NEW NONIONIC WATER-SOLUBLE PORPHYRINS - EVALUATION OF MANGANESE(III) POLYHYDROXYLAMIDE PORPHYRINS AS MRI CONTRAST AGENTS

A new series of metalloporphyrins (M = zinc(II) and manganese(III)), u tilizing polyhydroxylamide substituents to achieve water solubility, h as been synthesized and spectroscopically characterized. Two of these compounds, [Mn-III(TPPAS)Cl] and [Mn-III(TPPIS)Cl],have been evaluated as potential MRI contrast enhancement agents. The water proton magnet ic relaxation rate, (1/T-1), of aqueous [Mn-III(TPPAS)Cl] solutions ha s been measured as a function of held strength over the range of Larmo r frequencies from 0.01 to 30 MHz. Results show a typical relaxation r ate pattern, similar to other water-soluble manganese(III) porphyrin c ompounds, over this frequency range. Conductivity and osmolality measu rements for [Mn-III(TPPAS)Cl] in water demonstrate complete dissociati on of the chloride ion to yield [Mn-III(TPPAS)(H2O)(2)](+). The two ax ial water ligands provide a reasonable explanation as to the source of the greater than expected proton relaxation rate of manganese(III) po rphyrin compounds, in general. Variable-temperature NMR studies of the H(2)TPPAS and H2TPPIS free ligands reveal the occurrence of proton ta utomerism, as indicated by two temperature dependent H-beta pyrrole pr oton signals. Actual magnetic resonance images of Sprague-Dawley rats, to which [Mn-III(TPPAS)Cl] had been administered, showed significant image enhancement in the heart, liver, lungs and gastrointestinal trac t. However, with an acute toxicity of 0.1 mmol kg(-1), the cationic [M n-III(TPPAS) (H2O)(2)](+) compound is too toxic for clinical use. (C) 1998 Elsevier Science S.A. Al rights reserved.