title: DISCO--a general computer program for the computation of acid dissociation constants of polyprotic molecules in water and biological fluids, from nuclear magnetic resonance data: application to polyamines.
abstract: A new computer program, DISCO, running under Windows, has been developed under the project CSA98P22 falling within the Competitive Support Activities initiative launched within the EU 4th Framework Programme. DISCO allows the calculation of the stepwise acid dissociation constants of polyprotic molecules in water and in complex media (i.e., biofluids, etc.) from nuclear magnetic resonance (NMR) data (chemical shifts) by means of two derivative-free methods: Pit-mapping and Simplex. DISCO performances were tested using simulated-unaffected by experimental error-data sets, for systems having up to seven equilibrium constants and experimental NMR data of spermine, 6-monofluorospermine, and 6,6-difluorospermine, dissolved in D(2)O and in physiological solution (D(2)O/NaCl). Results demonstrated that (i) DISCO enables the determination of pK(A) values with high precision even when small-sized raw data sets are employed, when chemical shifts are measured with low precision (the usual condition in biofluids due to the impossibility to obtain narrow line shape), and when the guess solution, necessary as an initial step of the mathematical iterative process, is fixed within a large interval of variation; (ii) DISCO always converges to the root; (iii) DISCO permits the calculation of pK(A) values which lie within the observed pH range, independent of the narrowness of the pH range.
authors.affiliation: Physical and Chemical Exposure Unit, Institute for Health and Consumer Protection, European Commission Joint Research Centre, 21020 (VA), Ispra, Italy. fabiano.reniero@jrc.it
authors.forename: Fabiano
authors.initials: F
authors.lastname: Reniero
authors.forename: Claude
authors.initials: C
authors.lastname: Guillou
authors.forename: Chiara
authors.initials: C
authors.lastname: Frassineti
authors.forename: Stefano
authors.initials: S
authors.lastname: Ghelli
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D007552:Isotonic Solutions / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012965:Sodium Chloride / Q000737:chemistry; D012984:Software; D013096:Spermine / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D007552:Isotonic Solutions; D014867:Water; D013096:Spermine; D012965:Sodium Chloride