Inverse electron‐demand Diels‐Alder (iEDDA) bioorthogonal conjugation of half‐sandwich transition metallocarbonyl entities to a model protein. (18th January 2020)

• Record Type: Journal Article
• Authors: Jamroz, Daria; Fischer‐Durand, Nathalie; Palusiak, Marcin; Wojtulewski, Sławomir; Jarzyński, Szymon; Stępniewska, Marlena; Salmain, Michèle; Rudolf, Bogna
• Is Part Of: Applied organometallic chemistry. Volume 34:Number 4(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-01-18
• Subjects: iEDDA -- norbornene -- tetrazine -- metallocarbonyl complex -- bioconjugation; Organometallic chemistry -- Periodicals; Organometallic compounds -- Periodicals; 547.05
• DOI: 10.1002/aoc.5507
• Languages: English
• ISSNs: 0268-2605

Abstract

Abstract : Novel transition metallocarbonyl complexes carrying a norbornene or an oxanorbornene group were synthesized by [4 + 2] cycloaddition between the organometallic maleimide dienophiles and cyclopentadiene or furan, respectively. The oxanorbornene adduct was obtained as a mixture of endo and exo isomers as confirmed by X‐ray diffraction and NMR spectroscopy. The (oxa)norbornene groups further provided convenient chemical reporters to carry out inverse electron demand Diels‐Alder (iEDDA) reactions with tetrazine derivatives. Detailed kinetic studies with a model tetrazine revealed that faster rates of reaction were determined with both isomers of the oxanorbornene complex with respect to the norbornene complexes. Eventually, incorporation of metallocarbonyl entities into bovine serum albumin equipped with tetrazine handles was achieved as shown by IR spectroscopy of the protein conjugates. Abstract : A series of metallocarbonyl norbornenes was synthesized and their reactivity examined towards a model protein carrying the tetrazine entity. Infrared spectral characterization of the bioconjugates showed the presence of two characteristic bands in the 2000 cm −1 region confirming the successful labelling via iEDDA reaction.