A1 Ion Research Articles

Transient Receptor Potential A1 (TRPA1) Activity in the Human Urethra—Evidence for a Functional Role for TRPA1 in the Outflow Region

BackgroundA role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. ObjectivesTo investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. Design, settings, and participantsUrethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. MeasurementsThe expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (AI), cinnamaldehyde (CA), and NaHS (donor of H2S) on tension of urethral strips were investigated in tissue baths. Results and limitationsTRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed.In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations. ConclusionsThe localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.

650 Localization and Function of Transient Receptor Potential (Trp) A1 Ion Channel in the Enteric Nervous System

650 Localization and Function of Transient Receptor Potential (Trp) A1 Ion Channel in the Enteric Nervous System

Dimethyl Isotope-Coded Affinity Selection for the Analysis of Free and Blocked N-Termini of Proteins Using LC−MS/MS

Because of enhanced a(1) ion signals, dimethyl labeling is useful for identifying the N-termini of proteins or peptides. Herein, we describe a novel strategy that uses dimethyl isotope-coded affinity selection (DICAS) to isolate peptides that contain either the dimethylated or in vivo blocked N-termini of proteins for comprehensive sequence analyses by LC-MS/MS. In this method, dimethyl labeling at the protein level was first performed using formaldehyde-d(2) to label all unblocked protein N-termini and lysine residues, followed by trypsin digestion. The free N-terminal amines of internal peptides generated by digestion were captured by solid supports with aldehyde functionalities through reductive amination. The flow-through fractions, which contained either in vivo or in vitro blocked N-terminal peptides, were subjected to sequence analyses by LC-MS/MS. Owing to the unique feature of a1 signal enhancement associated with dimethylated peptides and the use of the deuterium reagent, the in vitro blocked (or in vivo free) N-termini of proteins could be easily differentiated from the in vivo blocked N-termini. Thus, their sequences and N-terminal modifications could be assigned unambiguously from MS/MS spectra. In this study, the completeness of the labeling and the efficiency of the isolation method were first confirmed by the use of a mixture of model proteins composed of hemoglobin, myoglobin, and alpha-lactalbumin. The N-termini of all three proteins, including both alpha and beta chains of hemoglobin as well as a signal sequence located in the N-termini of alpha-lactalbumin, were successfully identified. The protocol was then applied to the analysis of an unfractionated lysate of MCF-7 cells. Results indicate that more than 80% of the isolated peptides contained the N-termini of unique proteins, and many of them were consistent with known or inferred N-terminal processing such as methionine removal and acetylation. In addition, using the DICAS approach, we identified a novel N-terminal formylation for the Ig kappa chain V-III region SIE protein and a novel N-terminal signal sequence (1th-32th amino acid) for profilin.

Distribution and Function of the Hydrogen Sulfide–Sensitive TRPA1 Ion Channel in Rat Urinary Bladder

ObjectivesTo investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H2S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels. MethodsThe expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H2S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells. ResultsTRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells. ConclusionsThe expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H2S as a TRPA1 activator potentially involved in inflammatory bladder disease.

Enhanced a1Fragmentation for Dimethylated Proteins and Its Applications for N-Terminal Identification and Comparative Protein Quantitation

In this work, dimethyl labeling at the protein level was developed to assist the fragmentation of intact proteins using the Q-TOF instrument. It was shown that a1 ions were favorably enhanced upon collision-induced dissociation for dimethylated proteins with molecular mass below 20 kDa and without N-terminal modifications. This method is helpful in confirming proteolytic sites located at the N-terminus of proteins. Moreover, this labeling could be incorporated with stable isotopes for comparative profiling at the protein level, in which the heavily labeled and lightly labeled a1 ions were generated from the corresponding proteins upon high-voltage collisions in a broad mass region that covered all of the charge states of the proteins. Using hemoglobin as an example, a linear dynamic range from 1:1 to 1:20 was satisfactorily obtained with an R2 value greater than 0.99. This approach appears to be promising for top-down proteomics.

Deviation from the mobile proton model in amino‐modified peptides: implications for multiple reaction monitoring analysis of peptides

The study of peptide fragmentation is important to the understanding of chemical processes occurring in the gas phase and the more practical concern of peptide identification for proteomic analysis. Using the mobile proton model as a framework, we explore the effect of amino-group modifications on peptide fragmentation. Three aldehydes are used to transform the peptides' primary amino groups into either a dimethylamino or a heterocyclic structure (five- or six-membered). The observed fragmentation patterns deviate strongly from those observed for the analogous underivatised peptides. In particular, the a1 ion is the base peak in most tandem mass spectra of the derivatised peptides. The a1 ion intensity depends strongly on the N-terminal amino acid, with tyrosine and phenylalanine having the strongest enhancement. Despite the change in fragmentation patterns of the derivatised peptides, they still provide high-quality tandem mass spectra that, in many cases, are more amenable to database searching than the spectra of underivatised peptides. In addition, the reliable presence of the a1 ion facilitates rapid quantitative measurements using the multiple reaction monitoring approach.

Targeted comparative proteomics by liquid chromatography/matrix‐assisted laser desorption/ionization triple‐quadrupole mass spectrometry

Here we report the first application of a matrix-assisted laser desorption/ionization (MALDI) triple-quadrupole mass spectrometer for targeted proteomics. Employing an amine-specific isotopic labelling approach, the technique was validated using five randomly selected bovine serum albumin peptides differentially labelled at known ratios. An indirect benefit of the isotopic labelling technique is a significant enhancement of the a1 ion in tandem mass (MS/MS) spectra of all peptides studied. Therefore, the a1 ion was selected as the fragment ion for multiple reaction monitoring (MRM) in all cases, eliminating tedious method development and optimization. Accurate quantification was achieved with an average relative standard deviation (RSD) of 5% (n = 5) and a detection limit of 14 amol. The technique was then applied to validate an important virulence biomarker of the fungal pathogen Candida albicans, which was not accurately quantified using global proteomics experiment employing two-dimensional liquid chromatography/electrospray ionization tandem mass spectrometry (2D-LC/ESI)-MS/MS. Using LC/MALDI-MRM analysis of five tryptic peptides, the protein PHR1 was found to be upregulated in the hyphal (pathogenic) form of C. albicans by a factor of 7.7 +/- 0.8.

Beyond Quantitative Proteomics: Signal Enhancement of the a1 Ion as a Mass Tag for Peptide Sequencing Using Dimethyl Labeling

Stable isotope-based dimethyl labeling that produces a dimethyl labeled terminal amine or a monomethylated proline N-terminus by reductive methylation (Anal. Chem. 2003, 75, 6843-6852) was reported as a promising strategy for global quantitative proteomics because of the simplicity of the process and its fast and complete reaction. This labeling strategy provides a signal enhancement for the produced a1 ions, which are usually hard to detect among most of the nonderivatized fragments. To assist peptide sequencing, in this study, the enhanced a1 ion produced under either collision induced dissociation (CID) or post source decay (PSD) modes was further characterized and applied as a mass tag for fingerprinting the identity of N-terminal amino acid. On the basis of the analysis of standard peptides, tryptic digests of hemoglobin and cell lysates, it was proved that such signal enhancement occurred to a1 ions derived from all 20 of the amino acids residues and this phenomenon was explained based the formation of stable quaternary immoniun ions. Accurate determination of a1 ions was shown to increase the chance for peptide de novo sequencing and also provided higher confidence in the scores obtained when identifying a protein through database searching. In addition, the a1 ion was further demonstrated to be used as a universal tag for precursor ion scan in a Q-TOF instrument, leading to a greater number of peptide ions sequenced. Combined with the capability for differential quantitation, the stable isotope-based dimethyl labeling increases the usefulness of the labeling method for MS-based proteomics.

Fragmentation Mechanisms of Product Ions from Protonated Tripeptides

Dissociation chemistries of the primary fragment ions from the tripeptides, GAG and AGG, were examined both experimentally and theoretically, and compared with those from GGG [El Aribi, H.; Rodriquez, C. F.; Almeida, D. R. P.; Ling, Y.; Mak, W. W.-N.; Hopkinson, A. C.; Siu, K. W. M. J. Am. Chem. Soc. 2003, 125, 9229−9236]. Findings in this study with GAG and AGG confirm and extend those in the earlier study on GGG. Fragmentation of the b2 to a2 ion from GAG and AGG is qualitatively similar to that from GGG; stabilization by the methyl group, however, results in generally lower energies for GAG. Fragmentation of the a2 ion from GAG produces both the a1 (protonated methanimine) and the internal iminium ion (protonated ethanimine). By contrast, fragmentation of the a2 ion from AGG produces only the a1 ion (protonated ethanimine). In GAG, formation of the internal iminium ion requires an intramolecular proton transfer in the proton-bridged complex after cleavage of CO, which is absent in AGG. The a1 ion from GAG is postulated to form via cleavage of the vibrationally excited proton-bridged complex prior to proton transfer, favored under higher collision-energy conditions. The critical transition state in the fragmentation of the b2 to a1 ion is best described as a complex between the a1 ion and a carbene. Although details differ, in both GAG and AGG, there is a proton transfer from the terminal amino group to the carbene carbon and a second proton transfer from the ring nitrogen back to the terminal amino group. Separation of the components then yields the a1 ion and a neutral oxazolone.

Fragmentation of Protonated Tripeptides: The Proline Effect Revisited

The fragmentation of protonated tripeptides under metastable ion conditions and collision-induced conditions are reported. The majority of protonated tripeptides cleave at the C-terminal amide bond to form b2 and y1 ions, with the relative amounts depending on the proton affinities of the amino acids derived from the C-terminal amino acid residue. Protonated tripeptides that have a proline residue at the C-terminal position fragment almost exclusively by cleavage of the amide bond adjacent to the proline and give mainly y1 ions; where there is a proline residue in the central position, fragmentation of the protonated tripeptide occurs at both the N-terminal and the C-terminal amide bonds to form y2 and b2 ions; finally, two of the tripeptides with proline at the N-terminal position, Pro-Pro-Pro and Pro-Gly-Gly, fragment largely by cleavage at the N-terminal, the former by cleavage of the amide bond and the latter by direct formation of the a1 ion. Protonated Pro-Val-Gly fragments to give predominantly b2 ...

Elucidation of fragmentation mechanisms of protonated Peptide ions and their products: a case study on glycylglycylglycine using density functional theory and threshold collision-induced dissociation.

The fragmentation mechanisms of protonated triglycine and its first-generation dissociation products have been investigated using a combination of density functional theory calculations and threshold collision-induced dissociation experiments. The activation barrier measured for the fragmentation of protonated triglycine to the b(2) ion and glycine is in good agreement with a calculated barrier at the B3LYP/6-31++G(d,p) level of theory reported earlier [Rodriquez, C. F. et al. J. Am. Chem. Soc. 2001, 123, 3006-3012]. The b(2) ion fragments to the a(2) ion via a transition state structure that is best described as acylium-like. Contrary to what is commonly assumed, the lowest energy structure of the a(2) ion is not an iminium ion, but a cyclic, protonated 4-imidazolidone. Furthermore, fragmentation of the b(2) to the a(1) ion proceeds not via a mechanism that results in HNCO and H(2)C=C=O as byproducts, as have been postulated, but via a transition state that contains an incipient a(1) ion and an incipient carbene. The fragmentation of a(2) to a(1) proceeds via a transition state structure that contains the a(1) ion, CO and an imine as incipient components.

Reactivity in acid-catalyzed carbon–carbon heterolysis

Equilibrium and rate constants have been determined for the acid-catalyzed heterolysis of two alcohols, 9-xanthydrol and p-anisyldiphenylmethanol, and two sulfides, (9-xanthyl) methyl sulfide and (7-tropyl) methyl sulfide. These data together with literature information are compared with rate constants for acid-catalyzed C-C heterolysis of several (9-xanthyl) compounds, (7-tropyl) compounds, a set of 3-arylcyclobutanones, and two 2-arylnitrocyclopropanes, all of which fragment to carbocations plus a carbon-centered nucleofuge. The fragmentation mechanisms are shown to be A1 or A1(ion pair) except for the 2-arylnitrocyclopropanes which cleave in trifluoroacetic acid by a concerted mechanism. Rate comparisons among several unstrained substrate sets indicate that O-centered nucleofuges undergo acid-catalyzed heterolysis ca. 103-104 faster than S-centered nucleofuges and ca. 109-1014 faster than the C-centered nucleofuges used here. Factors assisting C-C heterolysis (and their effectiveness) include the acidity of the medium (strong); the basicity and nucleofugality of the nucleofuge (moderate); the stability of the electrofugic carbocation (strong); and relief of ring strain (enormous). Compared with acyclic cleavages, rate accelerations worth ca. 15 kcal/mol (for cyclobutanones) and ca. 27 kcal/mol (for nitrocyclopropanes) are found. These effects are discussed in terms of transition-state structure, aided by computational evidence.Key words: C-C heterolysis, fragmentation, acid catalysis, carbocation, ring strain.

Reactivity in acid-catalyzed carbon-carbon heterolysis

Equilibrium and rate constants have been determined for the acid-catalyzed heterolysis of two alcohols, 9-xanthydrol and p-anisyldiphenylmethanol, and two sulfides, (9-xanthyl) methyl sulfide and (7-tropyl) methyl sulfide. These data together with literature information are compared with rate constants for acid-catalyzed C-C heterolysis of several (9-xanthyl) compounds, (7-tropyl) compounds, a set of 3-arylcyclobutanones, and two 2-arylnitrocyclopropanes, all of which fragment to carbocations plus a carbon-centered nucleofuge. The fragmentation mechanisms are shown to be A1 or A1(ion pair) except for the 2-arylnitrocyclopropanes which cleave in trifluoroacetic acid by a concerted mechanism. Rate comparisons among several unstrained substrate sets indicate that O-centered nucleofuges undergo acid-catalyzed heterolysis ca. 10 3 -10 4 faster than S-centered nucleofuges and ca. 10 9 -10 14 faster than the C-centered nucleofuges used here. Factors assisting C-C heterolysis (and their effectiveness) include the acidity of the medium (strong); the basicity and nucleofugality of the nucleofuge (moderate); the stability of the electrofugic carbocation (strong); and relief of ring strain (enormous). Compared with acyclic cleavages, rate accelerations worth ca. 15 kcal/mol (for cyclobutanones) and ca. 27 kcal/mol (for nitrocyclopropanes) are found. These effects are discussed in terms of transition-state structure, aided by computational evidence.

The b1 ion derived from methionine is a stable species

Unimolecular fragmentation of the MH+ ions of a number of methionine derivatives such as H-Met-OMe, H-Met-β-naphthylamide, H-Met-Gly-OH, H-Met-Ala-OH and H-Met-Phe-OH results in formation of the methionine b1 ion (m/z 132) in significant yields. Since α-aminoacylium ions are generally unstable and not observed, it is proposed that the stable form of the b1 ion from these methionine derivatives is methyl-cationated α-amino-γ-thiobutyrolactone. Under low-energy collision-induced dissociation conditions this b1 ion readily loses CO to form the a1 ion, CH3SCH2CH2CH=NH2+. © 1998 John Wiley & Sons, Ltd.

Collision-Induced Dissociation Threshold Energies of Protonated Glycine, Glycinamide, and Some Related Small Peptides and Peptide Amino Amides

The energy thresholds for fragment ions from the collision-induced dissociation of the protonated amino acid glycine (Gly), glycinamides Gly-NH2 and Gly-NHCH3, the dipeptides Gly-Gly and Gly-Gly-NH2, and the peptides Gly-Gly-Gly and Gly-Gly-Gly-Gly were determined with a modified triple quadrupole mass spectrometer. The precursor ions were produced by electrospray. The threshold energies for the formation of the major fragment ions were determined by fitting the experimentally determined threshold curves to theoretical threshold equations following the procedure developed by Armentrout and co-workers. To obtain corrections for the kinetic shifts, several of the transition states were modeled by using ab initio or semiempirical calculations. The immonium ion, CH2NH2+, which is an a1 ion, was observed as a major fragment ion from precursor ions (H2NCH2CO-X)H+, where X = OH, NH2, NHCH3, and NH2COOH. The activation energies obtained from the thresholds were between 40 and 50 kcal/mol. These energies were in g...

Addition of acetaldehyde to the N-terminus of a recombinant Schistosoma mansoni glutathione S-transferase upon high-level expression in Saccharomyces cerevisiae.

Intracellular expression of recombinant Schistosoma mansoni protein p28 (Smp28) in soluble form to a concentration of more than 6 g/l culture in Saccharomyces cerevisiae was accompanied by a post-translational modification, which occurred during the late stage of the culture. The modified protein, which had a reduced isoelectric point, was isolated by anion-exchange HPLC and characterized by tryptic mapping by means of on-line reversed-phase HPLC/electrospray mass spectrometry. Comparison with non-modified recombinant Smp28 allowed us to localize the modification to the N-terminal hexapeptide AGEHIK, which had an increased mass of 26 Da. Reversed-phase HPLC of the modified peptide with a shallow acetonitrile gradient revealed the presence of two components of identical mass and amino acid composition. Both peptides were inaccessible to N-terminal Edman sequencing, indicating that a rearrangement of the N-terminal region of recombinant Smp28 had taken place during tryptic digestion leading to two isomeric, N-terminally blocked peptides. Deuterium-exchange mass spectrometry showed that the modified peptides lacked two exchangeable protons, suggesting cyclic modifications implying the N-terminal amino group. Tandem mass spectrometry by means of the nano-electrospray technique and collision-induced dissociation allowed us to identify the modified sites as Ala1, His4 and Lys6 based on a characteristic modified a1 ion of Ala1 (70.0 Da), a modified immonium ion of His4 (136.0 Da) and a modified y1" ion (173.2 Da) of Lys6. Combination of all the above results led to the conclusion that recombinant Smp28 was initially modified at its N-terminus by addition of acetaldehyde to form an aldimine which rearranged during tryptic digestion to two different cyclic peptides.

The B1-fragment Ion from Protonated Glycine is an Electrostatically-bound Ion/Molecule Complex of CH2=NH+2 and CO

The stability of the B1-ion from glycylglycine dipeptides was studied using collision-induced dissociation experiments and ab initio calculations. This study reveals that the B1-type ion from glycine should be considered as an electrostatically bound ion/moecule complex, which dissociates into a glycine immonium ion (A1) and a carbon monoxide molecule. The stability of this complex has been calculated at various levels of the theory. At the highest level of theory (#RHF/6-311G**) it is found that the energy requirement, including zero-point vibrational energy correction, for dissociation into a glycine immonium A1 ion and a neutral carbon monoxide CO molecule is −4.0 kJ mol−1. Furthermore it could be concluded that B1-ions from glycine are stable if they are present as N-acylated species. The formation of stable B ions requires at least two carbonyl groups in the peptide backbone moiety.

Positive ion EI mass spectra of 2,3,5-trisubstituted-1,5-benzothiazepines, diltiazem, clentiazem and their fat-soluble metabolites.

Diltiazem, clentiazem and their acidic and basic metabolites extractable with tert-butyl methyl ether, which are all 2,3,5-trisubstituted-1,5-benzothiazepines, were analysed by positive ion electron ionization (PIEI) mass spectrometry, and the structures of fragment ions and their fragmentation pathways were investigated. In all the mass spectra of these compounds, b1 ions ([R1 - CH = CH - OR2]+) or b2 ions ([R1 - CH = CH - OH]+, b1 - CH2CO; R2 = COCH3) were seen as the base peaks or one of the major peaks (R1 and OR2 are the substituents at position 2 and 3, respectively). These spectra varied greatly with the nature of the side-chain at position 5: in the spectra of compounds with a 5-(2-dimethylamino) ethyl group, the a1 ion, [CH2 = N(CH3)2]+, was the base peak ion; in those with a 5-(2-monomethyl-amino)ethyl group (trifluoroacetyl(TFA)-derivatives), no a1 ion peak was seen, but the a3 ion, [CH2CH2NCH3TFA]+, was one of the major peaks; in those of the derivatives bearing a 5-(2-amino) ethyl or -carboxymethyl group, no peaks indicating the structures of the side-chain group at position 5 could be seen. GC-mass chromatography using fragment ions such as the a1, a3, b1 and b2 ions enables detection of the unchanged drug and most of its metabolites obtained by extraction with organic solvents under acidic or basic conditions followed by derivatization.

Soil solution aluminium activity related to theoretical A1 mineral solubilities in four Australian soils

SUMMARYFour soils were treated with HNO3, CaCO3 and K2SO4 to enable observation of the response of the soil solution composition and the solution A1 ion activity (Al3+) to the treatments and to time. The clay fraction of three of the soils was dominated by illite, kaolinite and quartz. The fourth was minated by kaolinite and iron oxides. The initial pH in 0.01 M CaCl2 varied between 4.0 and 5.0 and the organic carbon content from 0.7 to 1.1%. The soil solutions from soils dominated by kaolinite, illite and quartz were generally supersaturated with respect to quartz and well ordered kaolinite, and unsaturated with respect to illite. The soil solutions from the soil dominated by kaolin and iron oxide were generally unsaturated with respect to quartz but still saturated with respect to ell crystallized kaolin. Within mineral groups such as Al2SiO5 compounds, A12Si2O5(OH)4 (kaolinite group), and Al(OH)3 (A1 oxide) minerals, the more soluble forms became less supersaturated or unsaturated with time for many treatments.Lime treatment usually increased the ion activity product of AI(OH)3 in all soils, and of minerals with the composition, Al2SiO5, in the illite/kaolinite soils. Acid treatment reduced the apparent solubility of Al(OH)3, and the A1 silicates in the Al2SiO5, and Al2, Si2, O5,(OH)4, mineral groups on all soils. These results are interpreted to indicate that lime treatment led to the formation of trace quantities of more soluble A1 minerals that subsequently controlled (Al3+), whereas acid treatment dissolved trace quantities of such minerals leaving less soluble minerals to control (Al3+). The results suggest that, in mineral soils such as these, (Al3+) is under the control of inorganic dissolution and precipitation processes. These processes conform to expectations given the free energy of various inorganic aluminium compounds. Furthermore the sequence of dissolution and formation processes appears to be governed by the Gay‐Lussac—Ostwald step rule.

Structure breaking and electron localization in liquid cryolite–sodium solutions

Abstract The continuous nonmetal-metal transition, which occurs on dissolving metals in molten salts, may be shifted to higher metal concentration in solutions involving polyvalent metal ions by the possibility that these metals go into lower oxidation states. We evaluate a microscopic model for these processes in the specific case of solutions of sodium metal in molten cryolite (AlF3 3NaF). The structure of the ionic melt is understood and calculable at the microscopic level in terms of a dominant six-fold coordinated trivalent state of the A1 ion (the (AlF6)3- complex) with some admixture of a four-fold coordinated trivalent state (the (AlF4)− complex). The sodium metal is assumed to enter the ionic liquid in the form of monovalent ions and electrons. Our calculations demonstrate how these added components break up the structure of the ionic melt to yield localization by the formation of Al ions in reduced valence states, and provide order-of-magnitude estimates for the free-energy changes involved in t...