Gebauer, Denis
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Non-stoichiometric hydrated magnesium-doped calcium carbonate precipitation in ethanol
The effect of Mg2+ on the precipitation pathway of CaCO3 in absolute ethanol has been studied to investigate the role of ion solvation in the crystallization process. Our data reveal that high concentrations of Mg2+ promote the precipitation of an amorphous transient phase together with non-stoichometric hydrated phases of calcium carbonate.
Liquid Metastable Precursors of Ibuprofen as Aqueous Nucleation Intermediates
The nucleation mechanism of crystals of small organic molecules, postulated based on computer simulations, still lacks experimental evidence. In this study we designed an experimental approach to monitor the early stages of the crystallization of ibuprofen as pharmaceutically eminent molecule and a model system for small organic molecules. We found that ibuprofen undergoes liquid-liquid phase separation prior to nucleation. The binodal and spinodal limits of the corresponding liquid-liquid miscibility gap were localized by combining potentiometric titration with 1 H NMR spectroscopy and additional analyses. We confirmed the liquid character of this initially formed phase by applying PFG-STE self-diffusion experiments ( 1 H NMR) and found an increase in viscosity sustaining the kinetic stability of the dense liquid intermediate. Intermolecular distances of ibuprofen within the dense liquid phase were found to be similar to those in the crystal forms, according to 2D 1 H- 1 H NOESY measurements. Hence, this dense liquid phase is identified as a precursor phase within a nucleation pathway of ibuprofen, in which densification is followed by structural order generation. Fundamentally, this discovery bears the opportunity and promise to enrich poorly soluble pharmaceuticals beyond classical solubility limitations in aqueous environments.
Baryte cohesive layers formed on a (010) gypsum surface by a pseudomorphic replacement
The mineral replacement of gypsum (CaSO4·2H2O) by baryte (BaSO4) is relevant to technological and industrial applications, including its use as a plaster or stone consolidant in cultural heritage conservation. In the present study, we provide experimental evidence suggesting that, during the interaction of gypsum cleavage surfaces with barium-bearing solutions, a pseudomorphic replacement takes place and results in the formation of a crystallographically oriented baryte layer. This mineral replacement process is favoured by the porosity generated, due to the differences in molar volume and solubility between parent and product sulfate phases, allowing the progress of the reaction. The homogeneous micrometre-sized layer of baryte occurs most likely via a fluid-mediated interface-coupled dissolution–precipitation mechanism. A certain degree of crystallographic control on the polycrystalline BaSO4 product layer by the structure of the parent substrate (gypsum) is confirmed by electron microscopy observations and X-ray diffraction analyses. The structural control exerted by the cleavage gypsum surface on the baryte layer can be defined by the epitactic relationship: Gyp (010) || Bar (010). The formation of baryte increases with reaction time until passivation occurs at the replacement interface, probably due to a decreased porosity and loss of connectivity that thereby prevents further reaction. The investigation of these processes occurring on freshly cleaved single crystals of gypsum were complemented by studying the replacement of polycrystalline gypsum cubes, showing a homogeneous baryte surface layer on the sample. The results of this study thus offer interesting insights into the application of the replacement of gypsum by baryte as a conservation method for gypsum sculptures and plasterwork, increasing their resistance against water and humidity while preserving the surface features of the original mineral substrate.
On Biomineralization : Enzymes Switch on Mesocrystal Assembly
Cellular machineries guide the bottom-up pathways toward crystal superstructures based on the transport of inorganic precursors and their precise integration with organic frameworks. The biosynthesis of mesocrystalline spines entails concerted interactions between biomolecules and inorganic precursors; however, the bioinorganic interactions and interfaces that regulate material form and growth as well as the selective emergence of structural complexity in the form of nanostructured crystals are not clear. By investigating mineral nucleation under the regulation of recombinant proteins, we show that SpSM50, a matrix protein of the sea urchin spine, stabilizes mineral precursors via vesicle-confinement, a function conferred by a low-complexity, disordered region. Site-specific proteolysis of this domain by a collagenase initiates phase transformation of the confined mineral phase. The residual C-type lectin domain molds the fluidic mineral precursor into hierarchical mesocrystals identical to structural crystal modules constituting the biogenic mineral. Thus, the regulatory functions of proteolytic enzymes can guide biomacromolecular domain constitutions and interfaces, in turn determining inorganic phase transformations toward hybrid materials as well as integrating organic and inorganic components across hierarchical length scales. Bearing striking resemblance to biogenic mineralization, these hybrid materials recruit bioinorganic interactions which elegantly intertwine nucleation and crystallization phenomena with biomolecular structural dynamics, hence elucidating a long-sought key of how nature can orchestrate complex biomineralization processes.
Pseudo-Biomineralization : Complex Mineral Structures Shaped by Microbes
Biomineralization is an active, biologically governed process of mineral formation, established early on in the history of life. The appearance of biomineralizing organisms heavily influenced the course of evolution, leading to the development of the large diversity of the extant taxa. Yet, we are still only beginning to grasp the intricate, genetically regulated mechanisms involved. Since prokaryotic organisms were the first to emerge from the primordial environments, we investigated bacteria–mineral interactions using titration and gas diffusion systems adapted to emulate conditions, which may have facilitated the development of biomineralization initially. By screening the minerals and bacteria from titration experiments with scanning electron microscopy, we discovered a broad spectrum of behavioral strategies employed by bacteria confronted with calcification, which fell into three main categories: (1) evasion of mineralization by the formation of the biofilm, (2) random embedding into the mineral, and (3) control over the mineral shape during its formation. The latter phenomenon we termed pseudo-biomineralization. Our experiments indicate that pseudo-biomineralization is an active process obligatorily reliant on the external calcifying conditions and allowing considerable degree of control over mineral shape, thus producing structures reminiscent of true biominerals. Here, we describe this notion for the first time, thus providing vital insight into the genesis of a transitional stage to calcium carbonate-based biomineralization systems.
Ubiquitin Designer Proteins as a New Additive Generation towards Controlling Crystallization
Proteins controlling mineralization in vivo are diverse, suggesting that there are various ways by which mineralization can be directed in bio-inspired approaches. While well-defined three-dimensional (3D) structures occur in biomineralization proteins, the design of synthetic, soluble, bio-inspired macromolecules with specific, reproducible and predictable 3D arrangements of mineral-interacting functions poses an ultimate challenge. Thus, the question how certain arrangements of such functions on protein surfaces influence mineralization, and in which way, subsequently, specific alterations affect this process, remains elusive. Here, we used genetically engineered Ubiquitin (Ub) proteins in order to overcome the limitations of generic bio-inspired additive systems. By advancing existing protocols, we introduced an unnatural amino acid and, subsequently, mineral-interacting functions via selective pressure incorporation and click chemistry, respectively, without affecting the Ub secondary structure. Indeed, as-obtained Ub with three phosphate functions at defined positions shows unique effects, based on a yet unmatched capability towards the stabilization of a film of a dense liquid mineral phase visible even by naked eye, its transformation into amorphous nanoparticles, and afterwards crystals with complex shapes. We thereby demonstrate that Ub designer proteins pose a unique, new generation of crystallization additives where the 3D arrangement of mineral-interacting functions can be designed at will, promising a future use for programmable, target-oriented mineralization control.
Short-Range Structure of Amorphous Calcium Hydrogen Phosphate
Calcium orthophosphates (CaPs) are the hard constituents of bones and teeth, and thus of ultimate importance to humankind, while amorphous CaPs (ACPs) may play crucial roles in CaP biomineralization. Among the various ACPs with Ca/P atomic ratios between 1.0–1.5, an established structural model exists for basic ACP (Ca/P = 1.5), while those of other ACPs remain unclear. Herein, the structure of amorphous calcium hydrogen phosphate (ACHP; Ca/P = 1.0) obtained via aqueous routes at near-neutral pH values, without stabilizers, was studied by experiments (mainly, TEM with ED, XRD, IR, and NMR spectroscopies, as well as XAS) and computer simulation. Our results globally show that ACHP has a distinct short-range structure, and we propose calcium hydrogen phosphate clusters (CHPCs) as its basic unit. This model is consistent with both computer simulations and the experimental results, where CHPCs are arranged together with water molecules to build up ACHP. We demonstrate that Posner’s clusters, which are conventionally accepted to be the building unit of basic ACPs, do not represent the short-range structure of ACHP, as Posner’s clusters and CHPCs are structurally distinct. This finding is important not only for the determination of the structures of diverse ACPs with varying Ca/P atomic ratios but also for fundamental understanding of a major mineral class that is central to biomineralization in vertebrates and, thus, humans, in particular.
Nucleation of hematite : A non-classical mechanism
Hematite (α-Fe2O3) is thermodynamically stable at ambient conditions, of vast geological importance, and widely used in applications. It forms at elevated temperatures, while room temperature reactions typically yield metastable akaganéite or ferrihydrite. The mechanistic key changes underlying this observation were explored in the present study. The entropic contribution to the pre-nucleation hydrolysis reaction categorically implies the presence of pre-nucleation clusters (PNCs) as fundamental precursors. The formation of hematite is then due to a change in the reaction mechanism above ~50 °C, where the reaction limitation towards oxolation within phase separated clusters is overcome. We propose a model that rationalizes the occurrence of hematite, akagenéite and ferrihydrite based upon the chemistry of olation PNCs. Supersaturation, or the temperature dependencies of olation and oxolation rates from monomeric precursors are irrelevant in this non-classical mechanism.
Impurity-free amorphous calcium carbonate, a preferential material for pharmaceutic and medical applications
Biomedical applications of calcium carbonate minerals have been receiving an increasing amount of attention. With a simple chemical composition, low production cost, and ease to produce in large quantities, this non-toxic (bio)mineral has been used preferentially in the pharmaceutical industry as a diluent, bulking or coating agent. Recently, novel products have been developed and amorphous calcium carbonate was successfully used as a hybrid carrier for drugs, proteins and genes. It is obvious that any impurities might have adverse effects in any of the aforementioned applications. However, the synthesis of impurity-free amorphous calcium carbonate often proves to be challenging due to its instability and rapid transformation to crystalline phases. Herein, we describe a novel, simple and scalable protocol for the synthesis of such impurity-free amorphous calcium carbonate nanoparticles that is potentially invaluable for critical health applications, improving the applicability of amorphous calcium carbonates in pharmaceutical and medical domains.
Designing Solid Materials from Their Solute State : A Shift in Paradigms toward a Holistic Approach in Functional Materials Chemistry
“Non-classical” notions consider formation pathways of crystalline materials where larger species than monomeric chemical constituents, i.e., ions or single molecules, play crucial roles, which are not covered by the classical theories dating back to the 1870s and 1920s. Providing an outline of “non-classical” nucleation, we demonstrate that prenucleation clusters (PNCs) can lie on alternative pathways to phase separation, where the very event of demixing is primarily based on not the sizes of the species forming, as in the classical view, but their dynamics. Rationalizing, on the other hand, that precursors that can be analytically detected in pre-nucleation stages and that play a role in phase separation must be considered PNCs and cannot be explained by classical notions, we outline a variety of systems where PNCs are important. Indeed, in recent years, with the advent of “non-classical” theories, a primary focus of research concentrated on the fundamental understanding of oligomeric/polymeric and particulate species involved in nucleation and crystallization processes, respectively. At the same time, the near-to unfathomable potential of “non-classical” routes for the synthesis of inorganic functional materials slowly unfolds. An overview of recent developments in the fundamental and mechanistic understanding of “non-classical” nucleation and crystallization in this Perspective then allows us to map out the potential of cluster/particle-driven mineralization pathways to intrinsically tailor the properties of inorganic functional (hybrid) materials via structuration from the nano- to the mesoscale. This is of utter importance for the functionality and performance of materials, as it may even confer emergent properties such as self-healing. Biominerals—often formed via particle accretion mechanisms—demonstrate this impressively and thus can serve as a further source of inspiration how to exploit nonclassical crystallization routes for syntheses of structured and functional materials. These new avenues to synthetic approaches may finally provide a holistic material concept, in which fundamental chemistry and materials science synergistically alloy.