Synthesis, Characterization, and Antibacterial Activity of Transition Metal Complexes With 5Hydroxy-7,4’-Dimethoxyflavone Shuang-Xi Wang, Fang-Jie Zhang, Qing-Ping Feng, and Yu-Lin Li SXW, FJZ, YLL. State Key Laboratory of Applied Organic Chemistry, Lanzhou University. -QPF. Department of Biology, Lanzhou University, Lanzhou, People’s Republic of China
ABSTRACT Complexes of Cut’, Nil’, Co”, Zn”, Fe “I, Cr”‘, Cd”, and Mn” with the natural product Shydroxy7,4’-dimethoxyflavone have been synthesized and the probable structures of these complexes have been proposed on the basis of elemental analyses, molecular weight determination, magnetic moments, and electronic and IR spectral data. The presence of coordinated and crystal water molecules was demonstrated by thermal studies. The antibacterial activity of the ligand and all the complexes has been determined on gram positive and gram negative bacteria. ‘.
INTRODUCTION Hydroxyflavones are a widely distributed group of natural products and have a broad spectrum of biological activity [l-3]. Moreover, it has been suggested that the
biological activity of an organic ligand can be increased on being coordinated or mixed with suitable metal ions [4, 51. This idea prompted ‘us to prepare hydroxyflavone-metal complexes with a view to evaluate their biological properties. Some hydroxyflavones, especially 3-hydroxy- and %hydroxyflavones, have been used as analytical reagents [6-81 based on the chelating ability of the hydroxyflavones with metals. However, as far as we have seen from the literature, there has been only one work concerning the isolation and characterization of the hydroxyflavone-metal complexes [9] and no systematic study on the biological activity of
Address reprint requests to: Professor Y. L. Li, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China. Journal of Inorganic Biochemistry, 46,251-257 (1992) @ 1992 Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, NY, NY 10010
251 0162-0134/!32/$5.00
252 S. -X. Wang et al.
the complexes has been reported. 5-Hydroxy-7,4’-dimethoxyflavone (1) is a natural product [lo] and its biological activity has been investigated [ 11 - 131. In this paper, we report the synthesis, characterization, and antibacterial activity of 5-hydroxy7,4’-dimethoxyflavone and its metal complexes.
1 3
R=H R=CH,
2
EXPERIMENTAL Preparation of Ligand 2’-Hydroxy-4,4’, 6’ -trimethoxychalcone reported method [ 141.
(2). 2 was prepared according to the
5,7,4’ - Trimethoxyflavone
(3). The mixture of 2’-hydroxy-4,4’,6’-trimethoxychalcone (2, 0.628g, 2mmol) and a catalytic amount of I, in 6 mL of dimethyl sulphoxide was refluxed for 20 min, then cooled, and poured into the solution of sodium thiosulphate. The precipitate was collected by filtration, air-dried, and recrystallized from methanol to give 3 in 80% yield. mp. 154-55’C (in [15], 156°C).
5-Hydroxy-7,4’-dimethoxyflavone. (1). 5,7,4’-Trimethoxyflavone (3, 0.4688, 1.5 mmol) was dissolved in 20 mL of warmed anhydrous toluene, then aluminum chloride (0.24 g, 1.8 mmol) was added. The mixture was refluxed for 20 hr. The solvent was evaporated and the residue was refluxed with 20 mL of 3% HCl for 0.5 hr. The crude product was collected by filtration and purified by chromatography on silica gel with benzene and recrystallization from CH,Cl,-EtOH to give 1 in 70% yield. mp. 173-174°C (in [lo], 175-176°C). 6,: 3.86 (6H, s),6.33,6.44 (each 1 H,d,J = 2.0 Hz),6.54 (lH,s),6.99,7.81 (each 2 H,d, J = 8.6 Hz). Preparation of Complexes CuL, - 2H,O, NiL, - 2H,O, and CoL, - 2H,O. 5-Hydroxy-7P’dimethoxyflavone (1 .O mmol) in 5 mL CH,Cl, was mixed with a solution of the appropriate metal salt (0.5 mmol) (CuCl, * 6H,O, NiCl, * 6H,O and CoCl, * 2H,O) in 3 mL CH,OH. A solution of sodium acetate (2.0 mmol) in 4 mL CH,OH was added dropwise to the mixture with stirring. The whole was stirred for 2 hr. The resulting crystalline solid was collected in filter, washed with CH,OH, Me&O, and Et,O, and dried in a vaccum desiccator over P40 ,a. MnL, * l.SH,O, ZnL, * H*O, and CdL, - H,O. A solution of an appropriate metal salt (0.5 mmol) (MnCl, - 4H,O, ZnCl, - 6H,O, and CdCl, *4H,O) in 3 mL CH,OH was added dropwise to a warmed solution of NaOH (1 .O mmol) and 5-hydroxy-7,4’dimethoxyflavone (1 .O mmol) in 6 mL CH,OH with stirring. The mixture was refluxed with stirring for 3 hr and cooled to room temperature. The resulting
COMPLEXES OF 5-HYDROXY-7,4'-DIMETHOXYFLAVONE
253
precipitate was collected in filter, washed with CH3OH, Me2CO, and Et20 and dried in a vacuum desiccator over P4Oi0. FeL 3 • 3 H ~ 0 and C r L 3 " 3 H 2 0 . These were prepared in a similar manner to that for Mn n, Zn n, and Cd n complexes, except that the molar ratio of metal:ligand used was 1:3.
Physical Measurements Cu, Co, Ni, Zn, Cd, Mn, Fe, and Cr contents of the complexes were estimated by standard methods. Carbon and hydrogen were determined using a Carbo Erba 1106 elemental analyzer. The IR spectra were recorded on a Nicolet-170SX FT-IR spectrophotometer in CsI disc in the range of 4000-200 cm-m. Electronic spectra were measured with Shimdzu UV-240 spectrophotometer in 190-900 nm region using a solution in DMF. ~H NMR spectra were obtained on a FT-80A spectrometer using CDCI 3 as solvent and TMS as the internal reference. The magnetic susceptibilities of the complexes were measured at room temperature and at 8000 G in a Gouy balance calibrated against Hg[Co(CMS)4]. Diagmagnetic corrections were calculated from Pascal's contants. Thermal characterization studies were carried out with a Du Pont 1090 thermal analyzer. RESULTS A N D D I S C U S S I O N The elemental analyses and molecular weight determination of the metal complexes (see Table 1) show that Cu Ix, Ni n, Co II, Zn n, Cd If, and Mn n form 1:2 (metal:ligand) complexes while Cr m and Fem form 1:3 (metal:ligand) complexes. These data also show that all the complexes contain coordinated or crystal water, which is also confirmed by thermal studies and IR spectra of the complexes. The complexes are colorfast and stable in air and insoluble in most common organic solvents, but they are slightly soluble in CH2CI 2 and CHC13, and easily soluble in DMF and DMSO. I R Spectral Studies A comparative study of the IR spectra of the complexes with that of ligands is given in Table 2. The appearance of new bands at 3375-3485 c m - ~ in the spectra of the complexes indicates the antisymmetric and symmetric OH ( H 2 0 ) stretching and
TABLE 1. Analytical and Physical Data of Ligand and Metal Complexes % found (Calcd) Compound
Color
C
Ligand CuL2-2H20
light yellow green yellowishgreen yellowishbrown yellow red green yellow light brown
68.32(68.46) 58.43 (58.82) 58.91(59.24) 59.51 (59.22) 59.91 (60.23) 60.89 (61.13) 61.06 (61.38) 56.19 (56.32) 60.03(60.35)
NiL 2" 2H20 CoL 2 • 2H20 ZnL 2 - H 2 0 FeL 3. 3H20
CrL 3 • 3H20 CdL 2 " H 2 0
MnL2. 1.5H20
H
Mol. Wt* M
4.71 (4.70) -4.14 (4.32) 9.42(9.16) 4.25 (4.35) 8.91 (8.52) 4.14 (4.35) 8.81 (8.55) 4.35 (4.13) 9.24(9.65) 4.41 (4.50) 5.32(5.59) 4.63 (4.51) 4.90(5.22) 3.62 (3.86) 15.14 (15.52) 3.92 (4.29) 7.75(8.13)
Found
Calcd
-681.27 671.31 671.31 655.81 982.61 972.89 708.71 651.94
-693.55 688.69 688.93 677.38 1000.85 997.00 724.40 675.94
* Molecular weight of the complexeswas determined by a cryoscopic method in DMSO.
254 S. -X. Wang et al. TABLE 2. Some Important in Ligand
IR Hands
(cm-‘)
and
Their Assignments
and Complexes UC-0
Compound Ligand
CuL, .2H,O NIL,. 2H,O CoL,*2H,O ZnL,*H,O FeL, * 3H,O
CrL, .3H,O CdL, *H,O MnL, * 1.5H,O
vOH
3188~ 3412b. 34OOb. 3415m 3375b. 345Ob. 3485b. 342Ob, 345Ob.
m m m m m m m
b, Broad; m, medium; vs. very strong;
vc=o
uc=c
1669s 1633~s 1633~s 1633~s 1633~s 1624~s 1625~s 163Ovs 1628~s
1605vs 1602s 1600s 1600s 1600s 1585s 1590s 1595s 1590s
s, strong;
6 O-H
(phenolic)
1336s 1563s 1561s 1561s 1568s 1571s 1571s 1570s 1568s
1162s 1180s 1179s 1179s 1180s 1173s 1175s 1171s 1172s
VM-0 566W 56lw 559w 55Qw 54Ow MOW
562~ 552~
w, weak.
H-OH bending modes. The OH (phenolic) stretching frequency at 3188 cm- ’ and OH (phenolic) bending frequency (in-plane) at 1336 cm-’ observed in the free ligand are absent in the spectra of the complexes, indicating the involvement of the phenolic group in complexes formation. The band at 1162 cm-’ due to UC-O (phenolic) in the free ligand is significantly shifted to higher frequencies in the complexes. This further confirms that the phenolic oxygen is coordinated to the metal ion. A strong band at 1669 cm-’ in free ligand assigned to c=o band is shifted to a low wave number in the complexes, indicating the coordination of the ligand to the metal ion through the carbonyl oxygen. Further, some new bands probably due to v,,,_,, modes [ 161 are also observed in the spectra of the complexes in the region 566-540 cm-‘. Using the above evidence, it is concluded that the ligand is a bidentate coordinating agent which forms a six-number ring around the metal ion via the phenolic and carbonyl groups. Magnetic Moments and Electronic Spectra The magnetic moments and electronic spectra of the complexes are listed in Table 3. The ~,s values of Cr ‘I’, Co”, and Ni” complexes are indicative of a high spin octahedral geometry around Cr”‘, Co”‘, and Ni”. The cc, values of Mn” and Fe”’ complexes show the presence of five unpaired electrons. Therefore, the two com-
TABLE 3. Magnetic Moments and Electronic Spectra of Metal Complexes Electronic Spectra (nm, DMF)
Compound
peff (BM)
Ligand
2.13 3.54 4.85 diamagnetic 5.90 3.76 diamagnetic 5.91
CuL, .2H,O NiL,*ZH,O CoL, .2H,O ZnL, * H,O FeL, * 3HsO CrL, * 3H,O CdL, . H,O MnL2’ 1.5HsO
C-T 230 232 -
B band (ph-ph*) 268 273 272 268 270 271 273 272 270
K band (r-r*) 289 325 318 316 320 316 322 320 315
R band (n-r*) 321 -
COMPLEXES OF 5-HYDROXY-7,4’-DIMETHOXYFLAVONE
255
plexes have octahedral or tetrahedral geometry. But considering their analytical data and the latter thermal studies, the Fe”’ and Mn” complexes may have octahedral and tetrahedral configurations, respectively. Zn” and Cd” complexes are diamagnetic, as expected, and presumably tetrahedral. The value of cc,, = 2.13 BM for Cu” complex shows that this complex is possibly is octahedral. The electronic spectra of all the complexes are similar, but they are different from that of the ligand. The band at 289 nm assigned to K band (x + ?r* transition) in the spectra of the ligand occurs as a large bathochromic shift and becomes broad and strong in the spectra of the complexes. This is indicative of the formation of complexes. The medium band at 321 nm assigned to R band. (n + ‘K*transition) in the spectra of the ligand disappears on the formation of complexes. It is possible that the R band occurs as a hypsochromic shift after formation of complexes and this causes the R band to be obscured by the K band of batbochromic shift. As a result, the K band is broadened. The strong bands at - 230 nm for Co” and Zn” complexes may be attributed to the charge transfer transition between metal and ligand. Unfortunately, the expected dd bands in the visible range (400-900 nm) in DMF solution for all the complexes, just like the report on the analogous complexes [9], fail to be detected. Therefore, the electronic spectra of the complexes give no significant information about the structures of the complexes. Thermal Studies Thermal data for dehydration and decomposition of metal complexes are given in Table 4. These data show that all the complexes contain crystal or coordinated water, which are consistent with the results of elemental analyses. The dehydrated temperature (1 lo- 146°C for Cu”, Co”, and Ni” complexes, 30-85°C for Cr”‘, Fe”‘, Mn”, Zn”, and Cd” complexes) and the corresponding weight loss (see Table 4) indicate the two molecules of water in the Gun, Con, and Ni” complexes are present as coordinated water, and the molecules of water in Cr”‘, Fe”‘, Mn”, Zn”, and Cd” complexes are present as crystal water. The results further support the structures proposed for metal complexes in the above magnetic studies. The complexes were found thermally stable and undergo decomposition within temperature 273-619°C. The final products are metal oxides in all cases. On the basis of the above discussion, the probable structures of the complexes are proposed and shown below:
M =
co, Cu,Ni
M = Cd,Zn,n
= 1
M = Cr,Fc,n
= 3
M = Mn, n = 1.5
ANTIBACTERIAL
ACTIVITY
The antibacterial activity of the ligand and its complexes was evaluated in vitro against the bacteria E. coli (gram negative), S. aureus (gram positive), and P. vulgaris (gram negative) (incubation period 37°C for 24 hr) at 0.1 and 0.01%
256
S. -X. Wang et al.
TABLE 4. Thermal Studies for Dehydration and DecompositionProcess of Metal Complexes % weight loss Thermal Reaction
Temperature ( “C)
Process
found
C&d
Endothermic Exothenuic
5.36 86.42
5.19 87.90
Endothermic Exothermic
5.43 87.86
5.23 88.55
CuL, * 2H,O + CuL, + 2H,O CUL,4 cue + products
132- 146 321-390
NiL, *2H,O -, NIL, + 2H,O NiL, -+ NiO + products
121-131 385-479
COL,*~H,O-ICOL,+~H,O COL, + co*o, + products
1 lo- 125 367-573
Endothermic Exothermic
4.% 87.64
5.23 87.30
ZnL, * H,O-r ZnL, + H,O ZnL, + ZnO + products
34-73 329-616
Endothermic
2.66 86.85
2.65 87.50
FeL, * 3H,O + FeL, + 3H20 FeL, + Fe,O, + products
37-85 323-549
Endothermic Exothermic
5.12 90.88
5.39 91.56
CrL,.3H,0+CrL,+3H20 CrL, + Cr*O, + products
30-47 273-360
Endothermic
5.17 91.16
5.41 91.94
CdL,*H,O+CdL, +H,O CdL, + Cd0 + products
41-62 375-609
Endothermic
2.32 81.61
2.48 81.82
31-83
Endothermic
3.68
343-502
Exothermic
86.21
3.99 86.74
MnL,.1.5H,O+MnL,+
1.5H,O
MnL,+MnO,+ products
”
concentrations using the inhibition zone technique [ 171. The results have been summarized in Table 5. The activity of the ligand and its complexes decreases on lowering the concentration. The activity of the ligand is low and enhanced on coordination with metal ions. In other words, the complexes are more active against the bacteria than the ligand.
TABLE 5. AntibacterialActivity of Ligsnds and Their Complexes Zone of Inhibition (mm) E. Coli
Compound Ligand CuL, * 2H,O NiL, .2H,O CoL, .2H,O ZnL, * H,O CdL, . H,O MnLz . 1.5Hz0 FeL, * 3H,O CrL, * 3H,O
S. aureus
0.1
0.01
0.1
6 10 9 10 11 11 7 10 8
7 6 8 8 7 6 6 6
6 8 10 9 12 45 9 11 8
P. vulgaris
0.01
0.1
0.01
-
7 9 16 12 9 24 8 10 12
6 6 11 8 6 17 7 8 8
6 7 6 7 14 7 8 7
COMPLEXES OF 5-HYDROXY-7,4’-DIMETHOXYFLAVONE
257
Also, it has been observed that Cd” complex is highly active against S. aweus and P. vulgaris.
REFERENCES 1. B. Havsteen, B&hem. Pharmacol. 32, 1141 (1983). 2. M. Aufmkolk and S. Ingbar, Pro. Clin. Biol. Res. 213, 333 (1986). 3. A. J. Vlietinck, D. A. VandenBerghe, and A. Haemers, Pro. Clin. Biol. Res. 288,283 (1988). 4. R. S. Strivastava, J. Inorg. Nucl. Chem. 42, 1526 (1980). 5. R. T. Jordan and L. M. Allen, Chemical Abstracts 111, 17704r (1989). 6. M. Katyal, Talanfa 15, 95 (1%8). 7. L. J. Porter and K. R. Markham, J. Chem. Sot. (c), 344 (1970). 8. A. Cabrera-Martin, J. S. Durand, and S. Rubio-Barroso, Anal. Chim. Acfa 1983, 263 (1986). 9. K. Hiraki, M. Onishi, T. Ikeda, K. Tomioka. and Y. Obayashi, Bull. Chem. Sot. Jpn. 51, 2425 (1978). 10. J. W. Clarklewis and I. Dains, Aust. J. Chem. 21, 425 (1%8). 11. J. Michael-Edwards, R. F. Raffauf, and P. W. Le-Quesene, J. Naf. Prod. 42, 85 (1979). 12. A. Morl, C. Nishino, N. Enoki, and S. Tawata, Phyfochemiwy 26, 2231 (1987). 13. A. Morl, C. Nishino, N. Enoki, and S. Tawata, Phytochemistry 27, 1017 (1988). 14. St. V. Kostanecki and J. Tambor, Chem. Ber. 37, 792 (1904). 15. C. Czaijkowski, St. V. Konstanecki, and J. Tambor, Chem. Ber. 33, 1991 (1900). 16. K. Nakamoto, In$rared and Raman Spectra of Inorganic and Coordination Compounds, 3rd Ed, John Wiley, New York, 1978. 17. R. S. Verma and S. A. Imam, Indian J. Microbial. 13. 45 (1973). Received December IO, 1991; accepted January 7, 1992
ABSTRACT Complexes of Cut’, Nil’, Co”, Zn”, Fe “I, Cr”‘, Cd”, and Mn” with the natural product Shydroxy7,4’-dimethoxyflavone have been synthesized and the probable structures of these complexes have been proposed on the basis of elemental analyses, molecular weight determination, magnetic moments, and electronic and IR spectral data. The presence of coordinated and crystal water molecules was demonstrated by thermal studies. The antibacterial activity of the ligand and all the complexes has been determined on gram positive and gram negative bacteria. ‘.
INTRODUCTION Hydroxyflavones are a widely distributed group of natural products and have a broad spectrum of biological activity [l-3]. Moreover, it has been suggested that the
biological activity of an organic ligand can be increased on being coordinated or mixed with suitable metal ions [4, 51. This idea prompted ‘us to prepare hydroxyflavone-metal complexes with a view to evaluate their biological properties. Some hydroxyflavones, especially 3-hydroxy- and %hydroxyflavones, have been used as analytical reagents [6-81 based on the chelating ability of the hydroxyflavones with metals. However, as far as we have seen from the literature, there has been only one work concerning the isolation and characterization of the hydroxyflavone-metal complexes [9] and no systematic study on the biological activity of
Address reprint requests to: Professor Y. L. Li, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China. Journal of Inorganic Biochemistry, 46,251-257 (1992) @ 1992 Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, NY, NY 10010
251 0162-0134/!32/$5.00
252 S. -X. Wang et al.
the complexes has been reported. 5-Hydroxy-7,4’-dimethoxyflavone (1) is a natural product [lo] and its biological activity has been investigated [ 11 - 131. In this paper, we report the synthesis, characterization, and antibacterial activity of 5-hydroxy7,4’-dimethoxyflavone and its metal complexes.
1 3
R=H R=CH,
2
EXPERIMENTAL Preparation of Ligand 2’-Hydroxy-4,4’, 6’ -trimethoxychalcone reported method [ 141.
(2). 2 was prepared according to the
5,7,4’ - Trimethoxyflavone
(3). The mixture of 2’-hydroxy-4,4’,6’-trimethoxychalcone (2, 0.628g, 2mmol) and a catalytic amount of I, in 6 mL of dimethyl sulphoxide was refluxed for 20 min, then cooled, and poured into the solution of sodium thiosulphate. The precipitate was collected by filtration, air-dried, and recrystallized from methanol to give 3 in 80% yield. mp. 154-55’C (in [15], 156°C).
5-Hydroxy-7,4’-dimethoxyflavone. (1). 5,7,4’-Trimethoxyflavone (3, 0.4688, 1.5 mmol) was dissolved in 20 mL of warmed anhydrous toluene, then aluminum chloride (0.24 g, 1.8 mmol) was added. The mixture was refluxed for 20 hr. The solvent was evaporated and the residue was refluxed with 20 mL of 3% HCl for 0.5 hr. The crude product was collected by filtration and purified by chromatography on silica gel with benzene and recrystallization from CH,Cl,-EtOH to give 1 in 70% yield. mp. 173-174°C (in [lo], 175-176°C). 6,: 3.86 (6H, s),6.33,6.44 (each 1 H,d,J = 2.0 Hz),6.54 (lH,s),6.99,7.81 (each 2 H,d, J = 8.6 Hz). Preparation of Complexes CuL, - 2H,O, NiL, - 2H,O, and CoL, - 2H,O. 5-Hydroxy-7P’dimethoxyflavone (1 .O mmol) in 5 mL CH,Cl, was mixed with a solution of the appropriate metal salt (0.5 mmol) (CuCl, * 6H,O, NiCl, * 6H,O and CoCl, * 2H,O) in 3 mL CH,OH. A solution of sodium acetate (2.0 mmol) in 4 mL CH,OH was added dropwise to the mixture with stirring. The whole was stirred for 2 hr. The resulting crystalline solid was collected in filter, washed with CH,OH, Me&O, and Et,O, and dried in a vaccum desiccator over P40 ,a. MnL, * l.SH,O, ZnL, * H*O, and CdL, - H,O. A solution of an appropriate metal salt (0.5 mmol) (MnCl, - 4H,O, ZnCl, - 6H,O, and CdCl, *4H,O) in 3 mL CH,OH was added dropwise to a warmed solution of NaOH (1 .O mmol) and 5-hydroxy-7,4’dimethoxyflavone (1 .O mmol) in 6 mL CH,OH with stirring. The mixture was refluxed with stirring for 3 hr and cooled to room temperature. The resulting
COMPLEXES OF 5-HYDROXY-7,4'-DIMETHOXYFLAVONE
253
precipitate was collected in filter, washed with CH3OH, Me2CO, and Et20 and dried in a vacuum desiccator over P4Oi0. FeL 3 • 3 H ~ 0 and C r L 3 " 3 H 2 0 . These were prepared in a similar manner to that for Mn n, Zn n, and Cd n complexes, except that the molar ratio of metal:ligand used was 1:3.
Physical Measurements Cu, Co, Ni, Zn, Cd, Mn, Fe, and Cr contents of the complexes were estimated by standard methods. Carbon and hydrogen were determined using a Carbo Erba 1106 elemental analyzer. The IR spectra were recorded on a Nicolet-170SX FT-IR spectrophotometer in CsI disc in the range of 4000-200 cm-m. Electronic spectra were measured with Shimdzu UV-240 spectrophotometer in 190-900 nm region using a solution in DMF. ~H NMR spectra were obtained on a FT-80A spectrometer using CDCI 3 as solvent and TMS as the internal reference. The magnetic susceptibilities of the complexes were measured at room temperature and at 8000 G in a Gouy balance calibrated against Hg[Co(CMS)4]. Diagmagnetic corrections were calculated from Pascal's contants. Thermal characterization studies were carried out with a Du Pont 1090 thermal analyzer. RESULTS A N D D I S C U S S I O N The elemental analyses and molecular weight determination of the metal complexes (see Table 1) show that Cu Ix, Ni n, Co II, Zn n, Cd If, and Mn n form 1:2 (metal:ligand) complexes while Cr m and Fem form 1:3 (metal:ligand) complexes. These data also show that all the complexes contain coordinated or crystal water, which is also confirmed by thermal studies and IR spectra of the complexes. The complexes are colorfast and stable in air and insoluble in most common organic solvents, but they are slightly soluble in CH2CI 2 and CHC13, and easily soluble in DMF and DMSO. I R Spectral Studies A comparative study of the IR spectra of the complexes with that of ligands is given in Table 2. The appearance of new bands at 3375-3485 c m - ~ in the spectra of the complexes indicates the antisymmetric and symmetric OH ( H 2 0 ) stretching and
TABLE 1. Analytical and Physical Data of Ligand and Metal Complexes % found (Calcd) Compound
Color
C
Ligand CuL2-2H20
light yellow green yellowishgreen yellowishbrown yellow red green yellow light brown
68.32(68.46) 58.43 (58.82) 58.91(59.24) 59.51 (59.22) 59.91 (60.23) 60.89 (61.13) 61.06 (61.38) 56.19 (56.32) 60.03(60.35)
NiL 2" 2H20 CoL 2 • 2H20 ZnL 2 - H 2 0 FeL 3. 3H20
CrL 3 • 3H20 CdL 2 " H 2 0
MnL2. 1.5H20
H
Mol. Wt* M
4.71 (4.70) -4.14 (4.32) 9.42(9.16) 4.25 (4.35) 8.91 (8.52) 4.14 (4.35) 8.81 (8.55) 4.35 (4.13) 9.24(9.65) 4.41 (4.50) 5.32(5.59) 4.63 (4.51) 4.90(5.22) 3.62 (3.86) 15.14 (15.52) 3.92 (4.29) 7.75(8.13)
Found
Calcd
-681.27 671.31 671.31 655.81 982.61 972.89 708.71 651.94
-693.55 688.69 688.93 677.38 1000.85 997.00 724.40 675.94
* Molecular weight of the complexeswas determined by a cryoscopic method in DMSO.
254 S. -X. Wang et al. TABLE 2. Some Important in Ligand
IR Hands
(cm-‘)
and
Their Assignments
and Complexes UC-0
Compound Ligand
CuL, .2H,O NIL,. 2H,O CoL,*2H,O ZnL,*H,O FeL, * 3H,O
CrL, .3H,O CdL, *H,O MnL, * 1.5H,O
vOH
3188~ 3412b. 34OOb. 3415m 3375b. 345Ob. 3485b. 342Ob, 345Ob.
m m m m m m m
b, Broad; m, medium; vs. very strong;
vc=o
uc=c
1669s 1633~s 1633~s 1633~s 1633~s 1624~s 1625~s 163Ovs 1628~s
1605vs 1602s 1600s 1600s 1600s 1585s 1590s 1595s 1590s
s, strong;
6 O-H
(phenolic)
1336s 1563s 1561s 1561s 1568s 1571s 1571s 1570s 1568s
1162s 1180s 1179s 1179s 1180s 1173s 1175s 1171s 1172s
VM-0 566W 56lw 559w 55Qw 54Ow MOW
562~ 552~
w, weak.
H-OH bending modes. The OH (phenolic) stretching frequency at 3188 cm- ’ and OH (phenolic) bending frequency (in-plane) at 1336 cm-’ observed in the free ligand are absent in the spectra of the complexes, indicating the involvement of the phenolic group in complexes formation. The band at 1162 cm-’ due to UC-O (phenolic) in the free ligand is significantly shifted to higher frequencies in the complexes. This further confirms that the phenolic oxygen is coordinated to the metal ion. A strong band at 1669 cm-’ in free ligand assigned to c=o band is shifted to a low wave number in the complexes, indicating the coordination of the ligand to the metal ion through the carbonyl oxygen. Further, some new bands probably due to v,,,_,, modes [ 161 are also observed in the spectra of the complexes in the region 566-540 cm-‘. Using the above evidence, it is concluded that the ligand is a bidentate coordinating agent which forms a six-number ring around the metal ion via the phenolic and carbonyl groups. Magnetic Moments and Electronic Spectra The magnetic moments and electronic spectra of the complexes are listed in Table 3. The ~,s values of Cr ‘I’, Co”, and Ni” complexes are indicative of a high spin octahedral geometry around Cr”‘, Co”‘, and Ni”. The cc, values of Mn” and Fe”’ complexes show the presence of five unpaired electrons. Therefore, the two com-
TABLE 3. Magnetic Moments and Electronic Spectra of Metal Complexes Electronic Spectra (nm, DMF)
Compound
peff (BM)
Ligand
2.13 3.54 4.85 diamagnetic 5.90 3.76 diamagnetic 5.91
CuL, .2H,O NiL,*ZH,O CoL, .2H,O ZnL, * H,O FeL, * 3HsO CrL, * 3H,O CdL, . H,O MnL2’ 1.5HsO
C-T 230 232 -
B band (ph-ph*) 268 273 272 268 270 271 273 272 270
K band (r-r*) 289 325 318 316 320 316 322 320 315
R band (n-r*) 321 -
COMPLEXES OF 5-HYDROXY-7,4’-DIMETHOXYFLAVONE
255
plexes have octahedral or tetrahedral geometry. But considering their analytical data and the latter thermal studies, the Fe”’ and Mn” complexes may have octahedral and tetrahedral configurations, respectively. Zn” and Cd” complexes are diamagnetic, as expected, and presumably tetrahedral. The value of cc,, = 2.13 BM for Cu” complex shows that this complex is possibly is octahedral. The electronic spectra of all the complexes are similar, but they are different from that of the ligand. The band at 289 nm assigned to K band (x + ?r* transition) in the spectra of the ligand occurs as a large bathochromic shift and becomes broad and strong in the spectra of the complexes. This is indicative of the formation of complexes. The medium band at 321 nm assigned to R band. (n + ‘K*transition) in the spectra of the ligand disappears on the formation of complexes. It is possible that the R band occurs as a hypsochromic shift after formation of complexes and this causes the R band to be obscured by the K band of batbochromic shift. As a result, the K band is broadened. The strong bands at - 230 nm for Co” and Zn” complexes may be attributed to the charge transfer transition between metal and ligand. Unfortunately, the expected dd bands in the visible range (400-900 nm) in DMF solution for all the complexes, just like the report on the analogous complexes [9], fail to be detected. Therefore, the electronic spectra of the complexes give no significant information about the structures of the complexes. Thermal Studies Thermal data for dehydration and decomposition of metal complexes are given in Table 4. These data show that all the complexes contain crystal or coordinated water, which are consistent with the results of elemental analyses. The dehydrated temperature (1 lo- 146°C for Cu”, Co”, and Ni” complexes, 30-85°C for Cr”‘, Fe”‘, Mn”, Zn”, and Cd” complexes) and the corresponding weight loss (see Table 4) indicate the two molecules of water in the Gun, Con, and Ni” complexes are present as coordinated water, and the molecules of water in Cr”‘, Fe”‘, Mn”, Zn”, and Cd” complexes are present as crystal water. The results further support the structures proposed for metal complexes in the above magnetic studies. The complexes were found thermally stable and undergo decomposition within temperature 273-619°C. The final products are metal oxides in all cases. On the basis of the above discussion, the probable structures of the complexes are proposed and shown below:
M =
co, Cu,Ni
M = Cd,Zn,n
= 1
M = Cr,Fc,n
= 3
M = Mn, n = 1.5
ANTIBACTERIAL
ACTIVITY
The antibacterial activity of the ligand and its complexes was evaluated in vitro against the bacteria E. coli (gram negative), S. aureus (gram positive), and P. vulgaris (gram negative) (incubation period 37°C for 24 hr) at 0.1 and 0.01%
256
S. -X. Wang et al.
TABLE 4. Thermal Studies for Dehydration and DecompositionProcess of Metal Complexes % weight loss Thermal Reaction
Temperature ( “C)
Process
found
C&d
Endothermic Exothenuic
5.36 86.42
5.19 87.90
Endothermic Exothermic
5.43 87.86
5.23 88.55
CuL, * 2H,O + CuL, + 2H,O CUL,4 cue + products
132- 146 321-390
NiL, *2H,O -, NIL, + 2H,O NiL, -+ NiO + products
121-131 385-479
COL,*~H,O-ICOL,+~H,O COL, + co*o, + products
1 lo- 125 367-573
Endothermic Exothermic
4.% 87.64
5.23 87.30
ZnL, * H,O-r ZnL, + H,O ZnL, + ZnO + products
34-73 329-616
Endothermic
2.66 86.85
2.65 87.50
FeL, * 3H,O + FeL, + 3H20 FeL, + Fe,O, + products
37-85 323-549
Endothermic Exothermic
5.12 90.88
5.39 91.56
CrL,.3H,0+CrL,+3H20 CrL, + Cr*O, + products
30-47 273-360
Endothermic
5.17 91.16
5.41 91.94
CdL,*H,O+CdL, +H,O CdL, + Cd0 + products
41-62 375-609
Endothermic
2.32 81.61
2.48 81.82
31-83
Endothermic
3.68
343-502
Exothermic
86.21
3.99 86.74
MnL,.1.5H,O+MnL,+
1.5H,O
MnL,+MnO,+ products
”
concentrations using the inhibition zone technique [ 171. The results have been summarized in Table 5. The activity of the ligand and its complexes decreases on lowering the concentration. The activity of the ligand is low and enhanced on coordination with metal ions. In other words, the complexes are more active against the bacteria than the ligand.
TABLE 5. AntibacterialActivity of Ligsnds and Their Complexes Zone of Inhibition (mm) E. Coli
Compound Ligand CuL, * 2H,O NiL, .2H,O CoL, .2H,O ZnL, * H,O CdL, . H,O MnLz . 1.5Hz0 FeL, * 3H,O CrL, * 3H,O
S. aureus
0.1
0.01
0.1
6 10 9 10 11 11 7 10 8
7 6 8 8 7 6 6 6
6 8 10 9 12 45 9 11 8
P. vulgaris
0.01
0.1
0.01
-
7 9 16 12 9 24 8 10 12
6 6 11 8 6 17 7 8 8
6 7 6 7 14 7 8 7
COMPLEXES OF 5-HYDROXY-7,4’-DIMETHOXYFLAVONE
257
Also, it has been observed that Cd” complex is highly active against S. aweus and P. vulgaris.
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