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.