Zinc K-edge X-ray absorption fine structure (XAFS) experiments were performed in the solid and solution states at low temperature (10 K), on dimeric and monomeric anti-inflammatory Zn(II) complexes of indomethacin [1-(4-ch lorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH] of the formula [Zn-2(Indo)(4)L-2] [L = pyridine (Py), NN-dimethylacetamide (DMA)], [Zn(Indo)(2)L-2] [L = ethanol (EtOH), methanol (MeOH)], and Zn(II) acetate dihydrate [Zn(OAc)(2)(OH2)(2)]. The bond distances and angles obtained from multiple-scattering fits to the XAFS data of the Zn(II) dimeric complexes in the solid and solution states exhibit excellent correspondence with those obtained from single crystal diffraction studies. The (ZnZn)-Zn-... separations of 2.97 and 2.96 Angstrom and carboxylato group O-C-O angles of 125degrees for powdered [Zn-2(Indo)(4)(Py)(2)] and [Zn-2(Indo)(4)(DMA)(2)] agree well with the XRD values of 2.969(1) and 2.9686(6) Angstrom and 125.8(4)degrees and 126.1(2)degrees, respectively. The calculated Zn-O-Rcoo and Zn-L bond distances of 2.03 and 2.04 Angstrom, or 2.02 and 1.98 Angstrom for Py or DMA complexes, respectively, also agree well with crystallographic data. The X-ray powder diffraction data on samples of the monomers exhibited additional reflections apart from those due to the crystallographically characterized cis-[Zn(eta(2)-O,O'-Indo)(2)L-2], but microanalyses were consistent with this formulation. Therefore, mixed models that contained the cis complex and a second component consisting of a trans-six-coordinate complex, a five-coordinate complex, or a four-coordinate complex were used to model the XAFS. The best fits to the XAFS data were obtained with a mixture of the cis-six-coordinate complex and a four-coordinate complex containing two monodentate Indo ligands. The bond lengths for the six-coordinate structure were consistent with those determined on a single crystal, and those for the four-coordinate complexes were consistent with related four-coordinate structures with two monodentate carboxylate ligands. Dissolution of the dimer (DMA adduct) in DMF resulted in a mixture of dimer and monomer species as shown by MS XAFS fitting. This is the first time that solution structures have been determined for anti-inflammatory Zn(II) complexes, and this is an important first step in understanding the pharmacology of the complexes.