{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:17:09Z","timestamp":1786375029187,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oral. Health"],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Silver(I)-diammine fluoride (SDF) and silver(I)-fluoride (SF) complexes have been successfully employed for the arrest of dental caries for many years. However, to date there are very few studies available reporting on the molecular structural compositional and solution status of these agents [typically applied as highly-concentrated 38% (w\/v) solutions]. Here, we explored the solution status and chemical constitution of commercially-available SDF and SF products, and secondly investigated the multicomponent interplay of these products with biomolecules present in intact human whole-mouth salivary supernatants (WMSSs) <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High-resolution <jats:sup>19<\/jats:sup>F NMR analysis was employed to explore SDF and SF product solutions, and to determine WMSS fluoride (F<jats:sup>\u2212<\/jats:sup>) concentrations, whereas ammonia (NH<jats:sub>3<\/jats:sub>) release form SDF was tracked by <jats:sup>1<\/jats:sup>H NMR spectroscopy. SEM and thin-film FTIR-ATR analyses were employed to explore the atomic and molecular compositions of sequentially-generated AgCl deposits and chromophoric Ag\/AgCl nanoparticles (CSNPs); the time-dependent generation of the latter was followed spectrophotometrically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:sup>19<\/jats:sup>F NMR spectra of aqueous SF solutions contained a very broad F<jats:sup>\u2212<\/jats:sup> signal (\u0394v<jats:sub>1\/2<\/jats:sub> 70\u2005Hz), demonstrating that much of its solvated F<jats:sup>\u2212<\/jats:sup> content was rapidly exchanging with Ag(I) on the NMR timescale, but those of SDF had a much sharper resonance, similar to that of \u201cfree\u201d F<jats:sup>\u2212<\/jats:sup> (4\u2005Hz). Moreover, further NMR results revealed that a popular SDF product contained high molar excesses of both F<jats:sup>\u2212<\/jats:sup> and NH<jats:sub>3<\/jats:sub>. Treatment of WMSSs with SDF and SF generated an off-white precipitate, which slowly developed into CSNPs at 23\u00b0C; SEM demonstrated high contents of both silver and chloride in this material (ca.1:1 atomic content ratio). FTIR-ATR analysis found that the CSNPs formed contained a range of salivary biomolecules, which appear to encapsulate the Ag\/AgCl core (significant thiocyanate contents were also found). In conclusion, NMR results acquired demonstrated that SF, but not SDF, product solutions feature rapidly-exchanging F<jats:italic><jats:sup>\u2212<\/jats:sup><\/jats:italic> between its \u201cfree\u201d and Ag(I)-bound forms, and that SDF contains large excesses of both F<jats:sup>\u2212<\/jats:sup> and its NH<jats:sub>3<\/jats:sub> ligands. Characterised AgCl deposits and CSNPs were sequentially produced from the interactions of these complexes with WMSS biomolecules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In view of their well-known microbicidal and cariostatic properties, the observed autobioconstruction of CSNPs involving salivary catalysis is of much therapeutic significance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/froh.2024.1373885","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T04:22:44Z","timestamp":1718166164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Explorations of the chemical constitution and aqueous solution status of caries-arresting silver(I)-diammine fluoride and silver(I)-fluoride products using high-resolution 19F NMR analysis. Spectroscopic and SEM investigations of their interactions with human saliva: evidence for the in vivo salivary-catalysed autoconstruction of Ag\/AgCl-based nanoparticles (IV-SCAN)\u2014part I"],"prefix":"10.3389","volume":"5","author":[{"given":"Kayleigh","family":"Hunwin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Edgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Botana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Armitage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Bhogadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unmesh","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Duffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Duffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyman","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Grootveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1600-0528.1997.tb00894.x","article-title":"Concepts of dental caries and their consequences for understanding the disease","volume":"25","author":"Fejerskov","year":"1997","journal-title":"Commun Dent Oral Epidemiol"},{"key":"B2","volume-title":"White Paper on Dental Caries Prevention and Management","author":"Pitts","year":"2016"},{"key":"B3","first-page":"86","article-title":"Developing explanatory models of health inequalities in childhood dental caries","volume":"21","author":"Pine","year":"2004","journal-title":"Commun Dent Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1177\/1757913915626744","article-title":"Spatial distribution mapping of drinking water fluoride levels in Karnataka, India: a study for further intervention regarding fluoride-related health effects","volume":"136","author":"Chowdhury","year":"2016","journal-title":"Perspect Public Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1177\/0022034508329406","article-title":"Silver diamine fluoride: a caries \u201csilver-fluoride bullet\u201d","volume":"88","author":"Rosenblatt","year":"2009","journal-title":"J Dent Res"},{"key":"B6","first-page":"661","article-title":"What value has argenti nitras as a therapeutic agent in dentistry?","volume":"12","author":"Stebbins","year":"1891","journal-title":"Int Dent J"},{"key":"B7","first-page":"901","article-title":"Preventive effect of silver nitrate","volume":"47","author":"Miller","year":"1905","journal-title":"Dent Cosmos"},{"key":"B8","first-page":"891","article-title":"A method of sterilizing and at the same time impregnating with a metal affected dentinal tissue","volume":"59","author":"Howe","year":"1917","journal-title":"Dent Cosmos"},{"key":"B9","doi-asserted-by":"publisher","first-page":"420","DOI":"10.14219\/jada.archive.1942.0211","article-title":"Studies on dental caries XIII: effects of ammoniac silver nitrate on caries in the first permanent molars","volume":"29","author":"Klein","year":"1942","journal-title":"J Am Dent Assoc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002279.pub2","article-title":"Fluoride varnishes for preventing dental caries in children and adolescents","volume":"5","author":"Marinho","year":"2002","journal-title":"Cochrane Database Syst Rev"},{"key":"B11","doi-asserted-by":"publisher","first-page":"CD002780","DOI":"10.1002\/14651858.CD002780.pub2","article-title":"One topical fluoride (toothpastes, or mouthrinses, or gels, or varnishes) versus another for preventing dental caries in children and adolescents","volume":"2004","author":"Marinho","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"B12","doi-asserted-by":"publisher","first-page":"CD002781","DOI":"10.1002\/14651858.CD002781.pub2","article-title":"Combinations of topical fluoride (toothpastes, mouthrinses, gels, varnishes) versus single topical fluoride for preventing dental caries in children and adolescents","volume":"2004","author":"Marinho","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"125","DOI":"10.12968\/jowc.2002.11.4.26389","article-title":"Silver. I: its antibacterial properties and mechanism of action","volume":"11","author":"Lansdown","year":"2002","journal-title":"J Wound Care"},{"key":"B14","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1159\/000093928","article-title":"Silver in health care: antimicrobial effects and safety in use","volume":"33","author":"Lansdown","year":"2006","journal-title":"Curr Probl Dermatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1177\/0022034517709738","article-title":"Formation of fluoridohydroxyapatite with silver diamine fluoride","volume":"96","author":"Mei","year":"2017","journal-title":"J Dent Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.jdent.2012.03.009","article-title":"Silver compounds used in dentistry for caries management: a review","volume":"40","author":"Peng","year":"2012","journal-title":"J Dent"},{"key":"B17","first-page":"848","volume-title":"Standard Potentials in Aqueous Solutions","author":"Bard","year":"1985"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2812","DOI":"10.1021\/ja512020w","article-title":"Fluoride-induced reduction of Ag(I) cation leading to formation of silver mirrors and luminescent ag-nanoparticles","volume":"137","author":"Maity","year":"2015","journal-title":"J Am Chem Soc"},{"key":"B19","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.adaj.2018.10.016","article-title":"Silver and fluoride content and short-term stability of 38% silver diamine fluoride","volume":"150","author":"Crystal","year":"2019","journal-title":"J Am Dent Assoc"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.3390\/app12031235","article-title":"Updates and original case studies focused on the NMR-linked metabolomics analysis of human oral fluids part I: emerging platforms and perspectives","volume":"12","author":"Grootveld","year":"2022","journal-title":"Appl Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3390\/metabo13070792","article-title":"Detection and quantification of ammonia as the ammonium cation in human saliva by 1H NMR. A promising probe for health status monitoring, with special reference to cancer","volume":"13","author":"Bhogadia","year":"2023","journal-title":"Metabolites"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1021\/es052295s","article-title":"Reexamination of hexafluorosilicate hydrolysis by 19F NMR and pH measurement","volume":"40","author":"Finney","year":"2006","journal-title":"Environ Sci Technol"},{"key":"B23","unstructured":"BrewerSA\n          United KingdomUniversity of LeicesterLow-Valent Fluoro-Complexes of the Transition Metals1993"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1472-6831-12-3","article-title":"Fluoride bioavailability in saliva and plaque","volume":"12","author":"Naumova","year":"2012","journal-title":"BMC Oral Health"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.procbio.2012.04.025","article-title":"Instant green synthesis of silver nanoparticles using Terminalia chebula fruit extract and evaluation of their catalytic activity on reduction of methylene blue","volume":"47","author":"Edison","year":"2012","journal-title":"Proc Biochem"},{"key":"B26","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1080\/17518253.2017.1360400","article-title":"Green synthesis of silver nanoparticles by using leaf extracts from the endemic Buddleja lobose hope","volume":"10","author":"Carmona","year":"2017","journal-title":"Green Chem Lett Rev"},{"key":"B27","doi-asserted-by":"publisher","first-page":"17702","DOI":"10.1007\/s11356-016-6945-1","article-title":"Bio-inspired sustainable and green synthesis of plasmonic Ag\/AgCl nanoparticles for enhanced degradation of organic compound from aqueous phase","volume":"23","author":"Devi","year":"2016","journal-title":"Environ Sci Pollut Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1039\/C5NJ02367J","article-title":"A rapid, facile and green synthesis of Ag@AgCl nanoparticles for the effective reduction of 2,4-dinitrophenyl hydrazine","volume":"40","author":"Devi","year":"2016","journal-title":"New J Chem"},{"key":"B29","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1111\/ipd.12005","article-title":"Fluoride and silver concentrations of silver diammine fluoride solutions for dental use","volume":"23","author":"Mei","year":"2013","journal-title":"Int J Paed Dent"},{"key":"B30","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/j.1834-7819.1997.tb00097.x","article-title":"Unacceptably high levels of fluoride in commercial preparations of silver fluoride","volume":"42","author":"Gotjamanos","year":"1997","journal-title":"Aust Dent J"},{"key":"B31","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.canlet.2020.02.020","article-title":"Biofluid diagnostics by FTIR spectroscopy: a platform technology for cancer detection","volume":"477","author":"Sala","year":"2020","journal-title":"Cancer Lett"},{"key":"B32","doi-asserted-by":"publisher","first-page":"112961","DOI":"10.1016\/j.molliq.2020.112961","article-title":"Saliva as a first-line diagnostic tool: a spectral challenge for identification of cancer biomarkers","volume":"307","author":"Paluszkiewicz","year":"2020","journal-title":"J Molec Liquids"},{"key":"B33","doi-asserted-by":"publisher","first-page":"117380","DOI":"10.1016\/j.molliq.2021.117380","article-title":"Biochemical composition and characteristics of salivary FTIR spectra: correlation analysis","volume":"341","author":"Bel\u2019skaya","year":"2021","journal-title":"J Mol Liquids"},{"key":"B34","doi-asserted-by":"publisher","first-page":"56575","DOI":"10.1039\/C7RA12082F","article-title":"Green-synthesised cerium oxide nanostructures (CeO2-NS) show excellent biocompatibility for phyto-cultures as compared to silver nanostructures (Ag-NS)","volume":"7","author":"Maqbool","year":"2017","journal-title":"RSC Adv"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3396","DOI":"10.1016\/S0021-9258(19)67806-3","article-title":"19F and 31P NMR spectroscopy of G protein alpha subunits. Mechanism of activation by Al3+ and F\u2212","volume":"266","author":"Higashijima","year":"1991","journal-title":"J Biol Chem"},{"key":"B36","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/(SICI)1099-1492(199910)12:6%3C345::AID-NBM580%3E3.0.CO;2-C","article-title":"1H NMR analysis of microbial-derived organic acids in primary root carious lesions and saliva","volume":"12","author":"Silwood","year":"1999","journal-title":"NMR Biomed"},{"key":"B37","year":"2019"},{"key":"B38","first-page":"266","article-title":"Superoxide dismutase enzyme and thiol antioxidants in gingival crevicular fluid and saliva","volume":"9","author":"Karim","year":"2012","journal-title":"Dent Res J (Isfahan)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1248\/jhs.46.343","article-title":"Cyanide and thiocyanate levels in blood and saliva of healthy adult volunteers","volume":"46","author":"Tsuge","year":"2020","journal-title":"J Health Sci"},{"key":"B40","first-page":"837","article-title":"Diurnal changes in salivary amino acid concentrations","volume":"24","author":"Nakamura","year":"2010","journal-title":"In Vivo"},{"key":"B41","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1111\/j.1600-0714.1984.tb01459.x","article-title":"Relationship at the human salivary peroxidase system to oral health","volume":"13","author":"Tenovuo","year":"1984","journal-title":"J Oral Pathol"},{"key":"B42","first-page":"425","article-title":"Diagnostic values of calcium and magnesium forms determined in human serum and saliva","volume":"15","author":"Andrusishina","year":"2010","journal-title":"J Elementol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0003-9969(98)00108-3","article-title":"Individual variations of pH, buffer capacity, and concentrations of calcium and phosphate in unstimulated whole saliva","volume":"44","author":"Larsen","year":"1999","journal-title":"Arch Oral Biol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.3390\/molecules25153494","article-title":"Increased antibacterial and antibiofilm properties of silver nanoparticles using silver fluoride as precursor","volume":"25","author":"Bertoglio","year":"2020","journal-title":"Molecules"},{"key":"B45","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.jdent.2014.05.017","article-title":"A new \u201csilver-bullet\u201d to treat caries in children\u2013nano silver fluoride: a randomised clinical trial","volume":"42","author":"dos Santos","year":"2014","journal-title":"J Dent"},{"key":"B46","first-page":"8882930","article-title":"Therapeutic use of silver nanoparticles in the prevention and arrest of dental caries","volume-title":"Bioinorg Chem Appl","author":"Butr\u00f3n","year":"2020"},{"key":"B47","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1680\/jsuin.20.00089","article-title":"One-pot green synthesis of Ag@ AgCl nanoparticles with excellent photocatalytic performance","volume":"9","author":"Guo","year":"2021","journal-title":"Surf Innov"},{"key":"B48","first-page":"79","article-title":"Development of a new fluoride colorimetric sensor based on anti-aggregation of modified silver nanoparticles","volume":"8","author":"Motahhari","year":"2021","journal-title":"Anal Bioanal Chem Res"},{"key":"B49","first-page":"E135","article-title":"Use of silver diamine fluoride for dental caries management in children and adolescents, including those with special health care needs","volume":"39","author":"Crystal","year":"2017","journal-title":"Pediatr Dent"},{"key":"B50","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0378-4347(95)00157-E","article-title":"Silver ion chromatography of lipids and fatty acids","volume":"671","author":"Dobson","year":"1995","journal-title":"J Chromatog B Biomed Sci Appl"},{"key":"B51","doi-asserted-by":"publisher","first-page":"052001","DOI":"10.1088\/1742-6596\/1073\/5\/052001","article-title":"Salivary and urinary assessment of fluoride and silver ion concentrations after silver diamine fluoride application in children: a prospective cohort study","volume":"1073","author":"Widianti","year":"2018","journal-title":"J Phys Conf Ser"},{"key":"B52","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/adj.12822","article-title":"Acidity, fluoride and silver ion concentrations in silver diamine fluoride solutions: a pilot study","volume":"66","author":"Patel","year":"2021","journal-title":"Aust Dent J"},{"key":"B53","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.identj.2023.05.001","article-title":"Stability of silver and fluoride contents in silver diamine fluoride solutions","volume":"73","author":"Yan","year":"2023","journal-title":"Internat Dent J"},{"key":"B54","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1159\/000325151","volume":"22","author":"Buzalaf","year":"2011","journal-title":"Fluoride and the Oral EnvironmentMonogr Oral Sci"},{"key":"B55","first-page":"3","article-title":"Defining the disease: an introduction","volume-title":"Dental Caries- the Disease and its Clinical Management","author":"Fejerskow","year":"2008"},{"key":"B56","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1046\/j.1365-263X.2001.00293.x","article-title":"Critical pH in resting and simulated whole saliva in groups of children and adults","volume":"11","author":"Anderson","year":"2001","journal-title":"Int J Paediatr Dent"}],"container-title":["Frontiers in Oral Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2024.1373885\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T04:22:53Z","timestamp":1718166173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/froh.2024.1373885\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":56,"alternative-id":["10.3389\/froh.2024.1373885"],"URL":"https:\/\/doi.org\/10.3389\/froh.2024.1373885","relation":{},"ISSN":["2673-4842"],"issn-type":[{"value":"2673-4842","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]},"article-number":"1373885"}}