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We speculate that these bulky C-terminal modifications may help maintain the threaded lasso topology of the compound synthesized by the macrolactam synthetase. This journal is © The Royal Society of Chemistry 2019.The O2 reduction reaction (ORR) catalysed by iron porphyrins with covalently attached pendant guanidine groups is reported. The results show a clear enhancement in the rate and selectivity for the 4e-/4H+ ORR. In situ resonance Raman investigations show that the rate determining step (rds) is O2 binding to ferrous porphyrins