Chemistry and biology of tricarbonyl complexes of technetium and rhenium

Abstract

Chapter One: Two of the most famous tripodal ligands, Kliui's cyclopentadienyltris(dialkylphosphito)cobaltate(III) and Trofimenko's hydrotris(1-pyrazolyl)borate, were studied with respect to their reactivity towards Alberto's tris(solvento)tricarbonyltechnetium(I) and tris(solvento)tricarbonylrhenium(I) cations. The reaction of [M(H2O)3(CO)3]+ (M = Tc, Re) with Na[CpCo[PO(OR)2]3] (NaLOR; R = Me, Et) in water produced the compounds M(CO)3(LoR). The two compounds M(CO)3(LoEt) were structurally characterized by single crystal X-ray crystallography. In both cases, the ligand LOEt was bound to the metal center in a tridentate fashion utilizing an 000 donor set. The ligands LOR can be used as models for facially coordinated triaqua groups owing to their position in the spectrochemical series. Therefore, these four compounds, M(CO)3(LoR), can be considered structural models for [M(H2O)3(CO)3]+. The reaction of [Re(CO)3(sol)3]+ (sol = H20, MeOH, MeCN) with K[HB(pz)3] (KTp) has yielded a variety of products depending on the solvent used. For the two protic solvents, mixtures of TpRe(CO)3 and a byproduct (NEt4)[Re2(CO)6(jg-pz)2([t-OR)] (R = H or Me) were obtained. The methoxy-bridged species has been isolated and fully characterized, and the crystal structure has been determined. While a chemical separation of the analogous hydroxy-bridged species from TpRe(CO)3 was not accomplished, a crystal of the compound was selected from the mixture, and a partial crystal structure was solved. When an aprotic solvent such as acetonitrile was used, only TpRe(CO)3 was obtained and was recovered in high yield.

(cont.) Chapter Two: N-(2-mercaptoethyl)picolylamine (MEPAH) was studied as a potentially biologically relevant ligand for the 'fac-[M(CO)3]+" core (M = Re, 99Tc, 99mTc). To this end, the complex Re(CO)3(MEPA) was synthesized. The reaction of MEPAH with fac-[Re(CO)3(MeCN)3]+ took place over the course of seconds, showing the high affinity possessed by this ligand for the "fac-[Re(CO)3]+" core. A single crystal X-ray diffraction study was performed, confirming the nature of Re(CO)3(MEPA), a rare mononuclear rhenium(I) thiolate complex. Exploration into derivatization of the ligand backbone has afforded the analogous N-ethyl complex, Re(CO)3(MEPA-NEt). Further work has given rhenium complexes of bioconjugated ligands, whereby biologically active molecules have been tethered to the ligand framework. The high affinity of the ligand for the metal, coupled with the ease of its derivatization, implies that this ligand system is promising for the purposes of 99mTc radiopharmaceutical development. Chapter Three: The bioevaluation of 99mTc complexes of derivatives of MEPAH is described. Complexes analogous to the tricarbonylrhenium(I) complexes described in Chapter 2 were synthesized and characterized by HPLC. After confirmation of the composition of these 99mTc complexes, in vitro and in vivo studies were performed. These compounds of the "fac-[99mTc(CO)3]+' core, containing the biologically active molecules morpholine and nornicotine, were evaluated for uptake by melanoma and brain tissue, respectively, in mice.