Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin
| Autor: | Martina Sanadar, Rui Ribeiro, Andrea Melchior, Chiara Nardon, Fabio Piccinelli, Chiara De Rosa, Marilena Tolazzi, Alejandro Giorgetti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Coordination sphere
Luminescence Protein Conformation Peptides and proteins Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Medicinal chemistry Hydrocarbons Aromatic Article Fluorescence Inorganic Chemistry chemistry.chemical_compound Europium Eu(III) complexes Coordination Complexes Pyridine Animals Physical and Theoretical Chemistry Isoquinoline Bovine serum albumin biology 010405 organic chemistry Ligand Water Titration Isothermal titration calorimetry Serum Albumin Bovine Stereoisomerism 0104 chemical sciences Enantiopure drug chemistry biology.protein Cattle Trifluoromethanesulfonate Protein Binding |
| Zdroj: | Inorganic Chemistry |
| Popis: | The cationic enantiopure (R,R) and luminescent Eu(III) complex [Eu(bisoQcd)(H2O)2] OTf (with bisoQcd = N,N′-bis(2-isoquinolinmethyl)-trans-1,2-diaminocyclohexane N,N′-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 calorimetry (ITC), molecular docking (MD), and molecular dynamics simulations (MDS). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digitoxin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the Eu(III) complexes. In fact, the presence of isoquinoline 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 ([Eu(bpcd)(H2O)2]Cl with bpcd = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N′-diacetate) interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules. The effect of the antenna moiety on the interaction of two new luminescent Eu(III) complexes with BSA was studied. Results show that the complexes can be conveniently exploited as optical probes for albumin serum proteins by means of opposite mechanisms (switch-on−off of the luminescent signal). |
| Databáze: | OpenAIRE |
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