Nitrite Mediated Photooxidation of Vanillin in Atmospheric ...
in water, shouldn’t they have a hard time dissolving in ...€¦ · Few examples of aldehyde...
Transcript of in water, shouldn’t they have a hard time dissolving in ...€¦ · Few examples of aldehyde...
1
Chemistry 106
Lecture 10: Organic Functional Groups
4/19/18
Our consideration of the behavior of ionizable drugs in buffered environments
gives rise to 2 questions:
Question 1: Since ionizable drugs are pretty much ionized at blood pH, how do they
cross the non-polar portion of biological membranes? That is, if they dissolve well
in water, shouldn’t they have a hard time dissolving in the fatty portion of the cell
membrane?
Answer: The key is “pretty much”. Since an ionizable drug will go back and forth
between ionized and unionized state, it can slip through the cell when unionized (so
long as the unionized form is fairly nonpolar. Recall Sorbitol is never ionized but is
always very polar and cannot cross the cellular barrier).
As an interesting side note, if an ionizable drug can move across a cellular
membrane into a region of different pH, it may become trapped depending on the
pH of that region; e.g. speeding removal of basic drugs by acidifying the urine
2
Drug of the Day, Pyrimethamine (Daraprim®)
Used in the treatment of protozoal infections, principally malaria (214 million
cases worldwide, resulting in 438,000 deaths. WHO 2016 malaria factsheet)
Inexpensive and extensively used for eradication programs in South America
and Asia, resistance has become commonplace (the first-line agent,
artemisinin, a traditional Chinese medicine isolated from sweet wormwood, is
also beginning to show resistance)
When used together with sulfadiazine, pyrimethamine may be used to treat the parasitic
infection toxoplasmosis, a rather rare protozoal infection that is seen more commonly in
cat fanciers who have AIDS.
4
Question 2: Why do we bother to make the salt form of ionizable drugs in the first
place, if they are going to become ionized in the buffered environment of the
body?
Answer: Speed counts! How fast a drug will dissolve is important and the ionization
status of a drug has a large role to play. If you are injecting morphine IV, you
certainly don’t want the morphine to dissolve slowly as it occludes [blocks] the site
it was injected into. In fact, you want it already dissolved so it can be rushed by
the bloodstream to where it is needed. On the other end of the spectrum, if you
wanted a slow release of drug, an oil-based formulation injected into a large muscle
group may be possible. The classic example is Depot Provera®.
5
Organic Functional Groups
There are certain arrangements of C, H, O, N, and X (where X is a halogen – F, Cl,
Br or I) that confer particular chemical and physical reactivities to organic
molecules (and thus drugs). Organic chemists refer to these as functional groups.
And there are 10 common ones. Most drugs contain more than 1 functional group,
as do the examples below – see if you can find all of them!
Alkenes
Contain a C=C double bond. General structure
R2
R3R1
R4 Where R = C or H
Drug example – vitamin A as an antioxidant vitamin. Also, as the molecule that
defines what light is to us (see last 4 pages)
O O
O
OH
O OH
HO.
.
Example: (-)-trans-9-tetrahydrocannabinol
Note that alternating double bonds in a 6-membered ring are not properly
considered alkenes – instead, these are “aromatic” compounds. Aromatic rings are
especially stable and as such are widely found in nature (and drugs which are either
derived from or mimic nature)
6
Alkynes
Contain a C to C triple bond. General structure
R2R1 Where R = C or H
Drug example – ethinyl estradiol
Haloalkanes
Carbon based molecules with a halogen (F, Cl, Br, I) attached
Drug examples – volatile anesthetics
FCl
F F
Br H CF3
O
CF3
H
H
FH
Halothane (Fluothane) Sevoflurane (Ultane)
Unnatural in terrestrial systems and difficult for the biological world to deal with
7
Ethers
Oxygen with carbon attached to either side. General structure
R1
OR2 Where R = C, cannot be H (or alcohol, water)
Drug examples – codeine, MDMA (Ecstasy)
Codeine MDMA
Example: (-)-trans-9-tetrahydrocannabinol
Notice the ether linkage is missing in cannabidiol (CBD, next page)
8
Alcohols
Carbon attached to O which is attached to H. General structure
R1
OH
Where R = C
Drug examples – many! See adrenaline on group exercise 2 and estradiol above,
oxycodone below
The “eth” in ethanol means 2 carbon atoms connected together. The “ol” in
ethanol means it is an alcohol – thus there is no uncertainty about the
structure of ethanol
Question: Is ethanol a drug?
Alcohol reactions: readily oxidized to aldehydes and ketones. Acts as major means
of conjugating (linking together) different molecules - see esters below. Hugely
important to the removal of drugs since the liver possesses a system for adding an
alcohol group, thus polarizing the molecule and hastening its elimination (not to
mention terminating the activity of the drug in the vast majority of cases)
Example: Oxycodone
Examples: (-)-trans-9-tetrahydrocannabinol, and cannabidiol
Question: Why is cannabidiol named cannabidiol?
9
Amines
Drug examples – many! See all the stimulant drugs written as bond-line formulas in
lecture 3, and all of the plant alkaloid drugs mentioned to date. General structure
R1N
R2R3 Where R = C or H (but not all 3 R = H or ammonia)
N
N
(S)-nicotine
In addition to promoting a sense of calm, nicotine is a terrific insecticide
Main reaction: weak base - ionizable when treated with acid. Make certain you can
distinguish between an amine and an amide – amides have an adjacent C=O and are
not basic
Aldehydes
C double bonded to O on end of molecule. General structure
R1
O
H Where R = C, H (if H, formaldehyde)
Few examples of aldehyde drugs, as they rapidly oxidize to carboxylic acids.
Example: Vanillin…ok, not really a drug (unless perhaps when mixed with cacao)
10
Ketones
C double bonded to O in interior of molecule. General structure
R1
O
R2 Where R = C, not H (if H, aldehyde)
Drug example – hydrocodone
Hydrocodone
Reactions: May be reduced to alcohol, do not oxidize to acids. As such found in
many drugs. Biological example of reduction to alcohol
OH
O
O
NADHOH
O
OH
Good Bad
Carboxylic Acids
General structure RCO2H, or
R1
O
OH Where R = C, H
11
Drug examples: Non-steroidal anti-inflammatory drugs
OO
OH
Naproxyn
Reactions: ionizable when treated with base. Condenses with alcohols to form
esters, condenses with amines to form amides
Esters
Condensation between carboxylic acid and alcohol, spitting out water. General
Structure
R1
O
OR2
Where R1 = C, H R2 = C (if H, a carboxylic acid)
Drug examples: Shorter acting local anesthetic agents
Procaine Benzocaine
Cocaine
Reaction: May be hydrolyzed (split with water) to carboxylic acid and alcohol
12
Amides
Condensation between carboxylic acid and amine, also spitting out water. General
structure,
R1
O
NR2
R3 Where R = C, H
Drug examples: Longer acting local anesthetic agents. Antibiotics (penicillins and
cephalasporins)
Lidocaine
N
S
OCO
2H
NH H
O
Benzylpenicillin(Penicillin G)
Reaction: May be hydrolyzed (split with water) to carboxylic acid and amine
Proteins are formed from amino acids, where the amine on one amino acid condenses
with the acid portion on another amino acid, which continues over and over
H2O
Serine Cysteine
14
11-cis-retinal (bent) binds to the protein opsin giving rise to rhodopsin (visual
purple)
Light strikes the 11-cis-retinal causing it to isomerize to 11-trans-retinal
(straight)
Since the 2 forms of retinal have different shapes, they change the shape
of the protein containing the retinal from rhodopsin to metarhodopsin.
By interacting with a protein [transducin] inside the rod cell, metarhodopsin
II ultimately keeps Na+ from entering the cell, which leads to a nerve
impulse interpreted in the brain as vision