No abstract

Veterinary anti-inflammatory Cu(II) complexes of indomethacin (1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH), of the general formula [Cu(2)(Indo)(4)L(2)] (L = N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), and water), were studied by zero-field and X-band EPR spectroscopies, electronic spectroscopy, magnetic measurements, and X-ray powder diffraction. The complexes are similar to Cu(II) acetate monohydrate, with a strong antiferromagnetic exchange interaction, J, ranging from -141 to -152 cm(-)(1). Variable temperature magnetic susceptibility data for all of the complexes are similar, with the exception of a [Cu(2)(Indo)(4)(H(2)O)(2)] complex, which displays an unusual increase in magnetic moment with decreasing temperature from 50 to 10 K. The X-ray powder diffraction patterns of the DMF and DMA dimers show that they are isostructural. Two isostructural H(2)O complexes were synthesized from different methods yet displayed different variable temperature magnetic susceptibity data. All of the [Cu(2)(Indo)(4)L(2)] complexes crystallize in the triclinic space group P&onemacr;. Single-crystal X-ray diffraction analysis of the DMF complex, [Cu(2)(Indo)(4)(DMF)(2)].1.6(DMF), shows that it is similar to the previously reported [Cu(2)(Indo)(4)(DMSO)(2)] with a Cu-Cu bond length of 2.630(1) Å, Cu-O(RCOO) of 1.960(4)-1.967(4) Å, and Cu-O(DMF) of 2.143(5) Å and crystal parameters a = 10.848(3) Å, b = 13.336(6) Å, c = 16.457(4) Å, alpha = 104.67(3) degrees, beta = 100.94(2) degrees, and gamma = 107.16(3) degrees. The X-ray structure of the DMF dimer does not exhibit strong intermolecular interactions due to the hydrophobic nature of the exterior. This may be important in facilitating its dissolution in micelles and transport through membranes.

Copper K-edge X-ray absorption spectroscopic (XAS) measurements were recorded for the veterinary antiinflammatory Cu(II) complexes of indomethacin (1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH), of the general formula [Cu(2)(Indo)(4)L(2)] (L = N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), and water), and [Cu(2)(OAc)(4)(OH(2))(2)] at room temperature and 10 K. The bond lengths and bridging O-C-O angles of the dimeric Cu(II) cage (Cu(2)O(10)C(8)) obtained from the multiple-scattering (MS) fitting of the X-ray absorption fine structure (XAFS) using a centrosymmetric model of [Cu(2)(Indo)(4)(DMF)(2)] gave Cu.Cu = 2.62(2) A, mean Cu-O(Ac) = 1.95(2) A, Cu-O(L) = 2.15(2) A, bridging O-C-O = 125(1) degrees, Cu displacement from plane 0.19 A compared with the XRD data Cu.Cu = 2.630(1) A, mean Cu-O(Ac) = 1.959 A, Cu-O(L) = 2.143(5) A, bridging O-C-O angles = 123.2(5) degrees, Cu displacement from plane 0.20 A. The excellent agreement between the XAFS- and XRD-derived data allowed the structures of related [Cu(2)(Indo)(4)L(2)] (L = DMA, NMP) complexes to be determined. All display a similar Cu(2)O(10)C(8) coordination geometry, which is independent of the nature of the axial ligand. While XAFS analysis of [Cu(2)(Indo)(4)(OH(2))(2)] and [Cu(2)(OAc)(4)(OH(2))(2)] indicates a coordination geometry similar to that of [Cu(2)(Indo)(4)L(2)] (L = DMF, DMA, NMP), removal of symmetry restraints in the MS model is required to obtain axial bond lengths comparable to those derived in the XRD structures of the acetate complex. For the Indo complex, the fitted bond lengths with the lower symmetry model give a mean Cu-L(OH2) bond distance within experimental errors of the value for [Cu(2)(Indo)(4)(DMSO)(2)] (2.16(2) A) (XRD). The difficulty in refining the Cu-O(OH2) distance of [Cu(2)(OAc)(4)(OH(2))(2)] and [Cu(2)(Indo)(4)(OH(2))(2)] using a centrosymmetric MS model is attributed to a symmetry reduction due to hydrogen-bonding effects characteristic of the aqua adducts, as is observed in the XRD structure of the acetate complex.