The rational design of conformationally
controlled foldable modules can lead to a deeper insight into the
conformational space of complex biological molecules where non-covalent
interactions such as hydrogen bonding and π-stacking are known to play a
pivotal role. Squaramides are known to have excellent hydrogen bonding capabilities
and hence, are ideal molecules for designing foldable modules that can mimic
the secondary structures of bio-molecules. The π-stacking induced folding of
bis-squaraines tethered using aliphatic primary and secondary-diamine linkers
of varying length is explored with a simple strategy of invoking small
perturbations involving the length linkers and degree of substitution. Solution
phase NMR investigations in combination with molecular dynamics simulations
suggest that bis-squaraines predominantly exist as extended conformations. Structures
elucidated by X-ray crystallography confirmed a variety of folded and extended
secondary conformations including hairpin turns and 𝛽-sheets which are determined by the hierarchy of
π-stacking relative to N–H···O hydrogen bonds.
Membrane-induced folding of the plant-stress protein Lti30.