A Dinuclear Mercury(II)‐Mediated Base Pair in DNA

Abstract

The first dinuclear metal-mediated base pair containing divalent metal ions has been prepared. A combination of the neutral bis(monodentate) purine derivative 1,N -ethenoadenine (ϵA), which preferentially binds two metal ions with a parallel alignment of the N-M bonds, and the canonical nucleobase thymine (T), which readily deprotonates in the presence of Hg and thereby partially compensates the charge accumulation due to the two closely spaced divalent metal ions, yields the dinuclear T-Hg -ϵA base pair. This metal-mediated base pair stabilizes the DNA oligonucleotide duplex as shown by an increase of 8 °C in its melting temperature. Formation of the base pair was demonstrated by temperature-dependent UV spectroscopy as well as by titration experiments monitored by UV and CD spectroscopy.

1,8‐Dimercuri‐6‐Phenyl‐1H‐Carbazole as a Monofacial Dinuclear Organometallic Nucleobase

“…For reference, similar melting temperatures have been reported for respective duplexes incorporating a mononuclear Hg II ‐mediated 5‐mercuricytosine–thymine or a canonical thymine–adenine base pair in the middle of the chain (56.1 and 56.9 °C, respectively) . On the other hand, the stabilization relative to the unmercurated duplex ON1 z ⋅ ON2 t is similar to the value previously reported for parallel‐stranded duplexes incorporating a dinuclear Hg II ‐mediated base pair between 1,N 6 ‐ethenoadenine and thymine …”

“…[9] On the other hand, the stabilization relative to the unmercurated duplex ON1 z·ON2 t is similar to the value previously reported for parallel-stranded duplexes incorporating ad inuclearH g IImediated base pair between 1,N 6 -ethenoadenine and thymine. [5] Previous studies with oligonucleotides incorporating coordinative or organometallic Hg II -mediatedb ase pairs have revealed less negative enthalpies and entropies of hybridization compared to unmodified duplexes, consistent with dehydration of the bridging Hg II ion. [9][10][11] However,t he pattern observed with ON1 z and ON1 z-Hg 2 was quite different.T he enthalpies( Table 2) and entropies (Table 3) of hybridizationw ere highly negative for all of the duplexess tudied and in most cases both values were more negative with ON1 z-Hg 2 than with ON1 z.O nly duplexes ON1 z·ON2 t and ON1 z-Hg 2 ·ON2 t Chem.E ur.J.…”

“…[4] Interestingly,r emarkable stabilization by dinuclearm etal-mediated hetero base pairs between one canonical ando ne artificial nucleobase has also been observed. [5] Inspired by these results,wereport herein the synthesis and hybridization studies of an oligonucleotide incorporating a1 ,8-dimercury-6-phenyl-1H-carbazole residue as the first example of ac ovalently metallated oligonucleotide with the potentialf or dinuclear metal-mediated base pairing. Unlike the previously reported 2,6-dimercuriphenol, [6] 1,8-dimercury-6-phenyl-1H-carbazole is monofacial, with the two Hg II ions bondedonthe same side of the carbazole base.…”

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

“…[10g, 31] 1,N 6 -Ethenoadenine (eA) is an adenine derivative with an appended aromatic ring that renders the former exocyclic nitrogen atom N6 an endocyclic one.The lone pairs of the N6 and N7 donor sites are oriented almost in parallel, making eA an ideal ligand to bring two linearly coordinating metal ions into close proximity. [38] Thea pplication of eAa sa na rtificial nucleobase hence enabled the formation of unprecedented dinuclear metal-mediated base pairs,including eA-Ag I 2 -eAas the first dinuclear metal-mediated homo pair of ap urine derivative (Figure 4d), [32] eA-Hg II 2 -T as the only dinuclear metal-mediated base pair with divalent metal ions, [33] and others. [39] Thestructure proposed for eA-Hg II 2 -T as depicted in Figure 4e slightly deviates from the one suggested in the original report but is more likely to represent the correct one.…”

“…By incorporating pyridine nucleosides Pyr into the center of the triplex d(T 10 PyrT 10 )·d(A 10 PyrA 10 )*d(T 10 PyrT 10 ), as table triple helix was obtained. As its thermal stability was significantly increased in the presence of Ag I ions, [26,28] b) Im Phen-Hg II -T; [29] c) Im Phen-Ag I -C; [29] d) eA-Ag I 2 -eA; [32] e) eA-Hg II 2 -T; [33] f) COO Im-Cu II -COO Im; [34] g) OH U-M-OH U(M= for example, Gd III ,Z n II ); [35] h) C Hg -T; [36] i) Phe Py Pd -T. [37] R, R' = DNA backbone.…”