List of unsolved problems in chemistry

Physical chemistry problems

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?
• Is it possible to create a practically useful lithium–air battery?

Organic chemistry problems

Main article: Organic chemistry

• What is the origin of homochirality in biomolecules?
• Why are accelerated kinetics observed for some organic reactions at the water-organic interface?
• Do replacement reactions of aryl diazonium salts (dediazotizations) predominantly undergo SN1 or a radical mechanism?
• Can an electrochemical cell reliably perform organic redox reactions?
• 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?

Inorganic chemistry problems

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?
• Does nitrogen admit metastable allotropes under standard conditions?
• Can new solvents or other techniques make direct carbon capture economical?
  • Can artificial photosynthesis make any common fuels?{{cite journal|last=Styring|first=Stenbjörn|title=Artificial photosynthesis for solar fuels|journal=Faraday Discussions|volume=155|date=21 December 2011|issue=Advance Article|pages=357–376
• What is a reliable synthesis and stabilization method for catenary allotropes of sulfur and carbon?

Biochemistry problems

Main article: Biochemistry

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

References

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]].
2. (2006). "The Chemistry of the Actinide and Transactinide Elements". Springer.
3. (2012). "A Critical Review of Li–Air Batteries". Journal of the Electrochemical Society.
4. (July 2005). "So much more to know". Science.
5. (2005). ""On Water": Unique Reactivity of Organic Compounds in Aqueous Suspension". Angewandte Chemie International Edition.
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.
7. Lowe, Derek. (24 Aug 2017). "Electrochemistry For All". [[American Association for the Advancement of Science]].
8. Miles, Ned Carter. (2023-08-05). "'Endless possibilities': the chemists changing molecules atom by atom". The Observer.
9. Potter, Brian. "The Story of Titanium".
10. Lewars, Errol G.. (2008). "Modeling Marvels: Computational Anticipation of Novel molecules". [[Springer Science+Business Media]].
11. (12 October 2016). "Direct Capture of carbon dioxide from Ambient Air". Chemical Reviews.
12. 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..
13. (2007). "MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1". [[MIT OpenCourseWare]].
14. Dill KA. (June 2008). "The Protein Folding Problem". Annu Rev Biophys.
15. Callaway, Ewen. (2020-11-30). "'It will change everything': DeepMind's AI makes gigantic leap in solving protein structures". Nature.
16. "Principles for designing ideal protein structures. | the Baker Laboratory".
17. (2012). "Microbial engineering for the production of advanced biofuels". Nature.