Silver(I)‐Mediated Base Pairs in DNA Sequences Containing 7‐Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson–Crick Base Pairs

Abstract

DNA sequences comprising noncanonical 7-deazaguanine ( G) and canonical cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as well as silver(I)-mediated base pairs by coordination to central silver(I) ions. Duplexes I and II containing G and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature-dependent UV spectroscopy, circular dichroism, and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated G-Ag -C Watson-Crick base pairs that preserve the original B-type conformation. Furthermore, additional studies performed on duplex III indicated that, in the presence of Ag ions, G-C and A-T Watson-Crick base pairs ( A, 7-deazadenine; T, thymine) can be converted to metallated G-Ag -C and A-Ag -T base pairs inside the same DNA molecule whilst maintaining its initial double helix conformation. These findings are very important for the development of customized silver-DNA nanostructures based on a Watson-Crick complementarity pattern.

5‐Aza‐7‐deaza‐2′‐deoxyguanosine and 2′‐Deoxycytidine Form Programmable Silver‐Mediated Base Pairs with Metal Ions in the Core of the DNA Double Helix

“…In addition, the formation of silver‐mediated c 7 A d (7‐deaza‐2′‐deoxyadenosine)‐dT base pairs was reported . Recently, silver‐mediated base pairing of self‐complementary oligonucleotides incorporating a 7‐deaza‐2′‐deoxyguanosine‐dC pair was reported . However, an X‐ray investigation on a related duplex showed that nonhelical structures exist when the sequence motif changes .…”

“…However, in the presence of silver ions, the 6‐mer duplex was already too stable to display a complete melting profile (see Figure S5 in the Supporting Information). A similar observation was made on a much longer 14‐mer oligonucleotide duplex with alternating dG‐dC . Consequently, studies were continued on the 4‐mer duplex of 5′‐d(GCGC) (Figure a,b and Figure S6 in the Supporting Information).…”

“…As 7‐deaza‐2′‐deoxyguanosine (c 7 G d ) shows a strong structural relationship to nucleoside dZ, we extended our studies to corresponding self‐complementary duplexes. As in the case of dG, the 4‐ and 6‐mer oligonucleotides 5′‐d(c 7 GCc 7 GC) and 5′‐d(c 7 GCc 7 GCc 7 GC) were synthesized in which 7‐deaza‐2′‐deoxyguanosine (c 7 G d ) replaces dG. These duplexes do not form left‐handed Z‐DNA .…”

“…Additional amounts of silver ions lead to an increase of the T m values. The 14‐mer oligonucleotides did not develop a complete melting profile . Apparently, the silver mediated base pairing is too strong and duplex dissociation is impaired even at higher temperatures.…”

“…Moreover, an X‐ray structure performed by Kondo illustrates that silver ions can replace protons in dG‐dC Watson Crick and related base pairs formed by canonical nucleosides . In solution entirely metallated base pairs containing 7‐deazaguanine were identified …”