The use of non-covalent interactions for the modification of nanoparticle surface and MRI contrast agent properties

The focus of this work is the non‐covalent modulation of MRI based nanotheranostics. This includes modification of nanoparticulate surface properties based on phosphonate‐guanidine hydrogen bonding, modulation of MRI contrast agent behavior based on guest‐host interactions, and masking of MRI contrast using a gelatin pill casing. Synthetic methodology for the synthesis of potential pharmaceutical entities is also described. ❧ Surface properties are key factors for controlling in vivo behavior of nanoparticulate drug delivery vehicles. A general procedure for the surface modification of hybrid gadolinium‐phosphonate coated gold nanoparticles was achieved via hydrogen bonding interaction with an amphiphilic fluoroalkyl monolayer. Along with an increase in hydrodynamic diameter, the coating interaction was characterized by a significant decrease in ¹⁹F T₁ of the coating monomer, allowing for potential ¹⁹F MRI based nanotheranostics. ❧ Controllable, non‐covalent interactions were also used to attenuate and reveal MRI contrast agents by hiding them in molecular hosts. A container‐shaped molecular host compound, which had previously demonstrated selective and strong binding affinities towards trimethylammonium functionality, was used. Modification of Gd•DOTA with the trimethylammonium moiety resulted in a dramatic decrease of contrast upon exposure to the molecular host. The masking event is accompanied by the assembly of contrast agent into a 7 nm micelle as characterized by DLS. The contrast agent guest was removed from the host via competitive binding in the presence of a stronger binding agent, resulting in a 31% contrast increase over the masked state. ❧ The release of MRI contrast agent from a gelatin pill casing was characterized. The masked MRI contrast agent was immediately revealed under acidic conditions, whereas it remained masked under neutral conditions for over ten minutes. The release of the gadolinium‐based MRI contrast agent was characterized by the decrease of T₁ in vitro, and MRI contrast observed in vivo. This MRI pill can potentially be used for imaging of gastric motility disorders such as gastroesophageal reflux disease and gastroparesis. ❧ Catalytic conditions for oxidation of azolines to azoles are also described. Azoles are biologically active marine cyclopeptides in which its synthesis have historically involved stoichiometric amounts of toxic reagents. By utilizing catalytic amounts of a copper catalyst and base, inexpensive and environmentally benign conditions for this bond transformation were achieved. Along with the catalytic copper conditions, copper‐free conditions involving stoichiometric amounts of base were also developed. These conditions demonstrated decreased reaction times over the catalytic copper conditions.