List of unsolved problems in chemistry

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]
What is the electronic structure of the high temperature superconductors at various points on the phase diagram? Can the transition temperature be brought up to room temperature? See Superconductivity.
How can one make a room-temperature superconductor?
Feynmanium: What are the chemical consequences of having an element, with an atomic number above 137, whose 1s electrons must travel faster than the speed of light? Is "Feynmanium" the last chemical element that can physically exist? The problem may actually occur at approximately Element 173, given the finite extension of nuclear-charge distribution. See the article on Extension of the periodic table beyond the seventh period and section Relativistic effects of Atomic orbital.
How can electromagnetic energy (photons) be efficiently converted to chemical energy? (E.g. splitting of water to hydrogen and oxygen using solar energy.)[9][10]
What is the structure of water? According to Science Magazine in 2005, one of the 100 outstanding unsolved problems in science revolves around the question of how water forms hydrogen bonds with its neighbors in bulk water.[5] See: water cluster.
What process creates the septaria in septarian nodules?
What is the explanation of the Mpemba effect?

“On Water”: Unique Reactivity of Organic Compounds in Aqueous Suspension†

Sridhar Narayan Dr., John Muldoon Dr., M. G. Finn Prof., Valery V. Fokin Prof., Hartmuth C. Kolb Prof. andK. Barry Sharpless Prof.
We thank Dr. Vladislav Litosh for carrying out preliminary work. Support from the National Institutes of Health, National Institute of General Medical Sciences (GM 28384), the National Science Foundation (CHE9985553), the Skaggs Institute for Chemical Biology, and the W. M. Keck Foundation is gratefully acknowledged. S.N. thanks the Skaggs Institute for a postdoctoral fellowship. We also thank Dr. Suresh Suri, Edwards Air Force Base, California, for a generous gift of quadricyclane. We urge our fellow chemists to float their problematic reactions on water and to send observations of success or failure to us at onwater@scripps.edu for public dissemination with attribution.