pKa (PhysChem Suite™)

pK_a describes how readily a molecule donates or accepts a proton at its ionization sites. It provides a standard way to compare ionization behaviour across chemically diverse compounds. pK_a is important because it determines the ionization state of a molecule at a given pH, directly influencing key properties such as solubility, permeability, absorption, distribution, and overall ADMET behaviour.

The pK_a Classic model is trained on more than 26,000 compounds and over 42,000 experimental pK_a values. pK_a predictions use multiple complementary algorithms and advanced similarity-based approaches to improve reliability across diverse chemical space.  

Our pK_a prediction modules are continuously refined to improve accuracy and expand chemical space coverage. Prediction accuracy depends on chemical class and applicability domain and can be further improved by training supported models with high-quality proprietary experimental data.

Classic Algorithm: 

• The internal training database is made up of >26,000 compounds, representing >42,000 pK_a values. 
• Uses Hammett-type equations for popular ionizable functional groups and carefully derived electronic substituent constants (σ) are used to predict pK_a values. 
• Accounts for tautomeric equilibria, covalent hydration, resonance effects, and α, β-unsaturated systems. 

GALAS Algorithm: 

• The internal training set contains >17,500 compounds representing >20,000 ionization centers. 
• A database of ionization centers, interaction constants, and interaction calculation methods are used to simulate complete distribution plots and produce a full range of protonation states across different pH conditions. 
• Generates full pH-dependent behaviour of molecules. 
• Provides outputs including pH-dependent net molecular charge, protonation state distributions, and average charge per ionization center 

pK_a (the acid dissociation constant) describes the inherent tendency of a compound or ionizable functional group to lose H⁺ and generate hydronium ions (H₃O⁺). 
pH measures the concentration of hydronium ions [H₃O⁺] in aqueous solution.

pH=−log[H₃O⁺]