Belén Vaz

Hollow‐Shelled Nanoreactors Endowed with High Catalytic Activity

Hollow-shelled nanoreactors have emerged as efficient structures to maximize the potential of nanoparticles in the field of catalysis. In this Concept article, we underline the importance of both the morphology of the active nanoparticles as well as the composition and porosity of the shell for the catalytic performance of the overall nanocomposite. Different configurations are discussed, with a focus on preparative methods and applications in organic synthesis. Perspectives on future designs that may offer new opportunities to improve the selectivity of the catalyzed transformations and add additional features are also addressed, in order to illustrate the potential of these unique nanostructures.

Functions, therapeutic applications, and synthesis of retinoids and carotenoids.

Carotenoids Rosana Álvarez,† Beleń Vaz,† Hinrich Gronemeyer,‡ and Ángel R. de Lera*,† †Departamento de Química Orgańica, Centro de Investigacioń Biomed́ica (CINBIO), and Instituto de Investigacioń Biomed́ica de Vigo (IBIV), Universidade de Vigo, 36310 Vigo, Spain ‡Department of Functional Genomics and Cancer, Institut de Geńet́ique et de Biologie Molećulaire et Cellulaire (IGBMC)/CNRS/INSERM/ULP, BP 10142, 67404 Illkirch Cedex, C. U. de Strasbourg, France

Macroscale Plasmonic Substrates for Highly Sensitive Surface-Enhanced Raman Scattering

The fabrication of macroscale optical materials from plasmonic nanoscale building blocks is the focus of much current multidisciplinary research. In these macromaterials, the nanoscale properties are preserved, and new (metamaterial) properties are generated as a direct result of the interaction of their ordered constituents.1 These macroscale plasmonic assemblies have found application in a myriad of fields, including nanophotonics, nonlinear optics, and optical sensing.2 Owing to their specific requirements in terms of size and shape, their fabrication is not trivial and was until recently restricted to the use of lithographic techniques, especially those based on electron- or ion-beam patterning.3 However, these techniques are not only expensive, time-consuming, and demanding but are also restricted to small simple and solid geometries, which are good for proof of concepts but less suitable for real-life applications. Approaches based on colloidal chemistry are gaining relevance as an alternative. During the past few years, several examples of the fabrication of organized particles have been reported, including the preparation of complex colloidal particles4 and the use of preformed colloids to create large crystalline organized entities known as supercrystals.5 The latter approach provides optical platforms with unprecedented plasmonic properties that can be exploited for the design of cheap ultrasensitive and ultrafast sensors with surface-enhanced Raman scattering (SERS)6 spectroscopy as the transducer.

Nanoreactors for simultaneous remote thermal activation and optical monitoring of chemical reactions.

We report herein the design of plasmonic hollow nanoreactors capable of concentrating light at the nanometer scale for the simultaneous performance and optical monitoring of thermally activated reactions. These reactors feature the encapsulation of plasmonic nanoparticles on the inner walls of a mesoporous silica capsule. A Diels-Alder cycloaddition reaction was carried out in the inner cavities of these nanoreactors to evidence their efficacy. Thus, it is demonstrated that reactions can be accomplished in a confined volume without alteration of the temperature of the bulk solvent while allowing real-time monitoring of the reaction progress.

Suzuki cross-coupling of meso-dibromoporphyrins for the synthesis of functionalized A2B2 porphyrins

Abstract C 2 -Symmetric meso -porphyrins have been prepared in high yields by a palladium-catalyzed cross-coupling reaction involving dibromoporphyrins and arylboronic acids.

Palladium Nanoparticle-Loaded Cellulose Paper: A Highly Efficient, Robust, and Recyclable Self-Assembled Composite Catalytic System

We present a novel strategy based on the immobilization of palladium nanoparticles (Pd NPs) on filter paper for development of a catalytic system with high efficiency and recyclability. Oleylamine-capped Pd nanoparticles, dispersed in an organic solvent, strongly adsorb on cellulose filter paper, which shows a great ability to wick fluids due to its microfiber structure. Strong van der Waals forces and hydrophobic interactions between the particles and the substrate lead to nanoparticle immobilization, with no desorption upon further immersion in any solvent. The prepared Pd NP-loaded paper substrates were tested for several model reactions such as the oxidative homocoupling of arylboronic acids, the Suzuki cross-coupling reaction, and nitro-to-amine reduction, and they display efficient catalytic activity and excellent recyclability and reusability. This approach of using NP-loaded paper substrates as reusable catalysts is expected to open doors for new types of catalytic support for practical applications.

9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice

The retinoid X receptors (RXRs) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors, thereby controlling a variety of (patho)-physiological processes. Although synthetic RXR ligands are developed for the treatment of various diseases, endogenous ligand(s) for these receptors have not been conclusively identified. We show here that mice lacking cellular retinol binding protein (Rbp1-/-) display memory deficits reflecting compromised RXR signaling. Using HPLC-MS and chemical synthesis we identified in Rbp1-/- mice reduced levels of 9-cis-13,14-dihydroretinoic acid (9CDHRA), which acts as an RXR ligand since it binds and transactivates RXR in various assays. 9CDHRA rescues the Rbp1-/- phenotype similarly to a synthetic RXR ligand and displays similar transcriptional activity in cultured human dendritic cells. High endogenous levels of 9CDHRA in mice indicate physiological relevance of these data and that 9CDHRA acts as an endogenous RXR ligand.

Total Synthesis of Enantiopure Pyrrhoxanthin: Alternative Methods for the Stereoselective Preparation of 4‐Alkylidenebutenolides

A new stereocontrolled total synthesis of the configurationally labile C37 -norcarotenoid pyrrhoxanthin in enantiopure form has been completed. A highly stereoselective Horner-Wadsworth-Emmons (HWE) condensation of a C17-allylphosphonate and a C20-aldehyde was used as the last conjunctive step. Both a Sonogashira reaction to form the C17-phosphonate and the final HWE condensation proved to be compatible with the sensitive C7-C10 enyne E configuration. Regioselective (5-exo-dig) silver-promoted lactonization reactions of three alternative pent-2-en-4-ynoic acid precursors with increased complexity, including a fully functionalized C20-fragment, were explored for the preparation of the γ-alkylidenebutenolide fragment. This survey extends the existing methodologies for the preparation of oxygen-containing carotenoids (xanthophylls) and streamlines the synthesis of additional members of the C37-norcarotenoid butenolide family of natural products.

Advances in drug design with RXR modulators.

Introduction: Retinoid X receptors (subtypes RXRα or NR2B1, RXRβ or NR2B2 and RXRγ or NR2B3, which originate from three distinct genes) are promiscuous partners with heterodimeric associations to other members of the Nuclear Receptor (NR) superfamily. Some of the heterodimers are “permissive” and transcriptionally active in the presence of either an RXR ligand (“rexinoid”) or a NR partner ligand, whereas others are “non-permissive” and unresponsive to rexinoids alone. In rodent models, rexinoids and partner agonists (mainly PPARγ, LXR, FXR) produce beneficial effects on insulin sensitization, diabetes and obesity, but secondary effects have also been noted, such as a raise in tryglyceride levels, supression of the thyroid hormone axis and induction of hepatomegaly. Areas covered: The authors review recent advances in rexinoid design, including further optimization of known scaffolds, and the discovery of novel RXR modulators by virtual ligand screening or from bioactive natural products. The understanding of rexinoid functions in permissive and non-permissive heterodimers is firmly based on structural knowledge. By strenghtening or disrupting the interaction surface with coregulators rexinoids exert agonist or (partial) antagonist activities. The activity state of the heterodimer can also be fine-tuned by the cellular context and the nature of coregulators. Expert opinion: The synthetic chemistry toolbox has provided a panel of agonists, partial (ant)agonists and/or heterodimer-selective rexinoids starting from existing, naturally occurring or serendipitously discovered scaffolds. These compounds have an unexplored therapeutic potential that might overcome some of the current limitations of rexinoids in therapy, such as hypertriglyceridemia.

Mechanistic and Sterochemical Insights on the Pt-Catalyzed Rearrangement of Oxiranylpropargylic Esters to Cyclopentenones

A mechanism for the rearrangement of oxiranylpropargylic esters to cyclopentenones catalyzed by PtCl(2) is proposed based on DFT calculations (M06/6-31++G(d,p)). Although the basic steps are coincidental with those proposed by Sarpong et al., who characterized a 2H-pyran as intermediate, calculations have revealed other intricate details of this complex rearrangement. The 2H-pyran is proposed to result from the ring-opening of a bicyclic oxonium ion that follows the nucleophilic capture by the epoxide of a platinum carbene generated by an initial Pt-mediated 1,2-propargylic rearrangement. The key steps in the evolution of this system are the electrocyclic ring-opening of the 2H-pyran to a α-methoxycarbonyl dienone and an iso-Nazarov ring closure. Prior to those, changes in hapticity and in the conformation of the dienone are required in order to produce the helical conformation needed to generate a single diastereomer of the cyclopentenone product obtained experimentally. The metal is needed well beyond the first step of the mechanism, and both electrocyclic reactions are favored by coordination to the metal when compared to their uncomplexed counterparts. Moreover, we have experimentally demonstrated that the rearrangement is stereoconvergent, a feature that is traced back to the initial configuration of the epoxide, which determines the somewhat counterthermodynamic placement of the metal syn to the methyl group of the stereogenic center in the 2H-pyran intermediate. Finally, starting from enantiopure oxiranylpropargylic ester 13, a racemate of cyclopentenone (R*,S*)-16 was obtained. Thus, the sequence does not proceed with memory of chirality, and the absolute stereochemical information is already lost at the stage of the 2H-pyran 14.