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Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quantum Chemical Methods

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Abstract

Health benefits of dietary phytochemicals have been suggested in recent years. Among 1000s of different compounds, Betalains, which occur in vegetables of the Cariophyllalae order (cactus pear fruits and red beet), have been considered because of reducing power and potential to affect redox-modulated cellular processes. The antioxidant power of Betalains is strictly due to the dissociation rate of the acid moieties present in all the molecules of this family of phytochemicals. Experimentally, only the pK a values of betanin were determined. Recently, it was evidenced it was evidenced as the acid dissociation, at different environmental pHs, affects on its electron-donating capacity, and further on its free radical scavenging power. The identical correlation was studied on another Betalains family compound, Betalamic Acid. Experimental evidences showed that the free radical scavenging capacity of this compound drastically decreases at pH > 5, but pK a values were experimentally not measured. With the aim to justify the Betalamic Acid behavior as free radical scavenger, in this paper we tried to predict in silico the pK a values by means different approaches. Starting from the known experimental pK as of acid compounds, both phytochemicals and small organic, two empirical approaches and quantum–mechanical calculation were compared to give reliable prediction of the pK as of Betalamic Acid. Results by means these computational approaches are consistent with the experimental evidences. As shown herein, in silico, the totally dissociated species, at the experimental pH > 5 in solution, is predominant, exploiting the higher electron-donating capability (HOMO energy). Therefore, the computational estimated pK a values of Betalamic Acid resulted very reliable.

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References

  1. Carratù B, Sanzini E (2005) Sostanze biologicamente attive presenti negli alimenti di origine vegetale. Ann Ist Super Sanità 41:7–16 (in Italian)

    PubMed  Google Scholar 

  2. Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Leborgne F (1999) Vegetables, fruits, and related nutrients and risk of breast cancer, a case–control study in Uruguay. Nutr Cancer 35:111–119

    Article  CAS  Google Scholar 

  3. Agarwal S, Rao AV (2000) Tomato lycopene and its role in human health and chronic diseases. Can Med Assoc J 163:739–744

    CAS  Google Scholar 

  4. McKeown N (1999) Antioxidants and breast cancer. Nutr Rev 57:321–323

    CAS  PubMed  Google Scholar 

  5. Scalbert A, Johnson IT, Saltmarsh M (2005) Polyphenols, antioxidants and beyond. Am J Clin Nutr 81:215S–217S

    Article  CAS  Google Scholar 

  6. Raederstorff D (2009) Antioxidant activity of olive polyphenols in humans, a review. Int J Vitam Nutr Res 79:152–165

    Article  CAS  Google Scholar 

  7. Herr I, Büchler MW (2010) Dietary constituents of broccoli and other cruciferous vegetables, implications for prevention and therapy of cancer. Cancer Treat Rev 36:377–383

    Article  CAS  Google Scholar 

  8. Tesoriere L, Allegra M, Butera D, Livrea MA (2004) Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs, potential health effects of betalains in humans. Am J Clin Nutr 80:941–945

    Article  CAS  Google Scholar 

  9. Frank T, Stintzing FC, Carle R, Bitsch I, Quaas D, Straß G, Bitsch R, Netzel M (2005) Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans. Pharmacol Res 52:290–297

    Article  CAS  Google Scholar 

  10. Kanner J, Harel S, Granit R (2001) Betalains a new class of dietary cationized antioxidants. J Agric Food Chem 49:5178–5185

    Article  CAS  Google Scholar 

  11. Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL (2002) Procyanidin dimer B2 [epicatechin-4β-8-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76:798–804

    Article  CAS  Google Scholar 

  12. Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M (2006) (–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103:1024–1029

    Article  CAS  Google Scholar 

  13. Tesoriere L, Fazzari M, Angileri F, Gentile C, Livrea MA (2008) In vitro digestion of betalainic foods. Stability and bioaccessibility of betaxanthins and betacyanins and antioxidative potential of food digesta. J Agric Food Chem 56:10487–10492

    Article  CAS  Google Scholar 

  14. Gliszczyńska-Swigło A, Szymusiak H, Malinowska P (2006) Betanin, the main pigment of red beet, molecular origin of its exceptionally high free radical-scavenging activity. Food Addit Contam 23:1079–1087

    Article  Google Scholar 

  15. Tesoriere L, Gentile C, Angileri F, Attanzio A, Tutone M, Allegra M, Livrea MA (2013) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. Eur J Nutr 52:1077–1087

    Article  CAS  Google Scholar 

  16. Gandía-Herrero F, Escribano J, García-Carmona F (2012) Purification and antiradical properties of the structural unit of betalains. J Nat Prod 75:1030–1036

    Article  Google Scholar 

  17. Fraczkiewicz R (2007) In: Testa B, van de Waterbeemd H (eds) Comprehensive medicinal chemistry II, vol 5. Elsevier, pp 603–626

  18. Perrin DD (1965) Dissociation constants of organic bases in aqueous solution: supplement 1972. Butterworths, London

    Google Scholar 

  19. Serjeant E, Dempesey BL (1979) Ionization constant of organic acids in aqueous solution. Pergamon, Oxford

    Google Scholar 

  20. Albert A (1963) In: Katritzky AR (ed) Ionization constant of heterocyclic substances in physical methods in heterocyclic chemistry. chapter 5, Academic Press, New York

  21. Sober HA (1968) CRC handbook of biochemistry. CRC Press, Cleveland

    Google Scholar 

  22. Perrin DD, Dempsey B, Serjeant EP (1981) pKa prediction for organic acids and bases. Chapman & Hall, London

    Book  Google Scholar 

  23. Dawson RMC, Elliott DC, Elliott WH, Jones KM (1986) Data for biochemical research. Oxford Science, Oxford

    Google Scholar 

  24. Washburn EW (1929) International critical tables. McGraw-Hill, New York

    Google Scholar 

  25. Hasanain F, Wang ZY (2008) New one-step synthesis of polyimides in salicylic acid. Polymer 49:831–835

    Article  CAS  Google Scholar 

  26. Borges F, Lima JLFC, Pinto I, Reis S, Siquet C (2003) Application of a potentiometric system with data-analysis computer programs to the quantification of metal-chelating activity of two natural antioxidants, caffeic acid and ferulic acid. Helv Chim Acta 86:3081–3087

    Article  CAS  Google Scholar 

  27. Abbasi S, Daneshfar A, Hamdghadare S, Farmany A (2011) Quantification of sub-nanomolar levels of gallic acid by adsorptive stripping voltammetry. Int J Electrochem Sci 6:4843–4852

    CAS  Google Scholar 

  28. Beltrán JL, Sanli N, Fonrodona G, Barrón D, Özkan G, Barbosa J (2003) Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic acids in water and acetonitrile–water media. Anal Chim Acta 484:253–264

    Article  Google Scholar 

  29. Du H, Chen X (2009) CD-MEKC method to analyze triterpene acids in traditional chinese medicines. J Braz Chem Soc 20:1268–1274

    Article  CAS  Google Scholar 

  30. Wybraniec S (2005) Formation of decarboxylated betacyanins in heated purified betacyanin fractions from red beet root Beta vulgaris L. monitored by LC–MS/MS. J Agric Food Chem 53:3483–3487

    Article  CAS  Google Scholar 

  31. Szegezdi J, Csizmadia F (2004) Prediction of dissociation constant using microconstants. In: 27th ACS American Chemical Society national meeting, Anaheim, CA, 28 March–1 April

  32. Szegezdi J, Csizmadia F (2007) Method for calculating pK a values of small and large molecules. In: 233rd ACS American Chemical Society national meeting, Chicago, IL, 25–29 March

  33. Epik version 2.0 (2009) Schrödinger, LLC, New York

  34. Shelley JC, Cholleti A, Frye LL, Greenwood JR, Timlin MR, Uchimaya M (2007) Epik, a software program for pKa prediction and protonation state generation for drug-like molecules. J Comput Aided Mol Des 21:681–691

    Article  CAS  Google Scholar 

  35. Bochevarov AD, Harder E, Hughes TF, Greenwood JR, Braden DA, Philipp DM, Rinaldo D, Halls MD, Zhang J, Friesner RA (2013) Jaguar, a high-performance quantum chemistry software program with strengths in life and materials sciences. Int J Quantum Chem 113:2110–2142

    Article  CAS  Google Scholar 

  36. Jaguar version 7.6 (2009) Schrödinger, LLC, New York

  37. MacroModel, version 10.0 (2013) Schrödinger, LLC, New York

  38. Liao C, Nicklaus MC (2009) Comparison of nine programs predicting pKa values of pharmaceutical substances. J Chem Inf Model 4912:2801–2812

    Article  Google Scholar 

  39. Neumeyer K, Ross T, Thomson G, McMeekin TA (1997) Validation of a model describing the effects of temperature and water activity on the growth of psychrotrophic pseudomonads. Int J Food Microbiol 38:55–63

    Article  CAS  Google Scholar 

  40. Mellefont LA, McMeekin TA, Ross T (2003) Performance evaluation of a model describing the effects of temperature, water activity, pH and lactic acid concentration on the growth of Escherichia coli. Int J Food Microbiol 82:45–58

    Article  CAS  Google Scholar 

  41. Nilsson T (1970) Studies into the pigmentsin beetroot Beta vulgaris L. vulgaris var. rubra L. Lantbrukshoegskolans Annaler 36:179–219

    CAS  Google Scholar 

  42. Manchester J, Walkup G, Rivin O, You Z (2010) Evaluation of pKa estimation methods on 211 druglike compounds. J Chem Inf Model 50:565–571

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Via Archirafi 32, 90123, Palermo, Italy

    Marco Tutone, Antonino Lauria & Anna Maria Almerico

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  1. Marco Tutone
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  2. Antonino Lauria
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  3. Anna Maria Almerico
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Correspondence to Marco Tutone.

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Tutone, M., Lauria, A. & Almerico, A.M. Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quantum Chemical Methods. Interdiscip Sci Comput Life Sci 8, 177–185 (2016). https://doi.org/10.1007/s12539-015-0101-3

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