Cyclopropane as an Unsaturation “Effect Isostere”: Lowering the Melting Points in Lipid-like Ionic Liquids

The replacement of unsaturation with a cyclopropane motif
as a
(bio)isostere is a widespread strategy in bacteria to tune the fluidity
of lipid bilayers and protect membranes when exposed to adverse environmental
conditions, e.g., high temperature, low pH, etc. Inspired by this
phenomenon, we herein address the relative effect of the cyclopropanation,
both cis and trans configurations,
on melting points, packing efficiency, and order of a series of lipid-like
ionic liquids via a combination of thermophysical analysis, X-ray
crystallography, and computational modeling. The data indicate there
is considerable structural latitude possible when designing highly
lipophilic ionic liquids that exhibit low melting points. While cyclopropanation
of the lipid-like ionic liquids provides more resistance to aerobic
degradation than their olefin analogs, the impact on the melting point
decrease is not as pronounced. Our results demonstrate that incorporating
one or more cyclopropyl moieties in long aliphatic chains of imidazolium-based
ionic liquids is highly effective in lowering the melting points of
such materials relative to their counterparts bearing linear, saturated,
or thioether side chains. It is shown that the cyclopropane moiety
effectively disrupts packing, favoring formation of gauche conformer in the side chains, resulting in enhancement of fluidity.
This was irrespective of the configuration of the methylene bridge,
although marked differences in the effect of cis-
and trans-monocyclopropanated ILs on the melting
points were observed.