Module 4: Structures And Reactions Of Biological Molecules Flashcards
Coenzyme
A small molecule which helps enzymes catalyse reactions
Important for building molecules such as fatty acids
What makes a molecule soluble in water?
Ionisable functional group(s)
R-OH
Alcohol
Example of an alcohol
Methanol
R-O-R
Ether
Example of an ether
Methyl ethyl ether
l
R-O-C-OH
l
Hemiacetal
l
R-O-C-O-R
l
Acetal
Which molecules are hemiacetal and acetal functional groups associated with?
Carbohydrates
O
ll
R-C-H
Aldehyde
Example of an aldehyde
Ethanal
Acetaldehyde
O
ll
R-C-R’
Ketone
Example of a ketone
Propanone (acetone)
O
ll
R-C-OH
Carboxylic acid
Example of a carboxylic acid
Ethanoic acid (acetic acid)
O
ll
R-C-OR’
Ester
Derivative of carboxylic acid
Example of an ether
Ethyl ethanoate
What molecules are carboxylic acids and esters associated with?
Lipids (and amino acids for carboxylic acid)
Are alcohols rare or common
Common
Are ethers rate or common?
Rare
Why are low molecular weight alcohols soluble in water?
Hydrogen bonding
This allows for bonding to active site of enzyme
Which nucleophilic reactions do alcohols undergo?
Substitution
Alcohols can combine with carboxylic acids to form _____
Esters
Primary alcohols are oxidised to form ____
Aldehydes
Aldehydes are oxidised to form _____
Carboxylic acids
Secondary alcohols are oxidised to form ____
Ketones
Which class of alcohol cannot readily be oxidised?
Tertiary alcohols
How does the silver mirror test distinguish an aldehyde from a ketone?
When placed in contact with a mild oxidant, an aldehyde will be oxidised, turning into a carboxylic acid
What molecules are used as oxidants for alcohols in the body? Give an example
Enzymes
Alcohol dehydrogenase to oxidise ethanol in the liver- turns into ethanal
Which is more reactive: ethers or esters? Why?
Esters
They are more easily cleaved by nucleophiles
What is an amine? Three classes
A nitrogen with 1-3 hydrocarbon groups bonded
Primary- 1 R
Secondary- 2 R
Tertiary- 3 R
What is an amide?
A nitrogen atom attached to three groups
- one of those is a C=O
Primary: C=O, H, H
Secondary: C=O, R’, H
Tertiary: C=O, R’, R”
What is an imine functional group?
A nitrogen double bonded to a carbon, and single bonded to a hydrocarbon group
R
\ /
C=N
/Main difference between amines and amides
Amines are significantly basic: they have a lone out of electrons on the nitrogen, available for bonding protons
Amides are not: their lone pair is not a available for bonding protons
Describe resonance in an amide
Amides have resonance because they flip between two structures
- One where N has the lone pair
- And one where O had the lone pair
The C=O bond is very polar, so O takes electrons from C, and in return C takes electrons from N
R-SH
Thiol
Alcohol analog
R-S-R’
Ether analog
R-S-S-R’
Disulfide
An oxidation reaction of thiol leads to what?
Disulfide
O
ll
HO-P-OH
l
OHPhosphoric acid
O
ll
HO-P-OR
l
OHAlkyl dihydrogen phosphate
O
ll
RO-P-OR
l
OHDialkyl hydrogen phosphate
O
ll
RO-P-OR
l
ORTrialkyl phosphate
What do alkyl dihydrogen phosphates and dialkyl hydrogen phosphates have in common?
Both strong acids- ionised at physiological pH (soluble)
What properties do phosphate groups bring to compounds?
Help to solubilise them in water
Resistance to hydrolysis (repels nucleophiles due to negative charge)
What does a biological target (host) need to form interactions with a small molecule (guest)? (3)
Right polarity
Right shape
Right stereochemistry e.g. chirality
Carbonyl compounds
Ones containing a C=O functional group
Aldehydes and ketones
Which carbonyl functional group has two alkyl groups?
Ketone
Which carbonyl functional group has an alkyl group and a hydrogen?
Aldehyde
Which carbonyl functional group tends to be at the ends of a carbon chain? Why?
Aldehyde
Because it has an H attached
Suffix of an aldehyde
-al
Suffix of a ketone
-one
Which reactions is carbonyl chemistry dominated by?
Addition reactions
Steps in the addition reaction of a carbonyl, using a strong nucleophile
Two steps
- Rate determining attack of nucleophile (on C)
- Fast attack of electrophile (on O)
Bond breaks and formations in the addition reaction of a carbonyl, using a strong nucleophile
Attack of nucleophile breaks Pi bond of C=O and forms single bond to C
Attack of electrophile forms single bond to O
What are H, H+ and H-
H = hydrogen atom (one electron)
H+ = proton (no electrons)
H- = hydride (electron shell is full)
LiAlH4 can do what to carbonyl compounds?
Reduce them back to their corresponding alcohols
Because it contains hydride (H-) that can act as a nucleophile
Adding an acid (H+) gives an alcohol
Is there a reaction intermediate or transition state in the addition reaction of a carbonyl compound using a strong nucleophile?
Yes- once nucleophile attacks, before electrophile attacks, there is a negatively charged transition state
Can nucleophiles be neutral?
Yes- they just need a non-bonding electron pair
What do we need to do before reacting a weak electrophile with a carbonyl compound?
Increase the positive charge on C (of C=O) by adding the electrophile first
What transition state do we get after adding the electrophile (first) to the carbonyl compound?
Carbocation
This is very attractive to the weak nucleophile
What charge does the weak nucleophilic atom have after bonding to the carbocation? (Addition reaction of carbonyl)
+1
Because the electrophile attacked first, producing carbocation
Carbocation has +1 charge, weak nucleophile has 0 charge, so when it attacks, the charge is transferred to the nucleophile
What occurs due to the positive charge of the nucleophilic atom?
(In addition reaction of carbonyl using a weak nucleophile)
The Nu-H bond breaks (fast step)
What is the slow step in the addition reaction of a carbonyl using a weak nucleophile?
Attack of nucleophile to carbocation
Which is the more reactive carbonyl functional group? Why? (2)
Aldehydes
- Less steric hinderance (Only one alkyl group)
- Less stability due to less alkyl groups donating electrons to reduce positive charge on C
In the slow step of an addition reaction to a carbonyl compound (weak nucleophile), we go from a ____ hybridised carbon to a ___ hybridised carbon
sp2 (trigonal planar- 3 groups attached)
sp3 (tetrahedral- 4 groups attached)
What weak nucleophile is used to turn a carbonyl into a hemiacetal?
Alcohol
Adding alcohol to carbonyl can turn it into hemiacetal. What will further alcohol addition produce? What kind of reaction is this?
Acetal
Substitution
Four steps in the substitution reaction to turn hemiacetal into acetal
- OH is a poor leaving group- so it’s protonated, forming carbocation
- Leaving group leaves (rate determining)
- Alcohol (nucleophile) attacks C, gaining its positive charge
- O-H bond is cleaved to get rid of positive charge, forming acetal
Which carbohydrates exist in hemiacetal form?
Monosaccharides e.g. glucose
In which carbohydrates does acetal join adjacent sugars?
Complex- oligosaccharides and polysaccharides e.g. starch and cellulose
How do amino compounds (R-NH2) act as nucleophiles?
Strong
Although they are neutral, the lone pair on nitrogen is more loosely held than the lone pair on an O, because N is less electronegative (orbital is further from the nucleus)
(Easier to share electrons)
Is the product of nucleophilic addition of amino compound to a carbonyl compound stable or unstable?
What will further reaction form?
Unstable
Imine
How is an imine formed from a nucleophilic addition product (from amino compound added to carbonyl)
What do equilibrium arrows between these steps mean?
OH is protonated
Leaving group (H2O) leaves forming a carbocation
Carbocation is deprotonated to form C=N double bond- amine
It’s a reversible process
How does 11-cis retinal turn into 11-trans-retinal? (Vision)
On absorption of a photon, the molecule becomes high energy
Pi bond breaks between C11-C12, allowing free rotation (and forming radicals)
As it loses energy, the Pi bond reforms in the new shape (trans)
What does the isomerisation of 11-retinal do in the body?
Triggers a series of events that send a signal form the eye to the brain
How do we produce more 11-cis-retinal?
The isomerisation process is reversed by enzymes
Most common form of monosaccharide
Aldose
What is a 2D drawing of a 3D structure called?
Fischer projection
What goes at the top of a Fischer projection?
The highest oxidised carbon
In a Fischer projection, is the longest carbon chain bonded horizontally or vertically?
Vertically
The bonds to the side of a Fischer projection project _____ the page
Out from the page
The up and down bonds of a Fischer projection project _____ the page
Into the page
How do we distinguish between D and L molecules in Fischer projections?
If the non-hydrogen atom points to the right= D
If it points to the left= L
How can we draw carbohydrates (two forms)?
Open chain structure
Ring structure
Why can a carbohydrate be drawn as a ring?
Because there’s free rotation about the single bonds
Anomeric carbon
A carbon bonded to two oxygens
Can be an acetal or hemiacetal group
5- membered ring
Furanose
Six-membered rings
Pyranose
Where do we draw oxygen in a carbohydrate ring?
Top right
Alpha (anomeric carbon)
Group off anomeric carbon (OH or OR) is on the opposite side (of the plane) to the side chain
Beta (anomeric carbon)
Group off anomeric carbon (OH or OR) is on the same side (of the plane) to the side chain
Cyclic forms of sugars are always in equilibrium with ___ _______
What is this process of re-closure called?
Free aldehyde
Mutarotation
What are the percentages of alpha, beta and open chain forms of sugar in solution?
37% alpha
63% beta
<1% open chain form
How do we know the percentages of alpha and beta sugars in solution?
By the way they rotate plane polarised light
Equatorial bonds
Bonds pointing slightly up and slightly down in a chair structure
Axial bonds
Groups pointing north and south in a chair structure
Which groups use equatorial bonds? Why?
Generally all groups: H atoms use axial bonds
Axial bonds aren’t suitable for larger groups because there’d be too much repulsion, raising the energy and making it more unstable
Reducing sugar
A hemiacetal sugar
- there must be free -CHO in solution to reduce silver
Why are acetals stable in the absence of H+?
OR is a poor leaving group
Would need to be protonated
Glycoside
Cyclic acetal
What is the bond between anomeric carbon and OR group called in a glycoside?
Glycosidic linkage
How can the substitution reaction of glucose with methanol produce both alpha and beta acetals?
The ethanol can attack from either above or below the plane
Non-reducing sugar
Acetal sugar
No reaction possible when there’s no open chain form
Which group links monosaccharides? At which points of the sugars?
Acetals
Anomeric carbon of one
OH of two
What is the reverse of acetal formation reaction?
Glycoside hydrolysis
Breaking the glycosidic linkage
How can monosaccharides differ? (5)
Number of carbons Stereochemistry Functional groups Ring size Orientation of groups
How do blood types differ?
By their extra sugar (or lack of)
Four examples of carboxylic acid derivatives
Ester
Amide
Acid anhydride
Acid chloride
Which L group of a carboxylic acid derivative has the strongest influence on the polarity of C?
Which has the weakest influence?
Chloride (in an acid chloride) and RCOO (in an acid anhydride)
R’HN (in an amide)
Why is an amide the least reactive carboxylic acid derivative?
The lone pair of electrons on the nitrogen create a Pi bond (N=C)
Reduces positive dipole on C
What two things does the substitution reaction of a carboxylic acid derivative depend on?
Strength of nucleophile
Reactivity of acid derivative
Oh which acid derivatives does the nucleophile strength not matter in a substitution reaction? Why?
Acid chlorides and acid anhydrides
Because the induced dipole on C is sufficient to attract weak and strong nucleophiles
Which acid derivatives require a strong nucleophile for substitution? Why?
Amides
Carboxylic acids
Esters
Positive dipole on C isn’t strong enough
What is the slow step, and intermediate in a substitution reaction of an acid derivative?
Addition of nucleophile
Unstable tetrahedral carbocation (wants to get rid of group with weakest bond)
Are the alkyl groups single or double bonded in fats?
Single
Are the alkyl groups single or double bonded in oils?
Why?
Double
Kinks in the tails make molecule more fluid and oil like
What is done to fats to prepare soaps?
Hydrolysis
What structures does soap form?
How do these work?
Micelles
Hydrophobic hydrocarbon chains cluster in the middle
Hydrophilic (polar) carboxylate groups are on the surface
Oil and dirt and trapped and dissolve in non-polar part of micelle
How is a liposome formed? What are they good for?
Lipid bilayer is unsaturated and folds into a liposome (double membraned micelle)
Drug delivery
Protease
Breaks down proteins (enzyme)
Amylase
Enzymes which break down starches
Lipases
Enzymes which break down fats and bread
Which two functional groups do amino acids contain?
NH2 amine
COOH carboxylic acid
What do the 20 naturally occurring amino acids have in common? (2)
All have a chiral carbon (except one)
All have same 3D arrangement around this chiral carbon
Alpha amino acid
An amino acid which has both amine and carboxylic acid groups on the chiral carbon
Do naturally occurring amino acids have R or S configuration?
Which fisher label do they have?
S (except cysteine)
L (including cysteine)
- NH2 group points to the left
What is the difference between amino acids?
Their side chain R
It can make them non-polar or polar, and acidic or basic
Acid-base properties of amino acids come from ______
The amine (base) The carboxylic acid (acid)
When we’re talking about the pKa of the amine group of an amino acid (pKa2), what should we keep in mind?
It is the pKa of it’s conjugate base NH3+
In a titration of an amino acid with a base, which groups react and in what order?
COOH ——> COO-
- first because COOH is the strongest acid
NH3+ ——> NH2
- once COOH has run out
What are the states of the amino acid groups in a zwitterion?
NH3+ and COO-
What do zwitterionic amino acids behave like?
Ionic salts
- high melting points
- solids
- soluble in water
pI
Isoelectric point
The pH at which the max number of molecules have a net zero charge (first equivalence point)
Where is the pI for simple amino acids?
Halfway between pKa1 and pKa2
Where is the pI for amino acids with acidic or basic R groups?
Between the two most similar pKa values
Name of the technique that discriminates molecules based on their overall charge
Electrophoresis
Amide bond formation involves which groups of an amino acid?
Amine NH2 of one bonding with the carboxylic acid COOH of the other
Peptide bond
Bond between two amino acids
What are the ends of amino acids that aren’t involved in the peptide bond called?
N-terminal and C-terminal
Are amides reactive to nucleophiles? Why?
They’re relatively unreactive
Resonance (due to lone pair on nitrogen) makes the central carbon less positive
What influence does the peptide bond have on molecule shape?
It has double bond character- restricted rotation
So the shape of the molecule is flat (in the same plane)
Peptide
Linear polymer of amino acids
Which terminus is written on the left when drawing a peptide?
N
C on the right
Why are peptides referred to as peptide chains?
Because the individual units can move in respect to each other (bond rotation)
How many amino acids does a molecule need to be considered a protein?
> 75
Four levels of protein structure
Primary- sequence of aa’s
Secondary- segments off structure along the chain
Tertiary structure- secondary elements fitting together
Quaternary structure- proteins/ peptide chains fitting together
Why do peptides adopt secondary structures?
To expose polar side chains, and bury non-polar ones
How are secondary structural elements in a peptide chain stabilised? What does this cause?
Hydrogen bonding
Kinks and turns in the chain
What shapes can be formed from peptide chains? (2)
Alpha-helices
Beta-sheets
What other bonding (other than H) can influence the shape of peptides?
Disulfide linkages
Thiol groups in cysteines can be oxidised by to give disulfide-linked dimer
Structure of insulin
Two peptide chains joined by disulfide bridges
To synthesise a peptide from two amino acids, what must we do before reacting them together?
Protect the group on each amino acid we don’t want to bond
Protecting group
Protects amino acid group we don’t want involved in next reaction
Examples: BOC, OMe (ester)
What role does an activator such as DCC play in peptide synthesis?
Facilitates the joining of two amino acids
How can reactivity of a peptide be achieved?
Heating with strong aqueous acid
Why do we need to hydrolyse peptide bonds?
To liberate amino acids we ingest
Apart from the low pH in our stomach, how do we hydrolyse peptide bonds?
Proteases (enzymes) catalyse the reaction
What does the enzyme chymotrypsin recognise?
Aromatic amino acid side chains
What do aromatic rings contain?
Benzene (C6H6)
What does the hydrophobic binding pocket in chymotrypsin do?
Recognises the aromatic ring and positions the peptide bond at the catalytic triad
What three molecules make up the catalytic triad?
Serine
Histadine
Aspartic acid
Which part of the catalytic triad acts as the nucleophile for the peptide bond?
O- of serine (OH bond cleaved)
Why does the chain of electron transfers along the catalytic triad start?
Aspartic acid exists as its conjugate base at physiological pH
It has an O- that shares electrons with H of histadine
What two main steps occur in peptide hydrolysis by chymotrypsin?
Peptide bond breaks, forming an intermediate ester
Intermediate ester is hydrolysed by ‘activated water’
Three key factors of carboxypeptidase and its role in hydrolysing peptide bonds
Holds reactants close together
Zn2+ makes C=O more susceptible to nucleophile attack
Deprotonates H2O to form OH- (much better nucleophile)
What part of a peptide does carboxypeptidase recognise?
The C-terminal of the amino acid
Why is OH of phenol (in tyrosine) more acidic than an OH group in another alcohol?
It’s conjugate base is very stable- at equilibrium there’ll be more of it
These is because the charge of the electrons is delocalised around the aromatic ring
