Host–GuestComplexes of Cyclopentadienyl IronDicarbonyl (CpFe(CO)₂) CO-Releasing Molecules with Cucurbit[7]uril

Iron­(II) cyclopentadienyl carbonyl complexes are promising as CO-releasing molecules (CORMs) for therapeutic applications. In common with other metallodrugs, the practical application of Fe-CORMs may require their conjugation with biocompatible carriers to improve their bioavailability and protect them from premature degradation. Here, we show that the CO-releasing properties of the complexes [CpFe­(CO)₂Cl] (<b>1</b>) and [CpFe­(CO)₂CH₂CONH₂] (<b>2</b>) are retained when noncovalently encapsulated within cucurbit[7]­uril (CB7), a well-established drug-enhancing excipient. The inclusion compounds were characterized in the solid-state by single-crystal and powder XRD, ATR-IR spectroscopy, Raman spectroscopy, TGA, and ¹³C­{¹H} CP MAS NMR. In the crystal structure of <b>2</b>@CB7, there are two crystallographically independent [<b>2</b>@CB7] binary complexes that differ in the orientation of the guest molecules inside the CB cavity. High-resolution ESI-MS and ¹H NMR studies verified the formation and stability of 1:1 <b>2</b>@CB7 inclusion complexes in an aqueous solution. In a physiological buffer, complex <b>2</b> is stable in the dark, but releases ca. 1.4 equiv of CO when irradiated with low-power cold white light, with a half-life (<i>t</i>_1/2) of 19.2 ± 1.9 min. The photodecarbonylation behavior of the complexes is largely maintained in the inclusion compounds, with <i>t</i>_1/2 of 10.0 ± 0.6 and 21.1 ± 1.9 min for encapsulated <b>1</b> and <b>2</b>.