Enhancing the Activity of Drugs by Conjugation to Organometallic Fragments

Resistance to chemotherapy is a current clinical problem, especially in the treatment of microbial infections and cancer. One strategy to overcome this is to make new derivatives of existing drugs by conjugation to organometallic fragments, either by an appropriate linker, or by direct coordination of the drug to a metal. We illustrate this with examples of conjugated organometallic metallocene sandwich and half‐sandwich complexes, Ru(II) and Os(II) arene, and Rh(III) and Ir(III) cyclopentadienyl half‐sandwich complexes. Ferrocene conjugates are particularly promising. The ferrocene–chloroquine conjugate ferroquine is in clinical trials for malaria treatment, and a ferrocene‐tamoxifen derivative (a ferrocifen) seems likely to enter anticancer trails soon. Several other examples illustrate that organometallic conjugation can restore the activity of drugs to which resistance has developed.