2022-11-29, Gindele, Maxim Benjamin, Malaszuk, Krzysztof K., Peter, Christine, Gebauer, Denis

We experimentally determined the characteristics and Langmuir parameters of the binding of calcium ions to different polycarboxylates. By using potentiometric titrations and isothermal titration calorimetry, the effects of side chain chemistry, pH value, and chain length were systematically investigated using the linear polymers poly(aspartic acid), poly(glutamic acid), and poly(acrylic acid). We demonstrate that for polymers with high polymerization degrees, the binding process is governed by higher-order effects, such as the change of apparent pKa of carboxyl groups, and contributions arising from the whole polymer chain while the chemistry of the monomer unit constituting the polymer plays a subordinate role. In addition, primary binding sites need to be present in the polymer, thus rendering the abundance and sequential arrangement of protonated and deprotonated groups important. The detection of higher-order effects contradicts the assumptions posed by the Langmuir model of noninteracting binding sites and puts a question mark on whether ion binding to polycarboxylates can be described using solely a Langmuir binding model. No single uniform mechanism fits all investigated systems, and the whole polymer chain, including terminal groups, needs to be considered for the interpretation of binding data. Therefore, one needs to be careful when explaining ion binding to polymers solely based on studies on monomers or oligomers.

2022-07-14, King, Michael, Avaro, Jonathan Thomas, Peter, Christine, Hauser, Karin, Gebauer, Denis

In experimental studies, heavy water (D₂O) is employed, e.g., so as to shift the spectroscopic solvent background, but any potential effects of this solvent exchange on reaction pathways are often neglected. While the important role of light water (H₂O) during the early stages of calcium carbonate formation has been realized, studies into the actual effects of aqueous solvent exchanges are scarce. Here, we present a combined computational and experimental approach to start to fill this gap. We extended a suitable force field for molecular dynamics (MD) simulations. Experimentally, we utilised advanced titration assays and time-resolved attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. We find distinct effects in various mixtures of the two aqueous solvents, and in pure H₂O or D₂O. Disagreements between the computational results and experimental data regarding the stabilities of ion associates might be due to the unexplored role of HDO, or an unprobed complex phase behaviour of the solvent mixtures in the simulations. Altogether, however, our data suggest that calcium carbonate formation might proceed “more classically” in D₂O. Also, there are indications for the formation of new structures in amorphous and crystalline calcium carbonates. There is huge potential towards further improving the understanding of mineralization mechanisms by studying solvent-mediated isotope effects, also beyond calcium carbonate. Last, it must be appreciated that H₂O and D₂O have significant, distinct effects on mineralization mechanisms, and that care has to be taken when experimental data from D₂O studies are used, e.g., for the development of H₂O-based computer models.

2021-07-19, Huang, Yu-Chieh, Rao, Ashit, Huang, Shing-Jong, Chang, Chun-Yu, Drechsler, Markus, Knaus, Jennifer, Chan, Jerry Chun Chung, Raiteri, Paolo, Gale, Julian D, Gebauer, Denis

Mechanistic pathways relevant to mineralization are not well-understood fundamentally, let alone in the context of their biological and geological environments. Through quantitative analysis of ion association at near-neutral pH, we identify the involvement of HCO₃ ^- ions in CaCO₃ nucleation. Incorporation of HCO₃ ^- ions into the structure of amorphous intermediates is corroborated by solid-state nuclear magnetic resonance spectroscopy, complemented by quantum mechanical calculations and molecular dynamics simulations. We identify the roles of HCO₃ ^- ions as being through (i) competition for ion association during the formation of ion pairs and ion clusters prior to nucleation and (ii) incorporation as a significant structural component of amorphous mineral particles. The roles of HCO₃ ^- ions as active soluble species and structural constituents in CaCO₃ formation are of fundamental importance and provide a basis for a better understanding of physiological and geological mineralization.

2020-06, Lukić, Miodrag J., Wiedenbeck, Eduard, Reiner, Holger, Gebauer, Denis

Although Al(III) hydrolysis, condensation, and nucleation play pivotal roles in the synthesis of Al-based compounds and determine their chemical behavior, we still lack experimental evidence regarding the chemistry of nucleation from solution. Here, by combining advanced titration assays, high-resolution transmission electron microscopy (HR-TEM), and 27Al–nuclear magnetic resonance spectroscopy, we show that highly dynamic solute prenucleation clusters (PNCs) are fundamental precursors of nanosolid formation. Chemical changes from olation to oxolation bridging within PNCs rely on the formation of tetrahedral AlO4 in solution and trigger phase separation at low driving force (supersaturation). This does not include the formation of Keggin-Al13 ions, at least during the earliest stages. The PNC pathway of the formation of Al(III) (oxy)(hydr)oxides offers new possibilities toward the development of strategies for controlling the entire crystallization process.

2022-11-17, Scheck, Johanna, Berg, John K., Drechsler, Markus, Kempter, Andreas, Van Driessche, Alexander E. S., Cölfen, Helmut, Gebauer, Denis, Kellermeier, Matthias

Nucleation is a unique process with broad relevance across a wide range of scientific disciplines and applications. While considerable progress in the understanding of the mechanisms underlying the nucleation of minerals from solution has been made for popular model systems such as calcium carbonate, corresponding detailed insights are still missing for other, less prominent minerals. Here, we present a potentiometric titration-based method that allows the early stages of the crystallisation of brucite, Mg(OH)₂, to be monitored and quantified. Together with complementary characterisation provided by (cryogenic) transmission electron microscopy, the collected data shed novel light on the species occurring prior to, during, and after nucleation of brucite. In the second part of the work, the newly developed approach was applied to investigate the effects of added poly(acrylic acid) on the different stages of the crystallisation process. The polymer is found to stabilise brucite nanoplatelets and co-precipitate with the inorganic phase, yielding a composite material. The methodology established in this study can readily be used to screen other chemistries for their ability to prevent magnesium hydroxide scaling and/or afford brucite nanomaterials with tailored properties.

2022-07, Gebauer, Denis, Gale, Julian D., Cölfen, Helmut

In this review article, selected, latest theoretical, and experimental developments in the field of nucleation and crystal growth of inorganic materials from aqueous solution are highlighted, with a focus on literature after 2015 and on non-classical pathways. A key point is to emphasize the so far underappreciated role of water and solvent entropy in crystallization at all stages from solution speciation through to the final crystal. While drawing on examples from current inorganic materials where non-classical behavior has been proposed, the potential of these approaches to be adapted to a wide-range of systems is also discussed, while considering the broader implications of the current re-assessment of pathways for crystallization. Various techniques that are suitable for the exploration of crystallization pathways in aqueous solution, from nucleation to crystal growth are summarized, and a flow chart for the assignment of specific theories based on experimental observations is proposed.

2021-02-03, Lu, Hao, Huang, Yu-Chieh, Hunger, Johannes, Gebauer, Denis, Cölfen, Helmut, Bonn, Mischa

Biomineralization occurs in aqueous environments. Despite the ubiquity and relevance of CaCO₃ biomineralization, the role of water in the biomineralization process has remained elusive. Here, we demonstrate that water reorganization accompanies CaCO₃ biomineralization for sea urchin spine generation in a model system. Using surface-specific vibrational spectroscopy, we probe the water at the interface of the spine-associated protein during CaCO₃ mineralization. Our results show that, while the protein structure remains unchanged, the structure of interfacial water is perturbed differently in the presence of both Ca²⁺ and CO₃^2– compared to the addition of only Ca²⁺. This difference is attributed to the condensation of prenucleation mineral species. Our findings are consistent with a nonclassical mineralization pathway for sea urchin spine generation and highlight the importance of protein hydration in biomineralization.

2022-08-29, Dong, Liang, Xu, Yun-Jun, Sui, Cong, Zhao, Yang, Gebauer, Denis, Rosenberg, Rose, Avaro, Jonathan Thomas, Lu, Yang, Cölfen, Helmut, Yu, Shu-Hong

Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.

2021-09-16, Lemke, Tobias, Edte, Moritz, Gebauer, Denis, Peter, Christine

Understanding the role of polymers rich in aspartic acid (Asp) and glutamic acid (Glu) is the key to gaining precise control over mineralization processes. Despite their chemical similarity, experiments revealed a surprisingly different influence of Asp and Glu sequences. We conducted molecular dynamics simulations of Asp and Glu peptides in the presence of calcium and chloride ions to elucidate the underlying phenomena. In line with experimental differences, in our simulations, we indeed find strong differences in the way the peptides interact with ions in solution. The investigated Asp pentapeptide tends to pull a lot of ions into its vicinity, and many structures with clusters of calcium and chloride ions on the surface of the peptide can be observed. Under the same conditions, comparatively fewer ions can be found in proximity of the investigated Glu pentapeptide, and the structures are characterized by single calcium ions bound to multiple carboxylate groups. Based on our simulation data, we identified three reasons contributing to these differences, leading to a new level of understanding additive-ion interactions.

2020-07-21, Wiedenbeck, Eduard, Gebauer, Denis, Cölfen, Helmut

The determination of solubility limits of compounds in water is unprecise and relies on certain prerequisites such as UV-Vis absorption activity. In this study we designed an experimental approach based on potentiometric titrations to determine solubility limits of various organic compounds by exploiting their pH-active carboxylic acid groups. By applying the law of mass action, utilizing a double-dosing method ensuring a constant compound concentration, it is possible to determine the intrinsic solubility limits, which are independent of the pH value. The derived equations enable the precise and fast determination of intrinsic solubility limits of organic compounds in aqueous solutions within 2 - 4 hours. Moreover, it is shown how the pK_a value can be determined based on titrations carried out at two different compound concentrations.