Organic Chemistry Functional Groups in Real Life
I always enjoy sharing how organic chemistry is part of our everyday life…and how it can save a life!
Case Information
A 56-year-old-man presents to the ED with progressive weakness. Until the onset of fatigue, he exercised daily at a gym. However, over a two-week period, the debility worsened such that he was unable to climb stairs and resorted to dragging himself up by the arms.
The patient’s medical history included gout, type 2 diabetes (well-controlled by insulin for 16 years), cardiomyopathy, chronic atrial fibrillation, and chronic renal insufficiency of four years’ duration associated with past nonsteroidal anti-inflammatory drug use. He was taking colchicine, allopurinol, warfarin, digoxin, and furosemide. Past surgical history consisted of right knee arthrocentesis and right midfoot fusion.
Muscle biopsy revealed variations in fiber size and configuration, as well as focal sarcoplasmic vacuoles. There were few neurovascular changes and no evidence of infiltration, vasculitis, or fibrosis.
Diagnosis
Colchicine-induced myopathy
Treatment
Cessation of the medication
The Structure of Colchicine and its functional groups
Colchicine is a drug used to treat gout. In this case, the drug that was being administered to treat the patient’s gout was actually causing the onset of progressive weakness (due to chronic renal insufficiency). Let’s take a look at the structure of Colchicine:
As we can see, there is a lot going on with this structure. Let’s begin by identifying a few functional groups on this molecule:
Nature, organic reactions and Colchicine
If we specifically focus on the ether functional groups, we could ask, “How does nature make the ether bonds?” Well, nature accomplishes this by using S-Adenosylmethionine (SAM):
We then could ask, “How do chemists make ether bonds in the laboratory? They use the Williamson ether synthesis reaction:
This reaction involves an alkoxide and an alkyl halide. With every reaction, you should break it down to what is the nucleophile and what is the electrophile; the nucleophile is what attacks and the electrophile is what is being attacked. Nucleophiles are either negatively charged or will have a lone pair that can be used to attack. Electrophiles are either positively charged or will contain double bonds, such as carbonyl compounds. Breaking the reaction down will help if the reaction involves complex molecules. Let’s take a look at the reaction of S-Adenosylmethionine (SAM) with an aromatic alcohol:
In this case, the oxygen is our nucleophile (negatively charged) and the sulfur is our electrophile (positively charged). But wait….now that the positive charge is gone on the sulfur, what about the negative change on the carbonyl group? Well, I have written it in this fashion just to give you an example of more complex structures. If we want to be more accurate, we could possibly rewrite the reaction mechanism as follows:
For practice, write down all the functional groups you see in S-Adenosylmethionine (SAM):
(This case was taken from clinicaladvisor.com)