Molecular Conformation and Crystal Lattice Energy Factors in Conformational Polymorphs

Abstract

In crystal structures of flexible molecules the total energy is a summation of the molecular conformer and crystal lattice energy contribution. These two energy factors are of comparable magnitude in organic solids because bond torsions and intermolecular interactions have similar energies, worth a few kcal mol-1. The two contributions may be additive or cancel one another. Polymorphism is likely in molecular systems wherein molecular conformer and crystal lattice energy effects compensate each other, i.e. a metastable conformer resides in a stable packing arrangement or a stable rotamer is assembled in a metastable crystal environment. Consequently, conformational polymorph energy differences occur in a small window of <3 kcal mol-1. Several organic conformational polymorph clusters that highlight this principle are discussed in this chapter