Evaluation of ACD/Structure Design Suite

Jeff Botts, Ph.D., Senior Scientist, Physical Chemistry & Spectroscopy, Aptuit

Chemistry World, November 2007

ACD/Structure Design Suite software provides a convenient resource database for dissociation constants (pK_a) and partition coefficients (logP) as well as a means to calculate predicted values when no analogous compounds are available.

Before using Structure Design Suite, manual searches of the literature for the reported values of similar structures, especially of reported dissociation constants, would be performed. If a similar structure could not be located, manual calculations of the anticipated pK_a value(s) using linear free energy relationships would be carried out. These activities generally require two to three days to complete.

The ACD/Labs pK_a module contained within Structure Design Suite greatly accelerates literature searches by providing predicted pK_a values based on chemical structure with the associated literature reference compounds. The predicted values tend to be close to the experimental values-usually within 0.5 pK_a units. Similar to using the pK_a module, the logP module also provides reliable estimates of logP values for neutral species. The same information that used to require a few days to obtain can now be acquired in about 15 minutes.

The logP value for ion pairs tends to be less reliable, however. While the aqueous solubility module is generally useful, the results are a somewhat less reliable indicator of the true solubility of the compounds studied. Possibly, this limitation reflects the intrinsic challenge of predicting solid state properties, which influence the solid state-solution equilibrium. Nevertheless, the solubility predictor is a good starting point for aiding in the design of formal solubility studies.

While the ACD/Labs software has its limitations, the software is a valuable supporting asset in the performance of physical chemistry studies.