Synthesis and reactivity of mixed nitrogen/sulfur metal complexes: Biomimetic models of peptide deformylase

This thesis discusses the design, synthesis, and characterization of model complexes of the active site of the enzyme peptide deformylase (PDF). Specifically, we describe the formation of small-molecule, biomimetic compounds containing a two nitrogen, one thiolate donor set as well as the metal complexes of these ligands. We have focused on the formation of the zinc-hydroxide complex of the 2-methyl-1-[methyl-(2-pyridin-2-ylethyl)amino]propane-2-thiolate, or PATH, ligand to model the catalytic hydrolase activity of PDF and report the reactivity of these compounds in herein.; Chapter 1 describes the background and significance of certain metalloenzymes and model complexes. The metalloenzymes carboxypeptidase A (CPA), thermolysin, and carbonic anhydrase (CAII) are described, as background, to a detailed discussion of peptide deformylase. Some important nitrogen containing ligands, such as trispyrazolylborate are also examined.; In Chapter 2, the synthesis and spectroscopic characterization of a new N2S ligand, PATH, is described. The metal complexes obtained from the PATH ligand including (PATH)ZnCH3, (PATH)ZnOH, [(PATH) 2Ni2]Br2 and [(PATH)2Fe2Cl 2] are discussed in detail.; Chapter 3 discusses the hydrolysis of an activated carboxylic ester, 4-nitrophenolate, by [(PATH)ZnOH]. The second order rate constant was determined by the initial rates method and a pH-rate profile was obtained. The p Ka of (PATH)ZnOH was determined by both the pH-rate profile and potentiometric titration. Also, for the first time activation parameters for the reaction between an (N2S)ZnOH complex and an ester were obtained from Arrhenius and Eyring plots. Through these experiments the mechanism of hydrolysis was determined to be simple nucleophilic attack.; In Chapter 4, a number of tripodal pyridyl/alkylthiolate and imidazole/alkylthiolate ligands, including L1H, DEATHMe,Me, and DEATH H,H are described. Their synthesis and spectroscopic characterization by 1H and 13C NMR spectroscopy are given in detail. The first X-ray crystal structures of L1H metal complexes are reported in this chapter.; Chapter 5 encompasses the unfinished work in regards to hydrolysis of phosphate esters. The data indicates that phosphate ester hydrolysis proceeds via a "hybrid" mechanism. The results in this chapter will be compared to Chapter 3, in which the hydrolysis of an activated ester was discussed.