My Recent Absence, Explained With 9 Molecules

by James

in Off Topic, Teaching

Hey folks – it’s been awhile! Let me explain.

It all started very innocently. In mid November I started noticing that a little bump I’d had on the back of my neck for what seemed like forever had started getting sore.

At first it was annoying. One Wednesday night I was taking a fencing lesson, and I noticed that putting on the mask rubbed it the wrong way. I didn’t think much of it.

Then, like Mt. St Helens, my bump started growing and growing. My neck grew extremely stiff, to the point where checking for traffic through my drivers side window required turning my entire torso. An eruption seemed imminent.

[My wife took a picture, which I’ll spare you from seeing because it’s extremely gross. Plus I’m squeamish which is the whole reason why I never had any intention of going to medical school. ]

It was an infected sebaceous cyst. My doctor had me take sulfamethoxazole to try to stem the bacterial infection.

1-sulfamethazole

Several days later I could barely get out of bed I was so tired, and on top of that, was getting fever and chills. Furthermore, as predicted, Mt. St. Helens had erupted from three separate peaks, and “lava” [that’s a euphemism for “sup” written backwards, folks] was flowing everywhere. Again, very gross.

200px-MSH80_eruption_mount_st_helens_05-18-80-dramatic-edit

Mt. St. Helens erupts

The cyst had to be removed, so I met with a surgeon who took a look at it. It was still a bit too messy to operate on, so I had to wait another several days for the surgery.  Since sulfamethoxazole was having no effect, I was put on clindamycin instead:

2-clindamycin

[Note the chiral centers there! We’ve got a sugar, first of all, and then a side chain containing a chlorine stereocenter. How many chiral centers in total? Answer at bottom]

Thankfully  the antibiotic was working to great effect. I was no longer feeling extremely tired and the fever/chills had gone away. I felt well enough to go to Mammoth Caves in Kentucky with my wife’s family when they came down the week of Thanksgiving and held a 30 pound toddler on my chest for 2 hours through the undeground caverns.

The next day was my surgery. The last thing I remember is being wheeled to the operating room and then, at some point which I do not recall, I must have been given a general anaesthetic because I woke up what must have been an hour later propped up in bed with bandages on the back of my neck.

Turns out they gave me propafol. which is delivered intravenously.

3-propofol

That was just to knock me out. The actual painkiller was fentanyl.

4-fentanyl

Recovering from anaesthesia was not fun. The remainder of Wednesday was spent either sleeping, or sitting in a chair doing my Abe Lincoln Monument impression with my stiff neck. The surgery also left my neck in considerable pain, but thankfully I’d been prescribed hydrocodone for these purposes, which was necessary in order to sleep.

5-hydrocodone

The next day I woke up with bloodshot eyes, a sore leg and a nosebleed that would not go away. After waiting on it for a day, on Friday I finally went to the hospital emergency to get it checked out.

After running the standard battery of tests, doctors told me that my platelet count was 34. Normal humans have platelet counts of 150-300. Below 20 they immediately start blood infusions.

The diagnosis was something called DIC (disseminated intravascular coagulation) which is when you have simultaneous bleeding and clotting [that pain in my leg?  blood clot].  The Wikipedia article on DIC was not very reassuring:

“The prognosis for those with DIC, regardless of cause, is often grim: Between 10% and 50% of patients will die ” 

DIC generally has a root cause, so the problem became trying to figure out what started it in the first place. So I was asked a series of questions about possible exposures to bacteria, viruses, and so forth, and then one of the doctors earnestly asked me:

“Have you been exposed to any chemicals?”

Having worked 10 years organic chemistry labs and having handled  a countless array of highly toxic environmental hazards [safely of course]  ?

“Pretty much all of them”, I replied.

Her face fell. “Oh. That’s going to complicate our analysis”.

Heh heh.

To make a long story short, they put me up in the part of the hospital usually reserved for transplant recipients and had me on serious antibiotic drip for 3 days.

I had read Evans’ and Boger’s papers on the synthesis of vancomycin several years ago but I had never “met” it in person. I can’t say it was pleasant to be on a vanco drip – never did I get more than 2 hours of consecutive sleep.

The molecule itself however, is as beautiful as they come:

6-vancomycin

[how many amino acids can you find? how many sugars?]

Simultaneously with vancomycin I was put on a drip of Zosyn, which is a penicillin derivative.  Over the years bacteria have developed resistance to penicillin by synthesizing proteins that break open the beta-lactam ring without harming the organism [beta lactamases]. Taking the arms race one step further, zosyn combines the penicillin antibiotic piperacillin with a beta-lactamase inhibitor tazobactam.

7-zosyn

Did it work?  It’s safe to say my stomach bacteria were nuked into submission. However it did not seem to be addressing the root cause of the illness.

After three days of whirlwind visits from doctors, the surgical team, hematologists, and (very kind) nurses drawing blood, I was given heparin [a blood thinner] to try to “free up” some of my platelets from the blood clot. This did the trick – my platelet count started moving up from the mid 40’s to the 60’s, the 80’s, and then – on my fifth day in the hospital – a three digit platelet count (and freedom).

220px-Heparin-2D-skeletal

Monomeric unit of heparin

My reward for leaving the hospital was to self-administer heparin for the next two weeks which was done by stabbing myself in the stomach twice a day on alternate sides . At last count platelets were up in the 213 range so things seem to be in the clear. To this day nobody knows exactly what caused this little adventure, although serious things such as leukemia have been ruled out.

As a healthy person who had previously never been admitted to hospital for any kind of illness, this was an eye opening lesson on the value of health insurance.

The minor surgery to remove the cyst – something considered to be a pretty routine procedure – cost over $16000. The 5 day hospital stay cost over $28000. Without insurance, this would have been financially crippling. With insurance, my out of pocket expenses will only be about 3k.
Screen Shot 2015-01-06 at 12.01.49 PM

So this little adventure, combined with the holiday break, and trying to finish up two big projects for MOC that I hope to announce shortly, explains the absence.

That, and learning to play the banjo I got for Xmas.

banjo

Hope you had a great break – and Happy New Year! In the next post we’ll get back to our series on alcohols, ethers, and other related molecules.


 

1) Clindamycin has 9 chiral centers.

2) The product of propofol chlorination would look like this. Both OH and isopropyl are o-p directors, but OH is a more activating group, so since “stronger donor wins” the Cl will end up para to the OH group:

10-propofol quiz

NOTE – commenter opsimath notes that the presence of OH strongly activates the ring and the AlCl3 catalyst would not be required in this case [this is also the case for halogenation of other highly activated rings such as furans, pyrroles and indoles] Textbooks often neglect to mention a subtle detail like this.

3) Vancomycin has 7 amino acids and 2 sugars.

Final note below – looking at the structure of propafol it is remarkable how close it is to the structure of the common food additive BHT. I wonder if BHT has ever been tested for anaesthetic properties?

 

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{ 14 comments… read them below or add one }

John Spevacek

“Tagged as : fun” ?!?!?!? Note to self: do not party with James. Or do anything else that he promises will be “fun”.

Glad your “cystectomy with extreme complications” all worked out. Stay healthy this year, ok?

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opsomath

You surely don’t need AlCl3 or other Lewis acids – Cl2 is plenty strong enough of an electrophile to react with that highly activated ring.

Oh, and glad you’re alive. :)

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James

You are correct – let me make a note of that on the post, even though many intro courses would neglect to mention such a subtle detail.

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Matt

You should check the location of the sugars in your vancomycin structure.

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James

Crap. You are right. Let me fix that…

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Stef

Gosh, sounds like you’ve had a terrible time of it, glad you’re back. :)
I am right in the middle of the Organic part of my Chemistry and your website is a lifeline. Thanks and wishing you a great new year!

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Ojaswi

Hey, good to hear u r back again. Stay healthy. My chemistry get its life always with ur blogs. ;)

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James

thanks!!

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Rich

I’m glad you survived, James. And I agree with you about the beauty of Vancomycin.

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Dan

Happy to hear you’re better, James!
-long-time MOC reader, graduate TA for a sophomore organic course

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James

thank you Dan!

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Andrew Galea

I admire your sense of humour…you’re an inspiration to teachers and students :)

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Frank Wong

Wow that’s a crazy story. That’s kind of scary that nobody knows what caused that severe of a complication. But I’m glad you’re doing better now James. I was pleasantly surprised by all the Orgo you managed to sneak into this post. haha *thumbs up*

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Enrico Bellomo

So glad you are OK! Wow, that was quite a scare. One question: Are you sure you self-administered heparin and not a low molecular weight variety of heparin such as enoxaparin, dalteparin or fondaparin? I know the LMWH can be administered as prefilled syringes. Also, as a matter of form, the structure of heparin is extremely complex and in fact contains a very important pentasaccharide unit that is necessary for its anticoagulation properties (see fondaparinux structure), which would have been nice to see in the structure you provided or at least a mention of its structural complexity so as to no assume it is a simple polymer composed of a disaccharide repeating unit.

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