Crystal structure of purines

Table 7.14. Distribution of hydrogen bonds in 18S crystal structures of purines and pyrimidines [61]...

There is a considerable variety of hydrogen bonds in the crystal structures of purine and pyrimidine bases, far more than in the carbohydrates and amino acids. 

The first recorded X-ray crystal structures of purines were those of adenine (1948) and guanine (1951) derivatives. Data for these and related purines are recorded in Table 5.1 and additional examples are collected in a publication (72PMH(5)l). Recently, results derived from precisely-determined X-ray crystal structures of 24 adenine and 10 guanine derivatives in both neutral and protonated forms have been published (82JST(78)1, 82JA3209). 

More than 150 crystal structures of purines, many of them related to adenine and guanine, have been published, These investigations have been expanded to cover nucleosides, nucleotides and other purine derivatives. The data are the subject of a recent review and also an earlier report. " The X-ray data of both neutral and protonated forms of adenine and guanine derivatives have been reported. -... 

Voet, D. and Rich, A., The crystal structures of purines, pyrimidines and their intermolecular complexes, Progress in Nucleic Acid Research and Molecular Biology, Vol. 10, Davidson, J.N. and Cohn, W.E., Eds., Academic Press, New York, 1970,183. 

The lac repressor monomer, a chain of 360 amino acids, associates into a functionally active homotetramer. It is the classic member of a large family of bacterial repressors with homologous amino acid sequences. PurR, which functions as the master regulator of purine biosynthesis, is another member of this family. In contrast to the lac repressor, the functional state of PurR is a dimer. The crystal structures of these two members of the Lac I family, in their complexes with DNA fragments, are known. The structure of the tetrameric lac repressor-DNA complex was determined by the group of Mitchell Lewis, University of Pennsylvania, Philadelphia, and the dimeric PurR-DNA complex by the group of Richard Brennan, Oregon Health Sciences University, Portland. 

Fig. 3. The structure of purine nucleoside phosphorylase determined using synchrotron radiation to a resolution limit of 3 A (crystals r32, a = 99.2 A = 92.1)...

The complex [(HLJZnCUJ (L = purine) has been shown to possess the tetrahedral structure (80) (Zn—Cl, 2.226-2.254 A Zn—N, 2.054 A).548 The interaction of 7-azaindole (81) with zinc chloride has been investigated, and the products [Znl CU] (Zn—Cl, 2.231, 2.212 A Zn—N, 2.063, 2.038 A) and [LH]2[ZnCU] have been structurally characterized.548 Complexes of zinc with cytosine,549 adenosine triphosphate550-552 and other purines553 have been investigated, and a crystal structure of the complex [ Zn(bipy)(H2ATP) 2] 4H2O551 has been described. 

Overlap Geometry A schematic representation of the proposed overlap geometry for proflavine intercalated into a deoxy pyrimidine(3 -5 )purine site is presented below with the (o) symbols representing the location of the phenanthridine ring protons. The mutual overlap of the two base pairs at the intercalation site involves features observed in the crystal structures of a platinum metallointercalator miniature dC-dG duplex complex (55) and the more recent proflavine miniature dC-dG duplex complex (48), as well as features derived in a linked-atom conformational calculation of the intercalation site in the proflavine DNA complex (51). [4]... 

The calculations indicate, in the first place, that in all azapurines studied the relative stabilities of the three tautomers decrease in the order N(9)H > N(7)H > N(8)H and this even in the case when the N(7)H tautomer is more stable than the N(9)H tautomer in the corresponding purine. The N(8)H tautomers always appear as fundamentally the least stable, about 20-30 kcal/mole less stable than the two other tautomers. Although the problem of the crystal structure of the purines and, in particular, of the occurrence in the crystal of the N(7)H or N(9)H tautomers will be discussed in a later section, it may be useful to note here that while the presence of the... 

Altogether, the results are less abundant than for the hydroxy-purines, in particular, concerning the utilization of the CNDO method. In fact, this method has been applied essentially to the evaluation of the relative stabilities of the N(7)H and N(9)H tautomer of 6-mercaptopurine (71) and (72), because of the interest of this particular datum in connection with the crystal structure of the... 

The problem may and has been considered also in relation to the crystal structure of other purines, although in somewhat less detail.173 Recent findings indicate that although the crystals of guanine, hypoxanthine, and 8-azaguanine contain the N(9)H tautomer of the bases,174 175 the crystal of 6-mercaptopurine monohydrate is made of the N(7)H form.176 177... 

In addition, the X-ray crystal structures of two 1,4-oxathiane derivatives were published (00AX1510, 01AX560) the di-axial conformation of the hydroxymethyl group in position 3 and of the l,9-dihydro-6//-purin-6-one group in position 6 in compound 82 is surprising (01AX560) (cf. Scheme 30). The X-ray structures of the sulfones of the isomeric 2,6-di-OEt-3-OMe-l,4-oxathianes were published (00CEJ1858) the 4,4-dioxa-... 

As neutron diffraction and more accurate X-ray crystal structure analyses have become available, it is clear that this configuration 1 is quite common in the crystal structures of many biological small molecules. Surveys of the peptide NH 0=C hydrogen bond [56] and hydrogen bonds in carbohydrates [57-59], amino acids [60], purines and pyrimidines [61] and nucleosides and nucleotides [62] indicate that between 25% and 40% of the bonds in a sample of structures may be of this type. 

To explore this difference more quantitatively, an attempt [306] was made to derive a potential energy function for the hydrogen bond that would reproduce the two-center NH 0 = C and O-H 0 = C bond-length distribution observed in the crystal structures of the purines and pyrimidines, described in Part IB, Chapter 7, i.e., relating the curves (a) and (b) in Fig. 2.4. Fitting the bond-length distribution curve to a Lennard-Jones type of potential energy function via a Helmholtz... 

Table 8.8. Three-center chelated hydrogen-bond configurations observed in the crystal structure of the purines, pyrimidines, nucleosides and nucleotides (normalized from X-ray data)...

Configurations involving simultaneously three-center and bifurcated hydrogen bonds are observed in the crystal structures of nucleic acid constituents purines, pyrimidines, nucleosides, nucleotides. 

Table 8.11. Geometry of four-center bonds in the crystal structures of the purines, pyrimidines (P P), nucleosides and nucleotides (N N)...

The proportion of three-center bonds in the pyrimidine, purine, and barbiturate crystal structures of about 30% is comparable to the number observed in the carbohydrate crystal structures (Thble 2.3). There is also a small proportion, about 1 %, of four-center bonds. A particular feature of the three-center bonds in these crystal structures is the occurrence of chelation, where both acceptor atoms are covalently bonded to the same atom(s), as in Fig. 15.7. 

Some of the hydrogen-bonded dimer configurations described in the matrices are observed in the crystal structures of the purines and pyrimidines, but this is by no means the general rule. This may be because the number of crystal structures in which self-base pairing occurs is relatively small compared with the number of possibilities. Certain arrangements appear to be particularly favored for reasons... 

In inosine, the NH2 at C(2) on guanine is removed, thereby reducing the hydrogen-bonding capability by a donor group with two functional hydrogens. 8-Bromoinosine is a rare example where the self-association of the purine residues occurs in the crystal structure of a nucleoside. 

The crystal structure of 8-bromoinosine [BRINOSIOI with two molecules A, B in the asymmetric unit (Fig. 17.60) contains a centrosymmetric base-pair configuration. It has an interesting overall pseudosymmetry, linking the functional ribosyl groups of one molecule to the purine of the other. 

Jeffrey GA (1989) Hydrogen bonding in crystal structures of nucleic acid components purines, pyrimidines, nucleosides and nucleotides. In Saenger W (ed), Landolt-BOrnstein. Numerical Data and Functional Relationships in Science and Technology. New Series, Group VII, Vol. Ib. Springer, Berlin, pp 277-348... 

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