Unsolved problems in chemistry tend to be ("can we make X compound") and are solved rather quickly, but here are some persistent questions with deep implications:
- Solvolysis of the norbornyl cation: Why is the norbornyl cation so stable? Is it symmetrical? This problem has been largely settled for the unsubstituted norbornyl cation, but not for the substituted cation.
- On-water reactions: Why are some organic reactions accelerated at the water-organic interface?
- Better-than perfect enzymes: Why do some enzymes exhibit faster-than-diffusion kinetics?
- Feynmanium: What are the chemical consequences of having an element (137) whose electrons must travel faster than the speed of light?
- Chemical transformation traversal: Is it practical to generate a database of chemical transformations and derive synthetic routes to any arbitrary compound?
- 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? Wikipedia: protein structure prediction
- Inverse protein-folding problem: Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions?
- What is the origin of homochirality in amino acids and sugars? Wikibooks: Organic Chemistry/Chirality#Chirality in biology
- Do sterics (electronic repulsion) or electronics (electronic polarization) have a greater effect on chiral induction in stereospecific and stereoselective chemical reactions?
- How can one design and make an effective catalyst for any desired reaction?
- How can electromagnetic energy (photons) be efficiently converted to chemical energy? (E.g. splitting of water to H2 and O using solar energy.)
- What are the chemical origins of life? How did non-living chemical compounds generate self-replicating, complex life forms?
- How does the flow of elements, energy, and electrons (oxidation states) drive the structure of local and global ecosystems?
Some of the most important unsolved problems in chemistry are classified as unsolved problems in biology.