CHLOROGENIC ACID – APPLICATION OF CONTEMPORARY DENSITY FUNCTIONALS TO A SINGLE MOLECULE

1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (81-88)

AUTHOR(S) / АУТОР(И): Svetlana Marković, Jelena Tošović

E-ADRESS / Е-АДРЕСА: mark@kg.ac.rs, jtosovic@umich.edu,

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DOI: 10.46793/ICCBI21.081M

ABSTRACT / САЖЕТАК:

Although chlorogenic acid (5-O-caffeoylquinic acid, 5CQA) is a dietary phenol known for its pharmacological and nutritional properties, its structural features and mechanisms of oxidative action have not been completely elucidated. Clarification of the 5CQA structure was conducted by comparing the experimental and simulated IR, Raman, 1H-NMR, 13C-NMR, and UV spectra. For this purpose, a comprehensive conformational analysis of 5CQA was performed to reveal its most stable conformations in the gas-state and solution. Excellent agreement between all experimental and simulated spectra indicates correct arrangement of the atoms in the 5CQA molecule. In addition, the most stable conformation in solution coincides with that predicted with sophisticated NMR experiments.

The quantum mechanics–based test for overall free-radical scavenging activity was applied for the investigation of antioxidative capacity of 5CQA relative to trolox (6-hydroxy-2,5,7,8- tetramethylchroman-2-carboxylic acid, Tx) as a reference compound. Hydrogen atom transfer (HAT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and single electron transfer – proton transfer (SET-PT) reactions of 5CQA and Tx with HO· and CH3OO· radicals were examined in benzene, pentyl ethanoate, and basic aqueous solutions. In non-polar solvents 5CQA reacts with HO· via HAT and RAF mechanisms, whereas HAT is the only reaction pathway with CH3OO·. At physiological conditions 5CQA exists in the form of monoanion and dianion. Both anionic forms undergo only HAT mechanism with CH3OO·. With HO·, the anions conform to the HAT, RAF, SPLET, and SET-PT mechanisms. Because all reactions of dianion are diffusion controlled, its contribution to scavenging HO· is comparable to that of more abundant monoanion. The calculated rate constant for overall reaction of 5CQA with HO· is in perfect agreement with the corresponding experimental value. The order of reactivity toward selected free radicals is the same in nonpolar and polar solutions: in comparison to Tx, 5CQA is more reactive toward HO·, but less reactive toward CH3OO·.

Very good agreement between the experimental and calculated results confirms the ability of contemporary density functionals to quantify subtle physico-chemical interactions.

KEY WORDS / КЉУЧНЕ РЕЧИ:

conformational analysis, vibrational spectra, NMR spectra, UV spectrum, QM-ORSA, non- polar solvents, basic aqueous solution, four antioxidative mechanisms, DFT calculations

REFERENCES / ЛИТЕРАТУРА:

  • B. Rimm, M.B. Katan, A. Ascherio, M J. Stampfer, W.C. Willett, Relation between intake of flavonoids and risk for coronary heart disease in male health professionals, Ann. Intern. Med. 125 (1996) 384-389.
  • Scalbert, G. Williamson, Dietary intake and bioavailability of polyphenols, J. Nutr. 130 (2000) 2073-2085.
  • Jayasena, A. Poljak, G. Smythe, N. Braidy, G. Münch, P. Sachdev, The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease, Ageing Res. Rev. 12 (2013) 867-883.
  • Suzuki, N. Yamamoto, H. Jokura, M. Yamamoto, A. Fujii, I. Tokimitsu, I. Saito, Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats, J. Hypertens. 24 (2006) 1065-1073.
  • W. Ong, A. Hsu, B.K.H. Tan, Chlorogenic Acid Stimulates Glucose Transport in Skeletal Muscle via AMPK Activation: A Contributor to the Beneficial Effects of Coffee on Diabetes, PLoS One 7 (2012) e32718.
  • A.N. Laranjinha, L.M. Almeida, V.M. Madeira, Reactivity of dietary phenolic acids with peroxyl radicals: antioxidant activity upon low density lipoprotein peroxidation, Biochem. Pharmacol. 48 (1994) 487-494.
  • -W. Wan, C.N.-Y Wong, W.-K. Pin, M.H.-Y Wong, C.-Y. Kwok, R. Y.-K. Chan, P. H.-F.Yu, S.-W. Chan, Chlorogenic Acid Exhibits Cholesterol Lowering and Fatty Liver Attenuating Properties by Up-regulating the Gene Expression of PPAR-a in Hypercholesterolemic Rats Induced with a High-Cholesterol Diet, Phytother. Res. 27 (2013) 545-551.
  • W. Ong, A. Hsu, B.K.H Tan, Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation, Biochem. Pharmacol. 85 (2013) 1341-1351.
  • Tošović, Strukturne i antioksidativne osobine hlorogenske kiseline, doctoral dissertation, University of Kragujevac (2019).
  • Marković, J. Tošović, D. Milenković, S. Marković, Revisiting the solvation enthalpies and free energies of the proton and electron in various solvents, Comput. Theor. Chem. 1077 (2016) 11-17.
  • Marković, J. Tošović, J. Dimitrić Marković, Synergic application of spectroscopic and theoretical methods to the chlorogenic acid structure elucidation, Spectrochim. Acta A 164 (2016) 67-75.
  • Marković, J. Tošović, Comparative study of the antioxidative activities of caffeoylquinic and caffeic acids, Food Chem. 210 (2016) 585-592.
  • Tošović, S. Marković, Structural and Antioxidative Features of Chlorogenic Acid, Croat. Chem. Acta 89 535-541 (2016).
  • Tošović, S. Marković, Reactivity of chlorogenic acid towards hydroxyl and methyl peroxy radicals relative to trolox in nonpolar media, Theor. Chem. Acc. 137 (2018) 76.
  • Tošović, S. Marković, Antioxidative activity of chlorogenic acid relative to trolox in aqueous solution – DFT study, Food Chem. 278 (2019) 469-475.
  • Forino, G.C. Tenore, L. Tartaglione, C. Dell’Aversano, N. Novellino, P. Ciminiello, (1S,3R,4S,5R)5-O-Caffeoylquinic acid: Isolation, stereo-structure characterization and biological activity, Food Chem. 178 (2015) 306-310.
  • Galano, J. R. Alvarez-Idaboy, A computational methodology for accurate predictions of rate constants in solution: Application to the assessment of primary antioxidant activity, J. Comput. Chem. 34 (2013) 2430-2445.
  • Kono, K. Kobayashi, S, Tagawa, K. Adachi, A. Ueda, Y. Sawa, H. Shibata, Antioxidant activity of polyphenolics in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen, Biochim. Biophys. Acta 1335 (1997) 335-342.