The Combined Fragmentation and Systematic Molecular Fragmentation Methods

CONSPECTUS: Chemistry, particularly organic chemistry, is mostly concerned with functional groups: amines, amides, alcohols, ketones, and so forth. This is because the reactivity of molecules can be categorized in terms of the reactions of these functional groups, and by the influence of other adjacent groups in the molecule. These simple truths ought to be reflected in the electronic structure and electronic energy of molecules, as reactivity is determined by electronic structure. However, sophisticated ab initio quantum calculations of the molecular electronic energy usually do not make these truths apparent. In recent years, several computational chemistry groups have discovered methods for estimating the electronic energy as a sum of the energies of small molecular fragments, or small sets of groups. By decomposing molecules into such fragments of adjacent functional groups, researchers can estimate the electronic energy to chemical accuracy; not just qualitative trends, but accurate enough to understand reactivity. In addition, this has the benefit of cutting down on both computational time and cost, as the necessary calculation time increases rapidly with an increasing number of electrons. Even with steady advances in computer technology, progress in the study of large molecules is slow. In this Account, we describe two related fragmentation methods for treating molecules, the combined fragmentation method (CFM) and systematic molecular fragmentation (SMF). In addition, we show how we can use the SMF approach to estimate the energy and properties of nonconducting crystals, by fragmenting the periodic crystal structure into relatively small pieces. A large part of this Account is devoted to simple overviews of how the methods work. We also discuss the application of these approaches to calculating reactivity and other useful properties, such as the NMR and vibrational spectra of molecules and crystals. These applications rely on the ability of these fragmentation methods to accurately estimate derivatives of the molecular and crystal energies. Finally, to provide some common applications of CFM and SMF, we present some specific examples of energy calculations for moderately large molecules. For computational chemists, this fragmentation approach represents an important practical advance. It reduces the computer time required to estimate the energies of molecules so dramatically, that accurate calculations of the energies and reactivity of very large organic and biological molecules become feasible.