| Since the development of the first metal N-heterocyclic carbenes (NHC) by Ofele and Wanzlick in the 1960s, investigation into this area has grown dramatically, especially after the synthesis of the first stable free metal carbene in 1991 by Arduengo. Since that time, metal carbenes have been synthesized for applications related to catalysis and more recently therapeutics. Research in the Youngs group has focused on applying the synthetic routes of Lin to make a variety of silver NHCs for medicinal purposes. More recently, encapsulation of the silver NHCs into nanoparticles have been investigated for sustained release and systemic delivery of the therapeutics.;This dissertation will focus on both the synthesis of some new silver NHCs as well as their encapsulation into biodegradable nanoparticles. Chapter 1 discusses the advantage of using silver as an antimicrobial and anticancer agent, as well as why NHCs were chosen. It will also provide an overview of research in the area of nanoparticles that are relevant to encapsulation of our silver NHC complexes. Chapter 2 details the synthesis of two new silver NHCs with methylbenzoate substituents attached, as well as the antimicrobial activity of these compounds. Chapter 3 describes a series of mono-halogenated compounds that were synthesized in order to determine their water-stability using 1H NMR spectroscopy. Chapter 4 will discuss the synthesis of one of our most active compounds to date as well as its encapsulation into the biodegradable, FDA approved nanoparticle poly(ethylene glycol)-poly(lactic acid) (PEG-PLA). The efficacy of the silver NHC-encapsulated nanoparticle on a small-cell lung cancer line is also presented. Finally, Chapter 5 will describe the in vivo toxicity results of the same nanoparticle system performed on two different strains of mice utilizing two different delivery methods, including nebulization and intravenous injection, to demonstrate the potential of this silver NHC-nanoparticle for antimicrobial and anticancer applications. |
