Lecture 6 Flashcards
What is heteroatom oxidation?
It’s when a heteroatom and a O bond to each other. The heteroatom get a positive charge and the oxygen get a negative charge.
X+ — O-
In heteroatom oxidation, what heteroatoms are the most important ones?
N and S
What is a-hydroxylation?
When a H, i a C—H near a heteroatom, gets replaced with a OH-group.
Why is hydroxylamine the most toxic one on page 46?
???
What is more toxic: aliphatic amines or aromatic amines?
Aromatic amines. Propably because they are unsaturated and have delocalized pi electrons.
Heteroatom oxidation: What is the major path?
N-oxidation. Where the aromatic amine reacts with P450 and a OH binds to the NH. This can either become a radical and lead to radical reactions, or it can kickout sulfite and it become a strong electrophile (?).
Heteratom oxidation: What is the minor path?
Epoxidation. An aromatic amine reacts with P450 and get epoxidised. The ring with the O continue to reacts and become OH and then react sith peroxidase and form a double bond to the O. It is a electrophile.
Is the leaving ability of a leaving group stronger if it is connected to a heteroatom or carbon? Why?
The leaving ability is stronger if it’s connected to a heteroatom because it allows Nu to attack on different positions.
Are weak acids strong or weak leaving groups? And weak bases?
Weak acids = bad leaving groups.
Weak bases = good leaving groups.
The best leaving groups want the electrons???
Why is the oxidation of 1-aminonaphthalene into hydroxyamine slower than 2-aminonaphthalene?
Because 1-aminonaphtalene have steric hinders.
Is DMSO mostly reduced or oxidized?
Its major “end product” has been oxidized while the minor has been reduced.
Draw the oxidation of a primary alcohol, secondary alcohol and acetone.
P. 51
When it comes to oxidation of alcohols and aldehydes: how does the concentration of NAD+ and NADPH affect it?
Low conc. of NAD+ and high conc. of NADPH: A reduction will take place.
High conc. of NAD+ and high conc. of NADPH: Oxidation is the primary pathway.
In mammals, what concentration levels do we have of NAD+ and NADPH?
We have high conc. of NAD+ and low conc. of NADPH —> oxidation is the primary pathway
Can tertiary alchols be oxidized to aldehydes or ketons? If no, how can it be oxidized?
No, because it doesn’t have any hydrogen on its carbon.
It can be oxidized in the beta-carbon (phase I) kr conjugation with glucuronic acid (phase II).
What 3 kind of phase I reductions is there?
- Reduction of ketones and aldehydes
- Reduction of oxidized heteroatoms
- Reductive dehalogenation
What can ketones and aldehydes be reduced to? What favors this?
They can be reduced to alcohols.
This is favored by a low conc. of NAD+ and high conc. of NADPH, and low conc. of oxygen (oxidation needs oxygen)!
Why are aromatic amines toxic?
Because they can form electrophiles and radicals.
What is reductive dehalogenation? What halogens?
It’s the removal of a halogen and it’s replaced with a H. X = Cl, Br, I.
During the metabolism of DDT, what steps are there?
- Reductive dehalogenation
- a-hydroxylation
- Get rid of HCl
- Hydolysis
—> major metabolite of DDT is DDA
Why is DDT NOT that dangerous to eat?
It is very lipophilic and it doesn’t have any polar groups (hydroxy groups, amino groups etc), it doesn’t dissolve very well in our stomach. If it is poorly dissolved, it is poorly absorbed —> most will go right through us.
Name the 2 phase I hydrolyses.
- Hydrolysis of epoxides
2. Hydrolysis of esters and amides
Are epoxides dangerous to humans?
Epoxides doesn’t have a very big chance of reaching DNA or protein, because our bodies takes care of epoxides very fast and efficient.
Why is the smoke from cigarettes and BBQ dangerous?
Because the chemical that comes from incomplete combustion is epoxidized, hydrolyzed and epoxidized again. The last epoxidation can’t fit for epoxide hydrolyze which means it can travel through our bodies and go to DNA and react with it —> toxic!
Metabolic activation.
