Metal-based ethanolamine-derived compounds: a note on their synthesis, characterization and bioactivity

Article abstract of DOI:10.1080/14756366.2016.1220375

Metal-based ethanolamines, (L¹)–(L⁴) coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in 1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These compounds were screened for their bactericidal/fungic

Full text of DOI:10.1080/14756366.2016.1220375

Journal of Enzyme Inhibition and Medicinal Chemistry
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Metal-based ethanolamine-derived compounds:
a note on their synthesis, characterization and
bioactivity
Muhammad Amjad, Sajjad H. Sumrra, Muhammad Safwan Akram & Zahid H.
Chohan
To cite this article: Muhammad Amjad, Sajjad H. Sumrra, Muhammad Safwan Akram & Zahid
H. Chohan (2016): Metal-based ethanolamine-derived compounds: a note on their synthesis,
characterization and bioactivity, Journal of Enzyme Inhibition and Medicinal Chemistry, DOI:
10.1080/14756366.2016.1220375
To link to this article: http://dx.doi.org/10.1080/14756366.2016.1220375
Published online: 24 Aug 2016.
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Date: 25 August 2016, At: 03:48

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ISSN: 1475-6366 (print), 1475-6374 (electronic)
J Enzyme Inhib Med Chem, Early Online: 1–10
2016 Informa UK Limited, trading as Taylor & Francis Group. DOI: 10.1080/14756366.2016.1220375
!
RESEARCH ARTICLE
Metal-based ethanolamine-derived compounds: a note on their
synthesis, characterization and bioactivity
Muhammad Amjad1, Sajjad H. Sumrra2, Muhammad Safwan Akram3, and Zahid H. Chohan4
2
1Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan, Department of Chemistry, Institute of Natural Sciences,
3
4
University of Gujrat, Gujrat, Pakistan, School of Science & Engineering, Teesside University, Middlesbrough, UK, and Department of Chemistry,
University of Sargodha, Bhakkar Campus, Pakistan
Abstract
Keywords
Metal-based ethanolamines, (L1)–(L4) coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in
1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These
compounds were screened for their bactericidal/fungicidal activity against a number of
bacterial (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi,
Staphylococcus aureus and Bacillus subtilis) and fungal strains (Trichophyton longifusus,
Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata)
alongside against a shrimp species known as Artemia salina. The screening results indicated
that metal complexes have significantly higher activity than uncomplexed ligands against one
or more bacterial/fungal species due to chelation. The ligand (L4) displayed good bacterial and
fungal activity as compared to other ligands. The antibacterial results revealed that the Zn(II)
complex (16) of (L4) was found to be the most active complex and Co(II) complex (14) of the
same ligand (L4), demonstrated the highest antifungal activity.
Antibacterial/antifungal, ethanolamine-
derived compounds, metal(II) complexes
History
Received 13 May 2016
Revised 17 July 2016
Accepted 1 August 2016
Published online 22 August 2016
Introduction
and the extent of denticity. The new series of ethanolamine-
derived compounds (E)-2-(((2-hydroxyethyl)
(L1)–(L4),
Bioactive transition metal complexes have gained increasing
interest in metal-based drug chemistry especially as therapeutic
agents. Since their discovery in 1864, Schiff’s bases have
contributed immensely to the development of co-ordination
chemistry and acting as an inspiration for the development of
novel compounds1. The Schiff bases are characterized by an imine
group and are formed as a condensation product2 of primary
amine with an aldehyde or ketone in the presence of a dehydrating
agent such as MgSO4. A number of Schiff’s base metal complexes
have displayed bioactivity as antibacterial3,4, antifungal5, antic-
ancer6,7,8, anti-inflammatory9, anticonvulsant10, antiviral11 and
analgesic12 agents. Although metal-based ethanolamines have
historically been subjected of many investigations13,14 due to their
use as buffers15, catalysts16, inhibitors17, ion exchangers18,
electroplating and dyes19, now they are garnering attention for
their biological20 role in plant growth21 regulation, bacterial and
fungal metabolism and as a cytotoxic agent22. Metal-based
compounds have also been reported to improve electron transfer
imino)methyl)phenol (L1), (E)-2-(((2-hydroxyethyl)imino)methyl)-
naphthalen-1-ol (L2), (E)-2-((4-nitrobenzylidene)amino)ethanol
(L3) and (E)-5-bromo-2-(((2-hydroxyethyl) imino)methyl)phenol
(L4) were synthesized from the reaction of 2-hydroxy-1-naphthalde-
hyde, 2-hydroxybezaldehyde, 5-bromo-2-hydroxybezaldehyde and
4-nitrobenzaldehyde, respectively, with ethanolamine in equimolar
ratio (Scheme 1). The synthesized ligands were further coordinated
with Co(II), Cu(II), Ni(II), and Zn(II) metals in 1:2 (metal:ligand)
molar ratio to produce new metal complexes (Scheme 2).
The synthesized ligands and their metal(II) complexes have
been screened in vitro for antibacterial activity against six
bacterial species (Escherichia coli, Shigella flexneri,
Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus
aureus and Bacillus subtilis) and for in vitro antifungal activity
against six fungal strains (Trichophyton longifusus, Candida
albicans, Aspergillus flavus, Microsporum canis, Fusarium solani
and Candida glabrata). Cytotoxicity of the compounds was
determined through the help of brine shrimp bioassay.
and efficiency in protein bioelectrochemistry23,24
.
One of the advantages of using Schiff’s bases is the ability to
control and tune the electronic and steric properties of the ligand
Materials and methods
attached to the metal. One of the strategies is an appropriate All the chemicals used were of analytical grade and were
choice of precursor, because that plays a pivotal role by allowing purchased from Sigma Aldrich. Infrared spectra of solid com-
control over nature of donor atoms, number of chelating moieties pounds (as KBr disc) were recorded on a Nicolet FT-IR Impact
400D infrared spectrometer. Elemental analysis was carried out
on Perkin Elmer and 1H and 13C NMR spectra were recorded on
a Bruker Spectrospin Avance DPX-400 spectrometer using TMS
as internal standard and d6-DMSO as a solvent. Electron impact
mass spectra (EIMS) were recorded on JEOL MSRoute instrument.
Address for correspondence: Zahid H. Chohan, Department of Chemistry,
University of Sargodha, Bhakkar Campus, Pakistan. E-mail:
dr.zahidchohan@gmail.com

2
M. Amjad et al.
J Enzyme Inhib Med Chem, Early Online: 1–10
Scheme 1. Preparation of ligands.
Scheme 2. Metal(II) complexes.
UV-Visible spectra were recorded on ultraviolet spectrometer- 4-nitrobenzaldehyde were individually dissolved in ethanol
1700 (Shimadzu, Japan) in the frequency range of 250–800 nm. (25 mL) and added respectively to a refluxed solution of
Molar conductance of metal complexes was measured using an ethanolamine in ethanol (10 mL) in an equimolar ratio. The
Inolab Cond 720 Conductivity Bridge at room temperature using reaction mixture was refluxed for 3 h and consequently pre-
0.001 molar solutions in DMF. A Stanton SM12/S Gouy balance cipitated while being monitored. The solid product thus obtained
was used to measure the magnetic susceptibility of the metal was filtered, washed with ethanol and dried. It was re-crystallized
complexes at room temperature using mercury acetate ligand as a in hot ethanol/methanol (1:1). The same method was used for the
standard. In vitro antibacterial, antifungal and cytotoxic properties preparation of all other ligands (L1)–(L4).
were studied in collaboration with Research Institute of
Chemistry, International Centre for Chemical Sciences, (E)-2-(((2-hydroxyethyl)imino)methyl)naphthalen-1-ol (L1)
University of Karachi, Pakistan and School of Science and
Yield: (1.64 g, 76%); mp 151 ꢀC; color (dark yellow); IR (KBr,
Engineering, Teesside University, UK.
cmꢁ1): 3438 (aryl-OH), 3385(alc-OH), 1627 (–HC¼N), 1603
(C–H) and 1584 (C¼C); 1H NMR (ppm d6-DMSO): ꢀ 3.65 (s, 1H,
Synthesis of ligands
alc-OH), 4.50 (t, 2H, C12–H), 5.85 (t, 2H, C11–H), 7.15 (d, 1H,
Different aldehydes such as 2-hydroxy-1-naphthaldehyde, J ¼ 9.0 Hz, C3–H), 7.41 (t, 1H, J ¼ 7.4 Hz, C6–H), 7.53 (t, 1H,
2-hydroxybezaldehyde, 5-bromo-2-hydroxybezaldehyde and J ¼ 7.4 Hz, C7–H), 7.80 (d, 1H, J ¼ 7.8 Hz, C4–H), 7.95 (d, 1H,

DOI: 10.1080/14756366.2016.1220375
Metal-based ethanolamine-derived compounds
3
J ¼ 9.0 Hz, C5–H), 8.22 (d, 1H, J ¼ 8.5 Hz, C8–H), 8.53 (s, 1H, (t, 1H, C6–H), 7.59 (t, 1H, C7–H), 7.90 (d, 1H, C4–H), 7.99(d, 1H,
C13–H), 9.88 (s, 1H, aryl-OH); 13C NMR (DMSO-d6): ꢀ 59.3 C5–H), 8.26 (d, 1H, C8–H), 8.64 (s, 1H, C13–H); 13C NMR
(C11), 69.5 (C12), 116.4 (C1), 122.1 (C6), 125.5 (C3), 126.2 (C8), (DMSO-d6, ꢀ, ppm): 60.1(C11), 70.3 (C12), 117.5 (C1), 129.1 (C6),
126.9 (C10), 127.7 (C7), 128.9 (C5), 134.3 (C9), 136.4 (C4), 159.6 125.5 (C3), 126.7 (C8), 127.5 (C10), 128.2 (C7), 129.6(C5), 135.0
(C2), 162.8 (C13); Mass Spectrum (ESI): [M]+ ¼ 215.25. UV- (C9), 136.4 (C4), 160.6 (C2), 163.9 (C13).
1
Visible: 27 335 and 31 284 cmꢁ1. Anal. Calc. for C13H13NO2
(215.25) C, 72.54; H, 6.09; N, 6.51; O, 14.87 and found C, 72.48; OH), 4.62 (t, 2H, C12–H),5.94 (t, 2H, C11–H), 7.07 (t, 1H, C4–H),
[Zn(L2)2] (8): H NMR (DMSO-d6, ꢀ, ppm): 3.79 (s, 1H, alc-
H 6.04; O, 14.83.
7.18 (d, 1H, C6–H), 7.51 (t, 1H, C5–H), 7.79 (d, 1H, C3–H), 8.63
(s, 1H, C13–H); 13C NMR (DMSO-d6, ꢀ, ppm): d 60.4 (C11), 70.7
(C12), 117.5 (C3), 119.3 (C1), 123.3 (C5), 131.1 (C6), 134.2 (C4),
161.0 (C2), 163.6 (C13).
[Zn(L3)2] (12): 1H NMR (DMSO-d6, ꢀ, ppm): 3.70 (s, 1H, alc-
OH), 4.60 (t, 2H, C12–H), 5.95 (t, 2H, C11–H), 7.23 (d, 1H, C3–
H), 7.55 (dd, 1H, C5–H), 8.19 (d, 1H, C6–H), 8.61 (s, 1H, C13–
H);13C NMR (DMSO-d6, ꢀ, ppm): ꢀ 59.8 (C11), 69.1 (C12), 118.7
(C3), 123.5 (C1), 125.7 (C5), 128.3(C4), 133.8 (C6), 160.2 (C2),
163.0 (C13).
[Zn(L4)2] (16): 1H NMR (DMSO-d6, ꢀ, ppm): 4.59 (t, 2H,
C12–H), 5.93 (t, 2H, C11–H), 8.18(dd, 2H, C2–-H and C6–H), 8.39
(dd, 2H, C3–H and C5–H), 8.62 (s, 1H, C13–H), 10.3 (s, 4H, H2O);
13C NMR (DMSO-d6, ꢀ, ppm): ꢀ 60.2 (C11), 69.7 (C12), 121.4
(C3), 122.9 (C5), 131.5 (C1), 131.8 (C6), 152.9 (C4), 159.7 (C2),
163.3 (C13).
(E)-2-(((2-hydroxyethyl)imino)methyl)phenol25 (L2)
Yield (1.22 g, 74%); mp 92 ꢀC; color (yellow); IR (KBr, cmꢁ1):
3450 (aryl-OH), 3380(alc-OH),1625 (–HC¼N) and 1596 (C¼C);
1H NMR (ppm d6-DMSO): ꢀ 3.63 (s, 1H, alc-OH),4.50 (t, 2H, C12-
H), 5.85 (t, 2H, C11–H), 7.0 (t, 1H, J ¼ 8.5 Hz, C4–H), 7.11 (d, 1H,
J ¼ 7.9 Hz, C6–H), 7.45 (t, 1H, J ¼ 7.5 Hz, C5–H), 7.69 (d, 1H,
J ¼ 7.8 Hz, C3–H), 8.50 (s, 1H, C13–H), 9.91(s, 1H, aryl-OH); 13C
NMR (DMSO-d6): ꢀ 59.4 (C11), 69.7 (C12), 117.5 (C3), 119.3 (C1),
121.7(C5), 131.1 (C6), 133.6 (C4), 159.9 (C2), 162.5 (C13); Mass
Spectrum (ESI): [M]+ ¼ 165.19. UV-Visible: 27 233 and
31 050 cmꢁ1. Anal. calcd. for C9H11NO2 (465.19): C, 65.44; H,
6.71; N, 8.48; O, 19.37. Found: C, 65.38; H, 6.67; N, 19.33.
(E)-4-Bromo-2-(((2-hydroxyethyl)imino)methyl)phenol (L3)
Yield (1.51 g, 78%); mp: 99 ꢀC, color (orange yellow); IR (KBr,
cmꢁ1): 3453 (aryl-OH), 3382(alc-OH), 1622 (–HC¼N) and 1590
(C¼C); 1H NMR (ppm d6-DMSO): ꢀ 3.67 (s, 1H, alc-OH),4.50 (t,
2H, C12–H), 5.85 (t, 2H, C11–H), 7.12 (d, 1H, J ¼ 8.7 Hz, C3–H),
7.50 (dd, 1H, J ¼ 8.7, 2.5 Hz, C5–H), 8.10 (d, 1H, J ¼ 2.5 Hz, C6–
H), 8.57 (s, 1H, C13–H), 9.93 (s, 1H, aryl-OH); 13C NMR
(DMSO-d6): ꢀ 58.9 (C11), 68.1 (C12), 118.7 (C3), 122.5 (C1),
125.2 (C5), 127.7 (C4), 133.1(C6), 159.2 (C2), 161.9 (C13); mass
spectrum (ESI): [M]+ ¼ 165.19. UV-Visible: 27 461 and
31 338 cmꢁ1. Anal. calcd. forC9H10BrNO2 (244.1): C, 44.29; H,
4.13; Br, 32.74; N, 5.74. Found: C, 44.23; H, 4.11; Br,32.68;
N, 5.70.
Biological activity
Antibacterial activity (in vitro)
All the newly synthesized ethanolamine-derived compounds
(L1)–(L4) and their metal(II) complexes (1)–(16) were screened
in vitro for their antibacterial activity against four Gram-negative
(E. coli, S. flexneri, P. aeruginosa, S. typhi) and two Gram-
positive (S. aureus, B. subtilis) bacterial strains by agar-well
diffusion method26. The wells (6 mm in diameter) were dug in the
media with the help of a sterile metallic borer with centers of at
least 24 mm apart. Two to eight hours old bacterial inocula
containing approximately 104–106 colony-forming units (CFU/
mL) were spread on the surface of the nutrient agar with the help
of a sterile cotton swab. The recommended concentration of the
test sample (1 mg/mL in DMSO) was introduced in the respective
wells. Other wells supplemented with DMSO and reference
antibacterial drug (imipenum) served as a negative and positive
control, respectively. The plates were incubated at 37 ꢀC for 24 h.
Activity was determined by measuring the diameter of clear zones
showing complete inhibition (mm). In order to confirm the effect
of DMSO in the biological screening, alternate studies on DMSO
solution showed no activity against any bacterial strains.
(E)-2-((4-nitrobenzylidene)amino)ethanol25 (L4)
Yield (1.55 g, 80%); mp: 88 ꢀC, color (reddish brown); IR (KBr,
cmꢁ1): 3460 (aryl-OH), 3390(alc-OH), 1632 (–HC¼N), 1595
(C¼C) and 1424 (NO2); 1H NMR (ppm d6-DMSO): ꢀ 3.69 (s, 1H,
alc-OH), 4.50 (t, 2H, C12–H), 5.85 (t, 2H, C11–H), 8.10 (dd, 2H,
J ¼ 8.7, 2.5 Hz, C2–H and C6–H), 8.33 (dd, 2H, J ¼ 8.7, 2.5 Hz,
C3–H and C5–H), 8.65 (s, 1H, C13–H); 13C NMR (DMSO-d6): ꢀ
59.3 (C11), 68.6 (C12), 120.6 (C3), 122.4 (C5), 130.5 (C1), 131.0
(C6), 152.3
(C4), 158.8(C2), 162.2 (C13); mass spectrum (ESI):
[M]+ ¼ 194.19. UV-Visible: 27 590 and 31 410 cmꢁ1. Anal.
calcd. for C9H10N2O3 (194.19): C, 55.67; H, 5.19; N, 14.44.
Found: C, 55.62; H, 5.16; N, 14.11.
Antifungal activity (in vitro)
Antifungal activity was studied against six fungal strains
(T. longifusus, C. albican, A. flavus, M. canis, F. solani and
C. glabrata). Sabouraud dextrose agar (Oxoid, Hampshire,
England) was seeded with 105 (cfu) mLꢁ1 fungal spore suspen-
sions and transferred to petri plates. Discs soaked in 20 mL
(200 mg/mL in DMSO) of the compounds were placed at different
positions on the agar surface. The plates were incubated at 32 ꢀC
for 7 days. The results were recorded as percentage of inhibition
and compared with the standard drugs miconazole and ampho-
tericin B.
Synthesis of the transition metal(II) complexes
All complexes were prepared according to the standard procedure
in which a methanol solution (20 mL) of the respective metal(II)
as a chloride (5 mmol) was added to a refluxed methanol solution
(30 mL) of the ligand (10 mmol). The mixture was further
refluxed for 3 h leading to a precipitated product. It was then
cooled to room temperature, filtered, washed with methanol and
finally with diethyl ether. The precipitated product thus obtained
was dried and recrystallized in a mixture of hot aqueous
methanol:ethanol (1:2) to obtain TLC pure product.
Minimum inhibitory concentration (MIC)
Compounds containing promising antibacterial activity were
selected for minimum inhibitory concentration (MIC) studies.
The MIC was determined using the disc diffusion technique27 by
preparing discs containing diluted samples at 10, 25, 50, and
NMR data of the Zn(II) complexes
[Zn(L1)2] (4): 1H NMR (DMSO-d6, ꢀ, ppm): 3.78 (s, 1H, alc-OH),
4.61 (t, 2H, C12–H), 5.91 (t, 2H, C11–H), 7.26 (d, 1H, C3–H), 7.46

4
M. Amjad et al.
J Enzyme Inhib Med Chem, Early Online: 1–10
Table 1. Physical measurements and analytical data of metal (II) complexes (1)–(16).
Elemental analysis (%)
Calc (Found)
No
Structure
Yield (%)
70
MW/Formula
[487.41]
M.P (ꢀC)
166–168
C
H
N
M
1
[Co(L1–H)2]
64.07(64.01)
4.96 (4.92)
5.75 (5.72)
12.09 (12.04)
C
26H24N2O4Co
[487.17]
26H24N2O4Ni
[492.02]
2
[Ni(L1–H)2]
[Cu(L1–H)2]
[Zn(L1–H)2]
[Co(L2–H)2]
[Ni(L2–H)2]
[Cu(L2–H)2]
[Zn(L2–H)2]
[Co(L3–H)2]
[Ni(L3–H)2]
[Cu(L3–H)2]
[Zn(L3–H)2]
[Co(L4)2]
70
75
83
71
74
81
82
85
80
84
80
74
82
77
78
220–222
185–187
197–199
175–176
230–232
194–196
270–272
225–227
194–196
214–216
211–212
176–177
206–208
190–191
278–280
64.10 (64.01)
64.77 (64.71)
63.23 (63.18)
55.82 (55.77)
55.86 (55.80)
55.16 (55.11)
54.90 (54.85)
39.66 (39.61)
39.68 (39.64)
39.33 (39.29)
39.20 (39.15)
44.92 (44.87)
44.94 (44.89)
44.49 (44.44)
44.32 (44.27)
4.97 (4.92)
4.92 (4.89)
4.90 (4.86)
5.21 (5.18)
5.21 (5.17)
5.14 (5.10)
5.12 (5.09)
3.33 (3.29)
3.33 (3.29)
3.30 (3.27)
3.29 (3.26)
4.61 (4.57)
4.61 (4.58)
4.56 (4.53)
4.55 (4.51)
5.75 (5.71)
5.69 (5.65)
5.67 (5.62)
7.23 (7.20)
7.24 (7.20)
7.15 (7.12)
7.11 (7.06)
5.14 (5.11)
5.14 (5.10)
5.10 (5.07)
5.08 (5.04)
11.64 (11.60)
11.65 (11.60)
11.53 (11.50)
11.49 (11.45)
12.05 (12.01)
12.92 (12.88)
13.24 (13.20)
15.22 (15.18)
15.16 (15.12)
16.21 (16.17)
16.61 (16.56)
10.81 (10.77)
10.77 (10.73)
11.56 (11.52)
11.86 (11.82)
12.24 (12.20)
12.20 (12.16)
13.08 (13.05)
13.41 (13.37)
C
3
C
C
C
26H24N2O4Cu
4
[493.89]
26H24N2O4Zn
[387.30]
18H20N2O4Co
[387.06]
18H20N2O4Ni
[391.91]
18H20N2O4Cu
[393.77]
5
6
C
7
C
8
C
18H20N2O4Zn
[545.09]
18H18Br2N2O4Co
9
C
10
11
12
13
14
15
16
[544.85]
18H18Br2N2O4Ni
[549.70]
C
C
18H18Br2N2O4Cu
[551.56]
C
18H18Br2N2O4Zn
[481.32]
C
18H22N4O8Co
[481.07]
18H22N4O8Ni
[485.84]
18H22N4O8Cu
[Ni(L4)2]
C
[Cu(L4)2]
C
[487.80] C18H22N4O8Zn
[Zn(L4)2]
100 g mLꢁ1 concentrations of the compounds along with stand- four ligands (L1)–(L4) (Scheme 1). These colored ligands were
ards at the same concentrations.
stable in both air and moisture. These microcrystalline solids
melted at 88–151 ꢀC and were soluble in DMSO and DMF at
room temperature and in methanol and ethanol on heating. The
ligands (L1)–(L3) were found to be tridentate and the ligand (L4)
to be bidentate which reacted readily with Co(II), Cu(II), Ni(II)
and Zn(II) metals as their chlorides in methanol to form their
metal(II) complexes (Scheme 2).
All the synthesized metal(II) complexes were microcrystalline
and had an intense color except Zn(II) complexes, which were off-
white. The metal(II) complexes decomposed (Table 1) without
melting and were insoluble in common organic solvents such as
ethanol, methanol, dichloromethane and acetone but soluble in
DMSO and DMF. The spectral data and elemental analysis of the
prepared ligands and their metal(II) complexes were in a good
agreement with their proposed structures, indicating the high
purity of all the compounds. The analytical data of the complexes
indicated a 1:2 metal: ligand stoichiometry.
Cytotoxicity (in vitro)
Brine shrimp assay was done using the protocol of Meyer et al.28,
the details of which are reproduced here. Brine shrimp (Artemia
salina leach) eggs were hatched in a shallow rectangular plastic
dish (22 ꢂ 32 cm), filled with artificial seawater prepared from
commercial salt mixture and double-distilled water. An unequal
partition was made in the plastic dish with the help of a perforated
device where approximately 50 mg of eggs were sprinkled into the
darkened larger compartment while smaller matter compartment
was exposed to the ordinary light. After two days, nauplii were
collected from the unsheltered side. A sample of the test
compound was prepared by dissolving 20 mg of each compound
in 2 mL of DMF. From this stock solutions 5, 50 and 500 mg/mL
were transferred to nine vials (three for each dilutions were used
for each test sample and LD50 was calculated as the mean of these
three values) and one vial was kept as control having 2 mL of
DMF only. The solvent was allowed to evaporate overnight. After
two days, when shrimp larvae were ready, 1 mL of seawater and
10 shrimps were added to each vial (30 shrimps/dilution) and the
volume was adjusted with seawater to 5 mL per vial28. After 24 h
the number of survivors was counted. Data were analyzed by a
computer program to determine the LD50 values29.
IR spectra
The significant and distinctive IR spectral bands are reported in
the experimental part and in Table 2. All Schiff’s base ligands
possessed potentially active donor sites capable of coordinating
with metal atoms such as azomethine nitrogen (–HC¼N),
aliphatic and aromatic hydroxyl (–OH) groups. The Schiff bases
(L1)–(L4) possessed the characteristic azomethine (–HC¼N)
stretching30 at 1622–1632 cmꢁ1 giving a clue of condensation
product. All the ligands (L1)–(L4) displayed aliphatic hydroxyl
(–OH) stretching at 3380–3390 cmꢁ1, however, ligands (L1)–(L3)
additionally showed aromatic hydroxyl (–OH) stretching31 at
3438–3390 cmꢁ1. The ligand (L4) showed a band at 1424 cmꢁ1
Results and discussion
The condensation reaction of ethanolamine with 2-hydroxy-1-
naphthaldehyde/2-hydroxy benzaldehyde/5-bromo-2-hydroxyben-
zaldehyde/4-nitrobenzaldehyde in an equimolar ratio afforded

DOI: 10.1080/14756366.2016.1220375
Metal-based ethanolamine-derived compounds
5
Table 2. Conductivity, magnetic and spectral data of metal(II) complexes (1)–(16).
No
ꢀM (ꢀꢁ1 cm2 molꢁ1
)
B.M ꢂeff
lm (cmꢁ1
)
IR (cmꢁ1
)
1
2
3
4
5
6
7
8
15.9
15.7
14.6
14.9
16.2
15.8
15.6
15.1
16.2
15.2
16.0
15.0
14.6
16.5
15.4
15.1
4.35
3.56
1.66
Dia
4.53
3.41
1.71
Dia
4.38
3.48
1.74
Dia
4.45
3.51
1.70
Dia
8723, 17 690, 29 820
8635, 17 717, 25 817, 29 781
8897, 17 783, 29 816
28 915
8650, 17 729, 29 841
8712, 17 761, 25 778, 29 738
8937, 17 892, 29 812
28 928
8680, 17 523, 29 831
8786, 17 777, 25 719, 29 781
8727, 17 765, 29 788
28 841
8790, 17 800, 29 805
8696, 17 871, 25 719, 29 778
8866, 17 857, 29 858
28 932
3370 (OH), 1616 (HC ¼ N), 1370 (C–O), 520 (M–N), 442 (M–O)
3372 (OH), 1615 (HC ¼ N), 1372 (C–O), 535 (M–N), 450 (M–O)
3371 (OH), 1620 (HC ¼ N), 1373 (C–O), 529 (M–N), 448 (M–O)
3373 (OH), 1618 (HC ¼ N), 1371 (C–O), 533 (M–N), 450 (M–O)
3366 (OH), 1612 (HC ¼ N), 1372 (C–O), 522 (M–N), 446 (M–O)
3365 (OH), 1610 (HC ¼ N), 1370 (C–O), 536 (M–N), 445 (M–O)
3365 (OH), 1615 (HC ¼ N), 1371 (C–O), 526 (M–N), 443 (M–O)
3368 (OH), 1613 (HC ¼ N), 1373 (C–O), 532 (M–N), 440 (M–O)
3368 (OH), 1611 (HC ¼ N), 1377 (C–O), 540 (M–N), 449 (M–-O)
3367 (OH), 1610 (HC ¼ N), 1376 (C–O), 524 (M–N), 453 (M–O)
3370 (OH), 1612 (HC ¼ N), 1375 (C–O), 536 (M–N), 448 (M–O)
3377 (OH), 1608 (HC ¼ N), 1377 (C–O), 528 (M–N), 451 (M–O)
3470 (H2O), 1620 (HC ¼ N), 540 (M–N), 455 (M–O)
9
10
11
12
13
14
15
16
3471 (H2O), 1622 (HC ¼ N), 544 (M–N), 459 (M–O)
3470 (H2O), 1623 (HC ¼ N), 541 (M–N), 460 (M–O)
3473 (H2O), 1619 (HC ¼ N), 543 (M–N), 463 (M–O)
1
resulting from NO2 vibrations. The comparison of the IR spectra proton observed at 7.50 ppm as a double of doublet. H NMR
of the Schiff’s bases (L1)–(L4) with their metal(II) complexes (1)– spectra of the ligand (L4) showed the C2–H, C6–H and, C3–H and
(16) indicated that the Schiff bases were principally coordinated C5–H protons at 8.10 and 8.33 ppm as double of doublet. The
to the metal(II) atoms in a bi- and tridentate fashion. The disappearance of hydroxyl proton at 9.88–9.93 ppm in the spectra
vibrations of azomethine-N group present in all the metal of Zn(II) complexes confirmed deprotonation and coordination of
complexes (1)–(16) and aliphatic-O appearing in the spectra of the hydroxyl-O with the metal atom. The coordination of the
metal(II) complexes (1)–(12) shifted to lower frequency (07– azomethine-N was evident by downfield shifting of all the proton
15 cmꢁ1) at 1608–1623 and 3365–3377 cmꢁ1, respectively, rep- signals in their Zn(II) complexes. A strong singlet was observed at
resenting the mode of coordination of the azomethine nitrogen32 10.3 ppm in the Zn(II) complex (16) due to the coordination of
and hydroxyl-O with the metal(II) atoms. Absence of bands at water molecule with the Zn(II) metal atom. All protons underwent
3438–3490 and 3380–3390 cmꢁ1 due to aliphatic and aromatic downfield shift by 0.05–0.12 ppm due to the increased conjuga-
ꢁ(OH) and consequent appearance of a new band33 at 1370– tion on coordination with the zinc metal atom. The number of
1377 cmꢁ1 attributed to ꢁ (C–O) in the metal(II) complexes (1)– protons calculated from the integration curves34 and obtained
(16), confirmed the deprotonation and coordination of aromatic values of the expected CHN analysis agreed well with each other.
and aliphatic ꢁ (OH) to the metal(II) atoms. The following
observations further support the mode of chelation:
ꢃ Appearance of the new bands at 520–543 and 440–460 cmꢁ1
could be assigned to v(M–O) and v(M–N) vibrations34 in the
metal complexes which are absent in ligands.
ꢃ The metal(II) complexes (13)–(16) demonstrated35 new broad
bands at 3468–3478 cmꢁ1 which can likely be attributed to
water molecules coordinated to the metal atoms. These bands
were only observed in the spectra of the metal complexes.
These clues supported the evidence of the participation of
azomethine-N and deprotonation/coordination of hydroxyl-O with
the metal(II) ions.
13C NMR spectra
The 13C-NMR spectra of the Schiff bases and their diamagnetic
Zn(II) complexes were recorded in DMSO-d6 and are reported
along with their possible assignments in the experimental section
and all the carbon atoms were found in the expected region. The
13C-NMR spectra of the Schiff base ligands (L1)–(L4) displayed
distinctive and representative (C11, C12) carbons of ethylene group
and (C13) carbons of azomethine (–HC¼N) at 58.9–69.7 and
161.9–162.8 ppm, respectively. The remaining other (C1)–(C10)
carbons of aromatic rings were observed at 116.4–159.9 ppm.
Downfield shifting of the azomethine carbons found in the
uncomplexed Schiff bases from161.9–162.8 ppm to 163.0–
163.9 ppm in their Zn(II) complexes was due to shifting of
1H NMR spectra
1H NMR spectra of the ligands (L1)–(L4) and their diamagnetic electronic density toward the Zn(II) ion. Similarly, all carbons of
Zn(II) complexes were recorded in DMSO-d6 and the details are methylene groups and aromatic rings being near to the coordin-
provided in the experimental section. 1H NMR spectradisplayed36 ation sites also showed downfield shifting by 0.5–1.1 ppm due to
characteristic azomethine (–HC¼N) protons at 8.53–8.65 ppm as the increased conjugation and coordination with the metal atoms.
a singlet providing a strong evidence for the condensation of The downfield shifting also confirmed the coordination of the
amino group of the ethanolamine with aldehydes. All of the azomethine to the zinc metal atom. Moreover, the presence of the
ligands (L1)–(L4) displayed aliphatic (–OH) proton at 5.63– number of carbons is well in agreement with the expected
5.99 ppm as a singlet and C11–H and C12–H protons at 4.50 and values37. Furthermore, the conclusions drawn from these studies
5.85 ppm as triplet, respectively. The ligands (L1)–(L3) possessed present further support to the modes of bonding discussed in their
1
aromatic (–OH) proton at 9.88–9.93 ppm. Ligand (L1) displayed IR and H NMR spectra.
other C3–5–H and C8–H protons as a double of doublet at 7.15–
8.22 ppm, respectively, but C6–H and C7–H protons appeared as a
Mass spectra
triplet at 7.41 and 7.53 ppm, respectively. Similarly, the ligand
The mass fragmentation pattern of the ligands (L1)–(L3) followed
the cleavage of C¼N (exocyclic) and C¼C bonds. The mass
spectral data and the stable fragmentation values of the ligands
have already been detailed in the experimental section. All the
(L2) exhibited C4–H and C5–H protons at 7.0 and 7.45 ppm as
triplet and, C3–H and C6–H protons as a doublet at 7.11 and
7.69 ppm, respectively. The C3–H and C6–H protons of ligand
(L3) were found at 7.12 and 8.10 ppm as a doublet and C5–H

6
M. Amjad et al.
J Enzyme Inhib Med Chem, Early Online: 1–10
ligands showed pronounced molecular ion peaks. The data of the spectral data of Ni(II) complexes showed46 the bands in the
Schiff bases shown by mass spectra strongly confirmed the region 8635–8786, 17 717–17 871 and 25 719–25 717 cmꢁ1
formation of the ligands possessing proposed structures and also, assigned,
respectively,
to
the
d–d
transitions
of
their bonding pattern.
3A2g(F)!3T2g(F) and 3A2g(F)!3T1g(F). Also, a strong band
due to metal to ligand charge transfer was appeared at 29 738–
29 781 cmꢁ1. The electronic spectra of all the Cu(II) complexes
exhibited47 absorption bands in the region at 8727–8937 and
17 765–17 892 cmꢁ1 which may be assigned to the transitions
2Eg!2T2g. The high energy band at 29 788–29 858 cmꢁ1 was
due to forbidden ligand to metal charge transfer. On the basis of
electronic spectra, octahedral geometry around the Cu(II) ion was
suggested. The Zn(II) complexes did not show any d–d transition
thus showing diamagnetic nature and their spectra
were dominated only by a charge transfer band48 at 28 841–
Molar conductances and magnetic measurements
Molar conductance studies of the metal(II) complexes (1)–(16)
were carried out in DMF and their molar conductance data (14.6–
16.9 ohmꢁ1 cm2 molꢁ1) showed (Table 1) that these complexes
were non electrolytic38 in nature. The magnetic moment (B.M)
values of all the metal(II) complexes (1)–(16) were measured at
room temperature. The observed magnetic moment value of
Co(II)complexes were found in the range of 4.35–4.53 B.M
indicating that Co(II) complexes as a high-spin with potentially
three unpaired electrons in an octahedral environment39. The
Ni(II) complexes displayed magnetic moment values in the range
of 3.41–3.56 B.M indicative of two unpaired electrons per Ni(II)
28 932 cmꢁ1
.
Biological screening
ion suggesting these complexes to have an octahedral40 geometry. Antibacterial bioassay (in vitro)
The measured magnetic moment values 1.66–1.74 B.M for Cu(II)
The newly produced Schiff’s bases (L1)–(L4) and their metal(II)
complexes are indicative of one unpaired electron per Cu(II) ion
for d9-system suggesting octahedral41 geometry. All the Zn(II)
complexes were found to be diamagnetic42 as expected.
complexes (1)–(16) were screened for their in vitro antibacterial
activity against E. coli, S. flexneri, P. aeruginosa, S. typhi,
S. aureus and B. subtilis bacterial strains according to the standard
procedures26 and results are reported in Table 3. The obtained
results were compared with those of the standardized drug sample
Electronic spectra
The UV-Visible spectra of all the ligands demonstrated two bands of imipenum (Figure 1). The synthesized ligand (L1) displayed a
at 27 233–27 590 cmꢁ1 and 31 050–31 410 cmꢁ1, respectively. The weaker (07–08 mm clearance zone (cz) or zone of inhibition)
first band appeared due to n–ꢃꢄ transition of –C¼N group, while activity against E. coli and B. subtilis and the remaining strains
the second band would be assigned to ꢃ–ꢃꢄ transition of the displayed moderate (10–13 mm) activity. Ligand (L2) presented a
phenyl group. After complexation, n–ꢃꢄ transition of ligand weaker (8 mm) activity against S. typhi and the remaining strains
shifted to a higher wavelength which revealed the coordination of showed moderate (9–13 mm) activity. Ligand (L3) demonstrated
ligand with metallic ions43,44. The electronic spectra of Co(II) moderate (11–12 mm) activity against S. flexneri, P. aeruginosa
complexes generally showed45 three absorption bands in the and B. subtilis and, other remaining strains observed significant
region 8650–8790, 17 523–17 800 and 29 805–29 841 cmꢁ1 which (16–17 mm) activity. The ligand (L4) experienced overall signifi-
may be assigned to 4T1g!4T2g(F), 4T1g!4A2g(F) and cant (15–17 mm) activity. The metal complex (1) showed
4T1g!4Tg(P) transitions respectively, and are suggestive of moderate (14 mm) activity against E. coli and B. subtilis and
octahedral geometry around the Co(II) ion. The electronic other remaining strains experienced significant (15–19 mm)
Table 3. Antibacterial bioassay of ligands (L1)–(L4) and metal(II) complexes (1)–(16).
[Zone of inhibition (mm)]
Gram-negative
Gram-positive
(f)
Compounds
(a)
(b)
(c)
(d)
(e)
(SA)
Average
L1
L2
L3
L4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
SD
08
13
16
16
14
17
16
13
18
16
17
20
20
22
20
18
21
20
19
22
25
13
11
12
17
19
18
17
16
17
18
19
17
21
16
17
24
23
17
22
21
26
11
12
11
15
17
12
18
19
19
16
15
19
17
19
16
19
16
21
17
22
25
10
08
17
17
15
17
13
16
14
13
16
15
22
19
21
23
20
22
19
24
27
13
09
16
16
19
18
16
20
12
14
16
16
22
23
19
20
19
24
25
21
27
07
11
12
15
14
14
12
15
18
16
16
17
18
21
20
21
18
22
20
21
28
2.50
1.86
2.61
0.89
2.59
2.45
2.34
2.59
2.73
1.76
1.38
2.50
2.10
2.53
1.94
2.32
2.58
2.37
2.80
1.17
1.17
10.33
10.67
14.00
16.00
16.50
16.00
15.33
16.50
16.33
15.50
16.50
17.67
20.00
20.00
18.83
20.83
19.67
21.00
20.33
21.83
25.83
Average activity of ligand (L1)–(L4) ¼ 12.75 mm; Average activity of complexes (1)–(16) ¼ 18.74 mm; (a) E. coli (b) S.
flexneri (c) P. aeruginosa (d) S. typhi (e) S. aureus (f) B. subtilis; SD: standard drug (Imipenum); weaker ¼ 0–08 mm,
moderate ¼ 09–14 mm, above 14 mm ¼ significant, SA: statistical analysis.

DOI: 10.1080/14756366.2016.1220375
Metal-based ethanolamine-derived compounds
7
activity. Complex (2) showed moderate (12–14 mm) activity (55–63%) activity against all fungal strains. The complex (1)
against P. aeruginosa and B. subtilis and left behind strains displayed significant (61–63%) activity against T. longifusus,
practiced significant (17–18 mm) activity. Compound (3) exhib- A. flavus and C. glabrata fungal strains, moderate (37–50%)
ited moderate (12–13 mm) activity against S. typhi and B. subtilis activity against C. albicans and M. canis, and weaker (16%)
and, left over demonstrated significant (16–18 mm) activity. activity against F. solani. Likewise, complex (2) had significant
Beside this, the compound (4) revealed significant (15–20 mm) (55–77%) activity against T. longifusus, A. flavus, M. canis, and
activity against all bacterial strains except E. coli which observed C. glabrata, and displayed weaker (25–26%) activity against
moderate (13 mm) activity. Also, the complexes (5) and (6) remaining two strains. Similarly, the compound 3 demonstrated
displayed moderate (12–14 mm) activity against Salmonella typhi significant (55–69%) activity against T. longifusus, A. flavus,
and Staphylococcus aureus and, remaining strains revealed M. canis, and C. glabrata, moderate (42%) against C. albicans
significant (17–19 mm) activity. However, the complexes and weaker (23%) activity against F. solani. The complex (4)
(7)–(16) displayed overall significant (15–25 mm) activity against comparably possessed significant (55–65%) activity against
all bacterial strains. The data reported in Table 3 clearly indicates T. longifusus, A. flavus, M. canis, and C. glabrata and moderate
that (L4) exhibited overall good bacterial activity as compared to (36–37%) activity was observed with rest of the fungal strains. On
other three ligands. The Zn(II) complex (16) of (L4) were found to the other hand, the compound (5)–(8) showed overall significant
be the most active complexes. The metal(II) complexes showed40 (55–75%) activity against all strains except M. canis which
higher activity results upon complexation rather than their displayed weaker (17–30%) activity. The compounds (9)–(16)
uncomplexed Schiff’s bases.
displayed overall significant (55–78%) activity against fungal
strains due to Br and NO2 groups attached with the aromatic rings.
(L4) showed overall good fungal activity as compared to other
three ligands due to nitro substitution. The Co(II) complex (14) of
(L4) was found to be the most active complex. The metal (II)
Antifungal bioassay (in-vitro)
The antifungal screening of all the synthesized compounds was
carried out against T. longifusus, C. albicans, A. flavus, M. canis,
F. solani and C. glabrata fungal strains (Table 4) according to the
literature protocol23. The results of inhibition were compared with
the results of standard drugs, miconazole and amphotericin B
(Figure 2). Ligand (L1) exhibited significant (55%) activity
against A. flavus fungal strain, moderate (37–45%) activity
against T. longifusus, M. canis and C. glabrata and weaker
(17%) activity against C. albicans and but inactive against
F. solani begging further investigation why that may be?
Similarly, the ligand (L2) possessed significant (56%) activity
against C. albicans and moderate (38–49%) activity against
T. longifusus, A. flavus, F. solani, weaker (30%) activity against
C. glabrata but no activity was observed in A. flavus. However,
the compound (L3) and (L4) displayed overall significant
Table 5. MIC (mg/mL) of the selected compounds (9), (10) and (12)–(16)
against selected bacteria.
Compounds E. coli S. flexneri P. aeruginosa S. typhi S. aureus
9
–
30.16
–
23.71
–
46.21
–
36.35
28.67
–
–
–
–
37.16
–
43.22
–
46.62
–
25.31
25.17
39.24
–
10
12
13
14
15
16
–
–
32.11
–
42.65
16.11
26.35
–
–
39.10
25.00
18.17
Table 4. Antifungal bioassay of ligands (L1)–(L4) and metal(II) complexes (1)–(16).
[% Inhibition (mm)]
Compounds
(a)
(b)
(c)
(d)
(e)
(f)
(SA)
Average
L1
L2
L3
L4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
SD
45
38
56
62
62
55
59
65
57
61
55
56
71
75
69
70
72
78
69
75
A
17
56
60
58
37
25
42
36
68
69
73
64
75
69
74
78
75
65
58
68
B
55
49
61
59
63
75
62
64
66
72
67
68
70
57
70
68
70
57
70
72
C
37
00
56
63
49
77
55
56
17
28
30
25
67
73
65
74
61
73
65
77
D
00
43
63
61
16
26
23
37
75
69
66
68
72
70
69
73
72
70
72
79
E
40
30
59
55
61
58
69
57
66
71
75
69
74
67
65
60
64
67
65
68
F
20.18
19.77
2.79
32.33
36.00
59.17
59.67
48.00
52.67
51.67
52.50
58.17
61.67
61.00
58.33
71.50
68.50
68.67
70.50
69.00
68.33
66.50
73.17
–
2.94
18.63
22.81
16.66
12.91
20.97
16.94
16.72
17.03
2.88
6.32
3.39
6.19
5.37
7.20
5.01
4.62
–
Average activity of ligands (L1)–(L4) ¼ 46.79%; Average activity of complexes (1)–(16) ¼ 62.51%; (a) T. longifusus (b) ¼
C. albicans (c) ¼ A. flavus (d) ¼ M. canis (e) ¼ F. solani (f) ¼ C. glabrata; SD: standard drugs MIC mg/mL; A:
Miconazole (70 mg/mL:1.6822 ꢂ 10ꢁ7 M/mL), B: Miconazole (110.8 mg/mL:2.6626 ꢂ 10ꢁ7 M/mL), C: Amphotericin B
(20 mg/mL:2.1642 ꢂ 10ꢁ8 M/mL), D: Miconazole (98.4 mg/mL:2.3647 ꢂ 10ꢁ7 M/mL), E: Miconazole (73.25 mg/mL:
1.7603 ꢂ 10ꢁ7 M/mL), F: Miconazole (110.8 mg/mL: 2.66266 ꢂ 10ꢁ7 M/mL); weaker ¼ 0–33%, moderate ¼ 34–54%,
55–100% ¼ significant; SA ¼ statistical analysis.

8
M. Amjad et al.
J Enzyme Inhib Med Chem, Early Online: 1–10
Table 6. Cytotoxicity (in vitro) of ligands (L1)–(L4) and their metal(II) complexes (1)–(16).
Compounds
LD50 (M/mL)
Compounds
LD50 (M/mL)
Compounds
LD50 (M/mL)
L1
L2
L3
L4
1
42.19 ꢂ 10ꢁ3
41.81 ꢂ 10ꢁ3
43.11 ꢂ 10ꢁ3
42.19 ꢂ 10ꢁ3
43.81 ꢂ 10ꢁ3
42.11 ꢂ 10ꢁ3
44.10 ꢂ 10ꢁ3
4
5
6
7
8
41.64 ꢂ 10ꢁ3
43.19 ꢂ 10ꢁ3
44.04 ꢂ 10ꢁ3
44.59 ꢂ 10ꢁ4
42.81 ꢂ 10ꢁ3
43.15 ꢂ 10ꢁ3
41.98 ꢂ 10ꢁ3
11
12
13
14
15
16
44.71 ꢂ 10ꢁ3
42.68 ꢂ 10ꢁ3
42.51 ꢂ 10ꢁ3
42.11 ꢂ 10ꢁ3
44.19 ꢂ 10ꢁ4
43.81 ꢂ 10ꢁ3
2
3
9
10
Figure 1. Comparison of antibacterial activity of Schiff’s bases versus metal(II) complexes.
Figure 2. Comparison of antifungal activity of Schiff’s bases versus metal(II) complexes.
complexes showed enhanced31 activity results rather than their the compounds either ligands or complexes showed cytotoxicity
uncomplexed Schiff’s bases upon complexation.
(1.64 ꢂ 10ꢁ3 to 4.71 ꢂ 10ꢁ3
)
against Artemia salina.
The cytotoxic data recorded in Table 6 revealed that almost all
compounds, ligands as well as metal complexes were inactive but
it was interesting to note that the metal complexes displayed better
potent cytotoxicity as compared to their parent ligands. This
activity relationship may help to serve as a basis for future
direction toward the development of certain cytotoxic agents for
clinical applications.
Minimum inhibitory concentration (MIC)
The synthesized ligands and their transition metal(II) complexes
showing promising antibacterial activity (480%) were selected
for MIC studies i.e. the compounds (9), (10) and (12)–(16) and the
results are reported in Table 5. The MIC values of these
compounds fall in the range 23.11–46.62 g/mL. Among these, the
compound (14) was found to be the most active possessing
maximum inhibition of 16.11 mg/mL against the bacterial strain
S. Aureus.
Conclusions
The synthesized ethanol-derived Schiff’s bases act as bi and
tridentate ligands for coordination with the Co(II), Cu(II), Ni(II)
and Zn(II) metal atoms. Physical (magnetic and molar conduct-
ance), spectral (IR, NMR, electronic) and analytical (C, H, N and
metalloelements percentage) data confirmed that the Schiff base
ligands are coordinated with the Co(II), Cu(II), Ni(II) and Zn(II)
Cytotoxicity (in vitro)
The Schiff bases and their metal(II) complexes were screened for
their cytotoxicity (brine shrimp bioassay) by using Meyer
protocol28. The data recorded in Table 6 indicated that none of

DOI: 10.1080/14756366.2016.1220375
Metal-based ethanolamine-derived compounds
9
14. Masoud MS, El-Einein SAA, Abed IM, Ali AE. Synthesis and
characterization of amino alcohol complexes. J Cood Chem 2002;
55:153–78.
metal atoms via azomethine-N, naphthalene-O, salicylidene-O
and ethanol-O showing an octahedral geometry. The obtained
results of antibacterial and antifungal activities indicated that the
metal complexes possessed better biological activity against one
or more bacterial and/or fungal strains as compared to their parent
uncomplexed ligands. It can be asserted that azomethine-N, nitro,
bromo and oxygen were the functional groups in the compounds
potentially responsible for the enhancement of bacterial and
fungal activities. However, brine shrimp assays revealed that these
compounds were limited in their cytotoxicity hinting at some
divergent apoptotic mechanisms.
´
15. Carrasco F. Ingredientes Cosmeticos. Diccionario de Ingredientes
´
Cosmeticos. 4th ed. Malaga, Spain; 2009:306.
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Acknowledgements
The authors are grateful to HEJ research Institute of Chemistry,
University of Karachi, Pakistan, for providing their help in taking
NMR, mass spectra and for the help in carrying out antibacterial,
antifungal and brine shrimp bioassays.
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compounds: synthesis of mono- and di-ethanolamine derived
ferrocenes with antibacterial, antifungal and cytotoxic properties.
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Declaration of interest
The authors declare no conflict of interest.
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