Two new series of ligands, SAPH ( 1–3) and DAPHS ( 4–6) related to the metal chelating portion of the anti-tumor drug bleomycin (BLM) have been synthesized and evaluated. These series differ from the related simplified models, PYML and AMPHIS by modifications of the primary amine of PYML and AMPHIS to a thio functionality (-SR) (R = CH 3, 1; R = CH 2C 6H 4OCH 3, 2; R = H, 3) in the SAPH ( 1–3) series and by the additional change of the secondary amino functionality of SAPH to an amido unit in the DAPHS ( 4–6) compounds. SAPH ( 1–3) and DAPHS ( 4–6) are, therefore, potentially five-coordinate N 4S donor ligands possessing imidazole, amide, pyridine, amine, and sulfhydryl moieties for SAPH-3 and imidazole, amide, pyridine, amide, and sulfhydryl for DAPHS-6. One:one metal:ligand complexes were prepared with Cu II, Fe II and Fe III. Frozen glass ESR spectra and electronic spectra at room temperature of the Cu II complexes show that the resultant coordination geometry and choice of ligand donor set is strongly influenced by pH. Cu II(SAPH-3) exhibits imidazole, pyridine, amine and sulfhydryl (N 3S) coordination in a trigonal bipyramidal complex at 2.80. The coordination changes to imidazole, deprotonated amide, pyridine and amine (N 4) at pH⩾ 5.80; the ESR spectra require rhombically distorted square- planar coordination similar to Cu II(AMPHIS) and Cu II(BLM) in this range. Cu II(DAPHS-6) exhibits ESR spectra indicative of 2N (imidazole, pyridine), 3N (imidazole, first amide, pyridine) and 4N (imidazole, pyridine, and both amides) coordination at pHs of 3.18, 5.62 and 8.00, respectively. Sulfhydryl coordination for Fe III(SAPH-3) is indicated by the presence of charge transfer bands (>400 nm) which are absent for the SCH 3 analog, Fe III(SAPH-1), and by the electrochemical behavior of Fe II(SAPH-3) above pH 6.9 where N 4S coordination is observed. Fe II(SAPH-1) reacts with molecular O 2 but possesses one-tenth the activity of Fe II(AMPHIS), in forming HO· or HO 2· radicals which escape the solvent cage of the Fe III complex for trapping by DMPO or PBN spin-trap scavengers. Fe II(SAPH-3) shows no free HO· trappable by DMPO during autoxidation, indicative of 2e − reduction steps. Fe II(SAPH-3) exhibits no reversible 1e − electrochemical wave from −0.64 to +1.24 V for forms having sulfhydryl coordination, but the same complex reacts rapidly with 2e − chemical oxidants (O 2, H 2O 2, Ru IV). Diamide analogs (DAPHS) also lack HO· or O 2 − generating activity.