Calculating Physiochemical Properties

There are a number of online websites that provide property calculations, however be careful not to post proprietary information.

pKa - Difficult to calculate accurately, there are a few sites that give experimentally determined data.

pKa Data Compiled by David Ripin and David Evans (Harvard University) Bordwell pKa Table Acidity in DMSO (Univ. of Wisconsin) Zirchrom list of over 600 acids and bases

See Also:- Dissociation constants of organic bases in aqueous solution. D.D. Perrin. Butterworths, 1965. Dissociation constants of organic acids in aqueous solution. G.Kortum, W.Vogel and K.Andrussow. Butterworth, 1961.

The Chemaxon website

A variety of calculation plugins are available for Marvin. It has a rich (and growing) list of editing features, is chemically aware and is able to call ChemAxon's structure based calculation plugins for structures on the canvas.

There are a couple of demo pages

Virtual Computational Chemistry Lab

This site provides free on-line tools, which are helpful in performing computational chemistry, ADME/T and chemoinformatics tasks including the building and visualisation of chemical structures, the calculation of molecular properties and the analysis of relationships between chemical structure and properties

On-line software includes:-

• ALOGPS 2.1 is the most accurate program to predict lipophilicity and aqueous solubility of molecules
• ASNN calculates highly predictive non-linear neural network models
• E-BABEL is molecular structure information interchange hub
• PNN produces clearly interpretable analytical non-linear models
• PCLIENT generates more than 3000 descriptors
• E-DRAGON calculates DRAGON molecular indices
• PLS implements original two-step descriptors selection procedure
• UFS produces a reduced data set that contains no redundancy and a minimal amount of multicollinearity

ChemSpider

Compiles published experimental data about compounds and provides a property prediction service using the ACDLabs Percepta platform, EPISuite and ChemAxon tools

ChEMBL

As well as a vast amount of biological data ChEMBL also collates published physicochemical data and generates a range of calculated properties for each molecule.

SPARC

SPARC Performs Automated Reasoning in Chemistry

Current implementations (selected references):

• pKa, Major reference:Hilal, Said, S. W. Karickhoff and L. A. Carreira, "A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKa's," Quant. Struc. Act. Rel., 14, 348 1995.
• Physical properties, Major references:S.H. Hilal, L.A. Carreira and S.W. Karickhoff, "Prediction of the Vapor Pressure, Boiling Point, Heat of Vaporization and Diffusion Coefficient of Organic Compounds" QSAR & Combinatorial Science, 565 22 (2003). S. H Hilal, L.A. Carreira and S.W. Karickhoff, "Prediction of the Solubility, Activity Coefficient, Gas/Liquid and Liquid/Liquid Distribution Coefficients of Organic Compounds", QSAR & Combinatorial Science, 23,709(2004).
• Hydrolysis Major references:S. H Hilal, S.W. Karickhoff, L.A. Carreira and B.P. Shrestha "Estimation of Carboxylic Acid Ester Hydrolysis Rate Constants", QSAR & Combinatorial Science, 22,917(2003) Tad S. Whiteside, S. H Hilal, and L.A. Carreira,"Estimation of phosphate ester hydrolysis rate constants I. Alkaline hydrolysis", QSAR & Combinatorial Science, 24,1(2005)
• Hydration Major reference: S.H Hilal, L.L Bornander, L.A. Carreira and S.W. Karickhoff, "Hydration equilibrium constants of aldehydes, ketones and quinazolines", QSAR & Combinatorial Science, 24,631(2005).
• Electron Affinity Major reference: S. H Hilal, S.W. Karickhoff, L.A. Carreira and C.M. Melton "Prediction of Electron Affinity by Computer," Quant. Struc. Act. Rel 12, 389 (1993).
• Heat of Formation Major references:Tad S. Whiteside and Lionel A. Carreira "Prediction of the Enthalpy of Formation of Hydrocarbons using SPARC", J. Theo. And Comp. Chem. 3,451(2004) Tad S. Whiteside and Lionel A. Carreira "Prediction of the Enthalpy of Formation of Halogenated Hydrocarbons Using SPARC", J. Theo. and Comp. Chem. 4,461(2005).

OSIRIS Property Explorer

Is an integral part of Actelion's inhouse substance registration system.It lets you draw chemical structures and calculates on-the-fly various drug-relevant properties whenever a structure is valid. Prediction results are valued and colour coded. Properties with high risks of undesired effects like mutagenicity or a poor intestinal absorption are shown in red. Whereas a green colour indicates drug-conform behaviour.

The same properties can be calculated within Datawarrior.

Many desktop applications include LogP and other property calculators including Vortex, ChemDraw, ChemDoodle, Molinspiration, ACDLabs Percepta platform, Stardrop.

Cheminformatics toolkits also provide means to access some calculated properties programmatically OpenBabel, RDKit and CDK

The critical thing to note is that they all use different algorithms so if you start using one package you can't necessarily compare the results with a different package. So if you want to change you will need to recalculate all old results. Whichever package you use it is always important to get experimental results for a couple of representative examples. This will give you a feel for the accuracy of any computed results.

Sirius Analytical website

There are a number of interesting webinars, posters and presentations available from the Sirius Analytical website (registration required) they cover the measurement and use of a variety of physicochemical properties including pKa, LogP and solubility.

Medicinal Chemistry Toolkit app

The Medicinal Chemistry Toolkit app for iOS is a suite of resources to support the day to day work of a medicinal chemist. Based on the experiences of medicinal chemistry experts, we developed otherwise difficult-to-access tools in a portable format for use in meetings, on the move and in the lab. The app is optimised for iPad and contains calculator functions designed to ease the process of calculating values of: Cheng-Prusoff; Dose to man; Gibbs free energy to binding constant; Maximum absorbable dose calculator; Potency shift due to plasma protein binding.

Asteris can calculate a range of simple “core properties”, such as logP, molecular weight, polar surface area and numbers of hydrogen bond donors and acceptors.

Last updated 15 December 2019