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

Abstract Mathematical models based on structure–activity relationships and perturbed molecular orbital theory have been developed to calculate the ionization p K a s for a large number of organic molecules. These models include resonance, direct and indirect electrostatic field effects, sigma induction, steric effects, differential solvation and hydrogen bonding. The thermodynamic microscopic ionization constants, p k i , of molecules with multiple ionization sites and the corresponding complex speciation as a function of pH have been determined using these chemical reactivity models. For a molecule of interest SPARC (SPARC performs automated reasoning in chemistry) calculates all of the microscopic ionization constants and the fraction of each species as a function pH along with the titration (charge) curve. The system has been tested on several biologically and environmentally important compounds.