explicaciones del ph

7/30/2019 Explicaciones Del pH

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5/24/2013 MEDC 501 Fall 2007 1

pKA and Ions in Solution

Chemical Equilibrium

A + B C + Dk1

k2

At equilibrium, k1 [A] [B] = k2 [C] [D]

EK

BA

DC

k

k

]][[

]][[

2

1

Le Chateliers Principle: When a stress is applied on a system at equilibrium,

the system will re-adjust to diminish the stress or counteract the change.


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H2O Equilibrium

EKOH

OHH

][

]][[

2

H2O H + OHk1

k2

+ _

142 105.55][]][[

WEE KKOHKOHH

1410log]][log[ OHH

14]log[]log[ OHH

14]log[]log[ OHH

14 pOHpH


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Ionization of a weak acid

CH3COOH + H2O H3O+

+ CH3COO-

]][[

]][[

32

33

COOHCHOH

COOCHOHKE

][

]][[][

3

332

COOHCH

COOCHOHKOHK AE

][

][log]log[log

3

33

COOHCH

COOCHOHKA

][

].[log

][

][log

3

3

acid

baseconjpH

COOHCH

COOCHpHpKA

ApKpHacid

baseconj

][

].[log Henderson-Haselbach Equation


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What is the physical meaning of pKA?

11

1][

].[log ApKpHacidbaseconj

22

2

][

].[log ApKpH

acid

baseconj

}{}{

][

].[log

][

].[log 21

2

2

1

1AA pKpHpKpH

acid

baseconj

acid

baseconj

212

2

1

1

].[

][

][

].[log AA pKpK

baseconj

acid

acid

baseconj

122

1

].[

].[log AA pKpK

baseconj

baseconj [Unionized Acid1] =

[Unionized Acid2]

If pKA1 = 4 and pKA2 = 1. 001.01010

].[

].[ 3)41(

2

1

baseconj

baseconj

].[001.0].[ 21 baseconjbaseconj ][

].[001.0

][

].[

2

2

1

1

acid

baseconj

acid

baseconj


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Consequences of Bond Polarity

Inductive Effect - Influence on pKa

CH3

O

O

HF

3C O

H

O

pKa 4.5 0.23

CH3COOH ClCH2COOH

pKa 4.5 2.9


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Inductive Effect - Additive Property

pKa

CH3COOH 4.5

ClCH2COOH 2.9

Cl2CHCOOH 1.3

Cl3CCOOH 0.7


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Inductive Effect - Distance Dependent Property

pKa

CH3CH2CH2COOH 4.8

ClCH2CH2CH2COOH 4.5

CH3CHClCH2COOH 4.1

CH3CH2ClCH2COOH 2.8


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Inductive Effect - Group Electronegativities

pKaNO2CH2COOH 1.7

ClCH2COOH 2.9COOHCH2COOH 2.8CNCH2COOH 3.5

Electron-withdrawing groups -C=N 0.5+1.0 = 1.5

-COOH 0.25+1.25+1.0+0 = 2.5

-CHO 0.25+1.25+0 = 1.5

-NO2 0.5+1.25+1.25 = 3.0


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pKa 6.1 5.7


Influence on pKa . through space effect

ClCl

COOHCOOH

Cl

Cl


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pKA and Solubility in Water

NN

NH

O

F COOH

Ciprofloxacin

(piperazine)

Antibacterial

(anthrax)


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A molecule may have more than one pKA value!!


Inductive Effect Multiple pKA values

OH O

OO

OH OH

OO

O O

OO

_ _ _

pKA = 2.8 pKA = 5.7

ONH

3

O

OHNH

3

O

ONH

2

OpKA = 2.35 pKA = 9.78

_ _+ +


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Natural Amino Acids Structure and pKA

R

NH2

HCOOH Structure of Amino Acid Residues

All L-configuration or R geometry(except for glycine)

Non-Polar R = Polar R =

Glycine H Serine HOCH2

Alanine CH3 Threonine CH3CH(OH)

Valine (CH3)2CH Cysteine HSCH2

Leucine (CH3)2CH2CH Tyrosine HOC6H4CH2

Isoleucine CH3CH2CH(CH3) Asparagine H2NC(O)CH2

Phenyalanine PhCH2 Glutamine H2NC(O)CH2CH2

Methionine H3CSCH2CH2

Tryptophan

NH

CH2

__


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Natural Amino Acids Structure and pKA

R

NH2

HCOOH Structure of Amino Acid Residues

All L-configuration or R geometry(except for glycine)

Acidic R = Basic R =

Aspartic Acid HOOCCH2 Lysine H2N(CH2)4

Glutamic Acid HOOCCH2CH2

Arginine H2NC(NH)NH(CH2)3

HistidineN

NH

H2C

__


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pKA Values of Natural Amino AcidsResidues pKA1 pKA2 Side-Chain pKA (group identification)

Non-Polar

Glycine 2.35 9.78

Alanine 2.35 9.87Valine 2.29 9.74

Leucine 2.33 9.74

Isoleucine 2.32 9.76

Phenyalanine 2.16 9.18

Methionine 2.13 9.28

Tryptophan 2.43 9.44

Hydrogen-bondingSerine 2.19 9.21

Threonine 2.09 9.10

Cysteine 1.92 10.78 8.33 (thiol group)

Tyrosine 2.20 9.11 10.13 (phenol group)

Asparagine 2.10 8.84

Glutamine 2.17 9.13

Acidic

Aspartic Acid 1.99 9.90 3.90 (g-COOH group)Glutamic Acid 2.10 9.47 4.07 (g-COOH group)Basic

Lysine 2.16 9.18 10.79 (-amino group)Arginine 1.82 8.99 12.48 (guanidino group)

Histidine 1.80 9.33 6.04 (imidazole group)


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pKA Values of Natural Amino Acids

and the Dominant Form

Serine

Cysteine

Tyrosine

Asparagine

Arginine

Aspartic Acid

Amino Acid pH 3.0 pH 7.0 pH 10.0


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Influence on pKa of bases

pKA = pH - log[RNH2]

[RNH3+]

RNH3+ + H2O H3O+ + RNH2

CH3CH2NH2 FCH2CH2NH2


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Inductive Effect

depend on the eW atom or eN atom is distance dependent may be re-inforced or cancelled is additive can affect the acidity or basicity of molecules can affect the physical properties of molecules


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Resonance EffectNH

2NH

2

pKa 9-11 ~5

Resonance, Aromaticity & Conjugation


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Resonance EffectNH

2NH

2

pKa 9-11 ~5

NH3+

NH3+

NH2

NH2

+ H2O + H3O+

+ H2O + H3O+


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Resonance Effect

pKa 4.2 3.4 4.5

COOH COOH

NO2

COOH

OMe

N

OOH

O O

OMe

OOH

N

O O

OO

OMe

OO

+ H2O + H3O+

+ H2O + H3O+

_

_

__+ +


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Resonance Effect

Electron-donating groups . OH, OMe, NH, NH2, NCH3

Electron-withdrawing groups . NO2, COOH, CHO, CN,SO3H, SO2NH2, SO2Cl


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Group Acid form Conjugate base form pKA

Amines RCH2NHR2+ RCH2NR2 8-11

Acids RCOOH RCOO- 3-5

Amides RCONH2 .. Does not ionize (neutral) ..

Alcohols ROH .. Does not ionize (neutral) ..

Phenols PhOH PhO- 9-11

Anilines PhNH3+ PhNH2 3-5

Imidazole 6.9

Pyridines 4-6

Imides 8-10

1,3-dicarbonyls 11-13

Imines ~7

Ketones R-C(=O)-R .. Does not ionize (neutral) ..

Aldehydes R-C(=O)-H .. Does not ionize (neutral) ..

Esters R-C(=O)-OR .. Does not ionize (neutral) ..

Ethers ROR .. Does not ionize (neutral) ..

NH

NH

+

NH

N

NH

+N

NH

O O

N

O O

_

O O

H H

O O

H

_

NNH

+

Group Acid form Conjugate base form pKA

Amines RCH2NHR2+ RCH2NR2 8-11

Acids RCOOH RCOO- 3-5

Amides RCONH2 .. Does not ionize (neutral) ..

Alcohols ROH .. Does not ionize (neutral) ..

Phenols PhOH PhO- 9-11

Anilines PhNH3+ PhNH2 3-5

Imidazole 6.9

Pyridines 4-6

Imides 8-10

1,3-dicarbonyls 11-13

Imines ~7

Ketones R-C(=O)-R .. Does not ionize (neutral) ..

Aldehydes R-C(=O)-H .. Does not ionize (neutral) ..

Esters R-C(=O)-OR .. Does not ionize (neutral) ..

Ethers ROR .. Does not ionize (neutral) ..

NH

NH

+

NH

N

NH

NH

+

NH

N

NH

+NNH

+N

NH

O O

N

O O

_NH

O O

N

O O

_

O O

H H

O O

H

_

O O

H H

O O

H

_

NNH

+

NNH

+

pKA Values of Common Organic Functional Groups


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Application of Henderson-Hasselbach Equation

1. Amphetamine has pKA of 9.8. Whatform will dominate at pH 2.8, 6.8,and 9.8?

CH3

NH3

CH3

NH2

+ H2O + H3O+

+

CH3

NH3

CH3

NH2

+ H2O + H3O+

+

log = pH - pKA[RNH2]

[RNH3+]

At pH 2.8

log = 2.8 9.8 = -7.0

= 10-7

[RNH2] = 10-7 [RNH3+] % [RNH2] = 10-7 0.00001%

% [RNH3+] = 100 - 10-5 99.99999 %RNH3

+ is an ion, therefore % ionization of

amphetamine is nearly 100% at pH 2.8

[RNH2][RNH3

+]

[RNH2][RNH3

+]

100

(1+10-7)

At pH 6.8

log = 6.8 9.8 = -3.0

= 10-3

[RNH2] = 10-3 [RNH3+] % [RNH2] = 10-3 0.1 %

% [RNH3+] = 100 - 10-1 99.9 %RNH3


amphetamine is nearly 100% at pH 6.8

[RNH2][RNH3

+]

[RNH2][RNH3

+]

100

(1+10-3)


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1. Amphetamine has pKA of 9.8. Whatform will dominate at pH 2.8, 6.8,and 9.8?

CH3

NH3

CH3

NH2

+ H2O + H3O+

+

CH3

NH3

CH3

NH2

+ H2O + H3O+

+


[RNH3+]

At pH 9.8

log = 9.8 9.8 = 0.0

= 100 = 1

[RNH2] = 1[RNH3+] % [RNH2] = 1 50 %

% [RNH3+] = 100 - 50 50 %RNH3


amphetamine is 50% at pH 9.8

[RNH2][RNH3

+]

[RNH2][RNH3

+]

100

(1+1)


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2. Meperidine is a narcotic analgesic.Its pKA is 8.7. It needs to beinjected (iv). What pH will you need

to make the solution of meperidine?


[RNH3+]

N

COOEt

H CH3

N

COOEt

CH3

++ H

2O + H

3O+

For meperidine to go into solution fully and easily, it

should be fully ionized. Therefore, protonated species

(the conjugate acid form, [A]), and not the base form

{[B]} should dominate.

[RNH2]

[RNH3+]

< 0.01 or 10-2

log < 2.0[RNH2][RNH

3

+]

pH pKA < 2.0 pH 8.7 < 2.0 pH < 2.0 + 8.7 pH < 6.7


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3. Hydrocortisone hemisuccinate has apKA of 5.1? It is a pro-drug form ofhydrocortisone, a steroidal anti-

inflammatory molecule. Why washemisuccinate derivative made?

O

O

O

OHOH

O

OH

O

OH

O

OHOH

Hydrocortisone hemisuccinate hydrocortisone

Hydrocortisone has poor solubility in water/blood. However, the hemisuccinate form

with a pKA of 5.1 generates good solubility (~100% ionized) at pH 7.2 (blood). Thus, it

can be injected directly in the vein for rapid anti-inflammatory activity. On the other

hand, hydrocortisone or its ester derivatives (acetate, valerate, etc) cannot be injected

into the vein directly because they will precipitate. If a solubilized form of

hydrocortisone or its ester is prepared and injected into a vein, dangerous possibilitiesof cutting of blood flow (and possibly death) exist!

explicaciones del ph

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