Noncovalent Binding of Some New Lipophilic Gadolinium DTPA Complexes to Human Serum Albumin. A Structure-Affinity Relationship

Abstract

Four Gadolinium⋅DTPA complexes bearing long lipophilic alkyl chains were synthesized: two bis[amide] and two 4-substituted derivatives. In two of them (one bis[amide] and one 4-substituted), the alkyl chain ends with a carboxylate function. Their relaxometric properties in H₂O show the self aggregation of Gd⋅DTPA-BdodecylAmide, the better stability of the 4-substituted derivatives vs. Zn transmetallation, and the very good stability of Gd⋅(4-(carboxyundecylisothiourea-Bz)DTPA). Amongst the four compounds, only Gd⋅(4-(carboxyundecylisothiourea-Bz)DTPA) shows a strong interaction with human serum albumin (HSA) as demonstrated by proton relaxometry and ESI mass spectrometry. These data highlight the importance of the negative charge on the alkyl chain in the context of the interaction of Gd⋅(4-substituted DTPA) derivatives with HSA.