| This work focuses on the synthesis and study of the water-soluble variants of an iron (III)-oxido-pyrazolato cluster, which retain the octanuclear entity, the Fe8(&mgr;4-O)4-motif common in minerals, allowing the evaluation of its effect on water-proton relaxation. Determination of the longitudinal and transverse relaxation rates of water in presence of the water-soluble paramagnetic cluster, establish the efficacy of this compound as a MRI contrast agent.;This Thesis describes the efforts through two different routes to synthesize the water-soluble derivative of the organosoluble [Fe8O4(4-R-pz) 12Cl4] cluster: (1) substitution at, of the 4-position of the pyrazole by a hydrophilic group, successfully leads to the synthesis of water-soluble analogs [Fe8O4(4-OHCH2CH 2-pz)12Cl4] and [Fe8O4(4-OHCH 2CH2CH2-pz)12Cl4]. These water-soluble analogues have been characterized by FTIR, 1H NMR, UV-Vis spectroscopy, X-ray crystallography and ESI-mass spectrometry. (2) Substitution of the four terminal halides by hydrophilic groups did not yield water-soluble product. Several organosoluble clusters were also synthesized, which though not useful for studies towards MRI contrast enhancement, were found to have interesting NMR properties.;Solubility of [Fe8O4(4-OHCH2CH 2-pz)12Cl4] in water, saline, buffer, protein solutions, including its behavior in aqueous solution with respect to pH, ionization, particle size and charge distribution, revealed the hydrolysis of Fe-Cl bond leading to the coexistence of [Fe8O4Cl 4-x-y(H2O)y(OH)x]y+ species. Aggregation among these hydrolyzed species lead to larger clusters. Preliminary theoretical studies by DFT methods concur with the experimental observations.;The relaxivity of the [Fe8O4(4-OHCH2CH 2-pz)12Cl4] compound was determined by spin inversion recovery and Carr-Purcell-Meiboom-Gill experiments: Plots of 1/Ti vs [Fe8] (i = 1, 2) gave r1=0.75 mM-1s -1, r2= 4.02 mM-1s-1 (at 1.3 T), r1=0.70 mM-1s-1, r2= 10.0 mM-1s-1(at 7.2 T), r 1= 0.70 mM-1s-1, r2= 15.0 mM -1s-1 (at 11.9 T) at 298 K. The r2/r 1 ratio identifies 3A as a T2 contrast agent, clinching the discovery of the first iron-based molecular T2 contrast agent. Relaxation experiments carried out at different fields (1.3 T, 7.2 T, 11.9 T) showed an increase in transverse relaxivity with higher magnetic fields, while the longitudinal relaxivity remained invariant.;Phantom images, done in order to visualize the effect of the contrast agent in vitro, are in accord with the results of the relaxometric studies. |
