Lec 3

Question 1

List the 4 factors that determine the acidity of a compound

Answer 1

• strength of the conjugate base (Y-) - electronegativity of Y - strength of the Y-H bond - nature of the solvent

Question 2

Give the order in descending acidity of the following C - OH groups, their pKa’s & explain your reasoning: Asp, Ser, Tyr

Answer 2

Strongest = Asp pKa = 4.5

• 2 resonance structures that exist of Asp help to spread out the -ve charge across both Os

Tyr pKa = 10

• 4 resonance structures
• however 3 of them unlikely because of the -ve charge on the C group

Ser pKa = 15 - -ve charge is just on the O and can’t be stabilised elsewhere

Question 3

Does a high or low pKa make it more likely that a substance will deprotonate (act as an acid)?

Answer 3

LOW pKa

Question 4

Give the order in descending ability to act as a base of the following C-NH2 groups, their pKa’s & explain your reasoning: Asn/Gln, Lys, His

Answer 4

Lys pKa = 10 - whilst doesn’t exist in deprotonated state frequently, it can donate a H+ - no resonance structures exist His pKa = 6.5 - equal amounts (ish) of de/protonated amounts - ability to act as both an acid and base - deprotonated is > stable because of the delocalised pi e- system (although protonated state is still stable the +ve charge split between the 2 Ns) Asn/Gln pKa = wasn’t stated - the lone pair on the N is part of the delocalised pi e- system and therefore is not available to bond to H+

Question 5

Which is more acidic - Ser/Cys? Give reasons for your answer

Answer 5

Ser the -ve charge on the S group is shared over a larger area therefore more stable

for O- , the -ve charge is shared over a small volume Ser is therefore > acidic

Question 6

Where are the acidic Hs positioned in Keto-enol tautomers?

Answer 6

alpha to the carbonyl

Question 7

Give the structure of propanone (Baker 3 notes) and complete the mechanism for the removal of the acidic H and formation of the enolate anion

Answer 7

Question 8

Why is it difficult to remove an acidic H from its bond to C? Give the pKa of this removal.

Answer 8

C is not electronegative and the resulting -ve charge on C is not stabilised by anything else

• however after removing the H the electrons subsequently move into the pi electron system making it easier for the H to be removed - pKa = 20
• e- put into a p orbital that overlaps with the pi electron system to form the enolate anion

Question 9

When does Arg acts a base? Does this ever occur? If not, what are the 2 other functions of Arg? (Rice)

Answer 9

• Arg acts as a base when deprotonated
• Deprotonated state v rarely occurs (especially in enzymes) because of its pKa (12.5)
• instead Arg acts as a +vely charged partner in an ion pair or as a H bond donor

Question 10

Draw the resonance structures of deprotonated & protonated forms of His

Answer 10

Question 11

Draw the resonance structures of Arg

Answer 11