Metal ions alternative base pairs

The first metal-ligand alternative base pair to be incorporated in DNA duplexes was of [3 -f-1] type and was reported by Meggers et al. in 2000 (96). This pair was based on tridentate pyridine-2,6-dicarboxylate (Dipic) and monodentate pyridine (py) ligands, which were introduced in complementary positions in the middle of a DNA duplex (Entry 14, Table V). The same group reported the incorporation in DNA duplexes of three other tridentate ligands that bear structural similarity to Dipic, namely, pyridine-2,6-dicarboxamide (Di-pam) (Entry 15, Table V) (120), pyridine-2,6-(N-methyl-)dicarboxamide (Me-Dipam) (120), and 2,6-bis(ethylthiomethyl)pyridine (SPy) (Entry 16, Table V) (106). In the absence of a metal ion, incorporation in DNA duplexes of any of the four tridentate ligands opposite a pyridine had a destabilization effect similar to that of a mismatch or completely prevented the formation of a duplex. 

In all the naturally occurring DNA and RNA double helices, the base pairs are of the Watson-Crick type A U(T) and O C. If DNA with the four nucleotides in random sequence [and not in alternating purine-pyrimidine sequence as in poly(dO-dC)] is exposed to different salt concentrations (and metal ions), it adopts two principal secondary structures A and B. 

The rich coordination chemistry of transition metal ions has been used not only to create metal-ligand complexes that play the role of alternative nucleo-base pairs within nucleic acid duplexes, but also to influence the secondary structure adopted by the nucleic acid, for example, hairpin, duplex, or triplex, and to create connectors for such nucleic acid structures. In this context, oligonucleotides that contain terminal ligands can lead to structures distinct from those accessible by using centrally-modified oligonucleotides, such as cyclic structures or hairpins (Fig. 3). 

Basic carriers (Table 27.1) consist mainly of amine-based compounds such as quaternary ammonium salts (e.g., Aliquat 336), tertiary amines (e.g., tri-n-octylamine [TOA], tri-isooctylamine [TlOA]), weakly basic compounds (e.g., alkyl derivatives of pyridine N oxides), and thiadiazine derivatives (e.g., 5-(4-phenoxyphenyl)-6/f-l,3,4-thiadiazin-2-amine [FFAT]). The reason for this classification is related to the similarity in the extraction mechanism involving the carriers discussed. In the case of fully substituted quaternary ammonium compounds (e.g., Aliquat 336), the carrier reacts as an anion exchanger forming an ion-pair with another anion from the feed phase, which can be a complex metal anion. In the case of amine and other weak bases mentioned earlier, the carrier must be protonated first in order to allow anion exchange with another anion from the feed phase or with a complex metal anion. Alternatively, the carrier may react directly with a protonated complex metal anion [16]. 

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