isotope effects occur only when solutes exchange hydrogen with the solvent or when there is a specific solute-solvent interaction near the reaction site. Both such phenomena are common for protic solvents, in which the hydrogen is exchangeable, and they may form dipole-dipole interactions or hydrogen bonds with polar molecules. Carbon-13 isotope effects Most organic reactions involve the breaking and making of bonds to a carbon; thus, it is reasonable to expect detectable carbon isotope effects. When 13C is used as the label, the change in mass of the isotope is only ~8%, though, which limits the observable kinetic isotope effects to much smaller values than the ones observable with hydrogen isotope effects. Compensating for variations in 13C natural abundance Often, the largest source of error in a study that depends on the natural abundance of carbon is the slight variation in natural 13C abundance itself. Such variations arise because the starting materials used in the reaction are themselves products of some other reactions that have kinetic isotope effects and corresponding isotopic enrichments in the products. To compensate for this error when NMR spectroscopy is used to determine the kinetic isotope effect, the following guidelines have been proposed: Choose a carbon that is remote from the reaction center that will serve as a reference and assume it does not have a kinetic isotope effect in the reaction. In the starting material that has not undergone any reaction, determine the ratios of the other carbon NMR peak integrals to that of the reference carbon. Obtain the same ratios for the carbons in a sample of the starting material after it has undergone some reaction. The ratios of the latter ratios to the former ratios yields R/R0. If these as well as some other precautions listed by Jankowski are followed, kinetic isotope effects with precisions of three decimal places can be achieved. Isotope effects with elements heavier than carbon Interpretation of carbon isotope effects are usually complicated by simultaneously forming and breaking bonds to carbon. Even reactions that involve only bond cleavage from the carbon, such as SN1 reactions, involve strengthening of the remaining bonds to carbon. In many such reactions, leaving group isotope effects tend to be easier to interpret. For example, substitution and elimination reactions in which chlorine act as a leaving group are convenient to interpret, especially since chlorine acts as a monatomic species with no internal bonding to complicate