Organic Chemistry

optically active?

(1) Look for chiral centers ? (No, then not optically active) (2) is it meso compounds (identical)? (Yes, not optically active) (3) specific rotation? If (+) (+) or (-) (-) then it is optically active If (+) (-) then racemic mixture ...optically inactive

Synthesis of carboxylic acids

(1) carboxylic acid --> acid halide (uses SOCl2 and PCl3 or PBr3) (replace OH group with halogen) (2) Carboxylic acid --> acid anhydride -condensation of 2 carboxylic acids with loss of water) OR -carboxylic acid and acid halide --> acid anhydride (3) carboxylic acid --> ester (uses alcohol R'OH) (replaces OH group with OR) (4) Amid (cannot be formed from carboxylic acids, but can be made from acid halides/acid anhydrides/esters with desired amine) acid halide + desired amine --> amide (replaces halogen group with amine)

Nuclear Magnetic Resonance (NMR) Spectroscopy

(1)chemically equivalent sets of Hydrogens in the molecule —> to be equivalent need to be in identical electronic environments, identical location, same signal/resonance, interchangeable by free rotation/symmetry operation (mirror image/rotational axis) Rules: (A) protons need to be attached to the same type of central atom (B) central carbon needs same # hydrogens attached to it as with the others (C) whose neighbors are the same type with the same number of hydrogens To solve ... find degree of unsaturation (2C +2)-X/2 If 0 then zero double bonds/rings and if 1 then 1double bond or ring And if 1 peak then equivalent Then draw structure (2) Splitting Occurs when nonequivalent hydrogens interact with each other Degree of splitting depends on the number of adjacent hydrogens, split into n+1 lines n= #of neighboring nonequivalent H Splitting (n+1) 0 neighbors = 1-singlet peak 1 neighbor = 2-doublet peak 2 neighbors = 3-triplet peak 3 neighbors = 4-quartet 4 neighbors = 5-quintet (or multiplet) 5 neighbors = 6-sextet (or multiplet) (3) integration-measuring area under each absorption peak (resonance) (4)chemical shift Location of resonance (set of peaks) Electronegativity of neighboring atoms, hybridization, and acidity and hydrogen bonding causes molecules to be more deshielded(downfield) -more a proton is deshielded (more distorted away from the atom the electron is), the further downfield (to the left) in an NMR spectrum it will appear. Alkyl (RxCH(4-x) 0-2ppm Alkyne (RC triple bond CH) 2ppm Alcohol (R-OH) 2-5ppm Benzylic (aromatic ring-ch2-R) 2.5-3.5ppm (R-CH2X) 2.5-4 (Vinyl c=c) 5-6 Aromatic (ring-R) 6.5-8 Aldehyde (RCHO) 9-10 Carboxylic acid (R-CO2H) 10-13

Lipids

****Better at storing energy than carbs (1) in cellular membranes, phospholipids constitute a barrier btw intracellular and extracellular environments (2) in adipose cells, triglycerides (fats) store energy (3) cholesterol is a special lipid that serves as the building block for the hydrophobic steroid hormone Fatty acid Structure: Saturated (C-C) Unsaturated (C=C) "kink" Even number of fatty acid are made in human cells Naming unsaturated lipids: (1) number carbons starting with carboxylic acid chains (2) double bonds are always Z or cis and indicate double bond with lower carbon (cis delta 3) Micelle: (1)hydrophobic interaction happens when hydrophobic tails interact with each other in the inside (2) solvation shell forms around hydrophobic interaction in which water molecules form around hydrophobic substance Ex soaps :sodium salts or fatty acid. Hydrophobic and hydrophilic (amphipathic) Triacylglycerol or triglyceride: 3 fatty acids esterified to a glycerol molecule Similar to saponification Hydrolysis of fats achieved through lipase: Fats are a better energy source than carbs because (1) packing: hydrophobicity of lipids allows fats to pack together more closely than carbs (more carbon per unit are in fat droplet (2) energy content: more energy carbon for carbon than carbs. Fats are more reduced already. For energy metabolism it is necessary for oxidation to release energy. Thus since carbohydrates are more oxidized to start with, oxidizing them releases less energy. Lipid bilayer membrane: Hydrophobjc interaction drive formation of bilayer. Once formed it is stabilized by van der waal forces between long tails. Saturated fatty acid have more van der waal interaction than unsaturated Structural determinate of membrane fluidity: (1) Degree of saturation (more saturated less membrane fluidity). Unsaturated fatty acid increases membrane fluidity and prevents from solidifying (decreases melting point) (2) Tail length (decrease in tail length, also increases fluidity (3) Amount of cholesterol (at low temps cholesterol increases fluidity (antifreeze)... at high temp cholesterol decreases fluidity) **cholesterol keeps fluidity to an optimal level Terpenes: A member of a broad class of compounds built from isoprene units (C5H8). May be linear or cyclic (1) monoterpene: 2 isoprene units (2) sesquiterpene: 3 isoprene units (3) diterpene: 4 isoprene units (4) triterepe: 6 isoprene units Terpenoid: contains isoprene units and O,N,S Steroids: All steroids have tetracyclic ring system based on structure of cholesterol Steroids are a hormone, but similar to lipids (because of hydrophobic). Steroid cholesterol Obtained from diet and synthesized in liver, carried in the blood packaged with fats and proteins (lipoproteins). Atherosclerotic vascular disease "buildup of cholesterol plaques in the inside of blood vessels" Cholesterol derived hormones are estrogen and testosterone which r steroid hormones (diffuse into cell and receptor inside cell) .... vs insulin (peptide hormone) hydrophilic so receptor is on outside celll surface

SN1 reaction

*unimolecular nucleophilic substitution reactions: 2 steps --> step one: leaving group leaves/ carbocation is formed SLOW STEP/RATE LIMITING --> step two: Racemixation occus as the nucleophile attacks equally on either side of carbocation 1. Leaving group leaves forming a positively charged carbocation (rate limiting step) -More substituted carbocation (electrophile) is tmore stable --> will dissociate to more stable intermediate faster, speeding up rate of entire rxn (3>2>1>methyl) *The rate of rxn depends only on the concentration of the substrate rate = k [R-L] R-L is the alkyl group containing the leaving group *Anything that accelerates the formation of the carbocation increase the rate of rxn 2. Nucleophile attacks the carbocation (unstable) *results in substitution product - Solvents must be polar, protic (water, alcohol) --> Alcohol (ROH) produced if water (H2O) is solvent --> Ether (ROR) produced if alcohol (ROH) is solvent

Carbohydrates

- can be broken down to co2 in process called oxidation - glucose is building block of carbohydrate - single sugar (monosaccharide), 2 sugars (disaccharide) bonded together via Glycosidic linkage (covalent) , several sugars bonded (oligosaccharide) and many make polysaccharide. - the carbons in the monosaccharide are numbered beginning with carbon #1 at the most oxidized end of the carbon chain, which is the end with the aldehyde or ketone. (But fructose Carbon #2 is most oxidized) D-sugars (OH on last carbon to right) L-sugars (OH on last carbon to left) Pyranose (6 membranes ring) - if C5 attack's C1 Fursnose (5 members ring) - if C4 attacks C1 Hemiacetal formed in sugars where the ring forms when the OH on C5 nucleophilically attacks the carbonyl carbon (C1). Chair confirmation stable for sugars Alpha anomeric carbon (face down) Beta anomeric carbon (face up) Mutarotation: interconversion btw 2 anomers Conversion from fisher : chair form : Haworth notation (Groups ok left in fisher notation are above the ring in Haworth notation (as in chair form). (1) draw basic structure of sugar (2) if sugar is D-sugar place -CH2OH above the ring on the carbon to the left of the oxygen. For an L-sugar place it below the ring. (C#6) (3) for an alpha sugar, place OH below the ring on the carbon to the right of the right oxygen (C#1). For a beta sugar place Oh above the ring. (4) OH groups that are on the right in the fisher projection go below the ring and those on the left go above, using CH2OH group as the reference point for both projections. Sucrose (Glc alpha 1,2 Fru) Lactose (Gal beta 1,4 Glc) Maltose (glucose,glucose-alpha) Cellobiose (glucose,glucose -beta) Cellulose is a polymer of cellobiose Glycogen: energy storage carbohydrate in animals. Composed of thousands of glucose units joined in alpha1,4 linkages and alpha1,6 branches Starch: energy storage carbs in plants Alpha1,4 linkages Humans cannot digest beta glycosidic linkages (exception to rule is lactase.) people without lactase is lactose malabsorber and any lactase eaten ends up in colon (gas dirrhea). If certain bacteria are present people with this problem are lactose intolerant. Hydrolysis of glycosidic linkages: Disaccharides and polysaccharides are broken down into their component monosaccharide by enzymatic hydrolysis. Water is nucleophilic and one of the sugar is the leaving group (the one that was the attacker) - hydrolysis of polysaccharides is enzymatically favorable and does not occur at a significant rate without enzymatic catalysis (increase rxn rate through lowering activation energy) Reducing sugars (Benedict test): Is a chemical essay that detects the carbonyl units of sugars (distinguished between hemiacetals from acetate). —>any carb that can be oxidized by Benedict's reagent is referred as reducing sugar (reduces Cu but in the process sugar is oxidized. - Hemiacetals are in equilibrium with the carbonyl (open chain) form. If hemiacetal is present Benedict test will test positive - acetal is present Benedict test will test negative - all monosaccharides, aldehyde, ketone, hemiacetals give a positive result in Benedict's test for reducing sugars. Acetals give a negative result cause they do not react with Cu and not in equilibrium with open chain (carbonyl form). Problem: to determine what is a reducing sugar look to see if free anomeric carbon (#1) if yes then reducing carbon, if no then not. - isomers have the same atoms but different bonds, unless they are also stereoisomers. Stereoisomers have the same atoms and the same bonds, but different bond geometries. All stereoisomers are either enantiomers or diastereomers. Some diastomere are epimers. (Sugars can be either epimers or enantiomers)

Proteins

-Biological molecules that act as enzyme, hormones, receptors, antibodies, and support structure inside and outside cells. -composed of 20 different amino acids linked in peptide bonds together in polymers. (Composition and sequence of amino acids in the polypeptide chain is what makes each protein unique) - Amino acids share same N-C-C backbone with unique feature is side chain (variable D group) All amino acids chiral except for glycine *** all animal amino acids have the L configuration (amino group to left in fisher projection) *** all naturally occurring animal carbohydrates have the D configuration (amino group to the right in fisher projection) For sugars: D sugar have R configuration L sugars have S configuration Only for sugars L is (-) and D is (+) For amino acids: (except cysteine) D sugar have R configuration L sugars have S configuration (1) (+) and (-) describe optical activity and mean same thing as d and l (2) R and S describe actual structure or absolute configuration (3) D and L tell us basic precursor of a molecule (D or L glyceraldehyde)

SN2 reaction

-bimolecular nucleophilic substitution reactions - only 1 step (concerted reaction) -nucleophile attacks the compound at the same time as the leaving group leaves -Nucleophile actively displaces the leaving group in a backside attack for this to occur (inversion of configuration), nucleophile must be strong & substrate can't be sterically hindered (less substituted groups on electrophile, the faster the nucleophile can have access to reaction site) -concentrations of substrate & nucleophile have role in determining the rate --> rate = k[Nu][R-L] -Position of the substituents around the substrate carbon is inverted -Solvants must be polar, aprotic (acetone. DMF-dimethylformamide, DMSO-dimethylsulfoxide)

Carbon Chain Prefixes and Alkane Names

1 carbon: Meth- (CH4) Methane 2 carbon: Eth- (CH3CH3) Ethane 3 carbon: Prop- (CH3CH2CH3) Propane 4 carbon: But- (CH3CH2CH2CH3) Butane 5 carbon: Pent- CH3-(CH2)3-CH3 pentane 6 carbon: Hex- CH3-(CH2)4-CH3 hexane 7 carbon: Hept- CH3-(CH2)5-CH3 heptane 8 carbon: Oct- CH3-(CH2)6-CH3 octane 9 carbon: non- CH3-(CH2)7-CH3 nonane 10 carbon: dec- CH3-(CH2)8-CH3 decane Cyclo- ring structure

aldol condensation

A reaction in which an aldehyde or ketone acts as both the electrophile and nucleophile, resulting in the formation of a carbon-carbon bond in a new molecule called an aldol. (1) Requires a strong base (or alkoxide RO-) to remove a proton adjacent to carbonyl group (2) One of aldehyde of ketone must act as a source for the enolate ion while the other aldehyde or ketone must come under nucleopilic attack by the enolate carbanion (3) Aldol condensation rxn does not require the 2 carbonyl groups that participate in the reaction to be the same (when different - crossed aldol condensation - one of carbonyl compounds is chose that it does not have any acidic alpha protons (cannot be nucleophilic) -must be electrophilic Thermodynamic product ( more substituted, high temp/small base) Kinetic control (less substituted, low temp/bulky bases) Retro-Aldol Reaction and Dehydration: (the OH group becomes a double bond at the adjacent carbon between alpha and beta carbons) to form beta unsaturated carbonyl compound **** to solve problems (1) Determine which molecule has alpha hydrogens so can add on to "stays same" (2) The other molecule becomes the nucleophile witht he beta OH group that will be added to the alpha site

Ultraviolet-Visible Spectroscopy

A type of optical spectroscopy that measures the absorption of light in the visible and ultraviolet regions of the spectrum; the spectra primarily provide structural information about the conjugation of multiple bonds in the compound being analyzed. Also called UV-Vis Spectroscopy. Absorb UV —> appears white/colorless Visible Purple —> 400-430 Blue —> 460 Green —> 560 Yellow —> 600 Orange —> 650 Red —> 800

Reactivity of carboxylic acid derivatives

Acid chloride > acid anhydride > esters > amides -reactivity of acid derivatives increase with decreasing basicity of leaving group good leaving group is it is a weak conjugate base of a strong acid

Acid-Base Chemistry

Acid donates e-/H+ Base accepts e-/H+ acid dissociation constant (ka) = products/reactants pH = -log[H+] pka = -log[ka] Amino acid is amphoteric: acid carboxylic acid group (pka = 2) stronger acid Basic amino group (pka = 9 or 10) weaker acid - low pH = High [H+] - Lower pka (same as higher ka) describes a stronger acid that can donate a proton even when there are already excess protons (high [H+], low pH) Henderson-Hasselbalch Equation: pH = pKa + log[A-base]/[HAacid] pH>pKa (high pH, low H+) deprotonated pH<pKa (low pH, high H+) protonated Amino group in an amino acid acts acidic if protonated (ammonium NH3+) To find net charge ... molecules are always gonna be in COOH and NH3+ compare the pka values go given ph and determine if it will be protonated or deprotonated and add up to find total net charge

Hydride Reduction of Aldehydes and Ketones

Aldehyde --> Primary Alcohol (using NaBH4- reducing agent) Ketone --> Secondary Alcohol (using LiAlH4 - reducing agent) Carboxylic acid --> Primary alcohol (using LiAlH4 - reducing agent)

common functional groups

Alkane (single bond btw carbons) Alkene (double bond btw carbons) Alkyne (thriple bond btw carbons) Alkyl halide (single bond btw "R" and halogen) Alcohol (single bond btw "R" and OH group) Thiol (single bond btw "R" and SH) Ether ("R"-oxygen-"R") Epoxide (triangle of oxygen on top and then carbons on either side base) Phenol (aromatic ring single bonded to OH) Aldehyde (R-C-H and C is double bonded to oxygen) Ketone (R-C-R and C is double bonded to oxygen) Hemiacetal Acetal Cyanohydrin Amine Imine Enamine Amide (RN-C-R and C double bonded to O) Carboxylic acid (R-C-OH and C double bonded to O) Acid Halide (R-C-X and C double bonded to O) Acid Anhydride (R-C-O-C-R and both C double bonded to another O) Ester (RO-C-R and C double bonded to another O) lactone lactam

Naming alkanes, haloalkanes, and alcohol

Alkanes: (1) look for longest carbon chain (2) name substituents (3) number carbon chain (but substituents need to be on lowest carbon) (4) name in alphabetical order (ignore di, tri, tetra) Haloalkanes: (1) look for longest carbon chain (2) name substituents (3) number carbon chain (but substituents need to be on lowest carbon) (4) name in alphabetical order with halogen named first(ignore di, tri, tetra) Alcohol: (1) look for longest carbon chain (2) name substituents (3) number carbon chain (but OH need to be on lowest carbon) (4) name in alphabetical order with the alcohol named last drop "e" and replace with "ol" (ignore di, tri, tetra) if 2 alcohols on the same carbon then it will be "diol" etc ...

acidity of organic compounds

All organic acids are weak acids because they do not completely dissociate in solution General thumb of organic compound acidity: Strong acids (HI, HBr, HCl, HNO3, H2SO4, HClO4) > sulfonic acid > carboxylic acid > phenols > alcohols and water > acid anhydrides > aldehydes and ketones > sp hybrid C-H bonds > sp2 hybridized C-H bonds > sp3 hybridized C-H bonds Acidity of carboxylic acids : Substitute the next to the carboxylic acid group can increase the acidity of this functional group by increasing the stability of the negative charge on the anion. Also more electronegative a substituent group is the more the greater inductive effect (acidity) Electron withdrawing groups (NO2) on phenols increase acidity (stabilized) Electron donating groups (NH2 or OCH3) on phenols decrease acidity (destabilized)

isoelectronic point

Amino acid is fully protonated (COOH, NH3+) and has net charge of +1 (fully protonated) Then remove (-H) first take it off the COOH then becomes COO- and is Ka1 with zwitterion with neutral charge 0 Then remove second (-H) now take it off the NH3+ group and becomes NH2 and is Ka2 with charge -1 (fully deprotonated) Zwitterion: molecule with positive and negative charges (dipolar) and is uncharged is referred to as isoelectric point Calculating pI: average the pKas of the functional group (with no acidic/basic functional groups in side chains) - (pKa1 + pKa2)/2

Amino acid separation - Gel electrophoresis

Amino acid is loaded onto a gel with constant pH then exposed to electric field. If pH of the gel is different than the pI of the amino acid each amino acid will bear an overall charge because pI is specific to the unique structure of the side chain of each amino acid pH > pI —> the charge on amino acid is negative —> the direction of migration is toward positive electrode pH < pI —> the charge amino acid is positive —> the direction of migration is toward negative electrode pH = pI —> the charge on amino acid is neutral (zwitterion) —> no migration Problems .... if they give pH and pI value compare the two and determine charge of a.a and migration If given pka values then compare it to the pH determine if protonated/deprotonated and find overall charge ... then able to tell the direction molecilenmigraes

Infrared Spectroscopy

An instrumentation method of analysis that identifies bonds from absorption of the infrared radiation of different wavelengths Vibrational frequencies are commonly given in terms of wavenumber (v). Wavenumber is simply the reciprocal of wavelength v=1/wavelength ... and directly proportional to frequency and the energy of radiation - higher the wavenumber, the higher the frequency, and the energy Common frequencies: C—O (1,100-1,150) C=O (1700 / 1680-1735) C=C (1650 / 1620-1680) C triple bonded C (2,100-2260) C triple bonded N (2200-2260) C—H sp3 (2800-3000) sp2 (3000-3100) sp (3300) N—H (2500-3100) O—H (3200-3600)

Diastereomers

Are stereoisomers that are not enantiomers Non-superimposable, non-mirror images Inverting at least one of chiral center within a molecule 2 chiral centers (R,R) and (R,S) /// (R,R) and (S,R) /// (S,S) and (S,R) /// (S,S) and (R,S) Have different melting points, boiling points, solubilities, dipole moments, specific rotations There is no relationship between the specific rotations of diastereomers as there is for enantiomers

ring strain

Bond angles between ring atoms deviate from the ideal angle predicted by hybridization of the atoms. Mostly affects cyclopropane and cyclobutane Cyclopropane treated with H2/Ni at 120degC --> propane (releases strain) Cyclobutane treated with H2/Ni at 120degC --> butane (releases strain)

amino acids

Building blocks of proteins -linked together in polypeptide chain Acidic amino acids (hydrophilic) Aspartic acid (Asp, D) Glutamic acid (Glu, E) *pka functional group is 4 *at physiological pH (7.4), deprotonated *3 acidic functional groups (2backbone groups) (1R group) Basic amino acids (hydrophilic) Histidine (His,H) Lysine (Lys, K) Arginine (Arg, R) Polar (hydrophilic) Cysteine (Cys,C) "sulfer containing" Tyrosine (Tyr, Y) "OH containing" Serine (Ser,S) "OH containing" Threonine (Thr, T) "OH containing" Aspargaine (Asn, N) Glutamine (Gln, Q) Nonpolar (hydrophobic) Glycine (Gly,G) Alanine (Ala, A) Valine (Val, V) Leucine (Leu, L) Isoleucine (Ile, I) Methionine (Met, M) "sulfur containing" Proline (Pro, P) Phenylalanine (Phe, F) Tryptophan (Trp, W)

Chiral center has absolute configuration

Cahn-Ingold-Prelog rules: (1) priority assigned to 4 different substituents on the chiral center according to increasing atomic number of atoms directly attached to the chiral carbon —>if isotopes present then priority among these are assigned on the basis of atomic weight with higher priority being assigned to the heavier isotope —>if identical atoms are attached to a stereocenter then the next atoms in both chains are examined until a difference is found (2) A multiple bond is counted as two single bonds for both of the atoms involved (3) Once priorities have been assigned, the molecule is rotated so that the lowest priority group points directly away from the viewer. —> CLOCKWISE = R —> COUNTERWISE = S Fisher projection (3D) —> vertical lines go back into the pages ... and horizontal lines come out of the page

Carbocations vs carbanion (rxn intermediate)

Carbocations: positively charged species with a full positive charge on carbon. (In sp2 hybridization with an empty p orbital, secondary 2deg) Tertiary (3) > 2 > 1 > methyl (less stable...) Left to right: More stable, less reactive, lower energy Carbanion: negatively charged species with a full negative charge localized on carbon Methyl > 1 > 2> 3 (less stable...) Left to right: More stable, less reactive, lower energy

Alcohols

Change end of "e" to "ol" Ch3OH methanol CH3CH2OH ethanol Ch3ch2ch3 propanol Ch3ch2ch2ch3 butanol ....

Decarboxylation of carboxylic acids

Decarboxylation describes the complete loss of the carboxyl group as carbon dioxide. Decarboxylation is common in biochemical pathways in the body. Pyruvate dehydrogenase complex, carries out the decarboxylation of pyruvate to help form acetyl-CoA, which can feed into the citric acid cycle.

Protein structure in 3D (4 levels of protein structure)

Denaturation refers to disruption of a proteins shape without breaking peptide bonds. Denatured by (1) urea (disrupting. H bonding) extremes of pH, extremes of temperature, changes in salt concentration (tonicity) ***Primary structure: amino acid sequence Contains peptide bonds linking one amino acid to the next in a polypeptide chain ***Secondary structure: H bonding between backbone groups Initial folding of a polypeptide chain into shapes stabilized by hydrogen bonds betweeen NH and CO groups. Certain motifs : alpha helix and beta pleated sheets —> Alpha helices: right handed, 5A in width with each subsequent amino acid raising 1.5A, 3.5 amino acids/turn, doesn't contain proline (ex are hormone receptors and ion channels in alpha transmembrane region). Alpha helicies favorable structure for hydrophobic transmembrane region because all polar NH and CO groups in the backbone are hydrogen bonded to each other on the inside of the helix, thus don't interact with hydrophobic membrane interior. Alpha helical regions that span membranes also have hydrophobic R groups which radiate out from the helix, interacting with hydrophobic interior of membrane. —> B pleated sheets: Also stabilize H bonding btw NH and CO groups in polypeptide backbone. But, H bonding occurs between resides distant from each other in the chain or even on separate polypeptide chains. (Extended rather than coiled with side chains directed above and below the plane of the B sheet) (1) Parallel B pleated sheet: one with adjacent polypeptide strands running in the same direction (2) Antiparallel B pleated sheet: polypeptide strands run in opposite directions. ***Tertiary structure: Hydrophobic/Hydrophilic interactions - interactions of R groups with each other and with solvent (water). Hydrophobic R groups tend to fold into the interior of the protein, away from the solvent, and hydrophilic R groups tend to be exposed to water on the surface of the protein Ex: van der waaal interactions btw two hydrophobic groups located far apart on polypeptide and Disulfide bridge in cysteine (not a good example cause not hydrophobic) but it still if formed in tertiary structure. Quaternary structure: various bonds btw separate chains - highest level of protein structure, describes interactions btw polypeptide subunits (single polypeptide chain that is part of a large complex containing many subunits - a multisubunit complex) - force stabilizing quaternary structure is generally the same as those involved in secondary and tertiary structures -noncovalent interactions (H bond and van der waal). Covalent bond may also be involved in quartnary structures -disulfide bridges holding subunits together (one covalent bond not involved is peptide bond) Ex: antibodies/large protein complex

size exclusion chromatography

Desperate large polymers from small oligiomeric fragments (stationary phase is chemically inert, porous polymer beads) Large molecules eluted first and faster Then smaller molecules eluted later Size of beads traps small molecules pathway (intraparticle slower) and large molecule pathway (interparticle faster)

geometric isomers

Diastereomers that differ in orientation of substituents around a ring or double bond If two high priority groups are on the same side (one hydrogen bond), the configuration at the double bond is (Z) If two high priority groups are on the opposite side of the double bonds (one hydrogen bond), the configuration is (E) If 2 highest priority group on same side (with 2 hydrogen bonds), the configuration is (cis) If 2 highest priority group on opposite side (with 2 hydrogen bonds), the configuration is (trans)

Proteins

Disulfide bridges: covalent bonds between cysteine R groups amino acids Peptide bonds: link amino acids together into polypeptide chains (covalent bond) (specifically amide bond between 2 amino acids) A peptide bond is formed between an carboxylic group of one amino acid and the alpha amino acid of another amino acid with the loss of water. - occurs by nucleophilic addition elimination -formation of polypeptide is not thermodynamically favorable and requires energy. Thus, naturally needs an enzyme. DCC coupling in order to synthesis peptides artificially in the laboratory - polypeptide chain N-C-C backbone .. amino terminus is the first end made during polypeptide synthesis and carboxyl is made last. Thermodynamics of the peptide bond: - The formation of a peptide bond with 2 amino acids is not thermodynamically favorable and requires energy - free energy must decrease for a rxn to proceed simultaneously and such a rxn will spontaneously proceed towards equilibrium. A dipeptide bond with amino acids is higher in free energy (less favorable) than 2 separate amino acids (less free energy, more favorable) Hydrolysis of a peptide bond (amide) to from a free amine and a carboxylic acid is thermodynamically favored (products have lower free energy) but kinetically low. - hydrolysis refers to any reaction in which water is inserted in a bond to cleave it. 2 common ways to accelerate the rate of peptide bond hydrolysis through 2 common ways (1) strong acids and heat (nonspecific way) (2) proteolytic enzymes (specific) The disulfide bond: Cysteine (polar amino acid) has a reactive SH (thiol group). Thiol of one cysteine can react with thiol of another cysteine to produce a covalent sulfur-sulfur bond —> disulfide bond —> making cystine molecule Disulfide bridges found in extracellular proteins (under oxidizing conditions) - important In stabilizing tertiary proteins structure

reducing agent

Donates electrons and becomes oxidized -reduces aldehydes/ketones/carboxylic acids into alcohols NaBH4 LiAlH4

Anomers

Epimers that form as a result of ring closure are known as anomers (SUGARS) In Haworth projection: C1 is anomeric carbon if OH down (alpha) of anomeric carbon if OH up (beta) of anomeric carbon Fisher -> Haworth projection -> chair form If OH on right (down right ) on the Haworth projection as ring structure Same thing from Haworth to chair form ... if OH down then OH in chair form points down (no matter equatorial or axial position)

Acid catalyzed ester hydrolysis mechanism

Ester + acid --> carboxylic acid and alcohol

Saponification (base mediated ester hyrolysis)

Ester with base --> carboxylic acid (without OH) and alcohol group

Mass Spectroscopy

Gives the MW and (in high resolution) the molecular formula by % abundance. The molecules of a sample are bombarded with electrons, causing them to break apart and ionize. These ions are accelerated through a magnetic field and the resulting force deflects the ions around a curved path. -> Radius of curvature of their path depends on the "mass to charge ratio" (m/z) of the ion. Most ions have a +1 charge. The magnetic field strength is altered to allow the passage of different sized ions through the flight tube and a computer records the amount of ions passing through at a given strength. Base peak: largest peak "Parent peak": peak made by the molecular ions (original molecules that did not fragment, missing one electron -> +1) should be on the right side of the spectrum with heavy isotopes. Common molecular weights CH3 —> 15amu OH —> 17amu O-C=O —> 44amu Br (2 peak equal) —> 35,37 Cl ( 2 peak but 1/3 in height) —> 79,81

Organometallic Reagents (nucleophilic addition)

Grignard Reagent Formation: R-Br + Mg --> R-MgBr Grignard Reaction: Aldehyde/Ketone and R''-MgBr --> OH-C-H and other 2 bonds are the R''group from grignard and the initial R group Protection of alcohols with (mesylates - mesyl chloride) and (tosylates - tosyl chloride)

Good leaving groups

Halogens Stabilized resonance groups

Nucleophile

Have Unshared pair of electrons or pi bonds and frequently (-) negative charge "nucleus loving" DONATE ELECTRONS ***Lewis Bases (strong bases) (1) Nucleophilicity increases as negative charge increases (NH2- more nucleophilic than NH3) (2) Nucleophilicity increases going down the periodic table within a particular group (F-<CL-<Br-<I-) (Going down a group, atoms get larger, more polarizable and more nucleophilic) (3) Nucleophilicity increases going left in the periodic table (NH2- more nucleophilic than OH-) (electronegative decreases going left, ... increased nucleophilic) Cl- H-O-R (alcohol) NH3 CN- (cyanid) H-O (negative) Alkene (double bond) CH3-MgBr

Electrophile

Have a full or partial positive (+)charge "love electrons" +++Accepts electrons Lewis acids H+ C-R3 + BH3 Ketone

Constitutional Isomer

Have same molecular formula, but their atoms connected together differently (n-hexane, 2-methylpentane, 3-methylpentane same molecular formula but diff name b/c diff connectivity)

conformational isomers

Have same molecular formula, same atoms connectivity, but differ from one another by rotation about a sigma bond Staggered vs eclipse confirmations Staggered: a sigma bond on one carbon bisects the angle formed by two sigma bonds on adjacent carbons Eclipse: a sigma bond on one carbon directly lines with a sigma bond on an adjacent carbon Flagged to Newman Projections Rules or vise versa (1) Determine if anti (staggered)/ parallel (eclipse) If looking at flagged molecule If "hash" then it goes on the right If "solid arrow" goes on left side Newman projections to flagged If anti (staggered), draw out flagged molecule as anti and molecule on right goes in "hash" on flagged and molecule on left goes on "solid arrow" If parallel (eclipse), draw out flagged molecule as parallel, and molecule on right goes in "hash" and molecule on left goes on "solid arrow" ***staggered conformation is most stable cause: (1) electron repulsion (covalent bonds repel one another composed of negative charged electrons and in staggered the sigma bonds are far apart as possible, but in eclipse it is directly aligned with one another) (2) steric hindrance (atoms attached to sigma bonds in the roomier staggered conformation where they are 60deg apart) Staggered (anti) —> eclipse —> staggered (gauche) —> eclipse (syn) —> gauche —> anti Anti conformation (abs min energy) MOST STABLE ...when 2 largest groups attached to adjacent carbons are 180deg apart Rotate 60deg then Eclipsed conformation (rel max energy) Gauche conformation (rel min energy) arises when 2 largest groups to adjacent carbon atoms are in a staggered conformation 60deg apart Syn conformation (abs max energy) 2 large groups directly aligned behind one another and are therefore the most crowded Cyclobutane —> chair confirmation is most stable when large group is Equatorial Methyl ch3 more stable in equatorial position If "hash" it is down.... when it translates to chair confirmation then determine axial or equatorial "solid arrow" it is up doesn't matter when it translates to chair confirmation then determine axial or equatorial

affinity chromatography

Highly specific interactions between macromolecules Used to purify proteins or nucleic acids from complex biochemical mixtures (cell lysates/growth media/blood) Specific binding to Target molecule traps onto stationary phase —> unwanted component washed —> then target protein is released off the solid phase in a highly purified state Large scale work - stationary phase is a column packed with a solid resin, and the sample is poured through the column. Small scale work - solid stationary phase is mixed into small tube with sample to allow interaction with the components of the mixture. —> sample centrifuged so heavy solid resin settles to the bottom of the tube. Since protein of interest is bound to solid resin, liquid (supernatant) is simple decanted, leaving the desired compound behind. Protein of interest-antibody-protein A/G/L-solid support bead (1) Cell lyates are collected and contain many proteins (2) an antibody against the protein of interest is added (3) protein A/G/L linked beads are added and bind antibodies (4) beads and complexes are collected by centrifugation (5) complexes containing only Protein of interest-antibody-protein A/G/L-solid support bead are purified Magnetic beads as the solid phase (1) addition of magnetic beads to mixture (2) magnetic beads have specific binding to proteins (3) supernatant removed (4) magnetic beads attached to protein of interest washed and released Affinity tag Molecular tag added to N-terminus and C-terminus of the protein (DNA sequences coding for affinity tags can be subcloned into a plasmid with gene of interest)

keto-enol tautomerization

Ketone --> Enol CH3-C-OH and main carbon double bonded to CH2 (using a strong base/acid or water)

Cyanohydrin Formation (nucleophilic addition)

Ketone/Aldehyde + cynide (C thriple bond to N) --> OH-C-(c triple bond to n) and on the other side of cardons are R1 and R2 groups.

Enamine Formation (nucleophilic addition)

Ketone/Aldehyde + secondary amine --> enamine (replaces carbonyl group with secondary amine R-C-R on top is secondary amine and shifts double bond to another adjacent carbon)

Imine Formation (nucleophilic addition)

Ketone/Aldehyde with primary amine (R'-NH2) --> imine (replaces carbonyl group with primary amine R-C-R on top is primary amine)

Stereoisomers

Molecules that have the same molecular formula and connectivity, but differ from one another only in the spatial arrangement of the atoms (no rotation of sigma bonds) Not superimposable and have chiral centers (4 groups different on the main carbon) #steroisomers equals 2^n (n=chiral centers)

High Performance Liquid Chromatography (HPLC)

More polar molecules elutes first since more affinity to mobile phase Less polar molecules elute later and slowed by interactions with the nonpolar stationary phase Pumping unit (contain polar mobile phase) which carries the sample that is injected into the HPLC column (contains nonpolar stationary phase). Sample is separated into constituent components, which are detected and analyzed as they exit column. Elucent collected after detection —> component can be isolated.

Gas Chromatography

More volatile (more likely evaporate) carried along by carrier gas at a faster rate (emerge from column first) Less volatile (less likely evaporate) will spend more time in dissolved liquid stationary phase (emerge from column later) Separation takes place between mobile gas phase and stationary liquid phase, separate mixtures based on their different volatilities.

nucleic acids

Nucleotide is building block of nucleic acids. Linked by anhydride linkage (high energy phosphate bond) Phosphorous is an inorganic molecule is able to donate 3 protons ka1=2.1, ka2=7.2,ka3=12.4 1 phosphate = orthophosphate, 2 phosphate =pyrophosphate Hydrolysis of pyrophosphate is extremely favorable Nucleoside: base + sugar Nucleotide: base + sugar + 1-3 phosphate ATP (Adenosine triphosphate): ATP is the universal short-term energy storage molecule. DNA (A-T, G-C) // RNA (A-U, G-C) Bases: (pyramidine/purine) Pyramidine: (thymine, uracile, cytosine) Purine: (adenine, guanine) Sugars: (ribose or 2'deoxyribose)

meso compound

One side of the molecule is the mirror image of the other side (identical)

acid-base extraction

Organic compounds that are basic (amines) can be extracted from mixtures of organic compounds upon treatment with dilute acid (5-10% HCl) —> protonate the basic functional group forming a positively charged ion (cationic salt) Extraction of organic amines R-NH2 + HCl —> NH4+ + Cl- Organic compounds that are carboxylic acids can be extracted from mixtures of organic compounds upon treatment with dilute weak base (NaHCO3 or NaOH) —> deprotonate the acidic functional group forming a negatively charged ion (anionic salt) Extraction of carboxylic acids R-COOH + NaHCO3 —> R-COO- Na+ + H2O + CO2 Extraction of phenols Phenol-OH + NaOH —> phenol-O- Na+ + H2O

Simple distillation

Performed to remove trace impurities based on significantly different boiling points (removing salt from water by evaporation)

Gabriel Malonic Ester Synthesis of Amino Acids

Phtalamidine + KOH/H2O + Malonic ester —> phtalamidine with malonic ester + NaOMe/Br-R —> phtalamidine with malonic ester and R group attached —> alpha amino acid NH3-C-R and Malonic ester groups changed to H and CO2H

Oxidation of Aldehyde and Ketone

Primary alcohol --> Aldehyde (using PCC - oxidizing agent) Secondary alcohol --> Ketone (using CrO3 or any aqueous oxidants)

Fractional distillation

Process that is used when the boiling point of the components in the liquid mixture is not large. Reaction flask with mixture to be purified with heat source—> distillation column, filled with packing material —> condensed to cool vapor —> collection flask with purified, lower boiling point component

Resolution of Enantiomers

React a racemic mixture (R) + (S) with a chiral compound (chiral probe) to form diastereomers, which can be separated (into an enantiomerically pure material)

Degree of saturation and unsaturation

Saturated: (C-C) contains no pi bonds and no rings Has 2n+2 hydrogen atoms Unsaturated: (C=C) contains at least one pi bond or ring Deg unsaturation = (2n+2)-x/2 n = #carbons x = #hydrogens and monocovalent atoms/halogens (no oxygen atoms). If nitrogen present replace each N by 1 Carbon and 1 Hydrogen. 1 degree of unsaturation: 1 pi bond (1 double bond) or one ring 2 degree of unsaturation: 2 pi bond (2 separate double bonds or one triple bond)

ion exchange chromatography

Separate based on varying charge Pass mobile liquid phase containing the analyte through column packed with solid stationary phase, utilizes a polymeric resin functionalized with either positive or negatively charged on polymer surface Cation exchange resin: Ion of interest is + charge (pI > pH) Negative resin beads attached So... Positive analyte attaches to the negative beads .. so the negative analyte elutes first(pI< pH) Then ... the positive analyte elutes later (pI > pH) Anion exchange resin: Ion of interest is - charge (pI < pH) Positive resin beads attached So... Negative analyte attaches to the positive beads .. so the positive analyte elutes first(pI > pH) Then ... the negative analyte elutes later (pI < pH)

column chromatography

Separate polar and more bulkier compounds Less polar compounds and nonpolar compounds travel faster down column and are collected first More polar compounds spend more time absorbed on the polar Solid phase and travel more slowly down the column than nonpolar compounds and are collected last Compounds to leave column are collected in order of polarity (lease polar to most polar) -column filled with silica gel and saturated with chosen organic solvent, mixture of compounds to be separated is then added to the top and allowed to travel down the silica-packed column.

liquid-liquid extraction

Separation of a compound based on its solubility in two different solvents in a container using separatory funnel. Solubility depends on polarity of the solute and polarity of the solvent (like dissolves like) Polar molecules are soluble in polar solvents Nonpolar molecules are soluble in nonpolar solvents Liquid liquid extraction —> organic compound is extracted with water (can remove highly polar or charged - inorganic salts, strong acids/bases, lower molecular compounds alcohols, amines, carboxylic acids)

Thin Layer Chromatography (TLC)

Small molecules separated based on polarity Less polar molecules interact more with liquid mobile phase travel faster up the glass place (and have a higher Rf factor) More polar molecules interact more solid stationary phase and are slow to travel and remain lower levels on the plate (have a lower Rf factor) Solid-liquid partitioning technique in which the mobile liquid phase ascends a thin layer of absorbent (generally silica) that is coated on supporting material such as glass plate (polar stationary phase) "Ratio to front" Rf = (distance traveled by an individual component) / (distance traveled by the solvent front) *Rf always positive and never greater than 1

inductive effect

Stabilize charge of intermediates by the sharing of electrons through sigma bonds Electrons withdrawing groups —> pull electron toward themselves through sigma bonds (groups more electronegative than carbon tend to withdraw) CARBANION Electron donating groups —> push electron density away from themselves through a sigma bond (groups less electronegative than carbon tend to donate) CARBOCATIONS

melting/boiling point

Strong intermolecular forces increases boiling and melting point. Weak intermolecular forces decreases boiling and melting point. Branching of hydrocarbon alkanes decreases surface area, decreases intermolecular force attraction, and thus decreases boiling and melting point. Higher Molecular weight increases surface area and thus increases boiling point and melting point •Small hydrocarbons (1-4carbons) tends to be gases at room temperature •Intermediate hydrocarbons (4-16carbons) tends to be liquids at room temperature •Large hydrocarbons (more than 16carbons) tends to be solids at room temperature Hydrogen bonding increases boiling and melting point (hydrogen bonding with intermolecular forces btw 2 molecules increases mp/bp.) (hydrogen bonding with intramolecular forces within molecules decreases mp/bp) To rank hydrocarbons in increasing np (1) count the carbons (one with lowest carbon has lower bp) (2) compare branching (one with more branching has lower bp) (3) count molecular weight (higher molecular weight has higher bp) (4) look for hydrogen bonding (higher bp) (H bonding is greater than molecular weight in terms of increasing molecular weight).

Epimers

Subclass of diastereomers that differ in their absolute configuration at a single chiral center Ex) D-galactose is a C-4 epimer of D-glucose Ex) D-allose is a C-3 epimer is D-glucose D = OH group on the highest carbon of sugar on the right side L = OH group on the highest carbon of sugar on the left side D and L, like R and S, are entirely unrelated to optical activity (+) or (-) R or S = absolute configuration (structure) D or L = relative configuration (structure) (+) or (-) = observed optical rotation (property)

oxidizing agent

The electron acceptor in a redox reaction (will be reduced) making the other reaction oxidized. - Oxidizing agent used in converting primary alcohol to aldehyde -Oxidizing agent used in converting secondary alcohol to ketone Aqueous oxidants Chromic acid (H2CrO4) Bichromate salt (Cr2O7 2-) Chromate Salt (CrO4 2-) Permaganate (MnO4 -) Chromium Trioxide (CrO3) Anhydrous Oxidant Pyridinum Chlorochromate (PCC)

Streamer synthesis

Transform aldehydes into alpha amino acids (racemic) Aldehyde + (NH4Cl, NaCN)/H2O —> R-C-CthriplebondN with NH2 replace carbonyl group this with H3O+ —> R-C-COOH and other 2 bonds are NH3+ and H

leaving group

Weak bases (I-, Br-, Cl-) are good leaving groups because their negative charge is stabilized due to their large size. Going down periodic table, (basicity decreases), leaving group ability increases (the weaker the base the better leaving group) ***Halogens, water, and (tosylate, mesylate, acetate) are most common leaving group

Distillation

a process used to separate dissolved solids from a liquid, which is boiled (to overcome intermolecular forces) to produce a vapor that is then condensed into a liquid

Electrophile

an electron-pair acceptor (Lewis acid) CR3+ Ketone BH3 H+

Nucleophile

an electron-pair donor (Lewis base) Cl- OH- R-OH CH2=CH2 R-MgBr NH3 Cynide (C thriple bond to N) Strength of nucleophile (1) increases with negative charge, (2) Going down a group with increasing polarity/atomic size, (3) to the left of a group with decreasing electronegativity

esterification reaction

carboxylic acid + alcohol R-OH) -> ester (R-C-OR with carbonyl group) + water

Reduction of carboxylic acids

carboxylic acid to primary alcohol (using reducing agent LiAlH4)

Nomenclature for substituents

methyl -CH3 Ethyl -CH2CH3 Propyl -CH2CH2CH3 Isopropyl CH3-CH-CH3 Butyl (n-butyl) -CH2CH2CH2CH3 sec-butyl CH3-CH-CH2CH3 tert-butyl (t-butyl) CH3CH3-C-CH3

Enantiomers

non-superimposable mirror images (non-identical) Invert every stereocenter within the molecule 1 chiral center (S,R) 2 chiral center (R,R) and (S,S) /// (R,S) and (S,R) --> Always have opposite absolute configurations -->Have same melting point, boiling point, polarity, and solubility Optical activity: compound that rotates the plane of polarized light --> Dextroratatory (d) (+) rotates light CLOCKWISE --> Levorotatory (l) (-) rotates light COUNTERCLOCKWISE Specific Rotation: Magnitude of rotation of plane-polarized light for any compound dependent on (1) structure of molecule, (2) concentration of the sample, (3) path length through which the light must travel *** A pair of enantiomers will rotate plane-polarized light with equal magnitude, but in opposite directions. Racemic mixture: 0 degree, not optically active (since one enantiomer will rotate plane-polarized light in one direction, while the other enantiomer will rotate light by the same magnitude in the opposite direction) specific rotation is 50/50 ***(+) and (-) sat nothing about whether the absolute configuration is "R" or "S". (no correlation, independent of each other).

Resonance effects

stabilize charge by delocalization through pi bonds Localized: e- that are confined to one orbital (bonding btw 2 arms or a lone pair orbital) Delocalized: e- allowed to interact with orbitals on adjacent atoms (no longer confined to original "space") Rules for resonance ***structures of lowest energy are the most important (1) octet rule is satisfied for all atoms (2) minimal formal charge (V - 1/2B - lonepair) better than large separation of charge (3) negative formal charge on atoms most electronegative. Positive formal charge on atoms least electronegative.

Acetal Formation (nucleophilic addition)

use of acid, water comes off, alcohol attacks Ketone/Aldehyde with HCl and R-OH (alcohol) --> hemiacetal (then treat with R-OH and remove water) --> acetal Hemiacetal: OH-C-OR (C also bonded to R and H or R and R ) **use strong acid or base for rxn Acetal: OR-C-OR (C also bonded to R and H or R and R) ***use only strong acid for rxn