Single-Stranded DNA as Supramolecular Template for One-Dimensional Palladium(II) Arrays.

Atomic-level control over the position and growth of a single and continuous metal chain is an ambitious goal that often requires complex and costly processes. Herein, we demonstrate that 1Pd-DNA molecules, comprising a continuous single chain of PdII ions, can be prepared by a simple self-assembly reaction between the complex [Pd(Cheld)(CH3 CN)] (1Pd_CH3 CN) (Cheld=chelidamic acid) and single-stranded DNA homopolymers (ss-DNA) containing adenine (A) or 7-deazaadenine (X) bases. The single PdII -base pairs [1Pd(N1-A)] and [1Pd(N1-X)] were synthesized and characterized in solution and solid-state (X-ray diffraction) revealing an arrangement similar to that of natural Watson-Crick base pairs. Subsequently, 1Pd-DNA hybrids were prepared, characterized, and their structures studied by small-angle X-ray scattering (SAXS) and ab-initio calculations. The results indicate that the 1Pd-DNA structures resemble that of double-stranded DNA, with one strand being replaced by a supramolecular stack of continuous PdII complexes.

Comparative Structural Study of Metal-Mediated Base Pairs Formed outside and inside DNA Molecules.

The formation of copper(II)-mediated base pairs involving pyridine-2,6-dicarboxylate derivatives and canonical nucleosides has proven to be a smart approach to introduce copper(II) ions at specific locations of DNA duplexes. However, the structural characteristics of these metalized base pairs have not yet been revealed, and their effect on DNA structures is difficult to assess. Herein, for the first time, we report on the different structural details of copper-mediated base pairs formed by themselves and in DNA duplexes. The individual base pairs [Cu(mcheld)(N3-Cyt)(H2O)]·3H2O (1Cu_Cyt), [Cu(mcheld)(N7-Ade)(H2O)2]·2H2O (1Cu_Ade), [Cu(mcheld)(N7-Gua)(H2O)] (1Cu_Gua), and [Cu(mcheld)(N1-7CAde)(H2O)]·H2O (1Cu_7CAde) were obtained from the reaction of the metal complex [Cu(mcheld)(H2O)2] (1Cu) (mcheld = 4-methoxypyridine-2,6-dicarboxylic acid) with model nucleosides (Cyt = N1-methylcytosine, Ade = N9-ethyladenine, Gua = N9-propylguanine, 7CAde = N9-propyl-7-deazaadenine). The crystal structure of the five complexes was determined by means of single-crystal X-ray diffraction. Furthermore, the formation of the 1Cu_Cyt and 1Cu_Gua base pairs in the middle of DNA duplexes, duplex DNA15 (917 atoms) and DNA10 (649 atoms), respectively, was studied using highly demanding ab initio computational calculations. These theoretical studies aimed to validate, from a structural point of view, whether base pairs of the kind 1Cu_nucleosides can be included in a DNA double helix and how this situation affects the double-helical structure. The results indicate that the 1Cu_Cyt and 1Cu_Gua base pairs can be formed in a DNA molecule without significant structural constraints. In addition, the double-helix DNA structure remains virtually unchanged when it contains these Cu(II)-mediated base pairs.

Highly Stable Double-Stranded DNA Containing Sequential Silver(I)-Mediated 7-Deazaadenine/Thymine Watson-Crick Base Pairs.

The oligonucleotide d(TX)9 , which consists of an octadecamer sequence with alternating non-canonical 7-deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double-stranded DNA through the formation of hydrogen-bonded Watson-Crick base pairs. dsDNA with metal-mediated base pairs was then obtained by selectively replacing W-C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag(+) ions, and its stability is significantly enhanced in the presence of Ag(+) ions while its double-helix structure is retained. Temperature-dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)-mediated base pairs. This strategy could become useful for preparing stable metallo-DNA-based nanostructures.

Lanthanide complexes containing 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one and their therapeutic potential to fight leishmaniasis and Chagas disease.

In the last years, numerous and significant advances in lanthanide coordination chemistry have been achieved. The unique chemical nature of these metal ions which is conferred by their f-electrons has led to a wide range of coordination compounds with interesting structural, physical and also biological properties. Consequently, lanthanide complexes have found applications mainly in catalysis, gas adsorption, photochemistry and as diagnostic tools. However, research on their therapeutic potential and the understanding of their mechanism of action is still taking its first steps, and there is a distinct lack of research in the parasitology field. In the present work, we describe the synthesis and physical properties of seven new lanthanide complexes with the anionic form of the bioactive ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO), namely [Ln(mtpO)3(H2O)6]·9H2O (Ln=La(III), Nd(III), Eu(III), Gd(III), Tb(III), Dy(III) and Er(III)). In addition, results on the in vitro antiproliferative activity against Leishmania spp. and Trypanosoma cruzi are described. The high activity of the new compounds against parasite proliferation and their low cytotoxicity against reference host cell lines show a great potential of this type of compounds to become a new generation of highly effective and non-toxic antiparasitic agents to fight the so considered neglected diseases leishmaniasis and Chagas disease.