(496a) Determining the Structure of Organic Rosette Nanotubes Using Multi-Scale Molecular Modeling: Ring Stack Vs Helical Tube

Rosette Nanotubes (RNTs) are tubular soft materials self-assembled from guanine-cytosine (G∧C) hybrid molecules, which can be covalently functionalized for use in various applications. They have been shown to be effective assemblies in regenerative medicine, drug display and delivery, and catalysis.

Previous spectroscopic studies suggest they have a structure which is formed by hexameric rings, maintained by self-complementary hydrogen bonds, that are further stacked and supported by π-π interactions, which form the ring-stacked RNTs. While this mode of association maximizes the hydrogen bonding interactions and results in efficient π-π stacking, it is also possible to envision that the G∧C modules assume a helical organization defining a tubular core (Fig. 1). Having knowledge of the structure of the RNT is important in the design and synthesis of novel motifs for various applications.

Imaging the nanotube using scanning tunneling microscopy (STM) proved inconclusive in differentiating the three configurations (Fig. 1). Furthermore, comparing the chemical shifts of the nitrogen atoms of the G∧C monomers of both the stacked-tube (ST) and helical tube (HT) configurations using quantum chemical calculations showed no significant difference between them.

We further investigated this possibility by using the lysine-functionalized RNT (K1-RNT) and applying multi-scale molecular modeling methods, which include Monte-Carlo conformational search, molecular dynamics, and the statistical mechanical theory of molecular liquids (3D-RISM theory). We considered three structures of the K1-RNT: ST, left-handed HT (LHT), and right-handed HT (RHT) (Fig. 2).

Our results suggest that the formation of ST, LHT, and RHT K1-RNTs in water are favorable and are enthalpically driven. Moreover, 3D-RISM analysis suggests that the RHT conformation is more probable than the ST and LHT RNTs and this is due to a more favorable solute-solvent interaction energy (Fig. 3). Using the 3D distribution of solvent sites around the RNTs (from 3D-RISM calculations), we were also able to determine the solvation structure and estimate the free energy of binding of each water molecule in the RNT channel (Fig. 4). The results also corroborate the higher probability of the RHT conformation occurring. Studies are being done to verify these findings.