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Promiscuity in Molecular Mimics of the Cysteine Dioxygenase: Effects of Selenium in the Substrate and Cobalt as the Central Metal Ion

Title: Promiscuity in Molecular Mimics of the Cysteine Dioxygenase: Effects of Selenium in the Substrate and Cobalt as the Central Metal Ion
Authors: Weißer, Kilian; Weber, Edgar T. K.; Velmurugan, Gunasekaran; Cula, Beatrice; Krause, Konstantin B.; Wolff, Siad; Bin Mubarak, Muhammad Qadri Effendy; Comba, Peter; De Visser, Samuel; Limberg, Christian
Source: Weißer, K, Weber, E T K, Velmurugan, G, Cula, B, Krause, K B, Wolff, S, Bin Mubarak, M Q E, Comba, P, De Visser, S & Limberg, C 2025, 'Promiscuity in Molecular Mimics of the Cysteine Dioxygenase: Effects of Selenium in the Substrate and Cobalt as the Central Metal Ion', Angewandte Chemie. International Edition. https://doi.org/10.1002/ange.202507578
Publication Year: 2025
Collection: The University of Manchester: Research Explorer - Publications
Subject Terms: nonheme iron enzymes; dioxygenase model; cystein dioxygenase; selenium; O2 activation
Description: Cysteine dioxygenase (CDO) catalyzes the conversion of cysteine with dioxygen to yield cysteine sulfinic acid, which lies at the branching point of cysteine catabolism. Despite many years of research there are still many questions related to its functioning. Thus, CDO is inactive with selenocysteine (Sec) or when the central iron ion is replaced by cobalt. In this context we report here biomimetic CDO models with bound selenocysteamine substrate ligands, namely [Tp Mes Fe(Se‐CH 2‐ CH 2‐ NH 2 )] and [Tp Mes* Fe(Se‐CH 2‐ CH 2‐ NH 2 )] (with Tp Mes = hydrotris(3-mesitylpyrazol-1-yl)borate, Tp Mes* = hydrobis((3-mesitylpyrazol-1-yl)(5-mesitylpyrazol-1-yl)borate) and in addition a cobalt-analogue [Tp Mes Co(Se‐CH 2‐ CH 2‐ NH 2 )]. Upon treatment of the Fe/Se homologues with O 2 – as in case of the parent cysteamine-bound complexes – the dioxygenation of the chalcogen atoms was observed. This suggests that the lack in reactivity of CDO-Sec towards O 2 does not originate in the electronic situation but in the surrounding protein matrix. Subsequent DFT calculations indeed showed lower initial barriers for selenocysteamine than for cysteamine in support of the experimental work. Replacing Fe by Co in the complex, i.e. [Tp Mes Co(Se‐CH 2‐ CH 2‐ NH 2 )], was found to – more slowly but selectively – yield the dioxygenation product Tp Mes Co(O 2 Se‐CH 2‐ CH 2‐ NH 2 )]. Hence, this is an experimental observation of a dioxygenation with O2 mediated by a cobalt center in a molecular compound, which is so far without precedence.
Document Type: article in journal/newspaper
Language: English
ISSN: 1433-7851; 1521-3773
Relation: info:eu-repo/semantics/altIdentifier/pissn/1433-7851; info:eu-repo/semantics/altIdentifier/eissn/1521-3773
DOI: 10.1002/ange.202507578
Availability: https://research.manchester.ac.uk/en/publications/037a46d9-a484-4923-9b04-97691e1d08d1; https://doi.org/10.1002/ange.202507578
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.D23FD081
Database: BASE