Yannick Tauran

Molecular recognition by gold, silver and copper nanoparticles

The intrinsic physical properties of the noble metal nanoparticles, which are highly sensitive to the nature of their local molecular environment, make such systems ideal for the detection of molecular recognition events. The current review describes the state of the art concerning molecular recognition of Noble metal nanoparticles. In the first part the preparation of such nanoparticles is discussed along with methods of capping and stabilization. A brief discussion of the three common methods of functionalization: Electrostatic adsorption; Chemisorption; Affinity-based coordination is given. In the second section a discussion of the optical and electrical properties of nanoparticles is given to aid the reader in understanding the use of such properties in molecular recognition. In the main section the various types of capping agents for molecular recognition; nucleic acid coatings, protein coatings and molecules from the family of supramolecular chemistry are described along with their numerous applications. Emphasis for the nucleic acids is on complementary oligonucleotide and aptamer recognition. For the proteins the recognition properties of antibodies form the core of the section. With respect to the supramolecular systems the cyclodextrins, calix[n]arenes, dendrimers, crown ethers and the cucurbitales are treated in depth. Finally a short section deals with the possible toxicity of the nanoparticles, a concern in public health.

A rapid and practical technique for real-time monitoring of biomolecular interactions using mechanical responses of macromolecules

Monitoring biological reactions using the mechanical response of macromolecules is an alternative approach to immunoassays for providing real-time information about the underlying molecular mechanisms. Although force spectroscopy techniques, e.g. AFM and optical tweezers, perform precise molecular measurements at the single molecule level, sophisticated operation prevent their intensive use for systematic biosensing. Exploiting the biomechanical assay concept, we used micro-electro mechanical systems (MEMS) to develop a rapid platform for monitoring bio/chemical interactions of bio macromolecules, e.g. DNA, using their mechanical properties. The MEMS device provided real-time monitoring of reaction dynamics without any surface or molecular modifications. A microfluidic device with a side opening was fabricated for the optimal performance of the MEMS device to operate at the air-liquid interface for performing bioassays in liquid while actuating/sensing in air. The minimal immersion of the MEMS device in the channel provided long-term measurement stability (>10 h). Importantly, the method allowed monitoring effects of multiple solutions on the same macromolecule bundle (demonstrated with DNA bundles) without compromising the reproducibility. We monitored two different types of effects on the mechanical responses of DNA bundles (stiffness and viscous losses) exposed to pH changes (2.1 to 4.8) and different Ag+ concentrations (1 μM to 0.1 M).

Cytosine: para-sulphonato-calix(4)arene assemblies: in solution, in the solid-state and on the surface of hybrid silver nanoparticles

The molecular recognition by para-sulphonato-calix[4]arene of cytosine, occurs in solution, in the solid-state and by assembly on the surface of para-sulphonato-calix[4]arene capped silver nanoparticles. Each of these states shows different modes of assembly; in solution a 1:1 complex is formed; in the solid state a 4:1 assembly exists, however some of the cytosine molecules are present as space fillers and do not participate in the host (guest complexes, finally on the surface of the hybrid silver/para-sulphonato-calix[4]arene nanoparticles a 2:1 cytosine/para-sulphonato-calix[4]arene assembly is observed. The assembly processes have been studied by DOSY NMR, fluorescence spectroscopy, Dynamic Light Scattering (DLS), Single Crystal Solid State Diffraction, Visible Spectroscopy and Electron Microscopy. The results demonstrate how cytosine initiates the aggregation of the hybrid silver/para-sulphonato-calix[4]arene hybrid nanoparticles.

Molecular Recognition and Transport of Active Pharmaceutical Ingredients on Anionic Calix[4]arene-Capped Silver Nanoparticles

A series of six anionic calix[4]arenes, having sulphonate, carboxylate, or phosphonate functions at either the para-aromatic position or the phenolic face were used to cap silver nanoparticles. Their molecular recognition properties were studied with regard to three active pharmaceutical ingredients, chlorhexidine, chloramphenicol, and. gentamycin sulfate. Of these APIs chlorhexidine is known to form cocrystals with the anionic calix[4]arenes, gentamicin sulfate is an aminoglycosidic antibiotic, and chloramphenicol is a neutral antibiotic. As expected the former two APIs show clear complexation behavior as demonstrated by shifts in the visible spectra whereas the last shows no modification in the wavelength of the plasmon resonance of the silver nanoparticles.

Anionic Calixarene-Capped Silver Nanoparticles Show Species-Dependent Binding to Serum Albumins

The anionic calixarenes para-sulphonatocalix[4]arene and 1,3-di-O-phosphonatocalix[4]arene, have been used to cap silver nanoparticles. The binding of these functional particles with regard to various serum albumins (bovine serum albumin, human serum albumin, porcine serum albumin and sheep serum albumin) has been studied by variable temperature fluorescence spectroscopy. The quenching of the fluorescence of the proteins was shown to vary as a function of the anionic calixarene capping molecule and also as a function of the origin of the serum albumin. It is thus possible to discriminate between the different species.

Direct measurement of the mechanism by which magnesium specifically modifies the mechanical properties of DNA

We examine the effect of physiological cations Na+, K+, Mg2+, and Ca2+ on the mechanical properties of bundles of λ-phage DNA using silicon nanotweezers (SNTs). Integrating SNTs with a microfluidic device allows us to perform titration experiments while measuring the effect in real-time. The results show that only for Mg2+ and in particular, at the intra-nuclear concentration (100 mM), the interaction occurs.

Elucidating the mechanism of the considerable mechanical stiffening of DNA induced by the couple Zn 2+ /Calix[4]arene-1,3-O-diphosphorous acid

The couple Calix[4]arene-1,3-O-diphosphorous acid (C4diP) and zinc ions (Zn2+) acts as a synergistic DNA binder. Silicon NanoTweezer (SNT) measurements show an increase in the mechanical stiffness of DNA bundles by a factor of >150, at Zn2+ to C4diP ratios above 8, as compared to Zinc alone whereas C4diP alone decreases the stiffness of DNA. Electroanalytical measurements using 3D printed devices demonstrate a progression of events in the assembly of C4diP on DNA promoted by zinc ions. A mechanism at the molecular level can be deduced in which C4diP initially coordinates to DNA by phosphate-phosphate hydrogen bonds or in the presence of Zn2+ by Zn2+ bridging coordination of the phosphate groups. Then, at high ratios of Zn2+ to C4diP, interdigitated dimerization of C4diP is followed by cross coordination of DNA strands through Zn2+/C4diP inter-strand interaction. The sum of these interactions leads to strong stiffening of the DNA bundles and increased inter-strand binding.

The solid-state structures of organic salts formed by calix[4]arene dihydroxyphosphonic acid with nucleic bases cations: adeninium, cytosinium, guaninium and uracilium

Abstract Calix[4]arene dihydroxyphosphonic acid has been demonstrated to possess an interesting range of biological properties, including atypical anti-cancer activity. The robustness of calix[4]arene dihydroxyphosphonic acid and its ubiquitous dimeric motif offers perspectives for pre-defined solid state complexation with small molecules. In the current article we describe co-crystals (organic salts) of calix[4]arene dihydroxyphosphonic acid with four nucleic base cations: adeninium, cytosinium, guaninium and uracilium. A number of characteristic interactions between the components in the four co-crystals are pointed out also using the Hirshfeld surface analysis. All the four co-crystals are based on layers of calix[4]arene dimers, alternating with layers of nucleic acid molecules. Two of the reported crystal structures (cytosinium and guaninium) are 1D channel-type structures, while the two others (adeninium and uracilium) represent 2D channel-type structures. In three out of four reported structures, interactions between the cations of nucleic bases are present generating 1D chains of cations. A constant motif is that the nucleic base is present in a type of cavity formed by one aromatic ring and a phosphonic acid moiety.

The solid-state structures of the ethanol solvated complexes of para-sulphonato-calix[4]arene with magnesium and calcium ions

The structures ethanol solvated complexes of para-sulphonato-calix[4]arene with magnesium and calcium have been determined. Both show the classical bilayer structure of para-sulphonato-calix[4]arene. The cations are situated between the bilayers. In the case of the magnesium complex the cation is octahedrally coordinated by six water molecules, however for the calcium complex the cation is coordinated in two different geometries by water molecules, bridging oxygen atoms of the sulphonate anions and an oxygen of an ethanol molecule. Both complexes contain an ethanol molecule embedded in the macrocyclic cavity.