Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin

The cationic enantiopure R) and luminescent Eu(III) complex [Eu(bisoQcd)(H2O)(2)] OTf (with bisoQcd = N,N'-bis(2-isaquinolinmethyl)-trarts-1,2diaminocyclohexane N/N1 -diacetate and OTf = triflate) was synthesized and characterized. At physiological pH, the 1:1 [Eu(bisoQcd)(H2O)(2)](+) species, possessing two water molecules in the inner coordination sphere, is largely dominant. The interaction with bovine serum albumin (BSA) was studied by means of several experimental techniques, such as luminescence spectroscopy, isothermal titration calorimeti-y (ITC), molecular docking (MD), and molecular dynamics simulations M11.-.)S). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digito)cin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the complexes. In fact, the presence of isoqiiinolirie rings drives the corresponding complex toward the protein superficial area containing the tryptophan residue 134 (Trp134). As the main consequence, the metal center undergoes the loss of one water molecule upon interaction with the side chain of a glutamic acid residue. On the other hand, the similar complex containing pyridine rings f[Eti(bpcd)(H2O)(2)]Cl with bpcd = N,N'-bis(2-pytidylmethyl)-trans-1,2-diaminocyclohexane N,N'-diacetate)interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules.