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 • Named according to the number of carbons they possess and existence as • polyhydroxy 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? • 4 • 16 • 32 • 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 a position • Amino acids have a chiral carbon (except glycine), are all L stereo-isomers. • Amino acids in solution Amino acid general structure Low pH High pH

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

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? • Arginine • Glutamate • Histidine • 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? • Primary • Secondary • Tertiary • 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: • have a polar region and a nonpolar region and are thus insoluble in water. • have a polar region and a nonpolar region and are thus help organic materials become water soluble. • are exclusively polar and thus dissolve in aqueous solutions. • 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 phosphoric anhydride 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/l; 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 Isolated Conjugated

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 Electron withdrawing = shift downstream Electron donating = shift upstream Integral Values = ? http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm#nmr1

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? • It increases the molecular weight of the molecules, causing them to move through the column faster. • It decreases the strength of the charge interactions between the molecules and the stationery phase. • It increases the charge differences between the negatively and positively charged molecules. • 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.

Organic Chemistry II