Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Severin Schneebeli

Second Advisor

Jianing Li


Use of supramolecular and mechanochemical assemblies has emerged as a promising approach to address a wide scope of chemical challenges including targeted drug delivery, environmentally responsible plastics, and molecular computers. Organization of molecules through intermolecular interactions — a core component of supramolecular chemistry — or through formation of a mechanochemical bonds results in materials with highly specific behavior. However, the synthesis of these materials is difficult, and computational models lack consistency in describing critical interactions which govern a system’s dynamics. As a result, new computational approaches to elucidate supramolecular behavior and synthetic strategies which readily provide access to useful topologies are needed. This dissertation presents two distinct molecular architectures, bridging the gap between biologically derived and entirely synthetic systems. For both systems, the intentional placement of functional groups within the molecular assembly is crucial to its well-defined behavior. The first portion of this dissertation discusses in silico investigations into DNA nanocage and human serum albumin (HSA) complexes.

The use of DNA nanotechnology for nanomedicine is a steadily growing field. Unfortunately, the low stability of DNA nanostructures (DNs) in biologically relevant conditions remains a major obstacle. The conjugation of serum proteins to DNs is an effective means of improving stability, particularly against nuclease degradation. Here, two decorated DNA nanocubes complexed with HSA were investigated using large scale all-atom molecular dynamics. These simulations reveal that in a cage with four (C4) or eight (C8) decorations, internalization of HSA maximizes dendrimer contacts, and is the preferred state of HSA. Moreover, a conformational difference between the "HSA in" states of each model is readily apparent. Finally, a swarm inspired approach to molecular dynamics coupled with Markov state modeling is used to describe the transitions between the "in" and "out" state in the C4-cage model.

The second portion of this dissertation presents the application and development of catalytic [2]rotaxanes. [2]Rotaxanes represent a subset of mechanically interlocked molecules (MIMs) comprised of one axle and one macrocyclic wheel. This portion of the dissertation first presents the development of a catalytic [2]rotaxane capable of distant end-group communication between reactive esters at either end of the axle. Using this communication, monoselective functionalization enabled the development of a rotaxane-based chemical logic gate. Next, a modification to the spatial presentation of the catalyst allowed for the selective synthesis of a "doubly-directional" asymmetric [2]rotaxane. This new approach to asymmetric rotaxane synthesis is both synthetically facile and readily adaptable to additional structural modifications.



Number of Pages

283 p.

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