Computer aided chemical speciation in designing metal-based potential anti-inflammatory agents

Includes bibliographical references (leaves 158-161).
The objective of this study was to develop copper based anti-inflammatory agents for the treatment of inflammation associated with Rheumatoid Arthritis. Four low molecular ligands, N,Nt-di(aminoethylene)-2,6-pyridine dicarbonylamine (PrDH), Bis-(N,N-dimethylethyl)-2,6-pyridinedicarboxamide (PrDM), N,N'-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (PrDPr) and 3,5-bis[(aminoethyl)ethanediamide]-4-oxahexacyclo-dodecane (PCUA) were designed and synthesised. The formation constants of these ligands with H+, Cu2+, Niz+, Znz+ and Caz+ were determined potentiometrically at 25°C and 0.15 mol dm-3 Na+Cr. The Cu(II) formed relatively more stable complexes than other three metal ions. The structures of the different Cu(II) species formed with these ligands were investigated using nuclear magnetic resonance(NMR), infrared (IR) spectroscopy, ultraviolet-visible (UV-visible) spectroscopy as well as molecular mechanics calculations. For the NMR spectroscopy, results showed that the central pyridyl nitrogen and amide nitrogen(s) as well as the terminal amino/pyridyl groups coordinate to the Cu(II) ion in solution. The IR results indicated that an amide nitrogen is coordinated to the Cu(II). The UV-visible study gave the smooth deconvoluted spectra of the individual species for the Cu(II)-PrDH, Cu(II)-PrDM and Cu(II)-PrDPr systems in support of the potentiometric results. The three studied ligands form tetragonally distorted octahedral MLH-l and MLH-z species with Cu(II). The molecular mechanics was used to calculate the internal strain energies of the different possible geometries of related complex species. A comparison of these energies was used to rationalize the different stabilities of these structures.