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Medical Chemistry Lecture 5 2007 (J.S.) Organic compounds Elements essential for life Hazardous substances
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05 elements _ros__org._comp

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Medical ChemistryLecture 5 2007 (J.S.)

Organic compounds

Elements essential for lifeHazardous substances

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Elements regularly occurring in the human body:

1 Essential macroelements (11)

2 Essential microelements (10 trace elements)

3 Elements likely essential (5 elements ?)

4 Other elements taken from the environment

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Essential macroelements

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Essential macroelements

Carbon, hydrogen, and oxygenare the fundamental elements of organic compounds.In heterotrophs, only organic compounds serve as source of carbon for the synthesis of body constituents. Organic nutrients (saccharides, fats, proteins) are oxidatively broken down to CO2. and water to supply free energy.

Nitrogen is important constituent of amino acids, proteins, and bases of nucleic acids. Amino acids and proteins represent the unique source of nitrogen for the biosynthesis of body constituents.

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Phosphorusoccurs in living organisms solely as derivatives of phosphoric acid: phosphate anions in all body fluids, phosphate esters (nucleotides, phosphate esters of sugars, phospholipids, phosphorylated protein, etc.), insoluble calcium phosphates in bones.SulfurIn the cells, organic compounds of sulfur(–II) are of decisive importance (thiols, disulfides and sulfides). Amino acids methionine and cysteine are the unique source of utilizable sulfur. Sulfate anions occur in all biological fluids, sulfate esters of saccharides are constituents of proteoglycans.

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Calcium and magnesium ionsoccur in all body fluids; Ca2+ mostly in extracellular fluid,Mg2+ predominantly within the cells. Both ions take partin the regulation of cellular functions. The basal mineral component of bone tissue is calcium phosphate.

Sodium, potassium, and chloride ionsare main ions of body fluids, essential in maintaining osmolality and water balance. Na+ and Cl– ions predominate in the extracellular, K+ ions in the intracellular fluid.

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Essential microelements (trace elements)

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IronAn adult human body contains about 4 – 5 g total iron. The adequate food intake of iron is 10 – 30 mg per day, on which is namely the synthesis of haemoglobin dependant.ZincAdult bodies contain about 2 g of zinc, mostly in skeletal muscles. The activity of several tens of enzymes depend on the sufficient food intake of zinc (the recommended intake 10 – 20 mg per day. CopperAbout 100 mg of copper occur in adult bodies, mostly as the essential constituent of enzymes. The recommended daily intake of copper is approximately 20 mg.

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CobaltOnly about 1 mg of cobalt is present in adult bodies, mostly in skeletal muscles and bones. The formation of red blood cells requires sufficient supply of cobalt in the form of cobalamine (vitamin B12).

Chromium, molybdenum, and manganeseare essential constituents or activators of some enzymes.In the body, the amount of each of those metals is not greater than 10 – 20 mg.

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IodineApproximately 200 μg of iodine represent the recommended daily intake that is essential for the biosynthesis of thyroid gland hormones – iodothyronines. The total amount in the human body is less than 20 mg.Seleniumand its compounds are very toxic in high doses. On the other hand, selenium is the essential component of several enzymes, e.g. of GSH peroxidase and deiodinases. The recommended daily dietary allowance for adult humans is 50 – 75 μg.FluorineFluoride anions occur in human bodies (about 2 – 3 g) mainly in bones and enamel of teeth.

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?

?

?

??

Likely essential elements

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Reactive oxygen species ( ROS )

Small amounts of ROS and other free radicals are formedin all cells. Because there are protective mechanisms thatkeep the concentration of reactive radicals low, the unwantedeffects may be tolerated without any impairment of health.

The primary ROS is the superoxide anion-radical that originates through one-electron reduction of dioxygen.From superoxide anion, hydroxyl radical and singlet oxygen can be formed.Hydrogen peroxide seems to be the less harmful product of partial detoxification of superoxide.

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Inactivationby antioxidants scavengers quenchers

superoxide dismutase

Harm toproteinsDNAmembraneslipoproteins

GSH peroxidasecatalase

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NoticeDon't confuse the following names of groups:

Name Meaning

Hydroxide

Hydroxyl

Hydroxy–

Hydroxo–

anion OH–

hydroxyl group –OH as substituent

prefix in the name of compounds denotingthe occurrence of a hydroxyl group(e.g. 2-hydroxypropanoic acid)

prefix in the names of complex compounds indicating the occurrence of a ligand OH–

(e.g. [Al(OH)4]– tetrahydroxoaluminate ion)

radical •OHHydroxyl radical

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Hazardous chemicalsDifferent sorts of risk:

Explosives and oxidizing compoundsFlammable substancesCorrosive chemicalsToxic substances - very toxic

toxic risk of irreversible effects

IrritantsAddictive and psychotropic drugs

etc.Directive rules for manufacturing, delivering, and handlingare issued authoritatively through legislation.

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EU Hazard symbols

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A plenty of substances can be viewed "toxic": common pharmaceuticals, certain products of human metabolism, carbon dioxide, water, etc; a comprehensive list of those substances cannot exist.As a rule, selected toxic chemicals are listed and subjected under the control in particular countries,depending on their ability to be harmful in very low doses

or to be mistaken for harmless compounds.

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Selected examples of inorganic toxic substances

Very toxic Other toxic

White modification of phosphorusand phosphides

Arsenic and all compoundsThallium and all compoundsSelenates (selenium(IV) compoundsTellurites (tellurium(IV) compounds)Cyanides of metals

NitritesFluoridesIodatesAntimony and all compounds Barium - Lead - Mercury - Selenium - Tellurium - Uranium -Copper(II) sulfateSilver nitrateCarbon monoxideHydrogen sulfide

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Carbon compoundsTypes of organic compounds

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Organic chemistry is the chemistry of carbon compounds

The name "organic" chemistry is a historical term accepted in the1st half of the 19th century on Berzelius proposal.It was assigned to chemistry dealing with compounds thought at that time as products of only living systems.

Millions of organic compounds exist, both natural and synthetic.The unique property of carbon atoms is their ability to share electrons not only with different elements (carbon exhibits a middle value of electronegativity) but also with other carbon atoms forming so long carbon chain and cycles (catenation).

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Classification of organic compounds

Derivatives of hydrocarbonscontaining functional groups on a hydrocarbon skeleton, e.g.

Hydrocarbons– acyclic (aliphatic)

saturated (only single bonds) unsaturated (with multiple bonds)unbranched ("straight" chains)branched

– cyclic alicyclic saturated or unsaturatedaromatic

oxygenous groups hydroxyl –OH, carbonyl >C=O, carboxyl –COOH,containing sulfur sulfanyl –SH, acidic sulfonyl –SO3H, containing nitrogen amino group –NH2, nitro group –NO2,

atom(s) of halogen,or heterocyclic rings.

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Carbon atoms of organic compounds are sometimesclassified as primary, secondary, and tertiary carbon atoms:The primary carbon atom is attached to only one other carbon

(the atom at the end of a chain).The secondary carbon atom is attached to just two other carbonsThe tertiary carbon atom is linked to three other carbons

(the atom at the branching point).

C–C–C–CC–C

C–C

How many primary, secondary, and tertiary carbon atoms are presentin the hydrocarbon whose carbon skeleton is ?

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Chemical formulasEmpirical formulas express only the relative elemental composition ofa compound (the result of elemental analysis) without recognizing itsmolecular mass: (CH2O)n

Molecular formulas of a compound describe the numbers of differentatoms present: C6H12O6

All the compounds that have the same molecular formulabut differ in molecular structure are called isomers.

Structural formulas that describe – only the sequence of atoms and the type of bonds (without regard to the arrangement in space) i.e. the constitution of a compound;

– the arrangement in space – the configuration of a compound;– noting also different states caused by free rotation round single bonds – different conformations of a molecule.

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CC

C

CC

OH

OHOHOHHOHH

CH2OH

HH

OCH–(CHOH)4–CH2OH

CC

C

CC

H

OHH

OHHOHH

C H 2O H

HHO

O

D-Glucose(Fischer convention)

C O

H

H

H

H

H

H

H

OH

OH

OH

HO

OH

D-Glucose

Example:Constitutional ("structural")

formula of a hexose16 stereoisomers exist

CH2OH

HCO

OH

OH

OH

OH

Abbreviated (condensed)structural formulas

Structural formulas that describethe configuration of particular stereoisomers

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Structural (constitutional) isomerismCompounds have the same molecular formula but different constitution.

– Carbon chain is unbranched ("straight") or branched

– Different position of a multiple bond in unsaturated hydrocarbons

– Cycloalkanes are isomeric with alkenes

– Multiple bonds bind two different atoms

CH3–CH2–CO

HCH2=CH–CH2OH

– Different position of atoms other than carbon in the chain

HN

NN

NH

CH3–CH2–O–CH2–CH3 CH3–O–CH2–CH2–CH3

– Different positions of substituents

CH3–CH2–CH2–CH3 CH3–CH CH3

CH3

CH2=CH–CH=CH2 CH2=C=CH–CH3 CH3–C≡C–CH3

CH2=CH–CH=CH2 CH2=CCH2

CH2

CH2–CH

CH2–CH

CH3–CH2–CH2OH CH3–CH–CH3

OH

NH2 NH2

HO OH

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Tautomerismis a specific type of constitutional isomerism.Some compounds (aldehydes and ketones, lactams, imines) may exist

as an equilibrium mixture of two forms (tautomers)that differ in the location of a proton and a double bond:

the lactam form the lactim formof uric acid (2,6,8-trihydroxypurine)

the keto form the enol form of a carbonyl compound

CH CO OH

C C

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Stereoisomeric compounds have the same constitution but different spatial arrangement.

If the two stereoisomers cannot be interconverted without breaking and remaking bonds, then they are

configurational isomers.If compounds are stereoisomers and bond rotation easily interconverts them, they are conformers (rotamers).

Configurational isomerismTwo types of configurational isomerism exist:

– cis-trans isomerism (geometric isomerism) and

– optical isomerism of chiral molecules.

Stereoisomerism

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Cis-trans isomerism (geometric isomerism)occurs in appropriately substituted alkenes and cycloalkanes.in which rotation either at carbon-carbon double bonds or due tothe existing cycle is restricted.Cis-trans isomers differ from one another only in the way the atoms or groups are positioned on the same side of the plane (cis-) – in alkenes the plane perpendicular to C=C bond, in cycloalkanes the ring plane – or on opposite sides of the plane (trans-).

Cis-trans isomers are separate and unique compounds, their physicaland chemical properties are different.

cis-butenedioic acid trans-butenedioic acid maleic acid fumaric acid

cis-1,2-dichlorocyclopentane andtrans-1,2-dichlorocyclopentane

If sometimes cis-trans nomenclature is ambiguous, the groups are assigned priority (Cahn-Ingold-Prelog system) and the prefixes Z- and E- instead of cis- and trans- are used.

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Optical isomerismChiral molecules do not have a plane of symmetry; a chiralmolecule is one that exhibits the property of "handedness".The mirror image of a chiral molecule cannot be superimposedof the molecule itself. Chiral molecules are optically active.

Stereogenic centres (i.e. mostly stereogenic carbon atoms with four different groups attached) give rise to stereoisomers.

If there is only one stereogenic centre in the molecule, just twooptically active stereoisomers exist. They are called enantiomers (optical antipodes), one is dextrorotatory, the other levorotatory.

D-(–)-lactic acid L-(+)-lactic acid

Enantiomers behave identically in nearly all properties.A mixture of equal parts of both is a racemic mixture thatshows no net optical rotation butcan be resolved.

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Assignment of configurationFischer projection formulasInstead of using dashed and solid wedges to show the three-dimensionalarrangements of groups in a chiral molecule, the flattened Fischer projection formulas are used

It is recommendable to draw carbon chains vertically.Horizontal lines connect the stereogenic centre to groups that project above the plane of the paper, towards the viewer.Vertical lines lead to groups that project below the plane of the paper, away from the viewer.

Without changing the configuration, Fischer formulas may only be turned 180° in the plane of the paper (but not 90°).

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Configuration D- and L-Assigning configurations on stereogenic centres as

D- (from Latin dexter, right) or L- (from laevus, left) was introduced by E. Fischer and is still in common use.

Configurations on stereogenic centres are compared with the configurations of D- and L-glyceraldehyde:

D-glyceraldehyde L-glyceraldehyde

Carbon chains are drawn vertically, the most oxidized carbon(with the lowest numerical locant) placed at the top.If then the hydroxyl or other heavy group is attached to the stereogenic carbon atom is on the right, the configuration is D-.The configuration of an enantiomer with the hydroxyl groupon the left is designated L-.

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Configuration R and SThe system R/S (Cahn-Ingold-Prelog system) is more universal thanthe assignment D- or L-.

The method:1 The four groups attached to the stereogenic centre are placed in a priority order a → b → c → d according to the atomic number of atoms directly attached: a for the highest atomic number, d for the lowest. If two or more of the directly attached are the same, the next outward atom should be assessed.2 Direct d away from yourself and observe the stereogenic centre.3 Use the "rule of a driving wheel": If the remaining groups (a → b → c) form a clockwise array, the configuration is designated R (rectus, right); a counter clockwise array is designated S (sinister, left)

ca

b

d a

b

c

(R)-lactic acid

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There is no obvious relationship between configurationD- and L- (as well as R or S) and sign of rotation (+) or (–).

Example:

D-(+)-glyceraldehyde D-(–)-glyceric acid[α]D

25° = – 2.0°[α]D25° = + 14.0°

oxidation

D-(–)-lactic acid D-(+)-ethyl lactate[α]D

25° = – 3.8° [α]D25° = + 11.5°

esterification

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If there are more (n) stereogenic centres in the molecule,the maximal number of stereoisomers equals 2n; there will be – a maximum of 2n/2 pairs of enantiomers, – other forms differing from the particular pair of enantiomers are diastereomers that are optically active but not mirror images of each other, and – occasionally, some symmetrical (optically inactive) diastereomers may exist called meso compounds. In contrast to enantiomers, diastereomers differ in some properties andexhibit different values of optical activity.Example: tartaric acid (2,3-dihydroxybutanedioic)

two identical stereogenic centres

L-(+)-tartaric acid(2R,3R)-

D-(–)-tartaric acid(2S,3S)-

mesotartaric acid(2R,3S)- ≡ (2S,3R)-

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Conformers of alkanes and cycloalkanes

Ethane CH3–CH3

Examples:

Butane CH3-CH2-CH2-CH3

staggered eclipsed

syn-periplanar syn-clinal anti-clinal anti-periplanar

Newman projectionsCH2 CH2

H3C

C H3

rotation aboutthe C–C bond

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Cyclohexane

CH2

CH2

CH2

CH2

H2C

H2C

chair conformation (twisted) boat conformation (twisted) chair conformation

axial positionsequatorial positions

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Fundamental classes of organic reactionsSubstitution – a group attached to a carbon atom is removed and another

one enters in its place; no change in unsaturation.

Addition – an increase in the number of groups bound to carbon (hybridization sp1→sp2→sp3), the molecule becomes more saturated; mostly it is a reduction.

Elimination – a decrease in the number of groups bound to carbon (hybridization sp3→sp2→sp1), the degree of unsaturation increases; mostly it is an oxidation.

Molecular rearrangement (isomerization) – functional groups migrate within molecules or carbon skeletons are

modified; – functional groups are transformed (e.g. keto-enol, Amadori shift).

Reagents: nucleophilic – offer an electron pair electrophilic – accept an electron pair radical-like – have an unpaired electron (reactions are

initiated thermally or photochemically)

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Types of covalent bond cleavage

Homolytic splitting results in two radicals:

X–Y X• + •Y X–Y + •R X–R + •Y

Binding of two radicals is colligation. Heterolytic cleavage will give a nucleophilic and an electrophilic particle:

X–Y X + Y+

X–Y + E+ X–E + Y+

X–Y + Nu X–Nu + Y

Binding of a nucleophilic to an electrophilic particle is coordination.