Synthesis, Monitoring, and Molechanical Action of Light-Driven Motorized Nanomachines
Garcia Lopez, Victor
Tour, James M.
Doctor of Philosophy
This dissertation describes the design and synthesis of a series of unimolecular nanomachines bearing a fast light-driven rotary motor (3 MHz at 25 °C) as a power unit and fluorophores for their monitoring. A well-tailored structural design that unifies the mechanism of propulsion and the requisite monitoring component, made possible the investigation of the diffusion of these nanomachines in solution and on surfaces, and their molechanical action in biological systems. To investigate the diffusion of nanomachines in solution, a series of Unimolecular Submersible Nanomachines (USN) bearing the light-driven rotary motor and cy5 fluorophores were synthesized. Through careful design of control molecules with no motor and with a slow motor (2 rph at 60 °C), we found using single molecule fluorescence correlation spectroscopy (FCS) that only the molecules with fast rotating speed (MHz range) show an enhancement in average diffusion by 26% when the motor is fully activated by UV light. A non-unidirectional rotating motor also results in a smaller, 10% increase in diffusion. Although USNs can increase their average diffusion in solution, little is known about their trajectories, mainly because the cy5 fluorophores are prone to photobleaching. Thus, new photostable USNs were synthesized as a first step towards the analysis of their trajectories in solution. The new USNs have the fast light-driven motor for propulsion and photostable cy5-COT fluorophores for their tracking. It was found that these cy5-COT fluorophores provide an almost twofold increase in photostability compared to the previous USN versions. By analyzing the rotation of a control molecule, it was demonstrated that the cy5-COT fluorophores do not affect the rotation of the motor. This improvement in photostability will further the study of the behavior of light-driven molecular machines in solution. To investigate the diffusion of motorized nanomachines at room temperature on non-conductive surfaces, a series of motorized nanocars were synthesized. The design includes a fast rotary light-driven motor, four adamantane wheels, and BODIPY fluorophores for their tracking by Single-Molecule Fluorescence Spectroscopy (SMFM). Through a series of iterations, the nanocars were optimized such that the motor keeps its fast rotation frequency in the presence of BODIPY. The high quantum yields and the photostability of the BODIPY make these nanocars suitable for SMFM tracking. A new molecular mechanical method or “molechanical” effect to open cellular membranes was developed. The molechanical action of several nanomachines was investigated. We demonstrated that molechanical action can induce the diffusion of analytes out of synthetic vesicles, the introduction of analytes into cells, rapid necrosis and enhanced diffusion of traceable molecular machines within cells.
Nanomachines; nanocar; light-driven motor; diffusion coefficient; fluorophore