New Nickel (II), Palladium (II), Platinum (II) complexes with aromatic methanesulfonylhydrazone based ligands. Synthesis, spectroscopic characterization and in vitro antibacterial evaluation

Abstract

Methanesulfonicacid hydrazide (a sulfonamide compound, msh: CH3SO2NHNH2)
14 derivatives: salicylaldehydemethanesulfonylhydrazone (salmsh), 2-
15 hydroxyacetophenonemethanesulfonyl hydrazone (afmsh), 2-hydroxy-3-
16 metoxybenzaldehydemethanesulfonylhydrazone (o-vanmsh) and their Ni(II), Pd(II) and Pt
17 (II) complexes have been synthesized. The structure of these compounds has been investigated
18 by using elemental analyses; FT-IR, 1H-NMR, LC-MS, UV-Visible spectrometric methods;
19 magnetic susceptibility; conductivity measurements; thermal studies. The antibacterial
20 activities of synthesized compounds have been determined in vitro against gram positive
21 bacteria; Staphylococcus aureus ATCC 25923, Bacillus cereus RSKK 709, and gram negative
22 bacteria; Pseudomonos aeruginosa ATCC 27853, Escherichia coli ATCC 35268 by paper
23 disc diffusion and microdilution broth methods. The biological activity screening showed that
24 metal complexes have more activity than their ligands against the tested bacteria.

Full text

Accepted Manuscript
New Nickel (II), Palladium (II), Platinum (II) complexes with aromatic metha‐
nesulfonylhydrazone based ligands. Synthesis, spectroscopic characterization
and in vitro antibacterial evaluation
Ümmühan Ö. Özdemir, Nesrin Akkaya, Neslihan Özbek
PII: S0020-1693(13)00033-9
DOI: http://dx.doi.org/10.1016/j.ica.2013.01.031
Reference: ICA 15312
To appear in: Inorganica Chimica Acta
Received Date: 13 July 2012
Revised Date: 11 January 2013
Accepted Date: 23 January 2013
Please cite this article as: Ü. Özdemir, N. Akkaya, N. Özbek, New Nickel (II), Palladium (II), Platinum (II)
complexes with aromatic methanesulfonylhydrazone based ligands. Synthesis, spectroscopic characterization and
in vitro antibacterial evaluation, Inorganica Chimica Acta (2013), doi: http://dx.doi.org/10.1016/j.ica.2013.01.031
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1
New Nickel (II), Palladium (II), Platinum (II) complexes with aromatic 1
methanesulfonylhydrazone based ligands. Synthesis, spectroscopic 2
characterization and in vitro antibacterial evaluation 3
4
Ümmühan Ö. Özdemir*a, Nesrin Akkaya a, Neslihan Özbek b 5
aDepartment of Chemistry, Faculty of Science, Gazi University, 06500 6
Teknikokullar, Ankara, Turkey 7
bDepartment of Chemistry Faculty of Education, Ahi Evran University, 40100 Kırşehir, 8
Turkey 9
10
Abstract 11
12
Methanesulfonicacid hydrazide (a sulfonamide compound, msh: CH3SO2NHNH2) 13
derivatives: salicylaldehydemethanesulfonylhydrazone (salmsh), 2-14
hydroxyacetophenonemethanesulfonyl hydrazone (afmsh), 2-hydroxy-3-15
metoxybenzaldehydemethanesulfonylhydrazone (o-vanmsh) and their Ni(II), Pd(II) and Pt 16
(II) complexes have been synthesized. The structure of these compounds has been investigated 17
by using elemental analyses; FT-IR, 1H-NMR, LC-MS, UV-Visible spectrometric methods; 18
magnetic susceptibility; conductivity measurements; thermal studies. The antibacterial 19
activities of synthesized compounds have been determined in vitro against gram positive 20
bacteria; Staphylococcus aureus ATCC 25923, Bacillus cereus RSKK 709, and gram negative 21
bacteria; Pseudomonos aeruginosa ATCC 27853, Escherichia coli ATCC 35268 by paper 22
disc diffusion and microdilution broth methods. The biological activity screening showed that 23
metal complexes have more activity than their ligands against the tested bacteria. 24
25

2
26
Keywords; Aromatic methanesulfonylhydrazone; Ni(II), Pd(II), Pt(II) complexes; 27
sulfonamide derivatives , antibacterial activity 28
29
Reprint requests to Dr. Ümmühan Ö. Özdemir 30
Fax: 90 312 2122279 31
E-mail: ummuhan@gazi.edu.tr (Ümmühan Ö. Özdemir) 32
33
1. Introduction 34
35
Sulfonyl hydrazones, derivatives of sulfonamide, exhibit several medicinal 36
applications. For example, 4-substituted benzenesulfonylhydrazone has been studied for 37
antibacterial activities [1], benzaldehyde arylsulfonylhydrazones possess antineoplastic 38
activity against human stomach cancer SGC 7901 [2], N-arylsulfonyl hydrazones have been 39
identified as novel inhibitors of IMP-1 a metallo- -lactamase enzyme [3], imidazol[1,2-a] 40
pyridines with arylsulfonylhydrazone substituents have been reported as novel PI3 kinase 41
p110a inhibitors[4]. 42
N-arylsulfonyl-3-acylindole derivatives have displayed potent anti-human 43
immunodeficiency virus type 1 (HIV-1) activity [5]. Inaddition, numerous sulfonamide 44
derivatives have been reported as carbonic anhydrase inhibitors [6], anticancerous [7] and 45
anti-inflammatory agents [8]. Transition metal complexes of hydrazides and sulfonamides 46
also find application in chemotherapy as well as their hydrazone derivatives [9]. Especially, 47
the search for platinum (II) complexes with anti-tumour properties has been going on through 48
the efforts of chemists from the medicinal chemistry field since the discovery of the anti-49
proliferation activity of cisplatin in the 1960s [10]. However, since the 1990s many trans 50

3
platinum complexes have been discovered with significant anti-tumour activity against 51
different tumour cells including these resistant to cisplatin [11-13]. Owing to the similar co-52
ordination modes of the cation Pd(II) and Pt(II) (d8-electron configuration) there has also been 53
renewed interest in attempts to obtain activity for cis and trans palladium(II) complexes [14-54
16] . Furthermore, somemixed ligand palladium(II) complexes have been shown to act as 55
potential anticancer agents [17-19]. 56
In our previous studies, we reported the antibacterial and cytotoxic effect of 57
methanesulfonic acid hydrazide and its sulfonylhydrazone derivatives [20-22], as well as its 58
metal carbonyl complexes [23,24]. Methane, ethane and prophanesulfonylhydrazone 59
derivatives and their transition metal complexes were synthesized and screened for 60
antimicrobial activity [25-27]. Furthermore, ethanesulfonylhydrazone derivatives and their 61
transition metal complexes were investigated inhibitory effects on carbonic anhydrase II (CA 62
II) enzyme [26]. 63
As part of our ongoing studies, methanesulfonicacid hydrazide (sulfonamide compound) 64
and its derivatives: salicylaldehydemethanesulfonylhydrazone (salmsh), 2-65
hydroxyacetophenone methanesulfonylhydrazone(afmsh) and 2-hydroxy-3-metoxy 66
benzaldehydemethanesulfonyl hydrazone (o-vanmsh) were synthesized. The structure of 67
salmsh and afmsh ligands were reported in our previous work [20, 28]. Ni(II) Pd(II) and Pt(II) 68
complexes of aromatic methanesulfonylhydrazone derivatives and ovanmsh ligand were 69
synthesized for the first time and characterized by using elemental analysis, FT-IR, LC-MS, 70
UV-Visible spectrometric methods, magnetic susceptibility, conductivity measurements and 71
thermal studies. The antibacterial activities of synthesized compounds have been determined 72
in vitro against gram positive bacteria; Staphylococcus aureus ATCC 25923, Bacillus cereus 73
RSKK 709, and gram negative bacteria; Pseudomonas aeruginosa ATCC 27853, Escherichia 74
coli ATCC 35268 by paper disc diffusion and microdilution broth methods. 75

4
2. Experimental 76
77
2.1. Physical measurements 78
79
The solvents used were purified and distilled according to routine procedures. 80
Methane sulfonyl chloride, hydrazine hydrate, salicylaldehyde, 2-hydroxyacetophenone, 2-81
hydroxy-3-metoxybenzaldehyde and anhydrous nickel , palladium and platinum chloride were 82
commercial products (purum). The elemental analyses (C, H, N and S) were performed on a 83
LECO–CHSNO - 9320 type elemental analyzer.1H-NMR spectra of dimethylsulfoxide-d6 84
(DMSO-d6) solutions of the compounds were recorded on a Bruker WM-400 spectrometer 85
(400 MHz) using tetra methyl silane as internal standard. D2O-exchange was applied to 86
confirm the assignment of the NH- and OH-signals .The infrared spectra of the compounds as 87
KBr-disks were recorded in the range of 4000-400 cm-1 with a Mattson 1000 FT spectrometer. 88
UV-Vis spectra were recorded on UNİCAM-UV 2-100 spectrophotometer. Melting points of 89
aromatic methanesulfonylhydrazone derivatives were determined with a Gallenkamp melting 90
point apparatus.The molar magnetic susceptibilities were measured on powdered samples 91
using Gouy method. The molar conductance measurements were carried out using a Siemens 92
WPA CM 35 conductometer. A Du Pont Instrument 951 thermal analyzer was used to record 93
simultaneously TG and DTA curves. The experiments were carried out in dynamic nitrogen 94
atmosphere (20 ml min−1) with a heating rate of 10 °C min−1 in the temperature range 30–95
400 °C using platinum crucibles. The microdilusion broth and disc diffusion method were 96
used to determine the antibacterial activity of compounds against the bacteria; Staphylococcus 97
aureus ATCC 25923, Bacillus cereus RSKK 709, Pseudomonos aeruginosa ATCC 27853, 98
Escherichia coli ATCC . 99
100

5
2.2. Synthesis of ligands 101
102
The procedure of preparation of aromatic methanesulfonylhydrazone derivatives are 103
similar to that applied by us [27]. Thus, solution of 1.10 g (10 mmol) methanesulfonicacid 104
hydrazide in 5 ml of ethanol was mixed with hot solution of 12 mmol of the corresponding 105
carbonyl compound (salicylaldehyde, 2-hydroxyacetophenone,2-hydroxy-3-106
metoxybenzaldehyde respectively) in 10 ml of ethanol and stirred for 1 h.. Upon cooling, the 107
obtained crystalline precipitates were filtered, washed with ethanol-ether, recrystallized from 108
water and dried in vacuo over P2O5. They are light yellow crystalline solids, stable at normal 109
conditions and soluble in methanol, ethanol, acetonitrile, dimethylformamide, DMSO; poorly 110
soluble in benzene and water. 111
112
2.3. Synthesis of Ni(II), Pd(II), Pt(II) complexes 113
114
All complexes are prepared by the following general method. A sample of anhydrous 115
MCl2 (M=Ni, Pd, Pt) (0,53 mmol) was dissolved in a mixture of methanol and acetonitrile (25 116
mL), and solution of methanesulfonylhydrazone derivatives (1,60 mmol) in a mixture of 117
acetonitrile (25 mL) and NaOH solution in methanol (1,60 mmol) was added. The reaction 118
mixture was heated under reflux for 1 h, at 40oC and left in ice bath for 3 h. The solid 119
complexes formed was collected by filtration, washed with a small volume of methanol and 120
ether, and then, were left in glass oven at 170oC for a 2 hours in vacuo to prevent the 121
hydration dried in a desiccators over CaCl2. 122
123
2.4. Procedure for antibacterial activity 124
125

6
The in vitro antibacterial activity of the free ligands and their complexes were tested 126
against the gram positive bacteria; Staphylococcus aureus ATCC 25923, Bacillus cereus 127
RSKK 709, and gram negative bacteria, Pseudomonas aeruginosa, ATCC 27853, Escherichia 128
coli ATCC 35268 by paper disc diffusion and micro dilution broth methods. 129
Bacteria cultures were obtained from Gazi University, Biology Department. Bacterial strains 130
were cultured overnight at 310o K in Nutrient Broth. During the survey, these stock cultures 131
were stored in the dark at 277o K. The inocula of microorganisms were prepared from 12 h 132
broth cultures and suspensions were adjusted to 0.5 McFarland standard turbidity. 133
134
2.4.1. Disc diffusion method 135
The synthesize compounds and complexes were dissolved in dimethylsulfoxide (20% 136
DMSO) to a final concentration of 5.0 mg mL−1 and sterilized by filtration by 0.45 μm 137
millipore filters. Antimicrobial tests were then carried out by the disc diffusion method using 138
100 μL of suspension containing 108 CFU mL−1 bacteria spread on a nutrient agar (NA) 139
medium. The discs (6 mm in diameter) were impregnated with 20 μL of each compound 140
(100μg/disc) at the concentration of 5.0 mg mL−1 and placed on the inoculated agar. DMSO 141
impregnated discs were used as negative control. Sulfamethoxazole (300 µg/disk) and 142
sulfisoxazole (300 µg/disk) were used as positive reference standards to determine the 143
sensitivity of one strain/isolate in each microbial species tested. The inoculated plates were 144
incubated at 37oC for 24 h for bacterial strains isolates. Antimicrobial activity in the disc 145
diffusion assay was evaluated by measuring the zone of inhibition against the test organisms. 146
Each assay in this experiment was repeated twice [29]. The values obtained are average of the 147
two results. Percentage of inhibition by comparing distance of the compounds to the positive 148
control using (Sulfamethoxazole) the equation below [30]: 149

7
%Inhibition =
diameter of the sample
diameter of the positive control * 100
150
151
2.4.2. Micro dilution assays 152
The inocula of microorganisms were prepared from 12 h broth cultures and 153
suspensions were adjusted to 0.5 McFarland standard turbidity. The test compounds dissolved 154
in 20% dimethylsulfoxide (DMSO) were first diluted to the highest concentration (8.0 mg 155
mL−1) to be tested, and then serial, two-fold dilutions were made in a concentration range 156
from 15.625 to 4000μg mL−1 in 10mL sterile test tubes containing nutrient broth. The MIC 157
values of each compound against bacterial strains were determined based on a micro-well 158
dilution method. 159
The 96-well plates were prepared by dispensing 95 μL of nutrient broth and 5 μL of 160
the inoculums into each well. One hundred μL from each of the test compounds initially 161
prepared at the concentration of 4000 μg mL−1 was added into the first wells. Then, 100 μL 162
from each of their serial dilutions was transferred into nine consecutive wells. The last well 163
containing 195 μL of nutrient broth without compound, and 5 μL of the inoculum on each 164
strip, was used as negative control. The final volume in each well was 200 µL. The contents 165
of the wells were mixed and the micro plates were incubated at 37oC for 24 h. All compounds 166
tested in this study were screened twice against each microorganism and the average was 167
taken. The MIC was defined as the lowest concentration of the compounds to inhibit the 168
growth of microorganisms [31]. 169
170
3. Results and Discussion 171
172

8
Analytical data and some physical properties of aromatic methanesulfonylhydrazone 173
and their complexes are listed in Table 1. The elemental analysis results show 1:2 (metal: 174
ligand) stoichiometry for all the complexes. The analytical results are in good agreement with 175
those required by the general formula (ML2).The molar conductivity (Λm) of 10−3 M solutions 176
of the complexes in MeOH at 25 C were measured and all the complexes were found non-177
electrolytic nature in the range of 3.3 - 5.9
-1 cm2 mol-1. 178
179
3.1. The characterization of compounds 180
181
3.1.1. IR spectra 182
The important diagnostic i.r. bands of aromatic methanesulfonylhydrazone and their 183
complexes are summarized in Table 2. Bands in the region of 3210, 3203 and 3217 cm-1 may 184
be due to ν(NH) stretching vibration for salmsh, afmsh and ovanmsh. The strong bands at 185
1624, 1622 and 1618 cm-1 are assigned to ν(C=N) stretching mode of the imine group for 186
ligands. These bands are shifted to lower wave number in all complexes. These shifts support 187
the participation of the imine group of these ligands in binding to the metal ions [25-27]. 188
Ligands also display bands at 1268, 1232 and 1247 cm−1 which are assigned to ν(C-O) 189
stretching vibrations for salmsh, afmsh, ovanmsh respectively. These bands are strongly 190
affected by chelation through the phenolic-CO groups of the aromatic 191
methanesulfonylhydrazone and the shift to higher wave numbers indicates the coordination of 192
phenolic-O donor atoms [32]. 193
194
3.1.2. NMR spectra 195
1H-NMR data of DMSO-d6 solutions of the aromatic methanesulfonylhydrazone are 196
collected in Table 3. salmsh and ovanmsh show signals at 8.27-8.17 ppm which are attributed 197

9
to the imines protons (-N=CH-). afmsh ( ketone derivative) show signals at 2.31 ppm which 198
is attributed to the -CH3C=N- protons [26]. 199
The signals of the HC=N and CH3C=N protons show no splitting, and the positions of the 200
signals of the ring protons are typical. In general, the multiplates observed at 6.88 -7.60 ppm, 201
6.89 -7.55ppm and 6.80 -7.10 ppm are asigned to salmsh , afmsh and ovanmsh ring protons; 202
respectively. Signals at 10.21 ppm and 11.00 ppm; 10.45 ppm and 11.68 ppm; 10.20 ppm and 203
11.06 ppm are assigned to the NH and OH protons, respectively for salmsh , afmsh and 204
ovanmsh. The high field shift of NH protons may be due to the involvement of this group with 205
a hydrogen bond in DMSO-d6, which is well known for its interaction with an amide proton 206
[33]. 207
3.1.3. Mass spectra 208
LC-MS data of aromatic methanesulfonyl hydrazone complexes are summarized in 209
Table 4 LC-MS spectra shows that [Ni(salmsh)2], [Ni(afmsh)2], and [Ni(ovanmsh)2], give the 210
molecular ions, [NiL2+2H]+ with the expected m/z values (intensity %)= 482.0 (30.0) , 510.03 211
(20.0) and 542.0 (40.1), [L+H]+ fragments are observed at 215.0 ( 100.0) , 229.05 (100.0) and 245.0 212
(100.0) as main peak for salmsh, afmsh and ovanmsh; respectively . [Pd(salmsh)2], [Pd(afmsh)2], 213
and [Pd(ovanmsh)2], give the molecular ion peaks, [PdL2]+ at the desired positions : m/z (intensity 214
%)= 532.9 (79.0), 561.01 (28.0) and 592.0 (5.1). [Pt(afmsh)2], [Pt(ovanmsh)2], give the molecular ions, 215
[PtL2-CH3]+ at the desired positions. m/z (intensity %)= 634.1(30) , 666.1(20) and [Pt(salmsh)2] 216
gives molecular ion, [PtL2+Na]+ at 621.20 (10). 217
218
3.1.4. Electronic spectra and magnetic behaviour 219
The significant electronic spectra of the complexes are recorded in methanol. The 220
important bands of the ligands and the complexes are observed in the region of 294-245 nm 221

10
and 340 -313 nm. These may be attributed, respectively, to π→ π* type and charge-transfer 222
transitions. The spectra of the Ni2+, Pd2+ and Pd2+ complexes show bands in the range of 460-223
498 nm. Hence, square-planar structures may be assigned to these complexes [34]. 224
The magnetic moments of complexes (as B.M.) were measured at room temperature. 225
The diamagnetic character of the nickel (II), platinum (II) and palladium (II) complexes 226
shows square-planar geometry for these complexes 227
228
3.1.5. Thermal decomposition studies 229
The Ni(II), Pd(II) and Pt (II) complexes were left in glass oven at 170oC for a 2 hours 230
in vacuo to prevent the hydration. The thermo grams of anhydrous of all complexes were 231
observed in the range of 35-700oC. As expected there was no mass loss up to 220oC. All 232
complexes have thermally decompose in the range of 220-700oC which means all complexes
233
doesn’t contain any coordinated or crystal water molecules [27] 234
235
3.2. Antibacterial activity results 236
237
The test compounds were screened in vitro for their antibacterial activity against two 238
Gram-positive species (Bacillus cereus and Staphylococcus aureus) and two Gram-negative 239
species (Eschericha coli and Pseudomonas aeruginosa) of bacterial strains by the disc 240
diffusion and micro dilution methods. The antibacterial results were given in Table 5 by disc 241
diffusion and Table 6-7 micro dilution methods. The results were compared with those of the 242
standard drugs sulfamethoxazole and sulfioxazole (Figure 1-2). 243
As the disc diffusion assay results evidently show (Table 5, Fig.1-2) that o-vanmsh has 244
exhibited the strong inhibition effect against most of test bacteria whereas salmsh and afmsh 245

11
have weaker activity. The structure–activity relationships (SAR) suggest that both methoxy 246
and azomethine (-NH-N= CH-) groups containing o-vanmsh have important effects on 247
maximum antibacterial activity. Similar results were also reported by Govindasami et al. [35]. 248
All ligands and their complexes show the the highest activities against S. aureus which is the 249
mostly effected by Pd(o-vanmsh)2 having the diameter zone of 18 mm. 250
All compounds except afmsh have modarete activity against P. aeruginosa at in the diameter 251
zone of 10-15 mm whereas sulfisoxazole, the drug used as standard, has been found less 252
active (8 mm) against the bacteria mentioned above. The aromatic metansulfonylhydrazone 253
complexes show remarkable increase in antimicrobial activity than the parent ligands. 254
Percentage of inhibition for the compounds exhibited in Fig.3 that was expressed as 255
excellent activity (120-200% inhibition), good activity (90-100% inhibition), moderate 256
activity (75-85% inhibition), significant activity (50-60% inhibition), negligible activity (20-257
30% inhibition) and no activity [36]. As seen in Fig.3, Pd(o-vanmsh)2 shows excellent activity 258
while other metal complexes except Ni(afmsh)2 have good activity or moderate activity 259
against S.aureus. Pt(afmsh)2, Ni(o-vanmsh)2, Pd(o-vanmsh)2 and Pd(salmsh)2 exhibit moderate 260
activity against P. aeruginosa, whereas rest of the complexes show negligible activity. Pd(o-261
vanmsh)2, Pd(salmsh) and Pt(o-vanmsh)2 exhibit significant activity against B. cereus. 262
According to the MIC’s results shown in Table 6, the compounds possess a broad 263
spectrum of activity against the tested bacteria at the concentrations of 31.25–2000 µg/mL 264
[37]. The o-vanmsh, Pd (o-vanmsh)2 and Pt (o-vanmsh)2 have shown activity against S. 265
aureus ATCC 25923 and B. cereus RSKK 709 at a concentration of 31.25 µg/mL, 62.5 266
µg/mL whereas sulfisoxazole, the drug used as standard, has been found less active against 267
the bacteria. Also, the antimicrobial activity is highly influenced by the nature of the 268
sulfonylhydrazone derivatives and the order of the activity in mM for all test bacteria is as 269
follows (Table 7): 270

12
Pd(o-vanmsh)2 >Pd(salmsh)2 > Pd(afmsh)2> Ni(o-vanmsh)2>Pt(o-vanmsh)2 >Pt(afmsh)2 > 271
o-vanmsh>Pt(salmsh)2> Ni(salmsh)2>Ni(afmsh)2>salmsh>afmsh 272
As seen in Table 7, metal complexes show significant activity against the microorganisms. It is 273
supposed that the increased lipophilic character of bulky complexes may be responsible for 274
their potent antimicrobial activity than ligands. The permeation of complexes through the 275
lipid layer of the cell membranes deactivates diverse cellular enzymes, which play a vital role 276
in various metabolic systems of these microorganisms [38, 39]. As a results, Pd(II) and Pt(II) 277
complexes are more active than Ni(II) complexes. 278
279
4. Conclusions 280
281
In this study we have reported the synthesis of aromatic methanesulfonyl hydrazone 282
derivatives and their Ni(II), Pd(II) and Pt (II) complexes. The structural characterizations of 283
the synthesized compounds were made by using the elemental analyses, spectroscopic 284
methods, magnetic and conductance studies, and thermal analysis. From the spectroscopic 285
characterization, it is concluded that aromatic methanesulfonylhydrazones act as a bidentate 286
ligands, coordinating through >C=N and phenolic –OH via deprotonation. Based on 287
physicochemical evidence, the proposed structure of sulfonamide derivatives and their 288
complexes are exhibited in Figure 4. N,O,S donors in sulfonylhydrazones are the most 289
important factors affecting the bioactivity. The biological activity screening showed that 290
complexes have more activity than ligands against the tested bacteria. Furthermore, our Pd(II) 291
and Pt(II) complexes showed the most activity against all bacteria. 292
293

13
Acknowledgements 294
The authors would like to thank Gazi University BAP (Grant No: 05/2012-12) for the 295
financial support of this project. 296
297
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[29] A.W. Bauer, W.M. Kirby, J.C. Sherris, M.Turck Am. J. Clin. Pathol. 45 (1966) 493. 342

15
[30] R.B. Mulaudzi, A.R. Ndhlala, M.G. Kulkarni, J.F. Finnie, J. Van Staden, J. of 343
Ethnopharmacology 135 (2011) 330. 344
[31] S.G. Küçükgüzel, A. Mazi, F. Sahin, S. Öztürk, J. Stables, Eur.J. Med. Chem 38 (2003) 345
1005. 346
[32] E. Keskioğlu, A. Balaban Gündüzalp, S. Çete, F. Hamurcu, B. Erk, Spect.Chim. Acta 347
Part A 70 (2008) 634. 348
[33] A.Balaban Gündüzalp, B. Erk, Russian Journal of Inorganic Chemistry 55(2010) 1094. 349
[34] A.B.P. Lever, Inorg. Electronic Spectroscopy, 2nd Edition, Elsevier, Amsterdam, (1984) 350
534. 351
[35] T. Govindasami, A. Pandey, N. Palanivelu, A. Pandey, International Journal of Organic 352
Chemistry 1 ( 2011) 71. 353
[36] N. Sultana, A. Naz, M.S. Arayne, M.A. Mesaik, J. Mol. Struct. 969 (2010) 17. 354
[37] Z.H. Chohan, A.U. Shaıkh, M.M. Nasee , C.T. Supuran, J. Enzyme. Inhib. Med. Chem. 355
21 (2006) 771. 356
[38] Z.H. Chohan, A. Scozzafava, C.T. Supuran, J. Enzyme. Inhib. Med. Chem. 17 (2002) 357
261. 358
[39] Z.H. Chohan, , C.T. Supuran, A. Scozzafava, J. Enzyme. Inhib. Med. Chem. 18 (2003) 1. 359
360
361
362
363
364
365

16
366
Figure Caption 367
368
Figure 1. Comparison of antibacterial activite of ligands, metal (II) complexes.and antibiotics 369
Figure 2. Average antibacterial activity of ligands and metal (II) complexes. 370
Figure 3. Percentage of inhibition of ligands and metal (II) complexes. 371
Figure 4. Structures of Ligands (a) and Complexes(b) 372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408

17
409
410
411
412
413
414
415
416 417
Fig. 1. Comparison of antibacterial activite of ligands, metal (II) complexes.and antibiotics 418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447

18
448
449
450
451
452
Fig. 2. Average antibacterial activity of ligands and metal (II) complexes. 453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481

19
482
483
484
485
486
487 488
Fig. 3. Percentage of inhibition of ligands and metal (II) complexes. 489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522

20
523
524
525
526
527
R
2
R
1
NH
S
H
3
C
C
OH
N
O
O
528 529
R1=H R2=H; salmsh 530
R1=CH3 R2=H; afmsh 531
R1=H R2=OCH3;ovanmsh 532
533
(a) 534
535
536
R
2
R
1
NH
SO
2
H
3
C
CN
OMNC
HN
SO
2
R
1
O
H
3
C
R
2
537 538
R1=H, R2=H; M=Ni; Nisalmsh; M=Pd;Pdsalmsh; M=Pt;Ptsalmsh 539
R1=CH3,R2=H; M=Ni; Niafmsh; M=Pd;Pdafmsh; M=Pt;Ptafmsh 540
R1=H, R2=OCH3; M=Ni; Niovanmsh;M=Pd;Pdovanmsh; M=Pt;Ptovanmsh 541
542
(b) 543
544
Fig. 4. Structures of Ligands (a) and Complexes(b) 545
546

21
547
Table 1
Analytical and physical data for aromatic methanesulfonylhydrazone derivatives and their complexes
550
found(calculated)
Compound Empirical Formula
(Formula Weight)
Colour
m.p.( ºC)
Yield
(%)
%C %H %N %S
salmsh C8H10N2SO3
214,11 white 149-150 50 44,38
(44,87)
4,49
(4,67)
12,92
(13,07)
14,41
(14,97)
afmsh C9H12N2SO3
228,12 white 161-162
55 49.1
(49.5)
5.3
(5.8)
11.5
(11.6)
13.0
(13.2)
o-vanmsh C9H12N2SO4
244,11
light
yellow 120-121 40 44,02
(44,27)
4,65
(4,91)
10,92
(11,47)
12,50
(13,13)
Ni(salmsh)2 C16H18N4S2O6 Ni
484,93 green 275 40 40,63
(39,62)
3,99
(3,71)
11,76
(11,54)
11,33
(13,22)
Pd(salmsh)2
C16H18N4S2O6Pd
532,62
orange
248 50 35,85
(36,07)
3,25
(3,37)
9,88
(10,51)
11,75
(12,03)
Pt(salmsh)2
C16H18N4S2O6 Pt
621,31
light
brown 258 35 29,98
(30,92)
2,59
(2,89)
8,81
(9,01)
10,03
(10,32)
Ni(afmsh)2 C18H22N4S2O6 Ni
512,95 green 242 45 41,80
(42,14)
4,00
(4,28)
9,90
(10,91)
11,55
(12,05)
Pd(afmsh)2 C18H22N4 S2O6 Pd
560,64
orange
260 40 39.2
(39.3)
4.3
(4.7)
9.9
(10.2)
11.2
(11.7)
Pt(afmsh)2 C18H22N4 S2O6 Pt
649,33 brown 220 40 39,9
(40,4)
5.1
(5.4)
9.0
(9.4)
10.6
(10.8)
Ni(ovanmsh)2 C18H22N4S2O8 Ni
544,93 green 234 35 39,06
(39,67)
3,85
(4,03)
9,50
(10,27)
10,98
(11,76)
Pd(ovanmsh)2
C18H22N4S2O8 Pd
592,93
orange
260 40 34,95
(36,45)
3,01
(3,71)
8,84
(9,44)
9,85
(10,81)
Pt(ovanmsh)2
C18H22N4S2O8 Pt
681,31 brown 230 30 30,85
(31,73)
3,14
(3,22)
8,76
(8,22)
9,65
(9,41)
551
552
553
554
555
556
557
558
559
560
561
562
563
564

22
565
566
567
Table2 568
Major i.r. absorption bands (cm-1) of aromatic methanesulfonyl hydrazone derivatives and their 569
complexes 570
571
comp.
Assign (NH ) (C=N) as(SO2) (CO) s(SO2 ) δ(NH ) δ(SO2 )
salmsh 3210s 1624s 1320s 1268s 1152s 670w 524m
afmsh 3203s 1622s 1322s 1232s 1153s 626m 515m
o-vanmsh 3217s 1618s 1320s 1247m 1159s 651m 520m
Ni(salmsh)2 3127s 1608s 1320s 1277m 1154s 652m 522m
Pd(salmsh)
2 3180s 1602s 1321s 1290m 1157s 660m 527m
Pt(salmsh)2 3203s 1602s 1319s 1295m 1154s 678m 539m
Ni(afmsh)2 3210s 1606s 1324s 1259m 1155s 625m 519m
Pd(afmsh)2 3196s 1578s 1340s 1273m 1157s 623m 515m
Pt(afmsh)2 3210s 1600s 1324s 1254m 1159s 628m 520m
Ni(ovanmsh)2 3198s 1604s 1320s 1257m 1159s 647m 514m
Pd(ovanmsh)
2 3210s 1600s 1317s 1265m 1143s 650m 520m
Pt(ovanmsh)2 3208s 1600s 1317s 1265m 1143s 650m 542m
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597

23
598
599
600
601
602
Table 3 603 1H-NMR spectroscopic data for aromatic methanesulfonylhydrazone derivatives in DMSO-d6 604
(ppm) 605
606
Assign. asalmsh aafmsh ovanmsh
CH3C=N - 2,31(s,3H) -
SO2CH3 3,06(s,3H) 3,08(s,3H) 2.95(s,3H)
OCH3 - - 3,86(s,3H)
CH =N 8.27(s,1H) - 8.17(s,1H)
NH 10.21(s,br) 10,45(s,1H) 10,20(s,1H)
Ar 6.88-7.60(mH) 6,89-7,55(mH) 6.80-7.10(mH)
OH 11.00(s,br) 11,68(s,1H) 11.06(s,1H)
aTaken from [20] 607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625

24
626
627
628
Table 4 629
The Mass Spectral data of aromatic methanesulfonyl hydrazone complexes 630
631
Compounds MW
Relative intensities of the major ions ( m/z, % )and assignment
Ni(salmsh)2 484,93 [M-2H]+ (482.0, %30), [L+H]+ (215,06, %100)
Pd(salmsh)2 532,62 [M]+ (532,97, %79), [M-H]+(531.0, %45), [M+Na]+ (554,96, %9), [L+H]+
(215,04, %100)
Pt(salmsh)2 621,31 [M+Na]+ (644,20, %10), [ L+CH3]+ (229,90 %100)
Ni(afmsh)2 512,95 [M-2H]+ (510,03, %20), [M]+(511,0,%3], [L+H]+ (229,05, %100)
Pd(afmsh)2 560,64 [M]+ (561,01, %28), [M+Na]+ (582,9, %62), [L+H]+(229,03 %100)
Pt(afmsh)2 649,33 [M-CH3]+ (634,1, %30), [L+H]+ (229,07, %100)
Ni(o-vanmsh)2 544,93 [M-2H]+ (542,0, %40.1), [L+H]+ (245,04, %100)
Pd(o-vanmsh)2 592,93 [M]+ (592,9, %5,1), [L-OCH3]+ (211,9, %5)
Pt(o-vanmsh)2 681,31 [M-CH3]+ (666,1, %20), [L+H]+ (245,05, %100)
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655

25
656
657
658
659
660
661
Table 5 662
Inhibition zone of aromatic methanesulfonylhydrazone derivatives and their complexes by disc 663
diffusion method (mm) 664
665
Diameter inhibition zone* (mm, 100µg/disk)
Gram -positive Gram- negative
Compounds
(µg/mL)
S. aureus ATCC
25923
B. cereus RSKK
709
P. aeruginosa
ATCC 27853
E.coli ATCC
35268
salmsh 13 12 10 10
afmsh 12 10 7 8
o-vanmsh 14 13 14 11
Ni(salmsh)2 15 - 12 11
Pd(salmsh)2 16 16 14 13
Pt(salmsh)2 15 13 11 12
Ni(afmsh)2 10 - 11 -
Pd(afmsh)2 15 12 12 11
Pt(afmsh)2 13 8 14 12
Ni(o-vanmsh)2 12 10 14 14
Pd(o-vanmsh)2 18 16 15 16
Pt(o-vanmsh)2 16 14 11 13
SD1 15 28 17 17
SD2 25 17 8 20
SD1: Sulfamethoxazole (300 μg/disk) SD2: sulfioxazole (300 μg/disk) <10: weak; > 10 moderate; >16: 666
significant *: Average values. 667
668
669
670
671
672
673
674

26
675
676
677
678
679
680
Table 6 681
The MIC’s ( g/mL) values of aromatic methanesulfonyl hydrazone derivatives and their 682
complexes 683
684
MIC* µg/mL
Gram –positiveGram- negative
Compounds
S. aureus ATCC
25923
B. cereus RSKK
709
P. aeruginosa
ATCC 27853
E.coli ATCC
35268
salmsh250 125 10001000
afmsh50050010001000
o-vanmsh31.25 62.5 500 500
Ni(salmsh)2500 500 1000 1000
Pd(salmsh)262.50 250 500 500
Pt(salmsh)2250 500 1000 1000
Ni(afmsh)2500 500 2000 2000
Pd(afmsh)2125 250 250 1000
Pt(afmsh)2125 500 1000 500
Ni(o-vanmsh)2500 500 500 1000
Pd(o-vanmsh)231.25 31.25 500 500
Pt(o-vanmsh)231.25 62.5 2000 1000
SD132166464
SD293.7537537523.5
SD1: Sulfamethoxazole SD2: sulfisoxazole *: Average values. 685
686
687
688
689
690

27
691
692
693
694
695
696
Table 7 697
The MIC’s values of aromatic methanesulfonylhydrazone derivatives and their complexes 698
(mM of 20%DMSO) 699
Gram -positiveGram- negative
Compounds S. aureus ATCC
25923
B. cereus RSKK
709
P. aeruginosa
ATCC 27853
E.coli ATCC
35268
salmsh1.1670.5844.6704.670
afmsh2.1922.1924.3834.383
o-vanmsh0.1280.2562.0482.048
Ni(salmsh)21.0311.0312.062.06
Pd(salmsh)20.0580.4690.9380.938
Pt(salmsh)20.0500.8051.6093.219
Ni(afmsh)20.9740.9743.9003.900
Pd(afmsh)20.2230.4460.4461.784
Pt(afmsh)20.19250.7701.5400.770
Ni(o-vanmsh)20.9170.9170.9171.835
Pd(o-vanmsh)20.0520.0520.8440.844
Pt(o-vanmsh)20.0460.0922.9351.468
SD10.1260.0630.2530.253
SD20.3511.4031.4030.088
SD1: Sulfamethoxazole SD2: sulfisoxazole 700
701
702

28
703
704
Graphical abstract 705
R
2
R
1
NH
SO
2
H
3
C
CN
OMNC
HN
SO
2
R
1
O
H
3
C
R
2
R1=H, R2=H; M=Ni; Nisalmsh; M=Pd;Pdsalmsh; M=Pt;Ptsalmsh
R1=CH3,R2=H; M=Ni; Niafmsh; M=Pd;Pdafmsh; M=Pt;Ptafmsh
R1=H, R2=OCH3; M=Ni; Niovanmsh;M=Pd;Pdovanmsh; M=Pt;Ptovanmsh

706
707

29
708
709
►Structures of aromatic methanesulfonylhydrazone complexes 710
►Percentage of inhibition of ligands and metal (II) complexes 711
712