Click chemistry has become a commonly used synthetic method due to the simplicity, efficiency, and high selectivity of this class of chemical reactions. Since their initial discovery, further click chemistry methods have been identified and added to the toolbox of click chemistry reactions for biomedical applications. However, selecting the most suitable reaction for a specific application is often challenging, as multiple factors must be considered, including selectivity, reactivity, biocompatibility, and stability. Thus, this review provides an overview of the benefits and limitations of well-established click chemistry reactions with a particular focus on the importance of considering reaction rates, an often overlooked criterion with little available guidance. The importance of understanding each click chemistry reaction beyond simply the reaction speed is discussed comprehensively with reference to recent biomedical research which utilized click chemistry. This review aims to provide a practical resource for researchers to guide the selection of click chemistry classes for different biomedical applications.

Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Methods: Here, via the copper-mediated ¹⁸F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the ¹⁸F-radiolabeled isotopolog of the Food and Drug Administration–approved PARP inhibitor olaparib. The use of the ¹⁸F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. Results: ¹⁸F-olaparib was taken up selectively in vitro in PARP-1–expressing cells. Irradiation increased PARP-1 expression and ¹⁸F-olaparib uptake in a radiation-dose–dependent fashion. PET imaging in mice showed specific uptake of ¹⁸F-olaparib in tumors expressing PARP-1 (3.2% ± 0.36% of the injected dose per gram of tissue in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of ¹⁸F-olaparib increased by 70% (P = 0.025). Conclusion: Taken together, we show that ¹⁸F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.

The development of medical imaging probes for magnetic resonance imaging (MRI) is a particularly dynamic area of research. At present, many prominent groups are dedicating significant resources to tailoring and optimising the performance of potential contrast agents. Whilst ¹H MRI has become an indispensable tool for the imaging of disease states, it frequently suffers from low contrast owing to background signal from intrinsic ¹H. As a result, increasing attention is being directed at compounds containing ¹⁹F as this nucleus has a similar NMR sensitivity to ¹H and, importantly, intrinsic ¹⁹F signals are virtually undetectable in vivo. For several decades, perfluorinated molecules (in which all of the C–H bonds in the parent molecule have been replaced with C–F bonds) and highly fluorous gases such as SF₆ have traditionally been used for these kinds of investigations and there have been some excellent reviews of these compounds and their applications. However, recently ¹⁹F imaging is showing signs of evolution, particularly as there have been several reports of fluorinated responsive (smart) agents, micelles, dendrimers and hyperbranched polymers being investigated as targets for ¹⁹F-MRI. Furthermore, examples of multimodal contrast agents containing ¹⁹F nuclei are also starting to emerge. In this review we aim to summarise these exciting recent chemical developments.

The synthesis of the novel ligand tris(2,2′-bipyrid-6-yl) methanol (L¹) is described. Co-ordination of the ligand to the first row transition metals (Mn²⁺ –Zn²⁺ ) as well as Cd²⁺ showed that the ligand formed complexes close to trigonal prismatic in geometry in the solid state. Analysis of the geometry of the co-ordination spheres showed varying degrees of trigonal prismatic and octahedral character. For each d-electron configuration, this could be related to the relative differences in ligand field stabilisation energies for the two geometries.