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 a lithium–air battery possible?

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 (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

 * 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?