Testing lanthanide(iii) complex stability using Eu(iii) luminescence – documenting complex formation and stability in any media

Abstract

Metal complexes in solution are relevant for diagnostics and therapy. Lanthanide(III) complexes are used in the clinic. As metal complexes are inherently labile, the stability of new complexes must be assessed. Here, we report a quick and straightforward method for testing complex stability using europium(III) luminescence. The performance of new complexes is compared to [Ln·DOTA]⁺ (DOTA = 1,4,7,10-tetraazadodecane-1,4,7,10-tetraacetic acid) and is challenged with DTPA (DTPA = diethylenetriamine pentaacetic acid). DOTA complexes are as stable as peptides at physiological pH, and DTPA forms highly thermodynamically stable lanthanide(III) complexes [Ln·DTPA]²⁻. By using these properties, a method to test lanthanide complex stability in solution was developed. Here, 1 (Kryptofix221, Cryptand[221] = 4,7,13,16,21-pentaoxa-1,10-diazabicyclo[8.8.5]tricosane), 2 (Kryptofix222, Cryptand[222] = 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane), and 3 (macropa, N,N′-bis[(6-carboxylate-2-pyridil)methyl]-4,13-diaza-18-crown-6) were used as lanthanide(III) complexes of unknown stability. Samples of each ‘new’ ligand system were prepared, and already here 1 and 2 were found to deviate significantly from the baseline for complex formation, while 3 formed a distinct europium(III) complex. Challenging the complexes with DTPA showed that the ‘new’ complexes were labile in our chosen medium. These results were supported by determination of solvation numbers q, and it was concluded that the method is robust and easy to use.