Novel bifunctional [16]anes4-derived chelators for soft radiometals

Natan J.W. Straathof, Charlotte B. Magnus, Fedor Zhuravlev, Andreas I. Jensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

55 Downloads (Pure)


The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS4 macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS4 in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions.

Original languageEnglish
Article number4603
Issue number15
Number of pages9
Publication statusPublished - 2021


  • Bifunctional chelators
  • Bio-conjugation
  • Radiation therapy
  • Sulfur containing macrocycles


Dive into the research topics of 'Novel bifunctional [16]anes4-derived chelators for soft radiometals'. Together they form a unique fingerprint.

Cite this