{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:21:06Z","timestamp":1775064066194,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation (RSF)","award":["21-12-00251"],"award-info":[{"award-number":["21-12-00251"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Iron-doped hydroxyapatite (Fe-HAp) is regarded as a promising magnetic material with innate biocompatibility. Despite the many studies reported in the literature, a detailed theoretical description of Fe inclusions is still missing. There is even no consensual view on what kind of Fe defects take place in Fe-HAp\u2014iron interstitial or calcium substitutions? In order to address these questions, we employ modern first-principles methodologies, including hybrid density functional theory, to find the geometry, electronic, magnetic and thermodynamic properties of iron impurities in Fe-HAp. We consider a total of 26 defect configurations, including substitutional (phosphorus and calcium sites) and interstitial defects. Formation energies are estimated considering the boundaries of chemical potentials in stable hydroxyapatite. We show that the most probable defect configurations are: Fe3+ and Fe2+ substitutions of Ca(I) and Ca(II) sites under Ca-poor conditions. Conversely, Fe interstitials near the edge of the hydroxyl channel are favored in Ca-rich material. Substitutional Fe on the P site is also a probable defect, and unlike the other forms of Fe, it adopts a low-spin state. The analysis of Fe K-XANES spectra available in the literature shows that Fe-HAp usually contains iron in different configurations.<\/jats:p>","DOI":"10.3390\/nano11112978","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T20:42:54Z","timestamp":1636317774000},"page":"2978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Iron in Hydroxyapatite: Interstitial or Substitution Sites?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-7905","authenticated-orcid":false,"given":"Leon","family":"Avakyan","sequence":"first","affiliation":[{"name":"Faculty of Physics, Southern Federal University, 5 Zorge St., 344090 Rostov-on-Don, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-2206","authenticated-orcid":false,"given":"Ekaterina","family":"Paramonova","sequence":"additional","affiliation":[{"name":"Institute of Mathematical Problems of Biology, Branch of Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, 1 Vitkevicha St., Pushchino, 142290 Moscow, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-9469","authenticated-orcid":false,"given":"Vladimir","family":"Bystrov","sequence":"additional","affiliation":[{"name":"Institute of Mathematical Problems of Biology, Branch of Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, 1 Vitkevicha St., Pushchino, 142290 Moscow, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-366X","authenticated-orcid":false,"given":"Jos\u00e9","family":"Coutinho","sequence":"additional","affiliation":[{"name":"I3N, Department of Physics, Campus Santiago, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Sandrine","family":"Gomes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-751X","authenticated-orcid":false,"given":"Guillaume","family":"Renaudin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1039\/B910885H","article-title":"Application of calcium phosphate nanoparticles in biomedicine","volume":"20","author":"Epple","year":"2010","journal-title":"J. Mater. Chem."},{"key":"ref_2","first-page":"14","article-title":"Computational studies of the hydroxyapatite nanostructures, peculiarities and properties","volume":"12","author":"Bystrov","year":"2017","journal-title":"Math. Biol. Bioinform."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fmats.2016.00059","article-title":"Apatite Glass-Ceramics: A Review","volume":"3","author":"Duminis","year":"2017","journal-title":"Front. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1080\/03639045.2018.1451879","article-title":"Calcium phosphate-based nanosystems for advanced targeted nanomedicine","volume":"44","author":"Carella","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0162-0134(92)80007-I","article-title":"Ferric iron in synthetic carbonate apatites: A M\u00f6ssbauer effect study","volume":"45","author":"Mayer","year":"1992","journal-title":"J. Inorg. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1021\/jp5114027","article-title":"Structural and Magnetic Phase Transformations of Hydroxyapatite-Magnetite Composites under Inert and Ambient Sintering Atmospheres","volume":"119","author":"Boda","year":"2015","journal-title":"J. Phys. Chem. C"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8389","DOI":"10.2147\/IJN.S147355","article-title":"Magnetic hydroxyapatite: A promising multifunctional platform for nanomedicine application","volume":"12","author":"Mondal","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.colsurfb.2016.06.042","article-title":"Different hydroxyapatite magnetic nanoparticles for medical imaging: Its effects on hemostatic, hemolytic activity and cellular cytotoxicity","volume":"146","author":"Laranjeira","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.actbio.2011.09.032","article-title":"Intrinsic magnetism and hyperthermia in bioactive Fe-doped hydroxyapatite","volume":"8","author":"Tampieri","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.1039\/C4TB00984C","article-title":"A hydroxyapatite\u2013Fe2O3 based material of natural origin as an active sunscreen filter","volume":"2","author":"Piccirillo","year":"2014","journal-title":"J. Mater. Chem. B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.msec.2016.01.071","article-title":"Magnetic hydroxyapatite coatings as a new tool in medicine: A scanning probe investigation","volume":"62","author":"Gambardella","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1039\/c3ce26683d","article-title":"Hollow magnetic hydroxyapatite microspheres with hierarchically mesoporous microstructure for pH-responsive drug delivery","volume":"15","author":"Lin","year":"2013","journal-title":"CrystEngComm"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.materresbull.2014.06.018","article-title":"Mesoporous Fe3O4 \/hydroxyapatite composite for targeted drug delivery","volume":"59","author":"Gu","year":"2014","journal-title":"Mater. Res. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1103\/PhysRev.185.477","article-title":"M\u00f6ssbauer Studies of Natural Apatite","volume":"185","author":"Ok","year":"1969","journal-title":"Phys. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"224107","DOI":"10.1103\/PhysRevB.66.224107","article-title":"Fe2+\/Fe3+substitution in hydroxyapatite: Theory and experiment","volume":"66","author":"Jiang","year":"2002","journal-title":"Phys. Rev. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11774","DOI":"10.1021\/ic801491t","article-title":"The Crystal Chemistry of Ferric Oxyhydroxyapatite","volume":"47","author":"Low","year":"2008","journal-title":"Inorg. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16457","DOI":"10.1039\/C6CP00474A","article-title":"Hydroxyapatite substituted by transition metals: Experiment and theory","volume":"18","author":"Zilm","year":"2016","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.actbio.2016.12.011","article-title":"Atomic scale modeling of iron-doped biphasic calcium phosphate bioceramics","volume":"50","author":"Gomes","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jssc.2018.06.032","article-title":"Fe incorporation into hydroxyapatite channels by Fe loading and post-annealing","volume":"265","author":"Kato","year":"2018","journal-title":"J. Solid State Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Renaudin, G., Gomes, S., and Nedelec, J.M. (2017). First-row transition metal doping in calcium phosphate bioceramics: A detailed crystallographic study. Materials, 10.","DOI":"10.3390\/ma10010092"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154706","DOI":"10.1063\/1.5025329","article-title":"Optoelectronics and defect levels in hydroxyapatite by first-principles","volume":"148","author":"Avakyan","year":"2018","journal-title":"J. Chem. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Martin, R., Reining, L., and Ceperley, D. (2016). Interacting Electrons, Cambridge University Press.","DOI":"10.1017\/CBO9781139050807"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"134106","DOI":"10.1103\/PhysRevB.67.134106","article-title":"Electronic and crystallographic structure of apatites","volume":"67","author":"Calderin","year":"2003","journal-title":"Phys. Rev. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155104","DOI":"10.1103\/PhysRevB.70.155104","article-title":"Electronic structure and bonding in calcium apatite crystals: Hydroxyapatite, fluorapatite, chlorapatite, and bromapatite","volume":"70","author":"Rulis","year":"2004","journal-title":"Phys. Rev. B"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245410","DOI":"10.1103\/PhysRevB.76.245410","article-title":"Electronic structure, bonding, charge distribution, and x-ray absorption spectra of the (001) surfaces of fluorapatite and hydroxyapatite from first principles","volume":"76","author":"Rulis","year":"2007","journal-title":"Phys. Rev. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"014102","DOI":"10.1103\/PhysRevB.75.014102","article-title":"First-principles study of vacancy formation in hydroxyapatite","volume":"75","author":"Matsunaga","year":"2007","journal-title":"Phys. Rev. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134108","DOI":"10.1103\/PhysRevB.84.134108","article-title":"First-principles study of the biomineral hydroxyapatite","volume":"84","author":"Slepko","year":"2011","journal-title":"Phys. Rev. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195302","DOI":"10.1088\/0022-3727\/48\/19\/195302","article-title":"Computational study of hydroxyapatite structures, properties and defects","volume":"48","author":"Bystrov","year":"2015","journal-title":"J. Phys. D Appl. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/2041050a0","article-title":"Crystal Structure of Hydroxyapatite","volume":"204","author":"Kay","year":"1964","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2138\/rmg.2002.48.1","article-title":"The Crystal Structure of Apatite, Ca5(PO4)3(F,OH,Cl)","volume":"48","author":"Hughes","year":"2002","journal-title":"Rev. Mineral. Geochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1126\/science.180.4090.1055","article-title":"Monoclinic hydroxyapatite","volume":"180","author":"Elliott","year":"1973","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1023\/A:1006610521173","article-title":"Preparation and dielectric property of sintered monoclinic hydroxyapatite","volume":"18","author":"Ikoma","year":"1999","journal-title":"J. Mater. Sci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395502","DOI":"10.1088\/0953-8984\/21\/39\/395502","article-title":"QUANTUM ESPRESSO: A modular and open-source software project for quantum simulations of materials","volume":"21","author":"Giannozzi","year":"2009","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"465901","DOI":"10.1088\/1361-648X\/aa8f79","article-title":"Advanced capabilities for materials modelling with Quantum ESPRESSO","volume":"29","author":"Giannozzi","year":"2017","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8207","DOI":"10.1063\/1.1564060","article-title":"Hybrid functionals based on a screened Coulomb potential","volume":"118","author":"Heyd","year":"2003","journal-title":"J. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224106","DOI":"10.1063\/1.2404663","article-title":"Influence of the exchange screening parameter on the performance of screened hybrid functionals","volume":"125","author":"Krukau","year":"2006","journal-title":"J. Chem. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1103\/PhysRevLett.77.3865","article-title":"Generalized Gradient Approximation Made Simple","volume":"77","author":"Perdew","year":"1996","journal-title":"Phys. Rev. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"085117","DOI":"10.1103\/PhysRevB.88.085117","article-title":"Optimized norm-conserving Vanderbilt pseudopotentials","volume":"88","author":"Hamann","year":"2013","journal-title":"Phys. Rev. B"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cpc.2015.05.011","article-title":"Optimization algorithm for the generation of ONCV pseudopotentials","volume":"196","author":"Schlipf","year":"2015","journal-title":"Comput. Phys. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174105","DOI":"10.1103\/PhysRevB.96.174105","article-title":"Theory of the carbon vacancy in 4 H-SiC: Crystal field and pseudo-Jahn-Teller effects","volume":"96","author":"Coutinho","year":"2017","journal-title":"Phys. Rev. B"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1021\/acs.jpcc.8b11350","article-title":"Sub-Band Gap Absorption Mechanisms Involving Oxygen Vacancies in Hydroxyapatite","volume":"123","author":"Bystrov","year":"2019","journal-title":"J. Phys. Chem. C"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"015008","DOI":"10.1088\/2516-1075\/aafc4b","article-title":"Can we rely on hybrid-DFT energies of solid-state problems with local-DFT geometries?","volume":"1","author":"Gouveia","year":"2019","journal-title":"Electron. Struct."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7649","DOI":"10.1103\/PhysRevB.38.7649","article-title":"First-principles study of the atomic reconstructions and energies of Ga- and As-stabilized GaAs(100) surfaces","volume":"38","author":"Qian","year":"1988","journal-title":"Phys. Rev. B"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4283\/JMAG.2011.16.3.201","article-title":"Structural, Magnetic, and Electronic Properties of Fe: A Screened Hybrid Functional Study","volume":"16","author":"Jang","year":"2011","journal-title":"J. Magn."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1021\/acs.jctc.6b00640","article-title":"When Density Functional Approximations Meet Iron Oxides","volume":"12","author":"Meng","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"042104","DOI":"10.1063\/1.5020134","article-title":"Iron and intrinsic deep level states in Ga2O3","volume":"112","author":"Ingebrigtsen","year":"2018","journal-title":"Appl. Phys. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1103\/PhysRevB.51.4014","article-title":"Periodic boundary conditions in ab initio calculations","volume":"51","author":"Makov","year":"1995","journal-title":"Phys. Rev. B"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"235104","DOI":"10.1103\/PhysRevB.78.235104","article-title":"Assessment of correction methods for the band-gap problem and for finite-size effects in supercell defect calculations: Case studies for ZnO and GaAs","volume":"78","author":"Lany","year":"2008","journal-title":"Phys. Rev. B"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10259","DOI":"10.1021\/ic2013107","article-title":"Simple, Unambiguous Theoretical Approach to Oxidation State Determination via First-Principles Calculations","volume":"50","author":"Sit","year":"2011","journal-title":"Inorg. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"345501","DOI":"10.1088\/0953-8984\/21\/34\/345501","article-title":"Self-consistent Aspects of X-ray Absorption Calculations","volume":"21","author":"Bunau","year":"2009","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"van Bokhoven, J.A., and Lamberti, C. (2016). X-ray Absorption and X-ray Emission Spectroscopy: Theory and Applications. X-ray Absorption and X-ray Emission Spectroscopy, John Wiley & Sons, Ltd.. Chapter X-ray Absorption and Emission Spectroscopy for Catalysis.","DOI":"10.1002\/9781118844243"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8543","DOI":"10.1021\/acs.jpcc.7b12797","article-title":"Insight from X-ray Absorption Spectroscopy to Octahedral\/Tetrahedral Site Distribution in Sm-Doped Iron Oxide Magnetic Nanoparticles","volume":"122","author":"Soldatov","year":"2018","journal-title":"J. Phys. Chem. C"},{"key":"ref_53","unstructured":"Lide, D.R. (2005). CRC Handbook of Chemistry and Physics, CRC Press. [88th ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D420","DOI":"10.1093\/nar\/gkr900","article-title":"Crystallography Open Database (COD): An open-access collection of crystal structures and platform for world-wide collaboration","volume":"40","author":"Merkys","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/0895795031000109670","article-title":"Thermo-elastic property of Ca(OH)2portlandite","volume":"23","author":"Fukui","year":"2003","journal-title":"High Press. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"025201","DOI":"10.1088\/2053-1591\/2\/2\/025201","article-title":"High pressure behavior of P2O5crystalline modifications: Compressibility, elastic properties and phase transitions","volume":"2","author":"Brazhkin","year":"2015","journal-title":"Mater. Res. Express"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.2138\/am.2009.3160","article-title":"Equation of state of -tricalcium phosphate, -Ca3(PO4)2, to lower mantle pressures","volume":"94","author":"Zhai","year":"2009","journal-title":"Am. Mineral."},{"key":"ref_58","unstructured":"Hughes, J., Fransolet, A., and Schreyer, W. (1993). The atomic arrangement of iron-bearing apatite. Neues Jahrbuch Fur Mineralogie-Monatshefte, Schweizerbart Science Publishers."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115308","DOI":"10.1016\/j.mseb.2021.115308","article-title":"Formation of vacancy point-defects in hydroxyapatite nanobelts by selective incorporation of Fe3+ ions in Ca(II) sites. A CL and XPS study","volume":"271","author":"Carrera","year":"2021","journal-title":"Mater. Sci. Eng. B"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/BF02553707","article-title":"Iron uptake by teeth and bones: A mossbauer effect study","volume":"37","author":"Bauminger","year":"1985","journal-title":"Calcif. Tissue Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"174101","DOI":"10.1063\/1.3491272","article-title":"On Koopmans\u2019 theorem in density functional theory","volume":"133","author":"Tsuneda","year":"2010","journal-title":"J. Chem. Phys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19917","DOI":"10.1039\/C4CP03113J","article-title":"Structural properties of iron-phosphate glasses: Spectroscopic studies and ab initio simulations","volume":"16","author":"Stoch","year":"2014","journal-title":"Phys. Chem. Chem. Phys."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/11\/2978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:26:34Z","timestamp":1760167594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/11\/2978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,5]]},"references-count":62,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nano11112978"],"URL":"https:\/\/doi.org\/10.3390\/nano11112978","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,5]]}}}