The stable configurations of o-phenylenes have helical tightly packed n-phenylenes with pi/pi stacking interactions. To investigate helical inversion pathways, we have studied theoretically the stable and transition-state geometries of tetrameric o-phenylenes (4-OP) using the density functional theory (DFT) method. We have found eight local minima and 22 transition-state structures. The pathway in which 4-OP converts from right- to left-handed geometry at once has activation energy as high as 40 kcal/mol, while a step-by-step reaction pathway through three different transition-states has much more lower activation energies. Therefore, one can conclude that the step-by-step inversion pathway is preferable for neutral 4-OP. (C) 2013 Elsevier B.V. All rights reserved.