Room-Temperature Synthesis of Re(I) and Tc(I) Metallocarboranes

A series of carborane derivatives bearing guanidine substituents were prepared and characterized, and their reactivity toward Re(I) and Tc(I) in aqueous media was evaluated. Guanidinylation was achieved by treating 1-aminomethyl-1,2-closo-dodecaborane with N 1,N 2-di-Boc-1H-pyrazole-1-carboxamidine, and the associated N-ethyl derivative, which produced the desired products in good (circa 50%) yield. These were deprotected and converted to the corresponding nido-carboranes, which, when combined with [M(CO)3(H2O)3]+ (M = Re and 99mTc) at room temperature for 3 h or 35 °C for 1 h, afforded the corresponding η5-metallocarborane complexes. Corresponding reactions involving carboranes without basic substituents generally require microwave heating at temperatures greater than 150 °C. The rate, yields, and the temperature of the reaction appear to be dependent on the basicity of the guanidines tested. The biodistribution of two of the 99mTc complexes, which are stable indefinitely in solution, were evaluated in vivo in CD1 mice and showed that the 99mTc–carboranyl guanidine complexes clear key nontarget organs and tissues within one half-life (6 h) and have properties that are desirable for developing targeted molecular imaging probes.