Abstract
Coupling the extraction and derivatization of flavonoids to the Citrus processing industry is attractive from both the environmental and economic points of view. In the present work, the flavonoid naringin, obtained by “green” extraction with a water:ethanol mixture from waste grapefruit industry, was hydrolyzed to obtain naringenin. This flavonoid was used to synthesize the complex trans-di(aqua) bis(7-hydroxy-2-(4-hydroxyphenyl)-4-oxo-5-chromanolato) copper (II). This compound was characterized by spectroscopic techniques (UV/Vis, IR, Raman, NMR and EPR), and by thermal analysis (TG and DSC). Then, a monocrystal of the complex obtained by dissolution and recrystallization in DMF was analyzed by single crystal X-ray diffraction. This is the first report of the crystal structure of a Citrus flavonoid complex. Additionally, its antiradical activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) was determined and compared with that for naringenin, demonstrating that coordination to copper enhances the antiradicalar activity of naringenin. According to the Mulliken population analysis conducted, by copper favors the delocalization and stabilization of the produced radical, since it acts as an electronic density acceptor.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agrawal PK, Schneider H-J (1983) Deprotonation induced 13 C NMR shifts in phenols and flavonoids. Tetrahedron Lett 24:177–180. https://doi.org/10.1016/S0040-4039(00)81359-3
Ajmala Shireen P, Abdul Mujeeb VM, Muraleedharan K (2017) Theoretical insights on flavanones as antioxidants and UV filters: a TDDFT and NLMO study. J Photochem Photobiol B 170:286–294. https://doi.org/10.1016/j.jphotobiol.2017.04.021
Amic D, Davidovic-Amic D, Beslo D, Rastija V, Lucic B, Trinajstic N (2007) SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem 14:827–845
Arif H, Sohail A, Farhan M, Rehman AA, Ahmad A, Hadi SM (2017) Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: a potential role in cancer chemoprevention. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2017.08.049
Barreca D et al (2017) Flavanones: citrus phytochemical with health-promoting properties. BioFactors 43:495–506. https://doi.org/10.1002/biof.1363
Bearpark M et al (2009) Gaussian 09, Revision A. 01. Gaussian Inc, Wallingford CT
Becke AD (1993) Becke’s three parameter hybrid method using the LYP correlation functional. J Chem Phys 98:5648–5652
Bencini A, Gatteschi D (1990) Spectra in extended lattices. Electron paramagnetic resonance of exchange coupled systems. Springer, Berlin. https://doi.org/10.1007/978-3-642-74599-7
Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Technol 28:25–30
Brodowska K (2013) Naringenin complexes with copper ions: potentiometric studies. Biotechnol Food Sci 77:44–53
Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muñiz P (2010) Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study. J Sci Food Agric 90:1238–1244. https://doi.org/10.1002/jsfa.3959
CrysAlis PRO (2015) Rigaku oxford diffraction. Rigaku Corporation, Tokyo
de Souza RFV, De Giovani WF (2004) Antioxidant properties of complexes of flavonoids with metal ions. Redox Rep 9:97–104. https://doi.org/10.1179/135100004225003897
Erlund I (2004) Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 24:851–874
Ferreira LMB, Kobelnik M, Regasini LO, Dutra LA, da Silva Bolzani V, Ribeiro CA (2017) Synthesis and evaluation of the thermal behavior of flavonoids. J Therm Anal Calorim 127:1605–1610. https://doi.org/10.1007/s10973-016-5896-6
Groom CR, Bruno IJ, Lightfoot MP, Ward SC (2016) The Cambridge structural database. Acta Crystallogr Sect B 72:171–179. https://doi.org/10.1107/S2052520616003954
Ilkay EO, Seyed FN, Maria D, Gian CT, Kowsar M, Seyed MN (2015) Naringenin and atherosclerosis: a review of literature. Curr Pharm Biotechnol 16:245–251. https://doi.org/10.2174/1389201015666141202110216
Jabbari M, Mir H, Kanaani A, Ajloo D (2014) Kinetic solvent effects on the reaction between flavonoid naringenin and 2,2-diphenyl-1-picrylhydrazyl radical in different aqueous solutions of ethanol: an experimental and theoretical study. J Mol Liq 196:381–391. https://doi.org/10.1016/j.molliq.2014.04.015
Khan MB et al (2012) Naringenin ameliorates Alzheimer’s disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model. Neurochem Int 61:1081–1093. https://doi.org/10.1016/j.neuint.2012.07.025
Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest 111:785–793. https://doi.org/10.1172/JCI200318182
Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785
Lever A (1984) Electronic spectra of dn ions. Inorgan Electr Spectr 2:376–611
Macrae CF et al (2006) Mercury: visualization and analysis of crystal structures. J Appl Crystallogr 39:453–457. https://doi.org/10.1107/S002188980600731X
Miehlich B, Savin A, Stoll H, Preuss H (1989) Results obtained with the correlation energy density functionals of Becke and Lee, Yang and Parr. Chem Phys Lett 157:200–206
Nakamoto K (2009) Infrared and Raman spectra of inorganic and coordination compounds, applications in coordination, organometallic, and bioinorganic chemistry. Wiley Inc., New York, pp 96–98
Neuman NI, Franco VG, Ferroni FM, Baggio R, Passeggi MCG, Rizzi AC, Brondino CD (2012) Single crystal EPR of the mixed-ligand complex of copper (II) with l-glutamic acid and 1,10-phenanthroline: a study on the narrowing of the hyperfine structure by exchange. J Phys Chem A 116:12314–12320. https://doi.org/10.1021/jp308745e
Patel K, Singh GK, Patel DK (2014) A review on pharmacological and analytical aspects of naringenin. Chin J Integr Med. https://doi.org/10.1007/s11655-014-1960-x
Pękal A, Biesaga M, Pyrzynska K (2011) Interaction of quercetin with copper ions: complexation, oxidation and reactivity towards radicals. Biometals 24:41–49. https://doi.org/10.1007/s10534-010-9372-7
Poore HD (1934) Recovery of naringin and pectin from grapefruit residue. Ind Eng Chem 26:637–639. https://doi.org/10.1021/ie50294a011
Pouchert C, Behnke J (1993) Aldrich® Library of 13C and 1H FT-NMR Spectra. Aldrich Chemical Co, St. Louis
Pulley GN (1936) Solubility of Naringin in water. Ind Eng Chem 8:360. https://doi.org/10.1021/ac50103a020
Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20:933–956
Rizzi AC, Neuman NI, González PJ, Brondino CD (2016) EPR as a tool for study of isolated and coupled paramagnetic centers in coordination compounds and macromolecules of biological interest. Eur J Inorg Chem. https://doi.org/10.1002/ejic.201690002
Robin J, Blanco S, Macoritto A, Soria F, Geronazzo H (2007) Obtención de prunina, ramnosa y naringenina por hidrólisis ácida de naringina. Actas XI Congreso Argentino de Ciencia y Tecnología de Alimentos Buenos Aires, Argentina 1:1–7
Scalmania G, Frisch MJ (2010) Continuous surface charge polarizable continuum models of solvation. I. General formalism. J Chem Phys 132:114110
Selvaraj S, Krishnaswamy S, Devashya V, Sethuraman S, Krishnan UM (2014a) Flavonoid–metal ion complexes: a novel class of therapeutic agents. Med Res Rev 34:677–702. https://doi.org/10.1002/med.21301
Selvaraj S, Krishnaswamy S, Devashya V, Sethuraman S, Krishnan UM (2014b) Investigations on the membrane interactions of naringin and its complexes with copper and iron: implications for their cytotoxicity. RSC Adv 4:46407–46417. https://doi.org/10.1039/C4RA08157A
Sheldrick G (2008) A short history of SHELX. Acta Crystallogr Sect A 64:112–122. https://doi.org/10.1107/S0108767307043930
Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr Sect C Struct Chem 71:3–8. https://doi.org/10.1107/S2053229614024218
Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G (2000) Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis 1502:139–144. https://doi.org/10.1016/S0925-4439(00)00040-5
Spek AL (2009) Structure validation in chemical crystallography. Acta Crystallogr Sect D Bioll Crystallogr 65:148–155. https://doi.org/10.1107/S090744490804362X
Stoll S, Schweiger A (2006) EasySpin, a comprehensive software package for spectral simulation and analysis in EPR. J Magn Reson 178:42–55. https://doi.org/10.1016/j.jmr.2005.08.013
Swarnkar G et al (2012) A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts. Br J Pharmacol 165:1526–1542. https://doi.org/10.1111/j.1476-5381.2011.01637.x
Tamayo LV et al (2016) Copper (II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action. Biometals 29:39–52. https://doi.org/10.1007/s10534-015-9894-0
Tan M, Zhu J, Pan Y, Chen Z, Liang H, Liu H, Wang H (2009) Synthesis, cytotoxic activity, and DNA binding properties of copper (II) complexes with hesperetin, naringenin, and apigenin. Bioinor Chem Appl. https://doi.org/10.1155/2009/347872
Uivarosi V, Badea M, Rodica O, Velescu B, Aldea V (2016) Synthesis and characterization of a new complex of oxovanadium (IV) with naringenin, as potential insulinomimetic agent. Farmacia 64:175–180
Unsalan O, Erdogdu Y, Gulluoglu MT (2009) FT-Raman and FT-IR spectral and quantum chemical studies on some flavonoid derivatives: baicalein and Naringenin. J Raman Spectrosc 40:562–570. https://doi.org/10.1002/jrs.2166
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40. https://doi.org/10.1016/j.cbi.2005.12.009
Wang H-L, Yang Z-Y, B-d Wang (2006) Synthesis, characterization and the antioxidative activity of copper (II), zinc (II) and nickel (II) complexes with naringenin. Trans Met Chem 31(4):470–474
Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5:14–14. https://doi.org/10.1186/1477-3163-5-14
Acknowledgements
We thank Universidad Nacional de Salta (Proyecto CIUNSa No 2227), Agencia Nacional de Promoción Científica y Tecnológica of Argentina (PICT 2012 No 0696) and Secretaría de Políticas Universitarias (PNo. 33-63-029-2014) for financial support. The authors acknowledge ANPCyT (Project No. PME 2006-01113) for the purchase of the Oxford Gemini CCD diffractometer. We also acknowledge Departamento de Física de la Materia Condensada, CNEA for the use of TGA facilities and Dra. Gabriela Levy for her helpful assistance. Universidad Nacional de Catamarca (UNCa) is also appreciated for their computation supports. G. Céliz, S. Suarez, C. D. Brondino, and F. Doctorovich are members of the Research Career of CONICET.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Celiz, G., Suarez, S.A., Arias, A. et al. Synthesis, structural elucidation and antiradical activity of a copper (II) naringenin complex. Biometals 32, 595–610 (2019). https://doi.org/10.1007/s10534-019-00187-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10534-019-00187-3