Lecture 2

Question 1

what is conformation?

Answer 1

the spatial arrangement of atoms affording distinction between stereoisomers which can be interconverted by rotations about formally single bonds.

Question 2

what is configuration?

Answer 2

the arrangement of atoms of a molecular eternity in space that distinguish stereoisomers.

Question 3

what are the types of conformations?

Answer 3

eclipsed and staggered (balanced)

Question 4

describe torsional strain.

Answer 4

strain resulting from eclipsed bonds.

Question 5

describe van der waals strain (steric strain)

Answer 5

strain that results from atoms being too close together.

Question 6

describe angle strain.

Answer 6

strain that results from distortion of bond angles from typical values. (Dictated by orbital hybridisation)

Question 7

calculation for c-c bond angles for flat rings

Answer 7

180x(n-2)/n
n= number of c-c bonds that constitute the ring.

Question 8

configuration of chiral molecules can affect…

Answer 8

their biological potency

Question 9

z-configuration and e-configuration

Answer 9

Z = vascular targeting agent
E = biologically inactive

Question 10

two examples of lipophilic interactions between aromatic rings in drug molecules and biological macromolecules.

Answer 10

• pi stacking
• intercalation

Question 11

substituent hydrophobicity equation

Answer 11

pi x = log P x - log P h

pi x = substituent hydrophobicity constant of substituent x

P x = partition coefficient for substituted compound with substituent x

P h = partition coefficient for unsubstituted compound without substituent x

Question 12

what is the substituent hydrophobicity constant?
pi x

Answer 12

the localised effect of functional groups on the lipophilicity of drug molecules.

Question 13

what does the substituent hydrophobicity constant measure?

Answer 13

the substituent hydrophobicity compared to hydrogen.

Question 14

what does a positive substituent hydrophobicity constant imply?

Answer 14

substituents are more hydrophobic than H
(e.g. F, Cl, Br, I)

Question 15

what does a negative substituent hydrophobicity constant imply?

Answer 15

substituents are less hydrophobic than H
(e.g. OH, COOH, NH2, NO2, CONH2, CF3, C triple bond N, SH)

Question 16

what happens in a single point change of functional groups within a series of convergent analogues?

Answer 16

pi can be used in equation instead of log P

Question 17

what happens in a single point change of functional groups within a series of convergent analogues?

Answer 17

pi can be used in equation instead of log P

Question 18

the inductive effect is divided into 2 groups depending on?

Answer 18

the strength of electron withdrawing

or

strength of electron donating nature in respect to hydrogen.

Question 19

Negative inductive effect (-I) - (electron withdrawing group)

Answer 19

NH3+ > NO2 > CN > SO3H > CHO > CO > COOH > COCl > CONH2 > F > Cl > Br > I > OH > OR > NH2 > C6H5 > H

Question 20

Positive inductive effect (+I) - (electron donating group)

Answer 20

C(CH3)3 > CH(CH3)2 > CH2CH3 > CH3 > H

Question 21

the C-H bond is usually considered non-polar however…

Answer 21

-there is a partial positive charge on H atom & patrial negative charge on C atom
- H atom acts as electron donating group
- cumulative donation turns the alkyl moiety into an electron donating group

Question 22

what is the mesomeric(M) / resonance(R) effect and how can this be visualised?

Answer 22

• the electron withdrawing or donating effect attributed to a substituent through delocalisation of p or pi electrons
• visualised by drawing various canonical forms.

Question 23

what is a negative resonance or mesmeric effect (-M or -R) ?

Answer 23

electron withdrawing group through pi bond.

E.g. -NO2, Carbony group (C=O), -C≡N, -COOH, -SO3H etc.

Question 24

what is a positive resonance or mesomeric effect (+M or +R) ?

Answer 24

electron donating group through pi bond.

E.g. -OH, -OR, -SH, -SR, -NH2, -NR2 etc.

Question 25

what does the hammett substituent constant measure?

Answer 25

-assesses the electronic effects of a substituent on a benzene ring.
- quantifies idea of electron donating and withdrawing
- includes inductive and mesmeric/resonance effects
- assesses effects at m- and p- positions.

Question 26

what does a positive hammett sunstituent constant mean?

Answer 26

-electron withdrawing substituents stabilize the carboxylate anion & increases acidity

Question 27

what does a negative hammett sunstituent constant mean?

Answer 27

electron donating substituents destabilize carboxylate anion and decreases acidity.

Question 28

hammett substituent constant calculation

Answer 28

sigma x = Log (K x / K h )