{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:53:37Z","timestamp":1787028817836,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Owing to the limitations of traditional systemic drug delivery in the treatment of bone diseases with side effects on normal cells, the selection of materials with high affinities for bones, as targeting ligands to modify drug carriers, has become an important research topic. Tetracyclines (TCs) have an adsorption effect on hydroxyapatite (HAp). Thus, they can be used as bone-targeting ligands and combined with drug carriers. In this study, density functional theory is used to analyze the interaction mechanism of TC, oxytetracycline (OTC), chlortetracycline, and HAp. We calculate the electrostatic potential (ESP) and molecular orbitals to predict the possible binding sites of TCs on the HAp surface. The adsorption energy is used to compare the affinities of the three TCs to HAp. An independent gradient model analysis is performed to study the weak interaction between TCs and HAp. The coordination bond between TCs and the HAp surface is evaluated by conducting a charge density difference analysis. The results show that OTC has the highest affinity to HAp because the introduction of hydroxyl groups change the adsorption configuration of OTC. Thus, OTC adsorbed on HAp in a broken-line shape exposes more binding sites. This study provides a theoretical basis for TCs as bone-targeting ligands in treating bone diseases and in improving the safety of treatment by selecting different bone-targeting ligands.<\/jats:p>","DOI":"10.3390\/ma15030797","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T08:37:18Z","timestamp":1642754238000},"page":"797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sorption Studies of Tetracycline Antibiotics on Hydroxyapatite (001) Surface\u2014A First-Principles Insight"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2402-3250","authenticated-orcid":false,"given":"Jiaming","family":"Song","sequence":"first","affiliation":[{"name":"The Conversationalist Club, School of Stomatology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai\u2019an 271016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiyu","family":"Cui","sequence":"additional","affiliation":[{"name":"The Conversationalist Club, School of Stomatology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai\u2019an 271016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-4498","authenticated-orcid":false,"given":"Xuran","family":"Mao","sequence":"additional","affiliation":[{"name":"The Conversationalist Club, School of Stomatology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai\u2019an 271016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixuan","family":"Huang","sequence":"additional","affiliation":[{"name":"The Conversationalist Club, School of Stomatology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai\u2019an 271016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul 08308, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-2633","authenticated-orcid":false,"given":"Hengbo","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Conversationalist Club, School of Stomatology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai\u2019an 271016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Mohamad, N.-V., Giaze, T.R., Chin, K.-Y., Mohamed, N., and Ima-Nirwana, S. (2019). Prostate Cancer and Bone Metastases: The Underlying Mechanisms. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102587"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1007\/s00520-016-3154-x","article-title":"Burden of symptoms associated with development of metastatic bone disease in patients with breast cancer","volume":"24","author":"Cleeland","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jconrel.2017.11.009","article-title":"Drug delivery systems functionalized with bone mineral seeking agents for bone targeted therapeutics","volume":"269","author":"Rotman","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ijpharm.2014.08.067","article-title":"Poly aspartic acid peptide-linked PLGA based nanoscale particles: Potential for bone-targeting drug delivery applications","volume":"475","author":"Jiang","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.2147\/IJN.S44393","article-title":"Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration","volume":"8","author":"Gu","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijpharm.2013.10.048","article-title":"Poly(\u03b3-benzyl-l-glutamate)-PEG-alendronate multivalent nanoparticles for bone targeting","volume":"460","author":"Noiray","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3181\/00379727-186-42590A","article-title":"Bone-Targeted Carbonic Anhydrase Inhibitors: Effect of a Proinhibitor on Bone Resorption In Vitro","volume":"186","author":"Pierce","year":"1987","journal-title":"Exp. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s13346-017-0394-3","article-title":"Bone-seeking agents for the treatment of bone disorders","volume":"7","author":"Cawthray","year":"2017","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Stapleton, M., Sawamoto, K., Alm\u00e9ciga-D\u00edaz, C.J., MacKenzie, W.G., Mason, R.W., Orii, T., and Tomatsu, S. (2017). Development of Bone Targeting Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071345"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1080\/10717544.2017.1347966","article-title":"Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of osteoporosis","volume":"24","author":"Xie","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/s13346-018-0561-1","article-title":"Bone-targeted delivery of simvastatin-loaded PEG-PLGA micelles conjugated with tetracycline for osteoporosis treatment","volume":"8","author":"Xie","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.2147\/IJN.S88798","article-title":"Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system","volume":"10","author":"Yuan","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.bmcl.2008.12.051","article-title":"Bone selective effect of an estradiol conjugate with a novel tetracycline-derived bone-targeting agent","volume":"19","author":"Neale","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.addr.2004.12.017","article-title":"Skeletal function and structure: Implications for tissue-targeted therapeutics","volume":"57","author":"Miller","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1002\/elps.200600004","article-title":"Proteomic analysis of cartilage- and bone-associated samples","volume":"27","author":"Lammi","year":"2006","journal-title":"Electrophoresis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.4028\/www.scientific.net\/AMR.47-50.1379","article-title":"An Experimental and Computational Study on Zn-Substituted Hydroxyapatite","volume":"47\u201350","author":"Ren","year":"2008","journal-title":"Adv. Mater. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1080\/00150193.2013.822774","article-title":"A Computational Study of the Properties and Surface Interactions of Hydroxyapatite, Structure and Properties: Modeling and Synchrotron Data Analysis of Modified Hydroxyapatite Structure","volume":"449","author":"Bystrov","year":"2013","journal-title":"Ferroelectrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s11914-020-00604-4","article-title":"Bone-Targeting Systems to Systemically Deliver Therapeutics to Bone Fractures for Accelerated Healing","volume":"18","author":"Nielsen","year":"2020","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.addr.2012.01.012","article-title":"Targeting polymer therapeutics to bone","volume":"64","author":"Low","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jconrel.2016.04.025","article-title":"Bone-targeted delivery of nanodiamond-based drug carriers conjugated with alendronate for potential osteoporosis treatment","volume":"232","author":"Ryu","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1039\/C2CS35265F","article-title":"Design, functionalization strategies and biomedical applications of targeted biodegradable\/biocompatible polymer-based nanocarriers for drug delivery","volume":"42","author":"Nicolas","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1359-0286(02)00117-1","article-title":"Biodegradable nanoparticles for drug delivery and targeting","volume":"6","author":"Hans","year":"2002","journal-title":"Curr. Opin. Solid State Mater. Sci."},{"key":"ref_23","first-page":"51","article-title":"Tetracyclines","volume":"128","year":"1973","journal-title":"Zbl. Bakt. Abt. II Bo."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"141975","DOI":"10.1016\/j.scitotenv.2020.141975","article-title":"Occurrence, fate, and risk assessment of typical tetracycline antibiotics in the aquatic environment: A review","volume":"753","author":"Xu","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1365-2885.1996.tb00054.x","article-title":"Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs","volume":"19","author":"Nielsen","year":"1996","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"128651","DOI":"10.1016\/j.chemosphere.2020.128651","article-title":"Photocatalytic degradation of tetracycline antibiotics using delafossite silver ferrite-based Z-scheme photocatalyst: Pathways and mechanism insight","volume":"270","author":"Guo","year":"2020","journal-title":"Chemosphere"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1039\/C8AN02284D","article-title":"Amplified colorimetric detection of tetracycline based on an enzyme-linked aptamer assay with multivalent HRP-mimicking DNAzyme","volume":"144","author":"Gong","year":"2019","journal-title":"Analyst"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.jsps.2021.04.017","article-title":"Determination of tetracycline, oxytetracycline and chlortetracycline residues in seafood products of Saudi Arabia using high performance liquid chromatography\u2013Photo diode array detection","volume":"29","author":"Alanazi","year":"2021","journal-title":"Saudi Pharm. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/208787a0","article-title":"Binding of Tetracyclines to Bone","volume":"208","author":"Perrin","year":"1965","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12161-020-01858-5","article-title":"Evaluation of Hydroxyapatite as Adsorbent in the Analysis of Trace Tetracyclines in Complex Matrices","volume":"14","author":"Zhou","year":"2020","journal-title":"Food Anal. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1051\/e3sconf\/20172200062","article-title":"Removal of oxytetracycline from aqueous solutions by hydroxyapatite as a low-cost adsorbent","volume":"22","author":"Harja","year":"2017","journal-title":"E3S Web Conf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"145291","DOI":"10.1016\/j.scitotenv.2021.145291","article-title":"Tetracyclines in the environment: An overview on the occurrence, fate, toxicity, detection, removal methods, and sludge management","volume":"771","author":"Jsa","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.scitotenv.2018.02.027","article-title":"Studies on adsorption of oxytetracycline from aqueous solutions onto hydroxyapatite","volume":"628\u2013629","author":"Harja","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1039\/D1QM00851J","article-title":"Recent advances in bone-targeting nanoparticles for biomedical applications","volume":"5","author":"Zhou","year":"2021","journal-title":"Mater. Chem. Front."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rogalski, W. (1985). Chemical Modification of the Tetracyclines. The Tetracyclines, Springer.","DOI":"10.1007\/978-3-642-70304-1_5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/177433a0","article-title":"Avidity of the tetracyclines for the cations of metals","volume":"177","author":"Albert","year":"1956","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.jcis.2010.04.081","article-title":"Studies on the sorption of tetracycline onto clays and marine sediment from seawater","volume":"349","author":"Wang","year":"2010","journal-title":"J. Colloid Interface Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"194103","DOI":"10.1063\/5.0007045","article-title":"CP2K: An electronic structure and molecular dynamics software package\u2014Quickstep: Efficient and accurate electronic structure calculations","volume":"152","author":"Iannuzzi","year":"2020","journal-title":"J. Chem. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-functional exchange-energy approximation with correct asymptotic behavior","volume":"38","author":"Becke","year":"1988","journal-title":"Phys. Rev. A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","author":"Grimme","year":"2010","journal-title":"J. Chem. Phys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10269","DOI":"10.1021\/j100142a004","article-title":"A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model","volume":"97","author":"Bayly","year":"1993","journal-title":"J. Phys. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1021\/j100373a017","article-title":"Use of the electrostatic potential at the molecular surface to interpret and predict nucleophilic processes","volume":"94","author":"Sjoberg","year":"1990","journal-title":"J. Phys. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1039\/C9EN00866G","article-title":"Insights into the adsorption mechanism and dynamic behavior of tetracycline antibiotics on reduced graphene oxide (RGO) and graphene oxide (GO) materials","volume":"6","author":"Ai","year":"2019","journal-title":"Environ. Sci. Nano"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17928","DOI":"10.1039\/C7CP02110K","article-title":"Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density","volume":"19","author":"Lefebvre","year":"2017","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: A multifunctional wavefunction analyzer","volume":"33","author":"Lu","year":"2012","journal-title":"J. Comput. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/15\/3\/797\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:05:11Z","timestamp":1760133911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/15\/3\/797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ma15030797"],"URL":"https:\/\/doi.org\/10.3390\/ma15030797","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,21]]}}}