(260u) Multi-Scale Molecular Modeling of Rosette Nanotubes Derived from a Tetracyclic GΛC Motif

Rosette nanotubes (RNTs) are soft organic nanomaterials self-assembled under aqueous conditions from Watson-Crick inspired guanine-cytosine (GÎ?C) hybrid building blocks with complementary hydrogen bonding and extensive Ï?-Ï? interaction sites. These materials have substantial design flexibility and a range of applications, which is partly attributed to their diverse surface functionalization and a chemically/physically tunable channel for guest molecule loading. Several studies have established their biocompatibility and applications in nanomedicine such as in coatings for medical devices, materials for tissue engineering and for drug display and delivery.

With novel applications in mind, particularly, drug delivery, a new tetracyclic GÎ?C motif, the yGÎ?C, was designed to self-assemble into RNT in water. The GÎ?C motif was functionalized by two lysine groups, which are known to give RNTs biocompatibility and therapeutic properties. To aid in the characterization of this new RNT, multi-scale molecular modeling techniques were applied to predict its structure in solution. Molecular dynamics (MD), molecular mechanics (MM), and the statistical mechanical theory of solvation, also known as the 3 dimensional reference interaction site model (3D-RISM) theory were applied to predict the self-assembly, conformation, and stability of yGÎ?C-RNTs. MM was used to determine the possible conformations of the individual motifs. From these, RNT models were built and MD simulations were run to determine the stability and probable structure of the nanotubes. The results suggest that the yGÎ?C motif can either form a 6-membered or 7-memebered ring stacks. 3D-RISM integral equations were then solved for the system to determine the thermodynamics and to propose a self-assembly pathway for the RNTs. Moreover, a model RNT from yGÎ?C motifs is proposed.

The yGÎ?C-RNTs have an inherent advantage of having a large channel, with diameters between 1.8 nm and 2.3 nm that could potentially host guest molecules suitable for various applications. In this study, the model RNT was used to hold guest molecules, phosphorodiamidate morpholino oligomer (PMO), paclitaxel (PTX), and doxorubicin (DOX). These molecules were chosen for their anti-cancer and other pharmaceutical attributes. MD simulations were run to determine the capability of the nanotube to capture and host the guest molecules. 3D-RISM was then used to determine the probable pathway and energies involved in encapsulating the drug molecules. Results indicate that the yGÎ?C-RNT can stably enclose PMO, PTX, and DOX. This suggests that yGÎ?C-RNT has high potential in biomedical applications. Experiments are currently being done to determine the structure of the RNTs and test these possibilities.