Adenine aromatic structure

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. 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

The alkaloids are also relevant to drug design. Alkaloids are complex heterocyclic compounds that contain nitrogen and thus have base-like (hence the term alkaloid ) properties they are extremely structurally diverse. Nicotine is one of the simplest alkaloids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as NAD" (oxidized form). The neurotransmitter serotonin is an alkaloid containing the aromatic indole ring system. 

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. 

A model of a flavin-based redox enzyme was prepared.[15] Redox enzymes are often flavoproteins containing flavin cofactors flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). They mediate one- or two-electron redox processes at potentials which vary in a range of more than 500 mV. The redox properties of the flavin part must be therefore tuned by the apoenzyme to ensure the specific function of the enzyme. Influence by hydrogen bonding, aromatic stacking, dipole interactions and steric effects have been so far observed in biological systems, but coordination to metal site has never been found before. Nevertheless, the importance of such interactions for functions and structure of other biological molecules make this a conceivable scenario. 

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. 

Hoechst 33258 binds to the minor groove of double-stranded DNA with a preference for the A-T sequence (Pjura et al. 1987). Interaction between DNA and proteins very often induces structural modifications in both interacting molecules. Such modifications in DNA can be characterized with 2-aminopurine (2AP), which is a highly fluorescent isomer of adenine. 2AP does not alter the DNA structure. It forms a base pair with thymine and can be selectively excited, since its absorption is red-shifted compared to that of nucleic acids and aromatic amino acids. In addition, its fluorescence is sensitive to the conformational change that occurs within the DNA (Rachofsky et al. 2001). 

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. 

Figure 18. A, Molecular structure of adenosine-S -mononicotinate showing the facility with which the two bases can stack. B, Temperature study of the circular dichroism of adenosine-5 -mononicotinate. A reciprocal relation is seen between the 260 nm band of adenine and the band near 270 mn of the nicotinate chromophore as the two aromatic chromophores stack at lower temperatures. Reproduced, with permission, from [31].

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