Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs.

Cystic fibrosis (CF) is a recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The recent development of a class of drugs called "correctors", which repair the structure and function of mutant CFTR, has greatly enhanced the life expectancy of CF patients. These correctors target the most common disease causing CFTR mutant F508del and are exemplified by the FDA-approved VX-809. While one binding site of VX-809 to CFTR was recently elucidated by cryo-electron microscopy, four additional binding sites have been proposed in the literature and it has been theorized that VX-809 and structurally similar correctors may engage multiple CFTR binding sites. To explore these five binding sites, ensemble docking was performed on wild-type CFTR and the F508del mutant using a large library of structurally similar corrector drugs, including VX-809 (lumacaftor), VX-661 (tezacaftor), ABBV-2222 (galicaftor), and a host of other structurally related molecules. For wild-type CFTR, we find that only one site, located in membrane spanning domain 1 (MSD1), binds favorably to our ligand library. While this MSD1 site also binds our ligand library for F508del-CFTR, the F508del mutation also opens a binding site in nucleotide binding domain 1 (NBD1), which enables strong binding of our ligand library to this site. This NBD1 site in F508del-CFTR exhibits the strongest overall binding affinity for our library of corrector drugs. This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.

Design of plasmonic directional antennas via evolutionary optimization.

We demonstrate inverse design of plasmonic nanoantennas for directional light scattering. Our method is based on a combination of full-field electrodynamical simulations via the Green dyadic method and evolutionary optimization (EO). Without any initial bias, we find that the geometries reproducibly found by EO work on the same principles as radio-frequency antennas. We demonstrate the versatility of our approach by designing various directional optical antennas for different scattering problems. EO-based nanoantenna design has tremendous potential for a multitude of applications like nano-scale information routing and processing or single-molecule spectroscopy. Furthermore, EO can help to derive general design rules and to identify inherent physical limitations for photonic nanoparticles and metasurfaces.

Enhancement of electric and magnetic dipole transition of rare-earth-doped thin films tailored by high-index dielectric nanostructures.

We propose a simple experimental technique to separately map the emission from electric and magnetic dipole transitions close to single dielectric nanostructures, using a few-nanometer thin film of rare-earth-ion-doped clusters. Rare-earth ions provide electric and magnetic dipole transitions of similar magnitude. By recording the photoluminescence from the deposited layer excited by a focused laser beam, we are able to simultaneously map the electric and magnetic emission enhancement on individual nanostructures. In spite of being a diffraction-limited far-field method with a spatial resolution of a few hundred nanometers, our approach appeals by its simplicity and high signal-to-noise ratio. We demonstrate our technique at the example of single silicon nanorods and dimers, in which we find a significant separation of electric and magnetic near-field contributions. Our method paves the way towards the efficient and rapid characterization of the electric and magnetic optical response of complex photonic nanostructures.

Multimodal plasmonics in fused colloidal networks.

Harnessing the optical properties of noble metals down to the nanometre scale is a key step towards fast and low-dissipative information processing. At the 10-nm length scale, metal crystallinity and patterning as well as probing of surface plasmon properties must be controlled with a challenging high level of precision. Here, we demonstrate that ultimate lateral confinement and delocalization of surface plasmon modes are simultaneously achieved in extended self-assembled networks comprising linear chains of partially fused gold nanoparticles. The spectral and spatial distributions of the surface plasmon modes associated with the colloidal superstructures are evidenced by performing monochromated electron energy-loss spectroscopy with a nanometre-sized electron probe. We prepare the metallic bead strings by electron-beam-induced interparticle fusion of nanoparticle networks. The fused superstructures retain the native morphology and crystallinity but develop very low-energy surface plasmon modes that are capable of supporting long-range and spectrally tunable propagation in nanoscale waveguides.

Molecular decay rate near nonlocal plasmonic particles.

When the size of metal nanoparticles is smaller than typically 10 nm, their optical response becomes sensitive to both spatial dispersion and quantum size effects associated with the confinement of the conduction electrons inside the particle. In this Letter, we propose a nonlocal scheme to compute molecular decay rates near spherical nanoparticles which includes the electron-electron interactions through a simple model of electronic polarizabilities. The plasmonic particle is schematized by a dynamic dipolar polarizability α(NL)(ω), and the quantum system is characterized by a two-level system. In this scheme, the light matter interaction is described in terms of classical field susceptibilities. This theoretical framework could be extended to address the influence of nonlocality on the dynamics of quantum systems placed in the vicinity of nano-objects of arbitrary morphologies.

Tailoring and imaging the plasmonic local density of states in crystalline nanoprisms.

Surface plasmon (SP) technologies exploit the spectral and spatial properties of collective electronic oscillations in noble metals placed in an incident optical field. Yet the SP local density of states (LDOS), which rule the energy transducing phenomena between the SP and the electromagnetic field, is much less exploited. Here, we use two-photon luminescence (TPL) microscopy to reveal the SP-LDOS in thin single-crystalline triangular gold nanoprisms produced by a quantitative one-pot synthesis at room temperature. Variations of the polarization and the wavelength of the incident light redistribute the TPL intensity into two-dimensional plasmonic resonator patterns that are faithfully reproduced by theoretical simulations. We demonstrate that experimental TPL maps can be considered as the convolution of the SP-LDOS with the diffraction-limited Gaussian light beam. Finally, the SP modal distribution is tuned by the spatial coupling of nanoprisms, thus allowing a new modal design of plasmonic information processing devices.

Plasphonics: local hybridization of plasmons and phonons.

We show that the interaction between localized surface plasmons sustained by a metallic nano-antenna and delocalized phonons lying at the surface of an heteropolar semiconductor can generate a new class of hybrid electromagnetic modes. These plasphonic modes are investigated using an analytical model completed by accurate Green dyadic numerical simulations. When surface plasmon and surface phonon frequencies match, the optical resonances exhibit a large Rabi splitting typical of strongly interacting two-level systems. Based on numerical simulations of the electric near-field maps, we investigate the nature of the plaphonic excitations. In particular, we point out a strong local field enhancement boosted by the phononic surface. This effect is interpreted in terms of light harvesting by the plasmonic antenna from the phononic surface. We thus introduce the concept of active phononic surfaces that may be exploited for far-infared optoelectronic devices and sensors.

Acousto-plasmonic and surface-enhanced Raman scattering properties of coupled gold nanospheres/nanodisk trimers.

This work is devoted to the fundamental understanding of the interaction between acoustic vibrations and surface plasmons in metallic nano-objects. The acoustoplasmonic properties of coupled spherical gold nanoparticles and nanodisk trimers are investigated experimentally by optical transmission measurements and resonant Raman scattering experiments. For excitation close to resonance with the localized surface plasmons of the nanodisk trimers, we are able to detect several intense Raman bands generated by the spherical gold nanoparticles. On the basis of both vibrational dynamics calculations and Raman selection rules, the measured Raman bands are assigned to fundamental and overtones of the quadrupolar and breathing vibration modes of the spherical gold nanoparticles. Simulations of the electric near-field intensity maps performed at the Raman probe wavelengths showed strong localization of the optical energy in the vicinity of the nanodisk trimers, thus corroborating the role of the interaction between the acoustic vibrations of the spherical nanoparticles and the surface plasmons of the nanodisk trimers. Acoustic phonons surface enhanced Raman scattering is here demonstrated for the first time for such coupled plasmonic systems. This work paves the way to surface plasmon engineering for sensing the vibrational properties of nanoparticles.

Damping of the acoustic vibrations of individual gold nanoparticles.

In this letter, the ultrafast vibrational dynamics of individual gold nanorings has been investigated by femtosecond transient absorption spectroscopy. Two acoustic vibration modes have been detected and identified. The influence of the mechanical coupling at the nanoparticle/substrate interface on the acoustic vibrations of the nano-objects is discussed. Moreover, by changing the environment of the nanoring, we provide a clear evidence of the impact of the surrounding medium on the damping of the acoustic vibrations. Such results are reported here for the first time on individual nanoparticles. This work points out a new sensing method based on the sensitivity of the acoustic vibration damping to the surrounding medium.

Challenges in nanofabrication for efficient optical metasurfaces.

Optical metasurfaces have raised immense expectations as cheaper and lighter alternatives to bulk optical components. In recent years, novel components combining multiple optical functions have been proposed pushing further the level of requirement on the manufacturing precision of these objects. In this work, we study in details the influence of the most common fabrication errors on the optical response of a metasurface and quantitatively assess the tolerance to fabrication errors based on extensive numerical simulations. We illustrate these results with the design, fabrication and characterization of a silicon nanoresonator-based metasurface that operates as a beam deflector in the near-infrared range.

Interconnect-Free Multibit Arithmetic and Logic Unit in a Single Reconfigurable 3 µm2 Plasmonic Cavity.

Processing information with conventional integrated circuits remains beset by the interconnect bottleneck: circuits made of smaller active devices need longer and narrower interconnects, which have become the prime source of power dissipation and clock rate saturation. Optical interchip communication provides a fast and energy-saving option that still misses a generic on-chip optical information processing by interconnect-free and reconfigurable Boolean arithmetic logic units (ALU). Considering metal plasmons as a platform with dual optical and electronic compatibilities, we forge interconnect-free, ultracompact plasmonic Boolean logic gates and reconfigure them, at will, into computing ALU without any redesign nor cascaded circuitry. We tailor the plasmon mode landscape of a single 2.6 µm2 planar gold cavity and demonstrate the operation and facile reconfiguration of all 2-input logic gates. The potential for higher complexity of the same logic unit is shown by a multi-input excitation and a phase control to realize an arithmetic 2-bit adder.

Gold nanoring trimers: a versatile structure for infrared sensing.

In this work we report on the observation of surface plasmon properties of periodic arrays of gold nanoring trimers fabricated by electron beam lithography. It is shown that the localized surface plasmon resonances of such gold ring trimers occur in the infrared spectral region and are strongly influenced by the nanoring geometry and their relative positions. Based on numerical simulations of the optical extinction spectra and of the electric near-field intensity maps, the resonances are assigned to surface plasmon states arising from the strong intra-trimer electromagnetic interaction. We show that the nanoring trimer configuration allows for generating infrared surface plasmon resonances associated with strongly localized electromagnetic energy, thus providing plasmonic nanoresonators well-suited for sensing and surface enhanced near-infrared Raman spectroscopy.

Mapping heat origin in plasmonic structures.

We investigate the physics of photoinduced heat generation in plasmonic structures by using a novel thermal microscopy technique based on molecular fluorescence polarization anisotropy. This technique enables us to image the heat source distribution in light-absorbing systems such as plasmonic nanostructures. While the temperature distribution in plasmonic nanostructures is always fairly uniform because of the fast thermal diffusion in metals, we show that the heat source density is much more contrasted. Unexpectedly the heat origin (thermal hot spots) usually does not correspond to the optical hot spots of the plasmon mode. Numerical simulations based on the Green dyadic method confirm our observations and enable us to derive the general physical rules governing heat generation in plasmonic structures.

Dual wavelength sensing based on interacting gold nanodisk trimers.

Fabrication and surface plasmon properties of gold nanostructures consisting of periodic arrays of disk trimers are reported. Using electron beam lithography, disk diameters as small as 96 nm and gaps between disks as narrow as 10 nm have been achieved with an unprecedented degree of control and reproducibility. The disk trimers exhibit intense visible and infrared surface plasmon resonances which are studied as a function of the disk diameter and of the pitch between trimers. Based on simulations of the optical extinction spectra and of the electric near-field intensity maps, the resonances are assigned to a single trimer response and to collective surface plasmon excitations involving electromagnetic interaction between the trimers. The sensing properties of the disk trimers are investigated using various coating media. The reported results demonstrate the possible use of gold disk trimers for dual wavelength chemical sensing.

Automated synthesis of a 96 product-sized library of triazole derivatives using a solid phase supported copper catalyst.

This article deal with the parallel synthesis of a 96 product-sized library using a polymer-based copper catalyst that we developed which can be easily separated from the products by simple filtration. This gave us the opportunity to use this catalyst in an automated chemical synthesis station (Chemspeed ASW-2000). Studies and results about the preparation of the catalyst, its use in different solvent systems, its recycling capabilities and its scope and limitations in the synthesis of this library will be addressed. The synthesis of the triazole library and the very good results obtained will finally be discussed.

Single plasmon spatial and spectral sorting on a crystalline two-dimensional plasmonic platform.

In the context of the emerging field of quantum plasmonics, we demonstrate in this manuscript the wavelength-dependent propagation and sorting of single plasmons launched in a two-dimensional crystalline gold flake by a broadband quantum nanoemitter. The stream of single plasmons in the visible is produced by a nanodiamond hosting a single nitrogen-vacancy color center positioned in the near field of the mesoscopic metallic microplatelet. Spatially and spectrally resolved images of the single plasmon propagation in the pristine hexagonal flake, and then in the same structure after insertion of a Bragg mirror, are obtained by filtered image-plane acquisitions on a leakage-radiation microscope. Our work on two-dimensional crystalline structures paves the way to future fundamental studies and applications in quantum plasmonics.

Sculpting nanometer-sized light landscape with plasmonic nanocolumns.

Plasmonic structures are commonly used to both confine and enhance surface electromagnetic fields. In the past ten years, their peculiar optical properties have given rise to many promising applications ranging from high density data storage to surface optical trapping. In this context, we investigated both far-field and near-field optical response of a collection of densely packed silver nanocolumns embedded in amorphous aluminum oxide using the discrete dipole approximation. In the far field, a good fit of the calculated to the experimental absorption spectra can only be achieved when in addition to interaction between neighboring nanocolumns, a nanorod shape with periodic shrinks mimicking the experimental morphology of the nanocolumns is used. In the near field, modulated field intensities following the nanocolumns distribution and tunable with the incident wavelength are predicted outside the region occupied by the nanocolumns. This plasmonic image transfer has a resolution of approximately 1.8D where D is the diameter of the nanocolumns that in our case is 2.4 nm.

Processing and near-field optical properties of self-assembled plasmonic nanoparticle networks.

We report on recent progress in the production and the deposition on surfaces of dielectric materials of self-assembled metallic nanoparticle systems able to organize into branched networks. We emphasize the interest of these new objects for tailoring novel near-field optical properties that could be the basis for optical energy transport in systems of extremely reduced sizes. The experimental optical spectra of such chain networks in solution can be very well reproduced by applying the coupled-dipole approximation scheme. In this paper, we apply this method to investigate the near-field optical properties of self-assembled plasmonic nanoparticle networks deposited on transparent surfaces.

"Flash" solvent-free synthesis of triazoles using a supported catalyst.

A solvent-free synthesis of 1,4-disubstituted-1,2,3-triazoles using neat azides and alkynes and a copper(I) polymer supported catalyst (Amberlyst) A21*CuI) is presented herein. As it provides the products in high yields and purities within minutes, this method thus being characterized as a "flash" synthesis, and was exemplified through the synthesis of a 24-compound library on a small scale.

In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic Liposomes Monitored by MRI.

PURPOSE: The development of theranostic nanocarriers as an innovative therapy against cancer has been improved by targeting properties in order to optimize the drug delivery to safely achieve its desired therapeutic effect. The aim of this paper is to evaluate the magnetic targeting (MT) efficiency of ultra-magnetic liposomes (UML) into CT26 murine colon tumor by magnetic resonance imaging (MRI). PROCEDURES: Dynamic susceptibility contrast MRI was applied to assess the bloodstream circulation time. A novel semi-quantitative method called %I0.25, based on the intensity distribution in T2*-weighted MRI images was developed to compare the accumulation of T2 contrast agent in tumors with or without MT. To evaluate the efficiency of magnetic targeting, the percentage of pixels under the intensity value I0.25 (I0.25 = 0.25(Imax - Imin)) was calculated on the intensity distribution histogram. RESULTS: This innovative method of processing MRI images showed the MT efficiency by a %I0.25 that was significantly higher in tumors using MT compared to passive accumulation, from 15.3 to 28.6 %. This methodology was validated by ex vivo methods with an iron concentration that is 3-fold higher in tumors using MT. CONCLUSIONS: We have developed a method that allows a semi-quantitative evaluation of targeting efficiency in tumors, which could be applied to different T2 contrast agents.