List of unsolved problems in chemistry

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

Can the transition temperature of high-temperature superconductors be brought up to room temperature?

Organic chemistry problems

What is the origin of homochirality in biomolecules?[1]
Why are accelerated kinetics observed for some organic reactions at the water-organic interface?[2]
Do replacement reactions of aryl diazonium salts (dediazotizations) predominantly undergo SN1 or a radical mechanism?[3]

Inorganic chemistry problems

Are there any molecules that certainly contain a phi bond?

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?[1][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]

References

"So much more to know". Science. 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524.
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.
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.
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.
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.
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.
Callaway, Ewen (2020-11-30). "'It will change everything': DeepMind's AI makes gigantic leap in solving protein structures". Nature. 588 (7837): 203–204. Bibcode:2020Natur.588..203C. doi:10.1038/d41586-020-03348-4. PMID 33257889. S2CID 227243204.
"Principles for designing ideal protein structures. | the Baker Laboratory". Archived from the original on 2013-04-01. Retrieved 2012-12-19.
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

"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]

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[Science-1] "So much more to know". Science. 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524.

[2] 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.

[3] 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.

[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. Bibcode:2020Natur.588..203C. doi:10.1038/d41586-020-03348-4. PMID 33257889. S2CID 227243204.

[8] "Principles for designing ideal protein structures. | the Baker Laboratory". Archived from the original on 2013-04-01. Retrieved 2012-12-19.

[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.