Organic Chemistry II

Organic Chemistry II

Biological Molecules Spectra Separations and Purifications

Organic Chemistry II

Biological Molecules Carbohydrates Amino acids and proteins Lipids Phophorous containing compounds

Biological Molecules-carbohydrates Polyhydroxy aldehyde or ketone Empirical formula often (CH2O)n Many contain N, P, or S Monosaccharide (1 unit), oligosaccharide (2-10), polysaccharides

(10+) Glucose and Fructose most common on MCAT

Carbohydrates- nomenclature, classification, and common names

# Carbons

Category Name Relevant examples

3 TrioseGlyceraldehyde,

Dihydroxyacetone

4 Tetrose Erythrose

5Pentose. Furanoses

(bent ring)Ribose, Ribulose,

Xylulose

6Hexose,

Pyranoses (chair)

Glucose, Galactose,

Mannose, Fructose

7 Heptose Sedoheptulose

Named according to the number of carbons they possess and existence aspolyhydroxy aldehydes (Aldoses) or polyhydroxy ketones (Ketoses)

Carbohydrates- nomenclature, classification, and common names

Common disaccharides and polysaccharides Sucrose: glucose + fructose (α 1,4) Maltose: glucose + glucose (α 1,4) Cellulose: (glucose)n (β 1,4) Lactose: galactose + glucose (β 1,4) Amylose: (glucose)n (α 1,4) Amylopectin (plants): branched glucose chains (α 1,4)

Branching (α 1,6) Glycogen (animals): branched glucose chains (α 1,4)

Branching (α 1,6)

Carbohydrates- absolute configuration

The last chiral center in an aldose chain (farthest from the aldehyde group) was chosen by Fischer as the D / L designator site

D: if the hydroxyl group in the projection formula points right

L: left directed hydroxyl group (the mirror image) then represented the L-family.

Absolute configuration, which is different from d/l (dextra/levarotary +/-) relative configuration based on rotation of light.

D sugars are the natural form we can assimilate following digestion. (Refer to the highest numbered chiral carbon)

How many stereoisomers exist for a molecule of D-glucose?

A. 4

B. 16

C. 32

D. 64

D-glucose

CarbohydratesEpimers and Anomers Epimers- A diastereoisomer that has the opposite configuration at only

one of two or more stereogenic centers. Ex/ Mannose and α-glucose

Anomers- a type of epimer. cyclic stereoisomers of sugars that differ only in their configuration at the hemiacetal (anomeric) carbon. Ex/ α-glucose and β-glucose

α-D-Glucose Mannose

α-D-Glucose β-D-Glucose

Carbohydrates- Cyclic structure and conformations

Many simple sugars can exist in a chain form or a ring form.

The ring form is favored in aqueous solutions

Alcohol group on the chiral carbon furthest from the carbonyl carbon may act as a nucleophile attacking the carbonyl carbon

Forms hemiacetals in aldoses and hemiketals in ketoses

Hemiacetal and Hemiketal Formation

Carbohydrates-hydrolysis of the glycoside linkage Hydrolysis of starch involves the cleavage of the acetal functional

groups with the addition of a molecule of water for each glycoside linkage

Hydroxyl group reacts with anomeric carbon Produces many molecules of glucose

Carbohydrates-hydrolysis of the glycoside linkage

This is done by the enzymes called glycosidases or amylases which are found in saliva.

These enzymes work only on alpha glycoside linkages and do not attack beta linkages. Such beta linkages are found in cellulose.

Amino Acids and Proteins Amino acids are the basic structural units of proteins

They contain an amino group, carboxyl group, a H atom, and a distinct R group (side chain)

AA have acidic and basic properties (zwitterions can be both proton acceptors and donors)

Most exist as zwitterions at physiological pH

Because they are dipolar (+ and – charges) they have unique isoelectric points, but there is no net charge on the molecule

AA and Proteins- absolute configuration at the position

Amino acids have a chiral carbon (except glycine), are all L stereo-isomers.

Amino acids in solution

Low pH High pH

Amino acid general structure

Amino AcidsTitrations and Isoelectric Point (pI)

Isoelectric point of a protein is the pH at which the amino acid exist as a zwitterion

Amino acids essentially exist as diprotic acids at low pH, and their titration curves resemble those of diprotic acids.

AA and Proteins-classification Polar side groups- hydrophilic

Face aqueous solution Nonpolar side groups- hydrophobic

Face interior of protein

Polar Nonpolar Acidic BasicAsparagineCysteineGlutamineSerineThreonineTyrosine

AlanineGlycineIsoleucineLeucineMethioninePhenylalanineProlineTryptophanValine

Aspartic AcidGlutamic Acid

ArginineLysineHistidine

Amino AcidsTitrations and Isoelectric Point (pI)

Amino acids can be separated by placing them in an electric field such as is the case in gel electrophoresis. If a solution of amino acids at pH 8 underwent electrophoresis, which of the following would most likely move the furthest towards the anode?

A. Arginine

B. Glutamate

C. Histidine

D. Lysine

AA and Proteins-reactions Peptide linkage (formation of an amide): This is the

covalent bond that joins amino acids together. Formed by a condensation reaction involving the formation of water (Dehydration synthesis)

It is formed between the alpha-amino group of one amino acid and the alpha-carboxyl group of another amino acid

The peptide bond is rigid due to resonance and partial C=N character.

+   + Water

AA and Proteins-reactions Hydrolysis: the reverse reaction Peptides and proteins chains have direction because the chains

have different ends, an alpha-amino end and an alpha-carboxyl end

By convention the amino end is taken as the beginning of a chain An amino acid sequence is written starting from the N-terminal

amino end Thus the tripeptide gly-ala-leu is not the same as leu-ala-gly

because the former has gly at the N-terminal and leu at the C-terminal whereas the latter has leu at the N-terminal and gly at the C-terminal. Chemically, in the former gly has a free amino group, and in the latter leu has a free amino group.

+

  + Water

AA and proteins-general principles 1o structure: the amino acid sequence of a protein written from

the amino to the carboxy terminus. 2o structure: certain common repeating structures found in

proteins: alpha-helix and beta-pleated sheet Tertiary structure: the full 3D folded structure of the

protein Quaternary Structure: protein polymers, e.g.

hemoglobin in is made of 4 proteins, 2 alpha globins and 2 beta globins

Which structure of a polypeptide is most likely affected by the double bond nature of the peptide bond?

A. Primary

B. Secondary

C. Tertiary

D. Quarternary

Lipids Lipids have hydrophobic (long hydrocarbon tails) and

hydrophilic (charged heads) ends Lipid bi-layers

(phospholipids) make up cell membranes

Molecules with polar and non-polar

groups are called amphipathic

http://kvhs.nbed.nb.ca/gallant/biology/phospholipid.jpg

LipidsFree Fatty Acids

Fatty acids- long carbon chain with carboxylic acid end. Serve as hormones and messengers-

eicosanoids Components of cell membranes Fuel for body

Stored as triacylglycerols Store more than twice the energy of carbohydrates and

proteins

Triacyl Glycerols (fats and oils) Glycerol backbone with three carboxylic acid derivatives

http://www.oliveoilsource.com/images/triglyceride.jpg

Triacyl Glycerols (fats and oils) Saturated: no double bonds; i.e. saturated with hydrogen

Unsaturated: has double bonds. Double bonds can be cis or trans and are bent. The more unsaturated means more irregular structure and a lower MP

Shorter chains also have a lower MP (fewer vDW interactions)

Lipases and phospholipases are enzymes that break up lipids

Treatment with NaOH (saponification) breaks the fat into glycerol and fatty acids. Soap used to be made this way

The Ca2+ ion in water, known as hard water, cross links the head groups causing the soap scum

Natural glyceraldehydes are always D

The salts of fatty acids are used as soaps because the salts:

A. have a polar region and a nonpolar region and are thus insoluble in water.

B. have a polar region and a nonpolar region and are thus help organic materials become water soluble.

C. are exclusively polar and thus dissolve in aqueous solutions.

D. are exclusively nonpolar and thus dissolve organic materials.

passage 28

Steroids

Steroids have a four ring structure

Cholesterol, a steroid derivative, is essential to fluid nature of the cell membrane

Cholesterol decreases the melting point and increases the boiling point.

Bacteria do not make steroids. http://www.emc.maricopa.edu/faculty/farabee/BIOBK/steroid_3.gif

http://www.ems.psu.edu/~radovic/cholesterol.gif

Terpenes

Terpenes are widespread in nature, mainly in plants as constituents of essential oils.

The building block is the

hydrocarbon isoprene Terpene hydrocarbons have molecular

formulas (C5H8)n Examples camphor, menthol, vitamin A1.

Phosphorus Compounds

ATP, ADP, TTP, GTP, CTP, UTP, Insecticides, phosphatidyl choline, protein phosphorylation, cell signaling

There is a large amount of energy stored in phosphoric acid bonds, so it is used for energy storage

P-O-P is the phosphoricanhydride bond (high energy). C-O-P is the

phosphoester bond.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/ATP.html

Phosphorous Compounds passage 31

Wittig reaction: is an important method for the formation of alkenes

The double bond forms specifically at the location of the original aldehyde or ketone

Spectra, Separations, and Purifications

Spectra Absorption spectroscopy Mass spectroscopy NMR spectroscopy Extraction

Separations and Purifications Distillation Chromatography Recrystallization

IR -Absorption wave number = 1/; 4000-625 cm-

Detects functional groups: polar bonds stretch at characteristic frequencies

Divide IR (4000 to 4000 into 4 regions) 4000-2500: N-H, C-H, O-H 2500-2000: Triple bonds (CtbC, CtbN) 2000-1500: Double bonds (C=O, C=C, C=N) 1500-400: Fingerprint region (most complex region of IR)

IR -Absorption

When a compound is exposed to infrared radiation, the polar bonds stretch and contract in a vibrating motion.

Different bonds vibrate at different frequencies In IR Spec, the frequency of IR light is slowly

changed and frequencies of absorption are recorded

No dipole moment = no energy is absorbed

UV -Absorption Detects conjugated C=C Changes in energy of molecular orbitals. When pi electron of conjugated

system is displaced, energy is absorbed Increase 30-40 nm for each additional C=C, increase 5 nm for each

additional alkyl group

Conjugated Isolated

Visible-Absorption

Visible region: 8+ double bonds, usually conjugated Beta carotene, 11 C=C, max absorbance at 497

nm, looks orange

Effects of structural changes on absorption indicators

Mass Spectrometry -Emission Molecules ionized by collision with high energy e- (dislodging a

valence e-, and yielding a cation), causing some of the molecules to fragment, (some +, -, and neutral).

Passage of charged fragments through magnetic field then sorts them according to their mass. m/z- mass:charge. z is usually one, so m/z gives mass of + charged

ions. Tallest peak (100%)- base peak, fragment in highest concentration. Unfragmented ion- parent peak, M+ (molecular ion) The peak furthest downfield is the unfragmented cation. The sample

passes through a magnetic field and detects the mass/charge (m/e) ratio

determines molecular weight

NMR: nuclear magnetic resonance

Can tell the protons and their environment. Nuclei align with a magnetic field. Bombarded with electromagnetic energy. Resonance frequency, the nuclei turn against the

magnetic field.• Shielding: e- environment of the proton• Integral value: # of equivalent protons• Spin-spin splitting: peaks splits into n+1. n is the number of adjacent, different protons

NMR: nuclear magnetic resonance

Nuclei with odd atomic/mass number exhibit nuclear spin When placed in external magnetic field, nuclei aligns its own field

with or against the external field (with = lower E, against = higher E).

When the nucleus is irradiated with photons, it can absorb energy and flip its orientation in the magnetic field => Resonance.

Electromagnetic radiation is held constant while magnetic field strength varies.

Shielding- EWG shield less and shift the peak downstream, EDG shield more and shift the peak upstream.

Aldehyde protons have a distinctive shift at 9.5ppm

NMR

http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm#nmr1

Integral Values = ?

Electron withdrawing = shift downstreamElectron donating = shift upstream

Separations and Purifications

Extraction: distribution of solute between two immiscible solvents. Solvents dissolve impurities and move them to aqueous layer for removal. Products remain in the organic layer. Like dissolves like. Add strong acid: protonates amines and bases to

make them polar Add weak base: deprotonates strong acids to make

them non-reactive Add strong base: deprotonates any remaining acids

* Dilute acids make organic bases soluble in water

* Dilute bases make organic acids soluble in water.http://orgchem.colorado.edu/hndbksupport

Separations and Purifications Distillation: Purification based on

boiling points Lower boiling point will distill first

Raoult’s law: PA = XAPAO

compounds in a mixture combine to boil off together at an intermediate boiling point

Azeotrope: A liquid mixture of two or more substances that retains the same composition in the vapor state as in the liquid state when distilled or partially evaporated under a certain pressure.

http://www.tiscali.co.uk/reference/encyclopaedia/hutchinson/m0020819.html

Simple vs. Fractional Distillation

Simple distillation- separates components by differences in BP of entire sample. Raoult’s Law

Fractional distillation- initial sample of distillate is continuously redistilled, thus at each point the sample boils at a lower and lower temperature, ultimately approaching the boiling point of the pure substance with the lower boiling point. Accomplished by the use of fractional distillation column,

packed with a suitable material which subjects a mixture to repeating vaporization-condensation cycles until a pure substance emerges.

Separations and Purifications-chromatography

Column chromatography: Add analyte to the top of the column (stationary phase)

Liquid solvent (eluent, mobile phase) is passed over the column

Different interactions with the column (based on size, polarity, etc.) leads to separation

Components are collected as the solvent drips from the column

Why does an increasing salt gradient release molecules from an ion-exchange column?

A. It increases the molecular weight of the molecules, causing them to move through the column faster.

B. It decreases the strength of the charge interactions between the molecules and the stationery phase.

C. It increases the charge differences between the negatively and positively charged molecules.

D. It fills the porous beads, thereby excluding entrance by the molecules into the column.

Separations and Purifications-chromatography

Gas-liquid chromatography: The sample is vaporized and injected into the

head of the chromatographic column

The sample is transported through the column by the flow of an inert, gaseous mobile phase

The column itself contains a liquid stationary phase which is adsorbed on to the surface of an inert solid

Separations and Purifications-chromatography

Paper chromatography: A sheet of paper is the inert phase Analyze complex mixtures, such as ink, by separating

them into the chemicals from which they are made Degree of retention of a component is called the

retardation factor(Rf)  =    distance migrated by an analyte (Da)

           distance migrated by the solvent (Ds)

Separations and Purifications-chromatography Paper chromatography:

A sheet of paper is the inert phase Analyze complex mixtures, such as ink, by separating

them into the chemicals from which they are made Degree of retention of a component is called the

retardation factor(Rf)  =    distance migrated by an analyte (Da)

           distance migrated by the solvent (Ds) Thin-layer chromatography:

an adsorption chromatography in which samples are separated based on the interaction between a thin layer of adsorbent and a selected solvent

same principles apply as in paper chromatography

http://www.agsci.ubc.ca/fnh/courses/food302/chromato/schromato03.htm

Separations and Purifications-chromatography Passages 29 and 32 Recrystaliztation:

Impurities stay in solution and the pure product crystallizes

Solvent choice, is most important. Solvent should dissolve product at high temperature and have high affinity for impurities at low temperature or no affinity at all at high temperature

According to the adage "like dissolves like," a solvent that has a similar polarity to the solute being dissolved will usually dissolve the substance very well.