Coupling approaches for [Pt(1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diamminocyclohexane)dihydroxide]²⁺ using hydrazone and oxime ligation

Established methods for conjugating biomolecules to non-conventional complexes such as [Pt(1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diamminocyclohexane)(OH)₂]²⁺ (Pt^IVPhenSS) are limited in scope. To address this, we investigated amide, ester, and carbamate strategies, however we encountered significant issues with stability and thus yield. To overcome these shortcomings, we examined an imine linking strategy, using hydrazone and oxime ligation, which proved to be rapid and effective. Here we detail the synthesis of seven platinum(IV) complexes derived from Pt^IVPhenSS which demonstrate the suitability of an imine conjugation method as a potential linking strategy. Furthermore, we tested these complexes in broad panel of cancer cell lines, identifying that this strategy did not diminish the biological activity of the complex.