Computational Prediction of the Supramolecular Self-Assembling Properties of Organic Molecules: Flexibility vs Rigidity

Two families of organic molecules with different backbones have been considered. The first family, composed by a substituted central phenyl is considered as flexible. The second one, based on a macrolactam-like unit, is considered as rigid. They have however a common feature, three amide moieties (as substituents for the phenyl and within the cycle for the macrolactam-like molecule) that allow hydrogen bonding when molecules are stacked. In this study we propose a computational protocol to unravel the ability of the different families to self-assemble into organic nanotubes. Starting from the monomer and going towards larger assemblies like dimers, trimers, and pentamers we applied different theoretical protocols to rationalize the behavior of the different assemblies. Both structures and thermodynamics were investigated to give a complete picture of the process. Thanks to the combination of a quantum mechanics approach and molecular dynamics simulations along with the use of tailored tools (non covalent interaction visualization) and techniques (umbrella sampling), we have been able to differentiate the two families and highlight the best candidate for self-assembling purposes.