Alkyl isonitriles, R—NC, have previously been shown to ligate the heme (haem) iron of cytochromes P450 in both accessible oxidation states (ferrous, Fe²⁺, and ferric, Fe³⁺). Herein, the preparation of four steroid-derived isonitriles and their interactions with several P450s, including the steroidogenic CYP17A1 and CYP106A2, as well as the more promiscuous drug metabolizers CYP3A4 and CYP2D6, is described. It was found that successful ligation of the heme iron by the isonitrile functionality for a given P450 depends on both the position and stereochemistry of the isonitrile on the steroid skeleton. Spectral studies indicate that isonitrile ligation of the ferric heme is stable upon reduction to the ferrous form, with reoxidation resulting in the original complex. A crystallographic structure of CYP17A1 with an isonitrile derived from pregnanalone further confirmed the interaction and identified the absolute stereochemistry of the bound species.

烷基异腈 (R-NC) 先前已被证明可以连接两种可氧化态（亚铁，Fe ²⁺和三价铁，Fe ³⁺）的细胞色素 P450 的血红素 (haem) 铁。本文描述了四种类固醇衍生的异腈的制备及其与几种 P450 的相互作用，包括类固醇生成 CYP17A1 和 CYP106A2，以及更混杂的药物代谢物 CYP3A4 和 CYP2D6。研究发现，对于给定的 P450，血红素铁与异腈官能团的成功连接取决于异腈在类固醇骨架上的位置和立体化学。光谱研究表明，三价血红素的异腈连接在还原为二价铁形式时是稳定的，并且再氧化产生原始复合物。CYP17A1 与孕酮衍生的异腈的晶体结构进一步证实了相互作用并确定了结合物质的绝对立体化学。