C2. Physiochemical properties

Question 1

MW?

Answer 1

Molecular weight

Question 2

HBA?

Answer 2

Hydrogen bond acceptors

Question 3

HBD?

Answer 3

Hydrogen bond donors

Question 4

logP?

Answer 4

Lipophilicity

Question 5

logD?

Answer 5

Lipophilicity (ionisation)

Question 6

Describe HBA and HBD

Answer 6

-A hydrogen bond donor (HBD) donates
a hydrogen bond e.g. N-H, O-H.
-A hydrogen bond acceptor (HBA)
accepts a hydrogen bond through its lone pair e.g. N, O.
-HBD = Total number of N-H and O-H bonds.
-HBA = Total number of N and O atoms with available lone pairs.

Question 7

O-H bond?

Answer 7

-can be HBA through Oxygen and HBD through O-H

Question 8

Describe amides

Answer 8

-Amides (and similar functional groups) exhibit a resonance effect.
-In these cases, nitrogen is sp2 hybridised.
-The nitrogen lone pair occupies an unhybridised p-orbital.
-There is a pi-system above and below the plane of the O=C-N bond.
ONE NOTE

Question 9

Conjugated definition?

Answer 9

system of overlapping p orbitals containing delocalised electrons

Question 10

resonance definition?

Answer 10

a way of describing bonding based on the ‘average’ structure as a result of different contributing forms

Question 11

Describe lipophilicity

Answer 11

-Lipophilicity refers to the ability of a molecule to dissolve in lipids.
-In medicinal chemistry the two adjectives to describe the scale are
lipophilic and polar.

Question 12

what is partition coefficient, P?

Answer 12

The partition coefficient, P, is a measure of lipophilicity.

Question 13

partition coefficient, P euation?

Answer 13

𝑃 = [𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑒] organic substance/ [𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑒] 𝑤𝑎𝑡𝑒𝑟
[Square Brackets] means ‘concentration’.
ONE NOTE

Question 14

logP equation?

Answer 14

𝑙𝑜𝑔𝑃 = 𝑙𝑜𝑔 ( [𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑒] organic sub /
[𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑒] 𝑤𝑎𝑡𝑒𝑟 )
-logP is the main descriptor of lipophilicity.

Question 15

Describe logP

Answer 15

-If logP = 5, then the molecule is 10^5 times more soluble in organic substance than in water.
-The higher the logP, the more lipophilic the molecule.
-logP can be negative for polar molecules.
-The typical range you will encounter is roughly −5 to +7.

Question 16

Guide to lipophilicity?

Answer 16

-Carbon based groups are lipophilic.
-Nitrogen and Oxygen based groups are polar.
-Aryl halogens are lipophilic.
-Larger halogens are more lipophilic.
-Charged groups are very polar.

Question 17

passive diffusion depends on?

Answer 17

-Depends on drug size and
lipophilicity.
-Smaller drugs diffuse faster
than larger drugs

Question 18

how does lipophilicity affect passive diffusion?

Answer 18

-If a drug is too polar, it cannot passively diffuse across the lipophilic
cell membrane.
-If a drug is too lipophilic, it is more susceptible to metabolism (and
other disadvantages).
-Need to hit the lipophilicity ‘sweet spot’…

Question 19

Describe Lipinski’s Rule of Five

Answer 19

-There are four rules in Lipinski’s Ro5… and they aren’t really rules!
-However they do provide a useful guide to design molecules which
are likely to be orally absorbed.
-logP ≤ 5
-MW ≤ 500
-HBA ≤ 10
-HBD ≤ 5
There are many exceptions to the rule