Inherent chirality

This phenomenon was described as resulting from "the absence of a place of symmetry or an inversion center in the molecule as a whole". Boehmer further explains this phenomenon by suggesting that if an inherently chiral calixarene macrocycle were opened up it would produce an "achiral linear molecule". There are two commonly used notations to describe a molecules inherent chirality: cR/cS (arising from the notation used for classically chiral compounds, with c denoting curvature) and P/M. Inherently chiral molecules, like their classically chiral counterparts, can be used in chiral host–guest chemistry, enantioselective synthesis, and other applications. There are naturally occurring inherently chiral molecules as well. Retinal, a chromophore in rhodopsin. exists in solution as a racemic pair of enantiomers due to the curvature of an achiral polyene chain.

History

Calixarenes

After creating a series of traditionally chiral calixarenes (through the addition of a chiral substituent group on the top or bottom rim of the macrocycle,) the first inherently chiral calixarenes were synthesized in 1982, though the molecules were not yet described as such. The inherently chiral calixarenes featured an XXYZ or WXYZ substitution pattern, such that the planar representation of the molecule does not show any chirality, and if the macrocycle were to be broken open, this would produce an achiral linear molecule. The chirality in these calixarenes is instead derived from the curvature of the molecule in space.

Definition

Due to the initial lack of a formal definition after the initial conception, the term inherent chirality was utilized to describe a variety of chiral molecules that don't fall into other defined chirality types. The first fully formulated definition of inherent chirality was published in 2004 by Mandolini and Schiaffino, (and later modified by Szumna):

inherent chirality arises from the introduction of a curvature in an ideal planar structure that is devoid of perpendicular symmetry planes in its bidimensional representation.

Inherent chirality has been known by a variety of names in the literature including bowl chirality (in fullerene fragments), intrinsic chirality, helicity (see section 3a) residual enantiomers (as applied to sterically hindered molecular propellers,) and cyclochirality (though this is often considered to be a more specific example and cannot be applied to all inherently chiral molecules).

A simple example of inherent chirality is that of corannulene commonly referred to as "bowl chirality" in the literature. The chirality of an unsubstituted corranulene (containing no classic stereogenic centers) cannot be seen in a 2D representation, but becomes clear when a 3D representation is evoked, as the C₅ symmetry of corranulenes provides the molecules with a source of chirality (figure 2.) Racemization of these molecules is possible through an inversion of curvature, though some inherently chiral molecules have inversion barriers comparable to a classic chiral center.