Exploring the capabilities of TDDFT calculations to explain the induced chirality upon a binding process: A simple case, 3-carboxycoumarin

The induced circular dichroism (ICD) spectra of 3-carboxycoumarin recorded at pH 7.4 in the presence of human and bovine serum albumins were used in correlation with theoretical (TDDFT) calculations to obtain the binding constants and information on the conformational changes of the ligand in the binding site. As it was shown that for the carboxylic acids or the carboxylate ions, the asymmetry element correlated with the occurrence of the ICD band in the presence of proteins is the torsion (τ) of the COOH (COO−) group in respect with the planar π system, TDDFT calculations were performed considering all the geometries characterized by 0 ⩽ |τ| ⩽ 90 deg. The simulated circular dichroism spectrum shows that the sequence of the signs and positions of the bands are correctly predicted as compared to the experimental ICD spectrum for a torsion of the carboxylate group in the range of 60−70 deg.

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► ICD spectra were used to estimate the binding constant of 3-carboxycoumarin with BSA.
► TDDFT calculations were performed considering different ligand conformations.
► TDDFT results were used to simulate the ECD spectra.
► All these data give information on the ligand conformation in the binding site.