Cyclopentadienyl Chemistry in Water: Synthesis and Properties of Bifunctionalized [(η5‑C5H3{COOR}2)M(CO)3] (M = Re and 99mTc) Complexes

Complexes of the [(η5-C5H4COOR)­M­(CO)3] type (M = 99mTc, Re; R = targeting function) are basic bioorganometallic structures with the potential of combining molecular imaging (99mTc) with therapy (cold Re or 186/188Re). So far, the single carboxylate group on the cyclopentadienyl ring (Cp–) limited targeting to one function. The concept of Cp– as a scaffold for attaching biological molecules could be extended substantially with two or more functionalities bound to the Cp– ligand. Accordingly, the rarely studied bis-substituted cyclopentadienyl ligands [C5H3(1,2-COOMe)2]− and [C5H3(1,3-COOMe)2]− were synthesized and their coordination to the fac-{M­(CO)3}+ moiety was studied in water. Both ligands are deprotonated at physiological pH and do not undergo Diels–Alder reactions. In water, they react directly with [Re­(OH2)3­(CO)3]+ to form [(η5-C5H3{1,2-COOMe}2)­Re­(CO)3] and [(η5-C5H3{1,3-COOMe}2)­Re­(CO)3]. Controlled hydrolysis at neutral to alkaline pH gives the monoesters and fully hydrolyzed [(η5-C5H3{1,2-COOH}2)­Re­(CO)3] and [(η5-C5H3{1,3-COOH}2)­Re­(CO)3]. Thermal treatment leads to decarboxylation and formation of [(η5-C5H4COOH)­Re­(CO)3]. The corresponding 99mTc homologues are directly accessible under slightly acidic conditions from [99mTcO4]− in high yields. In the presented strategy, the Cp– ring acts as a scaffold for attaching multiple targeting agents or pharmacophores at the same time.