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Unsolved Chemistry Problems

Title text: I'm an H⁺ denier, in that I refuse to consider loose protons to be real hydrogen, so I personally believe it stands for 'pretend'.

Explanation

This explanation may be incomplete or incorrect: Created by a caffeinated biochemist - Please change this comment when editing this page. Do NOT delete this tag too soon.

There is a list of mathematical problems that are yet to be solved (such as P=NP). This comic makes a spin on it, by stating that there are (as of yet) unsolved chemistry problems. The scientist at what is apparently the "grand opening" of a new chemistry lab lists several real chemistry problems, followed by one also-unsolved-but-less-scientific problem (the p in pH)

Arbitrary Enzyme Design:

Enzymes are catalytic proteins. Enzyme catalysis is often unique in comparison with other catalysis methods as it is highly specific, or tailored to a specific reaction. As such, enzyme catalysis, besides being the basis of all biochemical processes, is becoming increasing relevant to industrial synthesis processes. As enzymes can be easily synthetically produced through recombinant gene technology, being able to design an arbitrary enzyme for any reaction means that effectively any reaction can be relatively easily catalyzed, revolutionizing the chemical synthesis industry.

Protein Folding:

Proteins are large molecules that consist of chains of amino acids. These amino acids chains become folded in extremely complex ways into intricate 3D structures, and the way a protein is folded is of critical importance to its function. Because of the huge importance of proteins to biological life, biologists have devoted significant attention over many decades to the problem of protein structure prediction. This refers to the ability to predict the 3D structure of a protein based on the amino acid sequence, and remains one of the most important problems in computational biology. The ability to predict protein structure purely from amino acid sequence, the so-called "de novo" prediction, is known in computational biology as an unusually difficult problem due to the complexity of amino acid chains. Known as "Levinthal's paradox," the number of possible conformations from the backbone conformations alone is estimated to have in the ballpark of 10^300 different conformations. Despite this, protein folding occurs extremely quickly in reality. Because of this difficulty in sampling conformations, even with optimization, such as secondary structure prediction and Monte Carlo simulation, a "true" accurate simulation is extremely computationally expensive. Because of this, the most accurate solutions, such as AlphaFold, utilize a combination of homology modeling - sampling experimentally determined proteins with similar sequences to infer structural motifs and similarities - and deep learning to accurately guess protein structure.

Depolymerization:

Polymers are very large molecules formed out of repeating subunits called monomers. Monomers are molecules, typically organic in nature, that can bond with at least 2 other molecules, making long chains or networks. That process is known as polymerization. Depolymerization is breaking down polymers into the small molecules they were originally made from. This is done through a variety of processes such as using radiation, electrolysis, adding chemicals, and other means. Plastics are the best-known polymers, but cellulose, proteins, and DNA are also technically polymers. The huge number of varieties and mixtures in plastics makes recycling them a huge challenge, and there is increasing concern about plastic waste damaging the environment.

Polymerization is usually exothermic, releasing energy as heat. To reverse this would require adding energy, in a targeted way. Simply destroying a polymer, by means of highly-reactive chemicals, heat, or radiation, doesn't generally release the monomer molecules to a significant degree; most of the reaction products are highly degraded. Most polymers are made by a process of catalysis, with the small monomer molecules interacting via a catalyst structure, often in liquid form, and the eventual product is usually solid. To reverse this would require getting the catalyst to interact in a very precise way with the solid polymer, and it's relatively difficult for the catalyst structure to get into the proper configuration with the solid tangled polymer molecules.

Another highly-desired depolymerization process would be to convert cellulose into its component glucose molecules. That glucose could then be used for a variety of different purposes, including fermentation to alcohol to use as a fuel. Currently, when plants are grown, much of the solar energy and carbon dioxide they absorb ends up in the form of cellulose rather than as starch, sugar, protein, or other substances that we find useful. Our being able to make use of the cellulose would make farming much more energy-efficient. Some organisms are able to depolymerize cellulose by means of enzymes, but our ability to use similar processes on an industrial scale is still limited. (Those organisms use a complex multi-step biochemical process which essentially "invests" energy into splitting off a glucose molecule, then recoups the investment by metabolizing the glucose.) It's also possible to depolymerize cellulose at high temperature and pressure using nothing more than water and acid, but that process is energy-intensive. It might be possible to do it with a solar-heated reactor.

What the “p” in pH stands for:

“p” shows up in pH, pK_a, pK_b, and other things related to the concentration of H+ ions and OH- ions. The meaning of the "p" in "pH" has been the subject of much dispute. It is sometimes referred to as "power of Hydrogen", but the term was introduced by Søren Peter Lauritz Sørensen, who did not publish his results in English, and more accurately translates as "hydric exponent". The letter p could stand for the French puissance, German Potenz, or Danish potens, all referring to the concept of the "exponent" in exponential functions. (In English, unlike the previous languages, "potency" is not used to refer to the mathematical exponent. Potency can also be used to mean "power", or it could mean "potential".) All of these words for potency/exponent start with the letter p in French, German, and Danish, which were the languages in which Sørensen published.

Title Text: Hydrogen Denier

In the title text, Randall claims to be an H⁺ denier by refusing to consider loose protons to be hydrogen atoms, and as such, the “p” stands for pretend. Part of the joke is Randall's implication that this is a well-known conspiracy theory that he personally buys into (it isn't). The word "denier" is often used as shorthand for other conspiracy theories, such as a "climate change denier" or a "moon landing denier."

Here's a breakdown of this joke:

• H⁺ is the chemical symbol for a positively-charged atom of hydrogen, the smallest atom on the Periodic Table. Since hydrogen is normally just one proton and one electron, when you take the electron away, you make it positively charged (the + sign in the superscript) and you effecitvely end up with just a single loose proton. So the shorthand for "loose proton" is to refer to it as an H⁺ ion.

• pH is taught in high school science class to essentially measure the concentration of extra loose protons in, say, an aquarium. (Different fish prefer slightly different pH levels/alkilinity.) As mentioned earlier, you can interpret the term "pH" to be referring to the "p" of "H" -- the power/potency of H⁺ ions.

(Note that in reality, lone H+ ions do not exist in water, and instead they glom onto H2O molecules to form H3O+ and H5O2+/(H2O--H--OH2)+. If you don't know what these chemical symbols mean, don't worry about it.)

But as an H⁺ denier, Randall doesn't consider loose protons to be hydrogen atoms. He has a purist's view of hydrogen, that it is just "pretending" to be hydrogen as soon as it loses an electron. As a denier, he interprets the term "pH" as referring to the concentration of "pretend Hyodrgen."

Transcript

[Hairbun stands behind a lectern on a podium speaking into a microphone on the lectern. A Cueball like guy stands to the left and another Cueball like guy and Megan stand to the right. There is a large sign hanging in the background along with some ornaments.]

Sign: Grand Opening

Hairbun: Our lab will be working on chemistry's top unsolved problems: arbitrary enzyme design, protein folding, depolymerization, and, of course, the biggest one of all:

Hairbun: Figuring out what the "p" in "pH" stands for.

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