Wednesday, April 26, 2017

The Hemodote Potion


I am now in the home stretch of my semester with just three more weeks of classes before Finals week. Today, in my non-majors chemistry class we discussed the details of the final project: Designing a Magical Potion. To prepare the students for the project, I had written a Prologue to the project seven weeks ago, and I make occasional references to potions in class sessions. One class was dedicated to talking about drug design, after the students had learned about protein structure and intermolecular forces.

A couple of weeks ago I wrote a full example of what a Final Project would look like. Thus, I invented the Hemodote Potion. Along with this sample, I provided detailed parameters for the project, and in class today we discussed and agreed upon the final due date, and the mechanics of what, when and how to provide me information on their projects. I had included a question on the previous problem set asking the students to list two potions they might invent with a one-paragraph of justification for each.

In class we divided into small groups and batted around some initial ideas of the science and chemistry that needs to be considered, before having a whole-class discussion. Cure for cancer and levitation potions are inherently challenging, but we came up with some ideas for camouflaging, memory-enhancement, skin anti-aging, and more. The best suggestion from a student, which I would never have thought of myself, was a potion that magically and non-toxically dissolves the skin or peel of vegetables and fruits. Just pour the potion on the desired object and moments later you are ready to eat (or cook) the food item!

Here are the required components for the project (per my instructions to the students):

Think of your project as adding an entry to a Potions textbook. Your entry must contain:

1. Name of your potion and the names of the authors contributing to the entry.

2. Background information on why this is a useful potion. Key features of the active chemical substances and how they might interact should be described here.

3. Design Considerations: A detailed section that describes each of the important substances that will be included in the recipe. This is where you justify the proposed chemical interactions you hope to achieve, and how this might interact with the larger scale organism or object to which the potion is applied.

4. Amount Considerations: This is where you show calculations estimating how much of each active substance will be needed.

5. A Detailed Recipe as you might see in a cookbook.

6. A list of potential side-effects or cautions for your potion. This is not just a generic list but is tied to the effects of the specific potion you have proposed.

7. References

There are also certain requirements such as some number of chemical equations and structures, minimum number of active ingredients, and calculations involving masses, moles and molarity. No specialized reagents can be used directly. They must either be synthesized or extracted from a magical creature or plant. Two different font colors must be used to highlight the “creative” parts of the project and the “science-y” parts.

Hemodote is a powerful easy-to-use liquid antidote against hemoglobin poisons such as cyanide and carbon monoxide. I had sketched out my initial ideas in a previous blog post, but here is the more detailed version of the “Design Considerations” section in the full example provided to the students. I have made minor edits removing the figures, and I did not renumber the references since this text is about one page of a four-page document. I have a detailed recipe with calculations and amounts, but since I’m taking on the mantle of an alchemist, I will keep my recipe a secret for now. (My students have seen the full recipe.) Except I can’t resist telling you that I have good reason to believe that mincing and boiling the liver of the Blue Behemoth will provide one of the active ingredients. Enjoy!

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To counteract hemoglobin poisoning, there are two general approaches: (A) Introduce substances that bind cyanide or carbon monoxide more strongly compared to hemoglobin. (B) Provide an infusion of oxygen to reduce or prevent cell death due to the poison.

Two kits used to treat cyanide toxicity are Cyanokit and Nithiodote.6 The active agent in Cyanokit is hydroxocobalamin, a molecule closely related to hemoglobin and Vitamin B12.7 Hydroxocobalamin actively binds cyanide more strongly than hemoglobin, and thus can scavenge the cyanide away freeing the hemoglobin to bind to oxygen. The active center in hydroxocobalamin is a cobalt ion instead of an iron cation in hemoglobin. Cyanide displaces the hydroxide and binds strongly to the copper center. A natural source of hydroxocobalamin comes from eggs, dairy, and meat.

Nithiodote contains sodium thiosulfate (Na2S2O3) as an active ingredient. This compound can be prepared from mixing sulfur with concentrated lye (or sodium hydroxide, NaOH).8 In the presence of Na2S2O3, a natural enzyme in our bodies, rhodanese, converts cyanide into thiocyanate (SCN-).9 While both kits require intravenous transmission in the Muggle world, acquiring the equivalent of hydroxocobalamin from the appropriate magical creature should suffice for an oral potion.

The treatment for carbon monoxide poisoning is to obtain an oxygen infusion.10 This will also help in cases of cyanide poisoning. Finding a hyperbaric oxygen chamber or an oxygen tank to breathe from can be challenging when the cells in your body are being rapidly depleted of oxygen. One way to quickly deliver oxygen is by using hydrogen peroxide (H2O2). It rapidly decomposes into H2 and O2 because of the weak O–O single bond in H2O2. However H2O2 cannot be consumed directly because it is a very strong oxidizing agent and will damage the cells in our body.

Recent scientific work on delivering oxygen to cells in our body is to enclose calcium peroxide (CaO2) in a polycaprolactone polymer casing.11 Calcium peroxide can be synthesized by heating slaked lime (calcium hydroxide) with hydrogen peroxide.12

Ca(OH)2  +  H2O2  -->  CaO2  +  2 H2O

Caprolactones are cyclic esters and can be found naturally in flower aromas and insect pheromones.13 Using caprolactone as a monomer to form polycaprolactone requires catalysts that are specialty chemicals not found in nature but synthesized by chemists.14 However, extracting caprolactones from an appropriate magical insect or plant should also provide the catalysts needed to form an appropriate polycaprolactone that will encase the CaO2 for delivery into the bloodstream.

[6] http://emedicine.medscape.com/article/814287-treatment (Cyanide Toxicity Treatment & Management)
[7] https://en.wikipedia.org/wiki/Hydroxocobalamin
[8] https://www.youtube.com/watch?v=J_IboipV5A8 (Preparation of Sodium Thiosulfate)
[9] https://chemm.nlm.nih.gov/countermeasure_sodium-thiosulfate.htm (Reference to “Effects of thiosulfate on cyanide pharmokinetics in dogs”)
[10] http://www.mayoclinic.org/diseases-conditions/carbon-monoxide/basics/treatment/con-20025444 (Carbon Monoxide Poisoning Treatment)
[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708668/ (Oxygen Releasing Biomaterials for Tissue Engineering)
[12] https://en.wikipedia.org/wiki/Calcium_peroxide
[13] https://en.wikipedia.org/wiki/Caprolactone
[14] http://pubs.rsc.org/en/Content/ArticleLanding/2009/CS/b820162p (Synthesis of polycaprolactone: A review)

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