5+6. Biomolecules shapes and sizes

There are 3 key factors that determine molecular structure:

1. Bond length

2. Bond angle

3. Bond rotation

Bond length

Atomic bond length is the the distance between the nuclei of 2 covalently linked atoms. It is determined by:

1. The atomic radii of the atoms joined by the bond, i.e., the chemical identity of the atoms

2. The type of covalent bond, i.e., single, double, or triple

The length of a single covalent bond is equivalent to the sum of the atomic radii of the 2 bonded atoms

Double and triple bonds have shorter lengths: the increased electron density leads to a greater attractive force on the nuclei of the bonded atoms

Bond rotation

Bonded atoms adopt precise configurations dictated by repulsion of valence electron pairs. Groups of bonded atoms can adopt different orientations relative to each other, as a consequence of bond rotation

Overlapping sp³ hybrid orbitals on adjacent carbon atoms form a cylindrical symmetrical $\sigma$ bond. Because rotation about the bond does not affect the overlap of the bonding orbitals, there is no electronic energy barrier to rotation

Bond rotation cannot occur in double or triple bonds as this would disrupt the p orbital overlap, breaking the $\pi$ bond which is highly unfavourable energetically

Bond angles

Bond angles describes the 3D arrangement of 3 covalently bonded atoms. Atomic bond angles in molecules vary from 60^o-180⁰ depending on the chemical identity of the bonded atoms.

Different groups of atoms arrange themselves in specific orientations, a property that can be described in one of two ways:

1. Valence shell electron pair repulsion (VSEPR) theory

2. The hybridisation of atomic orbitals

VSEPR theory

This theory predicts the geometry of molecules based on minimizing the electrostatic repulsion of a molecules’s valence electrons around a central atom

1. The geometry adopted depends on the number of valence electron pairs

2. Bonding and non-bonding pairs are involved in repulsion

However, VSEPR theory makes the assumption that electrons exist as discrete objects.

Orbital hydridisation

Atomic orbitals do not exhibit the geometries predicted by VSEPR

The arrangement of valence electrons as predicted by VSEPR is due to the hybridisation of atomic orbitals which allows the electrons to adopt new geometries

Electron geometry Vs Molecular geometry

When looking at electron geometry, the presence of both bonding pairs and lone pairs are considered, whereas when looking at molecular geometry lone pairs are excluded in deciding the shape of the molecule (however their repulsion is still taken into account for estimating bond angles)

AXE method

The AXE method is used to determine molecular geometry

AX_nE_m - A: central atom, X: ligand(s) attached to A, E: lone pair(s) on A

Steric number - number of atoms (X) bonded to the central atom (A) and number of lone pairs (E) of valence electrons on A

Isomerism

The existence of different forms of molecules with the same chemical composition but with a different structure or configuration and generally with different physical and chemical properties

Constitutional isomers

Molecules that have the same molecular formula but different connectivities. There are 3 types:

1. Chain isomerism - arise as a consequence of chain branching

   

2. Regioisomerism - arise due to re-positioning of functional groups

   

3. Functional group isomerism - isomers containing different functional groups

   

Stereoisomers

Molecules that have the same molecular formula and sequence of bonded atoms (constitution), but differ only in the three-dimensional orientations of their atoms in space

Stereocentre: An atom with 3 or more attachments, where swapping 2 of these attachments leads to another stereoisomer

Enantiomers - 2 stereoisomers that are related to each other by a reflection. They are mirror images of each other and are non-superimposable. These have the same physical and chemical properties in non-chiral environments (except in the way they rotate plane-polarised light). However in chiral environments (such as biological systems) they react differently.

Diastereomers - Stereoisomers that have different configurations at one or more (but not all) stereocentres. (Not mirror images like enantiomers). This also includes cis/trans isomers

Assigning stereocentres - R/S nomenclature

1. Assign priority of the 4 groups using the Cahn-Ingold-Prelog convention (highest priority = greatest atomic number)

2. Rotate the molecule so that the lowest priority group points away from you

3. If the direction from highest to lowest priority group is clockwise (steer right) then it is the R enantiomer, if the direction from the highest to lowest priority group is anticlockwise (steer left) then it is the S enantiomer

Fisher projection

If the lowest priority group sits on the horizontal bond;

• and the direction from highest priority to lowest priority group is clockwise then it is the S enantiomer

• and the direction from highest priority to lowest priority group is anticlockwise then it is the R enantiomer

If the lowest priority group sits on the vertical bond;

• and the direction from highest to lowest priority group is clockwise then it is the R enantiomer

• and the direction from highest priority to lowest priority group is anticlockwise then is is the S enantiomer

D/L nomenclature

This nomenclature is mainly used for biological molecules and is based on the smallest 3-carbon monosaccharide, glyceraldehyde

Monosaccharides:

Aldehyde is drawn at the top, then the chiral carbon at the bottom is used to determine which enantiomer it is.

If the -OH at this carbon is on the right, it is the D enantiomer.

If the -OH is on the left, it is the L enantiomer.

Most natural monosaccharides are D-monosaccharides

Amino acids:

-COOH group is drawn at the top so that the -NH₂ group and H atom sit on the horizontal bond

If the -NH₂ group is on the left then it is the L enantiomer

If the -NH₂ group is on the right then it is the D enantiomer

All natural amino acids are L-amino acids

Cis/trans isomers

Cis/trans isomers (or geometric isomers) are stereoisomers describing the relative orientation of functional groups within a molecule. Geometric isomers occur in cases where there is restricted rotation about a bond. They usually have different physical and chemical properties

The cis isomer has the identical groups on the same side of the double bond, while the trans isomer has the identical groups on the opposite sides.

E/Z nomenclature can also be used if the carbons involved in the double bond are not attached to identical groups. The Z isomer has the highest priority groups on the same side of the double bond while the E isomer has the highest priority groups on opposite side of the double bond. Priority is assigned using the Cahn-Ingold-Prelog convention.

Conformers and rotamers

Conformational isomerism: a form of stereoisomerism in which isomers can be interconverted by rotations about formally single bonds

Rotamers: Set of conformers that arise from restricted rotation around a single bond, corresponding to local energy minima

Cycloalkanes: strain and conformational isomers

Cyclopropane - highly strained, sp³ carbons with bond angles of 60^o. No conformational isomers

Cyclobutane: Also strained (bond angles 90^o). Butterfly conformers preferred over fully eclipsed planar.

Cyclopentane: More stable (bond angles 108^o). 2 buckled isomers, planar is too strained due to eclipsed bonds

Cyclohexane: all conformers allow ~ 109.5^o bond angles. Boat is less stable due to repulsion between eclipsed bonds. The chair conformation can flip, exchanging axial and equatorial positions