Lec 4 LOs

Question 1

how do the electronic effects of substituent groups affect drug ionization, acidity, and basicity using Hammett’s values?

Answer 1

• we want unshared electron pairs that can be shared during resonance thru overlapping p-orbitals with aromatic systems
• o bonds are head to head
• pi bonds are side to side
  –> single bonds are o and double bonds are pi

Question 2

Define Hammett’s values

Answer 2

determines electronic effects of a functional group
- withdrawing and donating here
- determined by pKa
- same group can have a - value at one position and a + value at another

Question 3

Explain the difference in inductive effect and resonance effect

Answer 3

position is critical
- meta is inductive only
- other/ para are both
—-> resonance is through pi bonds and inductive is through both bonds

Question 4

electron-DONATING groups

Answer 4

negative value and decrease acidity ( more basic )
- inductive groups
– o bonds
– ex: alkyl groups
- resonance groups
– pi bonds and lone pairs
– ortho/para directing
– ex: OR, SR, OCOR, NH2, NR2, NHCOR

Question 5

Determine the change in acidity or basicity of a drug upon the change in the chemical substituents.

Answer 5

look at the values because the position determines if it is inductive or resonance effect
- donating groups increase pKa and is less acidic and more basic
- withdrawing groups decrease pKa and more acidic and less basic

Question 6

Why do we use F instead of H?

Answer 6

F is a isostere of H
– share a similar structure and electronic effects
– values are similar and little effect when using F
- H is metabolically vulnerable and F is metabolically resistant

Question 7

electron- WITHDRAWING groups

Answer 7

positive value and inc. acidity (less basic)
- inductive groups
– o bonds
– ex: NO2, CN, COOH, COOR, CHO, X, OR, SR
- resonance groups
– ortho/ para directing
– overlapping p-orbitals with electronegative groups
– ex: NO2, CN, CHO, COOR, SO2R