Molecular Tetris by sequence-specific stacking of hydrogen bonding molecular clips

ABSTRACT: A face-to-face stacking of aromatic rings is an effective non-covalent strategy to build functional architectures, as elegantly exemplified with protein folding and polynucleotide assembly. However, weak, non-directional, and context-sensitive van der Waals forces pose a significant challenge if one wishes to construct well-organized π-stacks outside the confines of the biological matrix. To meet this design challenge, we have devised a rigid polycyclic template to create a non-collapsible void between two parallel oriented π-faces. In solution, these shape-persistent aromatic clips self-dimerize to form quadruple π-stacks, the thermodynamic stability of which is enhanced by self-complementary N–H···N hydrogen bonds, and finely regulated by the regioisomerism of the π-canopy unit. With assistance from sufficient electrostatic polarization of the π-surface and bifurcated hydrogen bonds, a small polyheterocyclic guest can effectively compete against the self-dimerization of the host to afford a triple π-stack inclusion complex. A combination of solution spectroscopic, X-ray crystallographic, and computational studies aided a detailed understanding of this cooperative vs competitive process to afford layered aromatics with extraordinary structural regularity and fidelity. Stacking aromatic molecules through π–π interactions is a useful strategy to create ordered layers of small molecules, but the weak and non-directional nature of these forces creates a challenge in achieving long-range structural ordering. Here, a rigid molecular template that facilitates the creation of a non-collapsible void between two parallel π-faces is designed, and a central N–H motif is shown to increase the thermodynamic stability of self-dimerized assemblies and host–guest complexes via N–H…N hydrogen bonds.

SUBMITTER: Lee H 

PROVIDER: S-EPMC9814962 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature