List of unsolved problems in chemistry

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Unsolved problems in chemistry tend to be questions of the kind "Can we make X chemical compound?", "Can we analyse it?", "Can we purify it?" and are commonly solved rather quickly, but may just as well require considerable efforts to be solved. However, there are also some questions with deeper implications. This article tends to deal with the areas that are the center of new scientific research 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.[1]

Organic chemistry problems[edit]

  • Solvolysis of the norbornyl cation: Why is the norbornyl cation so stable? Is it symmetrical? If so, why? This problem has been largely settled for the unsubstituted norbornyl cation, but not for the substituted cation. See Non-classical ion.
  • On water reactions: Why are some organic reactions accelerated at the water-organic interface?[2]
  • What is the origin of the bond rotation barrier in ethane, steric hindrance or hyperconjugation?
  • What is the origin of the alpha effect? Nucleophiles with an electronegative atom and one or more lone pairs adjacent to the nucleophilic center are particularly reactive.
  • What is the nature of strong bonds between organic-sulfur (and higher chalcogen) compounds and gold?[3]
  • Many mechanisms proposed for catalytic processes are poorly understood and often fail to explain all relevant phenomena.

Biochemistry problems[edit]

  • Better-than perfect enzymes: Why do some enzymes exhibit faster-than-diffusion kinetics?[4] See Enzyme kinetics.
  • What is the origin of homochirality in amino acids and sugars?[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?[5][6]
  • 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?
  • What are the chemical origins of life? How did non-living chemical compounds generate self-replicating, complex life forms?
  • Protein design: Is it possible to design highly active enzymes de novo for any desired reaction?[7]
  • Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?[8]

Physical chemistry problems[edit]


  1. ^ For relevant citations also see the satellite pages
  2. ^ Unique Reactivity of Organic Compounds in Aqueous Suspension Sridhar Narayan, John Muldoon, M. G. Finn, Valery V. Fokin, Hartmuth C. Kolb, K. Barry Sharpless Angew. Chem. Int. Ed. 21/2005 p 3157 ,
  3. ^ Synthetic Remarks: "What is the true nature of gold-sulfur bonds?", by Fredrik von Kieseritzky, August 29th, 2013, at
  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. ^ a b c "So much more to know". Science 309 (5731): 78–102. July 2005. doi:10.1126/science.309.5731.78b. PMID 15994524. 
  6. ^ King, Jonathan (2007). "MIT OpenCourseWare - 7.88J / 5.48J / 7.24J / 10.543J Protein Folding Problem, Fall 2007 Lecture Notes - 1". MIT OpenCourseWare. Retrieved June 22, 2013. 
  7. ^
  8. ^
  9. ^ Duffie, John A. (2006). Solar Engineering of Thermal Processes. Wiley-Interscience. p. 928. ISBN 978-0-471-69867-8. 
  10. ^ Brabec, Christoph; Vladimir Dyakonov; Jürgen Parisi; Niyazi Serdar Sariciftci (2006). Organic Photovoltaics: Concepts and Realization. Springer. p. 300. ISBN 978-3-540-00405-9. 

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