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Updated: Oct 19, 2025

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry
Published on: February 4, 2017
SPAAC iClick: progress towards a bioorthogonal reaction in-corporating metal ions
Yu-Hsuan Shen1, Alec M Esper1, Ion Ghiviriga1
1University of Florida, Department of Chemistry, Center for Catalysis, P.O. Box 117200, Gainesville, FL, 32611, USA. veige@chem.ufl.edu.
Abstract:
Combining strain-promoted azide-alkyne cycloaddition (SPAAC) and inorganic click (iClick) reactivity provides access to metal 1,2,3-triazolates. Experimental and computational insights demonstrate that iClick reactivity of the tested metal azides (LM-N3, M = Au, W, Re, Ru and Pt) depends on the accessibility of the azide functionality rather than electronic effects imparted by the metal. SPAAC iClick reactivity with cyclooctyne is observed when the azide functionality is sterically unencumbered, e.g. [Au(N3)(PPh3)] (Au-N3), [W(η3-allyl)(N3)(bpy)(CO)2] (W-N3), and [Re(N3)(bpy)(CO)3] [bpy = 2,2'-bipyridine] (Re-N3). Increased steric bulk and/or preequilibria with high activation barriers prevent SPAAC iClick reactivity for the complexes [Ru(N3)(Tp)(PPh3)2] [Tp = tris(pyrazolyl)borate] (Ru-N3), [Pt(N3)(CH3)(PPr3)2] [Pr = isopropyl] (Pt(II)-N3), and [Pt(N3)(CH3)3]4 ((PtN3)4). Based on these computational insights, the SPAAC iClick reactivity of [Pt(N3)(CH3)3(P(CH3)3)2] (Pt(IV)-N3) was successfully predicted.
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