Di-copper(ii) DNA G-quadruplexes as EPR distance rulers.

Artificial metal-base tetrads composed of square-planar CuII(pyridine)4 complexes were covalently attached to both the 3' and 5' ends of tetramolecular DNA G-quadruplexes [Ld(G3-5)LdT]4 (L = pyridine ligand) of different lengths. Owing to the planar four-point attachment of the metal complexes, the magnetic orbitals (dx2-y2) of the d9-configured CuII cations are placed in a coplanar fashion, separated by the stacked guanine tetrads. Pulsed EPR-derived CuII-CuII distances and angles were found to be in agreement with those obtained from molecular dynamics simulations. DNA-confined transition metal spin labels open new ways to study oligonucleotide structure and DNA-protein complexes.

Structure-Property Relationships in CuII -Binding Tetramolecular G-Quadruplex DNA.

A series of artificial metal-base tetrads composed of a CuII cation coordinating to four pyridines, covalently attached to the ends of tetramolecular G-quadruplex DNA strands [LA-D d(G4 )]4 (LA-D =ligand derivatives), was systematically studied. Structurally, the square-planar [Cu(pyridine)4 ] complex behaves analogously to the canonical guanine quartet. Copper coordination to all studied ligand derivatives was found to increase G-quadruplex thermodynamic stability, tolerating a great variety of ligand linker lengths (1-5 atoms) and thus demonstrating the robustness of the chosen ligand design. Only at long linker lengths, the stabilizing effect of copper binding is compensated by the loss of conformational freedom. A previously reported ligand LE with chiral backbone enables incorporation at any oligonucleotide position. We show that ligand chirality distinctly steers CuII -induced G-quadruplex stabilization. 5'-End formation of two metal-base tetrads by tetramolecular G-quadruplex [LE2 d(G)4 ]4 shows that stabilization in the presence of CuII is not additive. All results are based on UV/Vis thermal denaturation, thermal difference, circular dichroism experiments and molecular dynamics simulations.

Copper-Induced Topology Switching and Thrombin Inhibition with Telomeric DNA G-Quadruplexes.

The topological diversity of DNA G-quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol-based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid-phase synthesis. Square-planar coordination to a CuII ion led to the formation of a highly stabilizing intramolecular metal-base tetrad, substituting one G-tetrad in the parent unimolecular G-quadruplex. For the Tetrahymena telomeric repeat, CuII -triggered switching from a hybrid-dominated conformer mixture to an antiparallel topology was observed. CuII -dependent control over a protein-G-quadruplex interaction was shown for the thrombin-tba pair (tba=thrombin-binding aptamer).

Self-assembled coordination cages based on banana-shaped ligands.

The combination of pyridyl ligands and square-planar Pd(ii) or Pt(ii) cations has proven to be a very reliable recipe for the realization of supramolecular self-assemblies. This tutorial review deals with the design, synthesis and host-guest chemistry of discrete coordination cages built according to this strategy. The focus is set on structures obeying the formula [PdnL2n] (n = 2-4). The most discussed ligands are bent, bis-monodentate bridges having their two donor sites pointing in the same direction. The structures of the resulting cages range from simple globules over intertwined knots to interpenetrated dimers featuring three small pockets instead of one large cavity. The cages have large openings that allow small guest molecules to enter and leave the cavities. Most structures are cationic and thus favour the uptake of anionic guests. Some examples of host-guest complexes are discussed with emphasis on coencapsulation and allosteric binding phenomena. Aside from cages in which the ligands have only a structural role, some examples of functional ligands based on photo- and redox-active backbones are presented.

Reversible stabilization of transition-metal-binding DNA G-quadruplexes.

You can't top the CopperTop: Tetramolecular G-quadruplexes modified with terminal pyridine ligands exhibit metal-triggered stabilization as monitored by thermal denaturation studies, circular dichroism, and nondenaturing gel electrophoresis. Formation of the square-planar Cu(II) (pyridine)4 complex was confirmed by EPR measurements. The metal complexation is fully reversible by removal of the transition metal with ethylenediaminetetraacetic acid (edta).

Counterion dynamics in an interpenetrated coordination cage capable of dissolving AgCl.

In solution, the eight BF(4)(-) counterions of a positively charged D(4)-symmetric interpenetrated [Pd(4)ligand(8)](8+) double cage (1) are localized in distinct positions. At low temperatures, one BF(4)(-) ion is encapsulated inside the central pocket of the supramolecular structure, two BF(4)(-) ions are bound inside the equivalent outer pockets, and the remaining five BF(4)(-) ions are located outside the cage structure (expressed by the formula [3 BF(4)@1][BF(4)](5)). On warming, the two BF(4)(-) ions in the outer pockets are found to exchange with the exterior ions in solution whereas the central BF(4)(-) ion stays locked inside the central cavity (here written as [BF(4)@1][BF(4)](7)). The exchange kinetics were determined by exchange spectroscopy (EXSY) NMR experiments and line-shape fitting in different solvents. The tremendously high affinity of this double cage for the binding of two chloride ions inside the outer pockets allows for complete exchange of two BF(4)(-) ions by the addition of solid AgCl to give [2 Cl+BF(4)@1][BF(4)](5). The uptake of the two chloride ions is allosteric and is thus accompanied by a structural rearrangement (compression along the Pd(4) axis) of the double cage structure. An analysis by using 900 MHz NOESY NMR spectroscopy shows that this compression of about 3.3% is associated with a helical twist of 8°, which together resemble a screw motion. As a consequence of squeezing each of the outer two pockets by 53%, the volume of the central pocket is increased by 43%, which results in an increase of 36% in the (19)F spin-lattice relaxation time (T(1)) of the central BF(4)(-) ion. The packing coefficients (PC) for the ions in the outer pockets (103% for BF(4)(-) and 96% for Cl(-)) were calculated.