Dess-Martin periodinane (DMP) and its derivatives are popular organic catalysts. DMP is extremely reactive in the presence of alcohols, catalyzing their oxidative conversion into ketones. However, despite their widespread use, this reactivity has not yet been explained. In the present work, a quantum chemical topological approach is taken to study the electronic structure of DMP. Topological analysis revealed two of the Iodine interpuncts ligand interactions to be notably weaker than the two others. Combined with study of the domain-averaged Fermi hole (DAFH), it was confirmed that the iodine center is λ 5 -hypervalent, forming two 3-center-4-electron and two 3-center-2-electrons bonds. The weakness of these multicenter bonds is ascribed to the high reactivity displayed by DMP. The ability to tune the ligand-iodine interactions is investigated by altering the electronic structure of the ligands. It is demonstrated that DAFH analysis offers powerful insight into the understanding of molecular reactivity.