Glucose

Glucose (Glc), a monosaccharide (or simple sugar) also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate. Glucose is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes (bacteria and archaea) and eukaryotes (animals, plants, fungi, and protists). The name glucose comes from the Greek word glykys (), meaning "sweet", plus the suffix "-ose" which denotes a sugar. Two stereoisomers of the aldohexose sugars are known as glucose, only one of which (Dglucose) is biologically active. This form (D-glucose) is often referred to as dextrose monohydrate, or, especially in the food industry, simply dextrose (from dextrorotatory glucose[1]). This article deals with the D-form of glucose. The mirror-image of the

molecule, L-glucose, cannot be metabolized by cells in the biochemical process known as glycolysis.

Structure

Glucose (C6H12O6) contains six carbon atoms, one of which is part of an aldehyde group, and is therefore referred to as an aldohexose. In solution, the glucose molecule can exist in an open-chain (acyclic) form and a ring (cyclic) form (in equilibrium). The cyclic form is the result of a covalent bond between the aldehyde C atom and the C-5 hydroxyl group to form a six-membered cyclic hemiacetal. At pH 7 the cyclic form is predominant. In the solid phase, glucose assumes the cyclic form. Because the ring contains five carbon atoms and one oxygen atom, which resembles the structure of pyran, the cyclic form of glucose is also referred to as glucopyranose. In this ring, each carbon is linked to a hydroxyl side group with the exception of the fifth atom, which links to a sixth carbon atom outside the ring, forming a CH2OH group. Glucose is commonly available in the

form of a white substance or as a solid crystal. It can also be dissolved in water as an aqueous solution.

Isomers
Aldohexose sugars have 4 chiral centers giving 24 = 16 stereoisomers. These are split into two groups, L and D, with 8 sugars in each. Glucose is one of these sugars, and L-glucose and D-glucose are two of the stereoisomers. Only 7 of these are found in living organisms, of which D-glucose (Glu), D-galactose (Gal), and D-mannose (Man) are the most important. These eight isomers (including glucose itself) are related as diastereoisomers and belong to the D series. An additional asymmetric center at C-1 (called the anomeric carbon atom) is created when glucose cyclizes and two ring structures called anomers are formed as -glucose and -glucose. These anomers differ structurally by the relative positioning of the hydroxyl group linked to C-1, and the group at C-6 which is termed the reference carbon. When D-glucose is drawn as a Haworth projection or in the standard chain conformation, the designation means that the hydroxyl group attached to C-1 is positioned trans to the -CH2OH group at C-5, while means it is cis. An inaccurate but superficially attractive alternative method of distinguishing from is by observing whether the C-1 hydroxyl is below or above the plane of the ring; this may fail if the glucose ring is drawn upside down or in an alternative chair conformation. The and forms interconvert over a timescale of hours in aqueous solution, to a final stable ratio of : 36:64, in a process called mutarotation. The ratio would be : 11:89 if it weren't for the influence of the anomeric effect.

Chair conformation
Due to the inherent tendency of the sp hybrid orbitals (and therefore the carbonhydrogen bonds) on tetravalent carbons to form bond angles of 109.5 , cyclohexane does not form a planar hexagonal arrangement with interior bond angles of 120 . The chair conformation is a term used for the most stable chemical conformation of a six membered single bonded carbon ring like cyclohexane. Derek Barton and Odd Hassel both shared the Nobel Prize for work on the conformations of cyclohexane and various other molecules. In the lowest-energy chair conformation, 6 of the 12 hydrogens are in axial positions (colored red)their C-H bonds are parallel to each other and appear to stick up and down from the ring structure, the other 6 are in equatorial positions (colored blue)they are splayed out around the perimeter of the ring. Note that in addition, one hydrogen at each position is "up" relative to the other being "down" at that position.

In stepping round the ring, it can be seen that the up-axial positions (H1 in the left-hand structure) alternate with up-equatorial positions (H2). Further, axial positions alternate sides around the ring (H1 axial-up vs H4 axial-down) and likewise the equatorial positions

(H2 equatorial-up vs H3 equatorial-down). For two substituents attached to adjacent carbons on the ring as trans-1,2-cyclohexane, the substituents must either both be axial or both be equatorial to remain on opposite sides of the ring. Similarly, for cis-1,2cyclohexane, one substituent must be axial and the other equatorial or vice versa. Various other substitution patterns are possible, each following the same patterns of relative geometric positioning. In a process known as ring flipping or chair-flipping, the conformation of the ring changes, leading to the axial hydrogens becoming equatorial and the equatorial hydrogens becoming axial. However, the relative direction of the hydrogens to the ring remains the same: an "up" axial hydrogen, when flipped, remains an "up" equatorial hydrogen. The two chair conformations may differ in stability depending upon the identity of the functional groups. Generally, substituents are most stable when in equatorial positions, as in this case there are no 1,3-diaxial interaction between the axial substituent group and any other axial groups on the ring. For example, if there is a methyl group on carbon 1 in an axial position, it will interact with the axial hydrogens on carbon 3 and carbon 5. However, when there are electronegative heteroatoms involved, the opposite may be observed; this is called the anomeric effect. Cyclohexane will be found in the chair formation 99.99% at 25 C (i.e., 99.99% of all molecules in a solution sample will be in the chair formation). The preference of a substituent towards the equatorial conformation is measured in terms of its A value, which is the Gibbs free energy difference between the equatorial and the axial conformers. A positive A value indicates preference towards the equatorial position.

The magnitude of the A values ranges from nearly zero for very small substituents such as deuterium, to about 5 kcal/mol for very bulky substituents such as the tert-butyl group.

Boat conformation
In addition to the chair conformation (1) with D3d symmetry cyclohexane can also exist in the half-chair or envelope (2), twist or twist-boat (3,5) with D2 symmetry and boat (4) conformers. Only the twist form is isolable as - like the chair form - it represents an energy minima. The boat conformation does not suffer from angle strain but has a higher energy than the chair form due to steric strain resulting from the two axial 1,4-hydrogen atoms, in what is called the flagpole interaction. The torsional strain in the boat conformation has a maximum value because two of the carbon bonds are eclipsed. Compare this to the chair with all bonds staggered and complete absence of torsional strain and the twist-boat with 4 out 6 bonds partially eclipsed. In the half-chair conformation 4 carbon atoms are located on a plane in which two bonds are fully eclipsed. The boat and envelope forms are transition states between the twist forms and the twist and chair forms respectively, and are impossible to isolate. The twist-boat conformation is 5.5 kcal/mol (23 kJ/mol) less stable than the chair conformation. The energies of the two transition states are 6.6 kcal/mol (28 kJ/mol) (boat) and 10.8 kcal/mol (45 kJ/mol) (half chair) higher than that of the chair.4 The ring flipping process can now be described with more precision as taking place through a twist-boat conformation and through two half-chair transition states.

The difference in energy between the chair and the twist-boat conformation of cyclohexane can be measured indirectly by taking the difference in activation energy for the conversion of the chair to the twist-boat conformation and that of the reverse isomerization. The concentration of the twist-boat conformation at room temperature is very low (less than 0.1%) but at 1073 kelvins this concentration can reach 30%. The reverse reaction is measured by IR spectroscopy after rapidly cooling cyclohexane from 1073 K to 40 K, freezing in the large concentration of twist-boat conformation.

[6.6]Chiralane is a point group T molecule wholly composed of identical fused twist-boat cyclohexanes. Another view.

Cyclohexane derivatives
Substituents found on cyclohexane adopt cis and trans formations and cannot be easily switched by simple single sigma bond rotation as with linear molecules. Cis formation means that both substituents are found on the upper side of the 2 substituent placements on the carbon, while trans would mean that they were on opposing sides. Despite the fact that carbons on cyclohexane are linked by a single bond, the ring remains rigid, in that switching from cis to trans would require breaking the ring. The nomenclature for cis is dubbed (Z) while the name for trans is (E) to be placed in front of the IUPAC name. For di-substituted cyclohexane rings (i.e. two groups on the ring), the relative orientation of the two substituents affect the energy of the possible conformations. For 1,2- and 1,4di-substituted cyclohexane, a cis configuration leads to one axial and one equatorial group. This configuration can undergo chair flipping. For 1,2- and 1,4-di-substituted cyclohexane, a trans configuration leads to either both groups axial or both equatorial. In this case, the diaxial conformation is effectively prevented by its high steric strain (four gauche interactions more than the diequatorial). For 1,3-di-substituted cyclohexanes, the cis form is diequatorial and the flipped conformation suffers additional steric interaction between the two axial groups. Trans-1,3-di-substituted cyclohexanes are like cis-1,2- and cis-1,4- and can flip between the two equivalent axial/equatorial forms.

Derivatives of cyclohexane do exist that have a more stable twist-boat conformation. An example is 1,2,4,5-tetrathiane, an organosulfur compound with 4 methylene groups replaced by a sulfide group thus removing unfavorable 1,3-diaxial interactions. In the tetramethyl analogue 3,3,6,6-tetramethyl-1,2,4,5-tetrathiane the twist-boat conformation actually dominates. Also in cyclohexane-1,4-dione with the steric 1,4-hydrogen interaction removed, the actual stable conformation is the twist-boat