A generalized handedness labeling strategy: Addressing latent handedness in chiral structures

We propose a strategy for treating the problem of assignment of handedness in a generalized way. The need for this generalization arises from an inherent pitfall of definitions of handedness: Given such a definition there exists at least one chiral structure for which handedness cannot be assigned. We demonstrate this situation for the helical and the CIP handedness conventions as well as for Ruch's potato, and provide an argument that the inability to assign handedness is a property of any labeling procedure. We categorize chiral structures for which handedness cannot be assigned as Latent Handedness structures. These structures - which define bounds for the range of applicability of labeling procedures - are analyzed in detail and serve here as a basis for the proposed generalized handedness assignment procedure. Since latent handedness structures show up particularly along chiral enantiomerization pathways, we concentrate on these processes with special attention to problems of helical transitions and helical handedness switching, which are the focus of much recent experimental work. Two interesting categories of enantiomerization pathways (J. Math. Chem., 23, 13 (1998)) are highlighted in the context of latent handedness: chiral enantiomerization routes which are totally of latent handedness, namely chiral processes for which it is not possible to assign handedness at any point; and enantiomerization pathways all points of which are of the same handedness except for the end points. Interestingly, quite often the chiral latent handedness structure and the chiral transition states are similar; an explanation is provided.