Química Supramolecular amb Jean-Marie Lehn

"La química supramolecular pot ajudar a fer medicaments més eficaços". Amb motiu de les II Jornades Doctorals organitzades el passat juny des del Departament de Química de la UAB, el Premi Nobel de Química de l'any 1987 Jean-Marie Lehn va visitar la nostra universitat per impartir una xerrada sobre el disseny de nanoestructures supramoleculars i les seves aplicacions. Aprofitant aquesta visita, des d'UAB Divulga li vam realitzar una entrevista per saber més coses sobre la química supramolecular, els límits entre la vida i la no-vida i l'impacte de rebre el Premi Nobel.Con motivo de las II Jornadas Doctorales organizadas el pasado junio desde el Departamento de Química de la UAB, el Premio Nobel de Química del año 1987 Jean-Marie Lehn visitó nuestra universidad para impartir una conferencia sobre el diseño de nanoestructuras supramoleculares y sus aplicaciones. Aprovechando esta visita, desde UAB Divulga le realizamos una entrevista para saber más sobre la química supramolecular, los límites entre la vida y la no-vida y el impacto de recibir el Premio Nobel.On the occasion of the II Doctoral Seminars, organised by the UAB Department of Chemistry, Nobel Laureate Jean-Marie Lehn, who received the Nobel Prize in Chemistry 1987, visited our university to give a speech on the design of supramolecular nanostructures and their applications. Taking advantage of his visit, UABDivulga interviewed him to learn more about supramolecular chemistry, the boundaries between life and non-life and the impact of receiving the Nobel Prize

Molecular Biodynamers:Dynamic Covalent Analogues of Biopolymers

Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications. In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of molecular biodynamers as structural or functional biomimetics of biopolymers, including DyNAs, glycodynamers, and dynamic proteoids. We introduce how chemists utilize various reversible reactions to generate molecular biodynamers with specific sequences and well-ordered structures in aqueous medium. We also discuss and list their potential applications in various research fields, such as drug delivery, drug discovery, gene sensing, cancer diagnosis, and treatment

A doubly hermaphroditic chiral crown ether

A single-crystal structure determination on the S-protected form of a chiral 18-crown-6 derivative known to be a selective catalyst for thiolysis reactions of amino acid derivatives has shown the molecule to crystallise in an unsolvated form where the macrocyclic ring has a conformation in which the dipoles of substituent amide units are aligned parallel. The resulting polar entities are linked through NH center dot center dot center dot O H-bonds and weaker interactions which can be considered to result in doubly hermaphroditic links, the whole crystal proving to be polar. The possible consequences of the observed secondary interactions, some being intramolecular, are considered in relation to the mechanism of catalysis by the isolated molecule

Ultra-strong coupling of molecular materials: spectroscopy and dynamics

We report here a study of light–matter strong coupling involving three molecules with very different photo-physical properties. In particular we analyze their emission properties and show that the excitation spectra are very different from the static absorption of the coupled systems. Furthermore we report the emission quantum yields and excited state lifetimes, which are self-consistent. The above results raise a number of fundamental questions that are discussed and these demonstrate the need for further experiments and theoretical studie

Synthetic polyamines stimulate in vitro transcription by T7 RNA polymerase.

The influence of nine synthetic polyamines on in vitro transcription with T7 RNA polymerase has been studied. The compounds used were linear or macrocyclic tetra- and hexaamine, varying in their size, shape and number of protonated groups. Their effect was tested on different types of templates, all presenting the T7 RNA promoter in a double-stranded form followed by sequences encoding short transcripts (25 to 35-mers) either on single- or double-stranded synthetic oligodeoxyribonucleotides. All polyamines used stimulate transcription of both types of templates at levels dependent on their size, shape, protonation degree, and concentration. For each compound, an optimal concentration could be defined; above this concentration, transcription inhibition occurred. Highest stimulation (up to 12-fold) was obtained by the largest cyclic compound called [38]N6C10.comparative studyjournal articleresearch support, non-u.s. gov't1994 Jul 25importe

Stable tumor vessel normalization with pO_{2} increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment

Tumor hypoxia is a characteristic of cancer cell growth and invasion, promoting angiogenesis, which facilitates metastasis. Oxygen delivery remains impaired because tumor vessels are anarchic and leaky, contributing to tumor cell dissemination. Counteracting hypoxia by normalizing tumor vessels in order to improve drug and radio therapy efficacy and avoid cancer stem-like cell selection is a highly challenging issue. We show here that inositol trispyrophosphate (ITPP) treatment stably increases oxygen tension and blood flow in melanoma and breast cancer syngeneic models. It suppresses hypoxia-inducible factors (HIFs) and proangiogenic/glycolysis genes and proteins cascade. It selectively activates the tumor suppressor phosphatase and tensin homolog (PTEN) in vitro and in vivo at the endothelial cell (EC) level thus inhibiting PI3K and reducing tumor AKT phosphorylation. These mechanisms normalize tumor vessels by EC reorganization, maturation, pericytes attraction, and lowering progenitor cells recruitment in the tumor. It strongly reduces vascular leakage, tumor growth, drug resistance, and metastasis. ITPP treatment avoids cancer stem-like cell selection, multidrug resistance (MDR) activation and efficiently enhances chemotherapeutic drugs activity. These data show that counteracting tumor hypoxia by stably restoring healthy vasculature is achieved by ITPP treatment, which opens new therapeutic options overcoming hypoxia-related limitations of antiangiogenesis-restricted therapies. By achieving long-term vessels normalization, ITPP should provide the adjuvant treatment required in order to overcome the subtle definition of therapeutic windows for in vivo treatments aimed by the current strategies against angiogenesis-dependent tumors