Of purine tautomers

The investigation of the chemical and physicochemical properties of purine tautomers, as well as their possible biological role, is still in a primitive form. Further developments are desirable and may have far reaching consequences for our understanding of the mechanism of life processes. 

Optical detection of magnetic resonance (ODMR) was attempted for measurements of the pH effects on the triplet state of purine to investigate the protonation site of purine at low temperatures (78JA7131). The ODMR spectrum did not show the presence of more than one triplet state at liquid helium temperatures. Since the protonated tautomers 1H,9H (3a) and H,1H (3b) have similar bond structures, their triplets should have similar zero-field parameters and are thus not easy to distinguish by ODMR. 

Molecular orbital theory indicates that there is little difference between the stability of the two tautomers of purine, 42 and 43. Molecular orbital calculations indicate that purine forms a monocation by protonation at N-3 or at A precise X-ray crystal-... 

Under physiologic conditions, the amino and oxo tautomers of purines, pyrimidines, and their derivatives predominate. 

Some of the impetus for studying tautomeric equilibria in heterocycles arises because of the postulate that point mutations in genetic material may be introduced when a given base exists in a tautomeric form during replication [279, 305-307], Cytosine, in particular, has imino and hydroxy tautomers that are within 3 kcal/mol of the global minimum illustrated above (because of the very large number of possible tautomers for the purines and pyrimidines, only the lowest energy tautomers are presented). This analysis has been made based on a... 

The vibration spectrum of the first excited state of guanine was measured using laser desorption jet-cooled resonance-enhanced multiphoton ionization (REMPI) spectrometry <1999JA4896>. The millimeter wave spectrum of purine was collected using a free jet spectrometer, and the observed rotational spectrum was assigned to the N(9)-H tautomer <1996CPL189>. 

Let us start with the basic problem of the four fundamental tautomers of purine. As stated before, although the molecule of purine is generally represented in the form N(9)H, in which a hydrogen atom as attached to N-9, tautomeric forms may naturally be considered, in which the proton is attached to the other nitrogens of the molecule, yielding the tautomers N(7)H, N(3)H, and N(1)H. In fact, although the majority of biological purines exist essentially as derivatives of the N(9)H tautomer, the crystalline form of purine... 

Concerning the electron affinities of the tautomers, both methods predict that they should be greater for the N (1 )H and N( 3)H tautomers than for the N(9)H and N(7)H ones. These properties are also probably overestimated in the CNDO procedure. No experimental information is available on the electron affinities of purines. 

Fig. 5. Computed polarization directions of the longest 77—77- absorption band in the four purine tautomers.

Fig. 6. Relative magnitudes and the directions of the dipole moments in the four purine tautomers (PPPCI method).

Recently, dipole moments for simple derivatives of the four tautomers of purine have been measured.93,101 Three series of derivatives have been investigated the iV-methyl-8-phenylpurines, the iV-methyl-6-thiomethylpurines, and the N-methyl-6-thiomethyl-8-phenylpurines. The results are summarized in Table VI. It can be seen that these measurements confirm the theoretical predictions very satisfactorily. It must, however, be mentioned that Dyer et al.l0z did not find any appreciable difference in the dipole moments of the 9-benzyl and 7-benzyl derivatives of 6-chloropurine (4.91 and 5.03 D, respectively). Moreover, Weiler-Feilchenfeld and Neiman101... 

Fig. 8. The intermolecular shielding values (AS) due to the ring current in the N(1)H and N(9)H tautomers of purine (in a plane 3.4 A distant from the molecular surface).

The interest in this problem was increased recently by the determination of a number of electronic properties of these two forms and by the confirmation given to theoretical predictions in this field. As seen in Table XIV, the most striking among these concerns the dipole moments and the ultraviolet spectra of the tautomers. Thus the theory predicts that the more stable N(7)H tautomer should have the lower dipole moment (by 3 D), a situation contrary to that observed in the purine series (Section IV) and that the N(7)H tautomer should be bathochromic with respect to the N(9)H one. 

The problem of the N(9)H 5 N(7) tautomerism of purines has recently gained increased interest following the already mentioned discovery by Watson et al.u that the crystal of purine contains the N(7)H form of the molecule. It consists of long chains of this tautomer, linked together by single hydrogen bonds, in the way illustrated in 86 for a dimer. 

It therefore appears plausible to admit that the main reason for the occurrence of the N(7)H tautomer in the crystal of purine resides, at least to a large part, in the greater interaction energy that may be obtained with this tautomeric form. 

It may perhaps be useful to remember that the dipole moments of the tautomers cannot and should not be considered as indicative of the relative values of such interactions in the first place, because appropriate calculations must be carried out in this case (as we have seen) in the monopole approximation and, second, because even in the dipole approximation, the mutual orientation of the dipoles of the interacting molecules is important. A glance at the data on the dipole moments of the different compounds mentioned here indicates that, in fact, there is no relation between the value of this moment in the different tautomers and the presence of such tautomers in the crystal. Thus, the dipole moments are predicted to be greater for the N(7)H form than for the N(9)H one in purine and adenine, but greater in the N(9)H form than in the N(7)H one in guanine, hypoxanthine, xanthine, 8-azaguanine, 8-azaxanthine, and 6-mercaptopurine. Also, no general relationship seems to exist between the relative values of the dipole moments and the stabilities of the different tautomers. 

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