173
calculations, a protocol has been established where the spectrum is first calculated
(by means of semi-empirical or ab initio methods) for a given configuration (or a
number of configurations, if several chiral centres exist) and then, band by band,
compared with an experimental spectrum. An agreement of the signs between the
calculated and measured spectrum is treated as an indication that the configuration
has been assigned correctly.
this method is very useful, especially in cases when a crystal suitable for X-ray
measurements cannot be obtained, but theoretical prediction of a Cd spectrum may
not be accurate for a number of reasons, which would affect the assignment. First,
all low-energy conformations should be accounted for with correct weights, since
the Cd spectrum is very sensitive to molecular conformation. Second, some of the
bands (especially those corresponding to Rydberg transitions) may change signs in
different solvents, an effect which is difficult to reproduce in silico. third, a calculation of an electronic Cd even for an isolated rigid molecule is a challenging task in
itself, especially when the size of a molecule precludes the use of many-configurational methods, and the only ab initio method which can be used is non-hierarchical
dFt. An interesting example of the use of electronic Cd for determination of the
absolute configuration of a series of compounds with a pharmaceutial potential is
the work carried out for trans-diastereomers of the natural cytokine modulator cytoxazone [84], which also illustrates some of the difficulties associated with the
method (eg. that the assignment of the absolute configuration is erroneous when a
popular B3LYP functional with a small basis set is used, and that it is essential to account for the presence of a solvent, even if only by means of polarizable continuum
model with no explicit solvent molecules).
In principle, the danger of erroneous assigment of the absolute configuration
is smaller in the case of vibrational chirooptical spectroscopic methods (vCd or
RoA), where there are much more signals than in the electronic spectrum and it is
enough if the sign of a majority of them is correctly predicted. however, the use
of electronic Cd is still more widespread, since the instruments are less expensive
and it is possible to use relatively small amounts of the optically pure enantiomer to
obtain the spectrum, which is not the case for example of RoA.
the use of electronic Cd for determination of absolute configuration is extensively reviewed in Refs. 85 and 86. For the comparison of advantages and disadvantages of using vibrational chiroptical methods for the absolute configuration
assignment the reader is referred to Refs. 87 and 88.
6.6 Chirality of Excited States—Circularly Polarized
Luminscence
As explained above, ECd is a differential absorption of left- and right circularly
polarized light by a chiral molecule. An analogous phenomenon, a differential emission of left- and right circularly polarized light, known as circularly polarized luminscence, CPL, can be observed in fluorescence and phosphorescence spectra. While
6 Electronic Circular dichroism Spectroscopy in Structural Analysis …
calculations, a protocol has been established where the spectrum is first calculated
(by means of semi-empirical or ab initio methods) for a given configuration (or a
number of configurations, if several chiral centres exist) and then, band by band,
compared with an experimental spectrum. An agreement of the signs between the
calculated and measured spectrum is treated as an indication that the configuration
has been assigned correctly.
this method is very useful, especially in cases when a crystal suitable for X-ray
measurements cannot be obtained, but theoretical prediction of a Cd spectrum may
not be accurate for a number of reasons, which would affect the assignment. First,
all low-energy conformations should be accounted for with correct weights, since
the Cd spectrum is very sensitive to molecular conformation. Second, some of the
bands (especially those corresponding to Rydberg transitions) may change signs in
different solvents, an effect which is difficult to reproduce in silico. third, a calculation of an electronic Cd even for an isolated rigid molecule is a challenging task in
itself, especially when the size of a molecule precludes the use of many-configurational methods, and the only ab initio method which can be used is non-hierarchical
dFt. An interesting example of the use of electronic Cd for determination of the
absolute configuration of a series of compounds with a pharmaceutial potential is
the work carried out for trans-diastereomers of the natural cytokine modulator cytoxazone [84], which also illustrates some of the difficulties associated with the
method (eg. that the assignment of the absolute configuration is erroneous when a
popular B3LYP functional with a small basis set is used, and that it is essential to account for the presence of a solvent, even if only by means of polarizable continuum
model with no explicit solvent molecules).
In principle, the danger of erroneous assigment of the absolute configuration
is smaller in the case of vibrational chirooptical spectroscopic methods (vCd or
RoA), where there are much more signals than in the electronic spectrum and it is
enough if the sign of a majority of them is correctly predicted. however, the use
of electronic Cd is still more widespread, since the instruments are less expensive
and it is possible to use relatively small amounts of the optically pure enantiomer to
obtain the spectrum, which is not the case for example of RoA.
the use of electronic Cd for determination of absolute configuration is extensively reviewed in Refs. 85 and 86. For the comparison of advantages and disadvantages of using vibrational chiroptical methods for the absolute configuration
assignment the reader is referred to Refs. 87 and 88.
6.6 Chirality of Excited States—Circularly Polarized
Luminscence
As explained above, ECd is a differential absorption of left- and right circularly
polarized light by a chiral molecule. An analogous phenomenon, a differential emission of left- and right circularly polarized light, known as circularly polarized luminscence, CPL, can be observed in fluorescence and phosphorescence spectra. While
6 Electronic Circular dichroism Spectroscopy in Structural Analysis …