri plates at room temperature. In
holes created by using a sterile cork borer, a sterile paper
4
2
2
Saln complexes.
1
MoO
2
Saln, H NMR (DMSO-d
6
2
O
3
overlapped with water of DMSO-d
6
), 6.94 (dd, J ¼ 8.1 Hz, 2H),
3
3
4
7.34 (t, J ¼ 7.9 Hz, 1H), 7.55 (d, J ¼ 7.9 Hz, 1H), 8.54 (d, J ¼
2.1 Hz, 1H), 8.82 (s, 1H), 10.53 (s, 1H) and 11.00 ppm (s, 1H,
ꢀ1
saturated with a solution (10 and 20 mg mL ) of HSaln ligand
CH]N) (Fig. S5 and S6†).
or its MSaln complexes was placed. The resultant plates were
1
3
C NMR (100 MHz, DMSO-d
6
, Dept-135): d 116.55 (CH),
), 126.86 (CH), 129.74 (CH),
), 147.07 (CH), 156.74 (CH), 157.73 (C ),
), 163.41 (CH, CH]N) and 169.92 ppm (C , C]O).
, 400 MHz): d 2.43 (s, 2H, H O),
ꢃ
14
incubated for 1 day at 37 C. Gentamycin, was used as
a positive control. There was no antibacterial potential of the
DMSO alone.
1
1
1
16.83 (CH), 119.82 (CH), 120.07 (C
31.53 (C
62.84 (C
q
q
), 141.06 (C
q
q
q
q
1
UO
2
Saln, H NMR (DMSO-d
6
2
3
3
3
4.5. Antifungal investigations
6
8
8
.98 (d, J ¼ 8.0 Hz, 1H), 7.20 (d, J ¼ 8.0 Hz, 1H), 7.40 (t, J ¼
3
3
.0 Hz, 1H), 7.59 (t, J ¼ 8.0 Hz, 1H), 7.81 (d, J ¼ 8.0 Hz, 1H), By applying the well diffusion method, HSaln ligand and its
3
.02 (s, 1H), 8.19 (d, J ¼ 8.0 Hz, 1H) and 9.34 ppm (s, 1H, CH] MSaln complexes were studied as antifungal reagents versus
N) (Fig. S7–S9†).
three fungal strains, Candida albicans, Aspergillus avus and
1
3
C NMR (100 MHz, DMSO-d
6
, Dept-135): d 110.23 (CH), Trichophyton rubrum, under the environment of potato
2
4
1
1
1
q q
17.03 (CH), 121.52 (CH), 126.95 (CH), 131.55 (C ), 132.73 (C ), dextrose agar. From the infected areas of the host plant, the
34.25 (CH), 151.57 (C
q
), 155.57 (C
q
), 161.20 (CH, CH]N) and applied fungal species were extracted, mixed with potato
74.11 ppm (C , C]O).
q
dextrose agar and poured in Petri dishes. Using DMSO as
ꢀ
1
4.2.4. Synthesis of VOSaln-Ph complex. To an aqueous a solvent, the compounds (10 and 20 mg mL ) were applied
solution of VO-Saln (5 mmol, 30 mL), a methanolic solution to the Petri dishes. The resultant plates were then incubated
ꢃ
of 1,10-phenanthroline (5 mmol, 10 mL) was added at room for 72 hours at 35 C. Fluconazole was used as a positive
ꢃ
temperature. The mixture was heated at 70 C for 3 hours control.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34325

View Article Online
RSC Advances
.6. Minimal inhibitory concentration (MIC) and activity
Paper
4
The type and magnitude of the chromism could be estab-
lished based on eqn (6):
index (A), of antimicrobial potential
To determine the MIC, a range of compound concentrations
were tested. The zone of inhibition (in mm) of the investi-
gated metal complexes was compared with available standard
drugs. The MIC is dened as the smallest concentration of
the compound that inhibits the growth of the
microorganisms.
A
free ꢀ Abonding
Chromism; % ¼
(6)
A
free
where, Afree is the absorbance of MSaln complexes in the
absence of DNA and Abonding is the absorbance at the maximum
absorption band of MSaln complexes with DNA in different
concentrations.
24,25
The activity index (A), is calculated from eqn (3):
4
.7.2. Hydrodynamic measurements. The hydrodynamic
measurements of the studied metal complexes (MSaln
complexes) with CT-DNA mixtures at 25 C were estimated as
Inhibition zoneðmmÞ
A ¼
ꢂ 100
(3)
Inhibition zone of standard drugðmmÞ
ꢃ
relative viscosities by using Ostwald micro-viscometer. The
time consumed for uidity (in seconds) of different concen-
trations of MSaln complexes, in the absence and to various
concentrations of MSaln complexes from 5.0 to 50.0 mM
under inert atmosphere, i.e. bubbling of nitrogen gas
through the mixed solution in the viscometer. By applying
4
.7. Interaction of CT-DNA with MSaln chelates
A stock solution of CT-DNA was prepared by mixing Tris–HCl (5
mM) and NaCl (50 mM) in deionized water (pH ¼ 7.5). The UV
absorbance of the DNA stock solution was measured at 260 nm
and its molar absorption coefficient calculated (6600
mol cm ). The electronic absorbance ratio (A260/A280) of the
stock DNA solution was 1.83 (almost between 1.8–1.9) indi-
cating that there was no protein contamination of the prepared
ꢃ
eqn (7), the viscosity was determined in the absence (h ) and
presence of different concentrations of MSaln complexes
ꢀ
1
ꢀ1
24,25
with CT-DNA (h):
ꢃ
t ꢀ t
h ¼
(7)
ꢃ
t
25
ꢃ
CT-DNA solution. The DNA stock solution was stored at 4 C
and used for 4 days only. The ethidium bromide (EB) concen-
where, t is the uid time of the mixed MSaln complexes with CT-
ꢃ
ꢀ
1
ꢀ1
DNA (seconds) and t is the buffer uid time. The relative
tration was evaluated at 480 nm (3 ¼ 5860 mol cm ). The
ꢃ
ꢀ
3
viscosity, h/h , was derived from the plotting the viscosity versus
interaction-binding experiments were performed with 10
M
1/R, where R was conrmed from eqn (8):
Tris-buffer (Tris–HCl (5 mM) and NaCl (50 mM) in Tris-buffer
with pH ¼ 7.5). Solutions of MSaln complexes were prepared
½DNAꢄ
R ¼
(8)
in fresh DMSO (VOSaln, VOSaln-Ph, UO
2
Saln, MnSaln and
½Compoundꢄ
MoO
2
Saln).
[DNA] is the CT-DNA concentration and [compound] is the
4.7.1. UV-visible spectroscopy. Using a given xed molar
concentration of MSaln complexes.
concentration of MSaln complexes in DMSO, the electronic
spectra were examined in the presence of various CT-DNA molar
4.7.3. Agarose gel electrophoresis. One of the most favored
concentrations. The absorbance values of CT-DNA alone (in tools to evaluate the binding of the studied compound with
14,24
absence of MSaln complex) were removed by adding the same DNA is agarose gel electrophoresis.
A stock solution of
concentration to the blank compartment. In this manner, the MSaln complexes was prepared by dissolving 20.0 mg of MSaln
ꢀ1
spectra changes could be attributed to the DNA–MSaln complexes in 20 mL of DMF. 25.0 mg mL of MSaln complexes
complexes. The binding constant, K
b
, was derived by plotting was mixed with separated DNA of CT-DNA (calf-thymus) and
ꢃ
[
DNA]/(3 ꢀ 3 ) against the concentrations of DNA, [DNA] from incubated at 37 C for 1 hour. Then, 30.0 mL was taken from the
a
b
14,24
eqn (4):
resulted interacted MSaln complexes–DNA solution and mixed
with bromophenol blue dye with equimolar ratios (1 : 1) and
(4) then charged to the electrophoresis chamber wells parallel to
a sample of the standard DNA marker in TBE buffer (50 mM
where, [DNA] is the CT-DNA concentration in mmoles, the Tris-base in pH 7.2 with 1 mM EDTA/1.0 l). The gel was run
½
DNAꢄ
½DNAꢄ
1
¼
þ Â
À
ÁÃ
3
a
ꢀ 3
f
3
b
ꢀ 3
f
Kb 3b ꢀ 3f
extinction coefficients of free, apparent and complete binding using 60 V for approximately 45 min.
of DNA with the reacting compound (MSaln complexes) are
represented as 3 , 3a and 3 , respectively. From the isolated agarose in 60.0 mL of hot Tris-acetate-EDTA buffer (TAE) (4.84 g
The agarose gel was prepared by dissolving 600.0 mg of
f
b
ꢀ
1
compound (MSaln complexes) calibration curve of
complex], as well as, CT-DNA calibration curve of Aabs/[DNA], was boiled for a few minutes. Aer cooling, the solution was
the values of 3 and 3 were calculated, respectively. K
was poured into a tted gas cassette with the comb. The gel was
calculated from the slope and the intercept ratio of the above allowed to cool gradually to room temperature until to be solid.
plotting. The standard Gibb's free energy, DG
acted CT-DNA with MSaln complexes, was recorded from eqn taining TAE buffer. The agarose gel was imagined and photo-
A
abs
/
Tris-base, pH 8.0 and 0.5 M EDTA L ). The obtained solution
[
f
a
b
s
b
, for the inter- The solid gel was placed in the electrophoresis chamber con-
24
(
5):
graphed in genius 3 Panasonic DMC-LZ5 Lumix DNA gel
documentation system.
s
b
DG
¼ RT ln K
b
(5)
34326 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
.8. Anticancer potential
RSC Advances
4
at least 50 cycles of calculation. The obtained molecular dock le
was created with different poses for HSaln ligand and its MSaln
complexes with rearrangement with the nal score function (S).
The score of the last stage (S) is that was not set to none. To
investigate the different poses, the browser of resulted database
was selected for the best.
The anticancer potential of HSaln ligand and its MSaln
complexes was examined at Cancer Biology Department, Phar-
macology Department, Cairo University and the National Cancer
Institute. Anti-cancer potential was tested against a HepG2 cell
line (hepatocellular carcinoma), a MCF7 cell line (breast carci-
noma) and an HCT-116 cell line (colon carcinoma), spectro-
scopically, the absorbance of each current compound was
determined with an ELISA microplate reader (Meter tech. S 960,
4
.10. Catalytic processes
Suzuki–Miyaura cross-coupling processes were carried out in
two necked round bottom ask (100 mL) with water circulatory
glass condenser, loaded with phenylboronic acid (1.0 mmol) in
“USA”) at 564 nm. The anticancer potential was visualized in vitro
25
using the Sulfo-Rhodamine-B-stain (SRB). To this end, a solu-
tion of HSaln ligand or MSaln complexes in DMSO (various
1
0
0 mL H
.10 mmol of MSaln complexes catalyst (VOSaln, VOSaln-Ph,
Saln or UO Saln). The reaction was initiated by
2
O, 2.1 mmol of potassium carbonate and charged with
ꢀ
1
concentrations 0, 1.0, 2.5, 5.0 and 10.0 mg mL ) was poured
dropwisely into a 96-multiwell plate, that contained a mono-layer
of the cancer cells (104 cells per well). The plate was then incu-
MnSaln, MoO
2
2
the addition of 1.2 mmol of 2-bromopyridine and the reaction
ꢃ
bated at 37 C for 48 h under inert atmosphere carbon dioxide
5%). Aer the addition of Sulfo-Rhodamine-B-stain (SRB), the
ꢃ
mixture was heated under reux conditions at 110 C for 6
(
hours in a thermostated oil bath.
plate was xed. Excess stain was removed by acetic acid and then
mixed with Tris–EDTA buffer. An ELISA plate reader was used to
The cross-coupling product was extracted by diethyl ether (30
mL) and dried by anhydrous magnesium sulfate and further
diluted with 10 mL of diethyl ether to make a dilute sample for
GC-MS analysis. The yield (in percentages) of C–C products were
resolved with Shimadzu Gas Chromatography Mass Spectrom-
eter (GC-MS) model QP2010 SE, with Rxi-5 Sil MS capillary
column (30 m length ꢂ 0.25 mm ID ꢂ 025 mm lm thickness).
determine the color intensity. The inhibitory concentration (IC50
was deduced by applying eqn (9):
)
25
ControlOD ꢀ Compound
OD
IC50ð%Þ ¼
ꢂ 100
(9)
ControlOD
ꢃ
The sample was injected into the GC-MS system at 25 C. The
ꢃ
4
.9. Molecular docking
Dell Precision™ T3600 Workstation Intel Xeon E5-1660 3.3 GHz,
6 GB 1600 MHz DDR3, ECC RDIMM 1 TB (7200 RPM), 1 GB
GC oven temperature was initiated at 40 C and xed for 60
ꢃ
ꢀ1
seconds. The rate of the temperature with 10 C min was
ꢃ
increased up to 200 C. The operation of the inlet was carried
out in the mode of splitless at 200 C, which was the mass
1
ꢃ
NVIDIA Quadro 2000, Windows 10 Professional (64 Bit) was
applied in order to investigate the current compounds molecular
docking (HSaln ligand and all MSaln complexes) with using
Molecular Operating Environment (MOE) package version
spectra temperature of the transfer line. The carrier gas was
ꢀ1
pure helium (99.999%), which owed with rate of 1 mL min
.
Lab solution soware was applied to analyze the yield
percentages of the obtained products.
2
018.01. X-ray analysis of a B-DNA dodecameric d(CGCG
0
0
AATTCGCG)2 crystal structure within 3 –5 direction (DNA code:
1
BNA) was applied in order to examine the docking at a resolu- Conflicts of interest
ꢁ
tion of 1.9 A. By importing the molecular structure of DNA with
its H atoms into MOE, the optimization energy could be calcu-
lated. The obtained structural model was submitted to the
systematic conformation search within a gradient of RMS of
There is no conict of interest in this manuscript.
Acknowledgements
ꢀ1
0
.01 kcal mol with negligible parameters in the Site Finder tool
This work was supported by the Deanship of Scientic Research
at King Faisal University, Al Ahsa, through a Nasher Track (No.
embedded in MOE. By means of ChemBio Draw Ultra 12.0, all
HSaln ligand and its MSaln complexes were drawn. For calcu-
lating the parameters of the investigated compounds using
molecular docking following changes were done: (1) adding the
hydrogen atoms; (2) applying the conformational search for all
HSaln ligand and its MSaln complexes; (3) MMFF94 force eld,
186121).
References
79
the best conformers obtained showed an energy decrease.
Energy reduction with the steepest algorithm was exercised, aer
1 P. A. Vigato and S. Tamburini, Coord. Chem. Rev., 2004, 248,
1717.
which the conjugate gradient method was applied until an RMS
2 R. M. Clarke and T. Storr, Dalton Trans., 2014, 43, 9380.
3 A. F. Shoair, A. R. El-Shobaky and H. R. Abo-Yassin, J. Mol.
Liq., 2013, 66, 687.
4 L. H. Abdel-Rahman, A. M. Abu-Dief, H. Mostafa and
S. K. Hamdan, Appl. Organomet. Chem., 2017, 31, e3555.
5 L. H. Abdel-Rahman, A. M. Abu-Dief, M. R. Shehata,
F. M. Atlam and A. A. H. Abdel-Mawgoud, Appl. Organomet.
Chem., 2019, e4699.
ꢀ1
ꢀ1
ꢁ
gradient reached 0.00001 kcal mol
A . In MOE 2016.08, the
standard molecular docking was exercised. The Alpha Triangle
placement that derives poses by random superposition of HSaln
ligand atoms triplets alpha sphere dummies in the target site was
used to detect the poses. The London dG scoring function
elucidated the free binding energy of the ligand from a given
pose. The best poses of the docked molecules were estimated by
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34327

View Article Online
RSC Advances
Paper
6
A. Lehwess-Litzmann, P. Neumann, C. Parthier, S. L u¨ dtke, 26 S. Shahzadi, S. Ali, S. K. Sharma and K. Qanungo, J. Iran.
R. Golbik, R. Ficner and K. Tittmann, Nat. Chem. Biol.,
011, 7, 678.
X. Liu, C. Manzur, N. Novoa, S. Celed ´o n, D. Carrillo and
J.-R. Hamon, Coord. Chem. Rev., 2018, 357, 144.
P. Adaeo, M. L. Kuznetsov, S. Barroso, A. M. Martins,
F. Avecilla and J. C. Pessoa, Inorg. Chem., 2012, 51, 11430.
D. Gong, B. Wang, X. Jia and X. Zhang, Dalton Trans., 2014,
Chem. Soc., 2010, 7, 419.
27 H. F. Abd El-Halim, G. G. Mohamed and E. A. M. Khalil, J.
Mol. Struct., 2017, 1146, 153.
28 Y.-T. Liu, J. Sheng, D.-W. Yin, H. Xin, X.-M. Yang, Q.-Y. Qiao
and Z.-J. Yang, J. Organomet. Chem., 2018, 856, 27.
29 C. M. Sharaby, M. F. Amine and A. A. Hamed, J. Mol. Struct.,
2017, 1134, 208.
2
7
8
9
4
3, 4169.
30 W. H. Mahmoud, N. F. Mahmoud and G. G. Mohamed, Appl.
Organomet. Chem., 2017, 31, e3858.
1
1
0 P. Das and W. Linert, Coord. Chem. Rev., 2016, 311, 1.
1 Z. Beigi, A. H. Kianfar, H. Farrokhpour, M. Roushani, 31 W. H. Mahmoud, R. G. Deghadi, M. M. I. El Desssouky and
M. H. Azarian and W. A. K. Mahmood, J. Mol. Liq., 2018,
49, 117.
2 W. Al Zoubi and N. Al Mohanna, Spectrochim. Acta, Part A,
014, 132, 854.
3 A. W. Jeevadason, K. K. Murugavel and M. A. Neelakantan,
Renewable Sustainable Energy Rev., 2014, 36, 220.
G. G. Mohamed, Appl. Organomet. Chem., 2018, 32, e4556.
32 W. H. Mahmoud, M. M. Omar, F. N. Sayed and
G. G. Mohamed, Appl. Organomet. Chem., 2018, 32, e4386.
33 W. H. Mahmoud, R. G. Deghadi and G. G. Mohamed, Res.
Chem. Intermed., 2016, 42, 7869.
34 R. Rasool and S. Hasnain, Spectrochim. Acta, Part A, 2015,
148, 435.
35 A. A. M. Belal, I. M. El-Deen, N. Y. Farid, R. Zakaria and
M. S. Refat, Spectrochim. Acta, Part A, 2015, 149, 771.
2
1
1
1
1
2
4 M. S. S. Adam and H. Elsawy, J. Photochem. Photobiol., B,
2018, 184, 34.
5 I. Correia, S. Roy, C. P. Matos, S. Borovic, N. Butenko,
I. Cavaco, F. Marques, J. Lorenzo, A. Rodr ´ı guez, 36 E. M. Zayed, A. M. M. Hindy and G. G. Mohamed, Appl.
V. Morenoe and J. C. Pessoa, J. Inorg. Biochem., 2015, 147,
34.
6 L. Krivosudsk ´y , P. Schwendt, R. Gyepes and Z. Z ´a k,
Organomet. Chem., 2018, 32, e3952.
37 E. M. Zayed, A. M. M. Hindy and G. G. Mohamed, Appl.
Organomet. Chem., 2018, 32, e4525.
1
1
1
Polyhedron, 2014, 81, 421.
7 L. Krivosudsk ´y , P. Schwendt, J. Simunek and R. Gyepes, J.
Inorg. Biochem., 2015, 147, 65.
38 E. M. Zayed, G. G. Mohamed, W. M. I. Hassan, A. K. Elkholy
and H. Moustafa, Appl. Organomet. Chem., 2018, 32, e4375.
39 E. M. Zayed, M. A. Zayed, A. M. M. Hindy and
G. G. Mohamed, Appl. Organomet. Chem., 2018, 32, e4603.
ˇ
18 J. C. Pessoa, J. Inorg. Biochem., 2015, 147, 4.
19 L. Lu, J. Yue, C. Yuan, M. Zhu, H. Han, Z. Liu and M. Guo, J. 40 F.-S. Han, Chem. Soc. Rev., 2013, 42, 5270.
Inorg. Biochem., 2011, 105, 1323.
41 H. M. Abd El-Lateef, M. S. S. Adam and M. M. Khalaf, J.
2
0 M. S. S. Adam, M. M. Youssef, M. F. Abo Elghar, A. M. Hafez
and U. El-Ayaan, Appl. Organomet. Chem., 2017, 31, e3650.
1 Z. Kazemi, H. A. Rudbari, M. Sahihi, V. Mirkhani,
M. Moghadam, S. Tangestaninejad, I. Mohammadpoor-
Taiwan Inst. Chem. Eng., 2018, 88, 286.
42 (a) M. S. S. Adam and A. D. M. Mohamad, Polyhedron, 2018,
151, 118; (b) M. S. S. Adam, M. A. Al-Omair and F. Ullah, Res.
Chem. Intermed., 2019, 45, 4653.
2
Baltork and S. Gharaghani, J. Photochem. Photobiol., B, 43 G. Scalese, J. Ben ´ı tez, S. Rost ´a n, I. Correia, L. Bradforda,
2
016, 162, 448.
M. Vieites, L. Minini, A. Merlino, E. L. Coiti n˜ o, E. Birriel,
J. Varela, H. Cerecetto, M. Gonz ´a lez, J. C. Pessoa and
D. Gambino, J. Inorg. Biochem., 2015, 147, 116.
2
2 A. Rauf, A. Shah, A. A. Khan, A. H. Shah, R. Abbasi,
I. Z. Qureshi and S. Ali, Spectrochim. Acta, Part A, 2017,
1
76, 155.
44 S. G. Rull, I. Funes-Ardoiz, C. Maya, F. Maseras,
M. R. Fructos, T. R. Belderrain and M. C. Nicasio, ACS
Catal., 2018, 8, 3733.
2
3 A. K. Saini, P. Kumari, V. Sharma, P. Mathur and
S. M. Mobin, Dalton Trans., 2016, 45, 19096.
2
4 (a) L. H. Abdel-Rahman, R. M. El-Khatib, L. A. E. Nassr, 45 P. K. Suganthy, R. N. Prabhu and V. S. Sridevi, Inorg. Chim.
A. M. Abu-Dief and M. Ismael, Spectrochim. Acta, Part A, Acta, 2016, 449, 127.
014, 117, 366; (b) L. H. Abdel-Rahman, A. M. Abu-Dief, 46 (a) A. A. Abdel Aziz, A. N. M. Salem, M. A. Sayed and
2
M. Ismael, M. A. A. Mohamed and N. A. Hashem, J. Mol.
Struct., 2016, 1103, 232; (c) L. H. Abdel-Rahman,
N. M. Ismail, M. Ismael, A. M. Abu-Dief and E. A. Ahmed,
J. Mol. Struct., 2017, 1134, 851.
M. M. Aboaly, J. Mol. Struct., 2012, 1010, 130; (b)
L. M. Kumar and B. R. Bhat, J. Organomet. Chem., 2017,
827, 41.
47 M. Wang, X. Yuan, H. Li, L. Ren, Z. Sun, Y. Hou and W. Chu,
Catal. Commun., 2015, 58, 154.
2
5 (a) L. H. Abdel-Rahman, A. M. Abu-Dief, R. M. El-Khatib and
S. M. Abdel-Fatah, Bioorg. Chem., 2016, 69, 140; (b) A. M. Abu- 48 H. Choudhary, P. Berton, G. Gurau, A. S. Myerson and
Dief, I. F. Nassar and W. H. Elsayed, Appl. Organomet. Chem., R. D. Rogers, Chem. Commun., 2018, 54, 2056.
016, 30, 917; (c) L. H. Abdel-Rahman, A. M. Abu-Dief, 49 S. Doherty, J. G. Knight, T. Backhouse, E. Abood,
2
M. O. Aboelez and A. A. H. Abdel-Mawgoud, J. Photochem.
Photobiol., B, 2017, 170, 271; (d) L. H. Abdel-Rahman,
M. S. S. Adam, A. M. Abu Dief, H. Moustafa, M. T. Basha,
A. S. Aboraia and H. E. Ahmed, Appl. Organomet. Chem.,
H. Alshaikh, A. R. Clemmet, J. R. Ellison, R. A. Bourne,
T. W. Chamberlain, R. Stones, N. J. Warren,
I. J. S. Fairlamb and K. R. J. Lovelock, Adv. Synth. Catal.,
2018, 360, 3716.
2018, 32, e4527.
34328 | RSC Adv., 2019, 9, 34311–34329
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
5
5
5
5
5
5
0 L. Li, J. Wang, T. Wu and R. Wang, Chem.–Eur. J., 2012, 18, 67 K. Y. El-Baradie, N. A. El-Wakiel and H. A. El-Ghamry, Appl.
842. Organomet. Chem., 2015, 29, 117.
1 S. More, S. Jadhav, R. Salunkhe and A. Kumbhar, Mol. Catal., 68 L. H. Abdel-Rahman, A. M. Abu-Dief, R. M. El-Khatib and
017, 442, 126. S. M. Abdel-Fatah, J. Photochem. Photobiol., B, 2016, 162, 298.
2 Y. Gu, I. Favier, C. Pradel, D. L. Gin, J.-F. Lahitte, R. D. Noble, 69 V. Ramakrishna and N. D. Reddy, Dalton Trans., 2017, 46,
M. G ´o mez and J.-C. Remigy, J. Membr. Sci., 2015, 492, 331.
8598.
3 J. D. Patil, S. N. Korade, S. A. Patil, D. S. Gaikwad and 70 F. Kong, C. Zhou, J. Wang, Z. Yu and R. Wang,
D. M. Pore, RSC Adv., 2015, 5, 79061. ChemPlusChem, 2013, 78, 1.
4 R. Wang, B. Twamle and J. B. Shreeve, J. Org. Chem., 2006, 71, 71 E. L. Kolychev, A. F. Asachenko, P. B. Dzhevakov, A. A. Bush,
7
2
426.
V. V. Shuntikov, V. N. Khrustalevc and M. S. Nechaev, Dalton
Trans., 2013, 42, 6859.
5 (a) M. S. S. Adam, A. D. Mohamad and O. M. El-Hady,
Monatsh. Chem., 2014, 145, 435; (b) I. Mohammed-Ziegler, 72 S. Fortun, P. Beauclair and A. R. Schmitzer, RSC Adv., 2017, 7,
Spectrochim. Acta, Part A, 2003, 59, 19. 21036.
6 Y.-Z. Cao, H.-Y. Zhao, F.-Y. Bai, Y.-H. Xing, D.-M. Wei, 73 R. Dakarapu and J. R. Falck, J. Org. Chem., 2018, 83, 1241.
5
S.-Y. Niu and Z. Shi, Inorg. Chim. Acta, 2011, 368, 223.
7 R. J. P. Williams, J. Phys. Chem., 1954, 58, 121.
74 J. M. Neely, M. J. Bezdek and P. J. Chirik, ACS Cent. Sci., 2016,
2, 935.
5
5
8 A. Einstein, B. Podolsky and N. Rosen, Phys. Rev., 1953, 47, 75 S. Vijjamarri, S. Streed, E. M. Serum, M. P. Sibi and G. Du,
77. ACS Sustainable Chem. Eng., 2018, 6, 2491.
9 R. Ramesh and S. J. Maheswaran, J. Inorg. Biochem., 2003, 96, 76 (a) L.-X. You, H.-J. Liu, L.-X. Cui, F. Ding, G. Xiong,
7
5
4
57.
S.-J. Wang, B.-Y. Ren, I. Dragutan, V. Dragutan and
Y.-G. Sun, Dalton Trans., 2016, 45, 18455; (b) R. Dakarapu
and J. R. Falck, J. Org. Chem., 2018, 83, 1241.
6
6
6
0 N. Pravin and N. Raman, Inorg. Chem. Commun., 2013, 36, 45.
1 M. S. S. Adam, Monatsh. Chem., 2015, 146, 1823.
2 U. K. Das, Y. Ben-David, G. Leitus, Y. Diskin-Posner and 77 (a) H. Vald ´e s, M. A. Garc ´ı a-Eleno, D. Canseco-Gonzalez and
D. Milstein, ACS Catal., 2019, 9, 479.
D. Morales-Morales, ChemCatChem, 2018, 10, 3136–3172;
(b) H. Vald ´e s, L. Gonz ´a lez-Sebasti ´a n and D. Morales-
Morales, J. Organomet. Chem., 2017, 845, 229–257; (c)
M. Asay and D. Morales-Morales, Dalton Trans., 2015, 44,
17432–17447.
6
6
6
3 L. H. Abdel-Rahman, A. M. Abu-Dief, E. F. Newair and
S. K. Hamdan, J. Photochem. Photobiol., B, 2016, 160, 18.
4 P. Jayaseelan, E. Akila, M. U. Rani and R. Rajavel, J. Saudi
Chem. Soc., 2016, 26, 625.
5 L. H. Abdel-Rahman, A. M. Abu-Dief, M. Basha and 78 M. Mastalir, E. Pittenauer, B. St ¨o ger, G. Allmaier and
A. A. H. Abdel-Mawgoud, Appl. Organomet. Chem., 2017, 31,
e3750.
K. Kirchner, Org. Lett., 2017, 19, 2178.
79 T. A. Halgren, J. Comput. Chem., 1996, 17, 490.
66 U. Jash, G. Chakraborty, S. Sinha, R. Sikari, R. Mondal and
N. D. Paul, Asian J. Org. Chem., 2018, 7, 1681.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 34311–34329 | 34329