Evaluating the interaction between di-fluorinated chalcones and plasmatic albumin

By using spectroscopic methods (fluorescence and circular dichroism), the interactions of three di-fluorinated chalcones (CH23F, CH25F and CH35F) with bovine serum albumin (BSA) in a PBS buffer solution (pH = 7.4), at 288 K, 293 K and 298 K, were probed. Molecular docking was performed to evaluate the main protein cavity for the BSA/chalcone interactions. Fluorescence quenching of the albumin by the di-fluorinated chalcones follow a combination of static and dynamic quenching mechanisms. The Stern-Volmer binding constant (K-a) values are in the range of 10(4)M(-1) indicating a moderate association between chalcones and BSA. Besides, circular dichroism data show that this association does not affect significantly the secondary structure of the albumin. The Forster resonance energy transfer (FRET) theory suggests that non-radiative energy transfer can occur from BSA to di-fluorinated chalcones (r approximate to 3 nm). The thermodynamic parameters Delta H degrees and Delta S degrees indicate that hydrogen bonding and/or hydrophobic interactions play a major role in the association, which is entropically driven. The enthalpy and entropy change values for CH25F and CH35F are similar, but very different for CH23F. The negative Delta G degrees values are consistent with a spontaneous association. The highest docking score suggests the Trp-212 site as the most probable binding site for the interaction between BSA with the di-fluorinated chalcones. Trp-212 residue interacts via hydrogen bonding with CH25F and CH35F. On the other hand, CH23F interacts via T-stacking with the Trp-212 residue and via hydrogen bonding with the Ser-343 residue. CH23F has the highest dipole moment value of all evaluated chalcones, having its fluorinated aromatic ring more exposed to the aqueous medium than inside the protein cavity. In addition to these results theoretical methods aimed to study the interaction BSA:CH2'3'F, BSA:CH2'5'F and BSA:CH3'5'F were also employed. (C) 2016 Elsevier B.V. All rights reserved.