A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKas

Abstract

Ionization pK a s for a large set of molecules were calculated using reactivity models developed in the computer program SPARC. SPARC uses relatively simple computational algorithms based on fundamental chemical structure theory to estimate ionization pK a s of organic molecules strictly from molecular structure. Molecular structures are broken at each essential single bond into functional units with intrinsic properties. Reaction centers (acid or base) are identified and the impact of appended molecular structure on ionization pK a is quantified by perturbation theory. Resonance, electrostatic, solvation and H‐bonding models have been developed and tested on 4338 pK a s for 3685 compounds. The RMS deviation for the acids and the amino reaction center was 0.36 pK a units whereas that for the in‐ring N and = N reaction centers was 0.41. Microscopic ionization constants, zwitterionic constants, isoelectric points, and molecular speciation as a function of pH can be calculated using the SPARC models.