The discovery of self-assembling peptides, which can form well-ordered structures, has opened a realm of opportunity for the design of tailored short peptide-based nanostructures. In this study, a combined experimental and computational approach was utilized to understand the intramolecular and intermolecular interactions contributing to the self-assembly of linear and cyclic tryptophan-tyrosine (WY) dipeptides. The density functional tight binding (DFTB) calculations with empirical dispersive corrections assisted the identification of the lowest energy conformers. Conformer analysis and the prediction of the electronic structure for the monomeric, dimeric, and hexameric forms of the cyclic and linear WY confirmed the contributions of hydrogen bonding, π–π stacking, and CH−π interactions in the stability of the self-assembled nanotubes. The influence of the processing conditions on the morphological and thermal characteristics, as well as the secondary structures of the synthesized nanostructures, were analyzed. Preliminary studies of the influence of the nanotubes on the fate of neuronal cell lines such as, PC-12 cells indicate that the nanotubes promote cellular proliferation, and differentiation in the absence of growth factors. The aspect ratio of the nanotubes played an essential role in cellular interactions where a higher cellular uptake was observed in nanotubes of lower aspect ratios. These results provide insight for future applications of such nanotubes as scaffolds for tissue engineering and nerve regeneration and in drug delivery.

Tyrosine-based dipeptides self-assemble to form higher order structures. To gain insights into the nature of intermolecular interactions contributing to the early stages of the self-assembly of aromatic dipeptides, we study the dimers of linear dityrosine (YY) and tryptophan–tyrosine (WY) using quantum-chemical methods with dispersion corrections and universal solvation model based on density in combination with energy decomposition and natural bond orbital (NBO) analyses. We find that hydrogen bonding is a dominant stabilizing force. The lowest energy structure for the linear YY dimer is characterized by O carboxyl ···H(O) tyr . In contrast, the lowest energy dimer of linear WY is stabilized by O carboxyl ···H(N) trp and π tyr ···π tyr . The solvent plays a critical role as it can change the strength and nature of interactions. The lowest energy for linear WY dimer in acetone is stabilized by O carboxyl ···H(O) tyr , π trp ···H(C), and π trp ···H(N). The Δ G of dimerization and stabilization energies of solvated dipeptides reveal that the dipeptide systems are more stable in the solvent phase than in gas phase. NBO confirms increased magnitudes for donor–acceptor interaction for the solvated dipeptides.

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