Controlling the Morphology and Orientation of the Helical Self‐Assembly of Pyrazine Derivatives by Tuning Hydration Shells

A combination of density functional theory (DFT) and classical molecular dynamics simulations is performed to unveil the guiding force in the self-assembly process of the pyrazine-based biopolymers to helical nanostructures. The highlight of the study shows the decisive role of the solvent-ligand H-bonding and the inter-molecular pi-pi stacking not only ensures the unidirectional packing of the helical structure but also the rotation of left-handed to the right-handed helical structure of the molecule. This transition is supported by the bulk release of the "ordered" water molecules. The extent of this bonding can be tuned by the temperature, concentration, and type of the metal ions. Smaller ions like Na⁺ and Al³⁺ destroy the structure, whereas bigger ions like Zn²⁺, Ni²⁺, and Au³⁺ preserve and rotate the structure according to their concentration. The interaction energy between the pyrazine derivatives is found to be high (-9000 kJ mol^-1) for right-handed rotation of the helix, which increases further with the addition of D-histidine, forming a superhelical structure (-10300 kJ mol^-1). The insights gained from this work can be used to generate nanostructures of desired morphology.