What is hydrolysis?
Breaking a bond by adding H2O.
- Amide to carboxylic acid and amine.
- Downhill NAC with tetrahedral intermediate.
- Can be catalyzed by either acidic or basic conditions.
Explain base catalyzed amide hydrolysis
- OH group’s O attacks C as double bonded Os electrons shift up.
- The bond attached to NR2 takes away H on O and leaves. H transfers electron to O. Double bonded Os electrons shift down.
- Final result is C double bonded to O and an O -. Also and NR2H group.
Why can amide hydrolysis be catalyzed by the addition of either acid or base?
- Amino acids contain both acidic and basic groups.
- The specific 3D orientation of amino acid side chains change in relation to the subtrate.
Explain acid catalyzed (H+) amide hydrolysis
- Double bonded O bonds to H and becomes +. Due to resonance, the C the positive O is bonded to is also electrophilic.
- Double bonded Os electrons shift up as a water attacks the electrophilic C.
- Lone groups on N steal H from bonded water. (Which now is a positive O)
- Double bonded O (now OH) shifts electrons down as NR2H leaves. Double bonded O is now positive.
- H leaves double bonded O by transferring electrons to it.
How does folding of proteins catalyze a reaction?
- Stabilize a transition state. (lowers activation energy)
- Destabilize (Raise energy of) ground state of substrates,
- Provide an alternative reaction pathway. (eg. temporarily covalently bond to substrate)
Explain chymotrypsin protease process
- N grabs H on serine while NAC occurs (Double bonded O shifts electrons up, O attacks C)
- Tetrahedral intermediate: Double bonded O shifts electrons down while NH group grabs H bonded to N and leaves.
- H2O attacks C, double bonded O shifts electrons up. His-N attacks H on the H2O
- Tetrahedral intermediate; C bonded to O, OH (H2O) and serine. His -N bonded to H. O shifts down electrons, serine O bond grabs H on His-N.
- Finally, NH2R, carboxylate, serine and his are separate.
What are lipids?
- Not a functional group definition.
- Defined by a physical characteristic (solubility)
- Gunk that can be extracted from an organism with non-polar solvent.
What are waxes?
- Esters of a long chain carboxylic acid and a long chain alcohol.
- Even number of Cs on left side (16-36)
- Even number of Cs on right side (24-36)
What are fats and oils?
- Triesters of glycerol and long chain carboxylic acid.
- E ve ucunda OH var.
What is saturated?
No double bonds in the long chain
What is unsaturated?
Some double bonds
What is polyunsaturated?
A lot of double bonds.
Why are saturated fats solid at room temperature?
Dense packing with no branching, london dispersion forces
What is Omega 3?
Double bond that starts from the 3rd carbon at the end
What is soap?
- Salt of fatty acid used for cleaning
- H on OH leaves, leaving behind O-. This then forms a salt with some cation.
- The O- side is hydrophilic, the carbon-hydrogen chain is hydrophobic.
What is detergent?
Surfactant or mixture of surfactants with cleaning properties in dilute solutions.
Soap and detergent are both
How do soap and detergent work?
Hydrophobic tail bonds to oil/fat dirt and coats it, hydrophilic tail dissolves it in water.
- Saponification is base catalyzed hydrolysis of an ester
- Double bonded O shifts electrons up as carbonyl is attacked by OH.
- There is tetrahedral intermediate. OR group leaves as double bonded O shifts down electrons. OR group is now negative since O is only bonded to R
- OR group steals off H from OH group bonded to carbonyl. The result is H being gone!
Why is the alpha carbon to a carbonyl nucleophilic?
Because its protons are acidic.
Explain base catalyzed keto-enol tautomerization
- Base grabs one alpha H. H transfers electrons to alpha carbon.
- Alpha carbon is now negative. Resonance structure is where O is negative and there is a double bond on alpha carbon.
- Negative O grabs H from BH.
Explain acid catalyzed keto-enol tautomerization
- Double bonded O grabs H from H-A. H transfers electrons to A.
- Resonance form with negative O with three bonds. Resonance is positive C.
- A grabs one H from alpha carbon. Electrons of H is transferred to central C as double bond.
In the equilibrium between keto and enol forms, which dominates?
The keto form dominates.
When does the enol form dominate keto form?
- When there is stabilization due to H bonds or conjugation.
- An example of this is when there are two ketos bonded together. The enol form with one double bonded O and another OH. H is stabilized through H-bond with O on the other side.
Describe the mechanism of acid catalyzed Br addition to acyl group.
- Double bonded O grabs H from Acid and becomes positive with three bonds.
- Double bonded O shifts electrons up as alpha proton’s electrons shift to form double bond.
- O shifts electrons back down as one of the double bonds grab a bromine.
- The other bromine (now negative) grabs H from positive OH. H shifts electrons to O so that it is neutral.
What happens if we use a really strong base in keto-enol tautumerization?
- Base grabs one alpha proton. Electrons from alpha proton form double bond. Double bonded O shifts electrons up.
- We form an enolate as the MINOR resonance structure. (conjugate base of enol.) C on the tip is negative and a really good nucleophile.
- Reprotonation to enol or keto form is disfavored.
Is enolate minor or major?
It is the minor resonance structure.
What is LDA?
An example of a really strong base that generates enolates.
What types of reactions to enolates take part in?
They act as nucleophiles in SN2 reactions
Explain SN2 with enolate as nucleophile
Attacks electrophilic carbon. In the same step, the leaving group leaves in one step. Draw this as a single line connecting electrophilic carbon and nucleophilic carbon.
What are aldol reactions?
- Enolate can attack an acyl copy of itself, since the c bonded to double bonded o is somewhat electrophilic.
- Only happen with weaker bases, where both forms of the enolate can exist in the pot.
Explain steps of aldol reactions?
- Base removes an alpha proton. Electrons from alpha proton are transferred as double bond. Double bonded O shifts electrons up.
- Minor resonance from of enolate attacks carbon on itself as the prior self shifts electrons up.
- Negative O grabs an H and forms an OH.
- The result is a beta-hydroxy carbonyl.
What is the result of aldol reactions?
What happens when we add heat and water to beta hydroxy carbonyls?
- They turn to alpha beta unsaturated carbonyls.
- This is because they are thermodynamically favored.
- OH group leaves. There is a double bond between alpha and beta.
Explain how beta hydroxy carbonyls convert to alpha beta unsaturated carbonyls with base catalysis.
- Base grabs H from alpha carbon. Electrons transfer to from double bond. Double bonded O shifts electrons up.
- O shifts electrons down. Double bond shifts to beta carbon. OH group leaves.
- Result is alpha beta unsaturated carbonyl.
Explain how beta hydroxy carbonyls convert to alpha beta unsaturated carbonyls convert to alpha beta unsaturated carbonyls with acid catalysis.
- Double bonded O grabs an H and becomes positive.
- H2O grabs one alpha proton. Electrons from alpha proton shift to become double bond. O shifts electrons up to become neutral.
- O shifts electrons down. Double bond shifts places. OH leaves.
Explain aldol reactions with esters?
- Nucleophile grabs alpha proton. Alpha proton shifts electrons to form double bond. O shifts electrons up.
- Minor resonance structure is enolate. Enolate attacks a copy of itself.
- Tetrahedral intermediate. Ester group leaves beta carbon.
- The result is a beta keto ester
What results from aldol reactions with ester?
Beta keto, ester
What is the general rule of decarboxylations?
If the pair of electrons left behind by the departure of CO2 can be stabilized by resonance, decarboxylation can occur.
Why does equilibrium for decarboxylations lie on the right?
CO2 is incredibly low in energy.
Explain decarboxylation in beta keto acid
O to H bond becomes double bond. Bond between CO2 and everything else is transferred to a carbon, which becomes negative. (Although resonance stabilized)
What undergoes decarboxylation?
Beta keto carboxylation.
Explain mechanism of carboxylation
- Base grabs an alpha proton. H transfers electrons to alpha carbon, making it negative.
- Negative then grabs a C on CO2 and bonds to CO (double bond) and Oi. O- grabs H back from base.
What is oxidation?
- Decrease in number of CH bonds
- Increase in number of C heteroatom bonds (particularly C-O bonds)
What is reduction?
- Increase in number of C-H bonds
- Decrease in number of C heteroatom bonds
Explain energy and redox?
- Oxidation results in energy being released.
- Reduction requires energy input.
Explain mechanism of carbonyl reduction
- NEGATIVE H (nucleophile) attacks carbonyl. O shifts electrons up.
- Tetrahedral intermediate. Negative O grabs H, resulting in OH.
What is the source of H- in the lab?
What is the source of H- in biology?
NADH, NADPH, FADH2
Explain NADH and NAD
- NAD is H- donor, reducing agent
- NADH is H- acceptor, oxidizing agent
How does NADH reduce?
H- is not generated at any point. It shifts directly from NADH to carbonyl.
How does NAD oxidize?
- H- is never generated.
- Base grabs H from OH, O shifts electrons from its bond to H to form double bond.
- At the same time H- acts as a leaving group and attached to NAD.
How does aldehyde dehydrogenase work?
- It oxidizes acetaldehyde to acetic acid.
- S-ALDH attacks carbonyl. O shifts electrons up. As O shifts electrons down, H acts as a leaving group and reduces NAD to NADH.
- Water then attacks carbonyl, resulting in the loss of S and ALDH.
Explain reduction of NADH
- Electrons from H directly bond to carbonyl
- Lone pairs on N transfer to left as double bond. The other double bond moves to the right
Explain keto-enol tautomerization from enol to keto
- OH loses H to B.
- Resonance structure with double bonded O and negative H. C gets H.