Structure and Conformation of Carbohydrates
1.1
39
The effects on the size of 2 J C,C across both oxygen and carbon atoms have been investigated
experimentally and theoretically [401,402]. Across the anomeric oxygen, the magnitude of
2 J C,C depends on the size of the torsional angle much more than on the torsional angle
but also depends on the C–O–C bond angle [402], making its use more difficult.
Three-Bond Coupling The magnitude of the coupling constant between protons on adjacent
carbons, 3 J H,H , is related to the torsional angle between the protons [403] by the Karplus
equation [404]. Several groups have modified the original equation to encode the effects of the
orientations and electronegativities of electronegative substituents on the magnitude of 3 J H,H
but the equation of Haasnoot et al. [405], derived using 3 J H,H values in six-membered rings,
has seen the most use. The electronegativity values used with it have been modified and it has
been reparameterized [406,407] to be:
3 J H,H = 14.63 cos
2 (φ) − 0.78 cos (φ) +
i
λi
0.34 − 2.31 cos
2 [s i (φ) + 18.4 |λi|]
(4)
where is the torsional angle, 8 i are the modified electronegativities, and s i is the sign factor,
either +1 or −1, defined according to the sign of the torsional angle [406]. Altona et al. have
noted that use of this equation is limited to unstrained saturated systems but molecular orbital
calculations have suggested that bond angle variation along the coupling path also influence
the size of 3 J H,H [408,409,410,411]. This latter factor may make Eq. (4) less accurate when
extended to furanosides or acyclic systems.
3 J H,H values have been used extensively to evaluate which conformation is present. When
conformational mixtures are present, the coupling constants for contributing conformers can
be measured below the temperature of coalescence or estimated from the Haasnoot–Altona
equation, Eq. (4). The position of the equilibrium is then evaluated by using the weighted average of the values for the contributors. This technique has been employed by many
researchers [119,130,140,191,205,412], largely because it is accepted that the methods available for estimating values for contributors are reasonably accurate. It has been justified theoretically [413].
Karplus-type equations have been developed for many other systems of interest, most notably
H–C–O-H [242,243], H–C–O–C [387,414,415], H–C–C-C [197,387], and C–O–C–C [416,
417]. It should be noted that coupling to hydroxyl protons can be observed in water or
water/acetone or water/DMSO mixtures if the NMR tubes are rinsed in phosphate buffers
and the carbohydrate derivatives are thoroughly deionized [239,249]. If the magnitudes of
the coupling constants to carbon are determined on natural abundance material, considerable
amounts are required. Alternatively, 13 C labeled material can be used [416,417,418,419] and
starting materials with varieties of labels are available.
Long-Range Coupling Long range coupling constants ( 4 J H,H and 5 J H,H ) were examined
in the early literature on NMR of carbohydrates [420,421]. In saturated systems, they are
largest over a W coupling pathway (< 2 Hz) and thus have some potential to reveal conformational information. They can be obtained conveniently using gradient-enhanced, two-dimensional homonuclear correlation techniques [422]. Long-range CH couplings ( 4 J COCCH and
4 J CCCCH ) to enriched 13 C atoms have also proven useful for conformational studies [198].
1.1
39
The effects on the size of 2 J C,C across both oxygen and carbon atoms have been investigated
experimentally and theoretically [401,402]. Across the anomeric oxygen, the magnitude of
2 J C,C depends on the size of the torsional angle much more than on the torsional angle
but also depends on the C–O–C bond angle [402], making its use more difficult.
Three-Bond Coupling The magnitude of the coupling constant between protons on adjacent
carbons, 3 J H,H , is related to the torsional angle between the protons [403] by the Karplus
equation [404]. Several groups have modified the original equation to encode the effects of the
orientations and electronegativities of electronegative substituents on the magnitude of 3 J H,H
but the equation of Haasnoot et al. [405], derived using 3 J H,H values in six-membered rings,
has seen the most use. The electronegativity values used with it have been modified and it has
been reparameterized [406,407] to be:
3 J H,H = 14.63 cos
2 (φ) − 0.78 cos (φ) +
i
λi
0.34 − 2.31 cos
2 [s i (φ) + 18.4 |λi|]
(4)
where is the torsional angle, 8 i are the modified electronegativities, and s i is the sign factor,
either +1 or −1, defined according to the sign of the torsional angle [406]. Altona et al. have
noted that use of this equation is limited to unstrained saturated systems but molecular orbital
calculations have suggested that bond angle variation along the coupling path also influence
the size of 3 J H,H [408,409,410,411]. This latter factor may make Eq. (4) less accurate when
extended to furanosides or acyclic systems.
3 J H,H values have been used extensively to evaluate which conformation is present. When
conformational mixtures are present, the coupling constants for contributing conformers can
be measured below the temperature of coalescence or estimated from the Haasnoot–Altona
equation, Eq. (4). The position of the equilibrium is then evaluated by using the weighted average of the values for the contributors. This technique has been employed by many
researchers [119,130,140,191,205,412], largely because it is accepted that the methods available for estimating values for contributors are reasonably accurate. It has been justified theoretically [413].
Karplus-type equations have been developed for many other systems of interest, most notably
H–C–O-H [242,243], H–C–O–C [387,414,415], H–C–C-C [197,387], and C–O–C–C [416,
417]. It should be noted that coupling to hydroxyl protons can be observed in water or
water/acetone or water/DMSO mixtures if the NMR tubes are rinsed in phosphate buffers
and the carbohydrate derivatives are thoroughly deionized [239,249]. If the magnitudes of
the coupling constants to carbon are determined on natural abundance material, considerable
amounts are required. Alternatively, 13 C labeled material can be used [416,417,418,419] and
starting materials with varieties of labels are available.
Long-Range Coupling Long range coupling constants ( 4 J H,H and 5 J H,H ) were examined
in the early literature on NMR of carbohydrates [420,421]. In saturated systems, they are
largest over a W coupling pathway (< 2 Hz) and thus have some potential to reveal conformational information. They can be obtained conveniently using gradient-enhanced, two-dimensional homonuclear correlation techniques [422]. Long-range CH couplings ( 4 J COCCH and
4 J CCCCH ) to enriched 13 C atoms have also proven useful for conformational studies [198].