Nucleic bases reactivity

Depending on the time elapsed since entering the low-chloride environment of the nucleus, for each isomer the real distribution in the cell nucleus appears somewhere between the columns headed 4 mM and 104 mu in Table 3. With the above times, the half-life for the Ptn complexes to reach equilibrium upon passing from a 104 mM to 4 mM ambient chloride environment at 45 °C is about one hour for the cis- and 0.2 h for the trans-isomer. Table 3 shows that except for a very significant contribution from the d.v-diaqua complex in 4 mM chloride, the most reactive species for both isomers at both chloride concentrations is the chloro-aqua that appears in the second row. Therefore, the main species of the drug reacting with nucleic bases upon entry into the cell nucleus is the choro-aqua species, which in about one hour becomes superseded by the hydroxo-aqua species for the cis-isomer. 

Various conceptual DFT-based reactivity indices in association with some new parameters are successfully employed in the development of stronger QSAR/QSTR models [332]. Deeper correlations of the toxicity of different classes of organic compounds like chlorinated benzenes [333], polychlorinated biphenyls [312, 334—336], and benzidine [337] at DFT level of theory are reported. The toxicity of the polychlorinated biphenyls as well as benzidine is itrfluenced by its electron affinity and planarity. The interactions of the chlorinated benzo-derivatives and benzidine with other biomolecules like nucleic acid/base pairs or aryl hydrocarbon hydroxylase (AHH) receptors are primarily of charge-transfer type, which can be quantitatively assessed from Parr to Pearson formula [254] and can be given as... 

Amine bases in nucleic acids can react with alkylating agents in typical Sjsj2 reactions. Look at the following electrostatic potential maps, and tell which is the better nucleophile, guanine or adenine. The reactive positions in each are indicated. 

The refinement of other analytical methods, such as electrophoresis [34,36], the various techniques of optical spectroscopy [103-105], and nuclear magnetic resonance [201], is supplemented by the recent advances in real-time affinity measurements [152,202], contributing to the understanding of biomolecular reactivity. Taken together, the improvement of analytical methods will eventually allow a comprehensive characterization of the structure, topology, and properties of the nucleic acid-based supramolecular components under consideration for distinctive applications in nanobiotechnology. 

The formation of an aldehyde group on a macromolecule can produce an extremely useful derivative for subsequent modification or conjugation reactions. In their native state, proteins, peptides, nucleic acids, and oligonucleotides contain no naturally occurring aldehyde residues. There are no aldehydes on amino acid side chains, none introduced by post-translational modifications, and no formyl groups on any of the bases or sugars of DNA and RNA. To create reactive aldehydes at specific locations within these molecules opens the possibility of directing modification reactions toward discrete sites within the macromolecule. 

Methods currently available for chemiluminescent detection of nucleic acids are not based on derivatization techniques that directly recognize one of the nucleic acid bases or nucleotides. For chemical derivatization-based chemiluminescent detection, the specific reactivity of alkyl glyoxals and arylglyoxals with adenine or guanine nucleotides has been investigated. 

The terminology nucleotide or nucleoside immediately directs our thoughts towards nucleic acids. Remarkably, nucleosides and nucleotides play other roles in biochemical reactions that are no less important than their function as part of nucleic acids. We also encounter more stmctural diversity. It is rare that the chemical and biochemical reactivities of these derivatives relate specihcally to the base plus sugar part of the structure, and usually reside elsewhere in the molecule. Almost certainly, it is this base plus sugar part of the structure that provides a recognition... 

It has been proposed that 8-aminodcoxyguanosinc is formed from the nitronate tautomer of 2-nitropropane either by base nitrosation followed by reduction, or via an enzyme-mediated conversion of the nitronate anion to hydroxyiam ine-O-sulfonate or acetate, which yields the highly reactive nitrenium ion NHj (Sodum et al., 1993). Sodum et al. (1994) have provided evidence for the activation of 2-nitropropane to an aminating species by rat liver aryl sulfotransferase in vitro and in vivo. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of nucleic acid modifications produced in the liver by 2-nitropropane treatment. Partially purified rat liver aryl sulfotransferase activated 2-nitropropane and its nitronate at neutral pH to a reactive species that aminated guanosine at the position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3 -phosphate 5 -phosphosulfate, and mercaptoethanol. It was inhibited... 

The study of the reactivity of the nucleic acid bases utilizes indices based on the knowledge of the molecular electronic structure. There are two possible approaches to the prediction of the chemical properties of a molecule, the isolated and reacting-molecule models (or static and dynamic ones, respectively). Frequently, at least in the older publications, the chemical reactivity indices for heteroaromatic compounds were calculated in the -electron approximation, but in principle there is no difficulty to define similar quantities in the all-valence or allelectron methods. The subject is a very broad one, and we shall here mention only a new approach to chemical reactivity based on non-empirical calculations, namely the so-called molecular isopotential maps. 

The purines and pyrimidines are relatively stable compounds with considerable aromatic character. Nevertheless, they react with many different reagents and, under some relatively mild conditions, can be completely degraded to smaller molecules. The chemistry of these reactions is complex and is made more so by the fact that a reaction at one site on the ring may enhance the reactivity at other sites. The reactions of nucleic acids are largely the same as those of the individual nucleosides or nucleotides, the rates of reaction are often influenced by the position in the polynucleotide chain and by whether the nucleic acid is single or double stranded. The reactions of nucleosides and nucleotides are best understood in terms of the electronic properties of the various positions in the bases.26 33 Most of the chemical reactions are nucleophilic addition or displacement reactions of types that are discussed in Chapters 12 and 13. 

Another source of modified bases in both DNA and RNA is spontaneous or "accidental" alteration. Nucleic acids encounter many highly reactive and mutagenic materials including hydroxyl radicals, formed from 02, and are able to convert guanine rings into 7,8-dihydro-8-oxoguanine.362 Other reactive and carcinogenic compounds can form adducts with nucleic acid bases.363 See Eq. 5-18 and also Chapter 27. 

There are many other alkylating agents which often display widely varying reactivity and specificity toward particular nucleic acid bases and particular nucleotide sequences. 

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