Development of Advanced Methodology for High-Resolution Imaging of Nonconductive Materials by Scanning Tunneling Microscopy

Scanning tunneling microscopy (STM) is known to provide the highest spatial resolution in real space imaging of materials, and its applications are most common among conductive and semi-conductive systems. The high tunneling barrier of insulators diminishes the tunneling probability, and makes it very difficult to reach high resolution. This dissertation introduces a simple method with broad applications, by using STM for high-resolution imaging of insulating materials such as the fourth and fifth generations of poly(amidoamine) hydroxyl-terminated dendrimers. The tunneling barrier is lowered by pre-coordination with Cu(II) or Pt(II) ions, enabling intramolecular hyperfine features to be resolved for the first time. These features correspond to dendrimer termini, for which the spatial distribution, size and overall number for each dendrimer can be determined. The deformation of dendrimers from the spherical geometry in solution phase to asymmetrical domes in ambient and in ultra high vacuum (UHV) can also be directly visualized and determined, including axis, height, asymmetry, and volume. From STM spectroscopy and prior knowledge of the STM imaging mechanism, metal ions were reduced to zerovalent metal(0) nanoparticles encapsulated by dendrimers in UHV, while ambient imaging was most likely via metal ion-facilitated charge transport. The results from this investigation brings us one step closer towards structural characterization at atomistic level, and should enable direct comparison of dendrimer structures with simulations, and deepen our understanding of charge transport in dendrimer systems.;Dendrimers have shown great potential in drug delivery because of their enhancement of drug solubility in aqueous media, leading to an increased in vivo circulation and efficacy to targets. The structure of drug-dendrimer complexes however, are not well known due to the difficulties associated with visualizing individual drug molecules attached to dendrimers. This dissertation expands upon the initial metal ion-doping approach to reveal the hierarchical structure of indomethacin-loaded poly(amidoamine) hydroxyl-terminated dendrimers. High-resolution STM images enable the identification and count of individual indomethacin molecules bound to the anterior of dendrimers. Removal of drug molecules by the STM tip allows calculation of individual drug-dendrimer binding energy, which is consistent with 1-3 hydrogen bonds. These investigations provide new insight into the hierarchical structure and nature of indomethacin-dendrimer interactions, and deepen our understanding of the stability and pharmacokinetic behavior of dendrimer-based drug delivery vehicles. Current efforts and future work will focus on the expansion of the drug-dendrimer concept towards covalent and bi-functional drug attachment in addition to elucidating the extent of metal ion doping in individual dendrimer molecules.