Enhanced Antioxidant Activity of Ursolic Acid by Complexation with Copper (II): Experimental and Theoretical Study

Abstract

The copper (II) complex of ursolic acid (Cu(II) UA) was synthesized and discussed in terms of its infrared, UV–visible spectra, quantum-chemical calculations at B3LYP/6-31G(d) level and antioxidant capacity. The copper (II) complex was stable in methanolic solution with the molar ratio metal:ligand 1:1. The data obtained by FT-IR confirmed the metal ion coordination through the carboxylate anion. The antioxidant properties of ursolic acid and its complex with Cu were discussed on the basis of energy of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and values of chemical reactivity parameters. The antiradical properties of ursolic acid and the Cu (II) complex were examined against DPPH• and HO• radicals, and the ferric reducing antioxidant power (FRAP) was examined. The Cu(II) complex showed higher antioxidant activity than ursolic acid, i.e., in DPPH• assay, the EC50 for UA was 47.0 mM, whereas, for Cu(II), UA EC50 = 19.5 mM; the FRAP value for UA was 20.8 µMFe2+, and 35.4 µMFe2+ for Cu(II) UA (compound concentration 3 mM). Although there was no distinct difference in the antioxidant activity against HO• between these two chemicals, they were both better HO• scavengers than DPPH• and showed different kinetics in the reaction with DPPH•.

Drug Design Strategies for the Treatment of Viral Disease. Plant Phenolic Compounds and Their Derivatives

“…The highest antioxidant activity compared to free phenolic compounds was noted in the case of La(III), Mg(II) complexes of apigenin, Cu(II), Fe(II), La(III), Ce(IV) and oxovanadium (IV) complexes of chrysin, calcium complex of gentisic acid and oxovanadium complex of luteolin (Kalinowska et al, 2020). The research by Samsonowicz et al Samsonowicz et al (2021) proved that Cu(II) complex of ursolic acid was characterized by greater antiradical activity against DPPH • than the ursolic acid alone. It was observed that the higher the concentration of the tested compounds, the greater their antioxidant activity was (Samsonowicz et al, 2021).…”

“…The research by Samsonowicz et al Samsonowicz et al (2021) proved that Cu(II) complex of ursolic acid was characterized by greater antiradical activity against DPPH • than the ursolic acid alone. It was observed that the higher the concentration of the tested compounds, the greater their antioxidant activity was (Samsonowicz et al, 2021). Świsłocka et al Świsłocka et al (2019) claimed that alkali metal (Li, Na, K) rosmarinates exhibit better antioxidant activity than rosmarinic acid.…”

“…It has been proven that Li, Na, K, Rb and Cs salts of 5-O-caffeoylquinic acid (chlorogenic acid) are more lipophilic than chlorogenic acid (Kalinowska et al, 2018;Kalinowska et al, 2014). Samsonowicz et al Samsonowicz et al (2021) reported that metal complexation is a well-known way to increase the solubility of parent ligand. Literature data showed that transition metal complexes with phenolic acids and flavonoids are characterized by higher bioavailability compared to pure ligands (Świderski et al, 2020).…”

“…Conducting research on the synthesis of new derivatives of phenolic compounds may contribute to obtaining new compounds with increased desirable biological properties (Kalinowska et al, 2016). The application of various analytical methods in conjunction with quantum-chemical calculations allows achieving information on the influence of metal ions on the antiviral properties of phenolic compounds (Samsonowicz et al, 2021). Thanks to this, it will be possible to select complexes with the strongest activity.…”

“…Thus, it is likely that metals will enhance the antiviral activity of phenolic compounds. Moreover, complexation of antioxidants with selected metal ions increases their effectiveness (Świsłocka et al, 2019;Kalinowska et al, 2020;Kalinowska et al, 2021;Parcheta et al, 2021;Samsonowicz et al, 2021). In addition, metal complexation of phenolic compounds raises their lipophilicity and bioavailability (Samsonowicz et al, 2015;Kalinowska et al, 2018;Świderski et al, 2020), and also gives the opportunity to introduce beneficial micro-and macroelements into the compound (Świderski et al, 2020).…”