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)-part I.

Introduction: 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) in vitro. Methods: High-resolution 19F NMR analysis was employed to explore SDF and SF product solutions, and to determine WMSS fluoride (F-) concentrations, whereas ammonia (NH3) release form SDF was tracked by 1H 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. Results: 19F NMR spectra of aqueous SF solutions contained a very broad F- signal (Δv1/2 70 Hz), demonstrating that much of its solvated F- content was rapidly exchanging with Ag(I) on the NMR timescale, but those of SDF had a much sharper resonance, similar to that of "free" F- (4 Hz). Moreover, further NMR results revealed that a popular SDF product contained high molar excesses of both F- and NH3. Treatment of WMSSs with SDF and SF generated an off-white precipitate, which slowly developed into CSNPs at 23°C; 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 - between its "free" and Ag(I)-bound forms, and that SDF contains large excesses of both F- and its NH3 ligands. Characterised AgCl deposits and CSNPs were sequentially produced from the interactions of these complexes with WMSS biomolecules. Discussion: In view of their well-known microbicidal and cariostatic properties, the observed autobioconstruction of CSNPs involving salivary catalysis is of much therapeutic significance.

Revisiting Fluoride in the Twenty-First Century: Safety and Efficacy Considerations.

Over 100 years of scientific literature is available which describes the long relationship between dentistry and the many possible applications of fluoride anion (F-) as successful therapeutic strategies. To date, systemic introduction of fluoride via water, milk and salt fluoridation, and fluoride-containing tablets, has been employed. Post-eruption topical fluoride products have also been introduced, such as fluoridated toothpaste, along with fluoride-containing rinses and varnishes. Importantly, a recent addition to the available armamentarium of fluoride therapeutics now exists in the form of metal ion-fluorido adducts, most especially silver(I)-diammine fluoride (SDF). In view of its high level of therapeutic success, very recently this agent was added to the World Health Authority's (WHO's) list of essential medicines available for the treatment and prevention of tooth decay. Overall, this current state of affairs merits a major review of all these fluoride-containing therapeutic compounds, together with their risks and benefits, both individually and collectively. In this study, a simple graphical tool has been developed for the rapid "on-site" evaluation of fluoride intake with respect to a range of oral healthcare products and body mass index is presented as a gauge of safety for the risk of fluoride toxicity in individual patients. This exposition commences with (a) an account of the history and value of fluoride therapeutics in clinical dentistry, including applications of monofluorophosphate and stannous fluoride; (b) an evaluation of the toxicological activities of fluoride, together with a summary of any reports, albeit very rare ones, arising from its clinically-driven overuse; (c) a history of the development, molecular structure, mechanisms of action, and therapeutic applications of SDF, including a summary of any possible toxic activities and effects arising from silver(I) ion rather than fluoride itself; and (d) the establishment of a working relationship between fluoride exposure and toxicity, with special reference to the instigation of newly-developed tabular/graphical reference guidelines for use by dental clinicians who employ fluoride-rich products in their practices. Particular attention is given to the oral care and treatment options of pediatric patients. In conclusion, applications of this unique monitoring tool may serve as a valuable toxicity guide for dental practitioners.