Synthesis and biological evaluation of tetrakis(acetylsalicylato)-mu-dicopper(II).

The synthesis of a copper-aspirin chelate, previously reported to be a more active anti-inflammatory agent than aspirin itself, is given. Reaction of potassium acetylsalicylate with cupric sulfate gave a stable copper complex, which analysis and molecular weight determination showed to be a 4:2 chelate structure. Oil-water partition measurements showed the complex to be 10-fold more oil soluble than aspirin. Biological evaluation in rats showed the copper complex of aspirin to be approximately equal to aspirin in reducing carrageenan-induced inflammation, but it was 1.7 times more active than aspirin in reducing the primary lesion of adjuvant arthritis. Whereas aspirin produced a 50% or greater incidence of GI erosions at doses of 100-300 mg/kg in rats, the copper complex caused no erosions in doses up to 1200 mg/kg.