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.

• What are the electronic structures of high-temperature superconductors at various points on their phase diagrams?^[1]
• Can the transition temperature of high-temperature superconductors be brought up to room temperature?^[1]
• Is Feynmanium the last chemical element that can physically exist? That is, 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?^[1][2]
• Is Neutronium-4 possible?
• How can electromagnetic energy (photons) be efficiently converted to chemical energy? For instance, can water be efficiently split to hydrogen and oxygen using solar energy?^[3][4]

• Is an abiologic origin of chirality as is found in (2R)-2,3-dihydroxypropanal (D-glyceraldehyde), and also in amino acids, sugars, etc., possible?^[5]
• Why are accelerated kinetics observed for some organic reactions at the water-organic interface?^{[6][non-primary source needed][citation needed]}
• What is the origin of the alpha effect, that is, that nucleophiles with an electronegative atom with lone pairs adjacent to the nucleophilic center are particularly reactive?^{[citation needed]}
• What is the nature of strong gold-chalcogens in thiols and other organochalcogens (i.e., sulfur and higher chalcogen-containing organic compounds)?^{[7][self-published source?][better source needed]}

In addition to these, it is noteworthy that many mechanisms proposed for catalytic processes are poorly understood^[which?] and often fail to explain all relevant phenomena.^{[citation needed]}

• Enzyme kinetics: Why do some enzymes exhibit faster-than-diffusion kinetics?^[8]
• 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][9] This has been achieved for several small globular proteins in recent years.^[10]
• 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?^[11]
• Biosynthesis: Can desired molecules, natural products or otherwise, be produced in high yield through biosynthetic pathway manipulation?^[12]

• "First 25 of 125 big questions that face scientific inquiry over the next quarter-century". Science. 309 (125th Anniversary). 1 July 2005.
• Unsolved Problems in Nanotechnology: Chemical Processing by Self-Assembly - Matthew Tirrell - Departments of Chemical Engineering and Materials, Materials Research Laboratory, California NanoSystems Institute, University of California, Santa Barbara [No doc at link, 20 Aug 2016]