Oxidative Cyclization and Enzyme-free Deiodination of Thyroid Hormones

19 January 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


We introduce the first non-enzymatic deiodination of thyroid hormones from a so far unknown hypervalent iodaoxinium state. After developing oxidative processes for thyroxine(T4)-derived model cyclic diaryliodonium salts, we successfully produced an iodaoxinium salt through the direct oxidation of O-and N-protected T4. DFT calculations revealed a novel halogen bonding-based deiodination mechanism, circumventing the traditional selenium-dependent pathways. Our findings open new avenues in thyroid hormone chemistry, suggesting alternative mechanisms for their involvement in metabolic processes, regulation of oxidative stress, and gene expression.


Hypervalent Iodine
Iodonium Salt
Halogen Bonding

Supplementary materials

Supporting Information
Experimental data and spectra


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