Exploring the Potential of Nonclassical Crystallization Pathways to Advance Cementitious Materials.

Understanding the crystallization of cement-binding phases, from basic units to macroscopic structures, can enhance cement performance, reduce clinker use, and lower CO2 emissions in the construction sector. This review examines the crystallization pathways of C-S-H (the main phase in PC cement) and other alternative binding phases, particularly as cement formulations evolve toward increasing SCMs and alternative binders as clinker replacements. We adopt a nonclassical crystallization perspective, which recognizes the existence of critical intermediate steps between ions in solution and the final crystalline phases, such as solute ion associates, dense liquid phases, amorphous intermediates, and nanoparticles. These multistep pathways uncover innovative strategies for controlling the crystallization of binding phases through additive use, potentially leading to highly optimized cement matrices. An outstanding example of additive-controlled crystallization in cementitious materials is the synthetically produced mesocrystalline C-S-H, renowned for its remarkable flexural strength. This highly ordered microstructure, which intercalates soft matter between inorganic and brittle C-S-H, was obtained by controlling the assembly of individual C-S-H subunits. While large-scale production of cementitious materials by a bottom-up self-assembly method is not yet feasible, the fundamental insights into the crystallization mechanism of cement binding phases presented here provide a foundation for developing advanced cement-based materials.

Cationic Coacervates: Novel Phosphate Ionic Reservoir for the Mineralization of Calcium Phosphates.

Cationic complex coacervates are contemplated for various medical applications controlling carrier or release processes. Here, lower Mw poly(allylamine hydrochloride) (15 kg/mol) and (hydrogen)phosphate as cross-linking units were chosen to facilitate a sufficient coacervation and subsequently a controllable phosphate release, essential for consecutive mineralization reactions. In addition, the rheological characteristics of the obtained coacervates were assessed, exhibiting a pronounced liquid character, which enables beneficial properties toward remineralization applications such as high wettability and moldability. In light of our results, macroscopic hydrogels are considered for the first time as an ion source for the mineralization of crystalline calcium phosphate phases, representing an entirely new class of preceding mineralization species for potential applications in dentistry and osteology.

Citrate Stabilizes Hydroxylapatite Precursors: Implications for Bone Mineralization.

Mineralization of hydroxylapatite (HAp), the main inorganic phase in bone, follows nonclassical crystallization routes involving metastable precursors and is strongly influenced by organic macromolecules. However, the effect of small organic molecules such as citrate on the formation of HAp is not well constrained. Using potentiometric titration experiments and titration calorimetry, in combination with a multianalytical approach, we show that citrate stabilizes prenucleation species as well as a liquid-like calcium phosphate precursor formed before any solid phase nucleates in the system. The stabilization of a liquid-like precursor phase could facilitate infiltration into the cavities of the collagen fibrils during bone mineralization, explaining the enhancement of collagen-mediated mineralization by citrate reported in previous studies. Hence, citrate can influence bone mineralization way before any solid phase (amorphous or crystalline) is formed. We also show that HAp formation after amorphous calcium phosphate (ACP) in the absence and presence of citrate results in nanoplates of about 5-12 nm thick, elongated along the c axis. Such nanoplates are made up of HAp nanocrystallites with a preferred c axis orientation and with interspersed ACP. The nanoplatelet morphology, size, and preferred crystallographic orientation, remarkably similar to those of bone HAp nanocrystals, appear to be an intrinsic feature of HAp formed from an amorphous precursor. Our results challenge current models for HAp mineralization in bone and the role of citrate, offering new clues to help answer the long-standing question as to why natural evolution favored HAp as the mineral phase in bone.

Modular Toolkit of Multifunctional Block Copoly(2-oxazoline)s for the Synthesis of Nanoparticles.

Post-polymerization modification provides an elegant way to introduce chemical functionalities onto macromolecules to produce tailor-made materials with superior properties. This concept was adapted to well-defined block copolymers of the poly(2-oxazoline) family and demonstrated the large potential of these macromolecules as universal toolkit for numerous applications. Triblock copolymers with separated water-soluble, alkyne- and alkene-containing segments were synthesized and orthogonally modified with various low-molecular weight functional molecules by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene (TE) click reactions, respectively. Representative toolkit polymers were used for the synthesis of gold, iron oxide and silica nanoparticles.

Ubiquitin Designer Proteins as a New Additive Generation toward Controlling Crystallization.

Proteins controlling mineralization in vivo are diverse, suggesting that there are various ways by which mineralization can be directed in bioinspired approaches. While well-defined three-dimensional (3D) structures occur in biomineralization proteins, the design of synthetic, soluble, bioinspired macromolecules with specific, reproducible, and predictable 3D arrangements of mineral-interacting functions poses an ultimate challenge. Thus, the question of how certain arrangements of such functions on protein surfaces influence mineralization and in what ways specific alterations subsequently affect this process remains elusive. Here we used genetically engineered ubiquitin (Ub) proteins in order to overcome the limitations of generic bioinspired 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 toward the stabilization of a film of a dense liquid mineral phase visible even with the naked eye and its transformation into amorphous nanoparticles and afterward 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 their future use for programmable, target-oriented mineralization control.

A non-classical view on calcium oxalate precipitation and the role of citrate.

Although calcium oxalates are relevant biominerals, their formation mechanisms remain largely unresolved. Here, we investigate the early stages of calcium oxalate formation in pure and citrate-bearing solutions. Citrate is used as a well-known oxalate precipitation inhibitor; moreover, it resembles the functional domains of the biomolecules that modulate biomineralization. Our data suggest that calcium oxalate forms after Ca2+ and C2O42- association into polynuclear stable complexes that aggregate into larger assemblies, from which amorphous calcium oxalate nucleates. Previous work has explained citrate inhibitory effects according to classical theories. Here we show that citrate interacts with all early stage CaC2O4 species (polynuclear stable complexes and amorphous precursors), inhibiting calcium oxalate nucleation by colloidal stabilization of polynuclear stable complexes and amorphous calcium oxalate. The control that citrate exerts on calcium oxalate biomineralization may thus begin earlier than previously thought. These insights provide information regarding the mechanisms governing biomineralization, including pathological processes (e.g., kidney stone formation).The formation mechanism of abundant calcium oxalate biomaterials is unresolved. Here the authors show the early stages of calcium oxalate formation in pure and citrate-bearing solutions by using a titration set-up in conjunction with solution quenching, transmission electron microscopy and analytical ultracentrifugation.