title: Azide vs Alkyne Functionalization in Pt(II) Complexes for Post-treatment Click Modification: Solid-State Structure, Fluorescent Labeling, and Cellular Fate.
abstract: 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.
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Regina
authors.initials: R
authors.lastname: Wirth
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: White
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Moghaddam
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Aurora L
authors.initials: AL
authors.lastname: Ginzburg
authors.affiliation: CAMCOR, University of Oregon , 1443 East 13th Avenue, Eugene, Oregon 97403, United States.
authors.forename: Lev N
authors.initials: LN
authors.lastname: Zakharov
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Haley
authors.affiliation: Department of Chemistry & Biochemistry and Institute of Molecular Biology, University of Oregon , Eugene, Oregon 97403-1253, United States.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: DeRose