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Acid Dissociation (pKa) Calculation with ACD/pKa

  • Calculate the acid dissociation constant (pKa) from structure. Color intensity of highlighted ionizable groups indicates acid/base strength
    Calculate the acid dissociation constant (pKa) from structure. Color intensity of highlighted ionizable groups indicates acid/base strength
  • See the contribution of various ionization states to pKa and visualize all ionized microspecies as a function of pH
    See the contribution of various ionization states to pKa and visualize all ionized microspecies as a function of pH


  • "The best software for routine logD and pKa predictions!"
    Susan Winks (H3D)


    "We chose [Percepta] because it is the industry standard for pKa and logD prediction…it will help us filter out compounds with undesirable physicochemical properties. The batch processing option will allow us to quickly triage large compound sets."
    Dr. Tom Carter (University of Oxford)

Predict pKa (acid dissociation/ionization) from structure

Access the most accurate acid dissociation constant values from the industry standard pKa calculator ACD/pKa.

How are pKa values calculated?

Classic Algorithm

A database of >17,000 compounds, representing >32,000 pKa values, is used in determination of pKa.

Hammet-type equations for popular ionizable functional groups, and carefully derived electronic substituent constants (σ) are used to predict the most accurate pKa values.

Tautomeric equilibria, covalent hydration, resonance effects, and α, β-unsaturated systems are taken into consideration in the calculations.

GALAS Algorithm

The internal training set is comprised of >17,500 compounds representing >20, 000 ionization centres.

A database of ionization centres, interaction constants, and interaction calculation methods are used to simulate a complete distribution plot of produce a full range of protonation states of the molecule at different pH conditions. pH dependency of net molecular charge, distribution of protonation states, and the average charge of each ionization centre is provided.

Acid Dissociation Constant (pKa) Calculator Features

  • Calculate the acid dissociation constant (pKa) under standard conditions (25°C, zero ionic strength) in aqueous solution for all stages of ionization from structure, SMILES string, or chemical name
  • Easily visualize ionizable groups through color shading (red = acidic, blue = basic, purple = amphoteric ionization centers; colour intensity indicates acid/base strength).
  • Understand pKa constants for all stages of ionization
    • Partial ionization reactions (microstages) listed with contribution of each microstage to the final pKa value (quoted as a percentage)
  • Understand the relevance of the predicted result through reliability range (in ±log units) and calculation protocols
  • Choose from two different predictive algorithms (ACD/pKa Classic and GALAS) for the most accurate pKa values
  • Improve prediction accuracy and expand domain applicability by training the model with experimental data
  • See the ionization reaction and pKa microstants for all ionizable species
    See the ionization reaction and pKa microstants for all ionizable species
  • Calculation protocol provides information about structural fragments used for the calculation of pKa
    Calculation protocol provides information about structural fragments used for the calculation of pKa
  • Visualize a plot of protonation states vs pH
    Visualize a plot of protonation states vs pH
  • ACD/pKa automatically checks for tautomeric forms
    ACD/pKa automatically checks for tautomeric forms

A Machine Learning pKa Calculator

Experimentally determined pKa values can be used to train the algorithms using the machine learning capabilities of the software. This both improves prediction accuracy and makes the model more relevant to your chemical space or project.

The Classic algorithm offers machine learning (training) and you do not have to be a computational chemist to use it.

Do you have a large curated set of experimentally measured pKa values?
Our development team is happy to collaborate with you to expand the applicability domain of our algorithms.

Deployment Options

Desktop/Thick client

Software installations for individual computers with a graphical user interface. Full physicochemical, ADME and toxicity calculator modules are available (with training capabilities) including the PhysChem Profiler bundle.

Batch

Screen tens of thousands of compounds with minimal user intervention—compatible with Microsoft Windows and Linux operating systems (OS). Plug-in to corporate intranets or workflow tools such as Pipeline Pilot.

Percepta Portal/Thin client

Web-based application for prediction of molecular properties (PhysChem, ADME, and toxicity) and data analysis. KNIME integration components available.

Host on your corporate intranet or the cloud. Available for Linux and Windows OS.

Resources

AppNote
The Importance of Training Predictors

This application note discusses the importance of using the machine learning (model training) capabilities of predictive models to improve accuracy.
Read more

Article
Determination of acid dissociation constants (pKa) of cephalosporin antibiotics: Computational and experimental approaches

Comparison of experimental and published pKa values for 88 cephalosporin antibiotics with ACD/pKa and other prediction software.
Read more

Article
Chromatographic retention behaviour, modelling and optimization of a UHPLC-UV separation of the regioisomers of the Novel Psychoactive Substance (NPS) methoxphenidine (MXP)

Software from ACD/Labs was used in the prediction of physical and chemical properties, and retention modelling and optimization.
Read more

What is the acid dissociation constant Ka?

The acid dissociation constant (Ka, also known as the acid-ionization constant) is a quantitative measure of the strength of an acid in solution (i.e. a measure of the tendency of a molecule to release H­+ and generate a hydronium ion (H3O+). A strong acid will completely dissociate in water (equilibrium favors the right hand of the equation below), while weak acids will not.

HA + H2O ⇌ H3O+ + A-

Ka is the equilibrium constant that describes the dissociation of a molecule and is expressed as a ratio of concentrations of the various species present

pKa expressed as a ratio of concentrations of the various species present

What is pKa?

The acid ionization constant (Ka) varies by orders of magnitude. It is therefore more intuitive to refer to such extreme numbers on a logarithmic scale. By convention the p in pKa was introduced to denote the negative logarithm (base 10).

pKa = -log10 Ka

Ka values are converted to pKa values as follows:

Phenol:
pKa = -log (1. 8 × 10-10) = 10.0

Acetic acid:
pKa = -log (1.8 × 10-5) = 4.8

There is no intrinsic reason to rule out pKa values less than 0 or greater than 14. For example, sulfuric acid, H2SO4, has a negative pKa for the loss of its first proton:

H2SO4 → HSO4- + H+ (pKa < 0)

Experimental determination of pKa values, however, is usually limited to between 1 and 13.

How are pKa and pH related?

pKa (the acid dissociation constant) describes the inherent property 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+]

How are pKa values used?

Synthetic chemists use the acid dissociation constant to understand what substances can be used to protonate or deprotonate a compound, to assist a reaction. In biochemistry pKa helps scientists understand the activity of enzymes and the stability of proteins.

In pharmacology, ionization of a compound changes its physical behavior and affects macro properties such as aqueous solubility and lipophilicity. pKa values are also used to understand more complex ADME characteristics.

pKa is used by chromatographers to select the appropriate pH of the mobile phase (buffer) for separations.

In environmental sciences acid-base equilibria of humic acids help establish the potability and treatment of water and provide information about the health of waterways such as lakes and rivers.

Ready to learn more?

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