The syntheses, crystal structures, and magnetic characterizations of three new hexanuclear iron(III) compounds are reported. Known [Fe6O2(OH)(2)(O2CBuI)(10)(hep)(2)] (1) is converted to new [Fe6O2(OH)(O2CBut)(9)(hep)(4)] (3) when treated with an excess of 2-(2-hydroxyethyl)-pyridine (hepH). Similarly, the new compound [Fe6O2(OH)(2)(O2CPh)(10)(heP)(2)] (2), obtained from the reaction of [Fe3O(O2CPh)(6)(H2O)(3)] with hepH, is converted to [Fe6O2(OH)(O2CPh)(9)(heP)(4)] (4) when treated with an excess of hepH. This can be reversed by recrystallization from MeCN. The cores of the four Fe-6 complexes all comprise two triangular [Fe-3(mu(3)-O)(O2CR)(3)(hep)](+3) units connected at two of their apices by two sets of bridging ligands. However, 1 and 2 differ slightly from 3 and 4 in the precise way the two Fe3 units are linked together. In 1 and 2, the two sets of bridging ligands are identical, consisting of one mu-hydroxo and two mu-carboxylate groups bridging each Fe-2 pair, i.e., a (mu-OH-)(mu-O2CR-)(2) set. In contrast, 3 and 4 have two different sets of bridging ligands, a (mu-OH-)(mu-O2CR-)(2) set as in 1 and 2, and a (mu-OR-)(2)(mu-O2CR-) set, where RO- refers to the alkoxide arm of the hep(-) chelate. Variable-field and -temperature dc magnetization measurements establish that 1 and 2 have S = 5 ground states and significant and positive zero-field splitting parameters (D), whereas 3 and 4 have S = 0 ground states. This dramatic difference of 10 unpaired electrons in the ground state S values for near-isomeric compounds demonstrates an acute sensitivity of the magnetic properties to small structural changes. The factors leading to this have been quantitatively analyzed. The semiempirical method ZILSH, based on unrestricted molecular orbital calculations, was used to obtain initial estimates of the Fe-2 pairwise exchange interaction constants (J). These calculated values were then improved by fitting the experimental susceptibility versus T data, using a genetic algorithm approach. The final J values were then employed to rationalize the observed magnetic properties as a function of the core topologies and the presence of spin frustration effects. The large difference in ground state spin value was identified as resulting from a single structural difference between the two types of complexes, the different relative dispositions (cis vs trans) of two frustrated exchange pathways. In addition, use of the structural information and corresponding J values allowed a magnetostructural correlation to be established between the J values and both the Fe-O bond distances and the Fe-O-Fe angles at the bridging ligands.