A series of iron(IV) oxo complexes, which differ in the donor (CH₂py or CH₂COO^–) cis to the oxo group, three with hemilabile pendant donor/second coordination sphere base/acid arms (pyH/py or ROH), have been prepared in water at pH 2 and 7. The ν_Fe═O values of 832 ± 2 cm^–1 indicate similar Fe^IV═O bond strengths; however, different reactivities toward C–H substrates in water are observed. HAT occurs at rates that differ by 1 order of magnitude with nonclassical KIEs (k_H/k_D = 30–66) consistent with hydrogen atom tunneling. Higher KIEs correlate with faster reaction rates as well as a greater thermodynamic stability of the iron(III) resting states. A doubling in rate from pH 7 to pH 2 for substrate C–H oxidation by the most potent complex, that with a cis-carboxylate donor, [Fe^IVO(Htpena)]²⁺, is observed. Supramolecular assistance by the first and second coordination spheres in activating the substrate is proposed. The lifetime of this complex in the absence of a C–H substrate is the shortest (at pH 2, 3 h vs up to 1.3 days for the most stable complex), implying that slow water oxidation is a competing background reaction. The iron(IV)═O complex bearing an alcohol moiety in the second coordination sphere displays significantly shorter lifetimes due to a competing selective intramolecular oxidation of the ligand.