CH203

Lecture 27
November 7, 2014

Acids and bases

Acids and Bases

Arrhenius:
An acid is a substance that produces H+ ions in aqueous soluCon.
A base is a substance that produces OH- ions in aqueous soluCon.

Brnsted and Lowry:
An acid is a substance that is a proton donor.
A base is a substance that is a proton acceptor.

conjugate acid-base pair
conjugate acid-base pair

HCl( aq )

Hydrogen
chloride
(acid)

H2 O ( l )

Water
(base)

C l - ( aq )

Chloride
ion
(conjugate
base of HCl)

H 3 O + ( aq )

Hydronium
ion
(conjugate
acid of H2O)

Acids and Bases

Brnsted-Lowry deniCons do not require water as a reactant.

 electrons as a Brnsted-Lowry base

Brnsted-Lowry base: A substance that is a proton acceptor.

The electrons of 2-butene (base) react with HBr (acid).

Acid and base strengths

The equilibrium expression for the dissociaCon of any uncharged
acid, HA,

can be wriSen as a raCo of the concentraCons of the products

divided by the concentraCons of the reactants

Acid and base strengths

The equilibrium constant, Keq, of the ionizaCon of acid HA in water
takes the form
+
A + H3O

HA + H2 O

Keq =

[H3 O ][A ]
[HA][H2 O]

Water as a solvent is present in a constant concentraCon of about

55.5 mol/L. MulCplicaCon of both sides by that constant gives a
new quanCty, Ka, the acid dissociaCon constant.
Ka = Keq[H2 O] =

[H 3 O+ ][A-]
[HA]
7

Acid and base strengths

Because acid strengths cover a wide range and are oZen numbers
with negaCve exponents, it is more convenient to express the Ka as
pKa (= -log10Ka)
AceCc acid has a pKa = 4.75 so


O
H

O+
-5
O Ka = 1.77 x 10 = H
H H3C

O


H3C
OH


AceCc acid in water is mostly unionized. It is a weak acid.
8

Acid and base strengths

pKa = -log10Ka

Hydrochloric acid has a pKa = -7 so

H
Cl-

O+

Ka = 107 =

HCl

Hydrochloric acid in water is ionized. It is a strong acid.

9

Acid and base strengths

10

Acid and base strengths

If the pKa < 0, then Ka > 1 (strong acid)

If the pKa 0, then Ka 1

If the pKa > 0, then Ka < 1 (weak acid)

11

Obtaining Keq from Ka

For the acid-base reacCon

HA + B A- + HB+

pKeq = pKHA pKHB+

12

Obtaining Keq from Ka

pKeq = pKHA pKHB+

pKeq = 4.76 - 9.24 = -4.48

Ke q = 3.0 x 104
At equilibrium, there are 30,000 molecules of acetate for every molecule of
unionized aceCc acid.
13

Amino acids

O
H2N
OH
L-Valine;
(S)-Valine

H2O
+H

O
3N

OL-Valine zwitterion

At pH values higher than the pKa of the carboxylic acid group (mean for the 20 common
amino acids is about 2.2), the negaCve carboxylate ion predominates. At pH values lower
than the pKa of the -ammonium group (mean for the 20 common -amino acids is about
9.4), the nitrogen is predominantly protonated. At a pH between 2.2 and 9.4, -amino
acids consist of the negaCvely-charged carboxylate group and the posiCvely-charged -
ammonium group and have a net charge of zero. This molecular state is known as a
zwiSerion, from the German Zwi$er meaning hybrid.

Below pH 2.2, the predominant form will have a neutral carboxylic acid group and a
posiCve -ammonium ion (net charge +1), and above pH 9.4, a negaCve carboxylate and
neutral -amino group (net charge 1).
14

Amino acids

A CtraCon curve of an amino

acid reveals the pH at which
the net charge on the
molecule is zero. This pH is
dened as the isoelectric
point (pI).

15

pH in vivo

16

pH in vivo
The Henderson-Hasselbalch equaCon (useful in calculaCng buer recipes):
[RNH2]
pH
=
pK
+
log
a
+

[RNH3 ]

The neurotransmiSer dopamine contains an amine group whose conjugate acid has a
pKa = 10.6. In a cell buered at pH = 7.3:
7.3 = 10.6 + log

-4

5 x 10

[RNH2]
+

-3.3 = log

[RNH3 ]

[RNH2]
+
[RNH3 ]

[RNH2]
+

[RNH3 ]
+

2 x 10

[RNH3 ]
[RNH2]

The concentraCon of the protonated amine is 2000x that of the neutral amine.
Typical amines are >99.9% protonated at physiological pH.

pH in vivo

Staurosporine, isolated in 1977 from the bacterium Streptomyces staurosporeus. The

bacterium synthesizes staurosporine as an anCfungal. Staurosporine is an inhibitor of a
broad spectrum of protein kinases. The inhibiCon potency is strongest for protein kinase
C (PKC). Staurosporine exhibits a strong cytotoxicity to some mammalian tumor cell
lines and induces cell apoptosis.
18

H
N










































pH in vivo

N O

H 3CO

1$0(6WDXURVSRULQH&*3
(;312
352&12
'DWHB
7LPH
,167580VSHFW
352%+'PP3$'8/&
38/352*]J
7'
62/9(17'062
16
'6
6:++]
),'5(6+]
$4VHF
5*
':XVHF
'(XVHF
7(.
'VHF
7'

NHCH3

&+$11(/I
18&+
3XVHF
6,
6)0+]
:':(0
66%
/%+]
*%
3&

0.97

1
3.16

2
3.17
1.23

3
3.30
1.19

4
1.06

5
2.03

6
1.04

7
1.08
2.20
2.13

2.07

8
0.98

1.00

ppm

19

pH in vivo

H
N

Aromatic halogenation
N

CH3

HN

H3C
O
O-demethylation

CH3

N-demethylation

20

pH in vivo
H
N

H
N

H3C

H3C

CH3
T3C

N+
CT3

CH3

CH3

N+
H
H

CH3

[Methyl-3H]N,N-Dimethylstaurosporine

21

pH in vivo

unbound ligand x empty receptor

Kd =
ligand-receptor complex
22

pH in vivo

23

Thermochemistry

24