Unsolved Problems in Chemistry

Originally posted 2011-10-23

A google search for “unsolved problems in chemistry” returns results that are quite disappointing. The wikipedia article is of uniformly low quality, and the remainder of the hits are of wikipedia clones, or of professors/graduate students’ speculation on how their personal research is an “important unsolved question in chemistry”. Many chemists seem unable to step outside the box where they do their research. I won’t claim that my list of “unsolved questions in chemistry” is completely free of bias. But anyway, here goes.

Unsolved Problems in Chemistry:

  1. The Origin of Life / Abiogenesis. ’Nuff said.
    • Homochirality: Why are L-amino acids and D-sugars so dominant in the biological world, and how did it happen? There’s been much more headway made on this problem than on other abiogenesis-related problems (See Viedma and Blackmond’s research on chiral amplification). The gist is that once a small enantiomeric bias is generated, most likely by statistical fluctuations, then there exist processes that can amplify this initial bias into homochirality.
    • RNA World Hypothesis: The conservation and ubiquity of RNA in core, central cell processes suggests that they might in fact be molecular fossils, a relic of an “RNA world” in which RNA was the first step towards modern life. The holy grail would be discovery of an RNA molecule capable of catalyzing its own replication from precursor nucleotides
    • Prebiotic sugar chemistry: How did sugars come about in the prebiotic world? An answer to this question is a prerequisite for the RNA world hypothesis. The formose reaction, which takes formaldehyde and outputs sugars, seems to be our leading candidate here, although the resulting complex sugar mix contains just about every sugar you could possibly imagine, and then some.
    • Prebiotic lipid chemistry: How did the first compartments come about? What is the chemical nature of the first micelles/lipid bilayers?
    • Traditional molecular paleontology: The investigation of fossil or chemical remains of the earliest forms of life, such as stromatolites or lipids embedded in sedimentary rocks.
    • Modern molecular paleontology: The investigation of biochemical renmants of the earliest forms of life. The relatively recent research into ribozymes is one good example.
  2. Chemistry on a medium scale. We understand small molecules very well (quantum mechanics and molecular orbital theory), and statistical physics / solid state physics / continuum mechanics gives us a good understanding of bulk material. However, we don’t understand what happens in between - molecules that are on the order of size of biological macromolecules. Delays/reticence in FDA approval of nanotechnology is mostly a “we have no clue what happens to these things in biological systems” response.
    • What are the chemical/electrical/mechanical properties of buckyballs, nanotubes, and graphene? Silicon computing can no longer assume bulk silicon properties - chips are now manufactured on a scale that requires consideration of quantum effects.
    • Grab bag: quantum dots, laws governing biomacromolecular interactions.
  3. A general solution, or better approximations to the Schrodinger/Dirac equation. All of chemistry essentially arises from quantum mechanics. If we could solve these equations faster and more accurately, then we could literally simulate all chemical reactions on a computer. Density Functional Theory (DFT) was a breakthrough that allowed significantly faster computations.
    • Protein folding is a busy area of research now
    • We still have no way to accurately model large numbers of solvent molecules, and most of our computations are done in unrealistic gas-phase conditions. (Gas-phase is a nice way to say, “Let’s pretend that this molecule doesn’t interact with anything”.)
  4. Energy, sustainable living. Resources in general. Can we rid ourselves of all dependence of finite resources, and rework our civilization to operate in a steady-state manner, with only solar energy as an energy input? Phosphates, helium, oil - these are all finite resources that are going to become very scarce within our lifetimes. Other longer-term finite resources exist.
    • Cheap, efficient solar photovoltaics.
    • Energy storage technology to deal with the sun’s passive-aggressive only-going-to-power-you-for-half-the-day personality.
  5. Honorable mention:

Solved Problems in Chemistry: Synthesis of an arbitrary, stable organic molecule. Yeah, that’s right. Total synthesis is dead. The porn industry innovates more than the field of total synthesis.