Synthesis, characterization and antibacterial properties of apatite-related zirconium, carbonate and zinc-containing calcium phosphates

Synthesis, characterization and antibacterial properties of apatite-related zirconium, carbonate and zinc-containing calcium phosphates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Synthesis, characterization and antibacterial properties of apatite-related zirconium, carbonate and zinc-containing calcium phosphates Nataliia Strutynska, Lidiia D. Dremova, OksanaV. Livitska, Iryna I. Grynyuk, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5346923/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Apatite-related zirconium, carbonate and zinc-containing calcium phosphates have been synthesized in aqueous solutions at different molar ratios Ca 2+ : Zr 4+ : Zn 2+ : PO 4 3- : CO 3 2- = (10-2x-y/2-z) : x : y : (6-z) : z (x = 0.05, 0.1, 0.5 and 1.0; y = 0.1, 0.5, z = 0, 0.5) and heated to 600 o C during 2 hours. X-ray powder diffraction and FTIR spectroscopy data confirmed the formation of single phase modified apatite-related calcium phosphates with partial substitution of PO 4 3- by CO 3 2- in anionic sublattice (B-type). The calculated lattice parameters for prepared Zr 4+ , Zn 2+ - modified calcium phosphates correlate with amount of dopants in their composition. The sizes of prepared phosphates do not depend on composition of initial solution and vary in the range 30-45nm. The highest antimicrobial effect against Staphylococcus aureus strain was found for phosphate Ca 9 Zr 0.5 (PO 4 ) 6 (OH) 2 (at its adding to 10 mM). Modification of Zr-containing calcium phosphate with carbonate anion and Zn 2+ decreased the Pseudomonas aeruginosa survival in ten times. zirconium zinc hydroxyapatite antibacterial effect Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Among a huge amount of complex oxide compounds, calcium phosphates occupy a unique place because of a great variety of possible composition, structural types and properties (physico-chemical, mechanical, thermal) which used in many branches of industry, ecology and medicine (George et al. 2022 ; Bhat et al. 2022 ; Gruselle et al. 2022 ; Fihri et al.). Hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HAP) is the main member of calcium phosphates raw, the most stable and the least soluble compound among them. Due to its chemical and structural similarity to the mineral part of bone and tooth tissues and biological qualities (biocompatibility, bioactivity, osteoconductivity), HAP and substituted analogs are widely used as a coating for orthopedic and dental implants, a component of calcium phosphate cements, drug delivery systems etc. (George et al. 2020 ; Fiume et al. 2021 ; Galotta et al. 2024 ; Lara-Ochoa et al. 2021 ). Flexibility of apatite framework allows to incorporate different cations and anions in its structure effecting physico-chemical characteristics and biological behavior. Synthesis of HAP and its derivatives in different forms includes a wide range of approaches: wet chemical synthesis (precipitation, sol-gel, hydrothermal), solid state reactions (mechanochemical, sintering), biomimetic (biomineralization, template-assisted synthesis) (Mashak et al. 2022 ; Hussain et al. 2024 ; Mohd Pu'ad et al. 2020; Munir et al. 2022 ). Carbonated hydroxyapatites are more similar to the inorganic component of human bones and can be used as non-toxic and bioresorbable materials for filling bone defects or as coatings of dental and orthopedic metal alloys. The carbonate groups create lattice distortion and crystal defects in apatite structure, cause lower crystallinity, improved solubility and bioactivity, reduce the thermal stability, effect mechanical behaviour. There facts indicate that the mechanical function of bone could be modulated and biomaterials based on carbonated HAP could be adapted to special medical needs (Thang et al. 2023 ; Yotsova et al. 2024; Shikawa et al. 2021; Safarzadeh et al. 2022 ). Carbonate ions could substitute phosphate (B-type) or hydroxide (A-type) in apatite structure or double substitution also occurs (AB-type). Carbonate substitution in bones is usually B-type (Nowicki et al. 2020 ; Petit et al. 2022 ; Sun et al. 2016 ). Zinc is one of the most important trace elements in the human body, which is present in all tissues and performs diverse roles, such as hormonal and enzyme activity, nucleic acid metabolism, maintenance of membrane structure and function, biomineralization and potentially pathological calcification etc. (Wen et al. 2023 ; Badea et al. 2023 ; Molenda et al. 2023). Zn incorporation in apatite structure was intensively explored in many studies (Nenen et al. 2022 ; Dornelas et al. 2024 ; Sirajunisha et al. 2021 ; Cuozzo et al. 2020 ; Ullah et al. 2020 ). It was reported that Zn-containing materials enhance bone repair through promoting cell proliferation, osteogenic activity, angiogenesis, and inhibiting osteoclast differentiation. Moreover, Zn-based HAPs posses effective antibacterial properties against various Gram-positive and Gram-negative strains (Mahanty et al. 2024; Okada et al. 2022 ; Uysal et al. 2021 ; Ullah et al. 2020 ; Lima et al. 2021 ). Many attempts were also made to incorporate zirconium ions (Zr 4+ ) in calcium phosphates structure including the creation of composites based on ZrO 2 and HAP with improved biological and mechanical properties and their possible use in dental and orthopedic fields (Sharifianjazi et al 2020 ; Bollino et al. 2017 ; Khoshsima et al. 2016 ; Ayoub et al. 2018 ; Elwira et al. 2021 ). S. aureus and P. aeruginosa strains are one of the dangerous pathogens, causative agents of infectious diseases with various clinical manifestations, in particular, joint and bone diseases, and are capable of causing sepsis, so the study of the effect of synthetic materials on S. aureus and P. aeruginosa is important for to evaluate their further practical use. The aim of the present study was to investigate the possibility of formation calcium phosphates in the systems Ca 2+ -Zr 4+ -Zn 2+ -PO 4 3− -CO 3 2− that predict of partial substitution of calcium atoms by zirconium atoms as well as complex substitution of calcium atoms by zirconium and zinc cations while phosphate anion by carbonate groups in apatite-type structure and influence of nature and amounts of dopants on antibacterial activity of prepared samples against S. aureus and P. аeruginosa strains. Experimental Preparation of doped calcium phosphates. Chemically modified apatite-related phosphates with general compositions Ca 10-2x Zr x (PO 4 ) 6 (OH) 2 , Ca 9.75-2x Zr x (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 and Ca 9-z-y/2 Zr 0.5 Zn z (PO 4 ) 6-y (CO 3 ) y (OH) 2 (x = 0.05, 0.1, 0.5 and 1.0; y = 0, 0.5; z = 0.1, 0.5) were synthesized from aqua solution at temperature 25 o C with further heating of solid powders to 600 o C during 2 hours. Compounds Ca(NO 3 ) 2 ·4H 2 O, Zn(NO 3 ) 2 ·6H 2 O, NH 4 HCO 3 , (NH 4 ) 2 HPO 4 , ZrO(NO 3 ) 2 were used as initial materials. Nitrates mixture (Ca(NO 3 ) 2 ·4H 2 O and Zn(NO 3 ) 2 ·6H 2 O) was dissolved in deionized water and necessary amount of ZrO(NO 3 ) 2 was added. After mixing of mixture during 15 min the solution containing phosphate and carbonate anions was added at intensive magnetic stirring. The obtained precipitates were stirred for 5 min and 3 ml of NH 3 *H 2 O was added. Then the water was evaporated and solid powders after grounding were annealed at 600 o C. Muffle furnace SNOL-7.2/1100 (TermoPro-601 temperature controller) was used for annealing of samples. Characterization of synthesized modified calcium phosphates. The phase composition of samples was investigated by X-ray powder diffraction method. XRD patterns were recorded using Shimadzu XRD-6000 diffractometer with Cu-Kα radiation (λ = 1.54178 Å, 2 θ = 5–60°, step size 0.01°). The crystalline phase was identified by reference to the ICDD (International Center for Diffraction Data) database for hydroxyapatite Ca 10 (PO 4 ) 6 (OH) 2 (#00-074-0565). Lattice parameters and crystallites size for modified calcium phosphates were calculated using Fullprof program and Shererra equation, respectively. Presence of different anions types in synthesized phases was confirmed by Fourier transform infrared spectroscopy (frequency range 400–4000 cm -1 ) for samples pressed in KBr pellets. PerkinElmer Spectrum BX spectrometer was used. Antibacterial activity Obtained modified calcium phosphates with different composition have been tested against opportunistic microorganisms: Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa АТСС 9027 after their sterilized by autoclaving at 0.75 atm and temperature of 112°C during 30 min. The different amounts (5 mM, 10 mM and 20 mM) of obtained samples were added overnight in sterile bottles with nutrient medium and 2% (10 5 CFU/ml) of S. aureus or P. aeruginosa strains. The growth of culture without sample was used as a control. The bottles were incubated at 37 ± 1 0 C for 24 h and then suspensions of bacterial culture with some samples were incubated on petri dishes containing tryptone soya agar. The amount of bacterial colonies of tested strains on the surface of the agar medium was calculated on the next day. Statistical analysis. Antibacterial data were presented as the mean (M) ± standard deviation (SD). Each experiment was repeated at least three times. Data processing was performed using the program ≪STATISTICA 7.0≫ (StatSoft Inc., Tulsa, OK, USA). The post-hoc-test using the criterion of LSD was used for assessing the reliability of quantitative indicators of differences in different strains. A P-value of ≤ 0.05 was considered as statistically significant to control and marked*. Compounds can be labeled with Arabic numerals. For example: Triphenylamine (1) (5.0 g, 20.4 mmol) and dry dimethylformamide (15.0 mL) were added into the mixture. ( Note : This is a significant change because Roman numerals were used in the previous journal format.) Reaction mechanisms can be labelled as numbered Schemes or Figures. Schemes do not have captions (see Scheme 1 below). All drawings and plots should be pasted into the document using the option “Paste Special” that simplifies their editing. Results and discussion All XRD patterns for prepared modified calcium phosphates are similar and correspond to apatite-type calcium phosphate standard pattern. For example XRD patterns for a raw of synthesized samples are shown in Fig. 1 . Any impurities were not detected for calcium phosphates which contain the highest among determined amounts of dopants that confirmed the preparation of single phase samples independ on amount of dopants. Calculation of lattice parameters showed decrease of parameter values comparing with hydroxyapatite (Са 10 (РО 4 ) 6 (ОН) 2 : а = 9.432 Å, c = 6.881 Å, 00-074-0565) with increasing of substitution degree in cationic sublattice that correlates with calcium Ca 2+ (1.06Å) and zirconium Zr 4+ (0.78Å) ion sizes (Table 1 ). Calculation of crystallite size of prepared modified calcium phosphates using XRD data and Scherrer’s equation showed the formation of nanoparticles in size range 30–45 nm (Table 1 ). Table 1 Crystallographic parameters and crystallite size for prepared complex-doped apatite-related calcium phosphates (hexagonal system, space group P6 3 /m ) Phosphate Cell parameters Crystallite size (nm) a = b , Å c, Å Ca 9.9 Zr 0.05 (PO 4 ) 6 (OH) 2 9.429(4) 6.887(8) 33 Ca 9.8 Zr 0.1 (PO 4 ) 6 (OH) 2 9.412(9) 6.881(4) 43 Ca 9 Zr 0.5 (PO 4 ) 6 (OH) 2 9.407(1) 6.878(3) 38 Ca 8 Zr(PO 4 ) 6 (OH) 2 9.383(1) 6.877(1) 31 Ca 9.65 Zr 0.05 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.415(6) 6.873(9) 35 Ca 9.55 Zr 0.1 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.397(8) 6.886(7) 38 Ca 8.75 Zr 0.5 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.391(2) 6.882(9) 36 Ca 7.75 Zr(PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.366(3) 6.877(2) 31 Ca 8.5 Zr 0.5 Zn 0.5 (PO 4 ) 6 (OH) 2 9.410(3) 6.871(4) 42 Ca 8.65 Zr 0.5 Zn 0.1 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.404(5) 6.863(8) 38 Ca 8.25 Zr 0.5 Zn 0.5 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 9.394(1) 6.856(6) 44 FTIR spectra for all samples contain typical bands of apatite-related calcium phosphate as well as its CO 3 2− substituted analogs and are shown in Fig. 2 . The main characteristic modes of phosphate tetrahedral were detected in the regions580-640 cm − 1 and 990–1220 cm − 1 attributed to stretching and deformation vibrations, respectively. The broad band in region 3200–3600 cm − 1 was attributed to adsorbed water and also includes of structurally-bound OH-group in apatite-type structure. The typical CO 3 2− bands are at 870–875, 1413–1468 cm − 1 that confirmed the partial substitution of PO 4 3− by CO 3 2− with formation of B-type carbonated apatite (Malyshenko et al. 2014 ; Strutynska et al. 2015 ; Strutynska et al. 2023 ) It was found that B-type carbonated apatite-related calcium phosphate showed lower powder crystallinity and enhances solubility of the apatite-type structure (Ezekiel et al. 2018 ). Antibacterial activity. The effect of different amount (5, 10 or 20 mM) of synthesized zirconium, carbonate- as well as zirconium, zinc and carbonate-containing apatite-related calcium phosphates against Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa АТСС 9027 has been investigated. Obtained results showed the better antibacterial activity of samples against S. aureus than that for P. aeruginosa (Fig. 3 and Fig. 4 ). It was found the influence of calcium phosphates composition on their activity against both strains (Fig. 3 and Fig. 4 ). In the case of complex modification of cationic and anionic sublattices of apatite-type calcium phosphate with zirconium and carbonate ions the activity against Staphylococcus aureus was some decreased than that was for Zr-containing phosphate (Fig. 3 . Sample 2 and Sample 1). S. aureus strain was inhibited by 7.4 or a lesser extent to 6.7 times compared to the control after 24 hours of incubation at added of Ca 9 Zr 0.5 (PO 4 ) 6 (OH) 2 (Sample 1) (10 or 20 mM) or Ca 8.75 Zr 0.5 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 (Sample 2) (10mM), respectively. Additional doping of Zr-containing calcium phosphate with zinc cations allow to increase of antibacterial activity (Fig. 3 , Sample 4 and Sample 5). The best antibacterial effect was found for phosphates Ca 8.5 Zr 0.5 Zn 0.5 (PO 4 ) 6 (OH) 2 (Sample 3 at its added of 20 mM) with a tenfold inhibition of the growth of S. aureus compared to the control after 24 h of incubation (the total amount of lgCFU/ml was 8,3 ± 0,05 and 9,03 ± 0,05, respectively). The powder of Ca 8.25 Zr 0.5 Zn 0.5 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 (sample 4 at its added of 10 mM) also inhibited the growth of S. aureus by 8.4 times compared to the control. Modification of Zr-containing apatite structure with carbonate anion insignificant improves of characteristic against P. aeruginosa (Fig. 4 , Sample 2), while the presence of Zn 2+ decreased the strain survival in ten times at adding of these samples in amount of 20 mM (Fig. 4 , Samples 3–4). It should be noted that in the case of samples Ca 8.65 Zr 0.5 Zn 0.1 (PO 4 ) 5.5 (CO 3 ) 0.5 (OH) 2 the increase of activity again P. aeruginosa took place at growing of amount of added sample from 5 mM to 20 mM (Fig. 4 , Sample 5). Thus, obtained results showed to decrease the Staphylococcus aureus strain survival in the presence of prepared zirconium, carbonate and zinc-containing apatite-related calcium phosphate that is important at creation materials for orthopedics. Conclusions According to X-ray powder diffraction and FTIR spectroscopy data the modified apatite-related calcium phosphates were synthesized. The calculated lattice parameters for prepared modified calcium phosphates correlate with amount of zirconium and zinc in their composition. The B-type substitution (PO 4 3- →CO 3 2- ) in the apatite-related structure was realized. The highest antimicrobial effect against Staphylococcus aureus strain was found for phosphate Ca 9 Zr 0.5 (PO 4 ) 6 (OH) 2 , which grown at increasing of added sample amount to 10 mM. Modification of Zr-containing calcium phosphate with carbonate anion insignificant improves of characteristic against Pseudomonas aeruginosa while the presence of Zn 2+ in their composition decreased the strain survival in ten times. Thus, obtained results confirm the possibility of complex incorporation of Zn 2+ , Zr 4+ and CO 3 2- in apatite-type structure of calcium phosphate and their effect on Pseudomonas aeruginosa that is important at creation of materials for medical purpose. 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J Aust Ceram Soc 57:869–897. 10.1007/s41779-021-00583-4 Wen X, Wang J, Pei X, Zhang X (2023) Zinc-based biomaterials for bone repair and regeneration: mechanism and applications. J Mater Chem B 11:11405–11425. 10.1039/D3TB01874A Yotsova R, Peev S (2024) Biological properties and medical applications of carbonate apatite: a systematic review. Pharmaceutics 16(2):291. 10.3390/pharmaceutics16020291 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5346923","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":374673954,"identity":"676f85af-9ca4-4be2-854b-e6d8f4b52965","order_by":0,"name":"Nataliia Strutynska","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYHADNgaGDweIU8rYwMBgANbCOINkLcw8xGgxZ2B//riy7U/idv5jiZ9tztxJbJBIfoBXi2UDj2Hj2TaDxJ0z0g5L59x4BtSSZoBXi8EBHsbGRqCWDTfYG6RzPhwGakkgpIX9IUTL+ePNvy3AWtI/ENDCYAjRciDtmDTDDZCWHAK2HOYxnNlwzth4w420NMueM4eN23jeFODXcrz9wceGMjnZDeePGd/4ceywbD97+ga8WhiYIZRjA0yADb96BLAnVuEoGAWjYBSMQAAATB5PveyilJAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9738-9689","institution":"Taras Shevchenko National University of Kyiv: Kiivs'kij nacional'nij universitet imeni Tarasa Sevcenka","correspondingAuthor":true,"prefix":"","firstName":"Nataliia","middleName":"","lastName":"Strutynska","suffix":""},{"id":374673955,"identity":"a620654d-4132-43ac-99d9-146c3edb80a0","order_by":1,"name":"Lidiia D. Dremova","email":"","orcid":"","institution":"Taras Shevchenko National University of Kyiv: Kiivs'kij nacional'nij universitet imeni Tarasa Sevcenka","correspondingAuthor":false,"prefix":"","firstName":"Lidiia","middleName":"D.","lastName":"Dremova","suffix":""},{"id":374673956,"identity":"d7c5de1e-d574-438f-983c-a4ca8dcced8b","order_by":2,"name":"OksanaV. Livitska","email":"","orcid":"","institution":"Enamine Ltd","correspondingAuthor":false,"prefix":"","firstName":"OksanaV.","middleName":"","lastName":"Livitska","suffix":""},{"id":374673957,"identity":"c6d16ec1-76d2-46e0-9c84-8cd4db0cf226","order_by":3,"name":"Iryna I. Grynyuk","email":"","orcid":"","institution":"National Technical University of Ukraine Igor Sikorsky Kyiv Polytechnic Institute: Nacional'nij tehnicnij universitet Ukraini Kiivs'kij politehnicnij institut imeni Igora Sikors'kogo","correspondingAuthor":false,"prefix":"","firstName":"Iryna","middleName":"I.","lastName":"Grynyuk","suffix":""},{"id":374673958,"identity":"892a1cf4-bf5d-4c22-bd28-ed825d2d1e28","order_by":4,"name":"Olga M. Vasyliuk","email":"","orcid":"","institution":"Institut mikrobiologii i virusologii im D K Zabolotnogo Nacional'na akademia nauk Ukraini","correspondingAuthor":false,"prefix":"","firstName":"Olga","middleName":"M.","lastName":"Vasyliuk","suffix":""}],"badges":[],"createdAt":"2024-10-28 12:03:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5346923/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5346923/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69379669,"identity":"c1415dae-3ecf-450a-bc1b-8cda0fe1f67d","added_by":"auto","created_at":"2024-11-19 18:16:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":80837,"visible":true,"origin":"","legend":"\u003cp\u003eXRD patterns for prepared phosphates with initial compositions: Ca\u003csub\u003e8\u003c/sub\u003eZr(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (a), Ca\u003csub\u003e7.75\u003c/sub\u003eZr(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (b)\u003csub\u003e, \u003c/sub\u003eCa\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (c) and Ca\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (d).\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5346923/v1/188f530d0d12f35d7065415e.png"},{"id":69379667,"identity":"7b408b4c-3550-4e30-b705-50508e530304","added_by":"auto","created_at":"2024-11-19 18:16:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31015,"visible":true,"origin":"","legend":"\u003cp\u003eFTIR spectra for prepared calcium phosphates with general compositions: (a) Ca\u003csub\u003e10-2x\u003c/sub\u003eZr\u003csub\u003ex\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e, (b) – Ca\u003csub\u003e9.75-2x\u003c/sub\u003eZr\u003csub\u003ex\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e, (x = 0.1 (curve 1), 0.5 (curve 2) and 1.0 (curve 3); Ca\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (a, curve 4) and Ca\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (b, curve 4).\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5346923/v1/26001f53365f4e3c567470dd.png"},{"id":69379668,"identity":"09994d8e-cb02-4099-a837-a5770cf2178e","added_by":"auto","created_at":"2024-11-19 18:16:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44852,"visible":true,"origin":"","legend":"\u003cp\u003eThe antibacterial activity against \u003cem\u003eStaphylococcus aureus\u003c/em\u003e ATCC 25923 for prepared samples: Ca\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2 \u003c/sub\u003e(sample 1), Ca\u003csub\u003e8.75\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (Sample 2), Ca\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 3) Ca\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u0026nbsp; (sample 4) and Ca\u003csub\u003e8.65\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 5) which were used in different amount (5, 10 and 20 mM) (M ±m, n = 4).\u003cem\u003e * – p \u0026lt; 0.05 compared to control.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5346923/v1/8e2a532a0899787dd0a91b84.png"},{"id":69379671,"identity":"b195adb7-0bc5-4cdb-a20f-931b9eb0ef5a","added_by":"auto","created_at":"2024-11-19 18:16:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28704,"visible":true,"origin":"","legend":"\u003cp\u003eThe antibacterial activity against \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e АТСС 9027 for prepared samples: Ca\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2 \u003c/sub\u003e(sample 1), Ca\u003csub\u003e8.75\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (Sample 2), Ca\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 3) Ca\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 4) and Ca\u003csub\u003e8.65\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 5) which were used in different amount (5, 10 and 20 mM) (M ±m, n = 4). \u003cem\u003e* – p \u0026lt; 0.05 compared to control.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5346923/v1/b5aa9430fd9249c8a9a9629e.png"},{"id":70178313,"identity":"1a3619b7-5e0c-4fe6-89bb-4e0bd6fc3dad","added_by":"auto","created_at":"2024-11-29 07:54:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":850462,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5346923/v1/3c600f25-338a-4e0f-945b-c43ed39502ec.pdf"}],"financialInterests":"","formattedTitle":"Synthesis, characterization and antibacterial properties of apatite-related zirconium, carbonate and zinc-containing calcium phosphates","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAmong a huge amount of complex oxide compounds, calcium phosphates occupy a unique place because of a great variety of possible composition, structural types and properties (physico-chemical, mechanical, thermal) which used in many branches of industry, ecology and medicine (George et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Bhat et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Gruselle et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Fihri et al.). Hydroxyapatite (Ca\u003csub\u003e10\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e, HAP) is the main member of calcium phosphates raw, the most stable and the least soluble compound among them. Due to its chemical and structural similarity to the mineral part of bone and tooth tissues and biological qualities (biocompatibility, bioactivity, osteoconductivity), HAP and substituted analogs are widely used as a coating for orthopedic and dental implants, a component of calcium phosphate cements, drug delivery systems etc. (George et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Fiume et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Galotta et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Lara-Ochoa et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Flexibility of apatite framework allows to incorporate different cations and anions in its structure effecting physico-chemical characteristics and biological behavior. Synthesis of HAP and its derivatives in different forms includes a wide range of approaches: wet chemical synthesis (precipitation, sol-gel, hydrothermal), solid state reactions (mechanochemical, sintering), biomimetic (biomineralization, template-assisted synthesis) (Mashak et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Hussain et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Mohd Pu'ad et al. 2020; Munir et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCarbonated hydroxyapatites are more similar to the inorganic component of human bones and can be used as non-toxic and bioresorbable materials for filling bone defects or as coatings of dental and orthopedic metal alloys. The carbonate groups create lattice distortion and crystal defects in apatite structure, cause lower crystallinity, improved solubility and bioactivity, reduce the thermal stability, effect mechanical behaviour. There facts indicate that the mechanical function of bone could be modulated and biomaterials based on carbonated HAP could be adapted to special medical needs (Thang et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Yotsova et al. 2024; Shikawa et al. 2021; Safarzadeh et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Carbonate ions could substitute phosphate (B-type) or hydroxide (A-type) in apatite structure or double substitution also occurs (AB-type). Carbonate substitution in bones is usually B-type (Nowicki et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Petit et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Sun et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eZinc is one of the most important trace elements in the human body, which is present in all tissues and performs diverse roles, such as hormonal and enzyme activity, nucleic acid metabolism, maintenance of membrane structure and function, biomineralization and potentially pathological calcification etc. (Wen et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Badea et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Molenda et al. 2023). Zn incorporation in apatite structure was intensively explored in many studies (Nenen et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Dornelas et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Sirajunisha et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Cuozzo et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Ullah et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). It was reported that Zn-containing materials enhance bone repair through promoting cell proliferation, osteogenic activity, angiogenesis, and inhibiting osteoclast differentiation. Moreover, Zn-based HAPs posses effective antibacterial properties against various Gram-positive and Gram-negative strains (Mahanty et al. 2024; Okada et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Uysal et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Ullah et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Lima et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMany attempts were also made to incorporate zirconium ions (Zr\u003csup\u003e4+\u003c/sup\u003e) in calcium phosphates structure including the creation of composites based on ZrO\u003csub\u003e2\u003c/sub\u003e and HAP with improved biological and mechanical properties and their possible use in dental and orthopedic fields (Sharifianjazi et al \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Bollino et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Khoshsima et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Ayoub et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Elwira et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eS. aureus\u003c/em\u003e and \u003cem\u003eP. aeruginosa\u003c/em\u003e strains are one of the dangerous pathogens, causative agents of infectious diseases with various clinical manifestations, in particular, joint and bone diseases, and are capable of causing sepsis, so the study of the effect of synthetic materials on S. aureus and P. aeruginosa is important for to evaluate their further practical use.\u003c/p\u003e \u003cp\u003eThe aim of the present study was to investigate the possibility of formation calcium phosphates in the systems Ca\u003csup\u003e2+\u003c/sup\u003e-Zr\u003csup\u003e4+\u003c/sup\u003e-Zn\u003csup\u003e2+\u003c/sup\u003e-PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3\u0026minus;\u003c/sup\u003e-CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2\u0026minus;\u003c/sup\u003e that predict of partial substitution of calcium atoms by zirconium atoms as well as complex substitution of calcium atoms by zirconium and zinc cations while phosphate anion by carbonate groups in apatite-type structure and influence of nature and amounts of dopants on antibacterial activity of prepared samples against \u003cem\u003eS. aureus\u003c/em\u003e and \u003cem\u003eP. аeruginosa\u003c/em\u003e strains.\u003c/p\u003e "},{"header":"Experimental","content":" \u003cp\u003e \u003cb\u003ePreparation of doped calcium phosphates.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eChemically modified apatite-related phosphates with general compositions Ca\u003csub\u003e10-2x\u003c/sub\u003eZr\u003csub\u003ex\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e, Ca\u003csub\u003e9.75-2x\u003c/sub\u003eZr\u003csub\u003ex\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e and Ca\u003csub\u003e9-z-y/2\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003ez\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6-y\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003ey\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (x\u0026thinsp;=\u0026thinsp;0.05, 0.1, 0.5 and 1.0; y\u0026thinsp;=\u0026thinsp;0, 0.5; z\u0026thinsp;=\u0026thinsp;0.1, 0.5) were synthesized from aqua solution at temperature 25 \u003csup\u003eo\u003c/sup\u003eC with further heating of solid powders to 600 \u003csup\u003eo\u003c/sup\u003eC during 2 hours. Compounds Ca(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e\u0026middot;4H\u003csub\u003e2\u003c/sub\u003eO, Zn(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e\u0026middot;6H\u003csub\u003e2\u003c/sub\u003eO, NH\u003csub\u003e4\u003c/sub\u003eHCO\u003csub\u003e3\u003c/sub\u003e, (NH\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003eHPO\u003csub\u003e4\u003c/sub\u003e, ZrO(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e were used as initial materials. Nitrates mixture (Ca(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e\u0026middot;4H\u003csub\u003e2\u003c/sub\u003eO and Zn(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e\u0026middot;6H\u003csub\u003e2\u003c/sub\u003eO) was dissolved in deionized water and necessary amount of ZrO(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e was added. After mixing of mixture during 15 min the solution containing phosphate and carbonate anions was added at intensive magnetic stirring. The obtained precipitates were stirred for 5 min and 3 ml of NH\u003csub\u003e3\u003c/sub\u003e*H\u003csub\u003e2\u003c/sub\u003eO was added. Then the water was evaporated and solid powders after grounding were annealed at 600 \u003csup\u003eo\u003c/sup\u003eC. Muffle furnace SNOL-7.2/1100 (TermoPro-601 temperature controller) was used for annealing of samples.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCharacterization of synthesized modified calcium phosphates.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe phase composition of samples was investigated by X-ray powder diffraction method. XRD patterns were recorded using Shimadzu XRD-6000 diffractometer with Cu-Kα radiation (λ\u0026thinsp;=\u0026thinsp;1.54178 \u0026Aring;, 2\u003cem\u003eθ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5\u0026ndash;60\u0026deg;, step size 0.01\u0026deg;). The crystalline phase was identified by reference to the ICDD (International Center for Diffraction Data) database for hydroxyapatite Ca\u003csub\u003e10\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (#00-074-0565). Lattice parameters and crystallites size for modified calcium phosphates were calculated using Fullprof program and Shererra equation, respectively.\u003c/p\u003e \u003cp\u003ePresence of different anions types in synthesized phases was confirmed by Fourier transform infrared spectroscopy (frequency range 400\u0026ndash;4000 cm\u003csup\u003e-1\u003c/sup\u003e) for samples pressed in KBr pellets. PerkinElmer Spectrum BX spectrometer was used.\u003c/p\u003e\n\u003ch3\u003eAntibacterial activity\u003c/h3\u003e\n\u003cp\u003eObtained modified calcium phosphates with different composition have been tested against opportunistic microorganisms: \u003cem\u003eStaphylococcus aureus\u003c/em\u003e ATCC 25923, and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e АТСС 9027 after their sterilized by autoclaving at 0.75 atm and temperature of 112\u0026deg;C during 30 min. The different amounts (5 mM, 10 mM and 20 mM) of obtained samples were added overnight in sterile bottles with nutrient medium and 2% (10\u003csup\u003e5\u003c/sup\u003eCFU/ml) of \u003cem\u003eS. aureus\u003c/em\u003e or \u003cem\u003eP. aeruginosa\u003c/em\u003e strains. The growth of culture without sample was used as a control. The bottles were incubated at 37\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003csup\u003e0\u003c/sup\u003eC for 24 h and then suspensions of bacterial culture with some samples were incubated on petri dishes containing tryptone soya agar. The amount of bacterial colonies of tested strains on the surface of the agar medium was calculated on the next day.\u003c/p\u003e \u003cp\u003e \u003cem\u003eStatistical analysis.\u003c/em\u003e Antibacterial data were presented as the mean (M)\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Each experiment was repeated at least three times. Data processing was performed using the program ≪STATISTICA 7.0≫ (StatSoft Inc., Tulsa, OK, USA). The post-hoc-test using the criterion of LSD was used for assessing the reliability of quantitative indicators of differences in different strains. A P-value of \u0026le;\u0026thinsp;0.05 was considered as statistically significant to control and marked*.\u003c/p\u003e \u003cp\u003eCompounds can be labeled with Arabic numerals. For example: Triphenylamine \u003cb\u003e(1)\u003c/b\u003e (5.0 g, 20.4 mmol) and dry dimethylformamide (15.0 mL) were added into the mixture. (\u003cb\u003eNote\u003c/b\u003e: This is a significant change because Roman numerals were used in the previous journal format.) Reaction mechanisms can be labelled as numbered Schemes or Figures. Schemes do not have captions (see Scheme 1 below). All drawings and plots should be pasted into the document using the option \u0026ldquo;Paste Special\u0026rdquo; that simplifies their editing.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cp\u003eAll XRD patterns for prepared modified calcium phosphates are similar and correspond to apatite-type calcium phosphate standard pattern. For example XRD patterns for a raw of synthesized samples are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Any impurities were not detected for calcium phosphates which contain the highest among determined amounts of dopants that confirmed the preparation of single phase samples independ on amount of dopants. Calculation of lattice parameters showed decrease of parameter values comparing with hydroxyapatite (Са\u003csub\u003e10\u003c/sub\u003e(РО\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(ОН)\u003csub\u003e2\u003c/sub\u003e: \u003cem\u003eа\u003c/em\u003e = 9.432 \u0026Aring;, \u003cem\u003ec\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6.881 \u0026Aring;, 00-074-0565) with increasing of substitution degree in cationic sublattice that correlates with calcium Ca\u003csup\u003e2+\u003c/sup\u003e (1.06\u0026Aring;) and zirconium Zr\u003csup\u003e4+\u003c/sup\u003e(0.78\u0026Aring;) ion sizes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Calculation of crystallite size of prepared modified calcium phosphates using XRD data and Scherrer\u0026rsquo;s equation showed the formation of nanoparticles in size range 30\u0026ndash;45 nm (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCrystallographic parameters and crystallite size for prepared complex-doped apatite-related calcium phosphates (hexagonal system, space group \u003cem\u003eP6\u003c/em\u003e\u003csub\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e/m\u003c/em\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePhosphate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eCell parameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCrystallite size (nm)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ea\u0026thinsp;=\u0026thinsp;b\u003c/em\u003e, \u0026Aring;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ec, \u0026Aring;\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e9.9\u003c/sub\u003eZr\u003csub\u003e0.05\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.429(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.887(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e9.8\u003c/sub\u003eZr\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.412(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.881(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.407(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.878(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e8\u003c/sub\u003eZr(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.383(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.877(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e9.65\u003c/sub\u003eZr\u003csub\u003e0.05\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.415(6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.873(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e9.55\u003c/sub\u003eZr\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.397(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.886(7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e8.75\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.391(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.882(9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e7.75\u003c/sub\u003eZr(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.366(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.877(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.410(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.871(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e8.65\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.404(5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.863(8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.394(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.856(6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFTIR spectra for all samples contain typical bands of apatite-related calcium phosphate as well as its CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2\u0026minus;\u003c/sup\u003e substituted analogs and are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The main characteristic modes of phosphate tetrahedral were detected in the regions580-640 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 990\u0026ndash;1220 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e attributed to stretching and deformation vibrations, respectively. The broad band in region 3200\u0026ndash;3600 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e was attributed to adsorbed water and also includes of structurally-bound OH-group in apatite-type structure. The typical CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2\u0026minus;\u003c/sup\u003e bands are at 870\u0026ndash;875, 1413\u0026ndash;1468 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e that confirmed the partial substitution of PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3\u0026minus;\u003c/sup\u003e by CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2\u0026minus;\u003c/sup\u003e with formation of B-type carbonated apatite (Malyshenko et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Strutynska et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Strutynska et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) It was found that B-type carbonated apatite-related calcium phosphate showed lower powder crystallinity and enhances solubility of the apatite-type structure (Ezekiel et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAntibacterial activity.\u003c/b\u003e The effect of different amount (5, 10 or 20 mM) of synthesized zirconium, carbonate- as well as zirconium, zinc and carbonate-containing apatite-related calcium phosphates against \u003cem\u003eStaphylococcus aureus\u003c/em\u003e ATCC 25923 and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e АТСС 9027 has been investigated. Obtained results showed the better antibacterial activity of samples against \u003cem\u003eS. aureus\u003c/em\u003e than that for \u003cem\u003eP. aeruginosa\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). It was found the influence of calcium phosphates composition on their activity against both strains (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the case of complex modification of cationic and anionic sublattices of apatite-type calcium phosphate with zirconium and carbonate ions the activity against \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was some decreased than that was for Zr-containing phosphate (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Sample 2 and Sample 1). \u003cem\u003eS. aureus\u003c/em\u003e strain was inhibited by 7.4 or a lesser extent to 6.7 times compared to the control after 24 hours of incubation at added of Ca\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (Sample 1) (10 or 20 mM) or Ca\u003csub\u003e8.75\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (Sample 2) (10mM), respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAdditional doping of Zr-containing calcium phosphate with zinc cations allow to increase of antibacterial activity (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Sample 4 and Sample 5). The best antibacterial effect was found for phosphates Ca\u003csub\u003e8.5\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (Sample 3 at its added of 20 mM) with a tenfold inhibition of the growth of \u003cem\u003eS. aureus\u003c/em\u003e compared to the control after 24 h of incubation (the total amount of lgCFU/ml was 8,3\u0026thinsp;\u0026plusmn;\u0026thinsp;0,05 and 9,03\u0026thinsp;\u0026plusmn;\u0026thinsp;0,05, respectively). The powder of Ca\u003csub\u003e8.25\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (sample 4 at its added of 10 mM) also inhibited the growth of \u003cem\u003eS. aureus\u003c/em\u003e by 8.4 times compared to the control.\u003c/p\u003e \u003cp\u003eModification of Zr-containing apatite structure with carbonate anion insignificant improves of characteristic against \u003cem\u003eP. aeruginosa\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Sample 2), while the presence of Zn\u003csup\u003e2+\u003c/sup\u003e decreased the strain survival in ten times at adding of these samples in amount of 20 mM (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Samples 3\u0026ndash;4). It should be noted that in the case of samples Ca\u003csub\u003e8.65\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003eZn\u003csub\u003e0.1\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e5.5\u003c/sub\u003e(CO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e0.5\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e the increase of activity again \u003cem\u003eP. aeruginosa\u003c/em\u003e took place at growing of amount of added sample from 5 mM to 20 mM (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Sample 5).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThus, obtained results showed to decrease the \u003cem\u003eStaphylococcus aureus\u003c/em\u003e strain survival in the presence of prepared zirconium, carbonate and zinc-containing apatite-related calcium phosphate that is important at creation materials for orthopedics.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAccording to X-ray powder diffraction and FTIR spectroscopy data the modified apatite-related calcium phosphates were synthesized. The calculated lattice parameters for prepared modified calcium phosphates correlate with amount of zirconium and zinc in their composition. The B-type substitution (PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3-\u003c/sup\u003e \u0026rarr;CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2-\u003c/sup\u003e) in the apatite-related structure was realized.\u003c/p\u003e \u003cp\u003eThe highest antimicrobial effect against \u003cem\u003eStaphylococcus aureus\u003c/em\u003e strain was found for phosphate Ca\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e, which grown at increasing of added sample amount to 10 mM.\u003c/p\u003e \u003cp\u003eModification of Zr-containing calcium phosphate with carbonate anion insignificant improves of characteristic against \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e while the presence of Zn\u003csup\u003e2+\u003c/sup\u003e in their composition decreased the strain survival in ten times. Thus, obtained results confirm the possibility of complex incorporation of Zn\u003csup\u003e2+\u003c/sup\u003e, Zr\u003csup\u003e4+\u003c/sup\u003e and CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2-\u003c/sup\u003e in apatite-type structure of calcium phosphate and their effect on \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e that is important at creation of materials for medical purpose.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest:\u003c/h2\u003e \u003cp\u003eauthors declare that they no know competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAcknowledgement.\u003c/h2\u003e \u003cp\u003eThis research was supported by National Research Foundation of Ukraine, Grant №2023.03/0109).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAyoub G, Veljovic D, Zebic ML, Miletic V, Palcevskis E, Petrovic R, Janackovic D (2018) Composite nanostructured hydroxyapatite/yttrium stabilized zirconia dental inserts \u0026ndash; The processing and application as dentin substitutes. 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J Aust Ceram Soc 57:869\u0026ndash;897. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s41779-021-00583-4\u003c/span\u003e\u003cspan address=\"10.1007/s41779-021-00583-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWen X, Wang J, Pei X, Zhang X (2023) Zinc-based biomaterials for bone repair and regeneration: mechanism and applications. J Mater Chem B 11:11405\u0026ndash;11425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1039/D3TB01874A\u003c/span\u003e\u003cspan address=\"10.1039/D3TB01874A\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYotsova R, Peev S (2024) Biological properties and medical applications of carbonate apatite: a systematic review. Pharmaceutics 16(2):291. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/pharmaceutics16020291\u003c/span\u003e\u003cspan address=\"10.3390/pharmaceutics16020291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"zirconium, zinc, hydroxyapatite, antibacterial effect","lastPublishedDoi":"10.21203/rs.3.rs-5346923/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5346923/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eApatite-related zirconium, carbonate and zinc-containing calcium phosphates have been synthesized in aqueous solutions at different molar ratios Ca\u003csup\u003e2+\u003c/sup\u003e : Zr\u003csup\u003e4+\u003c/sup\u003e : Zn\u003csup\u003e2+\u003c/sup\u003e : PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3-\u003c/sup\u003e : CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2-\u003c/sup\u003e = (10-2x-y/2-z) : x : y : (6-z) : z (x\u0026thinsp;=\u0026thinsp;0.05, 0.1, 0.5 and 1.0; y\u0026thinsp;=\u0026thinsp;0.1, 0.5, z\u0026thinsp;=\u0026thinsp;0, 0.5) and heated to 600 \u003csup\u003eo\u003c/sup\u003eC during 2 hours. X-ray powder diffraction and FTIR spectroscopy data confirmed the formation of single phase modified apatite-related calcium phosphates with partial substitution of PO\u003csub\u003e4\u003c/sub\u003e\u003csup\u003e3-\u003c/sup\u003e by CO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e2-\u003c/sup\u003e in anionic sublattice (B-type). The calculated lattice parameters for prepared Zr\u003csup\u003e4+\u003c/sup\u003e, Zn\u003csup\u003e2+\u003c/sup\u003e- modified calcium phosphates correlate with amount of dopants in their composition. The sizes of prepared phosphates do not depend on composition of initial solution and vary in the range 30-45nm. The highest antimicrobial effect against \u003cem\u003eStaphylococcus aureus\u003c/em\u003e strain was found for phosphate Ca\u003csub\u003e9\u003c/sub\u003eZr\u003csub\u003e0.5\u003c/sub\u003e(PO\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e6\u003c/sub\u003e(OH)\u003csub\u003e2\u003c/sub\u003e (at its adding to 10 mM). Modification of Zr-containing calcium phosphate with carbonate anion and Zn\u003csup\u003e2+\u003c/sup\u003e decreased the \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e survival in ten times.\u003c/p\u003e","manuscriptTitle":"Synthesis, characterization and antibacterial properties of apatite-related zirconium, carbonate and zinc-containing calcium phosphates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 18:16:13","doi":"10.21203/rs.3.rs-5346923/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fcb2ed31-6a09-47e9-b0bc-f80086d5c948","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-29T07:46:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 18:16:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5346923","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5346923","identity":"rs-5346923","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}