A complete catalytic cycle for H-2 oxidation on a model emulating the active site of Fe-only hydrogenases, [Fe-2(mu-DTMA) (CO)(4)(CN)(2)](2-) (DTMA = SCH2NHCH2S),. has been investigated using density functional theory (DFT). Our calculations show that the bridged CO group in the fully reduced species does not play a significant role on the H-2 activation. According to the studied mechanism. the rate-determining step is neither kinetically nor thermodynamically favorable for the second proton transfer. A modified model aiming to improve the catalytic efficiency has been designed and a plausible catalytic mechanism is suggested. In the new model, [Fe-2(mu-PDTN)(CO)(4)(CN)(2)](2-) (PDTN = SCH2CH(NH2)CH2S), a shorter proton transfer path has been obtained by changing the base position and the process is significantly facilitated. In the modified catalytic cycle, the highest barrier for H-2 oxidation is only 7.90 kcal mol(-1) (c) 2006 Elsevier B.V. All rights reserved.