Metal‐Mediated Deamination of Cytosine: Experiment and DFT Calculations

Abstract

A mechanism goes platinum: Hydrolytic deamination of cytosine is a major mutagenic event in DNA. Studies with a model system and DFT calculcations demonstrate that deamination is facilitated by coordination of the PtII center to the N3 atom (see scheme; C=cytosine, U=uracil).

(Dien)MII (M=Pd, Pt) and (NH3)3PtII complexes of 1-methylcytosine: Linkage and rotational isomerism, metal-promoted deamination, and pathways to dinuclear species

“…The pK a (N(4)H 2 ) of 1 was estimated to be approximately 13.5 in D 2 O, corresponding to ca. 13 in water (see Supporting Information) [16]. 1 …”

“…We have recently reported that Pt II (1-MeC-N3) complexes undergo cytosine deamination at alkaline pH to the corresponding 1-methyluracilate complexes Pt II (1-MeU-N3) [16]. With (dien)Pt II , a competing reaction takes place, however, in which the metal entity migrates from N3 of cytosine to the exocyclic N4 position (Scheme 1).…”

“…Recently yet another aspect of Pt-nucleobase chemistry has emerged, namely irreversible nucleobase modifications brought about by a coordinated Pt II . Thus, the transformations of cytosine to uracil [16] and of adenine to hypoxanthine [17] have been reported. In both cases the role of the coordinated Pt II is that of a Lewis acid which facilitates nucleophilic attack of OH À on the ring carbon atom carrying the exocyclic amino group.…”

Unusual Dimeric Zn(II)-cytosine complexes: New models of the interaction of Zn(II) with DNA and RNA

“…It is also unusual the situation involv- [35][36][37][38][39][40][41][42][43][44], Pd(II) [45,46] probably due to an initial N3 ! N4 migration of the transition metal [38,47,48]; other cases are (1-MeC-N3)-Cu(II)-(1-MeC-N4) 2 [49], (1-MeC-N3)-Ag(I)-(1-MeC-O2) [13], (1-MeC-N4) 2 -Cu(II)-(1-MeC-O2) 2 [50], and (1-MeC À -N4)-Pd(II)-(1-MeC-O2) [51]. The structure of [Zn 2 (1-MeC-N3) 4 (l-SO 4 ) 2 ] AE H 2 O (2) consists of assembled centrosymmetric dimers (Fig.…”

Mechanisms of Mutagenic DNA Nucleobase Damages and Their Chemical and Enzymatic Repairs Investigated by Quantum Chemical Methods

“…(Cadet & Vigny 1990;Chatgilialoglu et al 2000) Hence, they could act as a trap for a migrating electron hole. (Sponer et al 2004;Yao et al 2005) Unfortunately, however, despite detailed experimental study, the exact route by which such species' (8-oxoB and 8-oxoB • (-H7)) may be formed remains unclear. (Llano & Eriksson 2004b) We performed a computational investigation on the processes by which 8-OHB (aq) may be formed for purine, adenine and guanine.…”