Angewandte Chemie International Edition
Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
How Viable Is It to Prove Viability?
I read with interest the Angewandte article by Hoffmann, Schleyer and Schaefer, three giants in the field of theoretical organic chemistry, requesting more realism in reporting computational chemistry. This is an important objective because scientific honesty essentially requires realism and the absence of exaggeration. I am fully supportive of most of the sentiments expressed in their article, including the sections on accuracy and precision in the quantum chemical world, and on significant figures in theoretical calculations. I am also in full agreement with the section distinguishing kinetic and thermodynamic stability.
I also agree that it would be nice to be able to identify molecules as "viable" versus "fleeting". There are, however, potential problems in being able to do this on the basis of computations. It will certainly be possible to conclude in some instances that a molecule is likely to be capable of at least a fleeting existence if all the vibrational frequencies are real and there are no low-frequency decomposition modes. There will be other cases where it will be possible to conclude that a molecule is capable of at most a fleeting existence if all the vibrational frequencies are real but a low-energy decomposition pathway has been identified. The low-energy decomposition pathway would also demonstrate that the molecule is non-viable. However, to prove that a medium-sized or larger molecule is viable is a task almost without limits. For example, the prospective molecule would be required to survive all possible fragmentation, isomerization and dimerization reactions at room temperature, and it would be required to not react spontaneously with air or moisture. If we go beyond small molecules, I wonder whether it is feasible today to carry out the computational investigation of a sufficient number of these possible decomposition pathways to be able to prove with certainty that a molecule is viable? It goes back to Carl Sagan's often-quoted statement that "absence of evidence is not evidence of absence".
University of Sydney (Australia)