Synthesis of Tridentate Oligopyrroles and Coordination of Noble Metals

Abstract

Tripyrrolic and dipyrrolic fragments of oligopyrrolic pigments have been isolated from the degradation of heme and other tetrapyrroles in various biological settings. These biopyrrins contain characteristic pyrrolin-2-one termini and maintain the ability to coordinate a variety of transition metals. Metal complexes containing the tripyrrin-1,14-dione and dipyrrin-1,9-dione scaffolds have a rich ligand-based redox chemistry. These compounds undergo reversible pi-dimerization in solution and are of interest for several applications including supramolecular systems, redox-switchable fluorophores, catalysts, and photosensitizers in photodynamic therapy. This dissertation focuses on expanding the coordination chemistry of the tripyrrin-1,14-dione ligand and on synthetically modifying the existing scaffold to modulate its coordination and redox chemistry. Chapter 1 offers a summary of lower-order linear oligopyrroles derived from heme degradation and provides an overview of the coordination chemistry of tripyrrindione and dipyrrindione ligands and their properties. Chapter 2 describes the synthesis of three tripyrrindione complexes containing primary amines in the fourth coordination site, highlighting the ability to use amines as linkers to connect complexes of tripyrrindione radicals. Additionally, this chapter showcases the ability of a gold tripyrrindione complex to activate C-Cl bonds, and the product from the observed reactivity with dichloromethane was characterized by microcrystal electron diffraction (MicroED). Finally, Chapter 2 details the synthesis of a silver(I) tripyrrindione complex wherein the silver(I) reagent oxidizes and binds the tridentate ligand system. The complex formed from the one-electron reduction of the parent complex is fluorescent and it was isolated and characterized as an anionic silver(I) tripyrrindione radical. In Chapter 3, the synthesis, characterization, and coordination of the first meso-aryl tripyrrindione is described as well as its dimethoxytripyrrin precursor. These ligands coordinate palladium(II) in distinct ways: the dimethoxytripyrrin undergoes C(sp3)-H bond activation to form a cyclopalladate complex, whereas the meso-pentafluorophenyl tripyrindione binds as a trianionic ligand. Other synthetic pathways attempted to synthesize a meso-aryl tripyrrindione are also discussed. Additionally, attempted synthetic routes towards meso-aryl dipyrrindiones are discussed. In this context, the synthesis of a dimethoxydipyrrin is discussed along with its coordination to zinc to form a homoleptic complex. In Chapter 4, the synthesis of five pyridine dipyrrolinone ligands is described. The ligands coordinate palladium(II) in square planar geometries engaging an adventitious aqua ligand in hydrogen-bonding interactions. Electrochemical studies showed that the replacement of the central pyrrole with a pyridine makes ligand-based redox chemistry less accessible compared to that of trypyrrindione systems. In addition, the para-substituents on the pyridine ring had no major effects on the electronics of the complexes. These ligands react with gold(III) to form a gold(II) dimer, and crystallographyic analysis shows a chiral complex in which the chirality is induced by the twisting of the pyridine dipyrrolinone ligand due to stabilizing pi interactions. The gold(II) dimers are inert to thiols and do not interact with biomolecules such as thioredoxin reductase and DNA. Upon examination of their antiproliferative activities in A2780 ovarian cancer cells, the complexes had IC50 values in the low micromolar range and therefore showcased a novel class of gold-based compounds that will be investigated for anticancer applications.