Zinc(II), ruthenium(II), rhodium(III), palladium(II), silver(I), platinum(II) and MoO 2 2 + complexes of 2-(2′-hydroxy-5′- methylphenyl)-benzotriazole as simple or primary ligand and 2,2′- bipyridyl, 9,10-phenanthroline or triphenylphosphine as secondary ligands: Structure and anticancer activity

Article abstract of DOI:10.1016/j.molstruc.2013.11.039

New complexes of 2-(2′-hydroxy-5′-methylphenyl)-benzotriazole (Hhmbt), [Zn(hmbt)₂(H₂O)₂], [Zn(hmbt)(OAc)(H₂O)₂], [Pd(hmbt)(H₂O)Cl], [Pd(hmbt)₂], [M(PPh₃)(hmbt)Cl], [M(L)(hmbt)]Cl (M(II) = Pd, Pt; L = bpy, phen), [Ag₂(hmbt)₂], [Ag(phen)(hmbt)], [Ag(PPh₃)(hmbt)], [Rh(hmbt)₂(H₂O) ₂]Cl, [Ru(hmbt)₂(H₂O)₂], [Ru(PPh₃)(hmbt)₂Cl] and cis-[MoO₂(hmbt) ₂] have been synthesized. They have been structurally and spectroscopically characterized on the basis of elemental analysis, IR, NMR (¹H, ¹³C, ³¹P), UV-vis. and ESI-mass spectroscopy, thermal and molar conductivity measurements. 2-(2′-Hydroxy- 5′-methylphenyl)-benzotriazole behaves as a mononegative bidentate through the deprotonated phenolic oxygen and imine nitrogen atoms. The reported complexes have been tested against human breast cancer (MDA-MB231) and human ovarian cancer (OVCAR-8) cell lines. The complexes, [Ag(hmpbt)(PPh ₃)], [Rh(hmbt)₂(H₂O)₂]Cl, [Pt(phen)(hmbt)]Cl and [Pd(phen)(hmbt)]Cl exhibit the highest growth inhibitory activity with mean IC₅₀ values 1.37, 7.52, 5.24 and 4.85 μM (MDA-MB231) and 1.75, 8.50, 3.00 and 2.99 μM (OVACAR-8), respectively.

Full text of DOI:10.1016/j.molstruc.2013.11.039

Journal of Molecular Structure 1059 (2014) 193–201
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Zinc(II), ruthenium(II), rhodium(III), palladium(II), silver(I), platinum(II)
and MoO22þ complexes of 2-(20-hydroxy-50-methylphenyl)-benzotriazole
as simple or primary ligand and 2,20-bipyridyl, 9,10-phenanthroline
or triphenylphosphine as secondary ligands: Structure and anticancer
activity
b
b
c
Hala A. El-Asmy a, Ian S. Butler a, , Zhor S. Mouhri , Bertrand J. Jean-Claude , Mohamed S. Emmam ,
⇑
Sahar I. Mostafa c,
⇑
a Department of Chemistry, McGill University, Montreal, QC H3A 2K6, Canada
b Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, QC H3A 1A1, Canada
c Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
New complexes of 2-(20-hydroxy-50-methylphenyl)-benzotriazole have been synthesized and structur-
ally characterized. The reported complexes have been tested against human breast cancer (MDA-
MB231) and human ovarian cancer (OVCAR-8) cell lines.
ꢀ
New complexes of 2-(20-hydroxy-50-
methylphenyl)-benzotriazole
(Hhmbt) are reported.
ꢀ
ꢀ
Hhmbt coordinates via deprotonated
hydroxy and imine nitrogen.
Free Hhmbt and its complexes were
tested against breast cancer (MDA-
MB231) and ovarian cancer (OVCAR-
8) cell lines.
[Ag(hmpbt)(PPh3)] and
[Pd(phen)(hmbt)]Cl exhibit the
highest activity.
CH3
H3C
h
ν
O
H
O
H
ꢀ
N
N
Δ
N
N
N
N
a r t i c l e i n f o
a b s t r a c t
New complexes of 2-(20-hydroxy-50-methylphenyl)-benzotriazole (Hhmbt), [Zn(hmbt)2(H2O)2],
[Zn(hmbt)(OAc)(H2O)2], [Pd(hmbt)(H2O)Cl], [Pd(hmbt)2], [M(PPh3)(hmbt)Cl], [M(L)(hmbt)]Cl (M(II) = Pd,
Pt; L = bpy, phen), [Ag2(hmbt)2], [Ag(phen)(hmbt)], [Ag(PPh3)(hmbt)], [Rh(hmbt)2(H2O)2]Cl, [Ru(hmbt)2
(H2O)2], [Ru(PPh3)(hmbt)2Cl] and cis-[MoO2(hmbt)2] have been synthesized. They have been structurally
and spectroscopically characterized on the basis of elemental analysis, IR, NMR (1H, 13C, 31P), UV–vis. and
ESI-mass spectroscopy, thermal and molar conductivity measurements. 2-(20-Hydroxy-50-methylphenyl)-
benzotriazole behaves as a mononegative bidentate through the deprotonated phenolic oxygen and imine
nitrogen atoms. The reported complexes have been tested against human breast cancer (MDA-MB231) and
human ovarian cancer (OVCAR-8) cell lines. The complexes, [Ag(hmpbt)(PPh3)], [Rh(hmbt)2(H2O)2]Cl,
[Pt(phen)(hmbt)]Cl and [Pd(phen)(hmbt)]Clexhibit thehighestgrowthinhibitoryactivitywithmeanIC50 val-
Article history:
Received 1 October 2013
Received in revised form 14 November 2013
Accepted 14 November 2013
Available online 23 November 2013
Keywords:
Hhmbt
Zinc
Palladium
Platinum
Silver
ues 1.37, 7.52, 5.24 and 4.85
lM (MDA-MB231) and 1.75, 8.50, 3.00 and 2.99
lM (OVACAR-8), respectively.
Anticancer
Crown Copyright Ó 2013 Published by Elsevier B.V. All rights reserved.
⇑
Corresponding authors. Tel.: +20 100 8502625; fax: +20 50 2246781.
E-mail addresses: ian.butler@mcgill.ca (I.S. Butler), sihmostafa@yahoo.com
(S.I. Mostafa).
0022-2860/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.11.039

194
H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
ondary ligands. The anticancer activity of Hhmbt and its complexes
1. Introduction
have been tested against human breast cancer (MDA-MB231) and
human ovarian cancer (OVCAR-8) cell lines.
2-(20-Hydroxy-50-methylphenyl)-benzotriazole (Fig. 1) is com-
monly known as drometrizole. Drometrizole and its phenyl sub-
stituents are potent UV-light absorbers and constitute an
important class of industrial additives for polymers and light-stabi-
lized coatings. They are used in a variety of polymers including
polycarbonates, unsaturated polyesters, polystyrenes, acrylics,
polyvinyl chloride, thermoplastic polyesters, and polyacetals. They
have the common photochemical feature of strong absorption of
ultraviolet light (290–350 nm). This feature, as an ultraviolet ab-
sorber (UVA), is utilized commercially to impart light stability
(protection against photo-degradation) to a wide variety of poly-
mers (plastics, polyesters, celluloses, acrylates, dyes, rubber, syn-
thetic and natural fibers, waxes, detergent solutions, and
orthodontic adhesives) against discoloration and deterioration [1].
Dugdale and Cotton [2] has reported that benzotriazole forms a
strongly bonded chemisorbed two-dimensional barrier film less
than 50 Å thick, which may be a monomolecular layer, protects
copper and its alloys in aqueous media, various atmospheres, lubri-
cants, and hydraulic fluids [2]. Moreover, benzotriazole forms
insoluble precipitates with copper ions in solution, thereby pre-
venting the corrosion of aluminum and steel in other parts of a
water system [2].
2. Experimental
2.1. Materials and measurements
All reagents and solvents were purchased from Alfa/Aesar and
all manipulations were performed under aerobic conditions using
materials and solvents as received. [M(bpy)Cl2], [M(phen)Cl2],
[M(PPh3)2Cl2] (M(II) = Pd, Pt) [18] and [Ru(PPh3)3Cl2] [19]. DMSO-
d6 was used for the NMR measurements referenced against TMS.
The human breast cancer (MDA-MB231) and human ovarian
cancer (OVCAR-8) cell lines were obtained from the American
Type Culture Collection (ATCC catalog number). Cells were
maintained in Dulbecco’s Modified Eagle Medium (Wisent Inc.,
St-Bruno, Canada) supplemented with 10% FBS, 10 mM HEPES,
2 mM
L-gutamine and 100 lg/mL penicillin/streptomycin
(GibcoBRL, Gaithersburg, MD). In all assays cells were plated
24 h before drug treatment.
Infrared spectra were recorded on a Nicolet 6700 Diamond ATR
spectrometer in the 4000–200 cmꢂ1 range. NMR spectra were re-
corded on VNMRS 200 and 500 MHz spectrometer in DMSO-d6
using TMS as reference. Mass spectra (ESI-MS) were recorded using
LCQ Duo and double focusing MS25RFA instruments, respectively.
Electronic spectra were recorded in DMF using a Hewlett-Packard
8453 spectrophotometer. Thermal analysis measurements were
made in the 20–800 °C range at a heating rate of 20 °C minꢂ1 using
Ni and NiCo as references, on a TA instrument TGA model
Q500Analyzer TGA-50. Molar conductivity measurements were
carried out at room temperature on a YSI Model 32 conductivity
bridge.
The UV-stabilizer 2-(20-hydroxy-50-methylphenyl)-benzotria-
zole (Hhmbt) has been reported as a ligand for complexing VO2+
and MoO22þ to give [{VO(acac)2}(
l-hbmt)2] and cis-[MoO2
(acac)(hmbt)]. The X-ray crystal structures of both of complexes
have been also discussed [3]. The photolability of Hhmbt was ex-
plained due to an excited-state intramolecular proton transfer
through the intramolecular hydrogen bond (Form A, B; Scheme 1)
[4–6]. Thus, the replacement with a transition metal (chelates the
oxygen and nitrogen) with the investigation of its effect on the
photochemical and photophysical properties have been reported
[3].
2.2. Preparations
The complexes, [ReOX2(hmpbta)(APh3)]ꢁMeCN (X = Cl, Br; A = P,
As) and [ReBr2(hmpbta)(PPh3)]ꢁMeCN (hmpbta = 2-(20-hydoxy-50-
methylphenyl)-benzotriazole), have been prepared and character-
ized. The X-ray structure and DFT calculations for the disubstituted
[ReOCl(hmpbta)2] chelate have also been reported [7].
Over the past few years, our laboratory has been actively in-
volved in the synthesis of O,O; O,N; N,S and O,N,S-donors transition
metal complexes, which have been evaluated as anticancer agents
against either Ehrlich ascites tumor cells (EACs) [8–11] or human
cancer cell lines [12–14]. As a continuation of our interest in com-
plexes with O,N-donors [8,12,15–17], here we describe the prepa-
ration and characterization of new Zn(II), MoO22þ, Ru(II), Rh(III),
Pd(II), Ag(I), Pt(II) complexes with 2-(20-hydroxy-50-methyl-
phenyl)-benzotriazole (Hhmbt) as simple or primary ligand and
2,20-bipyridyl, 9,10-phenanthroline or triphenylphosphine as sec-
2.2.1. [Pd(hmbt)(H2O)Cl]ꢁ2H2O
An aqueous solution of K2[PdCl4] (0.16 g, 0.5 mmol; 5 mL) was
added to Hhmbt (0.113 g, 0.5 mmol) in EtOH (15 mL). The resulting
suspension was stirred at 80 °C for 2 h and a yellow solid was ob-
tained. It was filtered off, washed with water, ethanol and air-
dried. Yield: 0.195 g, 71%. Elemental Anal.: Calcd. C, 37.1; H, 3.8;
N, 10.0; Pd, 25.3 (C13H16N3O4Pd); Found: C, 37.2; H, 3.9; N, 10.3;
Pd, 25.4%. Conductivity data (10ꢂ3 M in DMF): KM = 8.0 ohmꢂ1. IR
(cmꢂ1):
(Pd–N), 461. Raman (cmꢂ1):
N), 1149; (Pd–O), 538; (Pd–N), 471; m
m
(C@N), 1600;
m
(CO), 1250;
(C@N), 1573;
(Pd–Cl), 194. 1H NMR
m
(N–N), 1141;
m
(Pd–O), 501;
m
m
m(CO), 1251;
m(N–
m
m
(ppm): 7.96 (H(3), d, J = 3 Hz, 1H); 7.65 (H(6), S, 1H); 7.23 (H(7),
d, J = 4.5 Hz, 1H); 7.40 (H(8), t, J = 4.2 Hz, 1H); 7.30 (H(9), t,
J = 4.2 Hz, 1H); 7.08 (H(10), d, J = 4.5 Hz, 1H); 2.40 (CH3, S, 3H).
UV–visible (nm): 248, 386, 468. MS (m/z): 331 (Calcd. 330.4),
226 (Calcd. 226.4).
3
2.2.2. [Pd(hmbt)2]
OH
2
4
5
An aqueous solution of K2[PdCl4] (0.16 g, 0.5 mmol; 5 mL) was
added to Hhmbt (0.225 g, 1 mmol) in MeOH containing KOH
(0.056 g, 1 mmol; 15 mL). The reaction mixture was stirred at 45°
C for 2 h. The orange solid was filtered off, washed with water, eth-
anol and air-dried. Yield: 0.320 g; 83%. Elemental Anal.: Calcd. C,
56.3; H, 3.6; N, 15.2; Pd, 19.2 (C26H20N6O2Pd); Found: C, 56.1; H,
3.5; N, 15.3; Pd, 19.1%. Conductivity data (10ꢂ3 M in DMF):
1
N
10
8
H3C
N
11
6
N
KM = 5.0 ohmꢂ1. IR (cmꢂ1):
1141; (Pd–O), 501;
(Pd–N), 473. Raman (cmꢂ1):
(CO), 1251; (N–N), 1148; (Pd–O), 538; (Pd–N), 471. UV–visi-
m(C@N), 1612;
m
(CO), 1251;
m(N–N),
9
12
m
m
m(C@N), 1572;
m
m
m
m
7
ble (nm):278, 388. MS (m/z): 554.5 (Calcd. 554.4), 329.4 (Calcd.
330.4), 226.7 (Calcd. 226.4).
Fig. 1. Structure of 2-(20-hydroxy-50-methylphenyl)-benzotriazole (Hhmbt).

H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
195
CH3
H3C
h
ν
O
H
O
H
N
N
Δ
N
N
N
N
(A)
(B)
Scheme 1. Enol-keto tautomeric (A and B) forms of Hhmbt.
2.2.3. [Pd(L)(hmbt)]ClꢁnH2O (L = bpy, n = 2; L = phen, n = 1)
To a stirred suspension of [Pd(bpy)Cl2] (0.03 g, 0.1 mmol) or
[Pd(phen)Cl2] (0.04 g, 0.1 mmol) in MeOH (10 mL) a solution of
Hhmbt (0.023 g, 0.1 mmol) in MeOH containing KOH (0.006 g,
0.1 mmol; 10 mL) was added drop by drop with stirring. The reac-
tion mixture was warmed for 48 h, upon which a yellow-orange
precipitate was filtered off, washed with MeOH, Et2O and dried
in vacuo.
2.2.5. [Pt(L)(hmbt)]ClꢁnH2O (L = bpy, n = 1; L = phen, n = 2)
A similar procedure as the palladium analogue was applied,
[Pt(L)Cl2] (L = bpy, phen) were used to produce yellow-orange
precipitates.
For [Pt(bpy)(hmbt)]ClꢁH2O: Yield: 0.35 g (60%). Elemental Anal.:
Calcd.: C, 43.9; H, 3.5; N, 11.1; Pt, 31.0 (C23ClH22N5O2Pt); Found: C,
43.7; H, 3.7; N, 11.0; Pt, 31.2%. Conductivity data (10ꢂ3 M in DMF):
KM = 80.0 ohmꢂ1. IR (cmꢂ1):
549;
(Pt–O), 550;
m
(C@N), 1607;
(Pt–N), 489. Raman (cmꢂ1):
(C@N), 1605;
(Pt–N), 486. 1H NMR (ppm): 8.34 (H(3), d,
m
(CO), 1251;
m(Pt–O),
For[Pd(bpy)(hmbt)]Clꢁ2H2O: Yield: 0.07 g (51%). Elemental
Anal.: Calcd. C, 49.5; H, 4.3; N, 12.6; Pd, 19.1 (C23H24N5O3Pd);
Found: C, 49.7; H, 4.2; N, 12.7; Pd, 19.1%. Conductivity data
m
m
m(CO), 1251;
m
m
J = 5.1 Hz, 1H); 7.68 (H(6), S, 1H); 7.49 (H(7), d, J = 4.8 Hz, 1H);
7.2 (H(8), t, J = 6.3 Hz,1H); 7.55 (H(9), t, J = 5.4 Hz, 1H); 6.76
(H(10), d, J = 6 Hz, 1H); 2.35 (CH3, S, 3H). MS (m/z): 574.3 (Calcd.
574.0).
(10ꢂ3 M in DMF): KM = 84.0 ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1621;
(Pd–N), 459. Raman
(N–N), 1141; (Pd–O), 501;
(Pd–N), 460. 1H NMR (ppm): 8.00 (H(3), d, J = 6 Hz, 1H); 7.75
m
(CO), 1251;
m
(N–N), 1141;
m(Pd–O), 500; m
(cmꢂ1):
m(C@N), 1602;
m(CO), 1251;
m
m
m
For [Pt(phen)(hmbt)]Clꢁ2H2O: Yield: 0.1 g (60%). Elemental
(H(6), S, 1H); 7.86 (H(7), d, J = 5.4 Hz, 1H); 7.73 (H(8), t, J = 5 Hz,
1H); 7.69 (H(9), t, J = 5 Hz, 1H); 7.22 (H(10), d, J = 5.2 Hz, 1H);
2.50 (CH3, S, 3H). MS (m/z): 486.4 (Calcd. 486.4), 368.2 (Calcd.
368.4), 292.4 (Calcd. 292.4), 262.4 (Calcd. 262.4), 156.3 (Calcd.
156.0).
Anal.: Calcd.: C, 46.0; H, 3.7; N, 10.7; Pt, 29.9 (C25ClH24N5O3Pt);
Found: C, 46.1; H, 3.8; N, 10.5; Pt, 29.7%. IR (cmꢂ1):
m
(C@N),
(Pt–N), 473. Ra-
(N–N), 1136; (Pt–O),
(Pt–N), 476. Conductivity data (10ꢂ3 M in DMF): KM = 79.0 -
ohmꢂ1 1H NMR (ppm): 7.96 (H(3), d, J = 3.9 Hz, 1H); 7.59 (H(6), S,
1600;
man (cmꢂ1):
550;
m
(CO), 1251;
m
(N–N), 1134;
m(Pt–O), 549; m
m
(C@N), 1605;
m(CO), 1251;
m
m
m
For[Pd(phen)(hmbt)]ClꢁH2O: Yield: 0.08 g (54%). Elemental
Anal.: Calcd. C, 53.2; H, 3.9; N, 12.4; Pd, 18.7 (C25H22N5O2Pd);
Found: C, 53.3; H, 4.0; N, 12.3; Pd, 18.6%. Conductivity data
.
1H); 7.06 (H(7), d, J = 1.8 Hz, 1H); 7.45 (H(8), t, J = 3.3 Hz, 1H); 7.42
(H(9), t, J = 3.3 Hz, 1H); 6.85 (H(10), d, J = 8.4 Hz, 1H); 2.35 (CH3, S,
3H). MS (m/z): 599.5 (Calcd. 599.0).
(10ꢂ3 M in DMF): KM = 81.0 ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1600;
(Pd–N), 495. Raman
(N–N), 1139; (Pd–O), 565;
(Pd–N), 495. 1H NMR (ppm): 7.96 (H(3), d, J = 5.1 Hz, 1H); 7.30
m
(CO), 1252;
m
(N–N), 1138;
m(Pd–O), 564; m
(cmꢂ1):
m
(C@N), 1604;
m
(CO), 1252;
m
m
2.2.6. [Pt(PPh3)(hmbt)Cl]
m
The synthesis of [Pt(PPh3)(hmbt)Cl] was achieved by a similar
procedure to that for Pd(II) analogue with [Pt(PPh3)2Cl2] replac-
ing[Pd(PPh3)2Cl2]. Yield: 0.21 g (82%). Elemental Anal.: Calcd.: C,
51.9; H, 3.5; N, 5.9; Cl, 5.0; Pt, 27.2 (C31ClH25N3OPt); Found: C,
(H(6), S, 1H); 7.60 (H(7), d, J = 4.5 Hz, 1H); 7.77 (H(8), t,
J = 4.2 Hz, 1H); 7.73 (H(9), t, J = 4.5 Hz, 1H); 7.22 (H(10), d,
J = 4.2 Hz, 1H); 2.50 (CH3, S, 3H). MS (m/z): 510.4 (Calcd. 510.4),
286.4 (Calcd. 286.4), 180.6 (Calcd. 180.0).
51.4; H, 3.6; N, 6.0; Cl, 5.4; Pt, 27.5%. Conductivity data (10ꢂ3
M
in DMF): KM = 3.0 ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1600;
(N–N), 1132;
(Pt–N), 492. Raman (cmꢂ1):
(C@N), 1598; (N–N), 1144; (Pt–O), 545; (Pt–N),
(Pt–P), 305; m(Pt–Cl), 227. MS (m/z): 716.5 (Calcd. 716.5).
m(CO), 1300;
m
m
m
(Pt–O), 514;
m
2.2.4. [Pd(PPh3)(hmbt)Cl]
m
(CO), 1301;
m
m
m
[Pd(PPh3)2Cl2] (0.175 g, 0.25 mmol) was added to Hhmbt
(0.057 g, 0.25 mmol) in CH2Cl2 (20 mL). The reaction mixture was
heated under reflux for 48 h. The yellow precipitate was filtered
off, washed with CH2Cl2 and dried in vacuo. Yield: 0.20 g; 86%. Ele-
mental Anal.: Calcd.: C, 59.2; H, 4.0; N, 6.7; Cl, 5.7; Pd, 16.9 (C31-
ClH25N3OPd); Found: C, 59.4; H, 4.1; N, 6.6; Cl, 5.6; Pd, 16.8%.
Conductivity data (10ꢂ3 M in DMF): KM = 7.0 ohmꢂ1. IR (cmꢂ1):
462;
m
2.2.7. [Ag2(hmbt)2]
Silver nitrate (0.085 g, 0.5 mmol) in water (1 mL) was added to
Hhmbt (0.113 g, 0.5 mmol) in MeOH containing KOH (0.028 g,
0.5 mmol; 15 mL). The reaction mixture was stirred at 40 °C in
the dark for 5 h. The pale-green solid was filtered off, washed with
water, MeOH, Et2O and dried in vacuo. Yield: 0.15 g (75%). Elemen-
tal Anal.: Calcd. C, 47.0; H, 3.0; N, 12.6% (C26H20N6O2Ag2); Found: C,
47.3; H, 3.2; N, 12.4%. Conductivity data (10ꢂ3 M in DMF):
m
(C@N), 1586;
N), 438. Raman (cmꢂ1):
1160; (Pd–O), 530; (Pd–N), 434;
UV–visible (nm): 280, 358, 388. MS (m/z): 628.2 (Calcd. 627.9).
m
(CO), 1307;
(C@N), 1585;
(Pd–P), 301;
m
(N–N), 1158;
m
(Pd–O), 532;
(CO), 1309;
(Pd–Cl), 199.
m
(Pd–
m
m
m(N–N),
m
m
m
m
KM = 6.0 ohmꢂ1. IR (cmꢂ1):
m(C@N), 1600; m(CO), 1250; m(N–N),

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H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
1144;
m
(Ag–O), 500;
m
(Ag–N), 465. Raman (cmꢂ1):
(Ag–O), 502; (Ag–N), 464. MS (m/
m
(C@N), 1598;
(10 mL). The reaction mixture was heated under reflux for 2 h dur-
ing which shiny green microcrystals were isolated, washed with
MeOH, Et2O and dried in vacuo. Yield: 0.26 g (83%). Elemental Anal.:
Calcd.: C, 62.4; Cl, 4.2; H, 4.1; N, 9.9 (C44ClH35N6O2PRu); Found: C,
62.5; Cl, 4.1; H, 4.4; N, 10.0%. Conductivity data (10ꢂ3 M in DMF):
m(CO), 1250;
m(N–N), 1147;
m
m
z): 332.22 (Calcd. 331.8).
2.2.8. [Ag(phen)(hmbt)]
Silver perchlorate (0.101 g, 0.5 mmol) in water (1 mL) was
added to phen (0.090 g, 0.5 mmol) in MeOH (10 mL). To the yellow
solution, Hhmbt (0.113 g, 0.5 mmol) in MeOH containing KOH
(0.028 g, 0.5 mmol; 10 mL) was added. The reaction mixture was
stirred in the dark for 3 h and the pale-yellow solid was filtered
off, washed with water, MeOH, Et2O and dried in vacuo. Yield:
0.21 g (72%). Elemental Anal.: Calcd. C, 58.6; H, 3.9; N, 13.7%
(C25H20N5OAg); Found: C, 58.9; H, 3.8; N, 13.6%. Conductivity data
KM = 4.0 ohmꢂ1. IR (cmꢂ1):
1131; (Ru–O), 519;
(Ru–N), 438. Raman (cmꢂ1):
(CO), 1262; (N–N), 1133; (Ru–O), 531; (Ru–N), 420. UV–visi-
m(C@N), 1633;
m
(CO), 1255;
m(N–N),
m
m
m(C@N), 1619;
m
m
m
m
ble (nm): 305, 362, 629. MS (m/z): 811.2 (Calcd. 811.1), 588.0
(Calcd. 587.1).
2.2.13. [Zn(hmbt)(OAc)(H2O)2]
Zn(OAc)2 (0.109 g, 0.5 mmol) in EtOH (5 mL) was added to
Hhmbt (0.113 g, 0.5 mmol) in EtOH (20 mL). The reaction mixture
was heated under reflux for 8 h. A pale-yellow precipitate was ob-
tained, washed with EtOH and dried in vacuo. Yield: 0.18 g (81%).
Elemental Anal.: Calcd.: C, 46.9; H, 4.0; N, 10.9 (C15H17N3O5Zn);
Found: C, 47.1; H, 4.2; N, 11.0%. Conductivity data (10ꢂ3 M in
(10ꢂ3 M in DMF): KM = 4.0 ohmꢂ1. IR (cmꢂ1):
1250; (N–N), 1141; (Ag–O), 514;
(Ag–N), 440. Raman (cmꢂ1):
(C@N), 1589, (CO), 1250; (N–N), 1143; (Ag–O), 553;
(Ag–N), 418. UV–visible (nm): 225, 269, 288, 441. MS (m/z):
m(C@N), 1590, m(CO),
m
m
m
m
m
m
m
m
511.3 (Calcd. 511.8), 287.3 (Calcd. 287.8).
DMF): KM = 9.0 ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1615;
(Zn–N), 441. Raman (cmꢂ1):
(N–N), 1131; (Zn–O), 548; (Zn–
m(CO), 1250;
2.2.9. [Ag(PPh3)(hmbt)]
m(N–N), 1132;
m(Zn–O), 520;
m
A similar procedure as [Ag(phen)(hmbt)] was applied, PPh3 was
replacing phen to produce a green precipitate. Yield: 0.29 g (86%).
Elemental Anal.: Calcd. C, 61.0; H, 4.4; N, 6.9% (C31H27N3O2PAg);
Found: C, 60.7; H, 4.4; N, 7.0%. Conductivity data (10ꢂ3 M in
m(C@N), 1612;
m(CO), 1258;
m
m
m
N), 459. 1H NMR (ppm): 8.06 (H(3), d, J = 3.3 Hz, 1H); 7.56 (H(6),
S, 1H); 7.31 (H(7), d, J = 6 Hz, 1H); 7.55 (H(8), t, J = 6 Hz, 1H);
7.52 (H(9), t, J = 5.7 Hz, 1H); 6.73 (H(10), d, J = 7.5 Hz, 1H); 2.47
(CH3, S, 3H). MS (m/z): 384.3 (Calcd. 384.5), 366.2 (Calcd. 366.5).
DMF): KM = 2.0 ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1609;
(Ag–N), 461. Raman (cmꢂ1):
(N–N), 1147; (Ag–O), 509; (Ag–
m(CO), 1250;
m(N–N), 1141;
m(Ag–O), 501;
m
m(C@N), 1607;
m
(CO), 1250;
m
m
m
2.2.14. [Zn(hmbt)2(H2O)2]
N), 464. 1H NMR (ppm): 7.96 (H(3), d, J = 4 Hz, 1H); 7.65 (H(6), S,
1H); 7.31 (H(7), d, J = 3.5 Hz, 1H); 7.40 (H(8), t, J = 8.5 Hz, 1H);
7.30 (H(9), t, J = 4.5 Hz, 1H); 6.73 (H(10), d, J = 8.5 Hz, 1H); 2.47
(CH3, S, 3H). UV–visible (nm): 257, 280, 339, 416. MS (m/z):
593.4 (Calcd. 593.8), 369.4 (Calcd. 369.8).
ZnCl2 (0.11 g, 0.5 mmol) in water (5 mL) was added to Hhmbt
(0.225 g, 1 mmol) in EtOH containing (0.028 g, 0.5 mmol; 20 mL).
The reaction mixture was heated under reflux for 4 h. An off-white
precipitate was obtained. It was filtered off, washed with water,
EtOH and dried in vacuo. Yield: 0.29 g (87%). Elemental Anal.:
Calcd.: C, 60.8; H, 3.9; N, 16.4 (C26H20N6O2Zn); Found: C, 61.0; H,
3.8; N, 16.3%. Conductivity data (10ꢂ3 M in DMF): KM = 11.0 -
2.2.10. [Rh(hmbt)2(H2O)2]Clꢁ5H2O
Hydrated rhodium trichloride (0.13 g, 0.5 mmol) was added to a
solution of AcONa (0.62 g, 7.5 mmol) in water (30 mL) and
Hhmbt(0.226 g, 1.0 mmol) was added. The mixture was refluxed
for 10 h and a yellow precipitate was obtained upon reducing the
volume. It was filtered off, washed with ice-cold water and air
dried. Yield: 0.35 g (60%). Elemental Anal.: Calcd.: C, 43.8; H, 4.3;
N, 11.8 (C26H35N6O7Rh); Found; C, 43.8; H, 4.2; N, 11.7%. Conduc-
ohmꢂ1. IR (cmꢂ1):
m
(C@N), 1613;
(Zn–N), 463. Raman (cmꢂ1):
(N–N), 1130; (Zn–O), 504;
(Zn–N), 464. 1H NMR
m
(CO), 1252;
m
(N–N), 1132;
m(Zn–O), 500;
(CO), 1250;
m
m(C@N), 1612;
m
m
m
m
(ppm): 8.00 (H(3), d, J = 2.8 Hz, 1H); 7.64 (H(6), S, 1H); 7.64
(H(7), d, J = 4.4 Hz, 1H); 7.21 (H(8), t, J = 4.4 Hz, 1H); 7.52 (H(9), t,
J = 6.4 Hz, 1H); 7.50 (H(10), d, J = 3.6 Hz, 1H); 2.47 (CH3, S, 3H).
MS (m/z): 513.1 (Calcd. 513.5), 289.1 (Calcd. 289.5).
tivity data (10ꢂ3
(C@N), 1604; (CO), 1251;
N), 471. Raman (cmꢂ1):
(C@N), 1602;
1148; (Rh–O), 497;
(Rh–N), 476. 1H NMR (ppm): 8.01 (H(3), d,
M
in DMF): KM = 79.0 ohmꢂ1
(N–N), 1146; (Rh–O), 506;
(CO), 1251;
.
IR (cmꢂ1):
(Rh–
(N–N),
m
m
m
m
m
2.2.15. Cis-[MoO2(hmpt)2]
m
m
m
[MoO2(acac)2] (0.164 g, 0.5 mmol) in methanol (2 mL) was
added HL1 (0.225 g, 1 mmol) in methanol containing KOH
(0.028 g, 0.5 mmol; 10 mL). The reaction mixture was heated un-
der reflux for 3 h. The pale yellow precipitate was filtered off,
washed with water and methanol, and finally air-dried.
Yield:0.089 g (23%). Elemental Anal.: Calcd.: C, 54.2; H, 3.5; N,
14.6 (C26H20N6O4Mo); Found: C, 54.5; H, 3.6; N, 14.7%. Conductiv-
m
m
J = 2.8 Hz, 1H); 7.62 (H(6), S, 1H); 7.21 (H(7), d, J = 2 Hz, 1H);
7.52 (H(8), t, J = 6 Hz, 1H); 7.50 (H(9), t, J = 5.6 Hz, 1H); 7.06
(H(10), d, J = 4.4 Hz, 1H); 2.48 (CH3, S, 3H). UV–visible (nm): 280,
310, 358, 408, 430. MS (m/z): 551.2 (Calcd. 551.0).
2.2.11. [Ru(hmbt)2(H2O)2]
ity data (10ꢂ3 M in DMF): KM = 4.0 ohmꢂ1. IR (cmꢂ1):
1604; (CO), 1253; (N–N), 1145; (O–Mo–O), 939;
560; (C@N), 1606; (CO), 1250;
(Mo–N), 470. Raman (cmꢂ1):
(N–N), 1149; (O–Mo–O), 942; (Mo–O), 570;
(Mo–N), 473. 1H
m
(C@N),
Hydrated ruthenium trichloride (0.102 g, 0.5 mmol) in water
(5 mL) was added to Hhmbt (0.34 g, 1.5 mmol) in EtOH (15 mL).
The mixture was heated under reflux for 6 h till a dark green pre-
cipitate formed. It was filtered off during hot, washed with hot
water, EtOH and air dried. Yield: 0.35 g (80%). Elemental Anal.:
Calcd.: C, 53.3; H, 4.3; N, 14.2 (C26H24N6O3Ru); Found; C, 53.5; H,
m
m
m
m(Mo–O),
m
m
m
m
m
m
m
NMR (ppm): 7.98 (H(3), d, J = 7 Hz, 1H); 7.02 (H(6), S, 1H); 7.54
(H(7), d, J = 7.5 Hz, 1H); 7.16 (H(8), t, J = 3.5 Hz, 1H); 7.52 (H(9), t,
J = 5 Hz, 1H); 7.19 (H(10), d, J = 3.5 Hz, 1H); 2.47 (CH3, S, 3H). MS
(m/z): 575.8 (Calcd. 575.9), 352.1 (Calcd. 351.9).
4.1; N, 14.4%. Conductivity data (10ꢂ3 M in DMF): KM = 5.0 ohmꢂ1
.
IR (cmꢂ1):
501;
(Ru–N), 468. Raman (cmꢂ1):
(N–N), 1143; (Ru–O), 502;
m(C@N), 1611;
m(CO), 1251;
m(N–N), 1137;
m(Ru–O),
m
m
(C@N), 1611;
m(CO), 1251;
2.3. Biological assay
m
m
m(Ru–N), 467. UV–visible (nm):
300, 340, 631. MS (m/z): 549.9 (Calcd. 549.1).
Growth inhibition assay; human breast cancer (MDA-MB231)
and human ovarian cancer (OVCAR-8) cells were plated at 3000
2.2.12. [Ru(PPh3)(hmbt)2Cl]
cells/well in 96-well (100 lL/well) flat-bottomed microliter plates
A stirred suspension of [Ru(PPh3)3Cl2] (0.25 g, 0.25 mmol) in
MeOH (10 mL) was added to a Hhmbt (0.09 g, 0.4 mmol) in MeOH
(Costar, Corning, NY). After 24 h incubation, the cells were exposed
to different concentrations of each compound continuously for

H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
197
5 days. Briefly, following drug treatment, the cells were fixed using
50 L of cold trichloroacetic acid (50%) for 2 h at 4 °C, washed with
water, stained with sulforhodamine B (SRB 0.4%) overnight at room
temperature, rinsed with 1% acetic acid and allowed to dry over-
night [20]. The resulting colored residue was dissolved in 200 lL
Tris base (10 mM, pH 10.0) and the optical density was recorded
at 490 nm using a microplate reader ELx808 (BioTek Instruments).
The results were analyzed by GraphPad Prism (GraphPad Software,
Inc., San Diego, CA) and the sigmoidal dose response curve was
used to determine 50% cell growth inhibitory concentration
(IC50). Each point represents the average of two independent
experiments performed in triplicate [20].
vibrations of the coordinated phen or bpy [15,28]. These bands
are at higher wavenumbers compared with those for the free phen
or bpy ligand indicating chelation [29].
l
In the 1000–750 cmꢂ1 region, the spectra of [MoO2(hmbt)2]
(Fig. 3) shows bands characteristic of the cis-MoO22þ units [30,31].
The IR bands at 939 (943 in Raman) and 897 (911 in Raman) cmꢂ1
are assigned to the vs(MoO2) and vas(MoO2) modes, respectively
[30,31]. As expected, the symmetric mode is weak in the IR spectra
and strong in Raman, while the opposite applies for the asymmet-
ric one. The appearance of two stretching bands is indicative of the
cis-configuration [15,32,33].
The IR and Raman spectra of the complexes show several bands
in 500–200 cmꢂ1 due to
stretches [26,33].
m(M–O), m(M–N), m(M–P) and m(M–Cl)
3. Result and discussion
3.2. NMR spectra
Section 2 describes the synthesis of the new complexes of 2-(20-
hydroxy-50-methylphenyl)-benzotriazole (Hhmbt) and lists their
elemental analyses and spectroscopic data, which are in excellent
agreement with the assigned formulae. The molar conductivities
The 1H NMR spectroscopic data for Hhmbt complexes in DMSO-
d6 are reported in the experimental section.
The spectrum of the free Hhmbt (see Fig. 1 for numbering
scheme) exhibits three singlets at d 3.34, 7.69 and 10.35 ppm
attributed to CH3, H(6) and OH, respectively. There are two triplets
at d 7.55 and 7.52 ppm and four doublets at d 8.03, 8.00, 7.24 and
7.05 ppm assigned to H(8), H(9), H(3), H(4), H(7) and H(10),
respectively. The sharp singlet due to OH proton, is missed in the
complexes, indicating the replacement of the hydroxy proton by
the metal ions [34]. On the other hand, the signals for H(7) and
H(10) are shifted downfield, indicating the complexation of hmbtꢂ
through the deprotonated hydroxy oxygen and imine nitrogen
atoms [35,36].
(
KM) in DMF at room temperature suggest all complexes to be
non-electrolytes except for,[M(L)(hmbt)]Cl (M(II) = Pd, Pt; L = bpy,
phen) and [Rh(hmbt)2(H2O)2]Cl, which show as 1:1 electrolytes
[21]. All the new complexes are microcrystalline or powder-like,
stable under normal laboratory conditions and soluble in DMF
and DMSO.
3.1. Vibrational spectra
The solid-state properties of 2-(20-hydroxy-50-methylphenyl)-
benzotriazole (Hhmbt; Fig. 1) were examined by IR and Raman
spectroscopy. The spectrum of Hhmbt was compared with those
of the complexes. Tentative assignments of selected IR bands are
reported in the experimental section. The IR spectrum of Hhmbt
The 1H NMR spectrum of [Rh(hmbt)2(H2O)2]Cl should show the
presence of fac and mer isomers since hmbtꢂ is an unsymmetrical
bidentate ligand (imine and deprotonated hydroxy oxygen atoms
are non-equivalent). In the fac isomer, the hmbtꢂ are equivalent
while in the mer they are different [10,37]. Two peaks are observed
for each proton assigned to cis-hmbtꢂ and cis-H2O configuration
(Fig. 4). This feature was further supported by 13C NMR spectrum,
and expected due to the bulky hmbtꢂ moieties.
exhibits a strong broad at band at 3400 cmꢂ1 due to
m(OH), support
the existence of Hhmbt in the enol form (Scheme 1) [3,7], this band
is missed on the complexes. These data are further supported by
the shift of the intense band near 1250 cmꢂ1 in the spectra of free
ligand to higher frequency, indicating the coordination of Hhmbt
through the deprotonated phenolic (C(2)–Oꢂ) [22,23]. These obser-
vations indicate the replacement of the acidic hydrogen by the me-
tal ion [13]. The strong band at 1600 (IR) and 1601 (Raman) cmꢂ1
in free ligand is characteristic of
coordination of the nitrogen to the metal ion would reduce the
electron density in the azomethine link and thus shifted (C@N)
The 1H NMR spectra of the [M(hmbt)(PPh3)Cl], [M(hmbt)(L)]Cl
(M(II) = Pd, Pt; L = bpy, phen), [Ag(PPh3)(hmbt)(H2O)] and
[Ru(PPh3)(hmbt)2Cl] complexes show complicated multiplets in
the d 7.6–8.4 and 7.2–7.8 ppm regions, which are assigned to bpy
or phen and PPh3 protons, respectively. The bpy or phen and
PPh3 protons show upfield shifts in comparison to those of
[M(L)Cl2] (M(II) = Pd, Pt; L = bpy, phen) and [Ru(PPh3)3Cl2]. This
observation is interpreted in term of strong binding of hmbtꢂ to
metal ions as compared to binding of chloride ion [9].
m(C@N) group. It is expected that
m
stretch [24]. In the spectra of the complexes, this band is shifted
to the region at 1604–1630 cmꢂ1 [25]. The band near 1131 cmꢂ1
in free Hhmbt is assigned to the m(N–N) stretch. In the complexes,
this band is shifted to lower wave number [26]. These means that
hmbtꢂ acts as a mononegative bidentate ligand, coordinating the
metal ions through the azomithine nitrogen and the deprotonated
hydroxy oxygen centers forming six-membered ring. In the com-
plex, [Zn(hmbt)(AcO)(H2O)2] (Fig. 2), two extra bands are observed
H3C
at 1532 and 1408 cmꢂ1 assigned to
m m
as(COOꢂ) and s(COOꢂ)
H2O
O
O
O
stretching vibration of the acetate group, respectively [15].
The separation between these two bands {
as(COOꢂ) and
s(COOꢂ) = 124 cmꢂ1}, indicating asymmetric bidentate coordina-
tion of the carboxylic group [15,16].
D = m
m
Zn
C
CH3
N
N
N
The presence of the coordinated PPh3 groups in
[M(hmbt)(PPh3)Cl] (M(II) = Pd, Pt), [Ru(PPh3)(hmbt)2Cl] and
[Ag(PPh3)(hmbt)(H2O)] is manifested by the strong IR bands near
H2O
1099 and 751 cmꢂ1, attributed to the
tions, respectively [27].
m(P–Cph) and d(C–CH) vibra-
The spectra of the complexes, [M(L)(hmbt)]Cl (M(II) = Pd, Pt;
L = bpy, phen) show bands near 1580, 1515, 1495, 1420 (phen)
and 854, 841, 750 and 725 (bpy) cmꢂ1 are attributed to the
c
(CH)
Fig. 2. Structure of [Zn(hmbt)2(H2O)2].

198
H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
[40]. Transitions below 400 nm are assigned to intra-ligand charge
transfer (n ? p⁄ and p⁄).
p
?
The electronic spectrum of the diamagnetic complex,
[Rh(hmbt)2(H2O)2]Cl, display bands at 589, 497 and 408 nm, which
resemble those of other octahedral Rh(III) complexes and may be
O
O
O
O
assigned to 1A1g ? 3T1g 1A1g ? 1T1g and 1A1g ? 1T2g transitions,
,
Mo
respectively [10,32,41].
N
N
N
N
The electronic spectra of the diamagnetic ruthenium (II) com-
N
N
plexes show intense transitions near 636 (1A1g ? 1T1g), 340
(1A1g ? 1T2g) and 300 (ligand (
p–dp)) nm [10]. These are attributed
to a low-spin octahedral geometry around Ru(II) [8,10]. The elec-
tronic spectra of the diamagnetic Pd(II), Pt(II) complexes exhibit
bands near 470 and 320 nm due to 1A1g ? 1Bg and 1A1g ? 1Eg tran-
sitions, respectively, in a square-planar configuration [42,43]. In
the complexes, [M(hmbt)(PPh3)Cl], [M(hmbt)(L)]Cl (M(II) = Pd, Pt;
L = bpy, phen), the absorption band at 370 nm is assigned to a
mixture of charge transfer from M(II) to the p⁄ orbital of bpy, phen
or PPh3 and d–d bands [10,42,43].
CH3
H3C
Fig. 3. Structure of cis-[MoO2(hmbt)2].
In the electronic spectrum of complex cis-[MoO2(hmbt)2] dis-
plays bands at 456 and 358 (shoulder) nm; the latter is assigned
to O2ꢂ ? Mo(VI) p–d transition and is characteristic of the
MoO22ꢂ moiety in octahedral geometry [10].
The 31P NMR spectra of the complexes, [M(hmbt)(PPh3)Cl]
(M(II) = Pd, Pt), [Ag(PPh3)(hmbt)] and[Ru(hmbt)2(PPh3)Cl] in
DMSO-d6 show sharp singlet near d 20.0 ppm, suggesting the pres-
ence of one coordinated PPh3 moiety in the complex [38].
The 13C NMR spectrum of Hhmbt in DMSO-d6 has been mea-
sured and assigned. The spectrum shows ten resonances at d
20.28, 118.24, 118.37, 125.36, 127.14, 127.80, 129.11, 132.04,
143.88 and 148.88 ppm, may be assigned to CH3(5), C(3), C(8,9),
C(4), C(6), C(7,10), C(1), C(5), C(11,12) and C(2), respectively. In
the complexes, the resonances for the carbon atoms adjacent to
the coordination sites, C(1), C(2), C(3), C(11) and C(12), are shifted
downfield relative to their positions in the free ligand (Table 1)
[39]. This feature may be due to an increase in the benzotriazole
ring current in C(11) and C(12) brought about by coordination to
triazole nitrogen center [18]. In the spectrum of [Rh(hmbt)2(H2-
O)2]Cl, two signals were observed for each carbon atom, supporting
the cis-configuration, which observed in the 1H NMR spectrum.
3.4. Mass spectra
The mass spectral data of the complexes are reported in the
Experimental section and their molecular ion peaks are in agree-
ment with their assigned formulae.
The mass spectrum of [Pd(hmbt)(H2O)Cl] shows fragmentation
patterns corresponding to successive degradations of the molecule.
The first signal at m/z 331 (Calcd. 330.4) with 50% abundance rep-
resents the molecular ion, [Pd(hmbt)]+. The spectrum exhibits one
more peak at 226.0 (Calcd. 226.4) corresponding to [Pd(hmbt-
C6H4N2)]+. The mass spectrum of [Pd(hmbt)2] shows the first peak
at m/z 554.5 (Calcd. 554.4) with 100% abundance corresponding to
[Pd(hmbt)2]+. The spectrum exhibits two more peaks at 329.4,
226.7 corresponding to [Pd(hmbt)]+, [Pd(hmbt-C6H4N2)]+ frag-
ments, respectively. The mass spectra of [Pd(bpy)(hmbt)]Cl and
[Pd(phen)(hmbt)]Cl show peaks at m/z 486.4, 510.4, respectively,
represent the molecular ions [Pd(bpy)(hmbt)]+ (Calcd. 486.4) and
[Pd(phen)(hmbt)]+ (Calcd. 510.4), respectively. The mass spectrum
of [M(hmbt)(PPh3)Cl] (M(II) = Pd, Pt) show signals at m/z 628.2
(Calcd. 627.9), Pd and 716.5 (Calcd. 716.5), Pt, in agreement with
the molecular ions [M(hmbt)(PPh3)Cl]+. The fragmentation pattern
of Pt(II) complex indicates the stepwise ligand loss to [Pt(PPh3)]2+
(457) [8]. The mass spectra of [Pt(bpy)(hmbt)]Cl and [Pt(phen)
(hmbt)]Cl show peaks at m/z 574.3 and 599.5, represent the molec-
ular ions [Pt(bpy)(hmbt)]+ (Calcd. 575.0) and [Pd(phen)(hmbt)]+
(Calcd. 599.0), respectively.
3.3. Electronic spectra
The electronic spectra of Hhmbt in EtOH and DMSO show three
bands near 250, 300 and 358 nm. The electronic spectra of the
complexes in H2O, MeOH, DMSO or Nujol in the 200–900 nm re-
gions contain intense bands due to ligand to metal charge-transfer
(LMCT) transitions and weaker bands assigned to d–d transitions
The mass spectrum of the complex, [Zn(hmbt)2(H2O)2] shows
the first signal at m/z 513.1 (Calcd. 513.5) with 100% abundance
corresponding to the molecular ion [Zn(hmbt)2]+. One more signal
at 289.1 (Calcd. 289.5) is associated with [Zn(hmbt)]+ fragment,
indicating step wise ligand loss [43].
The spectrum of [Rh(hmbt)2(H2O)2]Cl shows signal at 551.2
(Calcd. 551.1) corresponding to the molecular ion [Rh(hmbt)2]+.
The spectrum of [Ru(hmbt)2(H2O)2] shows a signal at m/z 549.9
(Calcd. 549.1) corresponding to [Ru(hmbt)2]+ [8] while that of
[Ru(PPh3)(hmbt)2Cl] shows peaks at m/z 812.2 and 588.0, which
correspond to [Ru(PPh3)(hmbt)2]+ (Calcd. 811.1) and [Ru(PPh3)
(hmbt)]+ (Calcd. 587.1), respectively, in agreement with step wise
ligand loss [10].
H3C
Ag
N
N
O
N
N
N
N
Ag
O
The spectrum of [Ag2(hmbt)2] (Fig. 4) shows signal m/z at 332.2
(Calcd. 331.8) with 8% abundance corresponding to [Ag(hmbt)]+.
The signal at 291.2 (Calcd. 289.8) is associated with [Ag(hmbt-
N3)]+ fragment. The spectrum of [Ag(PPh3)(hmbt)] shows peaks
CH3
Fig. 4. Structure of [Ag2(hmbt)2].

H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
199
Table 1
13C NMR spectral data of Hhmbt and its complexes.
Compounds
C1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
CH3
d
ppm
Hhmbt
129.11
132.00
131.54
131.80
131.82
132.41
131.23
148.88
152.00
152.90
153.06
153.00
154.04
153.81
118.24
118.98
118.56
118.81
118.43
118.61
118.78
125.36
125.67
125.89
126.06
125.68
125.54
125.59
132.04
132.32
132.33
132.61
132.21
132.25
132.09
127.14
127.43
127.40
127.56
127.78
127.65
127.88
127.80
127.98
127.99
128.24
128.80
128.41
128.00
118.37
119.04
119.32
119.49
119.00
119.73
119.09
118.37
119.18
119.55
119.84
119.87
119.79
119.68
127.80
129.30
129.32
129.73
129.06
128.98
129.07
143.88
148.43
147.90
148.12
148.76
147.99
148.31
143.88
148.56
148.29
148.55
149.04
148.87
148.97
20.28
21.09
21.11
21.36
22.01
21.98
20.98
[Pd(hmbt)(H2O)Cl]
[Rh(hmbt)2(H2O)2]Cla
[Zn(hmbt)(OAc)(H2O)2]
[Zn(hmbt)2(H2O)2]
Cis-[MoO2(hmpt)2]
a
Two signals for each C indicating cis-(hmbtꢂ)2 configuration.
at m/z 593.4 and 369.3, corresponding to [Ag(PPh3)(hmbt)]+ (Calcd.
[Pt(phen)(hmbt)]Cl.2H2O, is characterized by three steps in 30–
100, 101–300 and 301–650 °C regions. These are assigned to the
elimination of lattice water (Calcd. 5.3, Found 5.1%), ½ Cl2, phen
and C4H4 (Calcd. 39.9, Found 40.1%), C9H6N3 (Calcd. 23.3, Found
22.9%), fragments, respectively, leaving PtO residue at 700 °C
(31.4%) [10,27]. The thermogram of [Pt(bpy)(hmbt)]ClꢁH2O shows
the first endothermic weight loss between 35 and 150 °C, which
may correspond to the release of crystal lattice water and ½ Cl2
(Cacld. 8.5, Found 8.2%). The second decomposition step occurs be-
tween 151 and 320 °C, attributed to the loss of C6H4N fragment
(Calcd. 14.3, Found 14.6%) while the third one between 321 and
589 °C arise from the elimination of N2 and phen species (Calcd.
33.1, Found 33.1%). The fourth TG inflection lies in the 590–
700 °C range, arise from the release of C7H6 fragment (Calcd.
14.3, found 13.9%), leaving PtO (Calcd. 33.6, Found 34.6%).
593.8) and [Ag(PPh3)]+ (Calcd. 369.8) fragments, respectively.
3.5. Thermal measurements
The thermal stability and degradation behaviour of some of the re-
ported complexes, [Zn(hmbt)(OAc)(H2O)2], [Zn(hmbt)2], [Pd(hmbt)
(H2O)Cl]ꢁ3H2O, [Pd(hmbt)2], [Pd(hmbt)(PPh3)Cl], [M(bpy)(hmbt)]Cl
(M = Pd, n = 2; M = Pt, n = 1), [M(phen)(hmbt)]Cl (M = Pd, n = 1;
M = Pt, n = 2), cis-[MoO2(hmbt)2], [Ag2(hmbt)2], [Ag(PPh3)(hmbt)],
[Ru(hmbt)2(H2O)2], [Ru(PPh3)(hmbt)2Cl] and [Rh(hmbt)2(H2O)2]-
Clꢁ5H2O, were studied using the thermogravimetric (TG) technique.
The weight loss observed below 130 °C is due to dehydration as the
colours changed from pale to deeper [37,41].
The thermogram of [Zn(hmbt)(OAc)(H2O)2], shows the first-
step weight loss of 28.9% between 196 and 272 °C, which corre-
sponds to the release of two coordinated waters molecules per
molecule of complex, AcO and ½N2 (Calcd. 29.1%). The second
decomposition occurs between 272 and 359° C, which is attributed
to the loss of C7H6 and C6H4N2 fragments (Calcd. 50.5, Found
50.9%), leaving ZnO (21.2%). The thermogram of [Zn(hmbt)2(H2O)2]
shows TG inflection in the ranges 150–470 °C, arise from the re-
lease of two coordinated water, 2C7H6N3 and C6H4O fragments
(Calcd. 71.3, Found 70.7%), leaving ZnO as a residue.
The TGA data for the complex, [Rh(hmbt)2(H2O)2]Clꢁ5H2O,
shows three TG inflections in the ranges 65–213, 214–301 and
302–431 °C. The first weight loss may arise from the release of five
water of crystallization, two molecule water of coordination, ½ Cl2
and C6H4N3 fragments (Calcd. 39.2, Found 39.5%), C6H4 fragments
(Calcd. 10.6, found 10.3%) and C7H6N3O (Calcd. 19.7, Found
½
19.8%), respectively, leaving Rh2O3 as a residue at 700 °C (17.8%).
For the complex, [Ru(hmbt)2(H2O)2]ꢁ2H2O, four TG inflections in
the ranges 60–180, 181–350, 351–450 and 451–600 °C were ob-
served. The first one arise from the release of two water of crystal-
lization and two water of coordination (Calcd. 11.6, Found 11.8%),
2N2 molecules (Calcd. 9.0, Found 8.7%), C6H4N and C6H4 fragments
(Calcd. 26.7, Found 27.0%), and C7H6N and C7H6 fragments (Calcd.
32.5, Found 32.4%), respectively, leaving Ru2O3 as a residue at
700 °C (20.1%). The thermogram of [Ru(PPh3)(hmbt)2Cl], show
three TG inflections in the ranges 217–304, 305–389 and 390–
588 °C, arise from the release of ½ Cl2 (Calcd. 4.2, Found 4.3%),
C7H6N3 fragment (Calcd. 15.6, found 15.5%), 3Ph fragments (Calcd.
27.3, found 26.9%), and C6H4 and C7H6N2 fragments (Calcd. 22.9,
found 22.6%) respectively [33], leaving Ru2O3 as a residue at
700 °C (15.7%).
The thermogram of [Ag2(hmbt)2], shows the first-step weight
loss of 24.9% between 175 and 275 °C, may be attributed to the re-
lease of 2C6H4, ½ N2 (Calcd. 25.0%). The second step occurs be-
tween 276 and 430 °C, attributed to the loss of C6H4, N2 and ½
N2 (Calcd. 17.7, Found 17.1%). The last decomposition step occurs
between 431–510 °C, attributed to the loss of C7H6N2O (Calcd.
20.1, Found 19.7%), leaving Ag2O (34.9%). The complex, [Ag(PPh3)
(hmbt)], shows two TG inflections in the ranges 175–310 and
311–900 °C, arised from the release of PPh3 and C6H4N3 fragments
The thermogram of [Pd(hmbt)(H2O)Cl]ꢁ3H2O, shows the first-
step weight loss of 13.3% between 63 and 110 °C, which corre-
sponds to the release of three waters molecules (Calcd. 12.3%);
the relatively low temperature shows that these water molecules
are crystal lattice held [9,10,41]. Another endothermic decomposi-
tion occurs between 111 and 350 °C, which is attributed to the loss
of coordinated H2O, ½ Cl2 and C6H4 fragment (Calcd. 29.6, Found
29.4%) [27]. There is other TG inflection in 350–610 °C region,
may arise from the elimination of C7H6N3 (Calcd. 30.2, Found
30.5%) fragment, leaving PdO (28.0%). The thermogram of
[Pd(hmbt)2], is characterized by two steps in 225–425 and 426–
575 °C region. They are assigned to the elimination of C13H11N3,
C6H4N3 (Calcd. 58.8, Found 59.1%) and C7H6O (Calcd. 19.1, Found
18.8%), fragments, respectively, leaving PdO residue at 700° C
(22.1%) [27]. The thermogram of [Pd(bpy)(hmbt)]Clꢁ2H2O shows
the first endothermic weight loss between 23 and 150 °C, may be
due to the release of crystal lattice water and ½ Cl2 molecule
(Calcd. 12.8, Found 12.8%). The second decomposition step occurs
between 151 and 350 °C, attributed to the loss of bpy species
(Calcd. 28.0, Found 28.2%). The second TG inflection between 351
and 450 °C may arise from the elimination of C6H4N3 fragment
(Calcd. 21.2, Found 21.3%), leaving PdO (Calcd. 21.9%). The thermo-
gram of [Pd(phen)(hmbt)]ClꢁH2O shows weight losses in the 23–
150, 151–270, 271–580 and 581–900° C, which may correspond
to the release of crystal lattice water (Cacld. 3.2, Found 3.5%), ½
Cl2 and C7H6N2 species (Calcd. 27.2, Found 27.5%), ½ N2 and
C6H4N(Calcd. 21.0, Found 21.1%) and C12H10 (Calcd. 27.0, Found
26.5%) fragments, leaving PdO (18.21%). The thermogram of
(Calcd. 63.9, Found 63.9%), and C7H6O fragment (Calcd. 16.5,
½
Found 16.8%), leaving Ag2O as a residue (19.5%) [12].
3.6. Anticancer activity
Cis-platin is considered to be one of the best known small
metal-containing drug molecules. It acts as anticancer agent for

200
H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
Fig. 5A. IC50 values of [Ag(hmpbt)(PPh3)], [Rh(hmbt)2(H2O)2]Cl, [Pt(phen)(hmbt)]Cl and [Pd(phen)(hmbt)]Cl tested against the human breast cancer (MDA-MB231) cell lines.
Fig. 5B. IC50 values of [Ag(hmpbt)(PPh3)], [Rh(hmbt)2(H2O)2]Cl, [Pt(phen)(hmbt)]Cl and [Pd(phen)(hmbt)]Cl tested against the human ovarian cancer (OVCAR-8) cell lines.
Table 2
several human cancers, particularly, testicular and ovarian cancers
Anticancer activity of Hhmbt and its complexes against the human breast cancer
(MDA-MB231) and human ovarian cancer (OVCAR-8) cell lines.
[8–14]. Generally, the side effects, especially nephrotoxicity, limit
its widespread use in high doses [44]. The need to develop new
Compounds
IC50
(l
M)
IC50 (lM)
complexes with reduced nephrotoxicity and higher activity has
stimulated the synthesis of many new complexes. Over the past
years, a renewed interest in Zn(II), Ag(I), Pd(II) and Pt(II) complexes
as potential anticancer agents has developed in our laboratory [8–
14].
Human breast cancer
Human ovarian cancer
(MDA-MB231) cell lines
(OVCAR-8) cell lines
Hhmbt
[Zn(hmbt)2(H2O)2]
[Zn(hmbt)(OAc)(H2O)2] 37.75
>100
>100
87.55
84.69
33.20
37.37
23.54
2.99
3.00
13.54
1.75
We have recently examined the in vitro anticancer activity of
[Pd(bpy)(hmbt)]Cl
[Pt(bpy)(hmbt)]Cl
[Pd(phen)(hmbt)]Cl
[Pt(phen)(hmbt)]Cl
[Ag2(hmbt)2]
[Ag(PPh3)(hmbt)]
[Rh(hmbt)2(H2O)2]Cl
Cis-platin
45.96
18.89
4.85
5.24
14.13
1.37
DL-piperidine-2-carboxylic acid
(DL-H2pa) and its complexes,
trans-[Zn2( -Ca)2(Hpa)2Cl6], [Pd(bpy)(Hpa)]Cl and [M(pa)(PPh3)2]
l
against serous ovarian cancer ascites, OV 90 cell line [12]. The
ultimate goal of this research is to develop new complexes with
high efficacy against cancer cells. The in vitro anticancer activity
of the free Hhmbt and its complexes, [Zn(hmbt)2(H2O)2], [Zn
(hmbt)(OAc)(H2O)2], [M(bpy)(hmbt)]Cl, [M(phen)(hmbt)]Cl (M(II)
= Pd, Pt), [Ag2(hmbt)2], [Ag(PPh3)(hmbt)] and [Rh(hmbt)2(H2O)2]Cl
were tested against the human breast cancer (MDA-MB231) and
human ovarian cancer (OVCAR-8) cell lines in comparison to cis-
platin as a reference (Fig. 5; Table 2). The complexes, [Ag2(hmbt)2],
[Ag(hmpbt)(PPh3)], [Rh(hmbt)2(H2O)2]Cl, [Pt(phen)(hmbt)]Cl and
[Pd(phen)(hmbt)]Cl exhibit the highest growth inhibitory activity
7.52
32.0
8.50
30.86
namic strength of a typical coordination bond, are much weaker
than C–C, C–N or C–O covalent bonds; the data obtained from
TGA analysis, discussed above, confirming this feature. However,
the ligand exchange behavior in Pt complexes is quite slow, which
gives them high kinetic stability. Thus, the ligand exchange reac-
tions take place in minutes to days, rather than microseconds to
seconds as in case of Pd(II) complexes [46]. The high activity of
the complexes, [Ag2(hmbt)2] and [Ag(hmpbt)(PPh3)], is expected,
since Ag(I) complexes have been reported as active anti-cancer
agents and wound healing stimulators [13,47]. In addition, the
pulk PPh3 group and its slow hydrolysis may explain the activity
of the later complex with respect to the first one [9,10]. Moreover,
the kinetic trans effect is responsible for ligand exchange reactions;
i.e., donor atoms located trans to other donors with strong trans ef-
fect are more rapidly substituted than ligands in cis-positions [46].
These features may explain the activity of [Pt(phen)(hmbt)]Cl
(Fig. 6) and [Pd(phen)(hmbt)]Cl complexes, which may attribute
with mean IC50 values 14.13, 1.37, 7.52, 5.24 and 4.85
MB231) and 13.54, 1.75, 8.50, 3.00 and 2.99 M (OVACAR-8),
respectively; the IC50 values of cis-platin being 32.00 and
30.86 M.
lM (MDA-
l
l
Generally, it is accepted that binding of cis-platin to genomic
DNA (g-DNA) in the cell nucleus is the main event responsible
for its antitumor properties [45]. Thus, the damage induced upon
binding of cisplatin to g-DNA may inhibit transcription, and/or
DNA replication mechanisms. Subsequently, these alterations in
DNA processing would trigger cytotoxic processes that lead to can-
cer cell death. An important property of Pt(II) complexes is the fact
that Pt–ligand bonds (Pt–N, Pt–O, Pt–P), which have the thermody-

H.A. El-Asmy et al. / Journal of Molecular Structure 1059 (2014) 193–201
201
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Acknowledgements
We are grateful to the Ministry of Higher Education in Egypt (H.
El-Asmy) and a NSERC (Canada) Discovery grant (ISB) for the
financial support of this work.
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Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.
2013.11.039.