Structure of purines

Because of its historical association, the original ring numbering (1) adopted by Fischer is still used in preference to that of the Bing Index,7 standard for purine analogs, which designates purine as 9-(or 7-)/f-imidazo(4,5-dJpyrimidine. 

Structural Features Derived from Spectroscopic Studies 

Studies of tautomerism, in which the spectra of aminopurines and their substituted-amino analogs were compared, show clearly that the amino and not the imino form predominates.8 Confirmation has been supplied by infrared13 and by nuclear magnetic resonance studies on adenosine and guanosine.14,15 Alkylation of the pyrimidine ring nitro- 

Katritzky and A. P. Ambler, in Physical Methods in Heterocyclic Chemistry (A. R. Katritzky, ed.), Vol. II, Chapter 10. Academic Press, New York, 1963. 

Ciba Found. Symp., Chem. Biol. Purines p. 39 (1957). 

---

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)...

Narayana SVL, Bugg CE, Ealick SE. Refined structure of purine nucleoside phosphorylase at 2.75 A resolution. Acta Cryst D 1996 accepted. 

Discussing the biosynthetic pathways for amino acids and nucleotides together is a sound approach, not only because both classes of molecules contain nitrogen (which arises from common biological sources) but because the two sets of pathways are extensively intertwined, with several key intermediates in common. Certain amino acids or parts of amino acids are incorporated into the structure of purines and pyrimidines, and in one case part of a purine ring is incorporated into an amino acid (histidine). The two sets of pathways also share... 

Fedorov A, Shi W, Kicska GA, Fedorov E, Tyler PC, Furneaux RH, Hanson JC, Gainsford GJ, Larese JZ, Schramm VL, Almo SC (2001) Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. Biochemistry 40 853-860... 

In this chapter, we have reviewed some of our own work on solvation properties in supercritical fluids using molecular dynamics computer simulations. We have presented the main aspects associated with the solvation structures of purine alkaloids in CO2 under different supercritical conditions and in the presence of ethanol as co-solvent, highlighting the phenomena of solvent density augmentation in the immediate neighborhood of the solute and the effects from the strong preferential solvation by the polar co-solvent. We have also presented a summary of our results for the structure and dynamics of supercritical water and ammonia, focusing on the dielectric behavior of supercritical water as functions of density and temperature and the behavior of excess solvated electrons in aqueous and non-aqueous associative environments. 

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). 

In contrast to adenine and guanine the structure of purine in the crystal is well characterized as the N(7)// tautomer (65AX573). However even this is to some extent unexpected since calculations indicate that the N 7)H and N 9)H forms have similar stabilities. 

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. -... 

As described previously, the couphng constants also represent valuable parameters for studying the structure of purine derivatives. Unfortunately, the extraction of relevant chemical information (geometry and electronic structure) is not always straightforward, and couphngs often require careful analysis and interpretation. " ... 

II. The Structure of Purine Nucleosides Derived from Nucleic Acids. 302... 

The structure of purine ribonucleosides has recently been studied by proton-magnetic resonance, and the conformation of the D-ribofuranosyl residue in adenosine and inosine has been determined by an analysis of proton-magnetic resonance data C-2 is considered to be out of the plane defined either by C-1, 0, and C-4 or by C-1, 0, C-3, and C-4 and is pointing on the same side as the C-4—C-5 bond. A similar study of deoxy-ribonucleosides suggests that the ring-oxygen atom and, possibly, C-1 of this sugar moiety may be twisted out of the plane of the five-membered... 

For historical reasons, the numbering of purine (imidazo[4,5-d]pyrimidine) does not comply with lUPAC rules. The X-ray structure of purine shows that the imidazole part is planar and the fused pyrimidine ring deviates from a coplanar arrangement (see Fig. 6.20). Purine exists in two tautomeric forms, namely 7i/-purine 1 and 9//-purine 2, which are in equal concentration in solution (annular tautomerism). In the solid state, the 7//-form is dominant ... 

Fig. 1.20. Left The structure of Purine, Right The Purine derivatives Adenine and Guanine are found as bases in both DNA and RNA.

Trimethoprim and tetroxoprim inhibit folic acid synthesis, i. e., they specifically inhibit the dihydrofolate reductase which is responsible for synthesis of folic acid. They make possible the reduction of dihydrofolic acid to tetrahydrofolic acid. The structure of purines and pyrimidines is thereby interrupted, an essential step in the synthesis of proteinic and ribonucleic acid. This inhibitory effect is selective and affects bacteria only. 

Jardetzky CD, Jardetzky O (1960) Investigation of the structure of purines, pyrimidines, ribose nucleosides and nucleotides by proton magnetic resonance.il. J Am Chem Soc... 

Figure 6.59 Structure of purine alkaloids methylxantines (7-methylxanthine, theobromine, caffeine, theophylline, and paraxanthine) and methyluiic adds (theacrine, 1,3,7-lrimethyluric acid, methylliberine, and liberine).

Fischer also figured prominently in the elucidation of structures of purines, a class of compounds that have in common a nitrogen-carbon two-ring structure. One example of this class is caffeine (a good deal of this purine was consumed in the production of these very words), and another is uric acid. Uric acid is a purine found in the excreta of humans, birds, reptiles, and it is one source of the nitrogen richness of guano, or bird droppings, harvested in Chile for fertilizer. 

Figure 1 Examples of structures of purines (1) adenine (2) hypoxanthine (3) guanine (G). Pyrimidines (4) uracil (5) cytosine (C) (6) thymine (T). Nucleosides (7) adenosine (A) (8) uridine (U). Nucleotides (9) 3, 5 -cAMP (10) adenosine 5 -triphosphate. Dinucleotide (11) NAD +. ...

Structure of purine end pyrimidine bases, nucleosides and nucleotides... 

Fischer, Hermann Emil (1852-1919) German organic chemist who discovered the molecular structures of sugars, including glucose, found the structure of purines, isolated and identified amino acids, and worked on the structure of proteins. He received the Nobel Prize in chemistry in 1902 for his work on sugars and purines. 

Fig. 10.2. Structure of purine and pyrimidine analogues with antiviral activity.

---