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?
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

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 predominantly undergo S_N1 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 substituents and stereochemistry?
Can artificial enzymes replace the need for protecting groups when modifying sensitive compounds?

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?
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?
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?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?