List of unsolved problems in chemistry explained

This is a list of unsolved problems 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

See main article: Physical chemistry.

• Can the transition temperature of high-temperature superconductors be brought up to room temperature?
• How do the spin–orbit coupling, other relativistic corrections, and inter-electron effects modify the chemistry of the trans-actinides?^{[1] [2]}
• Is a lithium–air battery possible?^[3]

Organic chemistry problems

See main article: Organic chemistry.

• What is the origin of homochirality in biomolecules?^[4]
• Why are accelerated kinetics observed for some organic reactions at the water-organic interface?^[5]
• Do replacement reactions of aryl diazonium salts (dediazotizations) predominantly undergo S_N1 or a radical mechanism?^[6]
• Can an electrochemical cell reliably perform organic redox reactions?^[7]
• Which "classic organic chemistry" reactions admit chiral catalysts?
  • Is it possible to construct a quaternary carbon atom with arbitrary (distinguishable) substituents and stereochemistry?
• Can artificial enzymes replace the need for protecting groups when modifying sensitive compounds?^[8]

Inorganic chemistry problems

See main article: Inorganic chemistry.

• Are there any molecules that certainly contain a phi bond?
• Is there a less labor- or energy-intensive technique for titanium refinement than the Kroll process?^[9]
• Does nitrogen admit metastable allotropes under standard conditions?^[10]
• Can new solvents or other techniques make direct carbon capture economical?^[11]
  • Can artificial photosynthesis make any common fuels?^[12]
• What is a reliable synthesis and stabilization method for catenary allotropes of sulfur and carbon?

Biochemistry problems

See main article: Biochemistry.

• Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?^[13]
• 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?^{[4] [14]} This has been achieved for several small globular proteins in recent years.^[15] 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.^[16]
• 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?^[17]
• Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?^[18]

See also

• List of hypothetical technologies
• List of paradoxes
• List of philosophical problems
• List of purification methods in chemistry
• List of thermal conductivities
• List of undecidable problems
• List of unsolved deaths
• List of unsolved problems in astronomy
• List of unsolved problems in biology
• List of unsolved problems in computer science
• List of unsolved problems in economics
• List of unsolved problems in fair division
• List of unsolved problems in geoscience
• List of unsolved problems in information theory
• List of unsolved problems in mathematics
• List of unsolved problems in neuroscience
• List of unsolved problems in physics
• List of unsolved problems in statistics
• Lists of problems
• Outline of chemistry
• Outline of physics
• Unsolved problems in medicine

External links

• First 25 of 125 big questions that face scientific inquiry over the next quarter-century . Science . 309 . 125th Anniversary . 1 July 2005 .
• Unsolved Problems in Nanotechnology: Chemical Processing by Self-Assembly - Matthew Tirrell - Departments of Chemical Engineering and Materials, Materials Research Laboratory, California NanoSystems Institute, University of California, Santa Barbara [No doc at link, 20 Aug 2016]

Notes and References

1. Web site: Would element 137 really spell the end of the periodic table? Philip Ball examines the evidence. Philip Ball . November 2010 . Chemistry World. Royal Society of Chemistry.
2. Book: Lester R. . Morss . Norman M. . Edelstein . Jean . Fuger . The Chemistry of the Actinide and Transactinide Elements . 3rd . 2006 . Springer . Dordrecht, The Netherlands . 978-1-4020-3555-5.
3. Christensen . J. . Albertus . P. . Sanchez-Carrera . R. S. . Lohmann . T. . Kozinsky . B. . Liedtke . R. . Ahmed . J. . Kojic . A. . 10.1149/2.086202jes . A Critical Review of Li–Air Batteries . Journal of the Electrochemical Society . 159 . 2 . R1 . 2012 . free .
4. So much more to know . Science . 309 . 5731 . 78–102 . July 2005 . 15994524 . 10.1126/science.309.5731.78b . free .
5. 10.1002/anie.200462883. 15844112. "On Water": Unique Reactivity of Organic Compounds in Aqueous Suspension. 2005. Narayan. Sridhar. Muldoon. John. Finn. M. G.. Fokin. Valery V.. Kolb. Hartmuth C.. Sharpless. K. Barry. Angewandte Chemie International Edition. 44. 21. 3275–3279. free.
6. Ussing R, Singleton A . Isotope effects, dynamics, and the mechanism of solvolysis of aryldiazonium cations in water . Journal of the American Chemical Society . 127 . 9 . 2888–2889 . February 2005 . 10.1021/ja043918p. 15740124 . free.
7. Web site: Lowe . Derek . Derek Lowe (chemist) . 24 Aug 2017 . Electrochemistry For All . 23 August 2023 . In the Pipeline . American Association for the Advancement of Science.
8. News: Miles . Ned Carter . 2023-08-05 . ‘Endless possibilities’: the chemists changing molecules atom by atom . en-GB . The Observer . 2023-08-24 . 0029-7712.
9. Web site: Potter . Brian . The Story of Titanium . 2023-08-24 . Construction Physics . en . In the 1950s, it was hoped/assumed that a better process for producing titanium sponge would come along to replace the Kroll process, which is a laborious and energy-intensive batch process that must be done in an inert atmosphere. But such a process has never materialized...likewise, turning titanium sponge into metal is an energy and capital-intensive process [that] has also changed little since the 1950s..
10. Book: Lewars, Errol G. . Modeling Marvels: Computational Anticipation of Novel molecules . 2008 . . 978-1-4020-6972-7 . 10.1007/978-1-4020-6973-4 . 141–63 .
11. Sanz-Pérez. Eloy S.. Murdock. Christopher R.. Didas. Stephanie A.. Jones. Christopher W.. 12 October 2016. Direct Capture of carbon dioxide from Ambient Air. Chemical Reviews. 116. 19. 11840–11876. 10.1021/acs.chemrev.6b00173. 27560307. free.
12. Styring. Stenbjörn. Artificial photosynthesis for solar fuels. Faraday Discussions. 155. 21 December 2011. Advance Article. 357–376. 10.1039/C1FD00113B. 22470985. 2012FaDi..155..357S.
13. Hsieh M, Brenowitz M . 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 . August 1997 . 9268351 . 10.1074/jbc.272.35.22092. free .
14. Web site: King . Jonathan . MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1 . 2007 . . June 22, 2013 . dead . https://web.archive.org/web/20130928021907/http://ocw.mit.edu/courses/biology/7-88j-protein-folding-problem-fall-2007/index.htm . September 28, 2013 .
15. Dill KA . The Protein Folding Problem . Annu Rev Biophys . 37 . 289–316 . June 2008 . 18573083 . 10.1146/annurev.biophys.37.092707.153558 . 2443096. etal.
16. Callaway. Ewen. 2020-11-30. 'It will change everything': DeepMind's AI makes gigantic leap in solving protein structures. Nature. en. 588. 7837. 203–204. 10.1038/d41586-020-03348-4. 33257889 . 2020Natur.588..203C . 227243204 .
17. Web site: Principles for designing ideal protein structures. | the Baker Laboratory . 2012-12-19 . dead . https://web.archive.org/web/20130401070449/http://depts.washington.edu/bakerpg/drupal/node/465 . 2013-04-01 .
18. 10.1038/nature11478. 22895337. Microbial engineering for the production of advanced biofuels. Nature. 488. 7411. 320–328. 2012. Peralta-Yahya. Pamela P.. Zhang. Fuzhong. Del Cardayre. Stephen B.. Keasling. Jay D.. 2012Natur.488..320P. 4423203.