So much science!

I love teaching the introductory chemistry courses. It engages storytelling, explaining, defining and illustrating of fundamental ideas in my field of study. Last week, I substituted for my friend. The goal of the lecture was to cover Chapter 1, which was a daunting task considering I had 75 minutes to speak about only 28 slides. One of her slides had a URL that directed me to the embedded video below regarding the Law of Conservation of Mass. I found it underwhelming, what about you?


I spoke about atoms, molecules, reactions, and how chemistry is everywhere! I spoke about the good old 'Scientific Method' where you begin with an Observation followed by Hypothesis and then Experiments and lastly Results and Conclusions. After the class was over, I realized that I could have told a better story using more web-based resources. There's so much information publicly available and so much more behind various paywalls of academic publishing, I decided to pick one story and dig around to show you what resources I could use if I were to do the lesson again.



First of all, the Poisoner's Handbook is a fascinating account of how forensic science developed alongside environmental pollution and criminal homicide. There is a section there about leaded gasoline which is something students may be curious about if they have read the gas pumps having "Unleaded" gasoline. There's a reason the lead was added to fuel (to reduce engine knocking) and there was a reason that the lead was banned from fuel (it made people crazy).



I also chose the topic of lead poisoning because I love going to the Protein Data Bank and reading the stories they post on the Molecule of the Month. I love looking at the rendering of the protein, changing the colors and attributes, manually manipulating its orientation and putting it on auto-spin to appreciate its contours and crevices. What I like about this story is that it involves atoms (lead), small molecules (dimercaptosuccinic acid, DMSA) used in chelation therapy, large molecules (aminolaevulinic acid dehydratase or ALAD a.k.a. porphobilinogen synthase) and molecular assemblies.

DMSA-mercury(II) chelate

Another interesting part about this story is that I came across the picture of DMSA-mercury(II) chelate using text-based google image searching. Apparently there are people who advocate the adminstration of DMSA to rid the body of toxicity from mercury amalgams (tooth fillings). http://zap.intergate.ca/dmsa.html I looked at that structure because I was wondering which of the groups on the DMSA would bind to the metal. We call ligands that make two contacts to the metal "bidentate" meaning like they are a set of teeth that chomps down from top and bottom. The rendering above shows DMSA making four points of contact. I had a feeling it wasn't right.

EDTA-iron(III) chelate

The only ligand I think of that makes that much contact is ethylenediaminetetraacetic acid (EDTA) which is considered a hexadentate ligand, making six points of contact. As it turns out I'm not the only chemist that was "triggered" by the rendering of DMSA-mercury(II) chelate and it was a graduate student who posted it to Wikipedia based on their own idea of what it would look like (not on a crystal structure). https://en.wikipedia.org/wiki/Talk:Dimercaptosuccinic_acid

So I created the small molecule in two dimensions using ChemSketch, then copied that structure and optimized it in ChemSketch3D. The teal spheres are carbon atoms. It's possible to rotate that small molecule just like with the protein. The only thing I couldn't figure out how to do in ChemSketch is how to make the coordinate-covalent bonds between the ligand and the heavy metal atom. Maybe it's possible and I don't know how to do it, or maybe it isn't possible in that software.

I also explored the enzyme ALAD in the BRENDA (BRaunschweig ENzyme DAtabase) and MetaCyc (Metabolic Encyclopedia). These two sources of information tell me what the enzyme does and what other enzymes are related (structurally similar), and which organisms express this enzyme, and what steps in a pathway leading ultimately to the symptom of anemia are inhibited by the presence of lead. It's also a great way to get towards journal articles that can explain how we know what we know about this enzyme.

References

Camina, Casas, Castano, Couce, Gato, Herbello-Hermelo, Sanchez, Sordo and Torres. Journal of Inorganic Biochemistry 104 (2010) 599-610.

Andersen and Aaseth. Environmental Health Perspectives 110 (2002) 887-890.

George, Prince, Gailer, Buttigieg, Bonner Denton, Harris and Pickering. Chemical Research in Toxicology 17 (2004) 999-1006.

Choiniere, Scott, Gelb and Turecek. Analytical Chemistry 82 (2010) 6730-6736.

Erskine, Duke, Tickle, Senior, Warren and Cooper. Acta Crystallographica D56 (2000) 421-430.

George, et al. Figure 4

To be continued...