K. Chruszcz-Lipska and E. W. Blanch
68
Currently, RoA calculations may be performed using the gaussian ’09 [52]
(gaussian ’03 [53] was the first commercially available user-friendly software for
the dFt calculation of RoA spectra), dalton [54], or turbomole [55, 56] software
packages and also programs like CAdPAC [57] with which the first ab initio calculations of RoA were conducted. the calculation of the spectra using quantumchemical methods is an important aspect of the RoA technique and is fast becoming
the method of choice for obtaining detailed information about molecular structure
from experimental RoA spectra (Fig. 4.2).
Successful simulation of observed spectra can afford the complete solution of the
structure of the investigated compound, including its absolute configuration, conformation and, in the case of simultaneous existence of multiple conformers, also
their percentage populations at the selected temperature. Additionally, these calculations give us the opportunity to obtain knowledge about inter- and intra-molecular
interactions, especially between solvent molecules and the investigated compound.
our purpose is not here to give a detailed and full account of the theoretical calculations, which can be found in other sources, including new review articles [43, 44,
58–61] and books [62], but rather to present some examples that show the possibility
of application of dFt calculations in RoA spectroscopy of biological samples.
the calculation of vibrational RoA begins with building the structure that contains information specific to its stereochemical architecture. the next step is conducting the search over the conformational space to identify all of the lowest-energy
conformers of the investigated molecule. this conformational search can be done
in several ways. one of these is ‘manual’, the systematic specification of all angular degrees of freedom, including ring puckers and exploration of these degrees of
freedom by an appropriate program. this approach is good for small systems, especially if solvent effects are not significant and conformational flexibility is limited
like in the case of carenes, previously investigated by us (Scheme 1). Next, the set
of lowest-energy conformers is usually optimized at a higher level of dFt theory
using the basis set for the final RoA calculations. In the simplest case, only one
conformer is predicted to exist, but in most cases a few or even many conformers
significantly contribute to the equilibrium state. the conformers with an energy
higher than the lowest-energy conformer by about 2 kcal (8.4 kJ) or less cover over
95 % of the whole conformational population which is generally enough for the
reliable calculation of vibrational spectra. Next, for each fully optimized conformer
the vibrational frequencies and intensities are calculated and the total RoA specConformational population
Successful calculation
of experimental ROA spectrum
Absolute configuration
Conformation
Inter and intramolecular interactions
Fig. 4.2 Information obtainable from successful simulations of observed RoA spectra
68
Currently, RoA calculations may be performed using the gaussian ’09 [52]
(gaussian ’03 [53] was the first commercially available user-friendly software for
the dFt calculation of RoA spectra), dalton [54], or turbomole [55, 56] software
packages and also programs like CAdPAC [57] with which the first ab initio calculations of RoA were conducted. the calculation of the spectra using quantumchemical methods is an important aspect of the RoA technique and is fast becoming
the method of choice for obtaining detailed information about molecular structure
from experimental RoA spectra (Fig. 4.2).
Successful simulation of observed spectra can afford the complete solution of the
structure of the investigated compound, including its absolute configuration, conformation and, in the case of simultaneous existence of multiple conformers, also
their percentage populations at the selected temperature. Additionally, these calculations give us the opportunity to obtain knowledge about inter- and intra-molecular
interactions, especially between solvent molecules and the investigated compound.
our purpose is not here to give a detailed and full account of the theoretical calculations, which can be found in other sources, including new review articles [43, 44,
58–61] and books [62], but rather to present some examples that show the possibility
of application of dFt calculations in RoA spectroscopy of biological samples.
the calculation of vibrational RoA begins with building the structure that contains information specific to its stereochemical architecture. the next step is conducting the search over the conformational space to identify all of the lowest-energy
conformers of the investigated molecule. this conformational search can be done
in several ways. one of these is ‘manual’, the systematic specification of all angular degrees of freedom, including ring puckers and exploration of these degrees of
freedom by an appropriate program. this approach is good for small systems, especially if solvent effects are not significant and conformational flexibility is limited
like in the case of carenes, previously investigated by us (Scheme 1). Next, the set
of lowest-energy conformers is usually optimized at a higher level of dFt theory
using the basis set for the final RoA calculations. In the simplest case, only one
conformer is predicted to exist, but in most cases a few or even many conformers
significantly contribute to the equilibrium state. the conformers with an energy
higher than the lowest-energy conformer by about 2 kcal (8.4 kJ) or less cover over
95 % of the whole conformational population which is generally enough for the
reliable calculation of vibrational spectra. Next, for each fully optimized conformer
the vibrational frequencies and intensities are calculated and the total RoA specConformational population
Successful calculation
of experimental ROA spectrum
Absolute configuration
Conformation
Inter and intramolecular interactions
Fig. 4.2 Information obtainable from successful simulations of observed RoA spectra