Synthesis, Characterization, Stability and Cytotoxic Evaluation of Novel Titanium(IV) Complexes of 8-Hydroxyquinoline and 2-Hydroxy-N-phenylbenzylamine Derivatives

Article abstract of DOI:10.14233/ajchem.2020.22505

A new class of moisture stable heteroleptic titanium(IV) complexes, synthesized from 8-hydroxyquinoline of the type [(Q)₂Ti(2-O-5-XC₆H₃CH₂NC₆H₄R] (3a-j), was prepared by reacting the antecedent molecule [(Q₂)Ti(OiPr)₂] (2) with various 2-hydroxy-N-phenyl-benzylamine analogues in 1:1 molar ratios in dry toluene (where, HQ = 8-hydroxyquinoline; iPr = isopropyl; R = H, 4-CH3, 4-OCH3, 2-Cl, 4-Cl, 2-Br, 4-Br; X= H, Br). Moisture sensitive study disclosed that these new metal complexes were unreacted for 72 h. Mass spectral data were employed for proving the mono-nuclearity of the new derivatives. Thermal decomposition pattern of the new derivatives was explained by thermogravimetric analyses. Elemental analyses data are in concordance with their expected values. The hexa-coordinated way of titanium-ligand linkage is further proved through NMR, FTIR, and UV-visible spectral studies. The cytotoxic efficiency of new complexes was tested against MDA-MB-231 human breast carcinoma cell line. Complex 3a exhibited the highest cytotoxic potential of 0.039 μM in comparison to all its analogues of this series by employing cisplatin as the standard.

Full text of DOI:10.14233/ajchem.2020.22505

Asian Journal of Chemistry; Vol. 32, No. 3 (2020), 683-689
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22505
Synthesis, Characterization, Stability and Cytotoxic Evaluation of Novel Titanium(IV)
Complexes of 8-Hydroxyquinoline and 2-Hydroxy-N-phenylbenzylamine Derivatives
1,*
2
BLASSAN SAMUEL and MADHVESH PATHAK
1
2
Faculty of Education, St. Theresa International College, Bangkok-26120, Thailand
Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore-632014, India
Corresponding author: Fax: +66 3 7349936; Tel: +66 9 28707365; E-mail: blassansamuel@gmail.com
Received: 19 October 2019; Accepted: 3 December 2019; Published online: 31 January 2020;
*
AJC-19778
Ti(2-O-5-X-
A new class of moisture stable heteroleptic titanium(IV) complexes, synthesized from 8-hydroxyquinoline of the type [(Q)
CH NC R] (3a-j), was prepared by reacting the antecedent molecule [(Q )Ti(OiPr)
benzylamine analogues in 1:1 molar ratios in dry toluene (where, HQ = 8-hydroxyquinoline; iPr = isopropyl; R = H, 4-CH
2
C
6
H
3
2
6
H
4
2
2
] (2) with various 2-hydroxy-N-phenyl-
, 4-OCH , 2-
3
3
Cl, 4-Cl, 2-Br, 4-Br; X= H, Br). Moisture sensitive study disclosed that these new metal complexes were unreacted for 72 h. Mass spectral
data were employed for proving the mono-nuclearity of the new derivatives. Thermal decomposition pattern of the new derivatives was
explained by thermogravimetric analyses. Elemental analyses data are in concordance with their expected values. The hexa-coordinated
way of titanium-ligand linkage is further proved through NMR, FTIR, and UV-visible spectral studies. The cytotoxic efficiency of new
complexes was tested against MDA-MB-231 human breast carcinoma cell line. Complex 3a exhibited the highest cytotoxic potential of
0
.039 µM in comparison to all its analogues of this series by employing cisplatin as the standard.
Keywords: Cytotoxicity evaluation, 8-Hydroxyquinoline, Moisture Stability, Titanium complexes.
of titanium complexes in the moisture enriched conditions [10].
INTRODUCTION
The vulnerability of titanium complexes towards moisture is
due to the oxophilicity of the titanium atom [11]. Moisture
stable complexes are highly desirable for proper biological
evaluations [12].
Based on our studies, we have found that Ti(IV) complexes
with short Ti-N coordination bonds have exceptional stability
in the hydrous environment [11,13,14]. In view of this, 8-
hydroxyquinoline (8-HQ) is selected as a potential ligand for
the synthesis process. In the present series, we have synthesized
different metallacyclic heteroleptic titanium(IV) derivatives
by employing 8-hydroxyquinoline and various derivatives of
Non-communicable diseases have become the leading
causes of the ever-increasing mortality rate across the globe.
Surprisingly, the vast majority of this decreasing life expec-
tancy is due to cancer [1,2]. Though different kinds of drugs are
using in the treatment of cancer, complete recovery from it is
still a vexing issue. Metal-based drugs hold a strong history in
the field of cancer research [3,4]. The success story of cisplatin,
the first drug from the inorganic background, opened a new
window for the scholars to initiate their research in the synthesis
and biological evaluation of various metal complexes [5].
Among various metal complexes, titanium complexes become
attractive to the researchers due to their low toxicity and fewer
side effects [6].
A few titanium complexes such as budotitane and titanium
dichloride have displayed substantial anticancer abilities against
various cell lines [7]. However, their rapid hydrolysis in the
moisture environment rendered failure in the clinical trial [8,9].
TheAchilles heel in the titanium chemistry is the low stability
2
-hydroxy-N-phenylbenzylamines. Furthermore, we have
systematically monitored the ability of all these complexes to
withstand in hydrous conditions and found that all of them
are stable for 4 days. Additionally, anticancer potential of all
these complexes has evaluated against MDA-MB-231 human
breast carcinoma cell line by using cisplatin as the standard
drug.
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684 Samuel et al.
Asian J. Chem.
#
*
C-5 ), 132.6 (CH, C-4, C-4′), 131.3 (C, C-1 ), 130.4 (CH, C-
EXPERIMENTAL
All the reagents were purified either by distillation or by
#
4
), 129.6 (C, C-4a, C-4a′), 128.9 (CH, C-6, C-6′), 127.2 (CH,
* * * *
C-5 ), 126.1 (CH, C-3 ), 125.1 (CH, C-4 , C-5 ), 124.9 (CH,
re-crystallization and prior to the experiment were dried
thoroughly. Toluene (S.D. Fine Chemicals, b.p., 110.6 ºC) was
dried first by keeping over sodium wire for a night and later
refluxed on the fractionating column for 24 h and finally, it
was distilled off.
#
#
C-2 , C-6 ), 123.6 (CH, C-3, C-3′), 120.7 (CH, C-5, C-5′),
**
1
18.9 (CH, C-7, C-7′), 53.7 (CH
33.1222, C31 Ti (Calcd. 533.1219); Anal. calcd. (%)
Ti: C, 69.80; H, 4.35; N, 7.88; Ti, 8.97. Found
%). C, 69.92; H, 4.41; N, 7.93; Ti, 8.92.
(N-(4-Methylphenyl)benzylamine-2-ato)-bis(8-quino-
2
, C-1 ); HRMS: m/z (pos):
5
H
23
N O
3 3
for C31
H
23
N O
3 3
(
1
1
H NMR spectra: H NMR data were obtained from a
BRUKER Advance III NMR spectrometer in DMSO/CDCl
solution at 400 MHz frequency usingTMS as an internal standard.
[
3
linato)titanium(IV)] (3b): Colour: Reddish brown powder;
m.p. = 181-183 °C; % Yield: 98.1 %; Alcohol estimation
13
13
C NMR spectra: C NMR spectral studies of the new
titanium derivatives were performed in DMSO/CDCl solution
i
(
Pr OH): Calcd. 0.44 g, Found: 0.43 g; UV (DMSO) λmax (log
3
–1
ε, nm): 267 (5.46), 325 (5.53); IR (KBr, νmax, cm ): 2940,
on a BRUKER Advance III NMR spectrometer at 100 MHz
frequency.
2
1
4
8
914, 2860, 1614, 1573, 1494, 1463, 1448, 1373, 1319, 1251,
236, 1172, 1105, 1029, 1010, 950, 902, 821, 740, 713, 615,
FTIR analysis: FTIR spectra were taken on a Shimadzu
IR affinity 1 spectrometer with anhydrous KBr pellets in the
1
32; H NMR (400 MHz, DMSO) δ: 7.64 (2H, dd, J = 1.6,
*
.0 Hz, H-2, H-2′), 7.47 (1H, d, J = 8.0 Hz, H-6 ), 7.36 (1H,
-1
range of 4000-400 cm .
*
d, J = 8.0 Hz, H-3 ), 7.21 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′),
Mass analysis: Mass spectral data of the new titanium(IV)
complexes were recorded on HR-Q-Tof mass spectrometer.
Thermogravimetric analysis:Thermogravimetric analyses
of the new complexes were performed on a TA instrument SDTQ
00, USA at a heating rate of 10 ºC/min from 25 ºC to 900 ºC
under flowing nitrogen environment.
7
1
3
7
5
6
.06 (2H, dd, J = 1.6, 8.0 Hz, H-5, H-5′), 6.88 (2H, dd, J =
.6, 8.0 Hz, H-6, H-6′), 6.84 (2H, dd, J = 1.6, 8.0 Hz, H-3, H-
*
′), 6.75 (1H, t, H-4 ), 6.60 (2H, dd, J = 1.6, 9.6 Hz, H-7, H-
#
′), 6.52 (1H, d, J = 8.4 Hz, H-3 ), 6.36 (1H, d, J = 8.0 Hz, H-
6
#
#
#
), 6.31 (1H, d, J = 8.0 Hz, H-2 ), 6.22 (1H, d, J = 8.0 Hz, H-
*
**
##
), 5.74 (1H, t, H-5 ), 4.27 (2H, s, H-1 ) 2.16 (3H, s, H-4 );
Elemental analysis: Elemental analyses of the complexes
were carried out on an Elementar Vario EL III instrument.
UV analysis: The UV-visible spectra were taken over a
13
C NMR (100 MHz, DMSO) δ: 152.5 (C, C-8, C-8′), 151.0
*
#
(
C, C-2 ), 147.7 (CH, C-2, C-2′), 140.0 (C, C-1 ), 137.2 (C,
C-8a, C-8a′), 135.9 (CH, C-4, C-4′), 134.8 (C, C-4a, C-4a′),
-1
range of 200-800 cm using Jasco V-670 UV-Visible spectro-
photometer.
#
#
1
33.5 (CH, C-3 ), 132.2 (CH, C-5 ), 131.6 (CH, C-6, C-6′),
*
#
1
(
30.6 (CH, C-3, C-3′), 129.5 (C, C-1 ), 127.2 (C, C-4 ), 125.5
Synthesis of 2-hydroxy-N-phenylbenzylamines: Previ-
ously reported method [15] was adopted for the synthesis of
various derivatives of 2-hydroxy-N-phenylbenzylamines.
Synthesis of titanium(IV) derivatives: A previously
reported [16] synthetic route was adopted for the synthesis of
various new titanium(IV) derivatives.
Estimation of titanium and isopropanol: Estimation of
titanium was carried out by a known method [17] and chromate
oxidimetric method [18] employed for estimating the liberated
isopropanol during the reactions.
*
*
CH, C-6 ), 125.0 (CH, C-5, C-5′), 123.2 (CH, C-4 ), 122.6
* * #
(
CH, C-7, C-7′), 120.7 (CH, C-3 , C-5 ), 119.0 (CH, C-2 , C-
# ** ##
6
), 53.8 (CH
2
, C-1 ), 20.3 (CH
Ti (Calcd. 547.1375); Anal. calcd. (%)
Ti: C, 70.36; H, 4.60; N, 7.68; Ti, 8.66. Found
%). C, 70.26; H, 4.61; N, 7.60; Ti, 8.71.
(N-(4-Methoxyphenyl)benzylamine-2-ato)-bis(8-
3
, C-4 ); HRMS: m/z (pos):
5
47.1381, C32
H
25
N O
3 3
for C32
H
25
N O
3 3
(
[
quinolinato)titanium(IV)] (3c): Colour: Reddish brown
powder; m.p. = 187-189 °C; %Yield: 98.4 %;Alcohol estima-
i
tion (Pr OH): Calcd. 0.46 g, Found: 0.45 g; UV (DMSO) λmax
–1
Spectral data
(log ε, nm): 269 (5.48), 320 (5.55); IR (KBr, νmax, cm ): 2928,
2
1
905, 2859, 1591, 1573, 1510, 1494, 1463, 1446, 1373, 1319,
[
(N-(Phenyl)benzylamine-2-ato)-bis(8-quinolinato)-
1
230, 1105, 1004, 898, 821, 740, 711, 615, 430; H NMR
titanium(IV)] (3a): Colour: Reddish brown powder; m.p. =
i
(400 MHz, DMSO) δ: 7.77 (2H, dd, J = 1.6, 8.0 Hz, H-2, H-
1
78-180 °C; % Yield: 98.7 %; Alcohol estimation (Pr OH):
2
′), 7.43 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′), 7.39 (2H, dd, J
Calcd. 0.46 g, Found: 0.45 g; UV (DMSO) λmax (log ε, nm):
–1
= 1.6, 8.0 Hz, H-5, H-5′), 7.16 (2H, dd, J = 1.6, 8.0 Hz, H-6,
2
1
69 (5.45), 304 (5.51); IR (KBr, νmax, cm ): 2937, 2912, 2861,
815, 1749, 1600, 1573, 1494, 1463, 1448, 1373, 1319, 1257,
105, 1064, 1051, 1010, 898, 821, 786, 740, 711, 628, 422;
*
H-6′), 7.08 (1H, d, J = 7.6 Hz, H-6 ), 7.04 (1H, d, J = 8.4 Hz,
*
*
#
H-3 ), 7.00 (1H, t, H-4 ), 6.98 (1H, d, J = 7.6 Hz, H-3 ), 6.80
(2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 6.63 (1H, d, J = 7.6 Hz,
1
1
H NMR (400 MHz, DMSO) δ: 8.47 (2H, dd, J = 1.6, 8.0 Hz,
H-2, H-2′), 7.83 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′), 7.45
#
H-5 ), 6.58 (2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′), 6.56 (1H, d,
#
*
J = 3.6 Hz, H-2 ), 6.49 (1H, t, H-5 ), 6.42 (1H, d, J = 8.8 Hz,
(
2H, dd, J = 1.6, 8.0 Hz, H-5, H-5′), 7.10 (2H, dd, J = 1.6, 8.0
#
**
## 13
#
*
H-6 ), 4.31 (2H, s, H-1 ), 3.66 (3H, s, H-4 ); C NMR (100
Hz, H-6, H-6′), 7.06 (1H, t, H-4 ), 7.02 (1H, t, H-4 ), 6.99
*
#
#
MHz, DMSO) δ: 155.0 (C, C-2 ), 152.5 (C, C-8, C-8′), 151.1
(
6
2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 6.84 (2H, t, H-3 , H-5 ),
#
#
(
C, C-4 ), 147.7 (CH, C-2, C-2′), 136.6 (C, C-1 ), 134.7 (C,
.75 (2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′), 6.72 (1H, d, J = 6.0
*
#
*
C-8a, C-8a′), 132.6 (CH, C-4, C-4′), 131.7 (C, C-4a, C-4a′),
Hz, H-6 ), 6.67 (1H, t, H-5 ), 6.58 (1H, d, J = 4.0 Hz, H-3 ),
* *
#
#
130.4 (CH, C-6, C-6′), 129.6 (CH, C-4 , C-6 ), 128.5 (C, C-
* * *
6
4
.54 (1H, d, J = 4.8 Hz, H-2 ), 6.50 (1H, d, J = 7.6 Hz, H-6 ),
**
13
1 ), 127.1 (CH, C-3 ), 125.5 (CH, C-5 ), 125.0 (CH, C-3, C-
.37 (2H, s, H-1 ); C NMR (100 MHz, DMSO) δ: 152.5 (C,
*
#
3′), 123.6 (CH, C-5, C-5′), 120.7 (CH, C-7, C-7′), 119.0 (CH,
C-2 ), 151.0 (C, C-1 ), 147.7 (C, C-8, C-8′), 142.0 (CH, C-
#
#
#
#
C-3 , C-5 ), 116.9 (CH, C-2 , C-6#), 55.7 (CH , OCH ), 53.9
3
3
3
), 135.9 (CH, C-2, C-2′), 134.8 (C, C-8a, C-8a′), 133.4 (CH,

Vol. 32, No. 3 (2020)
Synthesis, Characterization, Stability and Cytotoxic Evaluation of Novel Titanium(IV) Complexes 685
*
*
i
(
(
6
4
CH
2
, C-1 ); HRMS: m/z (pos): 563.1330, C32
H
3
25
N
3
O
4
Ti
Ti: C,
8.22; H, 4.47; N, 7.46; Ti, 8.50. Found (%). C, 68.30; H,
.44; N, 7.53; Ti, 8.54.
(N-(2-Chlorophenyl)benzylamine-2-ato)-bis(8-quino-
m.p. = 189-190 °C; %Yield: 98.1 %;Alcohol estimation (Pr OH):
Calcd. 563.1325); Anal. calcd. (%) for C32
H
25
N
O
4
Calcd. 0.49 g, Found: 0.48 g; UV (DMSO) λmax (log ε, nm):
–1
263 (5.50), 322 (5.55); IR (KBr, νmax, cm ): 2952, 2911, 2867,
1732, 1600, 1573, 1494, 1463, 1373, 1319, 1259, 1170, 1122,
1
[
1105, 1004, 902, 821, 785, 742, 717, 628, 465; H NMR (400
linato)titanium(IV)] (3d): Colour: Reddish brown powder;
MHz, DMSO) δ: 8.50 (2H, dd, J = 1.6, 8.0 Hz, H-2, H-2′),
8.40 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′), 8.35 (2H, dd, J =
m.p. = 182-184 °C; % Yield: 98.2 %; Alcohol estimation
i
*
(
Pr OH): Calcd. 0.48 g, Found: 0.47 g; UV (DMSO) λmax (log
1.6, 8.0 Hz, H-5, H-5′), 7.98 (1H, d, J = 8.0 Hz, H-4 ), 7.92
–1
*
ε, nm): 262 (5.47), 308 (5.54); IR (KBr, νmax, cm ): 2944,
(1H, d, J = 8.0 Hz, H-3 ), 7.84 (2H, dd, J = 1.6, 8.0 Hz, H-6,
#
#
2
1
908, 2847, 1593, 1573, 1494, 1463, 1448, 1373, 1249, 1236,
H-6′), 7.75 (1H, d, J = 8.0 Hz, H-2 ), 7.43 (1H, t, H-3 ), 7.38
1
#
126, 1105, 1004, 894, 823, 785, 738, 711, 628, 432; H NMR
(2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 7.13 (1H, t, H-5 ), 7.09
(1H, s, H-6 ), 6.89 (1H, dt, H-4 ), 6.56 (2H, dd, J = 1.6, 8.0
#
*
#
(
(
(
400 MHz, DMSO) δ: 8.43 (1H, d, J = 7.6 Hz, H-3 ), 7.86
#
#
2H, dd, J = 1.6, 8.0 Hz, H-2, H-2′), 7.79 (1H, t, H-5 ), 7.71
Hz, H-7, H-7′), 6.38 (1H, d, J = 7.6 Hz, H-6 ), 4.2 (2H, s, H-
*
#
*
**
13
1H, d, J = 8.0 Hz, H-6 ), 7.37 (2H, t, H-4 , H-5 ), 7.16 (2H,
1 ); C NMR (100 MHz, DMSO) δ: 152.5 (C, C-8, C-8′),
*
#
dd, J = 1.6, 8.0 Hz, H-4, H-4′), 7.07 (2H, dd, J = 1.6, 8.0 Hz,
H-5, H-5′), 6.89 (2H, dd, J = 1.6, 8.0 Hz, H-6, H-6′), 6.84
150.1 (C, C-2 ), 147.7 (CH, C-2, C-2′), 142.1 (C, C-1 ), 136.8
* *
(C, C-1 ), 135.3 (C, C-8a, C-8a′), 134.3 (CH, C-4 ), 133.8
*
#
*
(
(
(
1H, d, J = 8.0 Hz, H-3 ), 6.62 (1H, d, J = 8.0 Hz, H-6 ), 6.46
(CH, C-4, C-4′), 132.2 (CH, C-6 ), 131.4 (C, C-4a, C-4a′),
*
#
#
2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 6.43 (1H, t, H-4 ), 6.32
129.6 (CH, C-3 , C-5 ), 128.9 (CH, C-6, C-6′), 127.2 (CH, C-
*
*
13
#
*
2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′), 4.21 (2H, s, H-1 ); C
4 ), 126.3 (CH, C-5 ), 124.9 (CH, C-3, C-3′), 123.3 (CH, C-5,
# #
NMR (100 MHz, DMSO) δ: 152.7 (C, C-8, C-8′), 151.1 (C,
C-5′), 120.7 (CH, C-7, C-7′), 118.9 (CH, C-2 , C-6 ), 112.4
*
* **
C-2 ), 147.7 (CH, C-2, C-2′), 142.2 (C, C-8a, C-8a′), 137.9
(CH, C-3 ), 55.2 (CH
2
, C-1 ); HRMS: m/z (pos): 611.0330,
Ti (Calcd. 611.0324); Anal. calcd. (%) for
Ti: C, 60.81; H, 3.62; N, 6.86; Ti, 7.82. Found
#
#
*
(
C, C-1 ), 136.7 (CH, C-3 ), 135.2 (C, C-1 ), 134.2 (CH, C-4,
C
C
31
H
22BrN
3
O
3
*
C-4′), 133.6 (C, C-4a, C-4a′), 132.2 (CH, C-6 ), 131.3 (CH,
31
H22BrN
3
O
3
*
#
C-4 ), 130.3 (CH, C-5 ), 129.6 (CH, C-6, C-6′), 127.3 (CH,
(%). C, 60.94; H, 3.51; N, 6.94; Ti, 7.93.
#
#
*
C-4 ), 126.3 (C, C-2 ), 125.4 (CH, C-5 ), 124.9 (CH, C-3, C-
′), 123.5 (CH, C-5, C-5′), 120.7 (CH, C-7, C-7′), 119.0 (CH,
[(N-(4-Methylphenyl)-5-bromobenzylamine-2-ato)-
bis(8-quinolinato)titanium(IV)] (3g): Colour: Reddish brown
powder; m.p. = 192-194 °C; %Yield: 98.6 %;Alcohol estima-
3
*
#
**
C-3 , C-6 ), 53.6 (CH
C
C
2
, C-1 ); HRMS: m/z (pos): 567.0834,
Ti (Calcd. 567.0829); Anal. calcd. (%) for
Ti: C, 65.57; H, 3.91; N, 7.40; Ti, 8.43. Found
i
31
H
22ClN
3
O
3
tion (Pr OH): Calcd. 0.50 g, Found: 0.49 g; UV (DMSO) λmax
–1
31
H22ClN
O
3 3
(log ε, nm): 264 (5.51), 315 (5.59); IR (KBr, νmax, cm ): 2944,
2900, 2845, 1815, 1724, 1614, 1573, 1519, 1494, 1462, 1373,
1319, 1257, 1236, 1122, 1105, 1082, 1002, 902, 823, 806,
(
%). C, 65.60; H, 3.92; N, 7.43; Ti, 8.41.
(N-(4-Chlorophenyl)benzylamine-2-ato)-bis(8-quino-
[
1
linato)titanium(IV)] (3e): Colour: Reddish brown powder;
785, 742, 715, 665, 430; H NMR (400 MHz, DMSO) δ: 8.51
m.p. = 197-199 °C; % Yield: 98.6 %; Alcohol estimation
(2H, dd, J = 1.6, 8.0 Hz, H-2, H-2′), 8.41 (2H, dd, J = 1.6, 8.0
i
#
(
Pr OH): Calcd. 0.50 g, Found: 0.49 g; UV (DMSO) λmax (log
Hz, H-4, H-4′), 8.36 (1H, d, J = 8.0 Hz, H-3 ), 7.99 (2H, dd, J
–1
ε, nm): 268 (5.48), 314 (5.55); IR (KBr, νmax, cm ): 2956,
= 1.6, 8.0 Hz, H-5, H-5′), 7.94 (2H, dd, J = 1.6, 8.0 Hz, H-6,
H-6′), 7.86 (2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 7.45 (2H, dd,
2
1
4
8
7
7
1
912, 2862, 1597, 1573, 1494, 1463, 1448, 1373, 1319, 1251,
236, 1174, 1126, 1105, 1002, 896, 823, 785, 742, 709, 628,
*
J = 1.6, 8.0 Hz, H-7, H-7′), 7.41 (1H, d, J = 8.0 Hz, H-4 ),
1
*
#
38; H NMR (400 MHz, DMSO) δ: 8.51 (2H, dd, J = 1.6,
7.07 (1H, s, H-6 ), 7.04 (1H, d, J = 8.8 Hz, H-5 ), 6.77 (1H, d,
*
#
.0 Hz, H-2, H-2′), 7.98 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′),
J = 6.0 Hz, H-3 ), 6.57 (1H, d, J = 8.0 Hz, H-2 ), 6.31 (1H, d,
*
#
**
##
.86 (2H, dd, J = 1.6, 8.0 Hz, H-5, H-5′), 7.74 (1H, t, H-4 ),
J = 8.0 Hz, H-6 ), 4.22 (2H, s, H-1 ), 2.12 (3H, CH
3
, H-4 );
13
.42 (2H, dd, J = 1.6, 8.0 Hz, H-6, H-6′), 7.36 (2H, dd, J =
C NMR (100 MHz, DMSO) δ: 152.5 (C, C-8, C-8′), 150.1
*
*
#
.6, 8.0 Hz, H-3, H-3′), 7.23 (1H, t, H-5 ), 7.15 (1H, d, J = 8.0
(C, C-2 ), 147.7 (CH, C-2, C-2′), 140.0 (C, C-1 ), 137.8 (C,
*
#
#
*
*
Hz, H-6 ), 6.98 (2H, d, J = 8.0 Hz, H-3 , H-5 ), 6.92 (1H, d, J
=
6
C-1 ), 136.3 (CH, C-4 ), 135.7 (C, C-8a, C-8a′), 134.5 (CH,
*
*
8.0 Hz, H-3 ), 6.86 (2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′),
C-4, C-4′), 132.9 (C, C-4a, C-4a′), 131.5 (CH, C-6 ), 130.6
#
#
**
13
#
#
#
.29 (2H, d, J = 8.4 Hz, H-2 , H-6 ), 4.33 (2H, s, H-1 ); C
(CH, C-6, C-6′), 129.6 (CH, C-3 , C-5 ), 128.9 (C, C-4 ), 126.3
*
NMR (100 MHz, DMSO) δ: 152.5 (C, C-8, C-8′), 151.1 (C,
(C, C-5 ), 124.9 (CH, C-3, C-3′), 123.6 (CH, C-5, C-5′), 120.7
*
#
#
#
*
C-2 ), 147.7 (CH, C-2, C-2′), 140.7 (C, C-1 ), 135.7 (C, C-8a,
C-8a′), 134.9 (CH, C-4, C-4′), 133.7 (C, C-4a, C-4a′), 132.7
(CH, C-7, C-7′), 118.9 (CH, C-2 , C-6 ), 112.4 (CH, C-3 ),
** ##
55.4 (CH
625.0489, C32
for C32 24BrN
2
, C-1 ), 20.3 (CH
Ti (Calcd. 625.0481);Anal. calcd. (%)
Ti: C, 61.36; H, 3.86; N, 6.71; Ti, 7.64. Found
3
, C-4 ); HRMS: m/z (pos):
*
#
#
(
C, C-1 ), 131.9 (CH, C-6, C-6′), 130.6 (CH, C-3 , C-5 ), 129.5
C, C-4 ), 127.1 (CH, C-5 ), 125.9 (CH, C-3 ), 124.9 (CH, C-
H
3
24BrN
O
3 3
#
*
*
(
4
(
H
O
3
*
*
, C-6 ), 123.6 (CH, C-3, C-3′), 122.6 (CH, C-5, C-5′), 120.7
(%). C, 61.42; H, 3.90; N, 6.75; Ti, 7.67.
#
#
**
CH, C-7, C-7′), 119.0 (CH, C-2 , C-6 ), 53.9 (CH
2
, C-1 );
Ti (Calcd.
Ti: C, 65.57; H,
.91; N, 7.40; Ti, 8.43. Found (%). C, 65.78; H, 3.86; N, 7.54;
[(N-(4-Methoxyphenyl)-5-bromobenzylamine-2-ato)-
bis(8-quinolinato)titanium(IV)] (3h): Colour: Reddish brown
powder; m.p. = 195-197 °C; %Yield: 98.2 %;Alcohol estima-
HRMS: m/z (pos): 567.0832, C31
H
22ClN
3
O
3
5
3
67.0829); Anal. calcd. (%) for C31
H22ClN
3
O
3
i
tion (Pr OH): Calcd. 0.44 g, Found: 0.43 g; UV (DMSO) λmax
–1
Ti, 8.33.
(log ε, nm): 263 (5.52), 330 (5.61); IR (KBr, νmax, cm ): 2932,
[(N-(Phenyl)-5-bromobenzylamine-2-ato)-bis(8-quino-
2904, 2856, 1573, 1462, 1373, 1319, 1259, 1230, 1172, 1105,
1
linato)titanium(IV)] (3f): Colour: Reddish brown powder;
1002, 900, 819, 785, 742, 715, 628, 613, 484; H NMR (400

686 Samuel et al.
Asian J. Chem.
#
MHz, DMSO) δ: 8.51 (2H, dd, J = 1.6, 8.0 Hz, H-2, H-2′),
J = 1.6, 8.0 Hz, H-7, H-7′), 7.15 (1H, d, J = 8.0 Hz, H-5 ),
*
*
8
1
6
8
.42 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′), 8.02 (2H, dd, J =
.6, 8.0 Hz, H-5, H-5′), 7.97 (2H, dd, J = 1.6, 8.0 Hz, H-6, H-
′), 7.89 (2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 7.79 (1H, d, J =
7.13 (1H, s, H-6 ), 6.88 (1H, d, J = 8.0 Hz, H-4 ), 6.56 (1H, d,
J = 8.0 Hz, H-3 ), 6.43 (1H, d, J = 8.0 Hz, H-2 ), 6.25 (1H, d,
, H-1 ); C NMR (100
MHz, DMSO) δ: 152.5 (C, C-8, C-8′), 150.2 (C, C-2 ), 147.7
(CH, C-2, C-2′), 140.8 (C, C-1 ), 137.3 (C, C-1 ), 136.8 (CH,
C-4 ), 134.7 (C, C-8a, C-8a′), 133.3 (CH, C-6 ), 132.2 (CH,
C-4, C-4′), 131.7 (C, C-4a, C-4a′), 130.9 (CH, C-6, C-6′), 129.6
(CH, C-3 , C-5 ), 128.9 (CH, C-4 ), 126.3 (C, C-5 ), 125.0
*
#
#
**
13
J = 8.0 Hz, H-6 ), 4.28 (2H, s, CH
2
*
*
.0 Hz, H-4 ), 7.50 (2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′), 7.46
*
#
#
*
(1H, d, J = 8.0 Hz, H-3 ), 7.37 (1H, d, J = 8.0 Hz, H-3 ), 7.17
*
#
*
*
(
1H, s, H-6 ), 7.03 (1H, d, J = 8.0Hz, H-5 ), 6.57 (1H, d, J =
#
#
8
1
1
1
.0 Hz, H-2 ), 6.35 (1H, d, J = 8.0 Hz, H-6 ), 4.09 (2H, s, H-
**
## 13
#
#
#
*
), 3.63 (3H, OCH
53.7 (C, C-8, C-8′), 151.1 (C, C-2 ), 148.7 (CH, C-2, C-2′),
40.2 (C, C-1 ), 137.6 (C, C-1 ), 136.5 (CH, C-4 ), 135.6 (C,
3
, H-4 ); C NMR (100 MHz, DMSO) δ:
*
(CH, C-3, C-3′), 123.6 (CH, C-5, C-5′), 120.7 (CH, C-7, C-
#
*
*
#
#
*
7′), 118.9 (CH, C-2 , C-6 ), 112.4 (CH, C-3 ), 55.4 (CH
2
, C-
Ti (Calcd.
Ti: C, 53.87;
**
C-8a, C-8a′), 133.9 (CH, C-4, C-4′), 132.9 (C, C-4a, C-4a′),
1 ); HRMS: m/z (pos): 688.9436, C31
H
21Br
2
N
3
O
3
*
#
1
5
1
2
4
6
3
31.5 (CH, C-6 ), 130.9 (CH, C-6, C-6′), 129.6 (CH, C-3 , C-
688.9429); Anal. calcd. (%). for C31
H21Br
N
2 3
O
3
#
#
*
), 128.3 (C, C-4 ), 125.9 (C, C-5 ), 124.4 (CH, C-3, C-3′),
H, 3.06; N, 6.08; Ti, 6.93. Found (%). C, 53.91; H, 3.11; N,
6.13; Ti, 7.01 (The numbering followed for the NMR inter-
pretation is indicated in Fig. 1).
22.9 (CH, C-5, C-5′), 120.4 (CH, C-7, C-7′), 117.3 (CH, C-
#
#
#
*
**
, C-6 ), 111.8 (CH, C-3 ), 55.7 (CH
2
, C-1 ), 21.9 (CH
); HRMS: m/z (pos): 641.0434, C32 Ti (Calcd.
Ti: C, 59.84; H,
.77; N, 6.54; Ti, 7.45. Found (%). C, 59.92; H, 3.81; N, 6.53;
3
, C-
#
H
24BrN
O
3 4
41.0430);Anal. calcd. (%) for C32
H24BrN
O
3 4
O
O
Ti, 7.57.
7
7'
O
O
3*
8
3
8'
8a'
[
(N-(2-Bromophenyl)-5-bromobenzylamine-2-ato)-
6
2* OH
Ti
6'
5'
4*
bis(8-quinolinato)titanium(IV)] (3i): Colour: Reddish brown
powder; m.p. = 189-191 °C; %Yield: 97.8 %;Alcohol estima-
8a
2#
5
1*
H
5
*
N 1
2
N
'
N
1#
4a
1'
3#
4
a'
X
i
6*
1**
tion (Pr OH): Calcd. 0.47 g, Found: 0.46 g; UV (DMSO) λmax
4
4'
2
4#
–1
(log ε, nm): 264 (5.53), 320 (5.58),; IR (KBr, νmax, cm ): 2946,
3'
6#
5#
R
2
1
7
911, 2842, 1726, 1597, 1573, 1494, 1462, 1456, 1373, 1361,
319, 1282, 1236, 1124, 1105, 1082, 1004, 898, 821, 785,
Fig. 1. Numbering followed for the NMR interpretation of the complexes
1
40, 717, 628, 461; H NMR (400 MHz, DMSO) δ: 8.50 (2H,
Cytotoxicity evaluation: The cytotoxicity ability of the
newly synthesized derivatives was carried out on MDA-MB-
#
dd, J = 1.6, 8.0 Hz, H-2, H-2′), 8.41 (1H, d, J = 8.0 Hz, H-3 ),
8
.35 (2H, dd, J = 1.6, 8.0 Hz, H-4, H-4′), 7.98 (1H, d, J = 8.0
231 human breast carcinoma cell line. The cell line was obtained
*
*
Hz, H-4 ), 7.92 (1H, d, J = 8.0 Hz, H-3 ), 7.42 (2H, dd, J =
from National Centre for Cell Science (Pune, India). Already
existing procedures [19,20] were adopted for the evaluating
cytotoxicity.
1
6
3
5
.6, 8.0 Hz, H-5, H-5′), 7.37 (2H, dd, J = 1.6, 8.0 Hz, H-6, H-
*
′), 7.17 (1H, s, H-6 ), 7.09 (2H, dd, J = 1.6, 8.0 Hz, H-3, H-
′), 6.91 (2H, dd, J = 1.6, 8.0 Hz, H-7, H-7′), 6.72 (1H, t, H-
#
#
#
RESULTS AND DISCUSSION
), 6.60 (1H, dt, H-4 ), 6.34 (1H, d, J = 8.0 Hz, H-6 ), 4.12
**
13
(
(
(
2H, s, CH
2
, H-1 ); C NMR (100 MHz, DMSO) δ: 153.4
The precursor titanium tetraisopropoxide [Ti(OPri) ] (1)
4
reacts with the bidentate ligand 8-hydroxyquinoline in 1:2
molar ratio in anhydrous toluene and produces the complex
[(Q )Ti(OPri) ] (2). Complex 2, on treating further with 2-
*
C, C-8, C-8′), 151.1 (C, C-2 ), 146.9 (CH, C-2, C-2′), 141.4
C, C-1 ), 136.1 (C, C-1 ), 134.6 (CH, C-4 ), 134.0 (C, C-8a,
#
*
*
*
C-8a′), 132.9 (CH, C-6 ), 132.5 (CH, C-4, C-4′), 131.2 (C, C-
2
2
#
#
4
1
a, C-4a′), 130.5 (CH, C-6, C-6′), 129.8 (CH, C-3 , C-5 ),
hydroxy-N-phenylbenzylamine in equimolar ratio produces
#
#
28.5 (CH, C-4 ), 126.6 (C, C-2 ), 124.4 (CH, C-3, C-3′), 122.7
titanium complexes of general formula [(Q) Ti(2-O-5-X-
2
#
(CH, C-5, C-5′), 120.5 (CH, C-7, C-7′), 117.4 (CH, C-6 ; C,
C H CH NC H R] (3a-j) as given in Scheme-I.
6
3
2
6
4
*
*
**
C-5 ), 112.9 (CH, C-3 ), 53.2 (CH
88.9438, C31 Ti (Calcd. 688.9429); Anal. calcd.
%) for C31 Ti: C, 53.87; H, 3.06; N, 6.08; Ti, 6.93.
Found (%). C, 53.93; H, 3.15; N, 6.14; Ti, 7.02.
(N-(4-Bromophenyl)-5-bromobenzylamine-2-ato)-
2
, C-1 ); HRMS: m/z (pos):
With the progress of the reaction, free isopropanol gets
6
(
H21Br
N O
2 3 3
released in the reaction mixture. The reaction mixture containing
toluene-isopropanol azeotrope was then subjected to iodome-
tric titration for the evaluation of reaction advancement. All
the reactions were very rapid and completed in 4-5 h. The newly
synthesized derivatives were pale yellow in appearance with
quantitative yields. These complexes are insoluble in most of
the organic solvents except in DMSO and purified with anhydrous
acetonitrile and toluene. Mono-nuclearity of all these complexes
has been proved through mass spectra.Various substituents used
for the synthesis of complexes are shown depicted in Table-1.
Elemental analysis: Elemental analyses have been carried
out in order to identify the percentage of various elements present
in the newly synthesized titanium complexes. The results were
very close to their theoretical values. The analysis results reaff-
irmed the mono-nuclearity of these complexes.
H21Br
N O
2 3 3
[
bis(8-quinolinato)titanium(IV)] (3j): Colour: Reddish brown
powder; m.p. = 185-187 °C; %Yield: 98.3 %;Alcohol estima-
i
tion (Pr OH): Calcd. 0.49 g, Found: 0.48 g; UV (DMSO) λmax
–1
(
log ε, nm): 265 (5.53), 324 (5.60); IR (KBr, νmax, cm ): 2967,
2
1
7
919, 2859, 1726, 1598, 1573, 1494, 1462, 1456, 1373, 1361,
319, 1259, 1236, 1172, 1122, 1105, 1078, 1002, 902, 806,
1
85, 742, 713, 628, 439; H NMR (400 MHz, DMSO) δ: 8.51
(2H, dd, J = 1.6, 8.0 Hz, H-2, H-2′), 8.35 (2H, dd, J = 1.6, 8.0
Hz, H-4, H-4′), 8.02 (2H, dd, J = 1.6, 8.0 Hz, H-5, H-5′), 7.89
2H, dd, J = 1.6, 8.0 Hz, H-6, H-6′), 7.80 (1H, d, J = 8.0 Hz,
(
#
H-3 ), 7.48 (2H, dd, J = 1.6, 8.0 Hz, H-3, H-3′), 7.44 (2H, dd,

Vol. 32, No. 3 (2020)
Synthesis, Characterization, Stability and Cytotoxic Evaluation of Novel Titanium(IV) Complexes 687
Anhydrous toluene
i
i
[
Ti(OPr ) ]
2 HQ
[(Q )Ti(OPr ) ]
i
4
+
2
2
+
2 Pr OH
(1:2)
(1)
(2)
o
1
00 - 120 C / 4-5 h
Anhydrous toluene
i
i
[
(Q )Ti(OPr ) ]
[(Q2)Ti(2-O-5-X-C6H3CH2NC6H4R)] +
2 Pr OH
2
2
+ 2-OH-5-X-C H CH NHC H R
6
3
2
6 4
(
1:1)
(2)
(3a-3j)
o
1
00 - 120 C / 4-5 h
i
[
Where, HQ = 8-hydroxyquinoline; Pr = isopropyl; R = H, 4-CH , 2-Cl, 4-Cl, 2-Br, 4-Br and X= H, Br]
3
Scheme-I
retical value of 14.10 %. The stable TiO obtained for other
2
TABLE-1
LIST OF SUBSTITUENTS USED FOR THE SYNTHESIS
complexes are 14.74 % (3e) and 13.18 % (3h) compared to
their expected value of 14.57 % and 13.03 %, respectively.
UV-visible spectral analysis: Dimethyl sulfoxide was
used for recording the UV-visible spectra of these derivatives.
Each complex exhibited multiple absorption bands. The first
λ-maximum is due to the n-π* transition and the absorption
bands appeared in the range 310-330 nm are due to the ligand
to titanium charge transfer [11,24].
Compd.
R
H
X
H
H
H
H
H
Compd.
R
H
X
Br
Br
Br
Br
Br
3
3
3
3
a
b
c
d
3f
3g
3h
3i
4-CH
4-OCH
2-Cl
4-CH
3
3
4-OCH
2-Br
3
3
3
e
4-Cl
3j
4-Br
NMR spectral analysis: In order to explain the NMR
spectra of all the newly synthesized derivatives, it had been
compared with the spectra of the free ligand molecules, which
were used for the synthesis of different derivatives [21-23].
The hydroxyl proton of phenols normally appears in the range
δ 8.5-10.5 ppm and the -NH proton observed at the region of
δ 4.5-6.5 ppm, respectively. Absence of -OH or -NH peak in
the spectra of the complexes is the strong evidence for the
removal of a proton from -OH and -NH groups as well as the
formation of new Ti-O and Ti-N bonds. The δ values of other
protons and carbons have appeared at their normal positions.
IR spectral analysis: IR interpretations have been made
by matching the spectra of the complexes with that of free ligands
employed for the preparation of the complexes [21-23]. The
Mass spectral analysis: High-resolution mass spectra were
employed for recording the molecular weight of the newly synthe-
sized titanium(IV) derivatives. Nuclearity of all these derivatives
was found as one. Additionally, the mass spectral data are close
to their expected molecular weight of the complexes.
Stability studies: The inability to stay in the hydrous condi-
tion is theAchilles heel of most of the titanium(IV) complexes.
Though some of the titanium complexes displayed promising
tumour-inhibiting potentials, their weak stability restrained
them from further development. The inability of titanium comp-
lexes to withstand in water enriched environment is due to the
oxophilicity of titanium. This results in the disintegration of
the complex into various ligand fragments as well as thermo-
dynamically stable titanium dioxide [11].
UV-visible spectroscopy was employed for the stability
evaluation. In the case of titanium complexes, absorption band
appeared in the range of 310-330 nm was the signature of the
ligand-to-metal charge transfer band (LMCT). This signal was
considered as a reference for the stability evaluation. The absor-
ption band is neither turning to zero nor changing its position
even after a period of 96 h in the hydrous environment. How-
ever, a small decrease noticed in the absorbance values in the
course of measurements could be considered as the slow disso-
ciation of the complexes in the moist medium. The enhanced
stability of these titanium(IV) derivatives is due to the small
Ti-N bond [11], which is missing in the case of well-known
tumour inhibiting complexes like Budotitane and Titanocene
dichloride. Fig. 2 represents the UV-visible absorption overtime
for the complex 3h.
Cytotoxicity evaluation:All the newly synthesized Ti(IV)
derivatives were subjected to cytotoxicity evaluation. The
cytotoxicity potential of titanium complexes was determined
according to reported procedures [19,20]. The study was perf-
ormed on MDA-MB-231 human breast carcinoma cell line
and found that all these new complexes have moderate tumour
inhibiting potentials.
-1
disappearance of a band in the range 3400-3100 cm indicates
the deprotonation of hydroxyl group and the subsequent form-
ation of metal-hetero atom bonds. Two new peaks have been
-1
observed in the range 635-610 and 455-430 cm were another
proof of the removal of protons from -OH and -NH groups
and the formation of Ti-O and Ti-N bonds.
Thermogravimetric analysis: In order to assess the thermal
stability and the decomposition pathway, thermogravimetric
analyses were performed up to 900 ºC for three complexes
(
3c, 3e and 3h). These molecules exhibited multiple decom-
position patterns due to the pyrolysis of organic moieties at
different temperatures. Complex 3c undergoes two decomposi-
tions before it reaches the thermodynamically stable form. The
first decomposition observed at 336.73 ºC is due to the pyrolysis
of aromatic moieties present in the Schiff′s base part of the
complex. At this stage, the complex suffered a weight loss of
39.40 % against the expected value of 40.33 %. The next stage
of dissociation appeared at 504.30 ºC and the molecule had
undergone a weight loss of 45.80 % against its theoretical value
of 45.48 %. This is due to the dissociation of quinoline moiety
present in the complex. The amount of TiO
2
obtained at the
end of the analysis was found as 14.80 % compared to the theo-

688 Samuel et al.
Asian J. Chem.
3
nation for these newly synthesized titanium(IV) complexes,
which were derived from various derivatives of 2-hydroxy-N-
phenylbenzylamines. Fig. 3 represents the proposed tentative
structure of the newly synthesized Ti(IV) derivatives.
9-5 0 min
9-5 1 h
9-5 2 h
9-5 3 h
9-5 4 h
9-5 5 h
9-5 6 h
9-5 7 h
9-5 8 h
9-5 24 h
9-5 48 h
9-5 72 h
9-5 96 h
2
1
0
R
X
N
O
O
N
O
N
-
1
2
00
300
400
500
Ti
Wavelength (nm)
Fig. 2. UV-visible absorption overtime for [(N-(4-methoxyphenyl)-5-
bromobenzylamine-2-ato)-bis(8-quinolinato)titanium(IV)] (3h)
upon addition of water
It has been found from the in-vitro study that all these
new derivatives (3a-j) have substantial antitumor activity
against the cell line tested. Complex 3a showed the highest
potential of 0.039 µM against 0.017 µM of cisplatin [25]. The
higher activity of this complex compared to all its analogues
is due to the presence of smaller and potent Schiff′s base ligands.
Additionally, complex 3e was found as the least active mole-
cule in this series and its low antiproliferative activity presum-
ably due to the presence of bulky electron-withdrawing group
in the complex. Antitumor efficiency of 4-methyl substituted
titanium(IV) derivative has been found as moderate. However,
a decrease in activity was observed while replacing the methyl
group with a methoxy moiety. This difference in activity is
because of the larger methoxy group. Complex without any
substitution on the aniline moiety exhibited more cytotoxic
potential than complexes with various substitutions. The cyto-
toxicity potential of complexes (3a-j) is depicted in Table-2.
Fig. 3. Proposed structure of the titanium(IV) derivatives
ACKNOWLEDGEMENTS
The authors thank St. Theresa International College,
Bangkok, Thailand andVellore Institute of Technology,Vellore,
India for providing necessary facilities to carry out this project
work.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests
regarding the publication of this article.
REFERENCES
1. F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre and A.
Jemal, CA Cancer J. Clin., 68, 394 (2018);
https://doi.org/10.3322/caac.21492
2
.
J. Ferlay, M. Colombet, I. Soerjomataram, T. Dyba, G. Randi, M. Bettio,
A. Gavin, O. Visser and F. Bray, Eur. J. Cancer, 103, 356 (2018);
https://doi.org/10.1016/j.ejca.2018.07.005
TABLE-2
CYTOTOXICITY VALUES OBTAINED FOR COMPLEXES 3a-j
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Compd.
IC (µM)
Compd.
IC (µM)
50
5
0
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3
a
0.0394 ± 0.0039
0.0877 ± 0.0057
0.1279 ± 0.0033
0.0748 ± 0.0084
0.1674 ± 0.0091
0.0474 ± 0.0049
3g
3h
3i
0.1366 ± 0.0052
0.1346 ± 0.0019
0.1142 ± 0.0027
0.1316 ± 0.0048
0.0166 ± 0.0047
–
4
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c
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3j
Cisplatin
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7
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3
e
f
(
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9
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The stability study confirms that all the newly synthesized
titanium(IV) derivatives have an ability to withstand in a moist
environment for a period of 96 h. The NMR and UV-visible
spectra are the direct proof of their stability. The binding of
titanium(IV) through nitrogen and oxygen atoms have been
confirmed by IR and NMR spectroscopy. Elemental analyses
and TGA results were in accordance with the theoretical values.
Monomeric nature of all these derivatives had been confirmed
through mass spectra. Therefore, based on the available liter-
ature and the characterization data, cis-octahedral geometry
had been proposed around titanium(IV) with hexa-coordi-
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