Lluïsa Pérez-García

Spontaneous resolution, whence and whither: from enantiomorphic solids to chiral liquid crystals, monolayers and macro- and supra-molecular polymers and assemblies

One of the great challenges in stereochemistry is the explanation of why some molecules resolve spontaneously while others do not. In this critical review the recent advances in the creation of chiral systems from achiral and racemic compounds in three-, two- and one-dimensional systems are discussed. There are some groups of molecules in some systems that do tend to display conglomerates, which may suggest that there are enantiophobic and enantiophilic molecules whose assembly is guided by the structural and thermodynamic properties of the systems in question.

Gemini Imidazolium Amphiphiles for the Synthesis, Stabilization, and Drug Delivery from Gold Nanoparticles

Gold nanoparticles (AuNPs) are considered useful vehicles for medical therapy and diagnosis. Despite the progress made in this field, there is need to find direct, reliable, and versatile synthetic procedures for their preparation as well as new multifunctional coating agents. In this sense, we have explored the use of imidazolium amphiphiles to prepare new AuNPs designed for anion recognition and transport. Thus, in this work we describe (a) the synthesis, by a phase transfer method, of new gold nanoparticles using gemini-type surfactants as ligands based on imidazolium salts, those ligands acting as transfer agents into organic media and also as nanoparticle stabilizers, (b) the examination of their stability in solution, (c) the chemical and physical characterization of the nanoparticles, using a variety of techniques, including UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), (d) toxicity data concerning both the imidazolium ligands and the imidazolium coated nanoparticles, (e) the assessment of their molecular recognition ability toward molecules of biological interest, such as anions and carboxylate containing model drugs, such as ibuprofen, (f) the study of their toxicity and those of their coating ligands, as well as their ability for cell internalization, and (g) the study of their ability for delivering anionic pharmaceuticals. The structurally governed triple role of those new gemini-type surfactants is responsible for the preparation, remarkable stability, and delivery properties of these functional AuNPs.

Iron oxide nanoparticles functionalized with novel hydrophobic and hydrophilic porphyrins as potential agents for photodynamic therapy

The preparation of novel porphyrin derivatives and their immobilization onto iron oxide nanoparticles to build up suitable nanotools for potential use in photodynamic therapy (PDT) has been explored. To achieve this purpose, a zinc porphyrin derivative, ZnPR-COOH, has been synthesized, characterized at the molecular level and immobilized onto previously synthesized iron oxide nanoparticles covered with oleylamine. The novel nanosystem (ZnPR-IONP) has been thoroughly characterized by a variety of techniques such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, X-ray photoloectron spectroscopy (XPS) and transmission electron microscopy (TEM). In order to probe the capability of the photosensitizer for PDT, the singlet oxygen production of both ZnPR-IONP and the free ligand ZnPR-COOH have been quantified by measuring the decay in absorption of the anthracene derivative 9,10-anthracenedipropionic acid (ADPA), showing an important increase on singlet oxygen production when the porphyrin is incorporated onto the IONP (ZnPR-IONP). On the other hand, the porphyrin derivative PR-TRIS3OH, incorporating several polar groups (TRIS), was synthesized and immobilized with the intention of obtaining water soluble nanosystems (PR-TRIS-IONP). When the singlet oxygen production ability was evaluated, the values obtained were similar to ZnPR-COOH/ZnPR-IONP, again much higher in the case of the nanoparticles PR-TRIS-IONP, with more than a twofold increase. The efficient singlet oxygen production of PR-TRIS-IONP together with their water solubility, points to the great promise that these new nanotools represent for PDT.

Supramolecular gels based on a gemini imidazolium amphiphile as molecular material for drug delivery

A novel physical gel was obtained using a gemini imidazolium-based amphiphilic molecule dissolved in ethanol-water mixtures. The structure of the gel is comprised of intertwining nanofibres with widths of approximately 80 nm. The ethanol/water ratio has an important influence on the gelation process: the gelator is sparingly soluble in water and soluble in ethanol. The gelator is capable of incorporating anionic drugs in its fibrillar network easily; sodium ibuprofenate, indomethacin and the sodium salt of methotrexate were used as model drugs that were incorporated into the quickly forming gels. The characterization of these composite xerogels was made by different microscopy techniques as well as X-ray powder diffraction. The ability of the amphiphile to form a gel is largely maintained in the presence of the different model drugs and the overall morphology of the gels (that present a fibre like structure in all cases with intertwined ribbons) is very similar. Furthermore the in vitro release of the drugs from the gel and the in vivo anti-inflammatory efficacy was studied. The overall results show better release profiles and anti-inflammatory efficacy for indomethacin, and prove the promise of this molecular gel in controlled drug release, in the present case dermatological application.

Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method.

Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then applied to a clinical study with high cardiovascular risk subjects, after the moderate consumption of red wine (RW) or dealcoholized red wine (DRW) for 28 days. Up to 21 resveratrol metabolites, including those formed by gut and microbial metabolism, were identified in 24-h urine samples. Interestingly, after long-term consumption of RW and DRW, resveratrol metabolite concentration significantly increased in urine with no differences between the two interventions, indicating that bioavailability and biotransformation of resveratrol is not affected by the alcoholic matrix of wine. In summary, we established a sensitive analytical assay for the quantification of a wide resveratrol metabolic profile in human urine, also regarding gut microbial-derived metabolites, which may also be applied to blood and tissue samples. The resveratrol metabolic pattern might therefore act as an excellent marker for the efficacy of resveratrol in clinical and epidemiological studies for the study of the beneficial effects of grape product consumption. In this sense, having a more precise concentration value of all the resveratrol metabolites in target tissues would finally lead to a better interpretation of the obtained results.

The self assembly of controllable [2]catenanes

The dynamic and electrochemical properties of two new [2]catenanes, in which bisparaphenylene-34-crown-10 is encircled by a cyclophane incorporating either (i) one bipyridinium and one bis(pyridinium)ethylene unit or (ii) two bis(pyridinium)ethylene units, are investigated in solution.

Highly Conductive Single-Molecule Wires with Controlled Orientation by Coordination of Metalloporphyrins

Porphyrin-based molecular wires are promising candidates for nanoelectronic and photovoltaic devices due to the porphyrin chemical stability and unique optoelectronic properties. An important aim toward exploiting single porphyrin molecules in nanoscale devices is to possess the ability to control the electrical pathways across them. Herein, we demonstrate a method to build single-molecule wires with metalloporphyrins via their central metal ion by chemically modifying both an STM tip and surface electrodes with pyridin-4-yl-methanethiol, a molecule that has strong affinity for coordination with the metal ion of the porphyrin. The new flat configuration resulted in single-molecule junctions of exceedingly high lifetime and of conductance 3 orders of magnitude larger than that obtained previously for similar porphyrin molecules but wired from either end of the porphyrin ring. This work presents a new concept of building highly efficient single-molecule electrical contacts by exploiting metal coordination chemistry.

Hydrogen bonded driven anion binding by dicationic [14]imidazoliophanes

Imidazolium units represent the main structural motifs for the formation of unconventional C–H···Cl– hydrogen bonds which become the noncovalent forces driving the anion interactions exibited by dicationic [14]imidazoliophanes in the solid state, while C–H···O hydrogen bonds with water play a crucial role in governing the conformation of the solid–state aggregates, as well as in solution, wherein NMR studies also reveal the importance of hydrogen bonds in controlling the tendency to anion binding.

Nanocarriers from dicationic bis-imidazolium amphiphiles and their interaction with anionic drugs

Dicationic gemini surfactants based on bis-imidazolium salts with bromide counterions were synthesized and shown to self-assemble into micellar-type structures in aqueous solution. The solubilisation capability of these micelles for anionic drugs (valproate) indicates their great potential as drug nanocarriers. A range of physicochemical techniques including surface tension, fluorescence spectroscopy, small-angle neutron scattering (SANS) and pulsed-gradient spin-echo nuclear magnetic resonance (PGSE-NMR) have been used to determine the nanocarrier (micelle) structure and to quantify the interaction of the drug with the nanocarrier. The insights gained here, structural activity relationships such as hydrophobic dependence of the CMC and drug binding isotherms, will allow for a rational optimization of molecular structure.

Non-classical [14]metaheterophanes containing betaine units. Synthesis, NMR spectroscopy and X-ray crystallography

The N-diphenylmethyl derivative 4 is the immediate precursor of the N-substituted dipolar [14]metaheterophane 3, and allows the convenient synthesis of the unsubstituted macrocycle 5, which can be transformed into the quadrupolar or dipolar heterophanes 1 and 2; the molecular structures of 1 and 2 were confirmed by single-crystal X-ray analysis.