On the Issue of Biological Activity of Cobalt bis(dicarbollide) Derivatives: Conformation of the [8-EtO-8’-I-3,3’-Co(1,2-C2B9H10)2]− Anion

The conformational mobility of the [8-EtO-8’-I-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ anion, which has been chosen as a model compound for many potential drugs based on cobalt bis(dicarbollide), was studied by ¹H NMR spectroscopy, single crystal X-ray diffraction and quantum chemical calculations. According to the results of quantum chemical calculations, the most favourable conformation for [8-EtO-8’-I-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ is the transoid conformation, which is stabilized by one pair of CH···I and one pair of CH···O(Et) intramolecular hydrogen bonds between the dicarbollide ligands. However, the difference in energy between the transoid and gauche conformations is rather small, while the cisoid conformation is energetically extremely unfavorable. The transoid conformation of the anion was found in the crystal structure of (Bu₄N)[8-EtO-8’-I-3,3’-Co(1,2-C₂B₉H₁₀)₂], while the ¹H NMR spectroscopy data suggest the presence of an equilibrium between the transoid and gauche conformations in solution. Both the transoid and gauche conformations of the anion have a low dipole moment, which is characteristic of most low molecular weight drugs. This may explain the ease of penetration of molecules containing this fragment through biological membranes and their observed increased biological activity.