BMP: Drug Design 2

Question 1

Draw a strucure of an alkane, alkene, alkyene and aromatic compound

Answer 1

1. single bonds between
2. Double bond
3. Tripple bond
4. Benzne

Question 2

1. Explain the change in boiling point when the carbon chain of an alkane is increased
2. What is boiling point?

Answer 2

1. Bpt increases due to increasing van der waals forces
2. The energy required to change a liquid to vapour phase

Question 3

What is the difference between conformation and configuaration?

Answer 3

• Conformation is the sets of possible shapes a molecule can have by rotation around a single bond
• Configuration: the relative position of atoms in a molecule that can only be exclusiveluy changed by the cleaving and forming of new chemical bonds

Question 4

What requires more energy changing conformation of configuration?

Answer 4

Configutation as bonds need to be beoken and reformed

Question 5

What is the type of hybridisation in a saturated HC and what bonds are presnet?

What is form is most stable? Why?

Answer 5

• SP3 and sigma no Pi
• Staggered has lowered energy and are more stable as there idn’t electrostatic replulsion of groups as in eclipsed bonds

Question 6

What is:

1. Tortional strain
2. Steric Strain (Van der Waals)
3. Angle strain?

Answer 6

1. Tortional strain is the repulsion force caused between electrons as a bond is rotated around a molecule. It is due to the strain that results from eclipsed bonds
2. Sterric strain is strain that results from atoms being too close
3. ANgle strain results from distortion of bond angles from typical values

Question 7

How is the bond angle of a saturated HC worked out?

Answer 7

C-C bond angle = ((180 x (n-2))/ n

Where n= the number of C-C bonds in ring

Question 8

What can the configuration of a saturated and unsatured HC effect?

Answer 8

Its biologival potency of a (chiral moecluel)

Question 9

What are examples of types of lipophillic bonding between aromatic compounds and macromolecules?

Answer 9

Pi-stacking

Intrcalation

Question 10

What is the substituent hydrophobicity constant (pi)?

Answer 10

The Substituent hydrophobiicty constant is a measure of a substituents hydrophobicity compared to hydrogen and effect on lipophillicty of adrug molecule

Question 11

How is the substituent hydrophobicity constant calculated?

Answer 11

π_x =logP_x - logP_H

Where π_x = Substituent hydrophobicity constant of substituent X

P_H = Partion coefficnet of unsubstitued compoud (without X)

P_x = The partion coefficent of the substituent compound with substiuent X

Question 12

What is the Pi of the following compounds?

Answer 12

Picl = 0.71

Pi = -1.49

Question 13

What does a negative and positive value of pi mean?

Answer 13

+VE means the substiuent is more hydrophobic than H

-VE means the substituent is more hydrophillic than H

Question 14

Calculate the substituent hydrophobity constant for a single point change of functional groups within a series of convergent analogs when you know the following:

picl = 0.71

Pi = -1.49

Answer 14

n a single point change of functional groups within a series of convergent analogs, π can be used instead of P.

Question 15

What is the inductive effect?

Answer 15

The inductive effect is the polarisation of a bond due to unequal sharing of electrons through a sigma bond

Question 16

Describe the 2 categories of inductive effect

Answer 16

• Negative inductive effect (-I) - EWG
  
  • This is when an Electrogenative atom attracts the electrons towards itself and gains a partial -ve charge and the group effected gain a partial +ve charge:
  • NH3+ > NO2 > CN > SO3H
• POstive inductive effect (+I) - EDG
  
  • This is when an EDG donates its elcterons
  • C(CH3)3 > CH(CH3)2

Question 17

What is the mesomeric/ resonance effect

Answer 17

The EWD or EDG effect attributed to a substituent through delocalisation of p or π electrons, which can be visualised by drawing various canonical forms, is known as mesomeric effect or resonance effect. It is symbolised by M or R

Question 18

What is negtatove and positive mesomeric effect

Answer 18

• -VE: EWG (through pi bond)
  
  • substituent draws electrons towards itself
• +VE: EDG

Question 19

What is Hammet Substitution constant (σ)

Answer 19

Asses the electronic effect of a substiuent on benzen rung

Quantifies the idea of EWG and EDG

Includes both the inductive and resonacne efect

Asseses effects at meta and para positions

Question 20

What are the positions of otho meta and para

Answer 20

Question 21

What are the effects of an EWG and EDG on a benzene carboxylic acid?

Answer 21

EWG: Stabilises the benze ring and increases acidity (if -cooh attached).

Decreases stability and activity

Question 22

What effect do EWG and EDG have on σ

Answer 22

EWG = +

EDG = -

Question 23

In what positions is the inductive and resonance effects strongest?

Answer 23

1. Resonance - ortho and para
2. Inductive - meta