The Influence of Amino Group Position on Aryl Moiety of SarAr on Metal Complexation and Protein Labelling

Vincent Jamier (1, 2) , Eskender Mume (3) , Cyril Papamicaël (2) , Suzanne V. Smith (3)

1 ANSTO - Australian Nuclear Science and Technology Organisation [Australie]
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
3 ANU - Australian National University

New hexaazamacrobicyclic cage bi-functional chelators (BFCs), 1-N-(3-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (m-SarAr) and 1-N-(2-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (o-SarAr), were synthesised. Their complexation with selected transitions metal ions i.e. CuII, CoII, and CdII was investigated over a range of pH at micromolar concentrations. CuII was complexed by m-SarAr and o-SarAr rapidly within 5 min in pH range of 5–9 at ambient temperature. In contrast, the complexation of CoII and CdII by these ligands was slower. The conjugation efficiencies of p-SarAr, m-SarAr, and o-SarAr to bovine serum albumin (BSA) were compared under various reactions. Conditions were optimised to a molar ratio of BSA/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/BFC of 1 : 250 : 50 in pH 5 buffer for 30 min at ambient temperature. Under these conditions, the average number of p-SarAr, m-SarAr, or o-SarAr attached to BSA were determined to be 2.21 ± 0.16, 4.90 × 10–1 ± 2.48 × 10–2, and 2.67 × 10–2 ± 2.67 × 10–3, respectively. This fundamental study clearly demonstrates that the position of the amine on the phenyl ring has a significant effect on the metal complexation and conjugation reactions with BSA.

Domains: Chemical Sciences

Vincent Jamier, Eskender Mume, Cyril Papamicaël, Suzanne V. Smith. The Influence of Amino Group Position on Aryl Moiety of SarAr on Metal Complexation and Protein Labelling. Australian Journal of Chemistry, 2016, 69 (9), pp.1054-1061. ⟨10.1071/CH15794⟩. ⟨hal-02046216⟩