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The results of molecular dynamic studies supported by the strong hydrogen-bonding equilibria of the participating atoms, radical stabilization energies, the pK<jats:sub>a<\/jats:sub> of the H-donor\/acceptor sites and the cyclooxygenase activity of pertinent muCOX-2 ravelled the working of the water\u2013peptide channel for coordinating the flow of H<jats:bold>\u0387<\/jats:bold>\/electron between the heme and Y385. Based on the working of H<jats:bold>\u0387<\/jats:bold>\/electron transfer channel between the 12.5\u00a0\u00c5 distant radical generation and the radical disposal sites, a series of molecules was designed and synthesized. Among this category of compounds, an appreciably potent anti-inflammatory agent exhibiting IC<jats:sub>50<\/jats:sub> 0.06\u00a0\u03bcM against COX-2 and reversing the formalin induced analgesia and carageenan induced inflammation in mice by 90% was identified. 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