Appl. Magn. Reson. 6, 521-528 (1994) Applied Magnetic Resonance �9 Springer-Verlag 1994 Printed in Austria

ESR Study of Cu(ll)-Indomethacin and Its Pyridine and DMF Adducts

L. David, O. Cosar, V. Chi~, A. Negoescu, and I. Vla~in

Department of Physies, University of Cluj-Napoca, Romania

Received December 17, 1993; revised February 22, 1994

Abstraet. Powder ESR spectra of [Cu2([nd)4](H20)2 at room temperature show the presence of copper acetate like dimers charactedzed by a slrong antiferromagnetie exchange interaction (J~--338 cm J). Two different monomeric speeies were evidenced in 40%Py+60%DMF solution absorbed on NaY zeolite: the Cu(Ind)2(DMF)2 with ah elongated tetragonal-octahedral symmetry and the Cu(Ind)2(Py) 2 with a CuN202 chromophore in a t r a n s square-planar arrangement. Only one monomeric species Cu(Ind)2(Py)2 was identified in 20%Py+80%DMF and 20%Py+80%Chloroform sotutions. The Cu(Py)42§ species of CuN 4 chromophore occurs in pyridine Cu(II)-indomethacin solution suggesting a decomposition of the solvit compound.

I. Introduction

The copper(II) complexes of inactive ligands and active anti-inflammatory drugs have been shown to be more active than the ligands themselves [1]. The most used anti-inflammatory drugs are carboxylic acids in which the carboxylate group is ava i l ab le for me ta l - l igand in teract ion [2]. In most cases their formula is [Cu2(O2CR)4L2] [R = alkyl or phenyl , L = H20, d ime thy l fo rmamide (DMF), dimethylsulfoxyde (DMSO) or pyridine (Py)] [3].

The isolation of mononuclear carboxylate-compounds has confirmed the existence of uni- and bi-dentate coordination modes of the ligands [3, 4].

For obtaining further structural information on some metal complexes with anti- inflammatory drugs, the [Cu2(Ind)4](H20)2 complex was prepared and investigated by ESR spectroscopy. Its binuclear structure is given in Fig. 1. The two copper(II) ions of spin 1/2 are coupled by a strong antiferromagnetic exchange interaction which results in a diamagnetic singlet ground state (S = 0) populated at low tem- perature a n d a thermally accessible paramagnetic triplet excited state (S = 1) [5, 6].

522 L. David et al.:

/

/ gH 3 CL

Fig. 1. The structure of the Cu2(Ind)4 complex.

The presenee of some monomeric species in various Cu(II)-Indomethaein solutions absorbed on NaY zeolite was also evideneed by the ESR method.

2. Experimental

The [Cu2(Ind4)](H20)2 complex was prepared according to the following procedure: indomethacin (0.05 mol) was dissolved in 50 mi of ethanol. ACuSO 4 solution pre- pared by adding 0.01 mol of CuSO4 to 25 mi of an ethanol-water mixture (1 : 1) was added to the first solution. This mixture was refluxed for 0.5 hours and then mixed with 300 mi of water. The green precipitate was filtered and washed with water. Finally the product was dried in air at room temperature. The (Cu:Zn) indomethacin complex was prepared in the same way.

The pyridine (Py), dimethylformamide-py¡ (DMF-Py) and chloroform-py¡ (Clf-Py) solutions of Cu(II)-Indomethacin complex having a concentration of 20 mg/ cm 3 were then prepared. The powder NaY zeolite was impregnated in the respec- tive solution for one hour. The excess of the solution was decanted and the pow- der dried in air.

ESR measurements were performed at 9.4 GHz (X-banal) using a standard JEOL- JES-3B equipmem, at 295 K.

3. Results and Discussion

The powder ESR spectrum of the [Cuz(Ind)4](H20)2 complex obtained at room temperature exhibits the absorption signals typical of randomly o¡ t¡ state (S = 1) species having an axial symmetry with a small rhombic distortion (Fig. 2).

ESR of Cu(II)-Indomethacin and Its Adducts 523

3300~

Bx2,y,~ --�91191

Fig. 2. Powder ESR spectrum of the [Cu:(lnd)4](H20)2 complex.

These dimeric species are characterized by a short Cu-Cu distance (= 2.7 A) and a strong antiferromagnetic exchange interaction ( J = - 3 3 8 cm -~) similar to those evidenced in other copper acetate like dimers. The magnetic field resonance val- ues of the parallel (z) and perpendicular (xy) fine structure components resulting from the zero-field splitting are indicated in Fig. 2.

The obtained spectrum can be adequately described by the following spin Hamil- tonian [6, 7]:

o_~ = flB.g.S + D(Sz 2- 2/3) + E(Sx 2- Sy 2) ,

where fl is the Bohr magneton, B the extemal magnetic field, g the anisotropic Lande splitting tensor and S the total spin vector. D and E are the zero-field splitting parameters.

The spin Hamiltonian parameters were determined in a relatively straightforward manner from the observed spectrum according to the procedure described by Chasteen [7]. The obtained values are: g~~ = 2.327; g• 2.040; D = 0.332 cm-~; E < 0.014 cm~; J = -338 C m 1.

Besides the three fine structure signals, there are also two absorptions at ~ 1600 G and = 3300 G, respectively. The weak half-field resonance is due to the forbidden AMs= + 2 transitions characteristic for dimeric species in which the Cu-Cu dis- tance is = 4-5 A [8-10]. The spin-spin coupling in these dimeric species is main- ly realized by dipole-dipole interaction.

The absorption observed at 3300G arises from the allowed AM~= +1 transitions characteristic to the above mentioned dimeric species with a zero field splitting parameter D = 0.332 cm -~ and to the monomeric impurities of S= 1/2. The num- ber of mononuclear species increases by a magnetical dilution with Zn(II). The

524 L. David e t a l . :

gj =2.0�91

gq= 2.335

Fig. 3. Powder ESR spectrum of the (Cu : Zn)-Indomethacin complex.

powder ESR spectrum of the (Cu : Zn)-Indomethacin complex in the 3200 G re- gion is shown in Fig. 3.

The characteristic parameters g~~ = 2.335, g . = 2.061, A, = 138 G and A• = 20 G suggest a tetrahedral (Td) coordination of the Cu 2§ ions [11, 12]. Using the LCAO- MO scheme described in these papers a mixture of 3dxy and 2 % 4pz copper or- bitals results for the paramagnetic ground state of the electron. The more intense g = 2.2 signal from the parallel band way be attributed to a small amount of mo-

go=2.1�91

Fig. 4. ESR spectrum of a 40%Py+60%DMF Cu(II)-Indomethacin solution.

ESR of Cu(II)-Indomethacin and Its Adducts 525

nomeric species with a dz2 ground state. A similar spectrum was reported by us

for Cu 2§ ions in water-ethanol mixtures at 77 K [13].

The monomeric species prevail also in Py, DMF and Clf solutions of the Cu(II)- Indomethacin compound.

Figure 4 shows the ESR spectrum of a 40%Py+60%DMF Cu(II)-Indomethacin so- lution at room ternperature. Its shape and the values of isotropic parameters (g0= 1.148; A0= 62 G) suggest the presence of Cu(II) pseudotetrahedral monomer- ic species [11].

The anisotropic spectra with four hyperfine lines in the g~~ region a n d a strong signal in the g• region were obtained for the Cu(II)-Indomethacin solutions ab- sorbed on NaY zeolite. They suggest that mononuclear Cu(II) species prevail in these samples.

The spectra of a Cu(II)-Indomethacin 20%Py+80%DMF solution absorbed on NaY zeolite (Fig. 5) show that in this case the copper(II) ion is in a trans square-pla- nar arrangement to the nitrogen atom of two pyridine molecules and to one car- boxylate oxygen atom from each of two indomethacin anions [14]. The values of gH = 2.287 and A H = 178 G and the appearance of five superhyperfine lines in the g• region due to the interactions of the paramagnetic electron with two equivalent nitrogen nuclei (IN= 1) confirm the existence of CuN202 chromophore (aN= 15 G).

ESR spectra of a Cu(II)-Indomethacin 40%Py+60%DMF solution adsorbed on NaY zeolite show the presence of two magnetically nonequivalent monomeric species (Fig. 6). One of them is characterized by gM~ = 2.318 and A H = 156 G and may be attributed to the Cu(Ind)2(DMF)2 species with an elongated tetragonal-octahedral symmetry due to the coordination of solvent molecules at the Cu 2+ ion along the Oz axis. The other set of parameters, g~~ = 2.273, .4, = 181 G confirm also the ex- istence of a Cu(Ind)2(Py)2 chromophore (aN= 14.7 G).

0N=15 G

Fig. 5. ESR spectrum of a 20%Py+80%DMF Cu(II)-Indometha~in solution adsorbed on NaY zeolite.

526 L. David et al,:

I

fJ Al| =I;IG J "gj:2,057

~~ --2.273

Fig, 6, ESR spectrum of a 40%Py+60%DMF Cu(II)-Indomethacin sotution adsorbed on NaY zeolite (a)_ Extended perpendicular absorption (b).

Only o n e C u ( P y ) 4 2+ t y p e monomeric species with C u N 4 chromophore occurs in the pyridine Cu(II)-Indomethacin solution (Fig. 7). The indomethacin ligand molecules ate completely substituted by pyridine molecules [15]. In this case there is also a strong interaction between the Cu 2+ ion and the solvent pyridine molecules along the Oz axis which leads to the broadening of the hyperfine lines from the parallel band (&i)-

The weak resolution of nitrogen superhyperfine lines in the g• region is also due to the strong dipole-dipole interactions between copper(II) and the neighboring

Att:IB2G

<-

T gx -- 2.o�91

Fig. 7. ESR specmnn of the pyridŸ Cu(II)-Indomethacin solution adsorbed on NaY zeolite.

ESR of Cu(II)-Indomethacin and Its Adducts 527

Fig. 8. ESR spectrum of the 20%Py+80%Clf Cu(II)-Indomethaein solution adsorbed on NaY zeolite (a). Extended perpendicular absorption (b).

pyridine molecules. The ESR spectrum of the 20%Py+80%Clf Cu(II)-Indomethacin solution adsorbed on NaY zeolite (Fig. 8) shows the presence of Cu(Ind)2(Py)2 mo- nomeric species.

Although the g, value in this case is close to that obtained for the Cu(Py)4 2§ monomeric species, the appearance of only five clearly resolved superhyperfine lines in the g• region suggests a CuNzO 2 chromophore.

4. Conclusions

Our ESR investigation of a powder sample of the Cu(II)-Indomethacin complex shows the presence of dimers similar to those of copper(II) acetate. The are char- acterized by a short Cu-Cu distance (---2.7 A) a n d a strong antiferromagnetic ex- change coupling ( J = - 3 3 8 cm-l).

A monomeric species of tetrahedral (Td) symmetry with a mixture of 3dxy and 2 % 4pz copper orbitals as the ground state of the paramagnetic electron was obtained by magnetical dilution with Zn(II).

The ESR spectra of Cu(II)-Indomethacin in various solutions suggest the presence of four different monomeric species.

Thus for the 40%Py+60%DMF Cu(II)-Indomethacin solution adsorbed on NaY zeo- lite the following two monomeric species occur: Cu(Ind)2(DMF)2 with an elongat- ed tetragonal-octahedral symmetry and Cu(Ind)2(Py)2 with a CuN202 chromophore in a square-planar arrangement.

528 L. David et al.:

The las t t y p e o f m o n o m e r i c s p e c i e s a p p e a r s a l so in 2 0 % P y + 8 0 % D M F a n d 2 0 % P y + 8 0 % C l f solut ions .

W h e n Cu( I I ) - Indomethac in is d isso lved in pyf id ine , the Cu(Py)42+ species is formed.

This sugges t the d e c o m p o s i t i o n o f the so lv i t compotmd.

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Author's address: Prof. Dr. Onue Cosar, Department. of Physics., University of Cluj-Napoca, 3400 Cluj-Napoca, Romania