Azide vs Alkyne Functionalization in Pt(II) Complexes for Post-treatment Click Modification: Solid-State Structure, Fluorescent Labeling, and Cellular Fate

Tracking of Pt­(II) complexes is of crucial importance toward understanding Pt interactions with cellular biomolecules. Post-treatment fluorescent labeling of functionalized Pt­(II)-based agents using the bioorthogonal Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction has recently been reported as a promising approach. Here we describe an azide-functionalized Pt­(II) complex, cis-[Pt­(2-azido­butyl)­amido-1,3-propane­diamine)­Cl2] (1), containing the cis geometry and difunctional reactivity of cis­platin, and present a comparative study with its previously described alkyne-functionalized congener. Single-crystal X-ray diffraction reveals a dramatic change in the solid-state arrangement with exchange of the alkyne for an azide moiety wherein 1 is dominated by a pseudo-chain of Pt–Pt dimers and anti­parallel alignment of the azide substituents, in comparison with a circular arrangement supported by CH/π­(CC) interactions in the alkyne version. In vitro studies indicate similar DNA binding and click reactivity of both congeners observed by fluorescent labeling. Interestingly, complex 1 shows in vitro enhanced click reactivity in comparison to a previously reported azide-appended Pt­(II) complex. Despite their similar behavior in vitro, preliminary in cellulo HeLa studies indicate a superior imaging potential of azide-functionalized 1. Post-treatment fluorescent labeling of 1 observed by confocal fluorescence microscopy shows nuclear and intense nucleolar localization. These results demonstrate the potential of 1 in different cell line localization studies and for future isolation and purification of Pt-bound targets.