Introduction to Chemistry for Medicine / Chemistry concepts for health professionals

What is organic chemistry?

  • refers to the study of carbon, its compounds and their reactions

Organic Molecules:

  • Contain a limited number of elements C, H, O, N mainly (S and F are also common in drug molecules)
  • Carbon bonds with other carbons to form single, double or triple bonds.
  • The number of C-C bonds affects the shape and the name.
  • Organic compounds can be straight chains, branching chains or cyclic in structures.
  • If there are no double/triple bonds the molecule is called saturated.
  • Are named systematically based on the number of carbons in the chain
  • Are named based on the major functional groups
  • Functional groups on molecules change their chemistry- how they react
  • You will need to be able to recognise some of the common functional groups to understand the chemistry of drugs.

Polarity and Molecules:

  • Molecules are polar if they contain atoms with different pull on the electrons (e.g O,N,S and halogens)
  • Molecules are polar when these different atoms are arranged non-symmetrically
  • Organic molecules containing O,N,S and halogens (Cl, F,l) can be polar.

Electronegativity:

  • In higher electronegative atoms e.g the core of the atom is more attractive to the electron.

What is a drug?

  • A medicine or other substances which has a physiological effect when ingested or otherwise introduced into the body.

What is drug target?

  • A molecular structure that will undergo a specific interaction with drug(chemicals) administered to treat or diagnose a disease. The interaction has a connection with the clinical effect.

A drug target:

  • Receptor
  • Ion-channel
  • Carrier proteins
  • Enzymes
    -or Other- DNA/RNA, lipids, carbohydrates

Drug Targets- Macromolecules:

  • Lipids:
    • cell membrane lipids
  • Proteins:
    • Receptors
    • Enzymes
    • Transport proteins (carrier proteins)
    • Structural proteins (tubulin)
  • Nucleic acid:
    • DNA
    • RNA
  • Carbohydrates:
    • Cell surface carbohydrates
    • Antigens and recognition molecules

Macromolecules:

  • Carbohydrates:
    • Repeating unit= monosaccharides
  • Lipids:
    • Repeating units= fatty acids
      -Nucleic acids:
    • Repeating unit= nucleotides
  • Proteins:
    • Repeating unit= amino acids

Absolute fundamentals of chemical bonding:

  • Every element and piece of matter is made up of atoms which are tiny and contain a centre called a nucleus.
  • Inside the nucleus are proteins and neutrons- which are made up of quarks
  • Quarks are tiny and bizarre.
  • Protons are positively charged and all elements on the periodic table have a different number of them
  • Electrons are negative particles that orbit the nucleus.

Bonds between atoms - 2 types of bonding exist

  1. covalent:
    • Non-polar covalent (equal sharing of electrons)
      • Polar covalent (unequal sharing of electrons )
  2. Ionic

Covalent Bonding:

  • Sharing of electrons- makes the atoms happy as they have the right number of electrons
  • Electrons are always shared in pairs- all chemical bonds are made up of 2 electrons

Ionic bonding:

  • One atom in the bond gives an electron to the other atom in the bond.
  • Each atom has the right number of electrons
  • Bonds are held together by the attraction of opposite charges.

Bonds Between atoms and molecules

  • Molecules are formed when 2 or more atoms bond together - intramolecular bonding.
  • But molecules also interact with each other.
  • Chemical bonding also occurs between molecules- intermolecular bonding

Bonds between molecules:

  • Temporary interactions=
    • Ionic bonding attraction
    • Hydrogen bonding
    • Van der waals forces
    • Ion-dipole attractions
    • Dipole-dipole attractions
  • Permanent interactions=
    • Covalent bonding ( forms a new molecule)

Ionic Bonds: between molecules:

  • Strongest forces between molecules
  • opposites attract
  • Closer= stronger
  • Stronger in hydrophobic environments
  • Attraction still strong with distance (compared to other forces)
  • Ionic bonds are the most important initial interactions as a drug enters the binding site.

Hydrogen bonds:

  • Weaker then ionic but stronger than Van der Waals
  • Between electron-deficient H and electron-rich (N or O)
  • The [e^-] deficient hydrogen is called a hydrogen bond donor ( HBD) - it donates itself
  • The [e^-] rich heteroatom is called a hydrogen bond acceptor (HBA)- accepts the H

Van der Waals Forces:

  • Very weak, occurs between hydrophobic regions of drug and target
  • Transient= attraction of temporary dipoles due to high and low electron densities
  • Interactions drop off rapidly with distance
  • Drug must be close to the binding region to occur.
  • The overall contribution of Van der Waals interactions can be crucial to binding.

Dipole-dipole interactions:

  • Occurs if the drug and the binding site both have dipole moments (e.g a ketone functional group)
  • These dipoles align with each other as the drug enter the binding site
  • Dipole alignment orientates the molecules in the binding site.
  • Orientation can be beneficial if other binding groups or detrimental depending on corresponding binding regions.
  • The strength of the interaction decreases with distance more quickly than with electrostatic interaction but less quickly than with Van der Waals interaction
  • Weaker than ionic but stronger than Van der Waals binding.

Ion-dipole interactions:

  • Occurs where the charge on one molecule interacts with the dipole moment of another.
  • Stronger than a dipole-dipole interaction.
  • Strength of interactions falls off less rapidly with distance than for a dipole-dipole interaction.