List of unsolved problems in chemistry

Physical chemistry problems

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?^[1]^[2]
Is it possible to create a practically-useful lithium–air battery?^[3]

Organic chemistry problems

What is the origin of homochirality in biomolecules?^[4]
Why are accelerated kinetics observed for some organic reactions at the water-organic interface?^[5]^{[non-primary source needed]}
Do replacement reactions of aryl diazonium salts (dediazotizations) predominantly undergo S_N1 or a radical mechanism?^[6]
Can an electrochemical cell reliably perform organic redox reactions?^[7]
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?^[8]

Inorganic chemistry problems

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?^[9]
Does nitrogen admit metastable allotropes under standard conditions?^[10]
Can new solvents or other techniques make direct carbon capture economical?^[11]
- Can artificial photosynthesis make any common fuels?^[12]
What is a reliable synthesis and stabilization method for catenary allotropes of sulfur and carbon?

Biochemistry problems

Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?^[13]
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?^[4]^[14] This has been achieved for several small globular proteins in recent years.^[15] 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.^[16]
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?^[17]
Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?^[18]

Physical chemistry problems