Carbohydrate conformation is the characteristic 3-dimensional shape of a carbohydrate. Conformations of monosaccharide and oligosaccharide heavily influence their reactivity and recognition by other molecules, which are essential to mammals and other organisms.
Lectins are an example of sugar binding proteins that are highly specific to the conformation of a particular carbohydrate. Specific carbohydrates serve as cell surface recognition signals for antibodies, hormones and toxins.[1] Steric and stereoelectronic effects are common interactions that dictate the 3-dimensional shape of a carbohydrate.
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Pyranose and furanose forms can exist in different conformers and one can interconvert between the different conformations if an energy penalty is met. For the furanose system there are two possible conformers: Twist (T) and Envelope (E). In the pyranose system four conformers are possible: Chair (C), Boat (B), Skew (S), Half-Chair (H) or Envelope (E). In all cases there are four or more atoms that make up a plane. In order to define which atoms are above and below the plane one must orient the molecule so that the atoms are numbered clockwise when looking form the top. Atoms above the plane are prefixed as a superscript and atoms below the plane are suffixed as a subscript. If the ring oxygen is above or below the plane it must be prefixed or suffixed appropriately
Chair conformation of six membered rings have a dihedral angle of 60° between adjacent substituents thus making it the most stable conformer. Since there are two possible chair conformation steric and stereoelectronic effects such as the anomeric effect, 1,3 diaxial interactions, dipoles and intramolecular hydrogen bonding must be taken into consideration when looking at relative energies. Conformations with 1,3 diaxial interactions are usually disfavored due to steric congestion and can shift equilibrium to the other chair form (example: 1C4 to 4C1). The size of the substituents greatly affects this equilibrium. However, intramolecular hydrogen bonding can be an example of a stabilizing 1,3 diaxial interaction. Dipoles also play a role in conformer stability, aligned dipoles lead to an increase in energy while opposed dipoles lead to a lowering of energy hence a stabilizing effect, this can be complicated by solvent effects. Polar solvents tend to stabilize aligned dipoles. All interaction must be taken into account when determining a preferred conformation
Conformations of five membered rings are limited to two, envelope and twist. The envelope conformation has four atoms in a plane while the twist form only has three. In the envelope form two different scenarios can be envisioned; one where the ring oxygen is in the four atom plane and one where it is puckered above or below the plane. When the ring oxygen is not in the plane the substituents eclipse and when it is in the plane torsional strain is relieved. Conformational analysis for the twist form is similar thus leading to the two forms being very close in energy.
Anomers are diastereoisomers of glycosides, hemiacetals or related cyclic forms of sugars, or related molecules differing in configuration only at C-1. When the stereochemistry of the first carbon matches the stereochemistry of the last stereogenic center the sugar is the α-anomer when they are opposite the sugar is the β-anomer.
Anomers can be interconverted through a process known as mutarotation. The anomeric effect more accurately called the endo-anomeric effect is the propensity for heteroatoms at C-1 to be oriented axially. This is counter intuitive as one would expect the equatorially anomer to be the thermodynamic product. This effect has been rationalized through dipole-dipole repulsion and n-σ* arguments.
The reverse anomeric effect, proposed in 1965 by R. U. Lemieux, is the tendency for electropositive groups at the anomeric position to be oriented equatorially.[2] Original publication reported this phenomenon with N-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4-methylpyridinium bromide. However, further studies have shown the effect to be a solvation and steric issue. It is accepted that there is no generalized reverse anomeric effect.
Rotation around the C-5/C-6 bond is described by the angle ω. Three possible staggered conformations possible; gauche-trans (gt), gauche-gauche (gg), trans-gauche(tg). The name indicates the interaction between O-5 and OH-6 first followed by the interaction between OH-6 and C-4
In addition to the factors affecting monosaccaride residues, conformational analysis of oligosaccharides and polysaccharides requires consideration additional factors.
Exo-anomeric effect is similar to the endo-anomeric effect. The difference being that the lone pair being donated is coming from the substituent at C-1. However, since the substituent can be either axial or equatorial there are two types of exo-anomeric effects, one from axial glycosides and one from equatorial glycosides as long as the donating orbital is anti-periplanar to the accepting orbital.[3]
Three angles are described by φ, ψ and ω (in the case of glycosidic linkages via O-6). Steric considerations and anomeric effects need to be taken into consideration when looking at preferred angles.
In solution, reducing monosaccharides exist in equilibrium between their acyclic and cyclic forms with less than 1% in the acyclic form. The open chain form can close to give the pyranose and furanose with both the α and β anomers present for each. The equilibrium population of conformers depends on their relative energies which can be determined to a rough approximation using steric and stereoelectronic arguments. It has been shown that cations in solution can shift the equilibrium.
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