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 References
* 6 External links

## Physical chemistry problems

Main article: Chemistry:Physical chemistry

* 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

Main article: Chemistry:Organic chemistry

* What is the origin of homochirality in biomolecules?[2]
* Why are accelerated kinetics observed for some organic reactions at the water-organic interface?[3][non-primary source needed]
* Do replacement reactions of aryl diazonium salts (dediazotizations) predominately undergo SN1 or a radical mechanism?[4]

## Inorganic chemistry problems

Main article: Chemistry:Inorganic chemistry

* Are there any molecules that certainly contain a phi bond?

## Biochemistry problems

Main article: Biology:Biochemistry

* Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?[5]
* 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][6] This has been achieved for several small globular proteins in recent years.[7] 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.[8]
* 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?[9]
* Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[10]

## 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. ↑ 2.0 2.1 "So much more to know". Science 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524. http://www.sciencemag.org/cgi/content/full/309/5731/78b.
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. ↑ 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.
5. ↑ 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.
6. ↑ 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.
7. ↑ Dill KA (June 2008). "The Protein Folding Problem". Annu Rev Biophys 37: 289–316. doi:10.1146/annurev.biophys.37.092707.153558. PMID 18573083.
8. ↑ 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. https://www.nature.com/articles/d41586-020-03348-4.
9. ↑ "Archived copy". http://depts.washington.edu/bakerpg/drupal/node/465.
10. ↑ 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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Unsolved problems by discipline

* Astronomy
* Biology
* Chemistry
* Computer science
* Economics
* Geoscience
* Information theory
* Linguistics
* Mathematics
* Medicine
* Philosophy
* Physics
* Statistics

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