Chemical structure: a pharmaceutical perspective 1-5

Question 1

What effects do functional groups have on drug behaviour (3)

Answer 1

1. electronic - donate/accept electrons
2. solubility
3. steric - shape

Question 2

what is resonance and induction

Answer 2

resonance = moving of lone pairs & double bonds in a conjugated system (lone pairs, double/triple bonds)

induction = intrinsic ability of an atom/group to withdraw/donate electrons depending on electronegativity

Question 3

what are the electronegativity effects (3)

Answer 3

less than 0.5 = non-polar (equally shared electrons)

0.5- 1.6 = polar (electrons spend more time closer to the electronegative atom)

greater than 2 = ionic (electrons allocated to the electronegative atom)

Question 4

what are electron-withdrawing groups, and what are electron-donating groups

Answer 4

EWGs = accept electrons, electrophiles

EDGs = donate electrons, nucleophiles

Question 5

what are examples of EWGs (12)

Answer 5

halogens
R-CF3
ionised amino (R-NH3+)
nitrile
alkoxy (R-OCH3)
nitro
hydroxy
sulfhydryl
aldehyde/ketone
aminde (R-C=O-N)
ester
sulfamide

Question 6

what are examples of EDGs (5)

Answer 6

aromatic hydroxyl (OH)
aromatic amino (NH2)
aromatic thiol (SH)
aromatic alkyl (CH3)
aromatic alkoxy (OCH3)

Question 7

what groups interact with water (4)

Answer 7

hydrogen bonding
ionisable groups (- charge bind w/ H, + w/ O) - effective
dipoles - little solubility
polar

Question 8

what are examples of H bonding groups (13)

Answer 8

-OH
-NH2, -NH
-NH3+
-COOH
-SH
-C=O
-O-
-NH2, N
-COO-
F
aromatic rings w/ electronegative group (e.g. N group)
H2O
-CONH2

Question 9

what are examples of lipid solubilising groups (4)

Answer 9

alkylic chains/rings
aromatic rings
unsaturated chains
non-polar molecules

Question 10

what does careful modification of the steric footprint of a drug lead to (3)

Answer 10

Increased selectivity for the biological target

enhanced binding interactions w/ the target & eliminate binding for another

favourable alteration of the rate of metabolism

Question 11

How can the hybridisation and shape of hydrocarbons be described (6)

Answer 11

Alkanes - saturated - sp3 - tetrahedral

Alkenes - unsaturated - sp2 trigonal planar

alkynes - unsaturates - sp - linear

aromatic arenes - unsaturated - sp2 - cyclic

s orbitals - 2 electrons
p orbitals - 6 electrons

Question 12

what are the features of aromatic hydrocarbons (4)

Answer 12

1. Conjugates hydrocarbons - pi bonds separated by single bonds (omega bonds)
2. rearrangement of lone pairs acting as a unique system
3. sp2 hybridisation
4. cloud of delocalised electrons (electron withdrawing behaviour) - high electron density

Question 13

what determines hydrophobicity/lipophilic (2)

Answer 13

1. long C-C and C-H bonds
2. Van der Waals, no dipoles, no H bonds

Question 14

what determines metabolic stability (6)

Answer 14

1. hydrocarbons
2. alkanes/cycloalkanes
3. bulky groups
4. electron-withdrawing groups
5. cyclic systems
6. Adding fluorine (F)

Question 15

what does flexibility allow and how does it come about

Answer 15

Flexibility allows adaptation to the conformation site through rotation.

Achieved with open chain chains containing single bonds.

Question 16

how does chirality affect drug molecules (3)

Answer 16

1. sp3 carbon with 4 different substituents = asymmetric
2. results in an active enantiomer and inactive enantiomer.
3. enantiomers have similar activity but different potencies

Question 17

what are the functional groups in fluoxetine

Answer 17

Question 18

How are hydrocarbons metabolised (5)

Answer 18

1. Metabolism of hydrocarbons is oxidative catalysed by the P450 enzyme
2. Metabolism can be omega or omega-1 hydroxylation
3. Omega hydroxylation = OH group added on the carbon at the end
4. Omega-1 hydroxylation = OH group on the carbon before the carbon at the end
5. When there are double bonds the P450 enzyme carries out dihydroxylation where the double bond is broken and replaced with two OH groups

Question 19

How are benzene rings metabolised (2)

Answer 19

1. insertion of an oxygen atom across the double bonds = toxic species & electrophile
2. hydrogenation