Molecules in Silico: The Generation of Structural Formulae and Its Applications

Abstract

In information processing, in combinatorial chemistry, in structure elucidation, and in several other fields of chemistry, the computer-aided generation of all structures (constitutional formulae) within a defined structure space has become increasingly important. In this brief review the mathematical foundations of the classical molecular model and thus of the generation process are outlined, and the current state of structure generation as applied in software developed by the Bayreuth group is discussed.

Computational mass spectrometry for small molecules

“…Molecular isomer generators such as MOLGEN [170,172], SMOG [173], and Assemble [174] have helped with the structural elucidation of unknowns for many years [175,176]. Recently, the open source software OMG was introduced [177].…”

“…In addition, the space of generated structures can be constrained by the presence or absence of certain substructures, see Section “Mass spectral classifiers”. An overview on generating structural formulas is given by Kerber et al [172]. Enumerating all possible isomers allows us to overcome the boundaries of database searching: Simply generate all molecular structures corresponding to the parent mass or molecular formula, and use the output of the structure generator as a “private database”.…”

“…Enumerating all possible isomers allows us to overcome the boundaries of database searching: Simply generate all molecular structures corresponding to the parent mass or molecular formula, and use the output of the structure generator as a “private database”. Unfortunately, this approach is only valid for relatively small compounds (say, up to 100 Da): For molecular formula C 8 H 6 N 2 O with mass 146 Da there exist 109 240 025 different molecular structures [172]. …”

Quantitative crystal structure descriptors from multiplicative congruential generators

“…their configuration and conformation (Kerber et al, 2004). Arguably the simplest structure descriptor of a molecule is its sum formula, encoding the information about the arithmetical proportions in which elements combine, i.e.…”

“…Again, similar approaches are well established in molecular chemistry, starting from Cayley's pioneering work on the enumeration of the constitutional isomers of the alkanes to modern computational approaches like the MOLGEN project (Kerber et al, 2004;Gugisch et al, 2007). The multiplicative congruential method not only offers a way for the generation of candidate structures for actual crystal structures, but also offers a systematic way of doing so, instead.…”