Dimerization of metallated nucleobase pairs via hydrogen-bond formation: open metallated base quartets of mixed adenine-N  3, guanine-N  7 complexes of trans-(H3N)2PtII with two different guanine–guanine pairing schemes

Meiser, Cordula; Freisinger, Eva; Lippert, Bernhard

doi:10.1039/a801507d

Cited by 36 publications

(23 citation statements)

References 29 publications

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“…Thus, Scheme 2a is an example for the involvement of a second nucleobase (X ϭ guanine) in self-association (v in Scheme 4), as are compounds V (14) and VI (15) tion (vii in Scheme 4). This pair by far exceeds the normal G,C Watson-Crick pair in strength (47)(48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds

Freisinger

Rother

Lüth

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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If two nucleobases are crosslinked by trans-a2Pt II , self-association via H bonding may take place either through individual bases or jointly through both bases. Due to the blockage of an acceptor site by the metal, the number of feasible pairing patterns can be reduced, and the preferred ones altered. If the metalated base pair as a whole undergoes association, base quartets can form. Various scenarios resulting from the application of guanine, hypoxanthine, and cytosine model nucleobases are discussed. Unconventional COH. . .N hydrogen bonding has been observed in several instances.H bonding ͉ platinum T he existence of cyclic guanine (G) quartets and the association of poly(G) and poly(I) into four-stranded structures have been known for quite some time (1, 2). Proof of the formation of G quartets in telomere sequences (3) and their existence in human cells (4), new insights on the structure of human telomeric DNA (5, 6), and, above all, implications that G quartets are potential drug targets for the chemotherapy of cancer, on the one hand, and can play a dysfunctional role, on the other (7), have made the field of DNA quadruplex structures a booming area. From an inorganic chemistry point of view, the involvement of metal ions in the formation and stabilization of G 4 structural elements is of particular interest. That these cations, K ϩ and Na ϩ under physiological conditions and many other cations under nonphysiological conditions, are absolutely essential for maintaining the G 4 structure elements has been recognized at an early stage. Moreover, it is now clear that a stem of G 4 quartets stabilizes other quartet structures, including those between dimers of Watson-Crick pairs, e.g., [GC] 2 (C, cytosine) (8).Small molecules that bind specifically to quadruplex DNA, thereby interfering with the enzyme telomerase or inhibiting expression of a crucial gene, are believed to be useful for chemotherapeutic applications. Among these, cationic porphyrins such as tetra-(N-methyl-4-pyridyl)porphine are particularly promising (4, 9, 10). Our interest in this area stems from our experience with metal-nucleobase complexes representing artificial base quartets that are cationic and flat and that have dimensions compatible with the natural base quartets. Because of their shape and charge, these compounds can be expected to have a natural affinity for tetra-stranded DNA in general and telomere sequences in particular. The use of metal ions (M) displaying linear coordination geometries and the fact that purine nucleobases, on simultaneous metal binding to N1 and N7, provide 90°angles between their M-N vectors and hence represent angular building blocks of squares and rectangles have enabled the construction of a variety of artificial M-base quartets (11-16). Examples are given in Scheme 1. Depending on the metal ions applied and the degree of crosslinking, these quartets can be kinetically labile or robust, also occasionally assembled by remarkably strong H bonds, even in solution. It will be our ultimate goal to probe t...

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Section: Discussionmentioning

confidence: 99%

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds

Freisinger

Rother

Lüth

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…[14] We could further demonstrate that coordinative metal binding in combination with interbase H bonding leads to additional variations in the kind of aggregations. [15±19] In a number of cases unexpected H bonding patterns were observed, such as interguanine triple H bonding, [16] a reinforced Watson ± Crick pairing scheme between guanine and cytosine, [17a, 19] a new base pairing scheme between guanine and cytosine, [17b] or H bonding involving an aromatic proton (H5) of a cytosine nucleobase and an imino group (N1) of a guanine base. [18] Mingos and co-workers have adopted a similar approach and exploited the directional interactions of H bonds between metal coordination compounds in studies aimed at crystal engineering.…”

Section: Introductionmentioning

confidence: 99%

Metal-Modified Nucleobase Sextet: Joining Four Linear Metal Fragments (trans-a2PtII) and Six Model Nucleobases to an Exceedingly Stable Entity

et al. 2001

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Crosslinking of three different model nucleobases (9-ethyladenine, 9-EtA; 9-ethylguanine, 9-EtGH; 1-methyluracil, 1-MeU) by two linear trans-aPtII (a = NH3 or CH3NH2) entities leads to a flat metal-modified base triplet, trans,trans-[(NH3)2Pt(1-MeU-N3)(mu-9-EtA-N7,N1)Pt(CH3NH2)2(9-EtGH-N7)]3+ (4b). Upon hemideprotonation of the 9-ethylguanine base at the N1 position. 4b spontaneously dimerizes to the metalated nucleobase sextet 5, [(4b)(triple bond)(4b-H)]5+. In this dimeric structure a neutral and an anionic guanine ligand, which are complementary to each other, are joined through three H bonds and additionally by two H bonds between guanine and uracil nucleobases. Four additional interbase H bonds maintain the approximate coplanarity of all six bases. The two base triplets form an exceedingly stable entity (KD = 500 +/- 150 M(-1) in DMSO), which is unprecedented in nucleobase chemistry. The precursor of 4b and several related complexes are described and their structures and solution properties are reported.

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“…Hence, one may conclude that the 2'-OH group is not involved in metal ion binding and that an interaction with N3 is responsible for the stability enhancement. It should be added here that it is becoming increasingly clear from solution [152][153][154] as well as X-ray crystal structure studies that the N3 site of a purine may bind metal ions [155][156][157][158][159][160]. For example, Pt 2+ [155] and Cd 2+ [156] bind via N3 to adenine derivatives, Pd 2+ to N6',N6',N9-trimethyladenine [157], Pt 2+ to a guanine derivative [158], as well as Cu 2+ [159] and Ni 2+ [160] to neutral adenine.…”

Section: Nucleoside 2'-and 3'-monophosphatesmentioning

confidence: 99%

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

Sigel

Skilandat

Sigel

et al. 2012

Metal Ions in Life Sciences

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Cadmium(II), commonly classified as a relatively soft metal ion, prefers indeed aromaticnitrogen sites (e.g., N7 of purines) over oxygen sites (like sugar-hydroxyl groups). However, matters are not that simple, though it is true that the affinity of Cd(2+) towards ribose-hydroxyl groups is very small; yet, a correct orientation brought about by a suitable primary binding site and a reduced solvent polarity, as it is expected to occur in a folded nucleic acid, may facilitate metal ion-hydroxyl group binding very effectively. Cd(2+) prefers the guanine(N7) over the adenine(N7), mainly because of the steric hindrance of the (C6)NH(2) group in the adenine residue. This Cd(2+)-(N7) interaction in a guanine moiety leads to a significant acidification of the (N1)H meaning that the deprotonation reaction occurs now in the physiological pH range. N3 of the cytosine residue, together with the neighboring (C2)O, is also a remarkable Cd(2+) binding site, though replacement of (C2)O by (C2)S enhances the affinity towards Cd(2+) dramatically, giving in addition rise to the deprotonation of the (C4)NH(2) group. The phosphodiester bridge is only a weak binding site but the affinity increases further from the mono-to the di-and the triphosphate. The same also holds for the corresponding nucleotides. Complex stability of the pyrimidine-nucleotides is solely determined by the coordination tendency of the phosphate group(s), whereas in the case of purine-nucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Cd(2+) with N7. The extents of the formation degrees of these chelates are summarized and the effect of a non-bridging sulfur atom in a thiophosphate group (versus a normal phosphate group) is considered. Mixed ligand complexes containing a nucleotide and a further mono-or bidentate ligand are covered and it is concluded that in these species N7 is released from the coordination sphere of Cd(2+). In the case that the other ligand contains an aromatic residue (e.g., 2,2'-bipyridine or the indole ring of tryptophanate) intramolecular stack formation takes place. With buffers like Tris or Bistris mixed ligand complexes are formed. Cd(2+) coordination to dinucleotides and to dinucleoside monophosphates provides some insights regarding the interaction between Cd(2+) and nucleic acids. Cd(2+) binding to oligonucleotides follows the principles of coordination to its units. The available crystal studies reveal that N7 of purines is the prominent binding site followed by phosphate oxygens and other heteroatoms in nucleic acids. Due to its high thiophilicity, Cd(2+) is regularly used in so-called thiorescue experiments, which lead to the identification of a direct involvement of divalent metal ions in ribozyme catalysis.

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Dimerization of metallated nucleobase pairs via hydrogen-bond formation: open metallated base quartets of mixed adenine-N 3, guanine-N 7 complexes of trans-(H3N)2PtII with two different guanine–guanine pairing schemes

Cited by 36 publications

References 29 publications

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds

Metal-Modified Nucleobase Sextet: Joining Four Linear Metal Fragments (trans-a2PtII) and Six Model Nucleobases to an Exceedingly Stable Entity

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

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Dimerization of metallated nucleobase pairs via hydrogen-bond formation: open metallated base quartets of mixed adenine-N 3, guanine-N 7 complexes of trans-(H3N)2PtII with two different guanine–guanine pairing schemes

Cited by 36 publications

References 29 publications

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a2PtII: Artificial nucleobase quartets and C—H…N bonds

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a2PtII: Artificial nucleobase quartets and C—H…N bonds

Metal-Modified Nucleobase Sextet: Joining Four Linear Metal Fragments (trans-a2PtII) and Six Model Nucleobases to an Exceedingly Stable Entity

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

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Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds

Canonical and unconventional pairing schemes between bis(nucleobase) complexes oftrans-a₂Pt^II: Artificial nucleobase quartets and C—H…N bonds