EM Lectures 1-2 Dell 2025

INTRO. Professor Anne Dell

  • Room 101b, SEC Building

  • Email: a.dell@imperial.ac.uk

  • Course: First Year Enzymes & Metabolism Organic Chemistry Lectures 1-2

Objectives of the Organic Chemistry Topic

  • Build upon Biological Chemistry knowledge.

  • Equip with understanding of chemical properties of biochemically important functional groups.

  • Apply knowledge of chemical reactions in a biochemical context.

  • Address gaps in understanding of:

    • Substitution reactions

    • Elimination reactions

    • Addition reactions

Lecture Outcomes

By the end of the 4 organic chemistry lectures, students should:

  • Understand reactivity of biologically important functional groups containing N, O, and S.

  • Understand hybridization in explaining shapes and reactivities.

  • Provide examples of:

    • Biochemically important nucleophiles, electrophiles, acids, bases, and leaving groups.

  • Grasp pH dependence of charge and reactivity.

    • Understand that H-bonding affects reactivity of N and O functional groups, but not S.

  • Correctly use curly arrows to depict chemical mechanisms.

  • Understand mechanisms of:

    1. Substitution at saturated carbon

    2. Elimination to form C=C

    3. Addition to C=C

    4. Addition at carbonyl carbon

    5. Substitution at carbonyl carbon

Topic Structure (Week 1)

  • Four lectures covering:

    • Overview of organic chemistry principles

    • Biochemically relevant functional groups – structure/reactivity

    • Organic reaction mechanisms 1

    • Organic reaction mechanisms 2

Peer-Assisted Learning (Week 2)

  • A 3-hour session in practical labs for group problem-solving.

  • Instructor support by Professor Dell and Dr. Michael Baker for questions.

Teams Q&A Session (End of Week 2)

  • Address outstanding questions.

  • Send questions in advance via email or ask during the session.

Recommended Textbooks

  • Crowe & Bradshaw "Chemistry for the Biosciences"

  • Any textbook titled "Organic Chemistry" recommended.

  • Preferred: John McMurry for biological examples.

Lecture Preparation

  • Prepare with writing materials/devices.

Actual lecture

for coenzyme A most important group is HS as it bonds with acetyl to form acetyl coA

Key Terms

Heteroatom=Atom other than C or H found in organic molecules.

Functional group= The part of the molecule with the heteroatom, important for reactivity, the chemical reactivity of biological molecules is associated with their functional groups. e.g thiogroup in coA

Nucleophile = Electronegative functional group with an electron pair that can be used for covalent bond formation with an electrophilic group that has an empty orbital.

Every base is a nucleophile so we can say in contest that base is used to form cov bond with electrophile. Nucleophile is marketing a new compound

Some good nucleophiles can be bad bases. Base is just 1 reaction → accepting the H+.

THink about what makes a good nucleophile or base.

Electrophile = Electron-deficient functional group that can accept a pair of electrons that can be used for covalent bond.

Curly arrows show movement of electrons to empty or potentially empty orbital

Crystallography is a way of crystallising proteins to see their structure. we now can crystalline them to see what is changing in actives site

Active site is not in solution, it is a few specific interactions

Polarized bonds = Uneven electron sharing between 2 joined atoms creates a dipole moment. more polarized - easier to distort the cloud,

if you remove the valence electrons, the shell electrons become polarised (Sulfur is more reactive than C for this reason even thought their electronegativity are very similar )

Polarizability = a measure of Ease of distortion of electron distribution.

Electronegativity = measure of strength of electron attraction by an atom.

Leaving group = part of the molecule that takes bonding electrons when a bond is broken during a reaction.

resonance and func groups

Resonance: Multiple arrangements of double bonds for electron distribution.When more than one arrangement of double bonds needs to be drawn in order to show the electronic distribution; we say the molecule exists as a “resonance hybrid”. Examples include aromatic rings such as indole (found in the sidechain of tryptophan).

Aromatic functional group: Planar rings with delocalized pi clouds that fit Hückel Rule (4n+2), where n is an integer.

  • Hückel Rule examples provided with integers for pi electrons.

Self-Check

  • Count pi electrons for sidechains of tyrosine, tryptophan, and histidine.

hybridization (focus on shape in this module)

hybridization= Mixing of atomic orbitals to make molecular orbitals. the shapes/orientation of hybrid orbitals are optimised for bond formation.

Main types relevant to biology: sp3 and sp2.

Hybridization Details

  • sp3 Hybridization:

    • 4 identical orbitals in a tetrahedron pointing to the corners.

    • Forms single bonds via head-on overlap.

    • if fewer than 4 bonds are required to satisfy shape and geometry and valence, 1< sp3 orbital are not in bonding but donate lone pairs

    • Lone pairs can be basic/nucleophilic and involved in hydrogen bonding.

  • sp2 Hybridization:

    • 3 identical orbitals in a trigonal planar configuration.

    • P orbital at right angles gives rise to double bonds via sideways overlap. p orbitals are not involved in hybridisation, p-p overlap = double bond

    • p orbitals are mandatory for regular and partial double bonds and resonance involving lone pairs.

    • sp2 can occur without double bond (e.g. peptide bond) in order to have peptide bond planar N has to be sp2 as well

Tautomers and Tautomerization

Tautomer= Structural isomers differing only in hydrogen and double bond positions.

Tautomerization= Reversible conversion between tautomers (e.g., keto→enol and imine→enamine). imino is nitrogen equivalent of carbonyl

Functional Groups

Oxygen-Based Functional Groups

  • Hydroxyl, alkoxyl, carbonyl groups (ketones, aldehydes, carboxylic acids, esters).

Nitrogen-Based Functional Groups

  • Amino, imino, amide.

Sulphur-Based Functional Groups

  • Thiol, thioether, thioester.

Key Topics in Functional Groups

  • Discuss hybridization, shapes, lone pairs, reactivity, electrophilicity, nucleophilicity, electronegativity, polarisability, H-bonding

Revision summary of esters, amides and thioesters:

The hybridisation of O and N, but not S,  changes from sp3 to sp2 when these atoms are connected to carbonyl groups to form esters, amides and thioesters, respectively.