The structural tautomerization/isomerization of heterocyclic molecules can often cause drastically different biological characteristics. We started a project to determine the free energy changes of tautomerization for a number of organic molecules, including imidazoles, oxazoles, isoxazoles, pyrazoles, triazoles, tetrazoles, pyridines, purines, and nucleic acid bases, in solutions of different solvents by using NMR experiments and a number of new computational models. Some preliminary results will be presented.