Influence of essential and non‐essential amino acids on calcium oxalate crystallization

The investigation on the mechanism of nucleation and growth of crystals at organic‐inorganic interfaces is crucial for understanding biological and physiological calcification processes such as the formation of urinary stones. The effects of five different amino acids on the crystallization of calcium oxalate have been investigated at pH 4.5 and 37 °C in aqueous solutions in the batch type crystallizer. The products were characterized by Scanning Electron Microscopy (SEM), Fourier Transfer Infrared Spectroscopy (FT/IR) and X‐Ray diffraction (XRD) analysis. Crystal size distribution (CSD) and filtration rate measurements were done. In order to determine the adsorption characteristics of amino acids on the calcium oxalate crystal surfaces, zeta potential measurements were also done and discussed. The results indicate that in the presence of all investigated amino acids, calcium oxalate monohydrate (COM) crystals were preferentially produced, but the crystal morphology varied with amino acid types and concentrations. Various crystal morphologies such as elongated hexagonal, coffin or platy habits were observed. In the presence of all investigated amino acids, the calcium oxalate crystallized in a monohydrate form. Electrostatic/ionic interaction, different adsorption properties and special functional effects of amino acids led to find different crystal morphology. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A study of primary nucleation of calcium oxalate monohydrate: II. Effect of urinary species

Kidney stones consist of various organic and inorganic compounds. Calcium oxalate monohydrate (COM) is the main inorganic constituent of kidney stones. However, the mechanisms for the formation of calcium oxalate kidney stones are not well understood. In this regard, there are several hypotheses including nucleation, crystal growth and/or aggregation of formed COM crystals. The effect of some urinary species such as oxalate, calcium, citrate, and protein on nucleation and crystallization characteristics of COM is determined by measuring the weight of formed crystals and their size distributions under different chemical conditions, which simulate the urinary environment. Statistical experimental designs are used to determine the interaction effects among various factors. The data clearly show that oxalate and calcium promote nucleation and crystallization of COM. This is attributed to formation of a thermodynamically stable calcium oxalate monohydrate resulting from supersaturation. Citrate, however, inhibits nucleation and further crystal growth. These results are explained on the basis of the high affinity of citrate to combine with calcium to form soluble calcium citrate complexes. Thus, citrate competes with oxalate ion for binding to calcium cations. These conditions decrease the amount of free calcium ions available to form calcium oxalate crystals. In case of protein (mucin), however, the results suggest that no significant effect could be measured of mucin on nucleation and crystal growth. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Calcium oxalate crystallization in the presence of amino acids,proteins and carboxylic acids

Reactive crystallization of calcium oxalate was investigated in the presence of amino acids, proteins and carboxylic acids at different pH and temperatures. Average particle size, filtration rates of calcium oxalate crystals obtained in the absence and presence of additives were determined. The influence of pH, temperatures and additives on crystal morphology of calcium oxalate were also investigated and discussed by SEM analysis. TG‐DTA, FT/IR and XRD analysis were carried out for all investigated conditions. Average particle size of calcium oxalate was affected significantly by the additive type and concentration. Variation of crystal morphology depending on type and concentration of the additives affected the filtration characteristics. Majority of calcium oxalate crystals occurred in the form of calcium oxalate monohydrate except those in the presence of tartaric acid. TG‐DTA, FT/IR and XRD analysis proved that calcium oxalate monohydrate and calcium oxalate dihydrate mixtures are formed in the presence of tartaric acid. The effect of all additives on scale formation was also investigated. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A study of primary nucleation of calcium oxalate monohydrate: I‐Effect of supersaturation

There are various organic and inorganic constituents in kidney stones. Among them, calcium oxalate monohydrate (COM) is the primary inorganic constituent of kidney stones. However, the mechanisms of formation of kidney stones are not well understood. In this regard, a basic study is carried out for better understanding of nucleation, crystal growth and/or aggregation of formed COM crystals. The primary nucleation of calcium oxalate monohydrate is studied at the laboratory scale using turbidity measurements. Calcium chloride and potassium oxalate solutions are mixed and then added to a Turbidimeter tube for continuous recording of turbidity. Induction time (time to induce formation of detectable crystals) is estimated from time‐turbidity graphs. The effect of some urinary species, such as oxalate and calcium, on nucleation and crystallization characteristics of COM is determined by particle size distribution analysis, measuring weight of crystals and calculation of relative supersaturation. The classical nucleation theory is applied at high supersaturation ratios (SR) ranging from 1.6 to 2.2. The results indicate that nucleation rate increases with increasing supersaturation ratio from 0.81 × 10²⁸ nuclei/cm³.sec at 1.6 SR, to 18.02 × 10²⁸ nuclei/cm³.sec at 2.2 SR. On the other hand, free energy change and radius of critical nucleus are decreased as supersaturation ratio is increased. The nucleation rates are higher than those reported in literature. Such discrepancy is discussed on the bases of differences in experimental techniques. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Influence of Bacillus subtilis on the growth of calcium oxalate

The influence of the bacteria Bacillus subtilis (B. subtilis) on the nucleation, growth and aggregation of calcium oxalate (CaOx) crystals in aqueous solution has been studied. The crystals obtained were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and X‐ray powder diffractometry. The results show that, in the presence of B. subtilis, quasi‐hexagonal calcium oxalate monohydrate (COM) crystals are obtained after 24 hours of reaction at a temperature of 30°C ± 1K. However, without the presence of the bacteria, irregular CaOx crystals were obtained which contain two crystal phases: COM and calcium oxalate dihydrate (COD). This suggests that B. subtilis may promote the crystallization of COM, the major component of urinary stone. The formation mechanism of CaOx crystals in the presence of B. subtilis is explored, indicating that the cell walls and extracellular proteins of the bacteria may act as templates to induce the nucleation, growth and aggregation of CaOx crystals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Analysis of the feasibility of Avrami equation to amino acid endcapped PPDO crystallization by using Malek and Mitsuhashi method

Typically, the crystallization kinetics behaviour of biodegradable polyester could be described by the Avrami equation; however, for the appropriate application of this equation, some assumptions are required. Under conventional conditions of isothermal crystallization without nucleating agents, homogeneous nucleation is the key factor for the compatibility of this equation. On account of structural characteristics, the homogeneous nucleation of polymers is possibly affected by several factors. In this study, we investigated the isothermal crystallization of four PPDOs end‐capped with amino acids, followed by the Avrami equation analysis. After employing the method reported by Malek and Mitsuhashi, the L‐Gly‐ end‐capped PPDO and L‐Leu‐, L‐Phe‐end‐capped PPDO crystallized at higher temperatures were not suitable for analysis by the Avrami equation. In addition, this result was substantiated by reasoning the polymer chains’ mobility which could be affected by the terminated amino acids’ steric hindrance and crystallization temperatures, subsequently affecting homogeneous nucleation.     

不同结构物质和有机基质对草酸钙晶体生长的促进作用

本文综述了有机大分子、小分子和有机基质对尿石矿物草酸钙(CaOxa)晶体成核、生长和聚集的促进作用.从促进物的分子结构和草酸钙晶体的晶面性质等方面讨论了不同类型促进物的作用机理.最后指出了该领域所面临的问题和将来的发展方向.     

Crystal growth of calcium oxalate induced by the extracts of Semen Plantaginis and Folium Pyrrosiae

The crystallization of calcium oxalate (CaOxa) in aqueous solutions of the extracts of Semen Plantaginis and Folium Pyrrosiae has been investigated, focusing on the inhibition mechanism of some herbs on stone formation. It has been shown that in the presence of extracts of above two herbs, calcium oxalate dihydrate (COD) crystals with typical morphologies of tetragonal bipyramids were obtained. This suggests that the extracts of Semen Plantaginis and Folium Pyrrosiae can promote the formation of thermodynamically unstable COD, and inhibit the formation of calcium oxalate monohydrate (COM), a major component of urinary stone. The formation mechanism of COD crystals induced by Semen Plantaginis and Folium Pyrrosiae is also discussed, indicating that the bioorganic molecules in the extracts of the herbs can induce the nucleation and growth of COD crystals. This study can help us make clear the inhibition mechanism of some herbs on stone formation that is in favor of the prevention and treatment of urolithiasis. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

温度变化对草酸钙晶体生长的影响

草酸钙(CaOxa)是泌尿系结石的主要成份,其生长过程受诸多因素的影响.本文研究了温度对CaOxa晶体成核、生长、聚集、晶相、形貌和溶解度等的影响及其机理,对防治泌尿系结石具有启示作用.但高温地区尿石症发病率高的深层次原因还有待进一步研究.     

Polymeric AdditiveS' Effect on Crystallization of Calcium Oxalate Scales

Laboratory studies concerned with the effects of polymeric additives on the crystallization of calcium oxalate dihydrate and calcium oxalate monohydrate are described and the results obtained are discussed. These compounds are major components of scales formed in some Australian sugar mills. The studies involved the measurement of crystallization induction periods and rates, in the presence and absence of additives. Crystal morphologies were also examined. A range of experimental conditions were employed, from studies in pure solutions of the lattice ions to those more directly comparable with the mill operation.     

A Stochastic Model for Nucleation Kinetics Determination in Droplet-Based Microfluidic Systems

The measured induction times in droplet-based microfluidic systems are stochastic and are not described by the deterministic population balances or moment equations commonly used to model the crystallization of amino acids, proteins, and active pharmaceutical ingredients. A stochastic model in the form of a Master equation is formulated for crystal nucleation in droplet-based microfluidic systems for any form of nucleation rate expression under conditions of time-varying supersaturation. An analytical solution is provided to describe the (1) time evolution of the probability of crystal nucleation, (2) the average number of crystals that will form at time t for a large number of droplets, (3) the induction time distribution, and (4) the mean, most likely, and median induction times. These expressions are used to develop methods for determining the nucleation kinetics. Nucleation kinetics are determined from induction times measured for paracetamol and lysozyme at high supersaturation in an evaporation-based high-throughput crystallization platform, which give low prediction errors when the nucleation kinetics were used to predict induction times for other experimental conditions. The proposed stochastic model is relevant to homogeneous and heterogeneous crystal nucleation in a wide range of droplet-based and microfluidic crystallization platforms.     

Influence of impurity on rhythmic crystallization of calcium carbonate in agar gel

During the gel growth of calcite crystals in test tubes, for a narrow concentration of inner and outer electrolytes we observed rhythmic crystallization of calcium carbonate. In this paper the effect of adding impurities on the pattern of periodic crystallization of calcium carbonate has been presented. The addition of impurities either increases or decreases the solubility of reaction product and hence may affect the rate of nucleation of calcium carbonate crystals. The variation of spacing coefficient and velocity constant due to the addition of impurities has also been studied.     

The mechanism of biological mineralization

The control of supersaturation and the nucleation and growth of crystals in calcium phosphate systems are important in relation to the physiological deposition of bone and tooth. Other calcium salts such as the carbonate and oxalate hydrates are significant components of pathological mineral deposits. The use of a highly reproducible seeded growth technique has enabled kinetic studies to be made of the crystal growth of these minerals. Under conditions of relatively high supersaturation, secondary nucleation may be induced upon the surface of the seed crystals. In the case of the calcium phosphates, temperature, supersaturation, surface concentration, pH, ionic strength and presence of foreign ions are very important in determining the nature of the phase which grows upon the added seed crystals. Kinetic considerations are of overriding importance in determining the course of the reactions. It is not possible to predict the phase which forms purely on the basis of thermodynamic solubility data. Thus, in solutions appreciably supersaturated with respect to both dicalcium phosphate dihydrate (DCPD) and hydroxyapatite (HAP), the addition of low concentrations of HAP seed results in the exclusive formation of DCPD whereas this phase is absent when the seed concentration is increased. The kinetic results for calcium oxalate and phosphates are discussed in terms of the important problems relating to tooth mineralization and the origin and growth of renal calculi.     

Thermodynamics and kinetics of calcium oxalate crystallization in the presence of amino acids

Specific features of the crystallization of calcium oxalates (CaC₂O₄) in the presence of amino acids have been established based on thermodynamic and experimental modeling. Phase formation in the Ca²⁺–C₂O₄ ^2-–H₂O–amino acid system in a wide range of variation in the component concentrations and solution pH have been theoretically investigated. The influence of pH on the thermodynamic stability of crystallizing compounds is considered. The effect of amino acids of different structures on the formation of the CaC₂O₄ solid phase in a prototype of physiological solution is analyzed. The kinetic crystallization parameters (induction period and rate constant) and crystallite growth are determined.     

药物结晶中的经典与非经典结晶路径

晶体的结晶路径分为经典结晶路径和非经典结晶路径。经典结晶路径往往涉及一些简单的化学结构,晶体的成核、生长是通过单体的依次添加实现的,经过长期研究,目前研究人员已对其有了较为深刻的理解并形成了一套相对完善的理论体系;但对于非经典的结晶路径,由于涉及复杂中间态粒子的形成和多步结晶过程,尚未获得全面、统一的理论支持。在药物结晶领域,有机分子构象自由度的引入增加了体系的复杂性,分子间弱的相互作用使得固态药物分子存在多晶型现象。由于药物的理化性质及生物利用度与其晶型息息相关,同时,药物结晶过程中出现的一些复杂中间态粒子往往会改变最终得到的药物晶型,因此迫切需要加强对药物晶体成核和生长路径的研究,以期发展能实现对药物晶体成核和生长过程主动控制的方法。本文简要综述了目前药物在溶液或熔体中结晶的经典与非经典结晶路径,包括奥斯特瓦尔德阶段定律、独立成核、交叉成核。从溶液化学的角度看,分子在浓溶液中会通过自组装形成结构合成子,成核与溶液中的生长单元、结构合成子密切相关。从分子水平上探索溶液中有关分子运动的信息、分析各体系下晶核与结构合成子之间的关系是区分两种结晶路径的关键所在,非经典结晶在药物结晶领域是机遇也是挑战。     

Kinetics of Dissolution of Calcium Oxalate Calculi in Physiological Solutions Containing Hippuric Acid

An analysis of the thermodynamics and kinetics of crystal growth and dissolution of slightly soluble salts in physiological solutions in the presence of complexing ions is made, accounting for conditions typical in human urine. It is found that hippuric acid, a normal physiological constituent of urine, acts at increased concentrations as a dissolving agent with respect to calcium oxalate and calcium oxalate calculi. The kinetics of dissolution of crystalline calcium oxalate calculi (CaOx) in physiological solutions containing hippuric acid in different concentrations is studied, using the change in the Archimedean weight of samples, immersed in the solution. The analysis of the experimental results enables the determination of the increased solubility of CaOx in the presence of hippuric acid and to characterize quantitatively this substance as a new and very prospective dissolving agent of CaOx calculi in human urine. A discussion is also given on the possible effect of hippuric acid as a neutral regulator of CaOx-supersaturation and crystallization in human and mammal urine.     

海带硫酸多糖防止草酸钙结石形成的体外模拟

采用扫描电子显微镜、X射线衍射法和红外光谱在草酸钙(CaOxa)结石患者尿液中研究了从海带中提取的硫酸多糖(LSPS)的防石作用.结果表明,LSPS可以抑制一水草酸钙(COM)的成核和聚集,并诱导二水草酸钙(COD)晶体形成.随着ESPS浓度从0增加到0.005, 0.02和0.20 mg/ml,COD的百分含量从0分别增加到22;, 55;和100;.这些结果表明LSPS是抑制CaOxa结石形成的一种潜在药物.     

Influence of clay suspensions on the precipitation of CaCO3 in seawater

The effect of montmorillonite and kaolinite, most common clay in marine water, on nucleation and growth of calcium carbonate in standard sea water was studied. Crystallization was induced by the degasification of the dissolved carbonic gas. It was shown by XRD and SEM analysis that CaCO₃ crystallize under its aragonite polymorph some either the clay concentration or type. It was also found that tested clays inhibited significantly the crystallization of calcium carbonate, especially for concentrations higher than 25 mgL^–1. From the fine analyses of the formed solid, it was suggested that the tested clays have an indirect effect on nucleation and growth of aragonite by increasing the Mg ions concentration, strong inhibitor of CaCO₃ formation, in the neighbourhood of clay particles where supersaturation is the higher and than crystallization can occur. In addition to its indirect role, kaolinite can interact with aragonite by adsorbing on their faces and blocking growth sites (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Growth aspects of barium oxalate monohydrate single crystals in gel medium

Single crystals of barium oxalate monohydrate (BaC₂O₄.H₂O, BOM) were grown in pure form by controlled diffusion of Ba²⁺ using the gel technique at different temperatures. Starting from aqueous Ba²⁺ chloride (BaCl₂) and acetic acid (C₂H₂O₄) in gel, this method offers a low‐cost and an easiest alternative to other preparation methods for the production of barium oxalate bulky single crystals. The optimal conditions for the growth of BOM crystals in silica gel were found by investigating different growth parameters such as gel pH, gel aging and crystallization temperature. Irrespective of all such crystallization environments, growth rate of the crystals were initially less and then exhibited supersaturation effect leading to non‐linearity. Gel aging and temperature has profound effect on nucleation density that resulted less number of crystals of maximum size in the gel matrix. Perfect single crystals were grown on gels of higher pH. The macropore morphology and porosity was controlled by changing age of the gel. It has been found that temperature has a fabulous effect in controlling the nucleation density by altering the supersaturation conditions for the formation of critical nuclei. The entire growth kinetics informed that the grown crystals were derived by the one dimensional diffusion controlled process. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Crystallization of potassium sulphate from glaserite

The crystallization of K₂SO₄ from aqueous solutions of glaserite (a double salt of sodium and potassium sulphate) was investigated in an MSMPR cooling apparatus at 35 °C. The precipitation of K₂SO₄ at an average purity of 93 wt.% was obtained and the crystallization kinetics were derived from the experimental data. The nucleation and growth rates here obtained were, respectively, remarkably higher and slightly lower than those relevant to pure K₂SO₄: this behaviour may be explained by a faster nucleation and a slower growth of crystals containing also Na₂SO₄. The effect of small (0.05%) calcium additions to the feed was also tested, which caused an increase of supersaturation and a depression of the growth kinetics, whereas the nucleation one was not appreciably modified.