Guanine bromination

One of the most important reactions of purines is the bromination of guanine or adenine at the C-8 position. It is this site that is the most common point of modification for bioconjugate techniques using purine bases (Figure 1.53). Either an aqueous solution of bromine or the compound N-bromosuccinimide can be used for this reaction. The brominated derivatives then can be used to couple amine-containing compounds to the pyrimidine ring structure by nucleophilic substitution (Chapter 27, Section 2.1). 

Conjugation via Bromine Activation of Thymine, Guanine, and Cytosine... 

Figure 27.4 Reaction of guanine bases with N-bromosuccinimide causes bromination at the C-8 position of the ring. Amine nucleophiles can be coupled to this active derivative by nucleophilic displacement. Reaction of diamine compounds results in amine-terminal spacers that can be further modified to contain detectable components.

Razskazovskiy et al. employ ESR spectroscopy at low temperatures to investigate electron transfer within brominated DNA [8]. The brominated DNA base electron traps were introduced by bromination of DNA in ice-cooled aqueous solution. The procedure is shown by NMR and GC/MS techniques to modify thymine, cytosine, and guanine, transforming them into 5-bro-mo-6-hydroxy-5,6-dihydrothymine, T(OH)Br, 5-bromocytosine, CBr, and 8-bromoguanine, GBr, derivatives. The bromination products formed in molar ratio close to T(OH)Br/CBr/GBr 0.2 1 0.23 and serve as internal electron scavengers on y-irradiation. Structurally the CBr and GBr are planar, but T(OH)Br is quite nonplanar with the bromine directly above the molecular plane. This disrupts the DNA base stack. Paramagnetic products that result... 

Additionally, C8 can have sufficient electron density to allow the attack of electrophiles. This is promoted by an electron-donating group attached to the ring system. As a consequence, adenine reacts with bromine to give an 8-bromo derivative whereas purine forms only an adduct. It has been reported that the guanine moiety within DNA can be attacked by electrophiles causing mutagenicity. 

Bromination has been widely studied and occurs readily with adenine, guanine, hypoxan-thine, xanthine, and methylated xanthines giving the 8-bromo analogs. 

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