HypCal, a general-purpose computer program for the determination of standard reaction enthalpy and binding constant values by means of calorimetry.

The program HypCal has been developed to provide a means for the simultaneous determination, from data obtained by isothermal titration calorimetry, of both standard enthalpy of reaction and binding constant values. The chemical system is defined in terms of species of given stoichiometry rather than in terms of binding models (e.g., independent or cooperative). The program does not impose any limits on the complexity of the chemical systems that can be treated, including competing ligand systems. Many titration curves may be treated simultaneously. HypCal can also be used as a simulation program when designing experiments. The use of the program is illustrated with data obtained with nicotinic acid (niacin, pyridine-3 carboxylic acid). Preliminary experiments were used to establish the rather different titration conditions for the two sets of titration curves that are needed to determine the parameters for protonation of the carboxylate and amine groups.

Kojic acid derivatives as powerful chelators for iron(III) and aluminium(III).

Proceeding from a ligand constituted by two units of kojic acid linked by a methylene group, which proved a very promising chelator for excess iron(III) and aluminium(III) pathologies, two new ligands have been designed and synthesized: one by adding a vanillin molecule in the linker and the second by adding an o-vanillin molecule. Both these ligands, on the basis of complex formation studies presented here, show significant potential as therapeutic agents for iron and aluminium overload. Protonation constants of the pure ligands have been determined by potentiometry, and standard reaction heats by calorimetry. Hydrogen bonding plays an important role in the protonation reactions. The crystal structures of both ligands have furthermore been resolved. Complex formation equilibria for the iron complexes have been studied by combined potentiometry-spectrophotometry and those of aluminium by potentiometry alone. All complexes were found to contain two metal ions. NMR diffusion measurements hardly applied to complex formation equilibria and the results of density functional theory (DFT) calculations were powerful tools in confirming the proposed reaction model and in evaluating the relative stabilities of the products. Further support was given by NMR chemical shift measurements and electrospray mass spectrometry.

Acidity constants in different media (I=0 and I=0.1 M KCl) from the uncertainty perspective.

Procedures for estimating the measurement uncertainty for the acidity constant Ka (or the pKa value) in different media (I=0 and I=0.1 mol L(-1) KCl), as determined by potentiometric titration, are presented. The uncertainty budgets (the relative contributions of the different input quantities to the uncertainty in the result) of the pKa (I=0) and pKa (I=0.1 mol L(-1) KCl) values are compared. Unlike the values themselves, the uncertainties and uncertainty budgets of the values are comparable. The uncertainty estimation procedures are based on mathematical models of pKa measurement and involve the identification and quantification of individual uncertainty sources according to the ISO GUM approach. The mathematical model involves 52 and 48 input parameters for pKa (I=0) and pKa (I=0.1 mol L(-1) KCl), respectively. The relative importance of each source of uncertainty is discussed. In both cases, the main contributors to the uncertainty budget are the uncertainty components due to the hydrogen ion concentration/activity measurement, which provide 63.7% (for pKa (I=0)) and 89.3% (for pKa (I=0.1 mol L(-1) KCl)) of the uncertainty. The remaining uncertainty contributions arise mostly from the limited purity of the acid. From this work, it is clear that the uncertainties of the pKa (I=0.1 mol L(-1) KCl) values tend to be lower than those of the pKa (I=0) values. The main reasons for this are that: (1) the uncertainty due to the residual liquid junction potential is nominally absent in the case of pKa (I=0.1 mol L(-1) KCl) due to the similarly high concentrations of background electrolyte in the calibration solutions and measured solution; (2) the electrode system is more stable in solutions containing the 0.1 mol L(-1) KCl background electrolyte and so the readings obtained in these solutions are more stable.

Determination of protonation constants of some fluorinated polyamines by means of 13C NMR data processed by the new computer program HypNMR2000. Protonation sequence in polyamines.

The p K(a) values of 6-fluoro-4,8-diazadodecane-1,12-diamine (6-fluorospermine) (1), 6,6-difluoro-4,8-diazadodecane-1,12-diamine (6,6-difluorospermine) (2), 6-fluoro-4-azaoctane-1,8-diamine (6-fluorospermidine) (3) and 6,6-difluoro-4-azaoctane-1,8-diamine (6,6-difluorospermidine) (4) in D(2)O solution have been determined at 40 degrees C from (13)C NMR chemical shifts data using the new computer program HypNMR2000. The enthalpies of protonation of compounds 1-4 and the parent amines spermine (5) and spermidine (6) have been determined from microcalorimetric titration data. The values of Delta H degrees were used to derive basicity constants relative to 25 degrees C. The NMR data have been analysed by two different methods to obtain information on the protonation sequence in the polyamines 1-5. The protonation sequence for spermine is related to its biological activity.