The Fine Structure of Hydroxypurines

Whatever be the difficulties in dealing satisfactorily with the problem of the lactam-lactim tautomerism in hydroxypurines, the predominance of the lactam tautomer granted, there remains the problem of the detailed structure of the most probable lactam form for each isomer. The problem is essentially that of the site of location of the imidazole proton. From that point of view forms 34-38 have to be considered for 2-hydroxypurine, forms 39—42 for 6-hydroxypurine (hypoxanthine), and forms 43-45 for 8-hydroxypurine. There are, in addition, some betaine tautomeric forms but these are probably of low stability and will not be considered further. Before describing the results of theoretical calculations, it may be useful to indicate that from the experimental point of view we may, in this respect, turn again for significant evidence to infrared spectroscopy 

Compound Tautomer i(D) D Theoret. Exptl. Theoret. Exptl. (D)  

6 The experimental absorption maxima are listed along the lines corresponding to the most stable tautomer of each hydroxypurine. In the case of 2- and 6 hydroxypurines for which there exist two tautomers of very close total energies they may represent the absorption of a mixture of such tautomers. c With respect to the most stable tautomer considered as zero energy. d Geometry following Spencer.98 

The results of the calculations on a number of essential electronic properties of oxypurines are presented in Table XIII and are compared, as far as possible, with the available experimental data. They indicate the following. 

In connection with the forthcoming discussion on the structure of the N(3)H tautomer of guanine (Section VIII), it may be interesting to point out that the N(3)H tautomers of hypoxanthine, of the general structure 46 (with the second proton at N-7 or N-9) are predicted to be about 8-14 kcal/mole less stable than the corresponding N(1)H tautomers, the N(3)H-N(7)H tautomer being more stable by about 6 kcal/mole than the N(3)H-N(9)H one. The structure of the 3-methylhypoxanthine is, in fact, presented by Bergmann et al.liZ as 47. 

An interesting difference predicted between the N(3)H-N(7)H and N(3)H-N(9)H tautomers concerns their dipole moments, the moment 

Altogether, it appears evident that calculations based on the lactam forms of hydroxypurines are susceptible of agreement with an extensive amount of experimental data concerning these compounds and offer therefore a complementary support for the representation of these molecules in such forms. 

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