Structural and reactivity relationships in aryland alkylamine bisphosphine complexes of Tc(I) and Re(I)

[摘要] English: The research project presents the synthesis and evaluation of the radiopharmaceutical model type of fac-[MI(CO)3]+ (M = Re or 99Tc] cores bearing neutral bidentate diphosphinoamine (PNP) ligands. A range of PNP ligands and fac-[M(CO)3(PNP)]+ (M = Re or 99Tc) complexes were prepared using methods described in literature and characterized by means of NMR, IR and Xray crystallography. These ligands were systematically altered in terms of electronic and steric properties. A total of sixteen ligands were evaluated during this study, namely N,N-Bis-(diphenylphosphino)- p-toluidine (1), N,N-Bis(diphenylphosphino)-4-chloroaniline (2), N,NBis( diphenyl-phosphino)-4-fluoroaniline (3), N,N-Bis(diphenylphosphino)-N-Bocethylenediamine (4), N,N-Bis(di-p-tolylphosphino)-p-toluidine (5), N,N-Bis(di-ptolylphosphino)- o-toluidine (6), N,N-Bis(di-p-tolyl-phosphino)cyclobutylamine (7), N,N-Bis(dip- tolylphosphino)cyclohexylamine (8), N,N-Bis(diphenyl-phosphineoxide)-p-toluidine (1a), N,N-Bis(diphenylphosphineoxide)-4-chloroaniline (2a), N,N-Bis(di-phenylphosphineoxide)-4- fluoroaniline (3a), N,N-Bis(diphenylphosphineoxide)-N-Boc-ethylene-diamine (4a), N,N-Bis(dip- tolylphosphineoxide)-p-toluidine (5a), N,N-Bis(di-p-tolylphosphineoxide)-o-toluidine (6a), N,N-Bis(di-p-tolylphosphineoxide)cyclobutylamine (7a) and N,N-Bis(di-p-tolylphosphineoxide) cyclohexylamine (8a). The solid state crystal structures of the ligands pFPh-PhPNP (3), Cbutyl-4-p-tolyl (7), Chzyl-4-ptolyl (8), pFPh-PhPNPO (3a), 5-p-tolyl-PNPO (5a) and Chzyl-4-p-tolyl-PNPO (8a) were reported and described, and revealed various interesting structural conformations. The reported X-ray crystallographic structure determinations further included six rhenium(I) and one technetium-99(I) tricarbonyl complexes namely: fac-[Re(pTol-PhPNP)(CO)3(OiPr)] (1c), fac- [Re(pClPh-PhPNP)(CO)3Br] (2c), fac-[Re(pFPh-PhPNP)(CO)3Br] (3c), fac-[Re(NBoc- PhPNP)(CO)3Br] (4c), fac-[Re(Cbutyl-4-p-tolyl)(CO)3Br] (7c), fac-[Re(Chzyl-4-ptolyl)( CO)3Br] (8c) and fac-[99Tc(Chzyl-4-p-tolyl)(CO)3Cl] (8d) respectively. Four of the reported solid-state rhenium complex structures showed a statistical disorder of the bromido ligand on the apical Br-Re-CO axes. A kinetic study of the formation of fac-[Re(NBoc-PhPNP)(CO)3Br] was conducted utilizing 31P time-resolved NMR. Experimental evidence indicated that the reaction proceeded towards product formation without any significant side reactions. Although limited data was available for this section, acceptable rate laws were identified and proposed, the most feasible consisting of a rapid pre-equilibrium followed by a rate-determining ring-closure by the PNP ligand (K1 = 58(16) M-1, k2 = 0.0013(1) s-1). Preliminary substitution reactions of the bromido ligand in fac- [Re(CO)3(PNP)Br] complexes with entering ligands such as PTA, pyridine and SCN- ions were conducted and the results illustrated that none of the entering ligands could displace the bromine ligand. Preliminary anti-mitochondrial activity of selected non-coordinated PNP ligand namely pTol- PhPNP (1), pClPh-PhPNP (2), pFPh-PhPNP (3) Chzyl-4-p-tolyl (8) and their respective fac- [Re(CO)3(PNP)Br] complexes were tested on Eremothecium ashbyii and Nadsonia fulvescens yeast cells. With the exception of pTol-PhPNP (1), none of the compounds evaluated displayed any cytotoxicity towards the Eremothecium ashbyii and Nadsonia fulvescens yeast cells.

[发布机构] University of the Free State