Hyperpolarized NMR Combined with Quantum Mechanical Simulations Reveal Atomistic Structures of Calcium Phosphate Prenucleation Clusters
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| Název: | Hyperpolarized NMR Combined with Quantum Mechanical Simulations Reveal Atomistic Structures of Calcium Phosphate Prenucleation Clusters |
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| Autoři: | Christopher Pötzl, Ertan Turhan, Christel Gervais, Thierry Azaïs, Dennis Kurzbach |
| Zdroj: | Analytical Chemistry. 97:20191-20200 |
| Informace o vydavateli: | American Chemical Society (ACS), 2025. |
| Rok vydání: | 2025 |
| Témata: | 104027 Computational chemistry, 104026 Spectroscopy, C-13, 106041 Structural biology, 106041 Strukturbiologie, 104017 Physikalische Chemie, 104027 Computational Chemistry, CHEMICAL-SHIFT PREDICTION, 104017 Physical chemistry, N-15, FIELD, CHARMM, 104026 Spektroskopie, NUCLEATION |
| Popis: | The discovery of solute precursors of crystalline materials, such as biominerals, recently challenged the classical nucleation theory (CNT). One emerging method for investigating these early-stage intermediates in solution is dissolution dynamic nuclear polarization (dDNP)-enhanced nuclear magnetic resonance (NMR) spectroscopy. Recent applications of dDNP to calcium carbonate (CaC) and calcium phosphate (CaP) mineralization have demonstrated the feasibility of identifying and tracing very early-stage prenucleation clusters (PNCs). However, the structural details remain difficult to resolve as dDNP is mainly limited to simple one-dimensional NMR detection. To overcome this bottleneck, we herein integrate hyperpolarized NMR of PNC with molecular dynamics simulations and quantum mechanical calculations to gain atomistic structural insights into CaP PNCs. By simulating the PNC structures, computing chemical shift parameters, and comparing these to hyperpolarized NMR "fingerprint" spectra, we demonstrate how to derive models of solution-state structural ensembles of PNC, even when very short-lived. With this approach, we find that the Ca/Pi ratio inside PNC tends to stay close to 1 independent of pH, while their sizes vary, leading to larger precursors under more basic conditions. At the same time, phosphate speciation within PNC was found to be independent of pH, as only monohydrogen phosphates participated in PNC formation. This latter feature also entailed a pH-independent local atomistic arrangement of phosphates coordinating a Ca(II) center, leading to constant Ca2+-Pi distances of similar to 3 and similar to 3.6 angstrom. These ion-to-ion distances agree with those found inside solid CaP phases such as brushite, octacalcium phosphate, or hydroxyapatite-a feature hinting toward the templating function of PNCs. Thus, our method (i) extends the methodological scope of hyperpolarized NMR by complementing one-dimensional fingerprint spectra with full structural models and (ii) sheds light on key intermediates that have been experimentally underexplored. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/acs.analchem.5c02945 |
| Přístupová URL adresa: | https://ucrisportal.univie.ac.at/de/publications/886a4042-3a8a-4476-b18a-027a1eb8c16f https://doi.org/10.1021/acs.analchem.5c02945 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....627b35776326d0dda8d8db4e318a2118 |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | The discovery of solute precursors of crystalline materials, such as biominerals, recently challenged the classical nucleation theory (CNT). One emerging method for investigating these early-stage intermediates in solution is dissolution dynamic nuclear polarization (dDNP)-enhanced nuclear magnetic resonance (NMR) spectroscopy. Recent applications of dDNP to calcium carbonate (CaC) and calcium phosphate (CaP) mineralization have demonstrated the feasibility of identifying and tracing very early-stage prenucleation clusters (PNCs). However, the structural details remain difficult to resolve as dDNP is mainly limited to simple one-dimensional NMR detection. To overcome this bottleneck, we herein integrate hyperpolarized NMR of PNC with molecular dynamics simulations and quantum mechanical calculations to gain atomistic structural insights into CaP PNCs. By simulating the PNC structures, computing chemical shift parameters, and comparing these to hyperpolarized NMR "fingerprint" spectra, we demonstrate how to derive models of solution-state structural ensembles of PNC, even when very short-lived. With this approach, we find that the Ca/Pi ratio inside PNC tends to stay close to 1 independent of pH, while their sizes vary, leading to larger precursors under more basic conditions. At the same time, phosphate speciation within PNC was found to be independent of pH, as only monohydrogen phosphates participated in PNC formation. This latter feature also entailed a pH-independent local atomistic arrangement of phosphates coordinating a Ca(II) center, leading to constant Ca2+-Pi distances of similar to 3 and similar to 3.6 angstrom. These ion-to-ion distances agree with those found inside solid CaP phases such as brushite, octacalcium phosphate, or hydroxyapatite-a feature hinting toward the templating function of PNCs. Thus, our method (i) extends the methodological scope of hyperpolarized NMR by complementing one-dimensional fingerprint spectra with full structural models and (ii) sheds light on key intermediates that have been experimentally underexplored. |
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| ISSN: | 15206882 00032700 |
| DOI: | 10.1021/acs.analchem.5c02945 |