Spectroscopic characterization and biological activity of salicylaldehyde thiazolyl hydrazone ligands and their metal complexes. Alaaddin Cukurovali* and ...
Springer 2006
Transition Metal Chemistry (2006) 31:207--213 DOI 10.1007/s11243-005-6353-8
Spectroscopic characterization and biological activity of salicylaldehyde thiazolyl hydrazone ligands and their metal complexes _ Alaaddin Cukurovali* and Ibrahim Yilmaz Faculty of Arts and Sciences, Chemistry Department, Firat University, 23119 Elazig, Turkey Sevda Kirbag Faculty of Arts and Sciences, Biology Department, Firat University, 23119 Elazig, Turkey Received 1 August 2005; accepted 24 October 2005
Abstract Two novel bidentate Schiff base ligands, 2-(2-hydroxy-3,5-dichloro/diboromo) benzaldehyde-[4-(3-methyl-3-mesitylcyclobutyl)-1,3-thiazol-2-yl]hydrazone, L1H, L2H and their transition metal complexes are reported. The new ligands and their complexes have been characterized by elemental analyses, LM, infrared, u.v.--vis, 1H- and 13Cn.m.r. spectroscopy, and magnetic susceptibility measurements. The thermal properties of all complexes have been investigated by TG technique. The complexes contain two monoanionic, bidentate NO ligands. It was found that all the complexes are mononuclear. Antimicrobial activities of the ligands and their complexes have been tested against five different microorganisms, and some of the complexes were found to be active against some of the microorganisms studied.
Introduction Thiazolyl and benzothiazolyl groups are of importance in biological systems as anti-inflammatory, analgesic agents and inhibitors on lipoxygenase activities [1, 2]. The effective role of the azomethine linkage in certain biological reactions [3] is well documented. This group of compounds is characterized by great biological activity; they play an important role in biological systems [4], and they are considered to be suitable models for pyridoxal and, in general, B6 vitamins [5]. Recently, some Schiff bases containing thiazolyl, thiazolinyl and benzothiazolyl groups have been synthesized and found to be effective as lipoxygenase’s inhibitors and anti-inflammatory agents [6]. On the other hand, cyclobutane carboxylic acids in different forms were described as highly potent l-Glutamate, Nmethyl-D-aspartate (NMDA) agonist, NMDA antagonists and anticonvulsive drugs [7--9]. Combining these facts along with the data that some Schiff base complexes have notable antitumor activity [10], led us to the preparation of these ligands and their metal complexes. These ligands containing cyclobutane, thiazole and Schiff base functions in their molecules, seem to be suitable candidates for further chemical modifications and may be pharmacologically active and useful as ligands in coordination chemistry. This paper deals with their preparation and characterization, as well as their complexes formed between * Author for correspondence: E-mail: acukurovali@firat.edu.tr
the Schiff base ligands L1H, L2H (Scheme 1) and cobalt(II), copper(II), nickel(II) and zinc(II) metal chlorides, and their biological activity study. As far as we know, this is the first report on these ligands.
Experimental Materials 2-Hydroxy-3,5-dichlorobenzaldehyde, 2-hydroxy-3,5-di bromobenzaldehyde, NaHCO3, metal salts and thiosemicarbazide were purchased from Merck (pure) and were used without further purification. 1-Mesityl-1methyl-3-(2-chloro-1-oxoethyl)cyclobutane was prepared according to the previously published procedure [11]. Solvents were of analytical grade and purified by standard methods where necessary. Physical measurements Microanalyses were performed on a LECO CHNSO932 auto elemental analysis apparatus. I.r. spectra were recorded on a Mattson 1000 FT-IR Spectrometer using KBr pellets. The 1H- and 13C-n.m.r. spectra were recorded on a Varian-Gemini 200 MHz at 50.34 MHz spectrometer. The electronic spectra of the ligand and the complexes were recorded in DMF solutions using a CECIL model CE 5502 u.v.--vis spectrophotometer. Magnetic susceptibilities were determined on a Sherwood Scientific magnetic susceptibility balance (Model
208 Cl(Br)
NH2
EtOH
H2NC(S)NHNH2 + OHC
C NH N CH S
HO
(1 or 2) +
O
Ms C Me
CH2Cl
Cl(Br)
NaHCO3
Ms
EtOH
Me
6 5 7
1
Cl(Br) 4
8
(1), = Cl HO (2), = Br
2 3
Cl(Br)
Cl(Br)
N NH N CH S
CH3 Ms = H3C
L1H, (3). = Cl L2H, (4). = Br
HO
Cl(Br)
CH3 Scheme 1.
MK1) at room temperature (20C) using Hg[Co(SCN)4] as the calibrant; diamagnetic corrections were made by using the Zinc(II) complex diamagnetisms of both ligands, directly measured by MK1 balance. Melting points were determined on a Gallenkamp melting point apparatus and checked by differential scanning calorimetry (DSC) and are uncorrected. Thermogravimetric curves were recorded on a Schimadzu TG-50 thermo balance. 1-(2-Hydroxy-3,5-dichlorbenzylidene) thiosemicarbazide (1) To a solution of thiosemicarbazide (0.91 g, 10 mmol) in 50 cm3 absolute EtOH, a solution of 3,5-dichlorosalicylaldehyde (1.91 g, 10 mmol) in 20 cm3 absolute EtOH were added dropwise at 60--70 C with continuous stirring. Expected solid product was formed in 2 min period. The course of the reaction was monitored by i.r. spectroscopy. After completing the reaction, the mixture was left to stand overnight. The solid product was filtered off, washed with H2O several times, dried in air and crystallized from aqueous EtOH (1:3). Characteristic 13C-n.m.r. peaks (DMSOd6, TMS, d ppm): 125.95 (C1), 152.36 (C2), 124.37 (C3), 131.44 (C4), 126.95 (C5), 127.10 (C6), 139.10 (C7), 179.91 (C8). 1-(2-Hydroxy-3,5-dibromobenzylidene) thiosemicarbazide (2) This compound was prepared by an analogous procedure, using 2-hydroxy-3,5-dibromobenzaldehyde in EtOH solvent. Characteristic 13C-n.m.r. peaks (DMSO-d6, TMS, d ppm): 130.83 (C1), 153.70 (C2), 113.81 (C3), 136.94 (C4), 114.78 (C5), 130.89 (C6), 140.34 (C7), 179.86 (C8). Schiff base ligands (L1H and L2H) The Schiff base ligands used in this work, L1H and L2H, were prepared by similar methods. To a suspen-
sion of (5 mmol) of [for L1H, 1-(2-hydroxy-3,5-dichlorobenzylidene) thiosemicarbazide (1.322 g), for L2H, 1(2-hydroxy-3,5-dibromobenzylidene) thiosemicarbazide (1.765 g)] in 30 cm3 absolute EtOH, a solution of 1.323 g (5 mmol) of 1-mesityl-1-methyl-3-(2-chloro-1oxoethyl) cyclobutane in 20 cm3 absolute EtOH was added in each case dropwise at ca. 30--40 C with continuous stirring and monitoring the course of the reaction with i.r. After completing the addition of the a-haloketone, the temperature of the mixture was raised to 50--55 C. Monitoring the visibility of the carbonyl group of 1-mesityl-1-methyl-3-(2-chloro-1oxoethyl) cyclobutane is easily done and then it is very easy to determine when the reaction is complete. The solution was then made alkaline with an aqueous solution of NH3 (5%) and solids (3) and (4) separated in both cases. The precipitates were filtered off, washed with aqueous NH3 solution several times, dried in air and crystallized from EtOH and dried and stored in a desiccator over CaCl2. Characteristic 13C-n.m.r. peaks for (L1H) (DMSO-d6, TMS, d ppm): 123.38 (C1), 145.78 (C2), 114.24 (C3), 128.12 (C4), 117.24 (C5), 125.15 (C6), 135.52 (C7), 152.71 (C8), 103.21 (C9), 136.39 (C10), 40.71 (C11), 41.91 (C12), 44.64 (C13), 26.29 (C14), 131.70 (C15), 128.18 (C16), 124.31 (C17), 130.75 (C18), 21.86 (C19), 22.84 (C20). Characteristic 13 C-n.m.r. peaks for (L2H) (CDCl3, TMS, d ppm): 122.47 (C1), 151.22 (C2), 112.95 (C3), 133.30 (C4), 113.57 (C5), 132.85 (C6), 145.39 (C7), 155.55 (C8), 101.39 (C9), 149.78 (C10), 31.92 (C11), 42.89 (C12), 45.03 (C13), 28.42 (C14), 137.72 (C15), 136.89 (C16), 132.46 (C17), 137.06 (C18), 22.46 (C19), 23.38 (C20). Cobalt(II) complexes A solution of Co(AcO)2 Æ 4H2O (0.0623 g, 0.25 mmol) in absolute EtOH (30 cm3) was added to a hot (60--70 C) solution of the ligand (0.50 mmol) [L1H (0.2371 g) or L2H (0.2815 g) in absolute EtOH (20 cm3) under a N2 atmosphere. The complex started to form immediately upon addition of the metal solu-
209 tion. The mixture was then refluxed for 15--20 min while being heated at 80 C. The precipitated complex was filtered off, washed with cold EtOH and H2O several times and dried in vacuo (over P4O10) and stored in a desiccator over CaCl2. Copper(II) complexes To a hot (60--70 C) solution of each ligand (0.50 mmol) [L1H (0.2371 g) or L2H (0.2815 g) in absolute EtOH (20 cm3) a solution of Cu(AcO)2 Æ H2O (0.0499 g, 0.25 mmol) in absolute EtOH (20 cm3) was added dropwise with stirring. The medium started to change colour immediately upon addition of Cu(AcO)2 Æ H2O solution. Stirring was then continued for 15--20 min at 80 C. The precipitated compound was filtered off, washed with cold EtOH and H2O, dried in vacuo over P4O10, and stored in a desiccator over CaCl2. Nickel(II) complexes Nickel complexes of the ligands L1H or L2H were prepared by an analogous procedure, using Ni(AcO)2 Æ 4H2O and absolute EtOH as solvent. Zinc(II) complexes These complexes were prepared from Zn(AcO)2 Æ 2H2O in absolute EtOH. 1 H-n.m.r. spectral data of (L1)2Zn (DMSO-d6, d, ppm) 1.51 (s, 6H, --CH3), 2.15 (s, 6H, p-CH3), 2.19 (s, 12H, o-CH3), 2.39--2.61 (m, 8H, --CH2--), 3.36 (q, j=9.0, 2H, >CH--), 6.43 (s, 2H, C--H, thiazole), 6.72 (s, 4H, Arom./mesityl), 7.52--7.56 (m, 8H, Aromatics), 8.31 (s, 2H, N=CH--); and of (L1)2Zn (DMSO-d6, d, ppm) 1.48 (s, 6H, --CH3), 2.14 (s, 12H, o-CH3), 2.20 (s, 6H, p-CH3), 2.56 (d, 8H, j = 8.7, --CH2--), 3.30 (q, 2H, j=8.8, >CH--), 5.95 (s, 2H, C--H, thiazole), 6.70 (s, 4H, Arom./mesityl), 7.14 (d, 4H, jm=2.3, aromatics), 7.63 (d, 4H, jm=2.2, aromatics), 8.22 (s, 2H, N=CH--). Characteristic 13C-n.m.r. spectral data are at: 124.21 (C1), 144.64 (C2), 114.77 (C3), 128.17 (C4), 117.04 (C5), 125.16 (C6), 136.65 (C7), 152.72 (C8), 103.20 (C9), 136.40 (C10), 40.74 (C11), 41.89 (C12), 44.62 (C13), 26.25 (C14), 131.70 (C15), 128.21 (C16), 124.30 (C17), 130.75 (C18), 21.88 (C19), 22.84 (C20) for (L1)2Zn and 123.27 (C1), 150.92 (C2), 113.25 (C3), 133.25 (C4), 113.52 (C5), 132.85 (C6), 146.41 (C7), 155.50 (C8), 101.40 (C9), 149.73 (C10), 31.94 (C11), 42.86 (C12), 45.05 (C13), 28.44 (C14), 137.72 (C15), 136.89 (C16), 132.42 (C17), 137.10 (C18), 22.48 (C19), 23.38 (C20) for (L2)2Zn. Preparation of microbial cultures Microorganisms provided from the culture collection of the Microbiology Laboratory of the Biological Sciences of Science and Art Faculty of Firat University, Turkey. In this work, Bacillus megaterium DSM
32 (B.m.), Staphylococcus aureus COWAN I (S.a.), Klebsiella pneumoniae FMC 5 (K.p), Escherichia coli ATCC 25922 (E.c.), and Candida albicans FMC 17 (C.a.), were used to investigate the bacteriological and antifungal activities of ligands and their transition metal complexes. The bacteria and yeast strains were inoculated into nutrient broth (Difco) and in malt extract broth (Difco), and incubated for 24 and 48 h, respectively. In the Disc Diffusion method, the sterile Mueller Hinton Agar (Oxoid) for bacteria and Saburoud Dextrose Agar for yeast were separately inoculated with the test microorganisms. The compounds, dissolved in CHCl3 as 50 lg/disc solutions, were placed in wells (6 mm diameter) placed in the agar media, and the plates were incubated at 32 C for bacteria (18--24 h) and at 25 C for yeast (72 h). The resulting inhibition zones on the plates were measured in mm after 48 h (Table 5). The control samples were only absorbed in CHCl3. The data reported in Table 5 are the average of three experiments.
Results and discussion The synthetic process for the synthesis of some of the starting substances and the ligands is shown in Scheme 1. The L1H ligand is very soluble in Me2CO, CHCl3, THF, DMF or DMSO, sparingly soluble in MeOH and EtOH, and L2H is very soluble in CHCl3, THF, and DMF; soluble in DMSO, and sparingly soluble in Me2CO and insoluble in MeOH an EtOH. Furthermore, the hot suspensions of the ligands were used during complexation. Attempts to crystallize the ligand complexes in different solvents failed. In general, reactions of the ligands, L1H and L2H, with metal salts were quick and gave good yields of mononuclear complexes corresponding to the general formula (L)2M; they are stable at room temperature and are soluble in DMSO and sparingly soluble in some other solvents, such as DMF and THF. The detailed analytical characterization data of (1), (2), L1H, L2H, and the complexes are summarized in Tables 1--4. Two of the starting substances (1) and (2) have similar spectra in the i.r. Both compounds have two sharp and strong peaks which are at 3460 and 3360 cm)1 and a broad multiplet peaks (for (1), 3155--3110 cm)1 and for (2), 3160--3115 cm)1 regions of the spectra). In this region mainly five different strong and sharp peaks were observed for both compounds. Two of them are from --NH2, one from -NH--, and one from --OH; the other one has not been identified. In the case of the ligands, this peak could not be observed. Their C=S peaks were observed at 1099 and 1094 cm)1, respectively for (1) and (2), while azomethine peaks of compounds occur at 1619 and 1609 cm)1, respectively. On the other hand, no C=O (carbonyl) peak for the compounds is observed. Therefore, observed data in their i.r. spectra imply the existence of compounds.
210 The appearance and positions of the relevant bands in the i.r. spectra of the ligands and the complexes reveal the donor sites of the ligands. The i.r. spectral data of the ligands and their metal complexes are listed in Table 2. Observation of the absence of C=S, C=O, --CH2--Cl and --NH2 absorptions in the i.r. spectra of the ligands L1H and L2H, and existing characteristic peaks indicate the formation of the expected compounds. The strong bands observed at 3115 cm)1 for both ligands, can be attributed to the --NH-- group vibrations. In the complexes, these bands are not shifted, but lost their intensities, and it may therefore be that the nitrogen atom of this group is not coordinated to the metal ions. The ligands exhibit broad medium intensity bands in the 2700--2560 cm)1 range which are assigned the intermolecular H-bonding vibrations (O--H N). This situation is common for aromatic azomethine compounds containing o-OH groups [12]. In the complexes, these bands disappear completely. The azomethine group vibrations of the free ligands occur at same wave number, 1614 cm)1. In the i.r. spectra of complexes, these bands were not observed at the same frequencies and the same intensities. They shift to different frequencies (1602-1619 cm)1) for L1H ligand and lower frequencies (1582--1584 cm)1) for L2H ligand and, at the same time, their intensities lowered. These results indicate that the azomethine groups were highly affected by
complexation. For the free ligands, the bands at 1144 and 1169 cm)1, respectively for L1H and L2H, can be attributed to the phenolic (C--O) group vibration [13]. In the metal complexes, these bands are shifted to different frequencies after complexation; higher frequencies (1159--1174 cm)1) for L1H and lower frequencies (1164--1159 cm)1) for L2H, indicating coordination of oxygen to the metal atoms. Despite their presence in the ligands and the possibility of complexation by C=N group and sulphur atom in the thiazole ring, the unchanged band positions for these groups in the i.r. spectra of the complexes indicates that the thiazole ring does not complex to the metal. Mainly two sharp signals were observed in the range 579--431 cm)1 of the i.r. spectra of the ligands. In the case of the complexes, there are several new signals in this range which can be attributable to the t(M--N) and t(M--O) modes [12]. The 1H-n.m.r. spectra of the starting substances (1), (2), and ligands were recorded in DMSO-d6, and assignments are given in detail in Table 3. As expected from the structures of starting substances (1) and (2), only aromatic, --NH--, --NH2, --N=CH-- and --OH peaks were observed. All of these protons, except aromatic and azomethine protons, are D2O exchangeable protons. --OH group signals for both compounds are broad singlets. This is the result of the presence of intramolecular hydrogen bonding [14]. Phenolic --OH
Table 1. Analytical and physical data of the compounds Compound
(1) (2) Ligand L1H (L1)2Co (L1)2Cu (L1)2Ni (L1)2Zn Ligand L2H (L2)2Co (L2)2Cu (L2)2Ni (L2)2Zn
F.W. (g mol)1)
264.13 353.03 474.45 1005.81 1010.42 1005.57 1012.27 563.35 1183.62 1188.23 1183.38 1190.07
Colour
White White Yellow Light brown Brown Dark yellow Yellow Light yellow Dark brown Green Brown Brown
M.p. (C)
259 248 228 311 245 326 334 237 347 247 358 369
Yield (%)
97 93 73 75 59 78 63 83 77 61 74 79
Found (Calcd.) (%) C H
N
36.5 26.9 60.5 57.0 57.0 57.4 57.1 51.4 48.9 48.3 48.6 48.4
16.1 12.1 9.0 8.2 8.6 8.5 8.5 7.4 7.2 7.2 7.3 6.9
(36.4) (27.2) (60.8) (57.3) (57.1) (57.3) (57.0) (51.2) (48.7) (48.5) (48.7) (48.4)
2.9 2.1 4.9 4.8 5.0 4.9 5.0 4.6 4.2 4.1 4.2 4.0
(2.7) (2.0) (5.3) (4.8) (4.8) (4.8) (4.8) (4.5) (4.1) (4.1) (4.1) (4.1)
S (15.9) (11.9) (8.9) (8.4) (8.3) (8.4) (8.3) (7.5) (7.1) (7.1) (7.1) (7.1)
12.3 9.3 6.9 6.4 6.7 6.4 6.6 5.5 5.4 5.3 5.3 5.6
(12.1) (9.1) (6.8) (6.4) (6.4) (6.4) (6.3) (5.7) (5.4) (5.4) (5.4) (5.4)
Table 2. I.r. spectral data (cm)1) of the ligands and their complexes Compound
t(OH)
t(N--H)
t(C=N) thiazole
t(C=N) azomethine
t(C--O)
t(C=S)
(1) (2) L1H (3) (L1)2Co (L1)2Cu (L1)2Ni (L1)2Zn L2 H (4) (L2)2Co (L2)2Cu (L2)2Ni (L2)2Zn
3465 3465 3280 ----3265 -----
3110 3115 3115 3117 3115 3117 3120 3115 3120 3117 3115 3120
--1569 1564 1574 1564 1564 1584 1582 1582 1584 1583
1619 1609 1614 1602 1609 1609 1619 1614 1609 1609 1602 1609
1154 1139 1144 1159 1174 1159 1164 1169 1164 1159 1159 1159
1099 1094 -----------
211 Table 3. The 1H-n.m.r. spectral data of (1), (2) and Schiff base ligands Functional group
--NH2 N=CH >CH---CH3 o-CH3 p-CH3 --CH2-C--H, thiazole --OH---NH-Arom/mesityl Aromatics
Chemical shift (d, ppm) (1)
(2)
8.27 8.34 ------11.57 8.27 -7.53 8.07
8.27 8.32 ------11.56 8.27 -7.75 8.15
(s, 2H) (s, 1H)
(br, 1H) (s, 1H) (s, 1H) (s, 1H)
(s, 2H) (s, 1H)
(br, 1H) (s, 1H) (s, 1H) (s, 1H)
L1H (3)
L2H (4)
-8.23 (s, 1H) 3.38 (q, J=8.9, 1H) 1.53 (s, 3H) 2.18 (s, 6H) 2.16 (s, 3H,) 2.42--2.59 (m, 4H,) 6.41 (s, 1H) --6.72 (s, 2H) 7.52 (d, Jm=2.0, 1H) 7.56 (d, Jm=2.1, 1H)
-8.03 3.26 1.47 2.12 2.21 2.53 5.93 10.20 10.20 6.69 7.19 7.63
(s, 1H) (q, J=8.9, 1H) (s, 3H) (s, 6H) (s, 3H) (d, J=8.7, 4H) (s, 1H) (br, 1H)* (br, 1H)* (s, 2H) (d, Jm=2.3, 1H) (d, Jm=2.2, 1H)
*--OH and --NH-- are seen at the same resonance.
groups of both compounds exhibit the downfield signals, according to --OH of a free phenol. Since the molecules have electron-attracting hetero-atom groups, this is an expected result. The protons on the benzene ring of the compounds exhibited doublet signals. These are expected couplings and their coupling constants confirm the character of the signals. The 13Cn.m.r. assignments of both compounds given in the Experimental section, the elemental analysis results and i.r. spectral bands support these findings. On the other hand, the detailed 1H-n.m.r. spectral data of the compounds are given in Table 3, and a more detailed spectral investigation of a similar cyclobutane compound, synthesized and published by the same authors, can be found in the literature [15]. Very similar spectra were obtained for the ligands. The single proton resonances in the 1H-n.m.r. spectra of these ligands occur at 8.23 ppm for L1H and at 8.03 ppm for L2H and have been assigned to the azomethine group proton. The --CH2-- proton resonances which indicate the compounds contain cyclobutane ring are at 2.42--2.59 region and 2.53 ppm (centred), respectively for L1H and L2H ligands. The intensity of the --OH and --NH-- resonances of the L1H ligand is very low; almost invisible. --OH and -NH-- resonances of L2H are at 10.20 ppm (centred) as broad singlet, is due to the presence of hydrogen bonding [13] formed between azomethine and o-OH of the molecules. The 1H-n.m.r. signal observed for the protons of C--OH and --NH-- disappeared upon addition of D2O to the solution. The aromatic ring resonances are observed at 7.42--7.56 and 7.19--7.63 ppm as doublets which are in agreement with the proposed structures, for L1H and L2H, respectively. The detailed 1 H-n.m.r. spectral data of the ligands are given in Table 3. The Zn(II) complexes of the ligands showed the same resonances as those of L1H and L2H except for the absence of the OH proton resonance and a small shift was observed for the azomethine proton resonance. The signal of methine group of the molecules, which should be 3.26--3.38 ppm, is overlapped with
DMSO H--D exchange signals. Other signals in the spectrum of the complexes are very broad and with high multiplicity. However, in comparison to the 1Hn.m.r. spectra of the ligands, the signals can be attributed to the specific protons. The detailed 13C-n.m.r. spectral data are given in the Experimental section. Azomethine carbon atoms are observed at 135.52 ppm and 145.39 ppm respectively for L1H and L2H. The 13 C-n.m.r. spectral data of the ligands confirm the 1H spectral results. The data obtained from elemental analyses, i.r., and 1H and 13C-n.m.r. spectra of L1H and L2H are consistent with data expected from the formula given in Figure 1. The 13C-n.m.r. spectral data of (L1)2Zn and for (L2)2Zn complexes of the ligands are given in the Experimental section. As easily can be seen from the data, there are fairly shifts on the azomethine carbon and aromatic carbon which bound to the phenolic oxygen. These results also support the coordination of metals via azomethine and phenolic oxygen. Thermal studies In each case by using approximately 10 mg samples, the thermogravimetric, TG, curves for the complexes were obtained at a heating rate of 10 C/min and a 30 ml/min flowing nitrogen atmosphere over a temperature range of 20--900 C. The TG curves showed that (Br)Cl Ms Cl(Br)
N
Me
NH N S
O
M
O
S
N NH N
(Br)Cl
Me Ms
Cl(Br)
M = CoII, CuII, NiII, ZnII
Fig. 1. Suggested structure of the ligands L1H and L2H complexes.
212 the thermal decomposition of the complexes takes place mainly in three steps, except for the Cu(II) complex which decomposes in several steps. TG studies of all the complexes showed no weight loss up to 197 C, indicating absence of H2O in the complexes. The first step in the decomposition sequence corresponds to the loss of mesityl groups in the Co, Ni and Zn complexes. In the second step, cyclobutane and thiazole groups eliminate from the complexes. The inflation of the TG curves of all the complexes at a temperature under [579 C for (L1)2Co, 538 C for (L1)2Cu, 713 C for (L1)2Ni and 844 C for (L1)2Zn, 688 C for (L2)2Co, 825 C for (L2)2Cu, 525 C for (L2)2Ni and 609 C for (L2)2Zn] indicates the decomposition of the fully organic part of the chelate, leaving metallic oxide at the final temperature [16, 17]. The observed weight losses for all complexes are in good agreement with the calculated values from their chemical formulas given in Table 1. All the complexes completely decompose to the corresponding metal oxides, Co3O4, CuO, NiO or ZnO. The electronic spectral bands of the complexes and ligands in DMF (110)3 mol Æ l)1) solvent are given in Table 4. For the ligands, the bands at the maximum or shoulder in the 415--473 nm regions are attributed to dipolar ketoamine tautomer forms of its zwitterionic dipolar structure which is characteristic for salicylaldimines [12]. The more intense 305--370 nm bands in the complexes may be due to the coincidence of charge transfer, d fi p* and L fi M transitions [15]. The band appearing at [535 nm for (L1)2Co and 540 nm for (L2)2Co] in the spectrum of the cobalt(II) complexes can be assigned to the transition 4 A2 fi 4T1(P) which is typical of tetrahedral cobalt(II) complexes. For the Ni(II) complexes the band occurring at [575 nm for (L1)2Ni and 584 nm for (L2)2Ni] is assigned to the spin forbidden transition 3 T1(F) fi 3T1(P) due to the tetrahedral structure around nickel(II) [18]. Conductance measurements It was found that Co(II), Cu(II), Ni(II) and Zn(II) complexes of the ligands are non-electrolytes [19] as shown by their molar conductivity (LM) measurements
in DMF, which are in the range 3.6--5.1 W)1 cm2 mol)1. Magnetic susceptibility studies The magnetic moments of the complexes were measured at room temperature and are listed in Table 4. Co(II), Cu(II) and Ni(II) complexes of both ligands are paramagnetic, while their Zn(II) complexes are diamagnetic, and their magnetic susceptibilities are: 4.21, 1.63 and 3.33 B.M. respectively for L1H ligand complexes; 4.42, 1.88 and 3.24 B.M. respectively for L2H ligand complexes. These data indicate two unpaired electrons for Ni(II) and three for Co(II). The magnetic moments of the Co(II) complexes of both ligands at room temperature fall in the range 4--5 B.M., which is characteristic for mononuclear, high-spin, tetrahedral Co(II) complexes. The magnetic moment values of the Ni(II) complexes of the ligands are also consistent with a tetrahedral geometry [20]. Existing data suggest a four coordinated CuN2O2 sphere for the copper ion in this complex. The magnetic moments at room temperature, [1.63 B.M. for (L1)2Cu and 1.88 B.M. for (L2)2Cu] are considerably lower than that expected for the spin-only contribution in a d9 system; this fact suggests a probable antiferromagnetic interaction between Cu(II) ions and consequently a planar or distorted tetrahedral arrangement of the four donor atoms around Cu(II) ion [21]. On the basis of the spectral and magnetic data, the cobalt, nickel, and zinc complexes have tetrahedral geometry, while copper complexes are in a planar or distorted tetrahedral structure [22]. The proposed structure of the complexes is given in Figure 1. The bacteriological and fungicidal activities of the some starting substances (1, 2), Schiff base ligands and their metal complexes were tested against two gram-positive (B. megaterium and S. aureus), two gram-negative bacteria (K. pneumoniae and E. coli.) and a yeast-like fungus C. albicans, mentioned above and in Table 5. The results show that starting substances and some complexes exhibited moderate biological activities towards some of the microorganisms under the test conditions. Unexpectedly, the most active compound
Table 4. Magnetic moments and electronic spectral data of the ligands and their complexes Compound 1
L H (3) (L1)2Co (L1)2Cu (L1)2Ni (L1)2Zn L2H (4) (L2)2Co (L2)2Cu (L2)2Ni (L2)2Zn *Shoulder.
kmax/nm (DMF)( e l mol)1 cm)1)
leff (B.M.)
290*(11770), 310*(9800), 320(9822), 335*(10247), 370(9189), 430*(464), 473*(239), 505(141) 270(77861), 335*(25440), 435(633), 535*(337) 330(31167), 425(4282), 525*(361), 640(169) 325(21613), 395(15617), 420*(180), 480*(136), 575(46), 635(79) 320(64516), 370*(56073), 400(427), 420(328), 500*(61) 305(4671), 365(3390), 415*(1771), 470(1206), 535(363) 305*(10914), 435(7802), 475*(429), 540(159), 600*(87) 430(37366), 465*(33869), 535(275), 575(154), 625(97), 685(66) 305(15443), 315(14194), 355(13388), 410*(196), 435(171), 460*(114), 584*(47) 295(67620), 320*(55410), 353*(51086), 390(4571), 470*(598)
-4.21 1.63 3.33 Dia -4.42 1.88 3.24 Dia
213 Table 5. Antimicrobial effects of the ligand and their complexesa Compound
B.m. DSM 32
S.a. COWAN I
K.p. FMC 5
E.c. ATCC 25922
C.a. FMC 17
(1) (2) (L1H) (3) (L2H) (4) (L1)2Co (L1)2Cu (L1)2Ni (L1)2Zn (L2)2Co (L2)2Cu (L2)2Ni (L2)2Zn A.10 B.30
16.00±0.33 17.00±0.33 ----------17.00±0.54 --
-13.00±0.57 ------10.00±0.54 ---17.00±0.57 --
17.00±0.54 20.00±0.33 ----14.00±0.54 12.00±0.57 ----16.00±0.33 --
---------------
-------------18.00±0.33
a Compound concentration=50 lg/disc. Including disc diameter (6 mm). A.10: Streptomycin Sulfat: 10 lg/disc; B.30: Nystatin: 30 lg/disc. The symbol (--) reveals that the compound has no activity against the microorganisms.
is one of the starting materials for the synthesis of the ligands. None of the compounds exhibited any biological activity against the gram-negative bacteria E. coli and the yeast, C. albicans. Since the compounds, ligands and their complexes, studied have similar functional groups with those mentioned above, it is expected them to exhibit similar biological activities. This expectation has not been realized. Despite the compounds are very similar to each other, any parallel structure--activity relationships have not been observed on the microorganisms studied. It is very difficult to explain this result. References 1. J.D. Hadjipavlou-Litina and A. Geronikaki, Arz. Forsch./Drug Res., 46, 805 (1996). 2. L.D. Hadjipavlou, A. Geronikaki and E. Sotiropoulou, Res. Commun. Chem. Pathol. Pharmacol., 79, 355 (1993). 3. J.D. Hadjipavlou-Litina and A.A. Geronikaki, Res. Commun. Chem. Pathol. Pharmacol., 96, 307 (1997). 4. M.R. Flack, R.G. Pyle, N. Mullen, M.B. Lorenzo, Y.W. Wu, R.A. Knazek, B.C. Nusule and M.M. Reidenberg, J. Clin. Endocrinol. Metab., 76, 1019 (1993). 5. T.M. Devlin, in Textbook of Biochemistry with Clinical Correlations, Wiley, New York, 1997, p. 449. 6. A. Geronikaki, D. Hadjipavlou-Litina and M. Amourgianou, Il Farmaco, 58, 489 (2003).
7. R.D. Allan, J.R. Hanrahan, T.W. Hambley, G.A. Johnston, K.N. Mewett and A.D. Mitrovic, J. Med. Chem., 33, 2905 (1990). 8. T.H. Lanthorn, W.F. Hood, G.B. Watson, R.P. Compton, R.K. Rader, Y. Gaoni and J.B. Moanhan, Eur. J. Pharmacol., 182, 397 (1990). 9. Y. Gaoni, A.G. Chapman, N. Parvez, P.C.K. Pook, D.E. Jane and J.C. Watkins, J. Med. Chem., 37, 4288 (1994). 10. D.B. Zamble and S.J. Lippard, Trends Biochem. Sci., 20, 435 (1995). 11. M.A. Akhmedov, I.K. Sardarov, I.M. Akhmedov, R.R. Kostikov, A.V. Kisin and N.M. Babaev, Zh. Org. Khim., 27, 1434 (1991) (USSR); Chem. Abstr., 116, 807 (1992). 12. M. Tumer, H. Koksal, M.K. Sener and S. Serin, Transition Met. Chem., 24, 414 (1999). 13. J.W. Ledbetter, J. Phys. Chem., 70, 2245 (1966). 14. G. Wojciechowski, P. Przybylski, W. Schilf, B. Kamienski and B. Brzezinski, J. Mol. Struct., 649, 197 (2003). 15. A. Cukurovali and I. Yilmaz, Pol. J. Chem., 74, 147 (2000). 16. W. Brzyska and A. Krol, Thermochim. Acta, 223, 241 (1993). 17. M. Nath, Thermochim. Acta, 185, 11 (1991). 18. S. Mayadevi and K.K.M. Yusuff, Synt. React. Inorg. Met.-Org. Chem., 27, 319 (1997). 19. W.J. Geary, Coord. Chem. Rev., 7, 81 (1971). 20. M.S. Masoud and Z.M. Zaki, Transition Met. Chem., 13, 321 (1988). 21. R. Lopez-Garzon, M.N. Moreno-Carrettero, M.A. Salas-Peregrin and J.M. Salas-Peregrin, Polyhedron, 12, 507 (1993). 22. N.N. Greenwood and A. Earnshaw, Chemistry of the Elements, 2nd edit., Butterworth Heinemann, 2001, vol. 28. p 1192.
TMCH 6353
