Beyond Gas Phase and Static Structures

In order to advance the usefulness of theoretical calculations in broader applications, the computations should be carried out for a system that describes experimental conditions as accurately as possible. To do this, consider the following topics for a description of a system beyond using a single static structure at 0 K conformational averaging of static gas phase structures (this has been partially addressed already in Sect. 3), solvent effects on static structures, zero-point and finite temperature vibrational averaging, and molecular dynamics (MD) or Monte-Carlo (MC) sampling without and with solvation. 

For instance, solvent effects can represent much more than just a small perturbation of the electronic structure of a molecule. Sometimes these effects can be strong enough that the chiroptical response can be dominated by their influence on the chiral solute. For instance, effects that should be considered are how a solvent shell perturbs the electronic structure of the solute (and therefore its chiral response [155]), or the possibility of a solute transferring its chirality to the surrounding solvent shell (influencing one particular solvent molecule [151] or the entire solvent shell [156]). Here and in the following discussions it is assumed that the solvent itself is not chiral, and therefore the only contributions to the chiroptical response of the solution are from the solute or from chirality induced by the solute in the solvent shell. 

There are many cases when the molecule of interest is not rigid and has more than one stable conformer under the experimental conditions, and more care has to be taken when interpreting the results. For example, Mazzeo et al. [157] studied three benzotricamphor derivatives. Two of them were rigid and a small basis set (B3LYP/6-31G ) produced optical rotation of the same sign and order of magnitude as found experimentally. However, [x]D of a benzotricamphor derivative with three benzylidene moieties added, which was expected to have only one predominant conformer (based on a conformational search performed with a molecular mechanics force field), was overestimated by more than a factor of 

The problems of conformational averaging and of considering solvent effects are interconnected. For instance, one of the more obvious effects when going from the gas phase to solution is the resulting change of mole fractions for solutes with multiple conformers [115, 159]. One example of this is epichlorohydrin, which is discussed elsewhere in this chapter. A conformer distribution with several thermally accessible conformers that have considerably different ORs and ECD spectra might also result in a marked temperature dependence of measured and simulated chiroptical properties. 

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In order to render the chapter sufficiently self-contained, the reader will find a theory and methodology section immediately following this introduction (Sect. 2). Literature covering a broad range of applications is reviewed in the subsequent sections, grouped by topics as follows. Section 3 Benchmarks of functionals and basis sets, small molecule test cases. Section 4 Beyond gas phase and static structures. Section 5 (mainly) Assignment of absolute configuration case studies. Section 6 Analysis methods for chiroptical properties. Section 7 Case studies where a variety of methods was used to probe ECD,... 

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