Contraction/extension molecular motion by protonation/deprotonation induced structural switching of pyridine derived oligoamides.

NMR, mass spectrometry and X-ray diffraction studies show reversible structural interconversion between helical and extended forms of pyridine derived oligoamide molecular strands, by simple protonation/deprotonation.

Homo- and heterometallic [2x2] grid arrays containing RuII, OsII, and FeII subunits and their mononuclear RuII and OsII precursors: synthesis, absorption spectra, redox behavior, and luminescence properties.

The absorption spectra, redox behavior, and luminescence properties (both at 77 K in rigid matrices and at room temperature in fluid solution) of a series of [2x2] molecular grids have been investigated. The latter were prepared either by means of sequential self-assembly, or by a stepwise protection/deprotection procedure, and are based on a ditopic hexadentate ligand 1 in which two terpyridine-like binding sites are fused together in a linear arrangement. The molecular grids studied include the homometallic species [[Fe(1)](4)](8+) (Fe(2)Fe(2)), and the heterometallic species [[Ru(1)](2)[Fe(1)](2)](8+) (Ru(2)Fe(2)) and [[Os(1)](2)[Fe(1)](2)](8+) (Os(2)Fe(2)).

Generation of bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library.

Ditopic dynamic combinatorial libraries were generated and screened toward inhibition of the bifunctional enzyme HPr kinase/phosphatase from Bacillus subtilis. The libraries were composed of all possible combinations resulting from the dynamic interconversion of 16 hydrazides and five monoaldehyde or dialdehyde building blocks, resulting in libraries containing up to 440 different constituents. Of all possible acyl hydrazones formed, active compounds containing two terminal cationic heterocyclic recognition groups separated by a spacer of appropriate structure could be rapidly identified using a dynamic deconvolution procedure.

DNA mismatch-specific base flipping by a bisacridine macrocycle.

Most, if not all, enzymes that chemically modify nucleobases in DNA flip their target base from the inside of the double helix into an extrahelical position. This energetically unfavorable conformation is partly stabilized by specific binding of the apparent abasic site being formed. Thus, DNA base-flipping enzymes, like DNA methyltransferases and DNA glycosylases, generally bind very strongly to DNA containing abasic sites or abasic-site analogues.

Supramolecular control of the template-induced selective photodimerization of 4-methyl-7-O-hexylcoumarin.

A symmetric ditopic molecular receptor (3), containing two identical hydrogen-bonding recognition subunits, was designed and synthesized. These subunits are capable of binding substrates with complementary donor and acceptor sites to form a supramolecular complex through hydrogen bonding. Receptor 3 was designed to accept two guest molecules, which are held in close proximity within the supramolecular species.

Molecular recognition of quadruplex DNA by quinacridine derivatives.

The interaction of monomeric and dimeric quinacridines with quadruplex DNA has been investigated using a variety of biophysical methods. Both series of compounds were shown to exhibit a high affinity for the G4 conformation with two equivalent binding sites. As shown from the SPR and dialysis experiments the macrocyclic dimer appears more selective than its monomeric counterpart.

Self-organization by selection: generation of a metallosupramolecular grid architecture by selection of components in a dynamic library of ligands.

Self-organization by selection is implemented in the generation of a tetranuclear [2 x 2] grid-type metallosupramolecular architecture from its components. It occurs through a two-level self-assembly involving two dynamic processes: reversible covalent bound connection and reversible metal ion coordination. Thus, mixing the aminophenol 3, the dialdehyde 4, and zinc acetate generates the grid complex 1a(Zn) via the assembly of the ligand 2a by imine formation and of the grid by zinc(II) binding.

Supramolecular spintronic devices: spin transitions and magnetostructural correlations in [Fe4IIL4]8+ [2x2]-grid-type complexes.

The magnetism of a series of tetranuclear complexes of the [Fe4IIL4]8+ [2x2]-grid-type was investigated, revealing the occurrence of spin transition behavior within this class of compounds. The phenomenon depends directly on the nature of the substituent R(1) in the 2-position on the central pyrimidine group of the ligand L. All Fe(II) ions in compounds with R(1) substituents favoring strong ligand fields (R(1)=H; OH) remain completely in the diamagnetic low-spin state.

Self-assembly, structure, and dynamic interconversion of metallosupramolecular architectures generated by Pb(II) binding-induced unfolding of a helical ligand.

The binding of lead(II) cations to the terpyridine-type subunits of the helical ligand 1 leads to the self-assembly of different polynuclear metallosupramolecular architectures of nanometric size. Three different entities are generated and may be interconverted as a function of metal/ligand stoichiometry: a [4 x 4]Pb(16)(II) grid-type array 2, a [4 # 4]Pb(12)(II) double-cross species 4, and an intermediate complex 3. The structures of 2 and 4 have been confirmed by X-ray crystallography; that of 3 is based on NMR spectral data.

Synthesis of ionisable [2 x 2] grid-type metallo-arrays and reversible protonic modulation of the optical properties of the [Co4(II)L4]8+ species.

The new bis-hydrazone based ligands A and B form ionisable [2 x 2] grid-type transition metal complexes whose properties may be modulated by multiple protonation/deprotonation as shown by the reversible change in optical properties of the [Co2(II)L4]8+ complexes depending on their protonation state.

Selective recognition of G-qQuadruplex telomeric DNA by a bis(quinacridine) macrocycle.

The interaction of G-quadruplex DNA with the macrocyclic compound BOQ1, which possesses two dibenzophenanthroline (quinacridine) subunits, has been investigated by a variety of methods. The oligonucleotide 5'-A(GGGT(2)A)(3)G(3), which mimics the human telomeric repeat sequence and forms an intramolecular quadruplex, was used as one model system. Equilibrium binding constants measured by biosensor surface plasmon resonance (SPR) methods indicate a high affinity of the macrocycle for the quadruplex conformation (K > 1 x 10(7) M(-)(1)) with two equivalent binding sites.

2-Aminopyrimidine directed self-assembly of zinc porphyrins containing bulky 3,5-di-tert-butylphenyl groups.

The 2-aminopyrimidin-5-yl ligand is revealed to be a promising candidate for the construction of supramolecular porphyrin arrays with broad absorption bands for efficient light-harvesting. 10-Mono- and 10,20-di(2-aminopyrimidin-5-yl) derivatives of 5,15-bis(3,5-di-tert-butylphenyl)porphyrin have been synthesized in high yield. Their Zn(II) salts show variable concentration and temperature-dependent UV/vis spectra in solution, consistent with supramolecular aggregation.

Dynamic chemical devices: generation of reversible extension/contraction molecular motion by ion-triggered single/double helix interconversion.

The polyheterocyclic strands 1-H and 2-H adopt a helical shape enforced by the pyridine-pyrimidine helicity codon. The crystal structure of 2-H shows the formation of stacks of dimers of right- and left-handed individual helices. Treatment of 1-H and 2-H with silver triflate results in the generation of double-helical entities 1-DH and 2-DH, containing two strands and two silver ions.

Functional supramolecular devices: [M4IIL4]8+ [2 x 2]-grid-type complexes as multilevel molecular electronic species.

The [M(4)(II)L(4)](8+) [2 x 2]-grid-type complexes 1-8 present a set of features of particular interest for potential applications. All complexes exhibit multiple reduction levels at low reduction potentials paired with rather high stability. The modulation of the reduction potentials is possible by introduction of appropriate substituents on the ligands.

Chemical biology of dynamic combinatorial libraries.

Dynamic combinatorial chemistry (DCC) is a recently introduced supramolecular approach to generate libraries of chemical compounds based on reversible exchange processes. The building elements are spontaneously and reversibly assembled to virtually encompass all possible combinations, allowing for simple one-step generation of complex libraries. The method has been applied to a variety of combinatorial systems, ranging from synthetic models to materials science and drug discovery, and enables the establishment of adaptive processes due to the dynamic interchange of the library constituents and its evolution toward the best fit to the target.

Aminoglycoside-derived cationic lipids as efficient vectors for gene transfection in vitro and in vivo.

Background: Cationic lipids are at present very actively investigated for gene transfer studies and gene therapy applications. Basically, they rely on the formation of DNA/lipid aggregates via electrostatic interactions between their cationic headgroup and the negatively charged DNA. Although their structure/activity relationships are not well understood, it is generally agreed that the nature of the positive headgroup impacts on their transfection activity.

Self-assembly, characterisation, and crystal structure of multinuclear metal complexes of the [2 x 3] and [3 x 3] grid-type.

The self-assembly of new multimetallic complexes of grid-type architecture is described. The binding of a set of tris-terdentate ligands, 1 a-1 d, based on terpyridine-like subunits, with different octahedrally coordinated metal ions leads to the formation of species whose structure depends strongly on the ligand, the metal ion, the counterion, the solvent, and the reaction conditions. Under suitable conditions, the [3 x 3] grid was obtained from the reaction of ligand 1 a with zinc tetrafluoroborate and from ligand 1 b with mercury triflate.

Helical self-organization and hierarchical self-assembly of an oligoheterocyclic pyridine-pyridazine strand into extended supramolecular fibers.

The synthesis and characterization of an alternating pyridine-pyridazine strand comprising thirteen heterocycles are described. Spontaneous folding into a helical secondary structure is based on a general molecular self-organization process enforced by the conformational information encoded within the primary structure of the molecular strand itself. Conformational control based on heterocyclic "helicity codons" illustrates a strategy for designing folding properties into synthetic oligomers (foldamers).

Synthesis and structures of zirconium amide-iodide complexes.

Zirconium amide-iodide complexes were synthesized for possible use as chemical vapor deposition precursors to zirconium nitride films. The series of six complexes Zr(NR(2))(4-n)I(n)(R = Me or Et; n = 1-3) was prepared by reacting ZrI(4) and Zr(NR(2))(4) in hot toluene. X-ray crystallographic analyses were performed for Zr(NMe(2))(3)I, Zr(NEt(2))(2)I(2), and Zr(NEt(2))I(3).

Drug discovery by dynamic combinatorial libraries.

Dynamic combinatorial chemistry is a recently introduced supramolecular approach that uses self-assembly processes to generate libraries of chemical compounds. In contrast to the stepwise methodology of classical combinatorial techniques, dynamic combinatorial chemistry allows for the generation of libraries based on the continuous interconversion between the library constituents. Spontaneous assembly of the building blocks through reversible chemical reactions virtually encompasses all possible combinations, and allows the establishment of adaptive processes owing to the dynamic interchange of the library constituents.

Transport of the highly charged myo-inositol hexakisphosphate molecule across the red blood cell membrane: a phase transfer and biological study.

To address the problem of delivering highly charged small molecules, such as phytic acid (InsP(6) or IHP), across biological membranes, we investigated an approach based on a non-covalent interaction between transport molecule(s) and IHP. Thus, we synthesized a collection of compounds containing IHP ionically bound to lipophilic (but non-lipidic) ammonium or poly-ammonium cations. First, we assessed the ability of these water-soluble salts to cross a biological membrane by measuring the partition coefficients between human serum and 1-octanol.

Electron transfer through bridging molecular structures.

Pairs of reducible pentakis(thiophenyl)benzene subunits are linked by different molecular structures as model compounds for reducible molecular-wire-type synthons showing varying electron-transfer ability as a function of the bridging structures, consisting of either para-divinylbenzene, bis-hydrazone, or diacetylene. Their electron-transfer ability from one reducible subunit to the other was investigated by electrochemical and spectroelectrochemical methods. In the case of the bis-hydrazone bridge and the diacetylene bridge, the solid-state structures support the experimental findings.

Dynamic chemical devices: modulation of contraction/extension molecular motion by coupled-ion binding/pH change-induced structural switching.

Dynamic chemical devices involve morphological or constitutional modifications in molecular or supramolecular systems, induced by internal or external physical or chemical triggers. Reversible changes in shape result in molecular motions and define motional dynamic devices presenting mechanical-like actions of various types. Suitably designed polyheterocyclic strands such as compounds 1-5 wrap into helical conformations.