{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:11:55Z","timestamp":1788930715929,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Scholarships Foundation (I\u039a\u03a5)","award":["NSRF 2014-2020"],"award-info":[{"award-number":["NSRF 2014-2020"]}]},{"name":"State Scholarships Foundation (I\u039a\u03a5)","award":["MIS 5000432"],"award-info":[{"award-number":["MIS 5000432"]}]},{"name":"Greece and the European Union (European Social Fund\u2014ESF)","award":["NSRF 2014-2020"],"award-info":[{"award-number":["NSRF 2014-2020"]}]},{"name":"Greece and the European Union (European Social Fund\u2014ESF)","award":["MIS 5000432"],"award-info":[{"award-number":["MIS 5000432"]}]},{"name":"Human Resources Development, Education and Lifelong Learning","award":["NSRF 2014-2020"],"award-info":[{"award-number":["NSRF 2014-2020"]}]},{"name":"Human Resources Development, Education and Lifelong Learning","award":["MIS 5000432"],"award-info":[{"award-number":["MIS 5000432"]}]},{"DOI":"10.13039\/501100003447","name":"Strengthening the Human Research Resources through the Implementation of Doctoral Research","doi-asserted-by":"publisher","award":["NSRF 2014-2020"],"award-info":[{"award-number":["NSRF 2014-2020"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003447","name":"Strengthening the Human Research Resources through the Implementation of Doctoral Research","doi-asserted-by":"publisher","award":["MIS 5000432"],"award-info":[{"award-number":["MIS 5000432"]}],"id":[{"id":"10.13039\/501100003447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The plethora of flavonoid antioxidants in plant organisms, widespread in nature, and the appropriate metal ions known for their influence on biological processes constitute the crux of investigations toward the development of preventive metallodrugs and therapeutics in several human pathophysiologies. To that end, driven by the need to enhance the structural and (bio)chemical attributes of the flavonoid chrysin, as a metal ion complexation agent, thereby rendering it bioavailable toward oxidative stress, synthetic efforts in our lab targeted ternary Cr(III)-chrysin species in the presence of auxiliary aromatic N,N\u2032-chelators. The crystalline metal-organic Cr(III)-chrysin-L (L = bipyridine (1) and phenanthroline (2)) compounds that arose were physicochemically characterized by elemental analysis, FT-IR, UV-Visible, ESI-MS, luminescence, and X-ray crystallography. The properties of these compounds in a solid state and in solution formulate a well-defined profile for the two species, thereby justifying their further use in biological experiments, intimately related to cellular processes on oxidative stress. Experiments in C2C12 myoblasts at the cellular level (a) focus on the antioxidant capacity of the Cr(III)-complexed flavonoids, emphasizing their distinct antiradical activity under oxidative stress conditions, and (b) exemplify the importance of structural speciation in Cr(III)-flavonoid interactions, thereby formulating correlations with the antioxidant activity of a bioavailable flavonoid toward cellular pathophysiologies, collectively supporting flavonoid introduction in new metallo-therapeutics.<\/jats:p>","DOI":"10.3390\/ijms23137171","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"7171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chromium Flavonoid Complexation in an Antioxidant Capacity Role"],"prefix":"10.3390","volume":"23","author":[{"given":"Sevasti","family":"Matsia","sequence":"first","affiliation":[{"name":"Laboratory of Inorganic Chemistry and Advanced Materials, School of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Tsave","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry and Advanced Materials, School of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Hatzidimitriou","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry, School of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-7989","authenticated-orcid":false,"given":"Athanasios","family":"Salifoglou","sequence":"additional","affiliation":[{"name":"Laboratory of Inorganic Chemistry and Advanced Materials, School of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nut. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.gene.2017.11.065","article-title":"LW-215, a newly synthesized flavonoid exhibits potent anti-angiogenic activity in vitro and in vivo","volume":"642","author":"Zhao","year":"2018","journal-title":"Gene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2174\/138955711794519546","article-title":"Flavonoids Health Benefits and Their Molecular Mechanism","volume":"11","author":"Xiao","year":"2011","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ullah, A., Munir, S., Badshah, S.L., Khan, N., Ghani, L., Poulson, B.G., and Jaremko, M. (2020). Important Flavonoids and Their Role as a Therapeutic Agent. Molecules, 25.","DOI":"10.3390\/molecules25225243"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1039\/D1FO02995A","article-title":"Inhibitory activity of flavonoids against human sucrase-isomaltase (\u03b1-glucosidase) activity in a Caco-2\/TC7 cellular model","volume":"13","author":"Rufino","year":"2022","journal-title":"Food Funct."},{"key":"ref_7","first-page":"130","article-title":"Flavonoids and phenolic acids as antioxidants in plants and human health","volume":"16","author":"Saxena","year":"2012","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105919","DOI":"10.1016\/j.phrs.2021.105919","article-title":"The antihypertensive potential of flavonoids from Chinese Herbal Medicine: A review","volume":"174","author":"Cao","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijantimicag.2005.09.002","article-title":"Antimicrobial activity of flavonoids","volume":"26","author":"Cushnie","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_10","unstructured":"Harborne, J.B., and Baxter, H. (1999). The Handbook of Natural Flavonoids, John Wiley and Sons."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ferraiuolo, S.B., Restaino, O.F., Guti\u00e9rrez-del-R\u00edo, I., Ventriglia, R., Cammarota, M., Villar, C.J., Lomb\u00f3, F., and Schiraldi, C. (2021). Optimization of Pre-Inoculum, Fermentation Process Parameters and Precursor Supplementation Conditions to Enhance Apigenin Production by a Recombinant Streptomyces albus Strain. Fermentation, 7.","DOI":"10.3390\/fermentation7030161"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3389\/fmicb.2017.00921","article-title":"De novo biosynthesis of apigenin, luteolin, and eriodictyol in the actinomycete Streptomyces albus and production improvement by feeding and spore conditioning","volume":"8","author":"Manteca","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mar\u00edn, L., Guti\u00e9rrez-del-R\u00edo, I., Entrialgo-Cadierno, R., Villar, C.J., and Lomb\u00f3, F. (2018). De novo biosynthesis of myricetin, kaempferol and quercetin in Streptomyces albus and Streptomyces coelicolor. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207278"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.1021\/acs.jafc.9b01329","article-title":"Metabolic engineering of Saccharomyces cerevisiae for de novo production of kaempferol","volume":"67","author":"Lyu","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fnagi.2019.00155","article-title":"Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders","volume":"11","author":"Ayaz","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tungmunnithum, D., Thongboonyou, A., Pholboon, A., and Yangsabai, A. (2018). Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: An Overview. Medicines, 5.","DOI":"10.3390\/medicines5030093"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Al-Ishaq, R.K., Abotaleb, M., Kubatka, P., Kajo, K., and B\u00fcsselberg, D. (2019). Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels. Biomolecules, 9.","DOI":"10.3390\/biom9090430"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104629","DOI":"10.1016\/j.phrs.2020.104629","article-title":"Flavonoids and type 2 diabetes: Evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy","volume":"152","author":"Hussain","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"541260","DOI":"10.3389\/fcell.2020.541260","article-title":"C2C12 Mouse Myoblasts Damage Induced by Oxidative Stress Is Alleviated by the Antioxidant Capacity of the Active Substance Phloretin","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116797","DOI":"10.1016\/j.lfs.2019.116797","article-title":"Chrysin: Pharmacological and therapeutic properties","volume":"235","author":"Naz","year":"2019","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/19768354.2020.1765019","article-title":"Antinociceptive effect of chrysin in diabetic neuropathy and formalin-induced pain models","volume":"24","author":"Hong","year":"2020","journal-title":"Anim. Cells Syst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jinorgbio.2016.07.015","article-title":"The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus II","volume":"163","author":"Tsave","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1089\/dia.2006.8.677","article-title":"Clinical Studies on Chromium Picolinate Supplementation in Diabetes Mellitus\u2014A Review","volume":"8","author":"Broadhurst","year":"2006","journal-title":"Diabetes Technol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jinorgbio.2018.02.001","article-title":"Synthetic investigation of binary-ternary Cr(III)-hydroxycarboxylic acid-aromatic chelator systems. Structure-specific influence on adipogenic biomarkers linked to insulin mimesis","volume":"184","author":"Tsave","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0026-265X(00)00121-1","article-title":"Synthesis and physicochemical properties of the Al(III), Ga(III) and In(III) complexes with chrysin","volume":"65","author":"Pusz","year":"2000","journal-title":"Microchem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1039\/C9DT04540F","article-title":"Structurally characterized gallium-chrysin complexes with anticancer potential","volume":"49","author":"Halevas","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.poly.2018.09.072","article-title":"Spectral and structural characterization of chromium(III) complexes bearing 7-oxo-7H-benzo[de]anthracen-3-yl-amidines ligand","volume":"157","author":"Kirilova","year":"2019","journal-title":"Polyhedron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ica.2006.07.097","article-title":"Synthesis, structural, spectroscopic and magnetic susceptibility studies of a soluble Cr(III)\u2013heida (2-hydroxyethyliminodiacetic acid) complex. Relevance to aqueous chromium(III)\u2013heida speciation","volume":"360","author":"Gabriel","year":"2007","journal-title":"Inorg. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1179\/135100004225003897","article-title":"Antioxidant properties of complexes of flavonoids with metal ions","volume":"9","year":"2004","journal-title":"Redox Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and biological activities of flavonoids: An overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"120407","DOI":"10.1016\/j.ica.2021.120407","article-title":"Structurally characterized zinc complexes of flavonoids chrysin and quercetin with antioxidant potential","volume":"523","author":"Halevas","year":"2021","journal-title":"Inorg. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111832","DOI":"10.1016\/j.jinorgbio.2022.111832","article-title":"Hydrophilic bis-MPA hyperbranched dendritic scaffolds as nanocarriers of a fully characterized flavonoid morin-Zn(II) complex for anticancer applications","volume":"232","author":"Halevas","year":"2022","journal-title":"J. Inorg. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"120062","DOI":"10.1016\/j.ica.2020.120062","article-title":"Structurally characterized copper-chrysin complexes display genotoxic and cytotoxic activity in human cells","volume":"515","author":"Halevas","year":"2020","journal-title":"Inorg. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132591","DOI":"10.1016\/j.molstruc.2022.132591","article-title":"Iron(III) and copper(II) complexes derived from the flavonoids morin and quercetin: Chelation, crystal structure and DFT studies","volume":"1257","author":"Tanui","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejmech.2015.04.040","article-title":"The role of antioxidants in the chemistry of oxidative stress: A review","volume":"5","author":"Pisoschi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6439138","DOI":"10.1155\/2018\/6439138","article-title":"Oxidative Stress in Muscle Diseases: Current and Future Therapy","volume":"2018","author":"Serra","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/s41598-020-57821-1","article-title":"Expression and functional analysis of the hydrogen peroxide biosensors HyPer and HyPer2 in C2C12 myoblasts\/myotubes and single skeletal muscle fibres","volume":"10","author":"Palomero","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6343","DOI":"10.1021\/jf060986h","article-title":"Iron chelation by the powerful antioxidant flavonoid quercetin","volume":"54","author":"Leopoldini","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0891-5849(95)02047-0","article-title":"Structural aspects of antioxidant activity of flavonoids","volume":"20","author":"Tromp","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/abbi.2000.2118","article-title":"Influence of metal ions on flavonoid protection against asbestos-induced cell injury","volume":"385","author":"Kostyuk","year":"2001","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"845208","DOI":"10.1155\/2014\/845208","article-title":"Synthesis of Cr(III)-Morin Complex: Characterization and Antioxidant Study","volume":"2014","author":"Panhwar","year":"2014","journal-title":"Sci. World J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0076-6879(90)86128-I","article-title":"Flavonoids as antioxidants: Determination of radical-scavenging efficiencies","volume":"186","author":"Bors","year":"1990","journal-title":"Meth. Enzymol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.theochem.2008.03.020","article-title":"Research on the chelation between quercetin and Cr(III) ion by Density Functional Theory (DFT) method","volume":"860","author":"Sun","year":"2008","journal-title":"J. Mol. Struct."},{"key":"ref_44","unstructured":"Bruker Analytical X-ray Systems, Inc (2006). Apex2, Version 2 User Manual, Bruker. M86-E01078."},{"key":"ref_45","unstructured":"Siemens Industrial Automation, Inc (1996). SADABS: Area-Detector Absorption Correction, Siemens Industrial Automation, Inc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1107\/S0021889807029238","article-title":"SUPERFLIP\u2014A computer program for the solution of crystal structures by charge flipping in arbitrary dimensions","volume":"40","author":"Palatinus","year":"2007","journal-title":"J. Appl. Cryst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1107\/S0021889803021800","article-title":"Software for guided crystal structure analysis","volume":"36","author":"Betteridge","year":"2003","journal-title":"J. Appl. Cryst."},{"key":"ref_48","unstructured":"Crystal Impact (2010). DIAMOND\u2014Crystal and Molecular Structure Visualization, Crystal Impact. Version 3.2e2."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, Y., McGivern, D.R., Cheng, L., Li, G., Lemon, S.M., Niu, J., Su, L., and Reszka-Blanco, N.J. (2015). Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135232"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/nbt.3582","article-title":"Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids","volume":"34","author":"Chaveroux","year":"2016","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:42Z","timestamp":1760139582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,28]]},"references-count":50,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137171"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137171","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,28]]}}}