Chapter 2 Flashcards
What are the properties of functional groups?
-Steric effects
-Electronic effects
-Solubility effects
What are steric effects?
Position of functional groups in 3-dimensional space and how it effects its neighbours
How do steric effects, affect drugs and their target?
-Enhance binding by keeping it in active form (more responsive to the target) -> f.e. Cl prevents rotation
-Increase selectivity (f.e. Trimethyl will select for ß receptor over alpha receptor as a target, bc ß rec. provides more space occupied by larger Trimethyl)
-alter or prevent metabolism: protection of amides from hydrolyzation by ortho substitutes
SHIELD against hydrolyzation
Explain the electronic effects of functional groups:
Ability to donate electrons to, or pull it from its neighbor
Movement of electrons through Resonance (adjacent double bonds) or Induction
How do electronic effects, affect drugs and their target?
Resonance: e- shared around a group of atoms with adjacent double atoms
Induction: Tendency to pull the atom towards the electronegative atom
For functional groups:
EDG e- donating: donated by a negatively charged atom or lone e- pair atom, this includes ALKYL groups (they are bad in withdrawing e(-))
EWG e- withdrawing: e- accepted by a positively charged atom or atom with high electronegativity (like halogen to fill the valence shell)
Which of the EDG and EWG is activating and deactivating groups?
e-donating groups are activating groups bc they are giving away an electron for potential reaction
e-withdrawing groups are deactivating groups because they cause stabilization by drawing electrons out of a bond = less chemically reactive
How does resonance stabilize chemical structures?
Electrons are the fuel for reactions, if the electron is moving around, that fuel is distributed in the structure which reduces the reactivity
Tendency to Resonance = Stability
How does induction work?
It depends on the electronegativity of atoms
the greater the EN of an atom the more it pulls electrons towards itself
How can atoms be e- donating and withdrawing?
Oxygen as an ether can donate e- via resonance (donating lone pair of electrons) or withdraw via induction
Why can Penicillin V can be given orally?
Because the oxygen can withdraw e- from the amide and thereby deactivates the structure (less likely for hydrolysis at amide) and making it stable in the stomach
What are the Solubility effects?
related to the water and lipid solublity and contribution to molecule solubility
What makes drugs more water soluble?
- Ionizable groups - acidic(-) or basic(+) f.e. (can be pos. or neg. charged which can attract H2O)
- Hydrogen bonding: dipole within a molecule (polar)
Dipole of a molecule interacts with a dipole in water
H-Bonding: Which atom is the H-bond acceptor/donor?
The more negatively charged atom is the acceptor (often O or N)
The more positively charged atom is the donor
H is always the donor
Halogens are always the acceptor
What contributes to lipid solubility?
-Hydrocarbon load: number of C-atoms
-Halogens: they are heavy and they contribute to lipid solubility
the heavier, the more lipid soluble
-Overall molecular weight
Why are Ester, Ether, and Halogens lipid soluble?
-Ester/ether: considered lipid soluble (lipophilic) and hydrophobic because the R-groups are carbons -> HC load
-Halogens: Lipid soluble bc of molecular weight
