Melting of nucleobases. Getting the cutting edge of "Walden's Rule"

Walden's Rule is an empirical observation of an invariant fusion entropy during fusion of non-associated organic compounds. For the five nucleobases, adenine, thymine, cytosine, guanine, and uracil, surprisingly high fusion temperatures and enthalpies have been measured using a specially developed fast scanning calorimetry method that prevents decomposition. Even when nucleobases admittedly possess very high fusion temperatures, e.g. the value of 862 K measured for guanine really exceeds all expectations of the feasible dimension of the fusion temperature for such a relatively small and simple organic molecule. Hirshfeld surface analysis has been applied in order to find out an explanation for such extremely unusual thermal behavior of nucleobases. We rationalized the observed trends in terms of fusion entropy (Walden's constant = 56.5 J K^-1 mol^-1) as the entropic penalty of fusion not only for "non-associated", as proposed by Walden in 1908, but also for "ideal associated" systems like nucleobases.