Click Chemistry and Radiochemistry: An Update

Abstract

The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide−alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide−alkyne cycloaddition and the inverse electron-demand Diels−Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based in vivo pretargeting.

Hydroxyapatite Nanocrystals Integrated into Mesoporous Silica for Sustained Delivery of Doxorubicin

“…Despite their undeniable advantages, radiolabeling techniques come with certain limitations and considerations. The choice of the appropriate radionuclide and labeling method must align with the specific research objectives, ensuring minimal interference with the material’s biological activity and physicochemical properties. , Additionally, the potential alteration of the material’s behavior due to the incorporation of the radiolabel should be carefully evaluated to avoid misleading conclusions during biodistribution analysis. Furthermore, the inherent radioactive decay of the label may raise concerns regarding radiation exposure, necessitating adherence to stringent safety protocols to protect researchers and the environment.…”

eTFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors

“…Considering all functional groups present in the peptide-chelator conjugate 10 , we decided to selectively couple the dye on the chelator at the late stage of the synthesis via click chemistry. We selected the strain promoted alkyne-azide cycloaddition (SPAAC), instead of the classical copper-catalyzed azide-alkyne Huisgen cycloaddition, to avoid the use of copper and its potential complexation by the chelate(Chen et al 2012 ; Cai and Anderson 2014 ; Bauer et al 2023 ).…”

Synthesis of C3-Substituted N1-tert-Butyl 1,2,4-Triazinium Salts via the Liebeskind–Srogl Reaction for Fluorogenic Labeling of Live Cells

“…Chemical reactions compatible with biological systems have applications in chemical biology, biomedicine, imaging, diagnosis, − and therapy. − Among the many bioorthogonal reactions now available, the inverse electron demand Diels–Alder reaction of 1,2,4,5-tetrazines with strained dienophiles meets the strict criteria for use in living organisms, − including humans . In recent years, researchers have made considerable efforts to fine-tune this bioorthogonal reaction for use in diverse applications. ,,, In addition to other promising synthetic methods, , cross-coupling reactions involving tetrazines provide many opportunities for modifying these heterodienes.…”