Investigation of Flavonoids Bearing Different Substituents on Ring C and Their Cu²⁺Complex Binding with Bovine Serum Albumin: Structure–Affinity Relationship Aspects

Abstract

The effects of 1:1 flavonoid-Cu(2+) complexes of four flavonoids with different C-ring substituents, quercetin (QU), luteolin (LU), taxifolin (TA), and (+)-catechin (CA), on bovine serum albumin (BSA) were investigated and compared with corresponding free flavonoids by spectroscopic analysis in an attempt to characterize the chemical association taking place. The results indicated that all of the quenching mechanisms were based on static quenching combined with nonradiative energy transfer. Cu(2+) chelation changed the binding constants for BSA depending on the structures of flavonoids and the detected concentrations. The reduced hydroxyl groups, increased steric hindrance, and hydrophilicity of Cu(2+) chelation may be the main reasons for the reduced binding constants, whereas the formation of stable flavonoid-Cu(2+) complexes and synergistic action could increase the binding constants. The changed trends of critical energy transfer distance (R(0)) for Cu(2+) chelation were contrary to those of binding constants.

Spectroscopic and molecular docking study on the structure–affinity relationship and mechanism in the interaction of genistein and its derivatives with bovine serum albumin

“…BSA contains hydrophobic groups in the interior of the tertiary structure and polar groups such as amino, hydroxyl, and sulfhydryl groups at the surface. Hydrogen bonding may take place between the hydroxyl groups of isoflavones and the polar groups at the BSA surface . Compared with GEN, GEN1 with the structure of a C ring opening, and increase of one in the number of hydroxyl groups on ring A stabilizes the interaction through hydrogen bonding between the hydroxyl groups in isoflavones and polar groups on the BSA surface, resulting in enhanced binding affinity between the isoflavones and BSA .…”

“…The possible mechanism may be that octyloxylation of GEN3 increases hydrophobicity and that hydrophobic interaction plays an important role in binding GEN3 to proteins . Octyloxylation of GEN3 decreased the polarity and enhanced the capacity to penetrate into the tryptophan‐rich hydrophobic regions of proteins, which are frequently buried in the interior of folded proteins . Compared with GEN3, the GEN2 hydroxyl groups located at the C7, C4′ positions were modified by esterification and trifluoromethylation, respectively.…”

“…Hydrogen bonding may take place between the hydroxyl groups of isoflavones and the polar groups at the BSA surface. [31] Compared with GEN, GEN1 with the structure of a C ring opening, and increase of one in the number of hydroxyl groups on ring A stabilizes the interaction through hydrogen bonding between the hydroxyl groups in isoflavones and polar groups on the BSA surface, resulting in enhanced binding affinity between the isoflavones and BSA. [32] Therefore, hydroxyl groups were the most important for isoflavones binding with BSA according to the formation of hydrogen bonding between isoflavones and the polar groups at the BSA surface.…”

“…[35] Octyloxylation of GEN3 decreased the polarity and enhanced the capacity to penetrate into the tryptophan-rich hydrophobic regions of proteins, which are frequently buried in the interior of folded proteins. [31] Compared with GEN3, the GEN2 hydroxyl groups located at the C7, C4′ positions were modified by esterification and trifluoromethylation, respectively. The affinity of GEN3 for BSA is about 1.07 times higher FIGURE 5 Double-log plots against log[Q] derived from the quenching of BSA by GEN (a), GEN1 (b), GEN2 (c), GEN3 (d), or GEN4 (e), respectively, in Tris buffer (pH 7.40) at 298 K in the presence of site markers than that for GEN2, with no significant difference between GEN3 and GEN2 for BSA.…”

Probing the interaction of human serum albumin with DPPH in the absence and presence of the eight antioxidants

“…Therefore, the decreased binding constants and the number of binding sites of DPPH with HSA by the introduction of the eight antioxidants may be suggest that the eight antioxidants can offer some protection HSA against DPPH radical threats. It is obvious that the protection of antioxidants is depended on the decrease in the binding constants and the number of binding sites [24,[28][29][30]. For the higher-affinity site, ascorbic acid, a-tocopherol, glutathione, melatonin, (+)-catechin hydrate, procyanidine B3, b-carotene and astaxanthin decreased the binding constants to 99.9%, 33.0%, 44.1%, 99.7%, 75.9%, 7.68%, 99.5%, and 93.6%, respectively, and decreased the number of binding sites to 46.0%, 1.29%, 2.95%, 39.7%, 9.69%, 1.01%, 38.8%, and 22.5%, respectively.…”