Lecture Lecture № № 99Heterofunctional Heterofunctional carboxylic carboxylic

acidsacids..

Prepared by ass. Medvid I.I.,Prepared by ass. Medvid I.I.,ass. Burmas N.I.ass. Burmas N.I.

OutlineOutline1.1. Physical and chemical properties of oxoacids. Physical and chemical properties of oxoacids.

Acetoacetic ester.Acetoacetic ester.2.2. Physical and chemical properties of halogenacidsPhysical and chemical properties of halogenacids3.3. Physical and chemical properties of hydroxyacids.Physical and chemical properties of hydroxyacids.4.4. Physical and chemical properties of phenolacids.Physical and chemical properties of phenolacids.5.5. Physical and chemical properties of aminoacids.Physical and chemical properties of aminoacids.6.6. Chloranhydrides of Chloranhydrides of carboncarbonicic acid acida) Physical and chemical properties of aa) Physical and chemical properties of a phosgenephosgene7. Amides of carbonic acid7. Amides of carbonic acida)a) Physical and chemical properties of an ureaPhysical and chemical properties of an ureab)b) Physical and chemical properties of a guanidinePhysical and chemical properties of a guanidine8. 8. Sulfoacids:Sulfoacids:a)a) aliphatic sulfoacidsaliphatic sulfoacidsb)b) aromatic sulfoacidsaromatic sulfoacids

9. Aminoacids9. Aminoacids1). α-Aminoacids as structure components of proteins.1). α-Aminoacids as structure components of proteins. 2). Classification and structure of aminoacids.2). Classification and structure of aminoacids.3). Chirality of aminoacids.3). Chirality of aminoacids. 4). Acid - base properties of aminoacids.4). Acid - base properties of aminoacids.5). Chemical properties of 5). Chemical properties of αα-aminoacids.-aminoacids. 6). Indentification of aminoacids.6). Indentification of aminoacids.7). Proteins. S7). Proteins. Structure of а proteintructure of а protein..8). 8). Globular and fibrous proteinsGlobular and fibrous proteins9). Simple and conjugated proteins.9). Simple and conjugated proteins.10.10.Peptides:Peptides:

a) aa) acid-base properties;cid-base properties;b) b) optical properties of peptides;optical properties of peptides;c) chemical properties of peptides;c) chemical properties of peptides;d) d) synthesis of peptides.synthesis of peptides.

The most important The most important heterofunctional heterofunctional carboxylic acids are hcarboxylic acids are halogenalogenoocarboxylic carboxylic acid (haloacid (haloggenenooacid), hacid), hyydrodroxxycarboxylic ycarboxylic acid (hacid (hyydrodroxxyacid) oyacid) oxxocarboxylic acid ocarboxylic acid (aldehyd(aldehydo-o- and keto and ketononoacid) and aminoacid) and amino- - ccarboxylicarboxylic acids (aminoacids)acids (aminoacids)

1. Oxoacids1. OxoacidsTo oxoacids include aldehydo- and ketonoacids. To oxoacids include aldehydo- and ketonoacids. These compounds include in the structure of the These compounds include in the structure of the carboxyl group, aldehyde functional group or ketone carboxyl group, aldehyde functional group or ketone functional group.functional group.

γ-ketovaleric acid,4-oxopentanoic acid,levulinic acid

acetoacetic acid,3-oxobutanoic acid,β-ketobutyric acid

oxalacetic acid,oxobutanedioic acid,ketosuccinic acid

glyoxylic acid,oxoethanoic acid

pyroracemic acid,2-oxopropanoic acid

Methods of extraction of oxoacidsMethods of extraction of oxoacids::1.1. Oxidation of hydroxyacids:Oxidation of hydroxyacids:

2.2. Hydrolysis dihalogenocarboxylic acidsHydrolysis dihalogenocarboxylic acids

+ H2OCH2C CH2

O

OH

[O]

OH

CHC CH2

O

OHO

lactic acid pyroracemic acidlactic acid pyroracemic acid

2,2-dichlorpropanoic acid pyroracemic acid (pyruvic acid) 2,2-dichlorpropanoic acid pyroracemic acid (pyruvic acid)

Chemical properties of oxoacidsChemical properties of oxoacids1.1. Decarboxylation of Decarboxylation of αα-oxoacids-oxoacids

2.2. Decarboxylation of Decarboxylation of ββ-oxoacids-oxoacids

CH3 C

O

COOHconc. H2SO4, t

CH3 C + CO2

O

Hpyroracemic acid acetaldehyd

CH3 C

O t

acetoacetic acid

CH2 COOH CH3 C CH3

Oacetone

- CO2

Acetoacetic esterAcetoacetic esterAcetoacetic ester synthesisAcetoacetic ester synthesis is a chemical reaction where is a chemical reaction where ethyl acetoacetate is alkylated at the α-carbon to both ethyl acetoacetate is alkylated at the α-carbon to both carbonyl groups and then converted into a ketone, or more carbonyl groups and then converted into a ketone, or more specifically an α-substituted acetone.specifically an α-substituted acetone.

Acetoacetic ester Acetoacetic ester is a is a tautomeric substance. He tautomeric substance. He characterized keto-enol tautomery. characterized keto-enol tautomery.

CH3 CO

OC2H5

ethylacetat

C2H5O- Na+

CH3 CO

CH2 COOC2H5

+ C2H5OH

acetoacetic aster

2

H3C-C-CH2-C

O

O

OC2H5

H3C-C=CH -C

OH

O

OC2H5

Acetoacetic ester ketone form ( 92,5% )

Acetoacetic ester enol form ( 7,5% )

TheThe enol form of "acetoacetic ester" stand by enol form of "acetoacetic ester" stand by formation of hydrogen bond:formation of hydrogen bond:

C

CH

C

O OH

H3C OC2H5

...

Chemical properties of acetoacetic ester:Chemical properties of acetoacetic ester:1.1. Reactions of ketone form:Reactions of ketone form:

2. Reactions to enol form:2. Reactions to enol form:a)a) interaction of “acetoacetic ester” with metallic interaction of “acetoacetic ester” with metallic

sodiumsodium

b)b) interaction of “acetoacetic ester” with NaOHinteraction of “acetoacetic ester” with NaOH

c) interaction “acetoacetic ester” with PCLc) interaction “acetoacetic ester” with PCL55

H3C-C=CH-C + 2Na

OH

O

OC2H5

H3C-C=CH -C

ONa

O

OC2H5

+H22 2

H3C-C=CH-C + NaOH

OH

O

OC2H5

H3C-C=CH -C

ONa

O

OC2H5

+H2O

Sodiumacetoacetic ester

ethyl-3-chlorbutene-2-oate

d) interaction of “acetoacetic ester” with bromine water.The discolouration of bromine water, that explained

unsaturated of "acetoacetic ester”.

e) interaction of “acetoacetic ester” with FeCL FeCL33

H3C-C-CH-C + Br2

OH

O

OC2H5

H3C-C- CH -C

OH

O

OC2H5

Br

Br-HBr

H3C-C-CH -C

O Br

O

OC2H5Bromacetoacetic ester

H3C-C=CH-C

OH

O

OC2H5

H3C-C=CH -C

O-Fe

O

OC2H5

Fe3+

violetcolour

The characteristic feature of The characteristic feature of “acetoacetic ester” is is the ability to the ability to ketone decompositionketone decomposition and acid and acid decompositiondecomposition . . Ketone decompositionKetone decomposition occurs when heated in the occurs when heated in the presence of the dilute solutions of acids or alkalis.presence of the dilute solutions of acids or alkalis.

Acid Acid decomposition of decomposition of “acetoacetic ester”

H3C-C-CH2 -CO

OC2H5

H2O; t, H+

+ C2H5OH

O

+ CO2H3C-C-CH3

O

CH3 C

O

CH2 COOC2H5

NaOH (conc.)CH3COONa + C2H5OH2

An “acetoacetic ester” used in the organic synthesis for the extraction used in the organic synthesis for the extraction of difference ketones and carboxylic acids.of difference ketones and carboxylic acids.

CH3 C

O

CH2 COOC2H5

C2H5O-Na+

CH3 C

O

CH COOC2H5-

CH3 C

O

CH COOC2H5

- Na+ CH3I

- NaI

CH3 C

O

CH

CH3

COOC2H5

sodium acetoacetic ester

methylacetoacetic ester

acid decomposition

ketone decomposition

NaOH (conc.)

H or OH (H2O)-+

CH3 C

O

CH2 CH3 + C2H5OH + CO2

butanon

CH3COONasodium acetate

+ CH3 CH2 COONa + C2H5OHsodium propionate

2. Halogenoacids2. HalogenoacidsHalogenoacidsHalogenoacids are the derivatives of carboxyl acids are the derivatives of carboxyl acids

that contain halogen radical (1 or more).that contain halogen radical (1 or more).

α-bromopropanoic acidα-bromopropanoic acid

2-bromopropanoic acid2-bromopropanoic acid

H3C CH C

Br

O

OH

3 2 1

2-bromo-3-methylbutanoic acid,α - bromoisovaleric acid

Cl

COOH

o-chlorobenzoic acid2-chlorobenzoic acid

Methods of extraction of hMethods of extraction of halogenalogenoocarboxylic acidcarboxylic acid ::1.1. Halogenation of saturated carboxylic acids:Halogenation of saturated carboxylic acids:

2.2. Hydrohalogenation of unsaturated carboxylic acidsHydrohalogenation of unsaturated carboxylic acids

3.3. Halogenation of aromatic carboxylic acids:Halogenation of aromatic carboxylic acids:

H3C CH2 CO

OHCl2

PH3C CH C

Cl

O

OHHCl+ +

H2C CH2 CO

OHH2C CH C

O

OH+ HCl

Clacrylic acid acrylic acid ββ-chloropropanoic acid-chloropropanoic acid

CO

OH

Cl2AlCl3

CO

OH

Cl

HCl+ +

m-chlorobenzoic acidm-chlorobenzoic acid

Physical and chemical properties of hPhysical and chemical properties of halogenalogenoocarboxylic acidcarboxylic acid For For physical propertiesphysical properties of halogencarboxylic acids are colorless liquids of halogencarboxylic acids are colorless liquids

or crystalline substance, soluble in water.or crystalline substance, soluble in water. Chemical properties:Chemical properties: in the molecule of halogenoacids either carboxyl in the molecule of halogenoacids either carboxyl

group or halogen radical can react.group or halogen radical can react.

As the halogen atom separation of carboxyl group inductive effect As the halogen atom separation of carboxyl group inductive effect decreases, and so the acidity decreases. In the transition from mono- to decreases, and so the acidity decreases. In the transition from mono- to di- and polyhalogencarboxylic acids the acidity increases. The most di- and polyhalogencarboxylic acids the acidity increases. The most powerful of carboxylic acid is trifluoroacetic acid – CFpowerful of carboxylic acid is trifluoroacetic acid – CF33-COOH (pKa -COOH (pKa 0,23)0,23)

CH3

CL

CH2 CH COOH

CH2

CL

CH2 COOHCH2

CH3

CL

CH COOHCH2

pKa 2,85 pKa 4,05

pKa 4,60

I. Carboxyl group can react with formation of:I. Carboxyl group can react with formation of:a)a) SaltsSalts

H2C CH2 CO

OHCl

NaOH H2C CH2 CO

ONaCl

H2O+ +

2 H2C CH2 CO

OHCl

2 Na 2 H2C CH2 CO

ONaCl

H2+ +

2 H2C CH2 CO

OHCl

MgO

H2C CH2 CO

OMg

OC

OH2C CH2

Cl

Cl

H2O+ +

H2C CH2 CO

OHCl

NaHCO3 H2C CH2 CO

ONaCl

H2CO3

H2O CO2

++

chloroacetat sodiumchloroacetat sodium

b) complex ethers:b) complex ethers:

c) amides:c) amides:

H2C CH2 CO

OH++

Cl

H2OHO CH3 H2C CH2 CO

OCl

CH3

methyl ether of methyl ether of ββ-chloropropanoic acid-chloropropanoic acid

H2C CH2 CO

OH+NH3+

Cl

H2C CH2 CO

NH2Cl

H2Ot=200o

amide amide ββ-chloropropanoic acid-chloropropanoic acid

II. Halogen radical can react with:II. Halogen radical can react with:a)a) ammonium:ammonium:

b) b) NaOH (water solution):NaOH (water solution): 1) for α-halogenoacids1) for α-halogenoacids

H2C CH2 CO

OHCl

2NH3 H2C CH2 CO

ONH2

NH4++ + HCl

ammonium salt of ammonium salt of ββ-aminopropanoic acid-aminopropanoic acid

CH3C CHO

OHCl

NaOHH2O CH3C CH

O

OHOH

NaCl+ +

lactic acid

2) for β-halogenoacids2) for β-halogenoacids

3) for γ,σ-halogenoacids3) for γ,σ-halogenoacids

CH2C CH2

Cl

O

OHNaOH

H2O

-NaClCH2C CH

OH

O

OHH

H2C CH CO

OH+

to

ββ-chloropropanoic acid -chloropropanoic acid ββ-hydroxypropanoic acid acrylic acid-hydroxypropanoic acid acrylic acid

CH2 CO

OHH2C CH2

Cl

NaOHH2O

-NaCl

CH2

CH2C

CH2

OO

+

γγ-butyrolactone-butyrolactone

Representatives of hRepresentatives of halogenalogenoocarboxylic acid carboxylic acid ::

Monochloroacetic acid Dichloroacetic acid Trichloroacetic acid

CCH2

O

OHCl

CCHO

OHCl

ClCC

O

OHCl

Cl

Cl

These acids are used in organic synthesis

Ureide of α-bromisovaleric acid (bromisoval) used in medical practice as a hypnotic.

CH3 CH

CH3

CHBr

O

NH

O

C NH2

C

3. 3. HydroxyacidsHydroxyacids HydroxyacidsHydroxyacids are the derivatives of carboxyl acids that are the derivatives of carboxyl acids that

contain –OH group (1 or more).contain –OH group (1 or more).

3 2 1CH3C CH

O

OHOH

β α

2-hydroxypropanoic acidα-hydroxypropanoic acid

tartaric acidα,α’-dihydroxysuccinic acid,2,3-dihydroxybutandioic acid,

lactic acid,α- hydroxypropanoic acid,2- hydroxypropanoic acid

malic acid,hydroxysuccinic acidhydroxybutanedioic acid

citric acid,2-hydroxy-1,2,3-propantricarboxylic acid

glycolic acid,hydroxyacetic acid,hydroxyethanoic acid

In a row of hydroxyacids often found the optical In a row of hydroxyacids often found the optical isomery.isomery.

D-, or (R,R)-tartaric acid

L-, or (S,S)-tartaric acid

mezo-, or (R,S)-tartaric acid

Methods of extraction of hydroxyacids:Methods of extraction of hydroxyacids:1.1. Hydrolysis of α-halogenoacidsHydrolysis of α-halogenoacids

2.2. Oxidations of diols and hydroxyaldehydesOxidations of diols and hydroxyaldehydes

3.3. Hydration of α,β-unsaturated carboxylic acidsHydration of α,β-unsaturated carboxylic acids

CH3C CHO

OHCl

NaOHH2O CH3C CH

O

OHOH

NaCl+ +

lactic acidlactic acid

CH3C CHO

HOH

CH2H3C CH

OHOH

CH3C CHO

OHOH

[O] [O]

CH CO

OHH2O+CH2 CH2C CH2

O

OH

H+

OH

ββ-hydroxypropanoic acid-hydroxypropanoic acid

4. Hydrolysis of hydroxynitriles (cyanohydrins)4. Hydrolysis of hydroxynitriles (cyanohydrins)

Physical and chemical properties of Physical and chemical properties of hydroxyhydroxycarboxylic acidcarboxylic acid

For For physical propertiesphysical properties of hydroxycarboxylic acids are of hydroxycarboxylic acids are colorless liquids or crystalline substance, soluble in water.colorless liquids or crystalline substance, soluble in water.

Chemical properties:Chemical properties: in the molecule of hydroxyacids ether – in the molecule of hydroxyacids ether –OH group or carboxyl group can react.OH group or carboxyl group can react.

Carboxyl group can react forming:Carboxyl group can react forming:a) salts:a) salts:

H2C CH2 CO

OHOH

NaOH H2C CH2 CO

ONaOH

H2O+ +

sodium sodium ββ-hydroxypropanoic acid-hydroxypropanoic acid

2 H2C CH2 CO

OHOH

2 Na 2 H2C CH2 CO

ONaOH

H2+ +

b) complex ethers:b) complex ethers:

2 H2C CH2 CO

OHOH

MgO

H2C CH2 CO

OMg

OC

OH2C CH2

OH

OH

H2O+ +

H2C CH2 CO

OHOH

NaHCO3 H2C CH2 CO

ONaOH

H2CO3

H2O CO2

++

H2C CH2 CO

OH++

OH

H2OHO CH3 H2C CH2 CO

OOH

CH3

methyl ether of methyl ether of ββ-hydroxypropanoic acid-hydroxypropanoic acid

c) amides:c) amides:

II. –OH group can react with:II. –OH group can react with:a)a) hydrohalogens (HCl, HBr, HI, HF)hydrohalogens (HCl, HBr, HI, HF)

b) can oxidizeb) can oxidize

H2C CH2 CO

OH+NH3+

OH

H2C CH2 CO

NH2OH

H2Ot=200o

amide of amide of ββ-hydroxypropanoic acid-hydroxypropanoic acid

HCl ++ H2OH2C CH2 CO

OHCl

CH2C CH2

O

OHOH

+ H2OCH2C CH2

O

OH

[O]

OH

CHC CH2

O

OHO

ββ-oxopropanoic acid-oxopropanoic acid

lactic acid lactide

3-hydroxybutanoic acid

butene-2-onic (crotonic) acid

Related to heat of:1. α-hydroxyacids

2. β-hydroxyacidsheating

3. γ-hydroxyacids

γ-butyrolacton 4-hydroxybutanic acid

heating

H

O

C

O H

C H 3

O

C

H

+

O

O H

CС H 3 С

O H

H

H 2 S O 4к .

t

HCOOH CO + H2Oк. Н2SO4, t

Ñ ÑH2COOHHOOCH2C

OH

COOH

H CO

OHC CH2COOHO

HOOCH2C

C CH3CH3

O

ê. H2SO4 +

CO H2O 2 CO2

t acetidicarbonic acid

Decomposition of α-hydroxyacids

acetic acid formic acid

Representatives of hydroxyacids:Representatives of hydroxyacids: Milk acidMilk acid . Milk acid is a trivial name because at . Milk acid is a trivial name because at

first it was extracted from milk. It is present in first it was extracted from milk. It is present in kefir yogurt, sour milk and other milk products. It can kefir yogurt, sour milk and other milk products. It can form in muscles during hard and prolonged work. That is why form in muscles during hard and prolonged work. That is why peoples can feel ache in their muscles after physical training. peoples can feel ache in their muscles after physical training. Salts of milk acid are used in medicine.Salts of milk acid are used in medicine.Apple acidApple acid . It is present in green apples . It is present in green apples and some and some berries. It takes part in biological berries. It takes part in biological processes in human processes in human organisms and organisms of other alive creatures. In industry organisms and organisms of other alive creatures. In industry it is used for manufacturing of wine, fruit waters and sweets. It it is used for manufacturing of wine, fruit waters and sweets. It is used in medicine for synthesis of some medical is used in medicine for synthesis of some medical preparations.preparations.Tartaric acidTartaric acid . It is present in grape. It is . It is present in grape. It is used in used in medicine for synthesis of some medicine for synthesis of some medical preparations.medical preparations.

CH3C CHO

OHOH

CH2 CO

OHCHC

O

HOOH

CH

CH

C

C

OH

OH

O

OH

O

OH

Citric acidCitric acid . It . It is present in is present in orange, lemon and other orange, lemon and other

citric fruits. It takes citric fruits. It takes part in part in biological biological processes in processes in human human organism.organism.

HO C

CH2

C

CH2OH

O

C

C

O

OH

O

OH

4. Phenolacids.4. Phenolacids.

o-hydroxycinnamic acid salicylic acid,2-hydroxybenzoic acid

4-hydroxybenzoic acid

3,4,5-trihydroxybenzoic acid,gallic acid

PhenolacidsPhenolacids are the derivatives of aromatic carboxyl acids that are the derivatives of aromatic carboxyl acids that contain –OH group (1 or more).contain –OH group (1 or more).

Methods of phenolacids extraction:Methods of phenolacids extraction:1.1. Carboxylation of Carboxylation of phenolsphenols by by carbon oxidecarbon oxide (IV): (IV): In the Kolbe synthesis, also known as the Kolbe–Schmitt reaction, In the Kolbe synthesis, also known as the Kolbe–Schmitt reaction,

sodium phenoxide is heated with carbon dioxide under pressure, and sodium phenoxide is heated with carbon dioxide under pressure, and

the reaction mixture is subsequently acidified to yield salicylic acidthe reaction mixture is subsequently acidified to yield salicylic acid::

2. Hydroxylation of arencarboxylic acids2. Hydroxylation of arencarboxylic acids

C

O

O-Na+ Cu(OH)2

- NaOH

CO

CuOH

O

t

- Cu

COOH

OH

KCOOH

SO3H

+ KOHalloying +

COO

K2SO3 + H2O

OH

- +

3 2

3. Alloying of sulphobenzoic acid with alkalis3. Alloying of sulphobenzoic acid with alkalis

m-sulphobenzoic acid potassuim salt of m-sulphobenzoic acid potassuim salt of 3-hydroxybenzoic acid3-hydroxybenzoic acid

COOH

OH OH

COONa+ CO2+ NaHCO3 + H2O

salicylic acid

Chemical properties of phenolacids: Chemical properties of phenolacids: Chemical properties of Chemical properties of phenolacids due to the presence phenolacids due to the presence

in their structure of carboxyl group, phenolic hydroxyl and the in their structure of carboxyl group, phenolic hydroxyl and the aromatic nucleus.aromatic nucleus.

DecarboxylationDecarboxylation

COOH

OH

COOH

OHBr

Br+ Br22 + HBr2

3, 5-dibromsalicylic acidwhite precipitate

1

23

4

5

6

Br

OHBr

BrCOOH

OHBr

Br+ Br2 + HBr + CO2

yellow precipitate

OH

COOH

NaHCO3

-CO2, -H2O

OH

COONa POCl3, C6H5ONa

-NaCl, -NaPO3

OH

OC6H5

O

CH3OH

(H2SO4)-H2O

OH

COOCH3NH3

OH

NH2

O

(CH3CO)2O

- CH3COOH

O

COOH

CH3

ONH2

OH

-C6H5OH

OH O

NH

OH

Salicylic acid

Sodium salicylate

C

Phenylsalicylate, salol

Methylsalicylate

C

Salicylamide

C

Acetylsalicylic acid,aspirin

C

Oxaphenamide

The best known aryl ester is O-acetylsalicylic acid, better The best known aryl ester is O-acetylsalicylic acid, better known as aspirin. It is prepared by acetylation of the phenolic known as aspirin. It is prepared by acetylation of the phenolic hydroxyl group of salicylic acid:hydroxyl group of salicylic acid:

Aspirin possesses a number of properties that make it an Aspirin possesses a number of properties that make it an often-recommended drug. It is an analgesic, effective in often-recommended drug. It is an analgesic, effective in relieving headache pain. It is also an antiinflammatory agent, relieving headache pain. It is also an antiinflammatory agent, providing some relief from the swelling associated with arthritis providing some relief from the swelling associated with arthritis and minor injuries. Aspirin is an antipyretic compound; that is, and minor injuries. Aspirin is an antipyretic compound; that is, it reduces fever. Each year, more than 40 million lb of aspirin it reduces fever. Each year, more than 40 million lb of aspirin is produced in the United States, a rate equal to 300 tablets is produced in the United States, a rate equal to 300 tablets per year for every man, woman, and child.per year for every man, woman, and child.

5. Aminoacids5. Aminoacids An An aminoacidaminoacid is an organic compound that is an organic compound that

contains both a amino (–NНcontains both a amino (–NН22) group and a ) group and a carboxyl (-СООН) group. The amino acids carboxyl (-СООН) group. The amino acids found in proteins are always α-amino acids.found in proteins are always α-amino acids.

Methods of aminoacids extraction:Methods of aminoacids extraction: 1.1. Effects of ammonia on halogencarboxylic acids :Effects of ammonia on halogencarboxylic acids :

2.2. Effects of ammonia and HCN on aldehydesEffects of ammonia and HCN on aldehydes

CH3 CH

Cl

COOH + NH3CH3 CH

NH2

COOH + NH4Cl2

CH3 CH

NH2

C NH2O; H+

- NH3

CH3 CH COOH

NH2

2CH3 C

H

NH HCNCH3 C

O

H

NH3

- H2O

αα-chlorpropanoic acid -chlorpropanoic acid αα-aminopropanoic acid-aminopropanoic acid

acetalaldehydeacetalaldehyde aldiminealdimine αα-aminopropanonitrile-aminopropanonitrile

αα-aminopropanoic acid-aminopropanoic acid

[ H ]

- H2O

COOH

NO2

COOH

NH2

CH2 CH COOH + : NH3 CH2

NH2

CH2 COOH

3. Accession of ammonia to the α, β–unsatured acids

acrylic acid

β-aminopropanoic acid

4. Reduce of nitrobenzoic acid

n-nitrobenzoic acid n-aminobenzoic acid

Optical propertiesOptical properties

Physical and chemical properties of aminoacidsPhysical and chemical properties of aminoacids

Both an acidic group (-СООН) and а basic group (-NНBoth an acidic group (-СООН) and а basic group (-NН22) are ) are present on the same carbon in an α-amino acid.present on the same carbon in an α-amino acid.

The net result is that in neutral solution, amino acid molecules The net result is that in neutral solution, amino acid molecules have the structure:have the structure:

А А zwitter-ion zwitter-ion is а molecule that has а positive charge on one is а molecule that has а positive charge on one atom and а negative charge on another atom. atom and а negative charge on another atom.

Reactions on a amino-group:Reactions on a amino-group:

R CH COOH

NH2

HClR CH COOH

NH3Cl+ -

chlorhydrolic salt

RI R CH COOH

NHR- HI

N-alkilderivate

R CH COOH

NHCOR

RCOCl

- HCl

N-acylderivate

HNO2

-N2, - H2OR CH COOH

OHhydroxyacid

Reactions to a carboxylic group:Reactions to a carboxylic group:

R CH COOH

NH2

NaOHR CH COONa

NH2sodium salt

ROH, H R CH COOR

NH2

- H2O

ester

R CH CONHR

NH2

RNH2

- H2O

amide

PCl5

- POCl3, - HClR CH COCl

NH2

chloranhydrid

- H2O

+

Heating of: Heating of: 1.1. αα-aminoacids-aminoacids

2.2. ββ-aminoacids-aminoacids

CH COOH

NH2

CH3

tN

C CH

CHN

CO

O

H

H

CH3

CH3

+ H2O2

2

CH COOHCHCH3 + NH3CH2 COOHCHt

CH3

NH2

αα-aminopropanoic acid-aminopropanoic acid

3,6-dimethyl-2,5-diketopiperazine3,6-dimethyl-2,5-diketopiperazine

ββ-aminooil acid crotonic acid-aminooil acid crotonic acid

N O + H2OCH2 COOHCH2

tCH2

NH2H

3. 3. γγ-aminoacids-aminoacids

γγ-aminooil acid -aminooil acid γγ-lactam -lactam

React React αα-aminoacids with ninhydrin-aminoacids with ninhydrin

OH

OH

O

O

+ H3N-CH-COO-

R

+

O

O

N-CH-COOH+H2O

R

Ninhydrin

O

O

N-CH-C

R

H

O

O

N=C-C

R

H2OH

NH2

O

O

2-aminoindandion

O

OHO

OH

H

H2N

O

O

OH

OH

O

O

+

O

O

NH

O

O

O

O

N

O

O

H+

Âlue - violet dye-stuff

Carbonic acidCarbonic acid (ancient name acid of air or aerial acid) (ancient name acid of air or aerial acid) has the formula Hhas the formula H22COCO33. It is also a name sometimes . It is also a name sometimes given to solutions of carbon dioxide in water, which given to solutions of carbon dioxide in water, which contain small amounts of Hcontain small amounts of H22COCO33. The salts of carbonic . The salts of carbonic acids are called bicarbonates (or hydrogen carbonates) acids are called bicarbonates (or hydrogen carbonates) and carbonates. It is a weak acid.and carbonates. It is a weak acid. Carbonic acid is diprotic: it has two hydrogen atoms which Carbonic acid is diprotic: it has two hydrogen atoms which may dissociate from the parent molecule. Thus there are two may dissociate from the parent molecule. Thus there are two dissociation constants, the first one for the dissociation into dissociation constants, the first one for the dissociation into the bicarbonate (also called hydrogen carbonate) ion HCOthe bicarbonate (also called hydrogen carbonate) ion HCO33¯̄:: HH22COCO33 HCO3⇌ HCO3⇌ ¯̄ + H + H++ KKaa11 = 2.5×10 = 2.5×10¯̄4 ; p4 ; pKKaa11 = 3.45 +/- 0,15 at 25 ° = 3.45 +/- 0,15 at 25 °TThe second for the dissociation of the bicarbonate ion into he second for the dissociation of the bicarbonate ion into

the carbonate ion COthe carbonate ion CO33²¯²¯:: HCOHCO33¯̄ CO⇌ CO⇌ 33 + H+ + H+ KKaa22 = 5.61×10−11 ; p = 5.61×10−11 ; pKKaa22 = 10.25 at 25 °C. = 10.25 at 25 °C.

HO C

Omonoethyl ester of carbonic acid, monoethyl carbonate

OC2H5

C

Odiethyl ester of carbonic acid, diethyl carbonate

OC2H5C2H5O

OHCl C

Omonochoranhydride carbonic acid ,chlorcarbonic acid

Cl C

Odichoranhydride carbonic acid , phosgene

Cl

HO C

Omonoamide carbonic acid,carbamic acid

NH2 C

Odiamide carbonic acid, carbamide, urea

NH2H2N

C

O ethyl ester of chlorcarbonic acid

OC2H5Cl C

Oethyl ester of carbamic acid, urethane

C2H5O NH2

Functional dFunctional derivates of carbonerivates of carbonicic acid. acid.

Cl C

Odichoranhydride carbonic acid , phosgene

ClCO + Cl2

hv

6. Chloranhydrides of 6. Chloranhydrides of carboncarbonicic acid acid

OHCl C

Omonochoranhydride carbonic acid ,chlorcarbonic acid

Cl C

Odichoranhydride carbonic acid , phosgene

Cl

Produces phosgene by interaction of carbon oxide (II) Produces phosgene by interaction of carbon oxide (II) with chlorine on the light.with chlorine on the light.

CO2 +Cl C

O phosgene

Cl H2O + HCl2

Physical and chemical properties of aPhysical and chemical properties of a phosgenephosgenePhosgenePhosgene is the chemical compound with the formula COCl is the chemical compound with the formula COCl22. . This colorless gas gained infamy as a chemical weapon during This colorless gas gained infamy as a chemical weapon during World War I, and is also a valued industrial reagent and building World War I, and is also a valued industrial reagent and building block in organic synthesis. In low concentrations, its odor block in organic synthesis. In low concentrations, its odor resembles freshly cut hay or grass. Some soldiers during the resembles freshly cut hay or grass. Some soldiers during the First World War stated that it smelled faintly of First World War stated that it smelled faintly of MMay Blossom. In ay Blossom. In addition to its industrial production, small amounts occur addition to its industrial production, small amounts occur naturally naturally byby the breakdown of chlorinated compounds and the the breakdown of chlorinated compounds and the combustion of chlorine-containing organic compoundscombustion of chlorine-containing organic compounds

1. 1. Hydrolysis of phosgene

2. Interaction of phosgene with alcohols

3. Interaction of phosgene with ammoium

+Cl C

O phosgene

Cl CH3OH + HClC

O methyl ester of chlorcarbonic acid

OC2H5Cl

+Cl C

O phosgene

Cl CH3OH + HClC

Odimethyl ester of carbonic acid

OCH3CH3O2 2

+Cl C

O phosgene

Cl NH3C

O

diamide carbonic acid, carbamide, urea

NH2H2N + HCl2 2

HO C

Omonoamide carbonic acid,carbamic acid

NH2

+ NH3 + HClC

O methyl ester of carbamic acid

H2N OCH3C

O methyl ester of chlorcarbonic acid

OCH3Cl

C

Odiethyl ester of carbonic acid, diethyl carbonate

OC2H5C2H5O C

Oethyl ester of carbamic acid, urethane

C2H5O NH2+ NH3+ C2H5OH

7. Amides of carbonic acidC

Odiamide carbonic acid, carbamide, urea

NH2H2N

Esters of carbamic acid are named urethanes

CH2

H2N C

O

O CH2 C

CH3

CH2 CH3

CH2 O C

O

NH2

meprothan (meprobamate),dicarbamate 2-methyl-2-propylpropandiol-1,3

Meprothan used in a medicine as a medicament, which has tranquilization and hypnotic effects.

C

Odiamide carbonic acid, carbamide, urea

NH2H2NNH3 + CO2

p, t + H2O2

Urea or carbamide is an organic compound with the chemical formula (NH2)2CO. The molecule has two amine (-NH2) residues joined by a carbonyl (-CO-) functional group. Urea was first discovered from urine in 1773 by the French chemist Hilaire Rouelle.In 1828, the German chemist Friedrich Wöhler obtained urea by treating of silver isocyanate with ammonium chloride in a failed attempt to prepare ammonium cyanate:

AgNCO + NH4Cl → (NH2)2CO + AgCl

In the industry urea produces by interaction of an ammonia with carbon oxide (IV)

C

O

urea

NH2H2N + HNO3 C

nitrate urea

NH2H2N

OH

+NO3

-

C

O

urea

NH2H2N + H2O NH3

+H or OH

-

CO2 + 2

Physical and chemical properties of an ureaPhysical and chemical properties of an ureaThe urea molecule is planar. Each carbonyl oxygen atom accepts four N-H-O hydrogen The urea molecule is planar. Each carbonyl oxygen atom accepts four N-H-O hydrogen bonds. This dense and energetically favourable hydrogen-bond network is probably bonds. This dense and energetically favourable hydrogen-bond network is probably established at the cost of efficient molecular packingestablished at the cost of efficient molecular packing.. The structure is quite open, the The structure is quite open, the ribbons forming tunnels with square cross-section. The carbon in urea is described as ribbons forming tunnels with square cross-section. The carbon in urea is described as spsp²² hybridized, the C-N bonds have significant double bond character, and the carbonyl hybridized, the C-N bonds have significant double bond character, and the carbonyl oxygen is basic compared to formaldehyde. Its high solubility is due to extensive oxygen is basic compared to formaldehyde. Its high solubility is due to extensive hydrogen bonding with water: up to eight hydrogen bonds may form - two from the hydrogen bonding with water: up to eight hydrogen bonds may form - two from the oxygen atom, one from each hydrogen atom and one from each nitrogen atom.oxygen atom, one from each hydrogen atom and one from each nitrogen atom.

1. 1. Interaction of an urea with strong acidsInteraction of an urea with strong acids

2. 2. Hydrolysis of an urea during to heatingHydrolysis of an urea during to heating

C

O

urea

NH2H2N + +C2H5I C2H5 NH C

O

NH2 HI

ethylurea

C

O

urea

NH2H2N + +CH3 C NH C

O

NH2 HCl

acetylurea

C

O

Cl O

CH3

44. . Interaction of an urea with halohenanhydrides of carboxylic Interaction of an urea with halohenanhydrides of carboxylic acids (acylation)acids (acylation)

3. 3. Interaction of an urea with halohenalkanes (alkylation)Interaction of an urea with halohenalkanes (alkylation)

Dicarboxylic acids can form with an urea cycle ureides. For example,barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in hot water. Barbituric acid is the parent compound of barbiturate medicine, although barbituric acid itself is not pharmacologically active.

C

O

urea

NH2H2N + +HNO2 CO2 N2 + H2O2 2 3

C

O

urea

NH2H2N + +NaOBr CO2 N2 + H2O3 2 + NaBr3

55. . Interaction of an urea with HNOInteraction of an urea with HNO22

66. . Interaction of an urea with water solution of Interaction of an urea with water solution of hypobromides. Thishypobromides. This reaction as the previous can be used toreaction as the previous can be used to quantitative determination of an ureaquantitative determination of an urea..

5. 5. Biuret reaction. Used for qualitative determination of an urea Biuret reaction. Used for qualitative determination of an urea and proteins, as containing in its structure of a groupand proteins, as containing in its structure of a group–С–СO-NH-.O-NH-.

COH2N

H2N +

+NH2

C O

NH2+H2N C NH2

O

3NH3 +C

N

NO C O

H

N HHC

Oisocyanuric acid

C

N

NO C OH

N

H

H

C

Ocyanuric acid

By-product of a biuret reaction is the isocyanuric acid, which By-product of a biuret reaction is the isocyanuric acid, which forms as a result of trimerazation of cyanuric acidforms as a result of trimerazation of cyanuric acid..

C

guanidine

NH2H2N + HCl C

guanidinium chloride

NH2H2N+

Cl-

NH NH2

C

guanidine

NH2H2N

NH

C

guanidine

NH2H2N

NH+

C2H5O C

O

CH2

C

OC2H5O

H2SO4; POCl3; H2

H2NN

N

2-aminopyrimidine

Physical and chemical properties of a guanidinePhysical and chemical properties of a guanidine

1. 1. Interaction a guanidine with acidsInteraction a guanidine with acids

2. 2. Interaction a guanidine with bifunctional compoundsInteraction a guanidine with bifunctional compounds(diesters, diketones)(diesters, diketones)

Arginine Arginine plays an important plays an important role in cell division, the healing of role in cell division, the healing of

wounds, removing ammonia wounds, removing ammonia from the from the body,body, immune function, and immune function, and ththee release release of hormonesof hormones..

The remain of guanidine is the structural components of The remain of guanidine is the structural components of many compounds. For example:many compounds. For example:

Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA.

StreptomycinStreptomycin is an antibiotic is an antibiotic drug, the first of a class drug, the first of a class of drugs of drugs called called aminoglycosides to be aminoglycosides to be discovered, and was the first discovered, and was the first antibiotic remedy for tuberculosis. antibiotic remedy for tuberculosis.

Streptomycin - (IUPAC) name 5-(2,4-diguanidino-3,5,6-trihydroxy-cyclohexoxy)- 4-[4,5-dihydroxy-6-(hydroxymethyl)-3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl-tetrahydrofuran-3-carbaldehyde

8. 8. SulfoacidsSulfoacids called the derivatives of organic called the derivatives of organic compounds in which an atom of hydrogen compounds in which an atom of hydrogen replaced by the residue of sulfuric acid – replaced by the residue of sulfuric acid – sulfogroup sulfogroup – – SOSO33H.H.

Aliphatic sulfoacidsAliphatic sulfoacids ССHH33-SO-SO22OHOH С СHH33--ССHH22-SO-SO22OHOH methanesulfonic acid ethanesulfonicmethanesulfonic acid ethanesulfonic acid acid

((methanesulfoacidmethanesulfoacid)) ((ethanesulfoacidethanesulfoacid))

Functional derivatives of sulfoacidsFunctional derivatives of sulfoacids

CHCH33-SO-SO22Cl - choranhydride of methanesulfoacid (methane Cl - choranhydride of methanesulfoacid (methane sulfonylchloride) sulfonylchloride)

CHCH33-SO-SO22ONa – sodium salt of methanesulfoacid ONa – sodium salt of methanesulfoacid (methanesulfate sodium) (methanesulfate sodium)

CHCH33-SO-SO22NHNH22 – amide of methanesulfoacid – amide of methanesulfoacid (methanesulfonamide) (methanesulfonamide)

CHCH33-SO-SO22-OC-OC22HH55 – ethyl ester of methanesulfoacid – ethyl ester of methanesulfoacid (ethylmetanesulfonate) (ethylmetanesulfonate)

Sulfonic acids are typically much stronger acids than Sulfonic acids are typically much stronger acids than their carboxylic equivalents, and have the unique their carboxylic equivalents, and have the unique tendency to bind proteins and carbohydrates tightly; tendency to bind proteins and carbohydrates tightly; most "washable" dyes are sulfonic acids (or have the most "washable" dyes are sulfonic acids (or have the functional sulfonyl group in them) for this reason. They functional sulfonyl group in them) for this reason. They are also used as catalysts and intermediates for a are also used as catalysts and intermediates for a number of different products. Sulfonic acids and their number of different products. Sulfonic acids and their salts (sulfonates) are used extensively in salts (sulfonates) are used extensively in obtaining obtaining such such diverse products like detergents, antibacterial drugsdiverse products like detergents, antibacterial drugs,, medicine with derivatives of sulfonic acidmedicine with derivatives of sulfonic acid, anion , anion exchange resins (water purification), and dyesexchange resins (water purification), and dyes. . The The simplest example is methanesulfonic acid, CHsimplest example is methanesulfonic acid, CH33SOSO22OH, OH, which is a reagent regularly used in organic chemistry. which is a reagent regularly used in organic chemistry. pp--ttoluenesulfonic acid is also an important reagent. oluenesulfonic acid is also an important reagent.

EExtractionxtraction of aliphatic sulfoacids : of aliphatic sulfoacids :1.1. Sulfochlorination:Sulfochlorination:

2.2. Sulfooxidation:Sulfooxidation:2R-H + 2SO2R-H + 2SO22 + O + O22 = 2R-SO = 2R-SO22OHOH

alkanesulfonic acidalkanesulfonic acid3. Oxidation of thiols:3. Oxidation of thiols:

CH3 CH3 + SO2 + Cl2hv

CH3 CH2 SO2Cl + HClethanesulfonylchloride

C2H5 SHKMnO4 or HNO3

C2H5 SO2 + H2O

ethanethiol ethanesulfoacid

4. Sulfonation of alkanes by conc. H4. Sulfonation of alkanes by conc. H22SOSO4 4 ::

5. 5. AAccessionccession of hydrosulfites to alkenes: of hydrosulfites to alkenes:

CH

CH3

CH3

H3C + SO3

H2SO4C

CH3

CH3

H3C SO2OH

isobutane2-methyl-2-propanesulfoacid

R CH CH2 + NaHSO3

R OORR CH2 CH2 SO2ONa

alkanesulfonate sodium

Chemical properties of aliphatic sulfoacidsChemical properties of aliphatic sulfoacids1. Formation salts of sulfoacids:1. Formation salts of sulfoacids:

CC22HH55-SO-SO22-OH + NaOH = C-OH + NaOH = C22HH55-SO-SO22-ONa + H-ONa + H22OO2 C2 C22HH55-SO-SO22-OH + 2 Na = 2 C-OH + 2 Na = 2 C22HH55-SO-SO22-ONa + H-ONa + H22

2. Formation of sulfonylchlorides2. Formation of sulfonylchloridesR-SOR-SO22-OH + PCl-OH + PCl55 = R-SO = R-SO22Cl + POClCl + POCl33 + HCl + HCl

3. Formation of sulfonamides3. Formation of sulfonamidesR-SOR-SO22-Cl + 2 NH-Cl + 2 NH33 = R-SO = R-SO22-NH-NH22 + NH + NH44ClCl

4. Formation esters of sulfoacids4. Formation esters of sulfoacidsR-SOR-SO22-Cl + 2 NaO-R-Cl + 2 NaO-R′′ = R-SO = R-SO22-O-R-O-R′′ + NaCl + NaCl

C2H5 SO2OH + CaC2H5 SO2

O

C2H5 SO2 OCa + H22

Aromatic sulfoacidsAromatic sulfoacidsSO3H

benzol sulfoacid

SO3H

p-toluol sulfoacid

CH3

SO3H

m-benzoldisulfoacid

SO3H

SO3H

1,3,5-benzoltrisulfoacid

SO3HH3OS

OH

SO3H

H2SO4

OH

H2SO4

OH

HO3St=-20 t=+100

o-hydroxybenzylsulphoacid p-hydroxybenzylsulphoacid

EExtractionxtraction of aromaric sulfoacids: of aromaric sulfoacids:

H2SO4

SO3H

H2O+ +

1. Sulfonation of aromatic ring1. Sulfonation of aromatic ring

CH3

+ H2SO4

25 C+

CH3 CH3

SO2OH

SO2OH

p-toluol sulfoacid 65%p-toluol sulfoacid 32%

+ H2O2 2 2

SO3H

+ SO3

210 C

H2SO4

SO3, 275C

Hg

SO3H

SO3H SO3HSO3H

SO3H

Chemical properties of aromatic sulfoacidsChemical properties of aromatic sulfoacidsI.I. Reactions of the sulfogroup:Reactions of the sulfogroup:a) formation salts of sulfoacids:a) formation salts of sulfoacids:

CC66HH55SOSO22OH + NaOH = COH + NaOH = C66HH55SOSO22Na + HNa + H22OOb) formation of sulfonylchlorides:b) formation of sulfonylchlorides:

CC66HH55SOSO22OH + PClOH + PCl55 = C = C66HH55-SO-SO22-Cl + POCl-Cl + POCl33 + HCl + HClCC66HH55 + 2 HO-SO + 2 HO-SO22Cl = CCl = C66HH55-SO-SO22Cl + HCl + H22SOSO44 + HCl + HCl

c) formation of sulfonamides:c) formation of sulfonamides:CC66HH55SOSO22Cl + 2 NHCl + 2 NH33 = C = C66HH55-SO-SO22-NH-NH22 + NH + NH44ClCl

d) formation esters:d) formation esters: CC66HH55SOSO22Cl + HO-CCl + HO-C22HH55 = C = C66HH55-SO-SO22-O-C-O-C22HH55 + HCl + HCl

e) reduced of the sulfogroup:e) reduced of the sulfogroup:

C6H5 SO2OH6 H

Zn+ H2SO4

C6H5 SH + 3 H2O

f) sf) synthesisynthesis of a saccharin of a saccharin

O

CH3

+ HOSO2ClCH3

SO2Cl

-

CH3

SO2Cl -NH4Cl

+ 2 NH3

CH3

SO2NH2

KMnO4

SO2NH2

COOH t

- H2O

o-toluolsulfonamide o-toluolsulfonamide of benzoic acid

o-toluolsulfonimide of benzoic acid

SO2

CN H

+ NaOH, H2O

SO2

C

O

N Na * 2 H20

saccharin

2

II. Reactions SII. Reactions SEE, S, SNN of sulfogroup: of sulfogroup:

C6H5 SO2OH C6H6 + H2SO4

t

HCl+ H2O

C6H5 SO2OH + NaOH C6H5SO2ONa + H2O

C6H5 SO2ONa+ NaOH C6H5ONa + H2O2 Na2SO4 +t

C6H5 ONa + H2CO4 C6H5OH + NaHCO3H+

C6H5 SO2ONa + NaCN C6H5CN + Na2SO3t, Sn

b) a reaction of alkalic floatingb) a reaction of alkalic floating

a) desulfonationa) desulfonation

SO3H

Cl2, FeCl3

Se

SO3H

Cl

III. Substitution reaction of atom H in the benzene nucleus

7.Sulphanylamidic preparations7.Sulphanylamidic preparations Sulfanilamide is a molecule containing the sulfonamide functional Sulfanilamide is a molecule containing the sulfonamide functional group attached to an aniline. Sulfanilamide is a sulfonamide group attached to an aniline. Sulfanilamide is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. meningeal infections. Their antibacterial action is inhibited by pus. Mechanism of action: Sulfanilamide is a competitive inhibitor of Mechanism of action: Sulfanilamide is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. Indication: For the these organisms for the synthesis of folic acid. Indication: For the treatment of vulvovaginitis caused by Candida albicanstreatment of vulvovaginitis caused by Candida albicans

Sulphanylamidic preparations. All sulphanylamidic Sulphanylamidic preparations. All sulphanylamidic medicines contain the next fragment:medicines contain the next fragment:

Albucyde (sulphacyl)Albucyde (sulphacyl) – is an antibacterial mean, is a part of eye- – is an antibacterial mean, is a part of eye-drops.drops.UrosulphaneUrosulphane – is an antibacterial mean by infection of urinal – is an antibacterial mean by infection of urinal canals.canals.NorsulphazolNorsulphazol – is used by pneumonia, meningitis, staphylococcal – is used by pneumonia, meningitis, staphylococcal and streptococcal sepsis, infectious diseases.and streptococcal sepsis, infectious diseases.BucarbaneBucarbane – is a hypoglycemic mean. – is a hypoglycemic mean.

NH2

O2SNH

CH3

O

NH2

O2SNH

NH2

O

S

N

NH2

O2SNH

NH2

O2SNH

NH

C4H9

O

C

Альбуцил,сульфацил

C

Уросульфан Норсульфазол

C

БукарбанAlbucyde Urosulphane Norsulphazol Bucarbane(sulphacyl)

9. Aminoacids.1). α-Aminoacids as structure components of

proteins. Next to water, proteins are the most abundant Next to water, proteins are the most abundant

substances in most cells - from 10% to 20% of the substances in most cells - from 10% to 20% of the cell’s mass. All proteins contain the elements carbon, cell’s mass. All proteins contain the elements carbon, hydrogen, oxygen, and nitrogen; most also contain hydrogen, oxygen, and nitrogen; most also contain sulfur. The presence of nitrogen in proteins sets them sulfur. The presence of nitrogen in proteins sets them apart from carbohydrates and lipids, which generally apart from carbohydrates and lipids, which generally do not contain nitrogen. The average nitrogen content do not contain nitrogen. The average nitrogen content of proteins is 15.4% by mass. Other elements, such as of proteins is 15.4% by mass. Other elements, such as phosphorus and iron, are essential constituents of phosphorus and iron, are essential constituents of certain specialized proteins. Casein, the main protein certain specialized proteins. Casein, the main protein of milk, contains phosphorus, an element very of milk, contains phosphorus, an element very important in the diet of infants and children. important in the diet of infants and children. Hemoglobin, the oxygen-transporting protein of Hemoglobin, the oxygen-transporting protein of blood, contains iron.blood, contains iron.

The word The word proteinprotein comes from the Greek comes from the Greek proteiosproteios, , which means "of first importance." This derivation which means "of first importance." This derivation alludes to the key role that proteins play in life alludes to the key role that proteins play in life processes. processes.

А А proteinprotein is in polymer in which the monomer units is in polymer in which the monomer units are aminoacids. Thus the starting point for а are aminoacids. Thus the starting point for а discussion of proteins is an understanding of the discussion of proteins is an understanding of the structures and chemical properties of aminoacids.structures and chemical properties of aminoacids.

An An aminoacidaminoacid is an organic compound that contains is an organic compound that contains both an amino (–NН3) group and a carboxyl (-both an amino (–NН3) group and a carboxyl (-СООН) group. The aminoacids found in proteins are СООН) group. The aminoacids found in proteins are always α-aminoacids - that is, aminoacids in which always α-aminoacids - that is, aminoacids in which the aminogroup is attached to the α-carbon atom of the aminogroup is attached to the α-carbon atom of the carboxylic acid carbon chain. the carboxylic acid carbon chain.

The general structural formula for an α-aminoacid is:The general structural formula for an α-aminoacid is:

The R group present in an α-aminoacid is called the The R group present in an α-aminoacid is called the aminoacid side chain. The nature of this side chain aminoacid side chain. The nature of this side chain distinguishes а-aminoacids from each other. Side chains vary distinguishes а-aminoacids from each other. Side chains vary in size, shape, charge, acidity, functional groups present, in size, shape, charge, acidity, functional groups present, hydrogen-bonding ability, and chemical reactivity.hydrogen-bonding ability, and chemical reactivity.

2). Classification and structure of 2). Classification and structure of aminoacids. aminoacids.

Over 700 different naturally occurring Over 700 different naturally occurring aminoacids are known, but only 20 of them, called aminoacids are known, but only 20 of them, called standard aminoacids, are normally present in proteins. standard aminoacids, are normally present in proteins. А А standard aminoacidstandard aminoacid is one of the 20 α-aminoacids is one of the 20 α-aminoacids normally found in proteins. Aminoacids are grouped normally found in proteins. Aminoacids are grouped according to side-chain polarity. In this system there according to side-chain polarity. In this system there are four categories: (1) nonpolar aminoacids, (2) are four categories: (1) nonpolar aminoacids, (2) polar neutral aminoacids, (3) polar acidicamino acids, polar neutral aminoacids, (3) polar acidicamino acids, and (4) polar basic aminoacids. This classification and (4) polar basic aminoacids. This classification system gives insights into how various types of system gives insights into how various types of aminoacid side chains help determine the properties aminoacid side chains help determine the properties of proteins.of proteins.

Nonpolar aminoacidsNonpolar aminoacids contain one amino group, contain one amino group, one carboxyl group, and a nonpolar side chain. one carboxyl group, and a nonpolar side chain. When incorporated into а protein, such When incorporated into а protein, such aminoacids are hydrophobic (“water fearing”); aminoacids are hydrophobic (“water fearing”); that is, they are not attracted to water molecules. that is, they are not attracted to water molecules. They are generally found in the interior of They are generally found in the interior of proteins, where there is limited contact with proteins, where there is limited contact with water. There are eight nonpolar aminoacids. The water. There are eight nonpolar aminoacids. The three types of polar aminoacids have varying three types of polar aminoacids have varying degrees of affinity for water. Within а protein, degrees of affinity for water. Within а protein, such aminoacids are said to be hydrophilic such aminoacids are said to be hydrophilic ("water-loving"). Hydrophilic aminoacids are ("water-loving"). Hydrophilic aminoacids are often found on the surfaces of proteins.often found on the surfaces of proteins.

Polar neutral aminoacidsPolar neutral aminoacids contain one amino group, contain one amino group, one carboxyl group, and а side chain that is polar but one carboxyl group, and а side chain that is polar but neutral. The side chain is neutral in that it is neither acidic neutral. The side chain is neutral in that it is neither acidic nor basic in solution at physiological pH. There are seven nor basic in solution at physiological pH. There are seven polar neutral aminoacids. polar neutral aminoacids. Polar acidic aminoacidsPolar acidic aminoacids contain contain one amino group and two carboxyl groups, the second one amino group and two carboxyl groups, the second carboxyl group being part of the side chain. In solution at carboxyl group being part of the side chain. In solution at physiological рН, the side chain of а polar acidic aminoacid physiological рН, the side chain of а polar acidic aminoacid bears а negative charge; the side-chain carboxyl group has bears а negative charge; the side-chain carboxyl group has lost its acidic hydrogen atom. There are two polar acidic lost its acidic hydrogen atom. There are two polar acidic aminoacids: aspartic acid and glutamic acid. aminoacids: aspartic acid and glutamic acid. Polar basic Polar basic aminoacidsaminoacids contain one amino groups and one carboxyl contain one amino groups and one carboxyl group, the second amino group being part of the side chain. group, the second amino group being part of the side chain. In solution at physiological рН, the side chain of а polar In solution at physiological рН, the side chain of а polar basic aminoacid bears а positive charge; the nitrogen atom basic aminoacid bears а positive charge; the nitrogen atom of the amino group has accepted а proton. There are three of the amino group has accepted а proton. There are three polar basic aminoacids: lysine, arginine, and histidine.polar basic aminoacids: lysine, arginine, and histidine.

According to the chemical origin of the residue According to the chemical origin of the residue connected with connected with αα-aminoacid fragment – -aminoacid fragment – CH(NH2)COOH, CH(NH2)COOH, αα-aminoacids divided on aliphatic, -aminoacids divided on aliphatic, aromatic and heterocyclic. aromatic and heterocyclic.

In heterocyclic In heterocyclic αα-aminoacids proline and oxyproline -aminoacids proline and oxyproline αα--aminoacid’s fragment presents in hetecyclic structure. aminoacid’s fragment presents in hetecyclic structure.

According to the quantity of –NH2 and –COOH groups in According to the quantity of –NH2 and –COOH groups in molecule molecule αα-aminoacids-aminoacids divided on monoaminocarbonic, divided on monoaminocarbonic, monoaminodicarbonic and diaminomonocarbonic.monoaminodicarbonic and diaminomonocarbonic.

Classification and structure of amino acidsClassification and structure of amino acids

The names of the standard aminoacids The names of the standard aminoacids are often abbreviated using three-letter codes. are often abbreviated using three-letter codes. Except in four cases, these abbreviations are Except in four cases, these abbreviations are the first three letters of the aminoacid’s name. the first three letters of the aminoacid’s name. In addition, а new one-letter code for In addition, а new one-letter code for aminoacid names is currently gaining aminoacid names is currently gaining popularity (particularly in computer popularity (particularly in computer applications). These abbreviations are used applications). These abbreviations are used extensively when describing peptides and extensively when describing peptides and proteins, which contain tens and hundreds of proteins, which contain tens and hundreds of aminoacid units. aminoacid units.

The essential aminoacids.The essential aminoacids. All of the 20 aminoacids All of the 20 aminoacids are necessary constituents of human protein. Adequate are necessary constituents of human protein. Adequate amounts of 11 of the 20 aminoacids can be synthesized amounts of 11 of the 20 aminoacids can be synthesized from carbohydrates and lipids in the body if а source of from carbohydrates and lipids in the body if а source of nitrogen is also available. Because the human body is nitrogen is also available. Because the human body is incapable of producing 9 of these 20 acids fast enough or incapable of producing 9 of these 20 acids fast enough or in sufficient quantities to sustain normal growth, these 9 in sufficient quantities to sustain normal growth, these 9 aminoacids, called essential aminoacids, must be obtained aminoacids, called essential aminoacids, must be obtained from food. Essential aminoacids are aminoacids that must from food. Essential aminoacids are aminoacids that must be obtained from food. An adequate human diet must be obtained from food. An adequate human diet must include foods that contain these essential aminoacids. The include foods that contain these essential aminoacids. The human body can synthesize small amounts of some of the human body can synthesize small amounts of some of the essential aminoacids, but not enough to meet its needs, essential aminoacids, but not enough to meet its needs, especially in the case of growing children. The 9 essential especially in the case of growing children. The 9 essential aminoacids for adults are histidine, isoleucine, leucine, aminoacids for adults are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. (In addition, arginine is essential for children).and valine. (In addition, arginine is essential for children).

А complete dietary protein А complete dietary protein contains all the contains all the essential aminoacids in the same relative amounts in essential aminoacids in the same relative amounts in which human being require them. А complete dietary which human being require them. А complete dietary protein may or may not contain all the nonessential protein may or may not contain all the nonessential aminoacids. Most animal proteins, including casein aminoacids. Most animal proteins, including casein from milk and proteins found in meat, fish, and eggs, from milk and proteins found in meat, fish, and eggs, are complete proteins, although gelatin is an are complete proteins, although gelatin is an exception (it lacks tryptophan). Proteins from plants exception (it lacks tryptophan). Proteins from plants (vegetables, grains, and legumes) have quite diverse (vegetables, grains, and legumes) have quite diverse aminoacid patterns, and some tend to be limiting in aminoacid patterns, and some tend to be limiting in one or more essential aminoacids. Some plant one or more essential aminoacids. Some plant proteins (for example, corn protein) are far from proteins (for example, corn protein) are far from complete. Others (for example, soy protein) are complete. Others (for example, soy protein) are complete. Thus vegetarians must eat а variety of plant complete. Thus vegetarians must eat а variety of plant foods to obtain all of the essential aminoacids in foods to obtain all of the essential aminoacids in appropriate quantities.appropriate quantities.

3). 3). Chirality of aminoacids.Chirality of aminoacids. Four different groups are attached to the α-carbon Four different groups are attached to the α-carbon

atom in all of the standard aminoacids except glycine, atom in all of the standard aminoacids except glycine, where the R group is а hydrogen atom. This means that where the R group is а hydrogen atom. This means that the structures of 19 of the 20 standard aminoacids possess the structures of 19 of the 20 standard aminoacids possess а chiral center at this location, so enantiomeric forms а chiral center at this location, so enantiomeric forms (left- and right-handed forms) exist for each of these (left- and right-handed forms) exist for each of these aminoacids. With few exceptions (in some bacteria), the aminoacids. With few exceptions (in some bacteria), the aminoacids found in nature and in proteins are isomers. aminoacids found in nature and in proteins are isomers. Thus, as is the case with monosaccharides, nature favors Thus, as is the case with monosaccharides, nature favors one mirror-image form over the other. Interestingly, for one mirror-image form over the other. Interestingly, for aminoacids the L isomer is the preferred form, whereas aminoacids the L isomer is the preferred form, whereas for monosaccharides the n isomer is preferred.for monosaccharides the n isomer is preferred.

The rules for drawing Fischer projections for aminoacid The rules for drawing Fischer projections for aminoacid structures follow :structures follow :

1. The - СООН group is put at the top of the projection, the R 1. The - СООН group is put at the top of the projection, the R group at the bottom. This positions the carbon chain vertically. group at the bottom. This positions the carbon chain vertically.

2. The – NН2 group is in а horizontal position. Positioning it on 2. The – NН2 group is in а horizontal position. Positioning it on the left denotes the L isomer, and positioning it on the right the left denotes the L isomer, and positioning it on the right denotes the D isomer.denotes the D isomer.

4). Acid - base properties of aminoacids.4). Acid - base properties of aminoacids. In pure form, aminoacids are white crystalline solids In pure form, aminoacids are white crystalline solids

with relatively high decomposition points. (Most amino acids with relatively high decomposition points. (Most amino acids decompose before they melt.) Also most aminoacids are not decompose before they melt.) Also most aminoacids are not very soluble in water because of strong intermolecular forces very soluble in water because of strong intermolecular forces within their crystal structures. Such properties are those often within their crystal structures. Such properties are those often exhibited by compounds in which charged species are present. exhibited by compounds in which charged species are present. Studies of aminoacids confirm that they are charged species Studies of aminoacids confirm that they are charged species both in the solid state and in solution. Both an acidic group (-both in the solid state and in solution. Both an acidic group (-СООН) and а basic group (-NН2) are present on the same СООН) and а basic group (-NН2) are present on the same carbon in an α-aminoacid.carbon in an α-aminoacid.

We learned that in neutral solution, carboxyl groups have We learned that in neutral solution, carboxyl groups have а tendency to lose protons (Н+), producing а negatively а tendency to lose protons (Н+), producing а negatively charged species:charged species:

––СООН = – СОО- + Н+СООН = – СОО- + Н+We learned that in neutral solution, amino groups have а We learned that in neutral solution, amino groups have а

tendency to accept protons (Н+), producing а positively tendency to accept protons (Н+), producing а positively charged species:charged species:

– –NHNH22 + H+ == –NH3+ + H+ == –NH3+As is consistent with the behavior of these groups, in As is consistent with the behavior of these groups, in

neutral solution, the –СООН group of an aminoacid neutral solution, the –СООН group of an aminoacid donates а proton to the –NH2 of the same aminoacid. donates а proton to the –NH2 of the same aminoacid. We can characterize this behavior as an internal acid — We can characterize this behavior as an internal acid — base reaction. The net result is that in neutral solution, base reaction. The net result is that in neutral solution, aminoacid molecules have the structure.aminoacid molecules have the structure.

Such а molecule is known as а zwitterion, from the Such а molecule is known as а zwitterion, from the German term meaning “double ion”. А German term meaning “double ion”. А zwitterion zwitterion is а molecule is а molecule that has а positive charge on one atom and а negative charge on that has а positive charge on one atom and а negative charge on another atom. Note that the net charge on а zwitterion is zero even another atom. Note that the net charge on а zwitterion is zero even though parts of the molecule carry charges. In solution and also in though parts of the molecule carry charges. In solution and also in the solid state, α-aminoacids are zwitterions. Zwitterion structure the solid state, α-aminoacids are zwitterions. Zwitterion structure changes when the pH of а solution containing an aminoacid is changes when the pH of а solution containing an aminoacid is changed from neutral either to acidic (low pH) by adding an acid changed from neutral either to acidic (low pH) by adding an acid such as НС1 or to basic (high pH) by adding а base such as such as НС1 or to basic (high pH) by adding а base such as NaOH. In an acidic solution, the zwitterion accepts а proton (Н+) NaOH. In an acidic solution, the zwitterion accepts а proton (Н+) to form а positively charged ion.to form а positively charged ion.

In basic solution, the –NH3+ of the zwitterion loses а proton, and а negatively In basic solution, the –NH3+ of the zwitterion loses а proton, and а negatively charged species is formed.charged species is formed.

Thus, in solution, three different aminoacid forms can exist (zwitterion, negative Thus, in solution, three different aminoacid forms can exist (zwitterion, negative ion, and positive ion). The three species are actually in equilibrium with each ion, and positive ion). The three species are actually in equilibrium with each other, and the equilibrium shifts with pH change. The overall equilibrium process other, and the equilibrium shifts with pH change. The overall equilibrium process can be represented as follows:can be represented as follows:

In acidic solution, the positively charged species on the left predominates; nearly In acidic solution, the positively charged species on the left predominates; nearly neutral solutions have the middle species (the zwitterion) as the dominant species; neutral solutions have the middle species (the zwitterion) as the dominant species; in basic solution, the negatively charged species on the right predominates.in basic solution, the negatively charged species on the right predominates.

The previous discussion assumed that the side The previous discussion assumed that the side chain (R group) of an aminoacid remains unchanged in chain (R group) of an aminoacid remains unchanged in solution as the pH is varied. This is the case for neutral solution as the pH is varied. This is the case for neutral aminoacids but not for acidic or basic ones. For these aminoacids but not for acidic or basic ones. For these latter compounds, the side chain can also acquire а latter compounds, the side chain can also acquire а charge, because it contains an amino or а carboxyl charge, because it contains an amino or а carboxyl group that can, respectively, gain or lose а proton. group that can, respectively, gain or lose а proton. Because of the extra site that can be protonated or Because of the extra site that can be protonated or deprotonated, acidic and basic aminoacids have four deprotonated, acidic and basic aminoacids have four charged forms in solution. The existence of two low-pH charged forms in solution. The existence of two low-pH forms for aspartic acid results from the two carboxyl forms for aspartic acid results from the two carboxyl groups being deprotonated at different pH values. For groups being deprotonated at different pH values. For basic aminoacids, two high-pH forms exist because basic aminoacids, two high-pH forms exist because deprotonation of the amino groups does not occur deprotonation of the amino groups does not occur simultaneously. The side-chain amino group simultaneously. The side-chain amino group deprotonates before the α-amino group.deprotonates before the α-amino group.

The The isoelectric pointisoelectric point for an aminoacid is the pH at which for an aminoacid is the pH at which the total charge on the aminoacid is zero. Every aminoacid has а the total charge on the aminoacid is zero. Every aminoacid has а different isoelectric point. Fifteen of the 20 amino acids, those different isoelectric point. Fifteen of the 20 amino acids, those with nonpolar or polar neutral side chains, have isoelectric points with nonpolar or polar neutral side chains, have isoelectric points in the range of 4.8 - 6.3. The three basic aminoacids have higher in the range of 4.8 - 6.3. The three basic aminoacids have higher isoelectric points (His = 7.59, Lys = 9.74, Arg = 10.76), and the isoelectric points (His = 7.59, Lys = 9.74, Arg = 10.76), and the two acidic aminoacids have lower ones (Asp = 2.77, Glu = 3.22).two acidic aminoacids have lower ones (Asp = 2.77, Glu = 3.22).

А рН below the isoelectric point favors the positively charged form of А рН below the isoelectric point favors the positively charged form of the aminoacid. Conversely, а рН above the isoelectric point favors the the aminoacid. Conversely, а рН above the isoelectric point favors the negatively charged form of the aminoacid.negatively charged form of the aminoacid.

When two electrodes (one positively charged and one negatively When two electrodes (one positively charged and one negatively charged) are immersed in а solution containing an aminoacid, molecules with а charged) are immersed in а solution containing an aminoacid, molecules with а net positive charge are attracted to the negatively charged electrode, and net positive charge are attracted to the negatively charged electrode, and negatively charged aminoacid molecules migrate toward the positively charged negatively charged aminoacid molecules migrate toward the positively charged electrode. The zwitterion form exhibits no net migration toward either electrode. The zwitterion form exhibits no net migration toward either electrode. This behavior is the basis for the measurement of isoelectric points. electrode. This behavior is the basis for the measurement of isoelectric points. The pH of the solution is adjusted until no net migration occurs.The pH of the solution is adjusted until no net migration occurs.

Mixtures of aminoacids in solution can be separated by using their Mixtures of aminoacids in solution can be separated by using their different migration patterns at various pH values. This type of analytical different migration patterns at various pH values. This type of analytical separation is called electrophoresis. separation is called electrophoresis. ElectrophoresisElectrophoresis is the process of is the process of separating charged molecules on the basis of their migration toward charged separating charged molecules on the basis of their migration toward charged electrodes.electrodes.

Methods of aminoscids obtainingMethods of aminoscids obtaining

Protein’s hydrolysis.Protein’s hydrolysis. It can be alkaline, It can be alkaline, acidic or fermentative hydrolysis. Widely acidic or fermentative hydrolysis. Widely use fermentative hydrolysis, for separation use fermentative hydrolysis, for separation of of αα-aminoacids ionchange -aminoacids ionchange chromatography is used.chromatography is used.

Microbiological synthesis.Microbiological synthesis. In these In these method use special microorganisms that method use special microorganisms that produce produce αα-aminoacids. -aminoacids.

5). Chemical properties of 5). Chemical properties of αα--aminoacidsaminoacidsA.A. Reaction on amino-groupReaction on amino-group

1) Formation of N-acylderivatives. This reaction use for blocking 1) Formation of N-acylderivatives. This reaction use for blocking (protection) of aminogroup at the synthesis of peptides. As (protection) of aminogroup at the synthesis of peptides. As acylation agents use benzoxycarbonylchloride (a) or tret-acylation agents use benzoxycarbonylchloride (a) or tret-butoxycarboxazide (b)butoxycarboxazide (b)

Blocked carbobenzoxygroup removed by catalytic hydrogenolysis or by action of HBr in acetic acid in cold.

Tret-butoxycarbonyl group destroyed by action of Tret-butoxycarbonyl group destroyed by action of triftoracetic acid:triftoracetic acid:

2) Deamination:2) Deamination:a)a) oxidation deaminationoxidation deamination – important pathway for the – important pathway for the

biodegradation of α-aminoacids:biodegradation of α-aminoacids:

b)b) hydrolytic deaminationhydrolytic deamination – reaction with nitrous acid. – reaction with nitrous acid. Aminoacids react with nitrous acid to give hydroxyacid Aminoacids react with nitrous acid to give hydroxyacid along with the evolution of nitrogen.along with the evolution of nitrogen.

The nitrogen can be collected and The nitrogen can be collected and measured. Thus this reaction constitutes one of the measured. Thus this reaction constitutes one of the methods for the estimation of amino acids.methods for the estimation of amino acids.

c) intramolecular deamination - unsaturated acids c) intramolecular deamination - unsaturated acids are formed:are formed:

d) redaction deamination – saturated carboxylic d) redaction deamination – saturated carboxylic acid formation:acid formation:

3) Tranceamination. Reaction goes under the 3) Tranceamination. Reaction goes under the present of enzymes tranceaminases and present of enzymes tranceaminases and coenzyme pyridoxalphosphate:coenzyme pyridoxalphosphate:

4) Interaction with carbonyl compounds:

5) Reaction with phenylisothiocyanate (Edmane 5) Reaction with phenylisothiocyanate (Edmane reaction). Form derivatives of 3-phenyl-2-reaction). Form derivatives of 3-phenyl-2-thiohydantoine (derivatives of thiohydantoine (derivatives of phenylthiohydantoine): phenylthiohydantoine):

6) Interaction with 2,4-dinitroftorbenzol (Senher’s 6) Interaction with 2,4-dinitroftorbenzol (Senher’s reagent):reagent):

B. Reaction on carboxyl groupB. Reaction on carboxyl group1) Formation of helate compounds ( complex 1) Formation of helate compounds ( complex

salts with ions of heard metals) salts with ions of heard metals)

2) Reaction with alcohols – difficult esters formation:2) Reaction with alcohols – difficult esters formation:

3) Reaction with ammonia – amides formation. The amides of 3) Reaction with ammonia – amides formation. The amides of aspartic and glutamic acid acids, asparagine and glutamine, play aspartic and glutamic acid acids, asparagine and glutamine, play important role in the transport of ammonia in the body.important role in the transport of ammonia in the body.

4) Formation of halogenanhydrides and anhydrides ( like carbonyl acids). Before these reaction blocked aminogroup by formation of N-acylderivatives.

5) 5) Decarboxylation.Decarboxylation. Aminoacids may be decarboxylated by heat, acids, bases or Aminoacids may be decarboxylated by heat, acids, bases or specific enzymes to the primary amines:specific enzymes to the primary amines:

Some of the decarboxylation reaction are of great importance in the body, Some of the decarboxylation reaction are of great importance in the body, decarboxylation of histidine to histaminedecarboxylation of histidine to histamine::

In the presence of foreign protein introduced into the body, very large In the presence of foreign protein introduced into the body, very large quantities of histamine are produced in the body and allergic reactions quantities of histamine are produced in the body and allergic reactions become evident. In extreme cases shock may result. The physiological become evident. In extreme cases shock may result. The physiological effects of histamine may be neutralized or minimized by the use of effects of histamine may be neutralized or minimized by the use of chemical compounds known as antihistamines.chemical compounds known as antihistamines.

C. Formation of salts. All aminoacids can react C. Formation of salts. All aminoacids can react with some inorganic acids and bases and with some inorganic acids and bases and form two kind of sold: form two kind of sold:

D. Peptide formation.D. Peptide formation. Two aminoacids can react in а Two aminoacids can react in а similar way - the carboxyl group of one aminoacid similar way - the carboxyl group of one aminoacid reacts with the amino group of the other aminoacid. reacts with the amino group of the other aminoacid. The products are а molecule of water and а molecule The products are а molecule of water and а molecule containing the two aminoacids linked by an amide containing the two aminoacids linked by an amide bond. Removal of the elements of water from the bond. Removal of the elements of water from the reacting carboxyl and amino groups and the ensuing reacting carboxyl and amino groups and the ensuing formation of the amide bond are better visualized formation of the amide bond are better visualized when expanded structural formulas for the reacting when expanded structural formulas for the reacting groups are used.groups are used.

In aminoacid chemistry, amide bonds that link aminoacids together are given the specific name of peptide bond. А peptide bond is а bond between the carboxyl group of one aminoacid and the amino group of another aminoacid. Under proper conditions, many aminoacids can bond together to give chains of aminoacids containing numerous peptide bonds. For example, four peptide bonds are present in а chain of five aminoacids.

Short to medium-sized chains of aminoacids are known as Short to medium-sized chains of aminoacids are known as peptides. А peptides. А peptidepeptide is а sequence of aminoacids, of up to 50 units, is а sequence of aminoacids, of up to 50 units, in which the aminoacids are joined together through amide in which the aminoacids are joined together through amide (peptide) bonds. А compound containing two amino acids joined (peptide) bonds. А compound containing two amino acids joined by а peptide bond is specifically called а dipeptide; three by а peptide bond is specifically called а dipeptide; three aminoacids in а chain constitute а tripeptide; and so on. The name aminoacids in а chain constitute а tripeptide; and so on. The name oligopeptide is loosely used to refer to peptides with 10 to 20 oligopeptide is loosely used to refer to peptides with 10 to 20 aminoacid residues and polypeptide to larger peptides. In all aminoacid residues and polypeptide to larger peptides. In all peptides, the aminoacid at one end of the aminoacid sequence has а peptides, the aminoacid at one end of the aminoacid sequence has а free H3N+ group, and the aminoacid at the other end of the free H3N+ group, and the aminoacid at the other end of the sequence has а free СОО- group. The end with the free H3N+ sequence has а free СОО- group. The end with the free H3N+ group is called the group is called the N-terminal endN-terminal end, and the end with the free , and the end with the free СОО- group is called the СОО- group is called the С-terminal endС-terminal end. By convention, the . By convention, the sequence of aminoacids in а peptide is written with the N-terminal sequence of aminoacids in а peptide is written with the N-terminal end aminoacid at the left. The individual aminoacids within а end aminoacid at the left. The individual aminoacids within а peptide chain are called aminoacid residues.peptide chain are called aminoacid residues.

The structural formula for а polypeptide may be The structural formula for а polypeptide may be written out in full, or the sequence of aminoacids present may written out in full, or the sequence of aminoacids present may be indicated by using the standard three-letter aminoacid be indicated by using the standard three-letter aminoacid abbreviations. The abbreviated formula for the tripeptide:abbreviations. The abbreviated formula for the tripeptide:

which contains the aminoacids glycine, which contains the aminoacids glycine, alanine, and serine, is Gly – Ala – Ser. When alanine, and serine, is Gly – Ala – Ser. When we use this abbreviated notation, by we use this abbreviated notation, by convention, the aminoacid at the N-terminal convention, the aminoacid at the N-terminal end of the peptide is always written on the left.end of the peptide is always written on the left.

The repeating chain of peptide bonds and α-carbon The repeating chain of peptide bonds and α-carbon atoms in а peptide is referred to as the backbone of the atoms in а peptide is referred to as the backbone of the peptide. The R group side chains are substituents on the peptide. The R group side chains are substituents on the backbone. Peptides that contain the same aminoacids but in backbone. Peptides that contain the same aminoacids but in different order are different molecules (structural isomers) different order are different molecules (structural isomers) with different properties. For example, two different with different properties. For example, two different dipeptides can be formed from one molecule of alanine and dipeptides can be formed from one molecule of alanine and one molecule of glycine.one molecule of glycine.

In the first dipeptide, the alanine is the N-terminal In the first dipeptide, the alanine is the N-terminal residue, and in the second molecule, it is the С-terminal residue, and in the second molecule, it is the С-terminal residue. These two compounds are isomers with different residue. These two compounds are isomers with different chemical and physical properties.chemical and physical properties.

The number of isomeric peptides possible The number of isomeric peptides possible increases rapidly as the length of the peptide chain increases rapidly as the length of the peptide chain increases. Let us consider the tripeptide Ala – Ser – increases. Let us consider the tripeptide Ala – Ser – Cys as another example. In addition to this sequence, Cys as another example. In addition to this sequence, five other arrangements of these three components five other arrangements of these three components are possible, each representing another isomeric are possible, each representing another isomeric tripeptide: Ala – Cys – Ser, Ser –Ala – Cys, Ser – Cys tripeptide: Ala – Cys – Ser, Ser –Ala – Cys, Ser – Cys – Ala, Cys – Ala – Ser, and Cys – Ser – Ala. For а – Ala, Cys – Ala – Ser, and Cys – Ser – Ala. For а pentapeptide containing 5 different aminoacids, 120 pentapeptide containing 5 different aminoacids, 120 isomers are possible.isomers are possible.

More than two hundred peptides have been More than two hundred peptides have been isolated and identified as essential to the proper isolated and identified as essential to the proper functioning of the human body. In general, these functioning of the human body. In general, these substances serve as hormones or neurotransmitters. substances serve as hormones or neurotransmitters. Their functions range from controlling pain to Their functions range from controlling pain to controlling muscle contraction or kidney fluid controlling muscle contraction or kidney fluid excretion.excretion.

Two important hormones produced by the pituitary gland Two important hormones produced by the pituitary gland are oxytocin and vasopressin, Each hormone is а nonapeptide are oxytocin and vasopressin, Each hormone is а nonapeptide (nine amino acid residues) with six of the residues hells in the (nine amino acid residues) with six of the residues hells in the form of а loop by а disulfide bond formed from the interaction of form of а loop by а disulfide bond formed from the interaction of two cysteine residues.two cysteine residues.

Oxytocin regulates uterine contractions and lactation. Vasopressin Oxytocin regulates uterine contractions and lactation. Vasopressin regulates the excretion of water by the kidneys; it also affects blood pressure. regulates the excretion of water by the kidneys; it also affects blood pressure. The structure of vasopressin differs from that of oxytocin at only two The structure of vasopressin differs from that of oxytocin at only two aminoacid positions: the third and eighth aminoacid residues. The result of aminoacid positions: the third and eighth aminoacid residues. The result of these variations is а significant difference in physiological action.these variations is а significant difference in physiological action.

6). Indentification of aminoacids.aminoacids.Biuret test. The protein is warmed gently with 10 % solution of sodium

hydroxide and then а drop of very dilute copper sulphate solution is added, the formation of reddish - violet colour indicates the presence of peptide link, – СО – NH – . The test is given by all proteins, peptones and peptides. Its name is derived from the fact that the test is also positive for the compound biuret, Н2Х –CONH – CONH2 obtained from urea by heating. It should be noted that dipeptides do not give the biuret test, while all other polypeptides do so. Hence biuret test is important to know whether hydrolysis of proteins is complete or not. If the biuret test is negative, hydrolysis is complete, at least to the dipeptide stage.

Xanthoprotein test. On treatment with concentrated nitric acid, certain proteins give yellow color. This yellow color is the same that is formed on the skin when the latter comes in contact with the concentrated nitric acid. The test is given only by the proteins having at least one mole of aromatic aminoacid, such as tryptophan, phenylalanine, and tyrosine which are actually nitrated during treatment with concentrated nitric acid. When you add after conc. HNO3 conc. NaOH forms light orange color (hynoid structure).

Millon's test.Millon's test. Protein Protein on adding Millon's reagent on adding Millon's reagent (а solution of mercuric and (а solution of mercuric and mercurous nitrates in nitric mercurous nitrates in nitric acid containacid containing а little nitrous acid) followed by heating ing а little nitrous acid) followed by heating the solution give а red prthe solution give а red preecipitate or colour. The test is cipitate or colour. The test is responded by the proteins having tyrosine. The responded by the proteins having tyrosine. The hydroxyphenyl group of tyrosine is the shydroxyphenyl group of tyrosine is the sttrucructture ure responsible for this test. Moreover, the non-proteinous responsible for this test. Moreover, the non-proteinous material having phenolic group also responds the test. material having phenolic group also responds the test.

Foll reaction. Foll reaction. This reaction reveals the sulfur This reaction reveals the sulfur containing aminoacids (cysteine, cystine). containing aminoacids (cysteine, cystine). Treatment of Treatment of the sulfur containing aminoacids with salt of lead and the sulfur containing aminoacids with salt of lead and alkali yields a black sediment. alkali yields a black sediment.

Adamkevich reaction. Adamkevich reaction. This reaction detects the This reaction detects the amino acid tryptophan containing indol ring. amino acid tryptophan containing indol ring. The The addition of the concentrated acetic and sulfuric acids to addition of the concentrated acetic and sulfuric acids to the solution of tryptophan results in the formation of the solution of tryptophan results in the formation of red-violet ring appearing on the boundary of different red-violet ring appearing on the boundary of different liquids. liquids.

Ninhydrin test. The ninhydrin colour reaction is the most commonly test used for the detection of aminoacids. This is an extremely delicate test, to which proteins, their hydrolytic products, and α-aminoacids react. Although the test is positive for all free amino groups in aminoacids, peptides, or proteins, the test is much weaker for peptides or proteins because not as many free groups are available as in aminoacids. For certain aminoacids the test is positive in dilutions as high as 1 part in 100,000 parts of water. When ninhydrin is added to а protein solution and the mixture is heated to boil, blue or violet color appears on cooling. The colour is due to the formation of а complex compound.

The test is also given by ammonia, ammonium The test is also given by ammonia, ammonium salts, and certain amines. Ninhydrin is also salts, and certain amines. Ninhydrin is also used as а reagent for the quantitative used as а reagent for the quantitative determination of free carboxyl groups in determination of free carboxyl groups in solutions of aminoacids.solutions of aminoacids.

Nitroprusside test.Nitroprusside test. Proteins containing free -SH Proteins containing free -SH groups (of cysteine) give а reddish colour with groups (of cysteine) give а reddish colour with sodium nitroprusside in ammonical solution.sodium nitroprusside in ammonical solution.

7). Proteins. S7). Proteins. Structure of tructure of thethe proteinproteins.s.

Proteins Proteins are polypeptides that contain more than are polypeptides that contain more than 50 aminoacid units. The dividing line between 50 aminoacid units. The dividing line between аа polypeptide and polypeptide and аа protein is arbitrary. The important protein is arbitrary. The important point is that proteins are polymers containing point is that proteins are polymers containing аа large large number of aminoacid units linked by peptide bonds. number of aminoacid units linked by peptide bonds. Polypeptides are shorter chains of aminoacids. Some Polypeptides are shorter chains of aminoacids. Some proteins have molecular masses in the millions. Some proteins have molecular masses in the millions. Some proteins also contain more than one polypeptide chain. proteins also contain more than one polypeptide chain. To aid us in describing protein structure, we will To aid us in describing protein structure, we will consider four levels of substructure: primary, secondary, consider four levels of substructure: primary, secondary, tertiary, and quaternary. Even though we consider these tertiary, and quaternary. Even though we consider these structure levels one by one, remember that it is the structure levels one by one, remember that it is the combination of all four levels of structure that controls combination of all four levels of structure that controls protein function.protein function.

The The primary structure of а proteinprimary structure of а protein is the sequence of aminoacids present in its is the sequence of aminoacids present in its peptide chain or chains. Knowledge of primary structure tells us which peptide chain or chains. Knowledge of primary structure tells us which aminoacids are present, the number of each, their sequence, and the length aminoacids are present, the number of each, their sequence, and the length and number of polypeptide chains.and number of polypeptide chains.

The first protein whose primary structure was determined was insulin, the The first protein whose primary structure was determined was insulin, the hormone that regulates blood-glucose level; а deficiency of insulin leads to hormone that regulates blood-glucose level; а deficiency of insulin leads to diabetes. The sequencing of insulin, which took over 8 years, was completed diabetes. The sequencing of insulin, which took over 8 years, was completed in 1953. Today, thousands of proteins have been sequenced; that is, in 1953. Today, thousands of proteins have been sequenced; that is, researchers have determined the order of amino acids within the polypeptide researchers have determined the order of amino acids within the polypeptide chain or chains.chain or chains.

The primary structure of а specific protein is always The primary structure of а specific protein is always the same, regardless of where the protein is found within an the same, regardless of where the protein is found within an organism. The structures of certain proteins are even similar organism. The structures of certain proteins are even similar among different species of animals. For example, the primary among different species of animals. For example, the primary structures of insulin in cows, pigs, sheep, and horses are very structures of insulin in cows, pigs, sheep, and horses are very similar both to each other and to human insulin. Until recently, similar both to each other and to human insulin. Until recently, this similarity was particularly important for diabetics who this similarity was particularly important for diabetics who required supplemental injections of insulin. required supplemental injections of insulin.

An analogy is often drawn between the primary An analogy is often drawn between the primary structure of proteins and words. Words, which structure of proteins and words. Words, which convey information, are formed when the 26 letters of convey information, are formed when the 26 letters of the English alphabet are properly sequenced. the English alphabet are properly sequenced. Proteins, which function biologically, are formed Proteins, which function biologically, are formed from the proper sequence of 20 aminoacids. The from the proper sequence of 20 aminoacids. The proper sequence of letters in а word is necessary for it proper sequence of letters in а word is necessary for it to make sense, just as the proper sequence of to make sense, just as the proper sequence of aminoacids is necessary to make biologically active aminoacids is necessary to make biologically active protein.protein.

The The secondary structure of а proteinsecondary structure of а protein is the arrangement in is the arrangement in space of the atoms in the backbone of the protein. Three major space of the atoms in the backbone of the protein. Three major types of protein secondary structure are known; the alpha types of protein secondary structure are known; the alpha helix, the beta pleated sheet, and the triple helix. The major helix, the beta pleated sheet, and the triple helix. The major force responsible for all three types of secondary structure is force responsible for all three types of secondary structure is hydrogen bonding between а carbonyl oxygen atom of а hydrogen bonding between а carbonyl oxygen atom of а peptide linkage and the hydrogen atom of an amino group (-peptide linkage and the hydrogen atom of an amino group (-NH) of another peptide linkage farther along the backbone. NH) of another peptide linkage farther along the backbone. This hydrogen-bonding interaction may be diagrammed as This hydrogen-bonding interaction may be diagrammed as follows:follows:

The The Alpha HelixAlpha Helix The alpha helix (α-helix) structure resembles а The alpha helix (α-helix) structure resembles а coiled helical spring, with the coil configuration maintained by hydrogen coiled helical spring, with the coil configuration maintained by hydrogen bonds between N – Н and С= О groups of every fourth aminoacid, as is bonds between N – Н and С= О groups of every fourth aminoacid, as is shown diagrammatically in Figure.2.shown diagrammatically in Figure.2.

Figure. Three representations of (а) the а helix protein structure. Figure. Three representations of (а) the а helix protein structure. Hydrogen bonds between amide groups (peptide linkages) are shown in (b) Hydrogen bonds between amide groups (peptide linkages) are shown in (b) and (с). (d) The top view of an а helix shows that amino acid side chains (R and (с). (d) The top view of an а helix shows that amino acid side chains (R groups) point away from the long axis of the helix.groups) point away from the long axis of the helix.

Figure. Two representations of the p pleated sheet protein structure. (а) А Figure. Two representations of the p pleated sheet protein structure. (а) А representation emphasizing the hydrogen bonds between protein chains. (b) А representation emphasizing the hydrogen bonds between protein chains. (b) А representation emphasizing the pleats and the location of the R groups. representation emphasizing the pleats and the location of the R groups. Proteins have varying amounts of α-helical secondary structure, ranging from Proteins have varying amounts of α-helical secondary structure, ranging from а few percent to nearly 100 %. In an α-helix, all of the aminoacid side chains а few percent to nearly 100 %. In an α-helix, all of the aminoacid side chains (R groups) lie outside the helix; there is not enough room for them in the (R groups) lie outside the helix; there is not enough room for them in the interior. Figure.3d illustrates this situation. This structural feature of the α-interior. Figure.3d illustrates this situation. This structural feature of the α-helix is the basis for protein tertiary structure.helix is the basis for protein tertiary structure.

The The beta pleated sheetbeta pleated sheet (β-pleated sheet) (β-pleated sheet) secondary structure involves aminoacid chains that secondary structure involves aminoacid chains that are almost completely extended. Hydrogen bonds are almost completely extended. Hydrogen bonds form between two different side-by-side protein form between two different side-by-side protein chains (interchain bonds) as shown in Figure.3, or chains (interchain bonds) as shown in Figure.3, or between different parts of а single chain that folds between different parts of а single chain that folds back on itself (intrachain bonds). The term pleated back on itself (intrachain bonds). The term pleated sheet arises from the repeated zigzag pattern in the sheet arises from the repeated zigzag pattern in the structure (Figure.3b). Aminoacid side chains are structure (Figure.3b). Aminoacid side chains are located above and below the plane of the sheet. Very located above and below the plane of the sheet. Very few proteins have entirely n helix or p pleated sheet few proteins have entirely n helix or p pleated sheet structures. Instead, most proteins have only certain structures. Instead, most proteins have only certain portions of their molecules in these conformations. portions of their molecules in these conformations. The rest of the molecule assumes а "random The rest of the molecule assumes а "random structure." It is possible to have both а helix and p structure." It is possible to have both а helix and p pleated sheet structures within the same protein. pleated sheet structures within the same protein.

Secondary Secondary ββ-structure of proteins contains -structure of proteins contains parallel (a) and antiparallel (b) fragmentparallel (a) and antiparallel (b) fragment

Collagen, the structural protein of Collagen, the structural protein of connective tissue (cartilage, tendon, and skin), connective tissue (cartilage, tendon, and skin), has а triple-helix structure. Collagen molecules has а triple-helix structure. Collagen molecules are very long, thin, and rigid. Many such are very long, thin, and rigid. Many such molecules, lined up alongside each other, molecules, lined up alongside each other, combine to make collagen fibers. Cross-combine to make collagen fibers. Cross-linking gives the fibers extra strength. linking gives the fibers extra strength.

The The tertiary structure of а proteintertiary structure of а protein is the is the overall three-dimensional shape that results overall three-dimensional shape that results from the attractive forces between aminoacid from the attractive forces between aminoacid side chains (R groups) that are widely side chains (R groups) that are widely separated from each other within the chain. А separated from each other within the chain. А good analogy for the relationships among the good analogy for the relationships among the primary, secondary, and tertiary structures of а primary, secondary, and tertiary structures of а protein is that of а telephone cord. The primary protein is that of а telephone cord. The primary structure is the long, straight cord. The coiling structure is the long, straight cord. The coiling of the cord into а helical arrangement gives the of the cord into а helical arrangement gives the secondary structure. The supercoiling secondary structure. The supercoiling arrangement the cord adopts after you hang up arrangement the cord adopts after you hang up the receiver is the tertiary structure.the receiver is the tertiary structure.

Interactions responsible for the tertiary structure.Interactions responsible for the tertiary structure. Four types of attractive interactions contribute to the tertiary Four types of attractive interactions contribute to the tertiary

structure of а protein:structure of а protein:1) covalent disulfide bonds, 1) covalent disulfide bonds, 2) electrostatic attractions (salt bridges), 2) electrostatic attractions (salt bridges),

3) hydrogen bonds,3) hydrogen bonds,

4) hydrophobic attractions.

All four of these interactions are interactions All four of these interactions are interactions between aminoacid R groups. This is а major between aminoacid R groups. This is а major distinction between tertiary-structure interactions and distinction between tertiary-structure interactions and secondary-structure interactions. Tertiary-structure secondary-structure interactions. Tertiary-structure interactions involve the R groups of aminoacids; interactions involve the R groups of aminoacids; secondary-structure interactions involve the peptide secondary-structure interactions involve the peptide linkages between aminoacid units. Disulfide bonds, the linkages between aminoacid units. Disulfide bonds, the strongest of the tertiary-structure interactions, result strongest of the tertiary-structure interactions, result from the –SH groups of two cysteine molecules from the –SH groups of two cysteine molecules reacting with each other to form а covalent disulfide. reacting with each other to form а covalent disulfide. This type of interaction is the only one of the four This type of interaction is the only one of the four tertiary-structure interactions that involves а covalent tertiary-structure interactions that involves а covalent bond. That – SH groups are readily oxidized to give а bond. That – SH groups are readily oxidized to give а disulfide bond, – S – S –. Disulfide bonds may disulfide bond, – S – S –. Disulfide bonds may involve two cysteine units in the same chain or in involve two cysteine units in the same chain or in different chainsdifferent chains. .

Figure. Four types of interactions between aminoacid R Figure. Four types of interactions between aminoacid R groups produce thetertiary structure of а protein. (а) Disulfide groups produce thetertiary structure of а protein. (а) Disulfide bonds. (b) Electrostatic interactions (salt bridges). (с) Hydrogen bonds. (b) Electrostatic interactions (salt bridges). (с) Hydrogen bonds. (d) Hydrophobic interactions. Electrostatic interactions, bonds. (d) Hydrophobic interactions. Electrostatic interactions, also called salt bridges, always involve aminoacids with charged also called salt bridges, always involve aminoacids with charged side chains. These aminoacids are the acidic and basic side chains. These aminoacids are the acidic and basic aminoacids. The two R groups, one acidic and one basic, interact aminoacids. The two R groups, one acidic and one basic, interact through ion — ion attractions. Figure.b shows an electrostatic through ion — ion attractions. Figure.b shows an electrostatic interaction.interaction.

Hydrogen bonds can occur between aminoacids with polar R Hydrogen bonds can occur between aminoacids with polar R groups. А variety of polar side chains can be involved, especially groups. А variety of polar side chains can be involved, especially those that possess the following functional groups:those that possess the following functional groups:

Hydrogen bonds are relatively weak and are easily disrupted by changes Hydrogen bonds are relatively weak and are easily disrupted by changes in pH and temperature. Hydrophobic interactions result when two nonpolar side in pH and temperature. Hydrophobic interactions result when two nonpolar side chains are close to each other, In aqueous solution, many proteins have their polar chains are close to each other, In aqueous solution, many proteins have their polar R groups outward, toward the aqueous solvent (which is also polar), and their R groups outward, toward the aqueous solvent (which is also polar), and their nonpolar R groups inward (away from the polar water molecules). The nonpolar nonpolar R groups inward (away from the polar water molecules). The nonpolar R groups then interact with each other. Hydrophobic interactions are common R groups then interact with each other. Hydrophobic interactions are common between phenyl rings and alkyl side chains. Although hydrophobic interactions between phenyl rings and alkyl side chains. Although hydrophobic interactions are weaker than hydrogen bonds or electrostatic interactions, they are a are weaker than hydrogen bonds or electrostatic interactions, they are a significant force in some proteins because there are so many of them; their significant force in some proteins because there are so many of them; their cumulative effect can be greater in magnitude than the effects of hydrogen cumulative effect can be greater in magnitude than the effects of hydrogen bonding. bonding.

An example of а protein with quaternary structure is An example of а protein with quaternary structure is hemoglobin, the oxygen-carrying protein in blood. It is а tetramer hemoglobin, the oxygen-carrying protein in blood. It is а tetramer in which there are two identical α chains and two identical β chains. in which there are two identical α chains and two identical β chains. Each chain enfolds а heme group, the site where oxygen binds to Each chain enfolds а heme group, the site where oxygen binds to the protein.the protein.

Figure. А schematic diagram showing the quaternary structure of the Figure. А schematic diagram showing the quaternary structure of the oxygen-carrying protein hemoglobin.oxygen-carrying protein hemoglobin.

8). Globular and fibrous proteins.8). Globular and fibrous proteins.On the basis of structural shape, proteins can On the basis of structural shape, proteins can

be classified into two major types: fibrous proteins be classified into two major types: fibrous proteins and globular proteins. А fibrous protein is а protein and globular proteins. А fibrous protein is а protein that has а long, thin, fibrous shape. Such proteins are that has а long, thin, fibrous shape. Such proteins are made up of long rod-shaped or string-like molecules made up of long rod-shaped or string-like molecules that can intertwine with one another and form strong that can intertwine with one another and form strong fibers. They are water-insoluble and generally have fibers. They are water-insoluble and generally have structural functions within the human body. А structural functions within the human body. А globular protein is а protein whose overall shape is globular protein is а protein whose overall shape is roughly spherical or globular. Globular proteins roughly spherical or globular. Globular proteins either dissolve in water or form stable suspensions in either dissolve in water or form stable suspensions in water, which allows them to travel through the blood water, which allows them to travel through the blood and other body fluids to sites where their activity is and other body fluids to sites where their activity is needed. Table. 1 gives examples of selected common needed. Table. 1 gives examples of selected common fibrous and globular proteins.fibrous and globular proteins.

Table. 1 Some common fibrous and globular proteinsTable. 1 Some common fibrous and globular proteins

The fibrous protein alpha keratin is particularly abundant in The fibrous protein alpha keratin is particularly abundant in nature, where it is found in protective coatings for organisms. It is the nature, where it is found in protective coatings for organisms. It is the major protein constituent of hair, feathers, wool, fingernails and toenails, major protein constituent of hair, feathers, wool, fingernails and toenails, claws, scales, horns, turtle shells, quills, and hooves. The structure of а claws, scales, horns, turtle shells, quills, and hooves. The structure of а typical alpha keratin, that of hair, is depicted in Figure. The individual typical alpha keratin, that of hair, is depicted in Figure. The individual molecules are almost wholly alpha-helical. Pairs of these helices twine molecules are almost wholly alpha-helical. Pairs of these helices twine about one another to produce а coiled coil. In hair, two of the coiled coils about one another to produce а coiled coil. In hair, two of the coiled coils then further twist together to form а four-molecule protofilament.then further twist together to form а four-molecule protofilament.

Figure. The coiled-coil structure of the fibrous protein alpha keratin.Figure. The coiled-coil structure of the fibrous protein alpha keratin.

9). Simple and conjugated proteins.9). Simple and conjugated proteins.Proteins are classified as either simple proteins Proteins are classified as either simple proteins

or conjugated proteins. А or conjugated proteins. А simple proteinsimple protein is made up is made up entirely of aminoacid residues. More than one entirely of aminoacid residues. More than one polypeptide chain may be present, but all chains polypeptide chain may be present, but all chains contain only aminoacids. А contain only aminoacids. А conjugated proteinconjugated protein has has other chemical components in addition to aminoacids. other chemical components in addition to aminoacids. These additional components, which may be organic These additional components, which may be organic or inorganic, are called prosthetic groups. А or inorganic, are called prosthetic groups. А prosthetic groupprosthetic group is а non-aminoacid unit is а non-aminoacid unit permanently associated with а protein. Conjugated permanently associated with а protein. Conjugated proteins may be further classified according to the proteins may be further classified according to the nature of the prosthetic group. For example, proteins nature of the prosthetic group. For example, proteins containing lipids, those containing carbohydrates, and containing lipids, those containing carbohydrates, and those containing metal ions are called lipoproteins, those containing metal ions are called lipoproteins, glycoproteins, and metalloproteins, respectively. glycoproteins, and metalloproteins, respectively. Table.2 gives further examples of the types of Table.2 gives further examples of the types of conjugated proteins.conjugated proteins.

Table.2. Types of conjugated proteinsTable.2. Types of conjugated proteins

10. 10. Peptides.Peptides.

a)a) Acid-base properties of peptides.Acid-base properties of peptides. Since none of the a-carboxyl groups and none Since none of the a-carboxyl groups and none

of the a-amino groups that are combined in peptide of the a-amino groups that are combined in peptide linkages can ionize in the pH zone 0 to 14, the acid-linkages can ionize in the pH zone 0 to 14, the acid-base behaviour of peptides is contributed by the free base behaviour of peptides is contributed by the free a-amino group of the N-terminal residue, the free a-a-amino group of the N-terminal residue, the free a-carboxyl group of the carboxyl-terminal carboxyl group of the carboxyl-terminal (abbreviated C-terminal) residue, and those R (abbreviated C-terminal) residue, and those R groups of the residues in inter mediate positions groups of the residues in inter mediate positions which can ionize. In long poly peptide chains the which can ionize. In long poly peptide chains the ionizing R groups necessarily greatly outnumber the ionizing R groups necessarily greatly outnumber the terminal ionizing groups. terminal ionizing groups.

b) Optical properties of peptides. b) Optical properties of peptides. If partial hydrolysis of a protein is carried out under If partial hydrolysis of a protein is carried out under

sufficiently mild conditions, the peptides formed are optically active, sufficiently mild conditions, the peptides formed are optically active, since they contain only L-aminoacid residues. In relatively short since they contain only L-aminoacid residues. In relatively short peptides, the total observed optical activity is approximately an peptides, the total observed optical activity is approximately an additive function of the optical activities of the component aminoacid additive function of the optical activities of the component aminoacid residues. However, the optical activity of long polypeptide chains of residues. However, the optical activity of long polypeptide chains of proteins in their native conformation is much less than additive, a fact proteins in their native conformation is much less than additive, a fact of great significance with regard to the secondary and tertiary of great significance with regard to the secondary and tertiary structure of proteins.structure of proteins.

c) Chemical properties of peptides.c) Chemical properties of peptides. The free N-terminal amino groups of peptides undergo the same kinds of The free N-terminal amino groups of peptides undergo the same kinds of

chemical reactions as those given by the a-amino groups of free aminoacids, such as chemical reactions as those given by the a-amino groups of free aminoacids, such as acylation and carbamoylation. The N-terminal aminoacid residue of peptides also acylation and carbamoylation. The N-terminal aminoacid residue of peptides also reacts quantitatively with ninhydrin to form colored derivatives; the ninhydrin reacts quantitatively with ninhydrin to form colored derivatives; the ninhydrin reaction is widely used for detection and quantitative estimation of peptides in reaction is widely used for detection and quantitative estimation of peptides in electrophoretic and chromatographic procedures. Similarly, the C-terminal carboxyl electrophoretic and chromatographic procedures. Similarly, the C-terminal carboxyl group of a peptide may be esterified or reduced. Moreover, the various R groups of group of a peptide may be esterified or reduced. Moreover, the various R groups of the different aminoacid residues found in peptides usually yield the same the different aminoacid residues found in peptides usually yield the same characteristic reactions as free aminoacids. One widely employed color reaction of characteristic reactions as free aminoacids. One widely employed color reaction of peptides and proteins that is not given by free aminoacids is the peptides and proteins that is not given by free aminoacids is the biuret reactionbiuret reaction. . Treatment of a peptide or protein with CuTreatment of a peptide or protein with Cu22+ and alkali yields a purple Cu+ and alkali yields a purple Cu22+-peptide +-peptide complex, which can be measured quantitatively in a spectrophotometer.complex, which can be measured quantitatively in a spectrophotometer.

d) Synthesis of peptides d) Synthesis of peptides

Scheme of synthesis of dipeptide alanine-glycineScheme of synthesis of dipeptide alanine-glycine 1) Protection of aminogroup of alanine1) Protection of aminogroup of alanine

2) Activation of carboxyl group of N-protected alanine2) Activation of carboxyl group of N-protected alanine

3)3) ProtectionProtection of carboxyl group of glycineof carboxyl group of glycine

4) Formation of peptide bond and removing of 4) Formation of peptide bond and removing of protectionprotection

Solidphases synthesis of peptidesSolidphases synthesis of peptides Tret-Tret-butoxycarbonbutoxycarbonyl group yl group destroyed by destroyed by action of action of mixture of mixture of waterbromine waterbromine and and triftoracetic triftoracetic acidacid

Amino group protection. The reactivity of an amino group is suppressed by converting it to an amide, and amino groups are most often protected by acylation. The benzyloxycarbonyl group is one of the most often used amino-protecting groups. It is attached by acylation of an aminoacid with benzyloxycarbonyl chloride.

The value of the benzyloxycarbonyl protecting group is that it is easily removed by reactions other than hydrolysis. In peptide synthesis, amide bonds are formed. We protect the N terminus as an amide but need to remove the protecting group without cleaving the very amide bonds we labored so hard to construct.

Removing the protecting group by hydrolysis would surely bring about cleavage of peptide bonds as well. One advantage that the benzyloxycarbonyl protecting group enjoys over more familiar acyl groups such as acetyl is that it can be removed by hydrogenolysis in the presence of palladium. The following equation illustrates this for the removal of the benzyloxycarbonyl protecting group from the ethyl ester of Z-Phe-Gly:

Alternatively, the benzyloxycarbonyl protecting group may be removed by treatment with hydrogen bromide in acetic acid:

Carboxyl group protection. Carboxyl groups of amino acids and peptides are normally protected as esters. Methyl and ethyl esters are prepared by Fischer esterification. Deprotection of methyl and ethyl esters is accomplished by hydrolysis in base. Benzyl esters are a popular choice because they can be removed by hydrogenolysis. Thus a synthetic peptide, protected at both its N terminus with a Z group and at its C terminus as a benzyl ester, can be completely deprotected in a single operation.

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