Formation constants of copper(i) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye

Protonation constants for the biologically-important thioamino acids cysteine (CSH), penicillamine (PSH) and glutathione (GSH), and the formation constants of their complexes with Cu(i), have been measured at 25 °C and an ionic strength of 1.00 mol dm-3 (Na)Cl using glass electrode potentiometry. The first successful characterisation of binary Cu(i)-CSH and Cu(i)-GSH species over the whole pH range was achieved in this study by the addition of a second thioamino acid, which prevented the precipitation that normally occurs. Appropriate combinations of binary and ternary (mixed ligand) titration data were used to optimise the speciation models and formation constants for the binary species. The results obtained differ significantly from literature data with respect to the detection and quantification of protonated and polynuclear complexes. The present results are thought to be more reliable because of the exceptionally wide pH and concentration ranges employed, the excellent reproducibility of the data, the close agreement between the calculated and observed formation functions, and the low standard deviations and absence of numerical correlation in the constants. The present formation constants were incorporated into a large Cu speciation model which was used to predict, for the first time, metal-ligand equilibria in the biofluids of the human eye. This simulation provided an explanation for the precipitation of metallic copper in lens and cornea, which is known to occur as a consequence of Wilson's disease

Thermodynamic modeling of crystal deposition in humans

The prevention and treatment of crystal deposition in the human body are based on the understanding of the physicochemical properties underlying the precipitation of the substances involved. Among these properties, the solubilities of the crystals are very important. Recently, experimentally determined solubility data of substances related to urolithiasis, such as calcium oxalate hydrates, uric acid and urates, cystine, and xanthine, were critically assessed. Unfortunately, reported solubilities of these substances were found to be either scarce or in large disagreement. Consequently, detailed studies were carried out in our laboratory, and the results will be discussed in this communication with emphasis on the thermodynamic consistency of the experimentally determined data. Since proper modeling of the solubilities of these substances in artificial urine solutions serves as a prerequisite for solubility predictions in real urine, the Joint Expert Speciation System (JESS) software package was employed to create a comprehensive computer model including the relevant, low-molecular inorganic and organic components of urine. The results of the simulations lead to some useful suggestions regarding the prevention and treatment of stone disease

The boehmite ‘solubility gap’

Boehmite, rather than gibbsite, precipitation has been proposed in the literature as a potential energy-saving modification of the Bayer process for the production of alumina. Previous experimental studies have reported that true equilibrium solubilities were not attained during boehmite precipitation. Instead, a pseudo-equilibrium or an apparent 'steady-state' aluminate concentration of about twice the boehmite solubility was reached. In this work, the dissolution and precipitation reactions in synthetic and plant liquors using seeds of (i) pure boehmite and (ii) various boehmite/gibbsite ratios were investigated at 95 °C. Only boehmite precipitation was observed on pure boehmite seed at relatively low supersaturation (alumina (A)/total caustic (TC) 0.56). The aluminate concentrations measured as a function of time decreased continuously and did not exhibit an apparent 'steady state'. Stable equilibrium, as established by boehmite solubility measurements, was approached very slowly but not attained even after ten weeks. At higher supersaturation (A/TC 0.67), after an initial desupersaturation, 'steady-state' aluminate concentrations of about twice the boehmite solubility were observed. There is convincing evidence that these 'steady states' correspond to metastable solubility equilibria with gibbsite, which is precipitated initially and gradually transforms into the stable phase, boehmite. Gibbsite also nucleated in the case of pure boehmite seeds. 'Steady states' were attained in one up to several days and remained constant for one to ten days. The length of these periods correlated with the gibbsite content of the seeds. After sufficient recrystallisation of gibbsite to boehmite, the aluminate concentrations decreased significantly and eventually approached boehmite solubility, thereby following a much slower precipitation kinetics typical for boehmite. Due to short observation times, previous workers did not detect the end of the 'steady-state' periods and therefore failed to identify the observed 'steady-state' aluminate concentrations as arising from metastable solubility equilibria with gibbsite

Solubility phenomena related to normal and pathological biomineralization processes

Biomineralization, which refers to the complex processes by which organisms form minerals, is frequently associated with a high degree of regulation on different hierarchical levels [1,2]. ‘Biologically controlled’ mineralization, in which extra-, inter- and intracellular activities direct the nucleation, growth and morphology of minerals that form ‘normal’ biomaterials such as bone and teeth [1,2], is fundamentally different from ‘biologically induced’ mineralization, which occurs as a result of interactions between biological activity (affecting e.g. the pH and composition of secretion products) and the environment [1,2]. Since there is little control of the biological system over the type and habit of minerals deposited, these vary as greatly as the environments in which they form and are often poorly defined, heterogeneous and porous [1,2]. Biologically induced mineralization is commonly associated with various bacterial activities and with epicellular mineralization in marine environments, occasionally leading to the complete encrustation of organisms, that sink subsequently and form sediments [1,2]. However, its characteristic features are also typical for uncontrolled ‘pathological’ crystallization resulting in painful or even life threatening conditions such as calculi formation (renal, biliary, pancreatic or sublingual), development of gout or arteriosclerosis, tissue calcification associated with cancer, etc

Preface

Prefac

Biomineralization – Medical Aspects of Solubility

Summary This title takes an interdisciplinary approach to the central role of solubility in pathological biomineralisation, ranging from traditional thermodynamics and kinetics to unusual concepts such as the PILP process. The scientific background and expertise of the contributors, ranges accordingly from solubility modelling and database development, renal stone and bone implant research, Mössbauer spectroscopy and structural chemistry to biochemistry and crystallisation. The chapters all have a quantitative, physico-chemical component rather than giving purely phenomenological descriptions. The contributors deal with aspects and concepts that have not previously been common in the study of pathological biomineralisation processes