Lucia Alderighi

Hyperquad simulation and speciation (hyss): a utility program for the investigation of equilibria involving soluble and partially soluble species

Abstract Hyperquad simulation and speciation (HySS) is a computer program written for the Windows operating system on personal computers which provides (a) a system for simulating titration curves and (b) a system for providing speciation diagrams. The calculations relate to equilibria in solution and also include the possibility of formation of a partially soluble precipitate. There are no restrictions as to the number of reagents that may be present or the number of complexes that may be formed.

In vivo assessment of free magnesium concentration in human brain by 31P MRS. A new calibration curve based on a mathematical algorithm.

Free cytosolic [Mg2+] can be assessed in vivo by 31P MRS from the chemical shift of β‐ATP which in turn depends on the fraction of total ATP complexed to Mg2+ ions. The reliability of these in vivo measurements depends on the availability of an appropriate in vitro calibration to determine the limits of chemical shifts of unbound ATP and Mg‐ATP complexes, using solutions that mimic the in vivo cytosolic conditions as far as possible. We used an algorithm and software to allow a quantitative definition of the Mg2+‐binding molecules to build a semi‐empirical equation that correlates the chemical shift of the β‐ATP signal to the [Mg2+] taking into account the amount of Mg2+ bound to all other constituents in solution. Our experiments resulted in a simple and reliable equation directly usable to assess in vivo the free cytosolic magnesium concentration of human brain by 31P MRS. Our method is also flexible enough to make it suitable for in vivo measurements of [Mg2+] in other organs and tissues.

In vivo 31P-MRS assessment of cytosolic [Mg2+] in the human skeletal muscle in different metabolic conditions

Cytosolic free [Mg(2+)] can be assessed in vivo by (31)P-MRS from the chemical shift of beta-ATP. The reliability of in vivo measurements depends on the availability of appropriate in vitro calibration curves obtained by using solutions that mimic the in vivo cytosolic conditions as far as possible. We build a semi-empiric equation that correlates the chemical shift of beta-ATP to free [Mg(2+)] taking into account the amount of Mg(2+) bound to all other ligands in solution. Our experiments resulted in a reliable ten-parameters equation directly usable to assess the cytosolic free [Mg(2+)] of human skeletal muscle at rest, during work and recovery. Our experiments also resulted in a new equation that allows the assessment of cytosolic pH from the chemical shift of Pi taking into account the measured free [Mg(2+)]. To perform simultaneous calculation of free [Mg(2+)] and pH in the skeletal muscle in different metabolic conditions we developed a specific software package available on Internet (http://www.unibo.it/bioclin) together with another program based on the equation previously obtained to calculate cytosolic free [Mg(2+)] in the human brain. The reliability and effectiveness of our equations and software were tested on the calf muscles of healthy volunteers at rest, during work and recovery.

Aqueous solution chemistry of beryllium

Publisher Summary This chapter discusses aqueous solution chemistry of beryllium. Complexes of the beryllium ion are always 4-coordinate with, at most, minor deviations from regular tetrahedral geometry. The tetra-aqua ion is a very stable entity and substitution of one or more water molecules by monodentate ligands is not thermodynamically favorable except with fluoride, hydroxide, and phosphonate ligands. The aqueous solution chemistry of this ion is dominated by the ease of hydrolysis with the formation, principally, of the hydroxo-bridged species [Be3(OH)3(H2O)6] 3+ . Complex formation, then, is a process in which the ligand is usually competing with the hydrolysis reaction as the aqua-ion is present only in strongly acid conditions (pH less than ca. 3) where many ligands are protonated. The only monodentate ligands that can compete with hydrolysis are fluoride and phosphonates. Chelating ligands can form stable complexes with beryllium by virtue of the chelate effect. Greater use of beryllium will require the consideration of its role in the environment, and knowledge of speciation in naturally occurring waters will be needed.

Preparative, potentiometric and NMR studies of the interaction of beryllium(II) with oxalate and malonate. X-ray structure of K3[Be3(OH)3(O2C–CH2–CO2)3]·6H2O

Abstract The complexes formed by beryllium(II) with the bidentate ligands oxalate, L=(O2C–CO2)2−, and malonate, L=(O2C–CH2–CO2)2−, have been investigated in aqueous solution using both potentiometric and 9Be NMR measurements. The species [BeL(H2O)2], [BeL2]2−, [Be3(OH)3L3]3− and [Be3(OH)3(H2O)3L]+ have been identified and their formation constants have been determined at 25°C in 0.5 mol dm−3 NaClO4. The malonate complexes are much more stable than the oxalate ones. New crystalline salts of formula K3[Be3(OH)3L3]·nH2O have been isolated using conditions established with the aid of speciation calculations. The structure of K3[Be3(OH)3(malonate)3]·6H2O has been determined by an X-ray structure analysis: orthorhombic, space group Pc21n, a=9.011(3), b=14.041(4), c=18.761(9) A, Z=4. Each beryllium atom is tetrahedrally coordinated by two hydroxo groups and two oxygen atoms from the chelating malonate. The (Be(OH))3 core is a puckered six-membered ring with each hydroxo group bridging two beryllium centres.

Thermodynamic and Multinuclear NMR Study of Beryllium(II) Hydrolysis and Beryllium(II) Complex Formation with Oxalate, Malonate, and Succinate Anions in Aqueous Solution

The hydrolysis of beryllium(II) and its complexation by oxalate, malonate, and succinate in 0.5 mol dm−3 NaClO4 aqueous solution at 298 K has been studied by means of potentiometric (pH-metric), microcalorimetric, and multinuclear NMR-spectroscopic measurements. The protonation properties of the three ligands have also been investigated by potentiometry and microcalorimetry under the same experimental conditions. Thermodynamic results are consistent with a previously proposed chemical model for beryllium(II) hydrolysis, involving the species [Be2OH]3+, [Be3(OH)3]3+, [Be5(OH)6]4+, [Be6(OH)8]4+, and Be(OH)2. Complex formation of beryllium(II) with the dicarboxylate ligands is invariably promoted by favourable entropic contributions (ΔS° > 0), while the enthalpic terms are always unfavourable (ΔH° > 0). Malonate forms by far the most stable complexes owing to a more favourable (less endothermic) enthalpic contribution. These data reflect the fitting of the “bites” of the ligands with the stereochemically required tetrahedral coordination geometry about the metal ion, as well as the ligand preorganization.

Solution Study, Crystal Structure and Relaxivity Properties of a Gd3+ Complex with an Uncharged Macrocyclic Ligand Bearing Four Amidic Side Arms

Equilibrium data on the interaction of DTMA [(DTMA = DOTA tetrakis(methylammide)] with Gd3+ in aqueous solution, properties of the complexes formed in the pH range 0.6–11.8, water proton relaxation rate enhancement, and the crystal structure analysis of the [Gd(DTMA)H2O]3+ complex are reported. In the crystal structure the metal ion is bound to the nitrogen atoms of the tetraazamacrocyclic moiety, to the amidic oxygen atoms, and to an oxygen atom of a water molecule. The nine donors are located at the vertices of a distorted square antiprism, which is capped by the coordinated water oxygen atom in the axial position. In solution [Gd(DTMA)]3+ is not very stable [logKML = 12.8(1)] and gives rise to the formation of [Gd(DTMA)OH]2+ [pKa = 7.9(1)] and [Gd(HDTMA)]4+ [logK(ML+H) = 3.4(1)]. The proton solvent relaxivity of aqueous complex solutions assumes a constant value in the pH range 3–8, increasing at higher and lower pH. For pH > 3 the data are in good agreement with a previous study on the same compound. For pH < 3 a new interpretation is presented, based on the formation of [Gd(HDTMA)]4+ and the release of Gd3+.

Beryllium binding to adenosine 5′-phosphates in aqueous solution at 25°C**

Equilibrium constants for the binding of beryllium(II) to the nucleotides: adenosine 5′–monophosphate, -diphosphate, and -triphosphate have been determined. The species formed are [BeL]( z −2)−, [Be(HL)]( z −3)−, [Be2(OH)L2](2z−3)− and [Be3(OH)3(HL)3](3z−6)−, where L z − represents the fully deprotonated nucleotide. When the complex contains a protonated ligand, the protonation site is an adenosine nitrogen. Formation of these complexes is unlikely to interfere, under physiological conditions, with the functioning of the nucleotides due to the precipitation of beryllium hydroxide in the pH range 6–7. **Dedicated to Professor Alfredo Mederos on the occasion of his retirement

Thermodynamics of the acid dissociation of BOPTA. Determination of equilibrium constants by means of 13C NMR spectroscopy

BOPTA, (9R,S)-2,5,8-Tris(carboxymethyl)-12-phenyl-11-oxa-2,5,8-triazadodecane-1,9-dicarboxylic acid, is a chelating agent whose gadolinium complex can be used as a magnetic resonance imaging contrast agent (MRI-CA) specific for the liver. The stepwise deprotonation constants for BOPTA were determined from a series of 13C NMR measurements by means of the new computer program HYPNMR and also from potentiometric titration data by means of the program HYPERQUAD. The first three stepwise protonation constants obtained by the NMR method are in very good agreement with those determined by potentiometry. In very acidic solutions the NMR method gave more reliable results because the glass electrode is susceptible to interference at low pH.The enthalpy changes for the protonation reactions have also been measured by microcalorimetry. The first two protonation reactions are exothermic, indicating that protonation occurs on amine nitrogen atoms, while the following protonation steps, being athermic, involve carboxylate groups.