Effects of Substituents on the Properties of Metal-Free MRI Contrast Agents

Abstract

Materials possessing electron spin can shorten the <i>T</i> ₁ relaxation times in magnetic resonance imaging (MRI). For example, gadolinium (Gd) complexes with seven f-orbital electrons are widely used as contrast agents in clinical applications. However, Gd has severe potential side effects, and thus metal-free alternatives are needed. Toward this end, we synthesized seven NO radicals consisting of a dioxa-azaspiro[4.5]decane framework having various substituents, <b>DAD-X</b> (X = methyl, ethyl, <i>n</i>-propyl, <i>c</i>-propyl, vinyl, phenyl, and 2-pyridyl), that functioned as metal-free MRI contrast agents. The relationship between (i) water-proton relaxivity and log <i>P</i> and (ii) reactivity for ascorbic acid and the spin density of the NO oxygen atom were established, which provided a basis for the rational design of practical metal-free contrast agents.