Estimation of microscopic, zwitterionic ionization constants, isoelectric point and molecular speciation of organic compounds

Mathematical models based on structure-activity relationships and perturbed molecular orbital theory have been developed to calculate the ionization p K(a) for a large number of organic molecules. These models include resonanc e, direct and indirect electrostatic field effects, sigma induction, steric effects, differential solvation and hydrogen bonding. The thermodynamic mi croscopic ionization constants, pk(i), of molecules with multiple ionizatio n sites and the corresponding complex speciation as a function of pH have b een determined using these chemical reactivity models. For a molecule of in terest SPARC (SPARC performs automated reasoning in chemistry) calculates a ll of the microscopic ionization constants and the fraction of each species as a function pH along with the titration (charge) curve. The system has b een tested on several biologically and environmentally important compounds. (C) 1999 Published by Elsevier Science B.V. All rights reserved.