Wikipedia list article

Unsolved problems in chemistry tend to be questions of the kind "Can we make X chemical compound?", "Can we analyse it?", "Can we purify it?" and are commonly solved rather quickly, but may just as well require considerable efforts to be solved. However, there are also some questions with deeper implications. This article tends to deal with the areas that are the center of new scientific research in chemistry. Problems in chemistry are considered unsolved when an expert in the field considers it unsolved or when several experts in the field disagree about a solution to a problem.

Physical chemistry problems

  • Can the transition temperature of high-temperature superconductors be brought up to room temperature?
  • What happens to the electron cloud at very high atomic numbers, when the innermost electrons would, using a non-relativistic model, be calculated to exceed the speed of light? While calculations assuming the nucleus as a charged point indicate that this should happen around element 137, more accurate ones which take into account the nucleus's finite size push this limit to around element 173.[1]

Organic chemistry problems

Biochemistry problems

  • Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?[4]
  • Protein folding problem: Is it possible to predict the secondary, tertiary and quaternary structure of a polypeptide sequence based solely on the sequence and environmental information? Inverse protein-folding problem: Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions?[2][5] This has been achieved for several small globular proteins in recent years.[6] In 2020, it was announced that Google's AlphaFold, a neural network based on DeepMind artificial intelligence, is capable of predicting a protein's final shape based solely on its amino-acid chain with an accuracy of around 90% on a test sample of proteins used by the team.[7]
  • RNA folding problem: Is it possible to accurately predict the secondary, tertiary and quaternary structure of a polyribonucleic acid sequence based on its sequence and environment?
  • Protein design: Is it possible to design highly active enzymes de novo for any desired reaction?[8]
  • Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[9]


  1. ^ Philip Ball (November 2010). "Would element 137 really spell the end of the periodic table? Philip Ball examines the evidence". Chemistry World. Royal Society of Chemistry.
  2. ^ a b "So much more to know". Science. 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524.
  3. ^ Narayan, Sridhar; Muldoon, John; Finn, M. G.; Fokin, Valery V.; Kolb, Hartmuth C.; Sharpless, K. Barry (2005). ""On Water": Unique Reactivity of Organic Compounds in Aqueous Suspension". Angewandte Chemie International Edition. 44 (21): 3275–3279. doi:10.1002/anie.200462883. PMID 15844112.
  4. ^ Hsieh M, Brenowitz M (August 1997). "Comparison of the DNA association kinetics of the Lac repressor tetramer, its dimeric mutant LacIadi, and the native dimeric Gal repressor". J. Biol. Chem. 272 (35): 22092–6. doi:10.1074/jbc.272.35.22092. PMID 9268351.
  5. ^ King, Jonathan (2007). "MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1". MIT OpenCourseWare. Archived from the original on September 28, 2013. Retrieved June 22, 2013.
  6. ^ Dill KA; et al. (June 2008). "The Protein Folding Problem". Annu Rev Biophys. 37: 289–316. doi:10.1146/annurev.biophys.37.092707.153558. PMC 2443096. PMID 18573083.
  7. ^ Callaway, Ewen (2020-11-30). "'It will change everything': DeepMind's AI makes gigantic leap in solving protein structures". Nature. 588 (7837): 203–204. doi:10.1038/d41586-020-03348-4.
  8. ^ "Archived copy". Archived from the original on 2013-04-01. Retrieved 2012-12-19.{{cite web}}: CS1 maint: archived copy as title (link)
  9. ^ Peralta-Yahya, Pamela P.; Zhang, Fuzhong; Del Cardayre, Stephen B.; Keasling, Jay D. (2012). "Microbial engineering for the production of advanced biofuels". Nature. 488 (7411): 320–328. Bibcode:2012Natur.488..320P. doi:10.1038/nature11478. PMID 22895337. S2CID 4423203.

External links