List of unsolved problems in chemistry

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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.

## Contents

* 1 Physical chemistry problems
* 2 Organic chemistry problems
* 3 Inorganic chemistry problems
* 4 Biochemistry problems
* 5 See also
* 6 References
* 7 External links

## Physical chemistry problems

Main article: Chemistry:Physical chemistry

* Can the transition temperature of high-temperature superconductors be brought up to room temperature?[citation needed]
* How do the spin–orbit coupling, other relativistic corrections, and inter-electron effects modify the chemistry of the trans-actinides?[1][2]
* Is it possible to create a practically useful lithium–air battery?[3]

## Organic chemistry problems

Main article: Chemistry: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][non-primary source needed]
* Do replacement reactions of aryl diazonium salts (dediazotizations) predominantly undergo SN1 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

Main article: Chemistry: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

Main article: Biology: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

* Lists of unsolved problems
* Outline of chemistry

## References

1. ↑ Philip Ball (November 2010). "Would element 137 really spell the end of the periodic table? Philip Ball examines the evidence". Royal Society of Chemistry. http://www.rsc.org/chemistryworld/Issues/2010/November/ColumnThecrucible.asp.
2. ↑ Morss, Lester R.; Edelstein, Norman M.; Fuger, Jean, eds (2006). The Chemistry of the Actinide and Transactinide Elements (3rd ed.). Dordrecht, The Netherlands: Springer. ISBN 978-1-4020-3555-5.
3. ↑ Christensen, J.; Albertus, P.; Sanchez-Carrera, R. S.; Lohmann, T.; Kozinsky, B.; Liedtke, R.; Ahmed, J.; Kojic, A. (2012). "A Critical Review of Li–Air Batteries". Journal of the Electrochemical Society 159 (2): R1. doi:10.1149/2.086202jes.
4. ↑ 4.0 4.1 "So much more to know". Science 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524.
5. ↑ 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.
6. ↑ Ussing R, Singleton A (February 2005). "Isotope effects, dynamics, and the mechanism of solvolysis of aryldiazonium cations in water". Journal of the American Chemical Society 127 (9): 2888–2889. doi:10.1021/ja043918p. PMID 15740124. Bibcode: 2005JAChS.127.2888U.
7. ↑ Lowe, Derek (24 Aug 2017). "Electrochemistry For All". American Association for the Advancement of Science. https://www.science.org/content/blog-post/electrochemistry-all.
8. ↑ Miles, Ned Carter (2023-08-05). "'Endless possibilities': the chemists changing molecules atom by atom" (in en-GB). The Observer. ISSN 0029-7712. https://www.theguardian.com/science/2023/aug/05/skeletal-editing-chemistry-molecule-atom-medicine-drug-development-sustainable.
9. ↑ Potter, Brian. "The Story of Titanium" (in en). https://www.construction-physics.com/p/the-story-of-titanium. "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. ↑ Lewars, Errol G. (2008). Modeling Marvels: Computational Anticipation of Novel molecules. Springer Science+Business Media. pp. 141–63. doi:10.1007/978-1-4020-6973-4. ISBN 978-1-4020-6972-7.
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. doi:10.1021/acs.chemrev.6b00173. PMID 27560307.
12. ↑ Styring, Stenbjörn (21 December 2011). "Artificial photosynthesis for solar fuels". Faraday Discussions 155 (Advance Article): 357–376. doi:10.1039/C1FD00113B. PMID 22470985. Bibcode: 2012FaDi..155..357S. https://zenodo.org/record/3426629.
13. ↑ 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.
14. ↑ King, Jonathan (2007). "MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1". MIT OpenCourseWare. http://ocw.mit.edu/courses/biology/7-88j-protein-folding-problem-fall-2007/index.htm.
15. ↑ Dill KA (June 2008). "The Protein Folding Problem". Annu Rev Biophys 37: 289–316. doi:10.1146/annurev.biophys.37.092707.153558. PMID 18573083.
16. ↑ Callaway, Ewen (2020-11-30). "'It will change everything': DeepMind's AI makes gigantic leap in solving protein structures" (in en). Nature 588 (7837): 203–204. doi:10.1038/d41586-020-03348-4. PMID 33257889. Bibcode: 2020Natur.588..203C. https://www.nature.com/articles/d41586-020-03348-4.
17. ↑ "Principles for designing ideal protein structures. | the Baker Laboratory". http://depts.washington.edu/bakerpg/drupal/node/465.
18. ↑ 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. doi:10.1038/nature11478. PMID 22895337. Bibcode: 2012Natur.488..320P.

## External links

* "First 25 of 125 big questions that face scientific inquiry over the next quarter-century". Science 309 (125th Anniversary). 1 July 2005. http://www.sciencemag.org/sciext/125th/.
* 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]

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