In this theoretical study, the sensitivity of Fe4S4 cluster properties, such as potential energy, spin coupling, adiabatic detachment energy, inner-sphere reorganization energy, and reactivity, to structural distortions is investigated. [Fe4S4(SH)4]3−/2−/1− model clusters anchored by fixed hydrogen atoms are compared with Fe4S4 clusters coordinated by ethyl thiolates with fixations according to cysteine residues in crystal structures. For the model system, a dependence of the ground-state spin-coupling scheme on the hydrogen–hydrogen distances is observed. The minima of the potential energy surface of [Fe4S4(SH)4]2−/1− clusters are located at slightly smaller hydrogen–hydrogen distances than those of the [Fe4S4(SH)4]3− cluster. For inner-sphere reorganization energies the spin-coupling scheme adopted by the broken-symmetry wave function plays an important role, since it can change the reorganization energies by up to 13 kcal mol−1. For most structures, [Fe4S4(SR)4]2− and [Fe4S4(SR)4]1− (R=H or ethyl, derived from cysteine) favor the same coupling scheme. Therefore, the reorganization energies for this redox couple are relatively low (6–12 kcal mol−1) compared with the 2−/3− redox couple favoring different spin-coupling schemes before and after electron transfer (14–18 kcal mol−1). However, one may argue that more reliable reorganization energies are obtained if always the same spin-coupling pattern is enforced. All theoretical observations and insights are discussed in the light of experimental results distilled from the literature.