Biological Chemistry: Isomerism and Functional Groups Study Notes

Introduction to Isomerism

• Definition: Isomerism is a situation where compounds possessing the same molecular formula can be represented by different structures.
• Characteristics:
  • It is common to encounter compounds with the same molecular formula but different physical and chemical properties.
  • Differences in properties may be slight or very remarkable.
  • The reason for these differences is attributed to how constituent atoms are linked to each other or how they are arranged in three-dimensional (3D) space.

Classification of Isomerism

• Primary Types: There are two primary categories, each with further subtypes.
  • Structural (Constitutional) Isomerism: Atoms and functional groups are linked in different ways.
  • Stereoisomerism: Isomers differ in the spatial arrangement of atoms in 3D space.

Subtypes of Isomerism

• Structural Isomerism:
  • Chain Isomerism: Differences in the carbon skeleton (straight vs. branched).
  • Positional Isomerism: Differences in the position of functional groups/substituents.
  • Functional Isomerism: Same formula, different functional groups.
  • Metamerism: Arising from unequal distribution of carbon atoms on either side of a functional group.
  • Tautomerism: Rapid interconversion involving proton and electron shifts.
  • Ring-chain Isomerism: Compounds with the same formula that can exist as an open chain or a ring.
• Stereoisomerism:
  • Geometric Isomerism: Differences in spatial arrangement about a double bond ($C=C$) or ring.
  • Optical Isomerism: Isomers that are non-superimposable mirror images of each other.

Structural (Constitutional) Isomerism

• Definition: The functional groups and atoms are linked in different ways. These isomers are assigned different IUPAC names because they may contain different functional groups.

Chain Isomerism

• Also known as skeletal isomerism.
• The components display differences in how atoms are arranged as straight chains or branched compounds.
• Commonly differs in the branching of carbon.
• Example: $C_5H_{12}$:
  • Pentane: $CH_3CH_2CH_2CH_2CH_3$ (straight chain).
  • Isopentane (2-Methylbutane): $CH_3CH(CH_3)CH_2CH_3$ (branched).
  • Neopentane (2,2-Dimethylpropane): $CH_3C(CH_3)_2CH_3$ (higher degree of branching).

Positional Isomerism

• The positions of functional groups or substituent atoms vary within the same carbon chain.
• Example: $C_3H_7Cl$:
  • The chlorine atom can be attached to different carbon atoms (e.g., 1-chloropropane vs. 2-chloropropane).

Functional Isomerism

• Also known as functional group isomerism.
• Compounds have the same chemical formula but different functional groups attached to them.
• Example: $C_3H_6O$:
  • Can represent different functional classes like aldehydes or ketones.

Tautomerism

• Refers to isomers that differ only in the position of protons and electrons.
• Tautomers typically exist together in equilibrium and easily interchange via an intramolecular proton transfer.
• Keto-enol Tautomerism: An important biological and chemical example involving the shift between a ketone/aldehyde and an alcohol (enol).

Stereoisomerism

• Compounds have the same chemical formula but different orientations of atoms in 3D space.
• These compounds are referred to as stereoisomers.

Geometric Isomerism (Cis-Trans Isomerism)

• Cause: Hindered rotation about a double bond system ($C=C$) or a ring system.
• The presence of the double bond introduces remarkable rigidity.
• Example: But-2-ene:
  • Cis-but-2-ene: Similar groups are on the same side of the double bond.
  • Trans-but-2-ene: Similar groups are on opposite sides.
• Properties:
  • It is impossible to convert the cis form to trans simply by rotating the doubly bonded carbons.
  • They are distinct compounds with different physical properties (stability, boiling point, and melting point).
  • For an alkene to exhibit this, the groups attached to the doubly bonded carbon atoms must be different.

Case Study: Butanedioic Acid

• Maleic Acid (Cis-butanedioic acid):
  • The $COOH$ groups are close together.
  • Can interact to eliminate water and form a ring anhydride at approximately $150\,^{\circ}C$.
  • The anhydride can be reconverted to the cis-isomer in the presence of water.
• Fumaric Acid (Trans-butanedioic acid):
  • $COOH$ groups are on opposite sides.
  • Cannot form a ring anhydride.
• Biological Significance: In living cells, the enzyme fumarase catalyzes the hydration of fumaric acid. Fumarase is stereospecific, meaning it works on fumaric acid but not the cis-isomer (maleic acid).

Optical Isomerism and Chirality

• Definition: Compounds with similar bonds but different spatial arrangements that form non-superimposable mirror images.
• Optical Activity: The ability to interact with and rotate plane-polarized light.
  • Dextro-rotatory (+): Rotates light to the right.
  • Leavo-rotatory (-): Rotates light to the left.
• Chiral Centers: A tetrahedral carbon atom bonded to four different groups. This is also called an asymmetric carbon, chiral center, or stereogenic center.
• Enantiomers: Optical isomers related as an object to its mirror image.
• Number of Isomers: Calculated using the formula $2^n$, where $n$ is the number of chiral centers.
  • Example: Tartaric acid.

Racemic Mixtures and Resolution

• Racemic Mixture: An equimolar mixture of two optically active isomers (one dextro, one leavo).
• Net Activity: They are optically inactive because the rotations cancel out.
• Example: $(+)$ lactic acid and $(-)$ lactic acid mixed equally.
• Resolution: The process of separating a racemic mixture into its constituent enantiomers.
• Biological Separation:
  • Penicillium glaucum can utilize $(+)$ lactic acid but not $(-)$ lactic acid.
  • Affinity chromatography can be used.
  • Combining a racemic mixture with another optically active compound for separation.

Properties of Enantiomers

• Physical Properties: Identical melting points, boiling points, densities, and solubilities in common solvents. They differ only in the direction they rotate plane-polarized light.
• Crystals: They form crystals of the same type, but one is the mirror image of the other (enantiomorphs).
• Chemical Properties: Identical when reacting with non-optically active reagents.
• Physiochemical and Biological Differences:
  • Adrenaline: $(-)$ adrenaline is more active in contracting blood capillaries than $(+)$ adrenaline.
  • Nicotine: $(-)$ nicotine is more poisonous than $(+)$ nicotine.

Polarimetry

• Definition: The process of producing plane-polarized light and determining the extent of rotation by an optically active compound.
• Components of a Polarimeter:
  • Light Source: Usually a sodium lamp producing yellow light at a wavelength of $589.3\,nm$ (the sodium D-line).
  • Polarizer: A polaroid or Nicol prism that produces plane-polarized light.
  • Sample Tube: Holds the solution under investigation.
  • Analyzer: A second polaroid or Nicol prism that rotates to measure the angle.
• Factors Affecting Rotation:
  • Nature of the molecules, concentration, temperature, wavelength of light, and the type of solvent used.

Specific Rotation Formula

Specific rotation is defined as the rotation given by $1.0\,g$ of sample in $1.0\,ml$ of solution in a tube with a path length of $1.0\,dm$.

$\left[\alpha\right]^{25}_D = \frac{\theta}{l \times c}$

Where:

• $\left[\alpha\right]^{25}_D$ = Specific rotation at $25\,^{\circ}C$ using the sodium D-line.
• $\theta$ = Observed rotation in degrees (positive or negative).
• $l$ = Length of the polarimeter tube in decimeters ($1\,dm = 10\,cm$).
• $c$ = Concentration of the sample in $g/ml$.

Functional Groups

• Importance: Functional groups are the primary determinants of the physical and chemical properties of organic molecules, more so than the branching or chain structure.
• Common Types:
  • Alcohols (Hydroxyl): $-OH$
  • Carboxylic Acid: $-COOH$
  • Alkanes: $-C-H$ or $-C-C-$
  • Alkenes: $-C=C-$
  • Alkynes: $-C\equiv C-$
  • Esters: $-COOR$
  • Acid Chlorides: $-COCl$
  • Acid Amides: $-CONH_2$
  • Acid Anhydrides: $-(CO)_2O$
  • Phenol: $C_6H_5OH$
  • Nitriles: $-C\equiv N$ or $-CN$
  • Carbonyls: Aldehydes and Ketones.
• Homologous Series: Groups of compounds represented by general formulas:
  • Alkanes: $C_nH_{2n+2}$
  • Alkenes: $C_nH_{2n}$
  • Alcohols: $C_nH_{2n+1}OH$

Hemiacetals, Hemiketals, Acetals, and Ketals

• Formation: Reversible reactions between alcohols and carbonyl compounds.
• Reactivity: Alcohols and carbonyls react to form compounds of biological importance (especially in carbohydrate chemistry).
• Aldehydes vs. Ketones: Aldehydes are generally more reactive toward nucleophiles than ketones.
  • Steric Factors: Ketones have two large R groups that hinder the attacking nucleophile.
  • Electronic Factors: Influence reactivity at the carbonyl carbon.

Reaction Process

1. Hemiacetal/Hemiketal Formation: One mole of aldehyde/ketone reacts with one mole of alcohol to form a hemiacetal or hemiketal.
   • Hemiacetal: Generally unstable except when part of carbohydrate structures.
2. Acetal/Ketal Formation: A second mole of alcohol reacts with the hemiacetal/hemiketal.
   • This is a condensation reaction because water ($H_2O$) is lost.

Hydrolysis

• Acetals and ketals can be broken down into the original aldehyde/ketone and two moles of alcohol.
• This process requires an acid catalyst or an enzyme.