J. C. Dobrowolsk et al.
136
of the other natural amino acids, the vCd spectra of asparagine, arginine hydrochloride, glutamine, isoleucine, leucine, lysine hydrochloride, threonine, allothreonine,
and valine were measured only in the 1980s by the Nafie group [147–150], whereas
it seems that those of aspartic and glutamic acids have not yet been registered.
5.6.2 Challenges for Computational Methods
In this Chapter, we briefly reviewed the application of theoretical studies to understand the relationship between the conformation of chiral molecules and experimental vCd and RoA spectra. thanks to the introduction of the analytic schemes
for the calculation of geometric derivatives of second-order molecular tensors,
routine calculations of spectra are possible, although the computational cost remains high, especially for RoA spectra. however, several challenges still exist
in computational chiroptical spectroscopy. We would like to mention some major
future directions:
1. state-of the-art choice of the method of calculation;
2. the problem of conformational flexibility of molecules;
3. the effects of solvent on the frequency and the intensity of chiroptical properties.
Recently, the coupled clusters (CC) approach has been applied to chiral molecules
containing up to 30 to 40 atoms. however, the level of dynamic electron correlation
and mechanical/electric anharmonicity needed to reproduce gas-phase measurements is still unclear. Also, the need to calculate geometric derivatives of the tensors
α, G’ and A with respect to the nuclear coordinates remains active. moreover, the
problem of basis set completeness at the CC and dFt levels of theory also belongs
to the first point, especially because the requirements of the basis set for RoA intensity calculations are more demanding than for vCd calculations.
the second point is related to biomolecules (amino acids) which can exist in several conformations. the number of conformations increases rapidly with molecular
size. thus, the difficulty in the location of relevant stable structures increases rapidly as well. different conformations can have very different vCd and RoA spectra;
therefore, for these conformationally flexible molecules, the use of the Boltzmann
averaging procedure in the calculation of the spectra is necessary. this means that
the relative energy of different conformations should be obtained with high accuracy. The question of whether to use the electronic energy differences (ΔE) or the
Gibbs energy differences (ΔG) remains open. Even though the zero-point vibrational energy (ZPE) is rarely considered, it may be necessary to get the correct sign
of several chiroptical properties [223].
the measurement of biomolecules in a water environment is one of the main
benefits of RoA over the vCd technique. however, solute-solvent interactions,
such as hydrogen bonds, cannot be properly described in the frame of the sole PCm
models. therefore, explicit solvation models are needed to account for the influence
of the environment on chiroptic spectra. Accurate sampling of the solute-solvent
136
of the other natural amino acids, the vCd spectra of asparagine, arginine hydrochloride, glutamine, isoleucine, leucine, lysine hydrochloride, threonine, allothreonine,
and valine were measured only in the 1980s by the Nafie group [147–150], whereas
it seems that those of aspartic and glutamic acids have not yet been registered.
5.6.2 Challenges for Computational Methods
In this Chapter, we briefly reviewed the application of theoretical studies to understand the relationship between the conformation of chiral molecules and experimental vCd and RoA spectra. thanks to the introduction of the analytic schemes
for the calculation of geometric derivatives of second-order molecular tensors,
routine calculations of spectra are possible, although the computational cost remains high, especially for RoA spectra. however, several challenges still exist
in computational chiroptical spectroscopy. We would like to mention some major
future directions:
1. state-of the-art choice of the method of calculation;
2. the problem of conformational flexibility of molecules;
3. the effects of solvent on the frequency and the intensity of chiroptical properties.
Recently, the coupled clusters (CC) approach has been applied to chiral molecules
containing up to 30 to 40 atoms. however, the level of dynamic electron correlation
and mechanical/electric anharmonicity needed to reproduce gas-phase measurements is still unclear. Also, the need to calculate geometric derivatives of the tensors
α, G’ and A with respect to the nuclear coordinates remains active. moreover, the
problem of basis set completeness at the CC and dFt levels of theory also belongs
to the first point, especially because the requirements of the basis set for RoA intensity calculations are more demanding than for vCd calculations.
the second point is related to biomolecules (amino acids) which can exist in several conformations. the number of conformations increases rapidly with molecular
size. thus, the difficulty in the location of relevant stable structures increases rapidly as well. different conformations can have very different vCd and RoA spectra;
therefore, for these conformationally flexible molecules, the use of the Boltzmann
averaging procedure in the calculation of the spectra is necessary. this means that
the relative energy of different conformations should be obtained with high accuracy. The question of whether to use the electronic energy differences (ΔE) or the
Gibbs energy differences (ΔG) remains open. Even though the zero-point vibrational energy (ZPE) is rarely considered, it may be necessary to get the correct sign
of several chiroptical properties [223].
the measurement of biomolecules in a water environment is one of the main
benefits of RoA over the vCd technique. however, solute-solvent interactions,
such as hydrogen bonds, cannot be properly described in the frame of the sole PCm
models. therefore, explicit solvation models are needed to account for the influence
of the environment on chiroptic spectra. Accurate sampling of the solute-solvent