Guanine, aromaticity structure

Because the chemical shifts of the nonexchangeable nucleobase proton signals are sensitive to (de)protonations of the aromatic structure, the absence of certain protonation shifts, or alterations in the expected pKa values, can give valuable information about the sites where platinum is bound. So, in N7-platinated guanine, no N7 protonation shift around pH 2 is observed, whereas the pKa of the N1 protonation decreases from 9.5 to 8.5 (54). 

Another property of pyrimidines and purines is their strong absorbance of ultraviolet (UV) light, which is also a consequence of the aromaticity of their heterocyclic ring structures. Figure 11.8 shows characteristic absorption spectra of several of the common bases of nucleic acids—adenine, uracil, cytosine, and guanine—in their nucleotide forms AMP, UMP, CMP, and GMP (see Section 11.4). This property is particularly useful in quantitative and qualitative analysis of nucleotides and nucleic acids. 

A complete understanding of the biochemical functions of DNA requires a clear picture of its structural and physical characteristics. DNA has significant absorption in the UV range because of the presence of the aromatic bases adenine, guanine, cytosine, and thymine. This provides a useful probe into DNA structure because structural changes such as helix unwinding affect the extent of absorption. In addition, absorption measurements are used as an indication of DNA purity. The major absorption band for purified DNA peaks at about 260 nm. Protein material, the primary contaminant in DNA, has a peak absorption at 280 nm. The ratio A26(j/A2m is often used as a relative measure of the nucleic acid/protein content of a DNA sample. The typical A260/Am for isolated DNA is about 1.8. A smaller ratio indicates increased contamination by protein. 

Unlike phenols (Section 26-l), structural analysis of many of the hydroxy-substituted aza-aromatic compounds is complicated by isomerism of the keto-enol type, sometimes called lactim-lactam isomerism. For 2-hydro xypyrimidine, 19, these isomers are 19a and 19b, and the lactam form is more stable, as also is true for cytosine, 15, thymine, 16, and the pyrimidine ring of guanine, 18. 

The specific hydrogen bonding that occurs between adenine and thymine or guanine and cytosine was of crucial importance in the development of the model for the structure of DNA by Watson and Crick. However, at that time, many people believed that guanine existed primarily as the enol tautomer and thymine as the dienol tautomer because both of these structures would be fully aromatic. 

Very few reports of the excited-state structural dynamics of the purine nucleobases have appeared in the literature. This lack of research effort is probably due to a number of factors. The primary factor is the lack of photochemistry seen in the purines. Although adenine can form photoadducts with thymine, and this accounts for 0.2% of the photolesions found upon UVC irradiation of DNA [67], the purines appear to be relatively robust to UV irradiation. This lack of photoreactivity is probably due to the aromatic nature of the purine nucleobases. A practical issue with the purine nucleobases is their insolubility in water. While adenine enjoys reasonable solubility, it is almost an order of magnitude lower than that of thymine and uracil, the two most soluble nucleobases [143], Guanine is almost completely insoluble in water at room temperature [143],... 

Competitive effects for the interactions of cisplatin with various active sites in the cellular environment are discussed in papers of Deubel.55,56 In the earlier paper, energetic and structural data of complexes with the different substituted ligands were explored. The more recent work deals with kinetic factors in the relation to the transition state (TS) for water replacement of the semihydrated cisplatin complex (cis-[Pt(NH3)2(H20)Cl]+ ) with either an N- or S-containing ligand (thiopheneimidazol, dimethyl sulphide, or methanethiolate which serve as amino acid models). Deubel concluded the kinetic preference of N-sites over S-nucleophiles where the important role is played by the electrostatic terms. In addition, the aliphatic/aromatic character of the substituent as well as the influence of different dielectric constants of the environment are very important. A more realistic model for the aqua-ligand replacement with adenine and guanine was studied in works of Chval et al.53,57 and Eriksson and coworkers.58 They performed independently the estimation of the thermodynamic and kinetic parameters of this process. 

In this case, the position C8 of guanine has been modified. The group of heterocyclic aromatic amines includes so many different compounds that a large variety of chemical structures of DNA adduction products formed by them can be expected. 

How can tautomerism explain why nucleic acids, such as uracil (C) and guanine (D), are aromatic even though this is not indicated in the structures shown below ... 

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