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Versatile Roles of Modifiers in Crystal Growth and Morphology Modification of Lithium Hydroxide Monohydrate
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Modifiers are commonly used in natural, biological, and synthetic crystallization to tailor the growth of diverse materials. Here, we identify tautomers as a new class of modifiers where the dynamic interconversion between solute and its corresponding tautomer(s) produces native crystal growth inhibitors. The macroscopic and microscopic effects imposed by inhibitor-crystal interactions reveal dual mechanisms of inhibition where tautomer occlusion within crystals that leads to natural bending, tunes elastic modulus, and selectively alters the rate of crystal dissolution. Our study focuses on ammonium urate crystallization and shows that the keto-enol form of urate, which exists as a minor tautomer, is a potent inhibitor that nearly suppresses crystal growth at select solution alkalinity and supersaturation. The generalizability of this phenomenon is demonstrated for two additional tautomers with relevance to biological systems and pharmaceuticals. These findings offer potential routes in crystal engineering to strategically control the mechanical or physicochemical properties of tautomeric materials.
The mechanisms by which organisms control the stability of amorphous calcium carbonate (ACC) are yet not fully understood. Previous studies have shown that the intrinsic properties of ACC and its environment are critical in determining ACC stability. Here, the question, what is the effect of bulk incorporation versus surface adsorption of additives on the stability of synthetic ACC, is addressed. Using a wide range of in situ characterization techniques, it is shown that surface adsorption of poly(Aspartic acid) (pAsp) has a much larger stabilization effect than bulk incorporation of pAsp and only 1.5% pAsp could dramatically increase the crystallization temperature from 141 to 350 °C. On the contrary, surface adsorption of PO43− ions and OH− ions does not effectively stabilize ACC. However, bulk incorporation of these ions could significantly improve the ACC stability. It is concluded that the stabilization mechanism of pAsp is entirely different from that of PO43− and OH− ions: while pAsp is effectively inhibiting calcite nucleation at the surface of ACC particle, the latter acts to modify the ion mobility and delay crystal propagation. Thus, new insights on controlling the stability and crystallization processes of metastable amorphous materials are provided. This work shows that the mechanisms by which additives stabilize ACC strongly depend on the characters of the additives and their spatial distribution within the nanoparticles. While polyaspartic acid effectively inhibits calcite nucleation at the surface of ACC particle, PO43− and OH− ions act to modify the ion mobility, therefore delaying crystal propagation.
The crystallization of magnesium ammonium phosphate hexahydrate (struvite) often occurs under conditions of fluid flow, yet the dynamics of struvite growth under these relevant environments has not been previously reported. In this study, we use a microfluidic device to evaluate the anisotropic growth of struvite crystals at variable flow rates and solution supersaturation. We show that bulk crystallization under quiescent conditions yields irreproducible data owing to the propensity of struvite to adopt defects in its crystal lattice, as well as fluctuations in pH that markedly impact crystal growth rates. Studies in microfluidic channels allow for time‐resolved analysis of seeded growth along all three principle crystallographic directions and under highly controlled environments. After having first identified flow rates that differentiate diffusion and reaction limited growth regimes, we operated solely in the latter regime to extract the kinetic rates of struvite growth along the [100], [010], and [001] directions. In situ atomic force microscopy was used to obtain molecular level details of surface growth mechanisms. Our findings reveal a classical pathway of crystallization by monomer addition with the expected transition from growth by screw dislocations at low supersaturation to that of two‐dimensional layer generation and spreading at high supersaturation. Collectively, these studies present a platform for assessing struvite crystallization under flow conditions and demonstrate how this approach is superior to measurements under quiescent conditions.
We discuss the high-pressure phases of crystalline lithium hydroxide, LiOH. Using first-principles calculations, and assisted by evolutionary structure searches, we reproduce the experimentally known phase transition under pressure, but we suggest that the high-pressure phase LiOH-III be assigned to a new hydrogen-bonded tetragonal structure type that is unique amongst alkali hydroxides. LiOH is at the intersection of both ionic and hydrogen bonding, and we examine the various ensuing structural features and their energetic driving mechanisms. At P = 17 GPa, we predict another phase transition to a new phase, Pbcm-LiOH-IV, which we find to be stable over a wide pres-sure range. Eventually, at extremely high pressures of 1100 GPa, the ground state of LiOH is pre-dicted to become a polymeric structure with an unusual graphitic oxygen-hydrogen net. However, because of its ionic character, the anticipated metallization of LiOH is much delayed; in fact, its electronic band gap increases monotonically into the TPa pressure range.
Taking the Cystine
Kidney stones that form from l -cystine are much less common than those forming from calcium oxalate monohydrate, but are more likely to cause chronic kidney disease. Rimer et al. (p. 337 ; see the cover; see the Perspective by Coe and Asplin ) designed two structural mimics for l -cystine. Atomic force microscopy showed that at low concentrations, the mimics could change the l -cystine crystal habit and inhibit overall crystal growth. These structural mimics may thus offer hope for treating cystinuria.
There is a deep and useful connection between statistical mechanics (the behavior of systems with many degrees of freedom
in thermal equilibrium at a finite temperature) and multivariate or combinatorial optimization (finding the minimum of a given
function depending on many parameters). A detailed analogy with annealing in solids provides a framework for optimization
of the properties of very large and complex systems. This connection to statistical mechanics exposes new information and
provides an unfamiliar perspective on traditional optimization problems and methods.
Interactions between molecular modifiers and crystal surfaces govern numerous processes and structural outcomes of natural, biological, and synthetic crystallization. An efficient method of tailoring modifier-crystal interactions involves the design of imposters with structures and chemical functionalities that closely match those of the solute with subtle changes that preserve molecular recognition for modifier binding to crystal surfaces. Modifiers can function as inhibitors, promoters, or combinations of both to alter processes of crystal nucleation and growth. Here, we examine molecular modifiers that perturb the crystallization of ammonium urate (NH4HU), a pathological component of kidney stones, and a model system for assessing modifier-crystal interactions. Bulk crystallization assays were used to identify effective inhibitors and promoters of NH4HU crystallization. Two potent inhibitors, methyluric acid (MA) and poly(ethyleneimine) (PEIM), were identified where PEIM completely suppresses crystal growth at concentrations above 1.0 μg/mL, and MA displays a maximum growth inhibition of 60%. Time-resolved studies using a combination of microfluidics and atomic force microscopy elucidated the mechanisms by which each modifier influences layer generation and spreading on crystal surfaces. We used these techniques for select modifiers to quantify their effects on the anisotropic rates of crystallization and concomitant impact on crystal size and morphology. In situ characterization revealed that subtle changes in modifier functionality determine whether these imposters operate by either step pinning or kink blocking mechanisms. We demonstrated that molecular imposters of NH4HU crystallization operate by multiple, and sometimes opposing, roles of promotion and inhibition depending on the judicious selection of growth conditions. Collectively, our findings uncover trends among molecular imposters that are unique in relation to previously reported cases of crystal growth modification.
Mineral surface properties and mineral-aqueous interfacial reactions are essential factors affecting the geochemical cycle, related environmental impacts, and bioavailability of chemical elements. Compared to macroscopic analytical instruments, an atomic force microscope (AFM) provides necessary and vital information for analyzing mineral structure, especially the mineral-aqueous interfaces, and has excellent application prospects in mineralogical research. This paper presents recent advances in the study of properties of minerals such as surface roughness, crystal structure and adhesion by atomic force microscopy, as well as the progress of application and main contributions in mineral-aqueous interfaces analysis, such as mineral dissolution, redox and adsorption processes. It describes the principles, range of applications, strengths and weaknesses of using AFM in combination with IR and Raman spectroscopy instruments to characterization of minerals. Finally, according to the limitations of the AFM structure and function, this research proposes some ideas and suggestions for developing and designing AFM techniques.
Designing (macro)molecules controlling crystallization is an essential approach to regulate structure and properties of crystalline materials and circumvent detrimental mineralization in nature, biological, and synthetic systems. Here we discovered four novel, natural polyphenols, including gallic acid, ellagic acid, punicalagin, and tannic acid, as a new class of inhibitors for nucleation and crystal growth of calcium oxalate (CaOx), a primary constitution of kidney stones. Study of time-resolved growth reveals that polyphenols regulate the kinetics of crystal-liquid interface acting as a dual role of growth promoter and inhibitor which displays a new record of growth promotion up to 75% or complete suppression, dependent upon the modifier concentration. Time-elapsed in situ atomic force microscopy measurements unveil these modifiers regulate the growth mode from spiral-mediated to generation of two-dimensional (2D) islands and layer spreading mechanism, leading to formation of step bunches growing out of (010) surface and forming macroscopically crystal whiskers. The governing regime between growth promotion and inhibition is determined by inhibitors concentration but can be influenced by crystallization driving force. Such unique growth mechanism of crystal whiskers may also provide potential implications for understanding and synthesizing branched and hierarchical structures of biomimetic materials.
Tailor‐made auxiliaries are generally less stereochemically discriminating of crystals grown from the melt than crystals grown from solution. However, it is possible to make supramolecular inferences using well‐chosen additives in the manner taught to us by Lahav and Leiserowitz. Spherulites manifesting needle‐like growth and small angle branching grow frequently from supercooled melts under high crystallization driving forces, along one principal crystallographic direction. If this direction is polar, it is important to establish its absolute sense as a basis for understanding growth at the interface between crystals and melt. This assignment, for polycrystalline ensembles, is beyond the capabilities of X‐ray crystallography. Two examples of this discrimination are described with tailor‐made additives, one for the β form of resorcinol and another for form I of L‐malic acid. Assigning the absolute sense of a polar axis with molecular additives is a problem that resembles both the science and style of previous experiments from the Weizmann Institute.
The effect of different chelating agents on the crystallization of CaCO3, polymorphism and morphology of CaCO3 in the presence of barium were studied at 100 °C. The samples were characterized using FTIR, Raman spectroscopy, XRD and FESEM techniques. The study revealed that without any chelating agents, in the presence of different volumes of 0.1 M Ba²⁺ ion solution, stabilization of a binary mixture of rhombohedral calcite and flower-like vateritewas facilitated. In the presence of EDTA, the phenomenal transformation of calcite to vateritewas observed. Pure calcite has resulted in the presence of Nitrilotriacetic acid (NTA) in the presence of Ba²⁺ ions. Blending EDTA with NTA favoured a binary mixture of spherical vaterite and calcite. The probable mechanism for stabilization of various polymorphs by the additives and effect of blending of additives for better scale inhibition efficiency has been discussed.
This study investigated the pressure leaching of lithium and other valuable metals from lepidolite using NaOH and Ca(OH)2. The findings showed that NaOH concentration, temperature, and stirring rate are the most significant process parameters. The addition of Ca(OH)2 facilitates the leaching of lithium and minimizes the concentration of silicate and fluoride in the leach liquor by forming solid phases identified as Ca3Al2Si3O12 CaF2 and NaCaHSiO4, with a loss of about 7% NaOH. The leaching efficiencies after 2 h were 94% Li, 98% K, 96% Rb, and 90% Cs under the most suitable conditions (250 °C, 320 g/L NaOH, liquid-to-solid ratio of 10, 300 rpm stirring speed, lime addition of 0.3 g/g). Precipitation of lithium as Li3PO4 by adding phosphoric acid and subsequent conversion of Li3PO4 to LiOH using Ca(OH)2 recovered 83% of lithium as LiOH allowing recycling the rest along with 93% of NaOH for leaching.
Increasing commercial application of state of the art crystal structure prediction to aid solid form discovery of new molecular entities allows the experimentalist to target the polymorphs with desired properties. Here we remind ourselves that in this field the gap between such prediction and experimentation can be vast, the latter depending strongly on kinetic processes not accounted for in the computations. Nowhere is this gap more evident than in examples of so-called "elusive" polymorphs, forms that have been found difficult to crystallize, sometimes taking years to appear or sometimes disappearing altogether. In attempting to probe the origins of such phenomena this work targets a well-known, relatively simple molecule, paracetamol (PCM), and explores the structural and kinetic origins of its elusive nature. It is noted that in general comparisons of the kinetic factors (nucleation and crystal growth) between polymorphs have rarely been reported and of course in cases where one or more forms is "elusive" this will, by definition, be essentially impossible. PCM however offers a unique opportunity and we show how the recent discovery of the impact of metacetamol (MCM) in stabilizing PCM form II can be used to advantage, enabling otherwise impossible comparative kinetic experiments to be made. Resulting from this study we now appreciate that MCM has a selective impact in blocking the growth of the thickness and width of PCM form I while it has no impact on form II. This is interpreted in terms of strong adsorption of MCM on the {011} faces (width and thickness) of form I in orientations that inhibit crystal growth ("wrong" orientations). Of more significance here is the use of the additive in allowing an otherwise impossible comparison of linear growth rates of forms I and II. This leads to the appreciation that only through calculation of growth volumes can we finally appreciate how the relative growth kinetics lead inevitably to the elusive nature of Form II.
In many instances, it is reported that growth inhibitors contain-ing carboxyl groups can potentially interact with metal cations on a crystal surface to suppress the growth of crystallization. There are fewer reports about modifiers which operate as growth promoters, whereby modifier−crystal interactions accel-erate the growth of crystallization. Here, we present that the acetate (ACE), as an alcohol metabolite, is able to obviously promote the growth of the pathology crystallization of gout not only under model physiological conditions but in the Na+, K+, Ca2+ and hyaluronate- ion-containing solutions. This approach could help our understanding the association between alcohol consumption and increased risk of recurrent gout attacks, since the “triggers”, that is, crystallization factors immediately before gout attacks, still remain speculative. Finally, possible explana-tion for effect of ACE on monosodium urate monohydrate (MSUM) growth is proposed on the basis of quantum chemical calculations (QCC).
Pyridoxine hydrochloride, commonly known as vitamin B6 (VB6), is considered as one of the most essential vitamin enhancer. Understanding its crystal morphology is of paramount interest in pharmaceutical industry. Herein, we systematically investigate the crystallization of VB6 in the absence and presence of 0.5 mM~2 mM nonionic and ionic surfactants by single crystal growth experiments and theoretical calculations. VB6 crystals exhibit the most common block-like morphology in aqueous and non-ionic surfactant solution, while needle-like crystals are observed, for the first time, in ionic surfactant solutions. Two surfaces, (100) and (010) play a decisive role in modulating the crystal morphology. The preferential adsorption of anionic sodium dodecyl sulfate surfactant on the radial (010) surface inhibiting its growth over the axial (100) surface results in high aspect ratio of the crystals. On the other hand, the cationic hexadecyl trimethyl ammonium bromide surfactant enhances both the surfaces growth by promoting Cl- ions integration to the surfaces. The zwitterionic dodecyl dimethyl betaine surfactant hinders (010) surface growth by surface adsorption while promotes (100) surface growth by accelerating Cl- integration. Besides, a slight growth inhibition of both the surfaces by the nonionic Tween 80 surfactant is due to surfactants crowding on the growing surfaces.
We present results on dynamic testing for calcium oxalate (CaOx) crystal growth inhibition of many of the known polyprotic additives previously investigated by static methods, as well as a few new additives that we have proposed. The dynamic tests include fluid mixing and flow through tube blocking equipment whilst measuring the pressure drop due to build-up of CaOx scale. Simple solutions supersaturated with only calcium and oxalate ions, as well as a more complex solutions containing the typical ions found in urine were investigated. Using these optimum concentrations in the dynamic tube blocking rig, it was found that the ranking and inhibition efficacy of the tested additives was very similar in both the simplified system, containing only calcium and oxalate ions, and the synthetic urine. Polyprotic acids with only a few acid groups, such as citric acid, hydroxycitric acid and phytic acid, were found to be less effective as CaOx inhibitors compared to larger polycarboxylic acids such as polyaspartic acid, carboxymethylinulin and polyglutamic acid. Potassium hydroxycitrate, which has been proposed as a better chemical treatment for CaOx kidney stone patients, showed a small improvement in performance over citric acid or magnesium citrate.
Interactions of macromolecules with growing crystalline surfaces play an important role in biomineralization, determine survival of some organisms at low temperatures, and offer a range of potential industrial applications. The current understanding of crystal growth processes in the presence of macromolecules, including peptides and proteins, is reviewed, with a focus on interactions between macromolecules and surfaces of crystalline materials, macromolecule adsorption on different types of crystal surfaces, crystallization kinetics in the presence of macromolecular additives, macromolecule incorporation, and defect generation. Throughout, special attention is paid to the selectivity of macromolecule adsorption on, and incorporation within, crystal surfaces. The special role played by the size and complexity of macromolecules as compared to other crystallization additives is emphasized.
Purpose of review:
This review discusses the role of molecular modifiers as inhibitors of kidney stone formation, drawing largely from in-vitro evidence while also citing relevant in-vivo studies. An emphasis is placed on physical observations of crystal growth inhibition, including mechanisms of action that focus predominantly on the literature of calcium oxalate and L-cystine.
Recent findings:
The last decade has witnessed several breakthroughs in the identification of molecules with promise to curb kidney stone formation, as well as discoveries of the mechanisms by which these molecules (or combinations thereof) function as inhibitors of pathological crystal growth. Studies of L-cystine and calcium oxalate crystallization have uncovered inhibitors that are more effective than current therapies. In-vitro assays using advanced techniques such as atomic force microscopy have been able to characterize modifier-crystal interactions and the mechanisms of crystal growth inhibition. A recent study of calcium oxalate crystals uncovered a new inhibition pathway leading to crystal dissolution at relatively low modifier concentrations.
Summary:
Advanced methods of identifying therapeutics for kidney stone disease have created a greater awareness of the potential impact of crystal modifiers in pathological crystallization. Many natural and synthetic species have the capacity to act as growth inhibitors; however, the challenge of bridging in-vitro and in-vivo evidence has proven to be difficult. Future effort to better integrate laboratory research, clinical trials and animal studies has the potential to broaden our understanding of crystal growth modification and its role in mitigating pathological crystallization.
In this study, methyl paraben (MP) was selected as the model component, and acetaminophen (APAP), p-methyl acetanilide (PMAA) and acetanilide (ACET), which share the similar molecular structure as MP, were selected as the three tailor-made additives to study the effect of tailor-made additives on the crystal growth of MP. HPLC results indicated that the MP crystals induced by the three additives contained MP only. Photographs of the single crystals prepared indicated that the morphology of the MP crystals was greatly changed by the additives, but PXRD and single crystal diffraction results illustrated that the MP crystals were the same polymorph only with different crystal habits, and no new crystal form was found compared with other references. To investigate the effect of the additives on the crystal growth, the interaction between additives and facets was discussed in detail using the DFT methods and MD simulations. The results showed that APAP, PMAA and ACET would be selectively adsorbed on the growth surfaces of the crystal facets, which induced the change in MP crystal habits.
Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization-citrate and hydroxycitrate-exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.
Crystallization is often facilitated by modifiers that interact with specific crystal surfaces and mediate the anisotropic rate of growth. Natural and synthetic modifiers tend to function as growth inhibitors that hinder solute attachment and impede the advancement of layers on crystal surfaces. There are fewer examples of modifiers that operate as growth promoters whereby modifier-crystal interactions accelerate the kinetic rate of crystallization. Here we examine two proteins, lysozyme and lactoferrin, which are observed in the organic matrix of three types of pathological stones: renal, prostatic, and pancreatic stones. This work focuses on the role of these proteins in the crystallization of calcium oxalate monohydrate (COM), the most prominent constituent of human kidney stones. Using a combination of experimental techniques, we show that these proteins, which are rich in L-arginine and L-lysine amino acids, promote COM growth. The synthesis and testing of peptides derived from contiguous segments of lysozyme's primary amino acid sequence revealed subdomains within the protein that operate either as an inhibitor or promoter of COM growth, with the latter exhibiting efficacies that nearly match that of the protein. We observed that cationic proteins promote COM growth over a wide range of modifier concentration, which differs from calcification promoters in literature that exhibit dual roles as promoters and inhibitors at low and high concentration, respectively. This seems to suggest a unique mechanism of action for lysozyme and lactoferrin. Possible explanations for their effects on COM growth and crystal habit are proposed on the basis of classical colloidal theories and the physicochemical properties of peptide subdomains, including the number and spatial location of charged and/or hydrogen-bonding moieties.
The effect of l-valine on the growth of the l-alanine (011) surface from solution crystallization is studied by combining single-crystal growth experiments and molecular simulation. For the first time, an unusual promotion effect of l-valine on l-alanine crystal growth, after the initial inhibition effect, is found when the impurity concentration is higher. Through molecular simulation, it is revealed that this unusual promotion effect is due to the close interaction between l-alanine and l-valine, which repels H2O around solute molecules and therefore eliminates the negative effect of H2O on surface diffusion of l-alanine.
Given the importance of organic crystals in a wide range of industrial applications, the chemistry, biology, materials science, and chemical engineering communities have focused considerable attention on developing methods to control crystal structure, size, shape, and orientation. Tailored additives have been used to control crystallization to great effect, presumably by selectively binding to particular crystallographic surfaces and sites. However, substantial knowledge gaps still exist in the fundamental mechanisms that govern the formation and growth of organic crystals in both the absence and presence of additives. In this review, we highlight research discoveries that reveal the role of additives, either introduced by design or present adventitiously, on various stages of formation and growth of organic crystals, including nucleation, dislocation spiral growth mechanisms, growth inhibition, and nonclassical crystal morphologies. The insights from these investigations and others of their kind are likely to guide the development of innovative methods to manipulate crystallization for a wide range of materials and applications. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering Volume 5 is June 07, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
The molecular recognition and interactions governing site specific adsorption of growth inhibitors on crystal surfaces can be tailored in order to control the anisotropic growth rates and physical properties of crystalline materials. Here we examine this phenomenon in calcium oxalate monohydrate (COM) crystallization, a model system of calcification with specific relevance for pathological mineralization. We analyzed the effect of three putative growth inhibitors - chondroitin sulfate, serum albumin, and transferrin - using analytical techniques capable of resolving inhibitor-crystal interactions from interfacial to bulk scales. We observed that each inhibitor alters surface growth by adsorbing on to distinct steps emanating from screw dislocations on COM surfaces. Binding of inhibitors to different crystallographic faces produced morphological modifications that are consistent with classical mechanisms of layer-by-layer crystal growth inhibition. The site specific adsorption of inhibitors on COM surfaces was confirmed by bulk crystallization, fluorescent confocal microscopy, and atomic force microscopy. Kinetic studies of COM growth at varying inhibitor concentrations revealed marked differences in their efficacy and potency. Systematic analysis of inhibitor combinations, quantified via the combination index, identified various binary pairings capable of producing synergistic, additive, and antagonistic effects. Collectively, our investigation of physiologically-relevant biomolecules suggests potential roles of COM inhibitors in pathological crystallization and provides guiding principles for biomimetic design of molecular modifiers for applications in crystal engineering.
Agglomerates of naproxen, carbamazepine and lactose were developed by two spherical crystallization techniques, i.e., a spherical agglomeration method for carbamazepine and an emulsion diffusion method for naproxen and lactose. Physical characteristics of the crystals were studied for the morphology of crystals using scanning electron microscope, for the identification of polymorphism by X-ray powder diffraction (XRPD) and for thermodynamic properties using differential scanning calorimetery (DSC). The results showed that the flow and packing properties of agglomerates, represented in terms of the angle of repose and changes in tapping density, were much improved by these techniques compared with those of conventional crystals. This may be due to the spherical shape of agglomerated particles, since the area of contact in the powder bed for spherical agglomerates was smaller than that for other crystal shapes. Under static compression the acceptable tablet with a sufficient strength was produced successfully without capping, although the capping occurred with the original unagglomerated crystals. The improved compactibility of agglomerates was attributed to their structural characteristics. Scanning electron microscope showed that the agglomerates were comprised of small crystals and this particular structure was responsible for large relative volumes change which occurred during the early stage of the compression process, as a consequence of fragmentation. XRPD and DSC results showed that during the agglomeration process, naproxen did not undergo any polymorphic changes. XRPD and DSC results for carbamazepine and lactose revealed that during the agglomeration process, carbamazepine Form III changed to Form I and some of α-lactose monohydrates were converted to anhydrous β-lactose.
I. Crystal Surfaces in Equilibrium with the Surrounding Medium 117 The Surface Energy of Crystals 117 1. Kinks in Elementary Steps 117 2. Crystal Surface Energy. Herring's Formula 118 3. Corner Points in the Profiles of Crystal Surfaces 119 4. Surface Stability Conditions 120 5. The Equilibrium Shape of an Open Curve 121 II. Crystal Growth from Vapor 122 6. Particles Adsorbed on a Surface 123 7. The Motion of an Isolated Step 123 8. Parallel Sequences of Elementary Steps 124 9. The Normal Rate of Spiral Growth 124 10. The Motion of Macroscopic Steps 126 11. Some Experimental Results 128 12. Evaporation 129 III. Crystal Growth from the Solution and from the Melt 129 13. Introduction 129 14. The Motion of a Parallel Sequence of Elementary Steps 130 15. The Normal Growth Rate 131 16. Some Experimental Results 131 17. Growth from the Melt 132 18. The Diffusion Field and Rate of Advance of a Macroscopic Step 133 IV. The Interaction of Growing Crystals with Impurities 134 19. The Influence of Impurities on the Growth Rate 134 a) Strongly Adsorbed Impurities Captured by a Growing Crystal 135 b). Impurity Poisoning of Sinks 135 20. Nonequilibrium Capture of Impurities in Crystal Growth 137 21. Dislocation Production in Impurity Capture 139 V. Etching 139 VI. Collective Effects in the Movement of Steps 140 22. "Shock Waves" of Step Density 141 23. A Kinetic Equation for Steps 143 References 145
In this paper, the biomineralization of calcium carbonate through the cooperative interactions between self-assembled monolayers (SAMs) and multiple soluble additives was first investigated. The polymorphs and morphologies of products were well controlled by the existence of ordered surface and the co-effect of silk fibroin and magnesium ions. It was found that polymorphs and morphologies of products were determined by silk fibroin, magnesium ions had a promotional effect at lower concentration of magnesium ions, while at higher concentration of magnesium ions, the growth of vaterite crystals was stabilized. This work avails us to clarify the exact role of silk fibroin and inorganic ions in the biomineralization mechanism under a mimicking condition approaching the natural environment.
The demonstration of stereoselective habit modification in molecular crystals using “tailor-made” (or structurally related) additives, over the last two decades, has been a milestone in understanding the phenomenon of molecular recognition at crystal interfaces. The centrosymmetric α-glycine crystal has provided a classic example in earlier studies for elucidating the mechanisms of such stereoselective processes. In these previous studies, with chirally resolved (l or d-amino acids) and racemic α-amino acids (dl-amino acids) as tailor-made additives, habit modification was observed to be along the enantiopolar b-axis of α-glycine crystals. Revisiting this work has, however, revealed additional habit modification along the c-axis of the α-glycine crystal with certain α-amino acids as additives (viz. aspartic acid and glutamic acid). In the presence of l-Asp and l-Glu, the (01̄1) and (01̄1̄)faces were of morphological importance and with the d-amino acids, the (011) and (011̄) faces were well-developed. On the basis of the fact that these amino acids exist in two charged states (zwitterion and anion) and building on the stereoselectivity mechanism, it is surmised that the zwitterionic species interact along the b-axis of the α-glycine crystal and the anions alter their interaction from the crystallographic b-axis to the c-axis, due to electronic repulsive forces acting at the docking sites on the (010) and (01̄0) faces. In this paper, we have used optical microscopy, molecular modeling, and IR spectroscopy to demonstrate and explain the newly observed habit modification.
We report here an approach for predicting charge distributions in molecules for use in molecular dynamics simulations. The input data are experimental atomic ionization potentials, electron affinities, and atomic radii. An atomic chemical potential is constructed by using these quantities plus shielded electrostatic interactions between all charges. Requiring equal chemical potentials leads to equilibrium charges that depend upon geometry. This charge equilibrium (QEq) approach leads to charges in excellent agreement with experimental dipole moments and with the atomic charges obtained from the electrostatic potentials of accurate ab initio calculations. QEq can be used to predict charges for any polymer, ceramic, semiconductor, or biological system, allowing extension of molecular dynamics studies to broad classes of new systems. The charges depend upon environment and change during molecular dynamics calculations. We indicate how this approach can also be used to predict infrared intensities, dielectric constants, and other charge-related properties.
This experimental study presents in situ measurements of step migration rates for layer growth of calcite at various levels of superaturation and fluid Sr concentrations. Our results show that Sr has complex behavior as an impurity. At low concentrations, Sr promotes faster growth. This effect may be associated with slight shifts in calcite solubility when Sr is incorporated or may be due to as yet uncharacterized kinetic effects. At higher concentrations, Sr stops step advancement by pinning kink-sites or step edges. The threshold concentration of Sr needed to halt growth is positively correlated with supersaturation.
In nature, living organisms use peptides and proteins to precisely control the nucleation and growth of inorganic minerals and sequester CO(2)via mineralization of CaCO(3). Here we report the exploitation of a novel class of sequence-specific non-natural polymers called peptoids as tunable agents that dramatically control CaCO(3) mineralization. We show that amphiphilic peptoids composed of hydrophobic and anionic monomers exhibit both a high degree of control over calcite growth morphology and an unprecedented 23-fold acceleration of growth at a peptoid concentration of only 50 nM, while acidic peptides of similar molecular weight exhibited enhancement factors of only ∼2 or less. We further show that both the morphology and rate controls depend on peptoid sequence, side-chain chemistry, chain length, and concentration. These findings provide guidelines for developing sequence-specific non-natural polymers that mimic the functions of natural peptides or proteins in their ability to direct mineralization of CaCO(3), with an eye toward their application to sequestration of CO(2) through mineral trapping.
Current gradient-corrected density-functional approximations for the exchange energies of atomic and molecular systems fail to reproduce the correct 1/r asymptotic behavior of the exchange-energy density. Here we report a gradient-corrected exchange-energy functional with the proper asymptotic limit. Our functional, containing only one parameter, fits the exact Hartree-Fock exchange energies of a wide variety of atomic systems with remarkable accuracy, surpassing the performance of previous functionals containing two parameters or more.
Magnesium is a key determinant in CaCO3mineralization; however, macroscopic observations have failed to provide a clear physical understanding of how magnesium modifies
carbonate growth. Atomic force microscopy was used to resolve the mechanism of calcite inhibition by magnesium through molecular-scale
determination of the thermodynamic and kinetic controls of magnesium on calcite formation. Comparison of directly measured
step velocities to standard impurity models demonstrated that enhanced mineral solubility through magnesium incorporation
inhibited calcite growth. Terrace width measurements on calcite growth spirals were consistent with a decrease in effective
supersaturation due to magnesium incorporation. Ca1−xMgxCO3solubilities determined from microscopic observations of step dynamics can thus be linked to macroscopic measurements.
The effects of pH on the calcium phosphate phase, of Tris and of amino acids, such as aspartic acid, glutamic acid, and serine on hydroxyapatite formation and morphology, were studied in double diffusion experiments. In this system, hydroxyapatite was only formed when the pH was around 7.4 or higher for the duration of the reaction. A decrease in pH resulted in the transformation of hydroxyapatite to octacalcium phosphate. Amino acids and Tris or the buffering capacity of Tris have an effect on the morphology of the synthetic hydroxyapatite. The presence of the additive results in spheres consisting of needles, blades or plates depending on the reaction system.
We present a unified model for complete crystal-growth inhibition based on the thermodynamics of interfaces. The premise for our model is that the adsorption of inhibitor leads to a reduction in interfacial tension or edge energy for the crystal surface or step, respectively. In our formulation, the work to add a layer or grow a step increases due to the difference in interfacial tensions or edge energies for surfaces with and without an adsorbed inhibitor. For a large enough difference in interfacial tensions or edge energies, complete inhibition of growth is realized when the total work does not decrease as more crystals are formed. We demonstrate that our model can provide a theoretical description of critical subcooling data for ice with antifreeze proteins and glycoproteins, critical subcooling data for hydrates and ionic crystals, and critical supersaturation data for various crystal systems.
The crystallization of materials from a supersaturated solution is a fundamental chemical process. Although several very successful models that provide a qualitative understanding of the crystal growth process exist, in most cases the atomistic detail of crystal growth is not fully understood. In this work, molecular dynamics simulations of the morphologically most important surfaces of barite in contact with a supersaturated solution have been performed. The simulations show that an ordered and tightly bound layer of water molecules is present on the crystal surface. The approach of an ion to the surface requires desolvation of both the surface and the ion itself leading to an activated process that is rate limiting for two-dimensional nucleation to occur. However, desolvation on specific surfaces can be assisted by anions adsorbed on the crystal surface. This hypothesis, corroborated by crystallization and scanning electron microscopy studies, allows the rationalization of the morphology of barite crystals grown at different supersaturations.
Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.
The composition of biologic molecules isolated from biominerals suggests that control of mineral growth is linked to biochemical features. Here, we define a systematic relationship between the ability of biomolecules in solution to promote the growth of calcite (CaCO3) and their net negative molecular charge and hydrophilicity. The degree of enhancement depends on peptide composition, but not on peptide sequence. Data analysis shows that this rate enhancement arises from an increase in the kinetic coefficient. We interpret the mechanism of growth enhancement to be a catalytic process whereby biomolecules reduce the magnitude of the diffusive barrier, Ek, by perturbations that displace water molecules. The result is a decrease in the energy barrier for attachment of solutes to the solid phase. This previously unrecognized relationship also rationalizes recently reported data showing acceleration of calcite growth rates over rates measured in the pure system by nanomolar levels of abalone nacre proteins. These findings show that the growth-modifying properties of small model peptides may be scaled up to analyze mineralization processes that are mediated by more complex proteins. We suggest that enhancement of calcite growth may now be estimated a priori from the composition of peptide sequences and the calculated values of hydrophilicity and net molecular charge. This insight may contribute to an improved understanding of diverse systems of biomineralization and design of new synthetic growth modulators.
In the following article studies pertaining to “in situ” interactions of growing biogenic crystals (calcium phosphates, carbonates and oxalates) with, soluble, surface active molecules, including small, highly charged organic molecules, natural and synthetic polymers and synthetic surfactants, are discussed. Such interactions are at the roots of crystallization processes occurring in nature (biological mineralization) and in the controlled production of materials with well defined crystal structure, morphology and phase composition. The main characteristics of the crystals, including crystallographic data, and of the organic molecules, including their molecular structures, are briefly described. Most of the model crystals are crystal hydrates, whose dominant crystal planes are covered with continuous layers of structural water molecules (hydrated layer). The experimental methods reviewed include kinetic experiments determining induction times and/or the rates and rate controlling mechanisms of seeded and unseeded crystallization, techniques for the characterization of the nascent solid phase(s), and techniques, suitable for the assessment of interactions on the molecular level.