Induction of axial chirality in divanillin by interaction with bovine serum albumin

Abstract

Vanillin is a plant secondary metabolite and has numerous beneficial health applications. Divanillin is the homodimer of vanillin and used as a taste enhancer compound and also a promissory anticancer drug. Here, divanillin was synthesized and studied in the context of its interaction with bovine serum albumin (BSA). We found that divanillin acquires axial chirality when complexed with BSA. This chiroptical property was demonstrated by a strong induced circular dichroism (ICD) signal. In agreement with this finding, the association constant between BSA and divanillin (3.3 x 105 mol-1L) was higher compared to its precursor vanillin (7.3 x 104 mol-1L). The ICD signal was used for evaluation of the association constant, demonstration of the reversibility of the interaction and determination of the binding site, revealing that divanillin has preference for Sudlow’s site I in BSA. This property was confirmed by displacement of the fluorescent markers warfarin (site I) and dansyl-L-proline (site II). Molecular docking simulation confirmed the higher affinity of divanillin to site I. The highest scored conformation obtained by docking (dihedral angle 242°) was used for calculation of the circular dichroism spectrum of divanillin using Time-Dependent Density Functional Theory (TDDFT). The theoretical spectrum showed good similarity with the experimental ICD. In summary, we have demonstrated that by interacting with the chiral cavities in BSA, divanillin became a atropos biphenyl, i.e., the free rotation around the single bound that links the aromatic rings was impeded. This phenomenon can be explained considering the interactions of divanillin with amino acid residues in the binding site of the protein. This chiroptical property can be very useful for studying the effects of divanillin in biological systems. Considering the potential pharmacological application of divanillin, these findings will be helpful for researchers interested in the pharmacological properties of this compound.

Entropy‐driven binding of octyl gallate in albumin: Failure in the application of temperature effect to distinguish dynamic and static fluorescence quenching

“…This is the case of studies focused on the determination of binding characteristics of potential ligands with albumins . In this regard, bovine serum albumin (BSA) has been applied in numerous studies involving different ligands; and fluorescence quenching is the usual physicochemical approach to study these interactions . BSA is used as a model protein to study the interaction between drugs and albumins .…”

Induced CD of iron(ii) clathrochelates: sensing of the structural and conformational alterations of serum albumins

“…To evaluate the preferable iron(II) clathrochelate binding site in serum albumins, we carried out experiments of clathrochelate displacement by specific binders of albumin sites 1 and 2, warfarin and ibuprofen, respectively. 3,13,40 These site-specific binders show high affinity to albumin, with measured binding constants of about 2.5 Â 10 5 M À1 for warfarin, 60 and 2 Â 10 6 M À1 for ibuprofen. 61 Upon binding to serum albumin, neither warfarin nor ibuprofen exhibit any ICD spectra in the visible spectral range.…”

“…Thus, a significantly higher percentage of clathrochelate molecules is bound to albumins at a 2 : 1 molar ratio for the conditions of the CD experiment, and induced CD was clearly observed. The clathrochelate binding site was evaluated by displacement of clathrochelate upon addition of site markers: (i) warfarin, 3,41 and (ii) ibuprofen. 13 A 50-fold excess (2 Â 10 À3 M) of warfarin or ibuprofen was added to a mixture of protein (c albumin = 8 Â 10 À5 mol l À1 ) and clathrochelate (c clt = 4 Â 10 À5 mol l À1 ).…”

“…61 Upon binding to serum albumin, neither warfarin nor ibuprofen exhibit any ICD spectra in the visible spectral range. 3 Therefore, evaluation of the iron(II) clathrochelate preference to certain binding sites is performed by monitoring the changes in the ICD spectra of clathrochelate upon the addition of each of these site-specific binders.…”

“…1 Biological macromolecules exhibiting inherent chirality are able to induce asymmetry of achiral organic and coordination compounds, and therefore may cause an appearance of a signal in their CD spectra. [2][3][4] These induced CD (ICD) bands are very sensitive to the arrangement of the binding sites of hosting biomolecules. 4 As a result, the chirality of small molecules gained upon their binding to proteins may reflect both the structural alterations and the conformation transitions of proteins (to be observed via changes in the ICD spectra).…”