Ana Gimeno

Competitive Gold‐Activation Modes in Terminal Alkynes: An Experimental and Mechanistic Study

The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross-over experiments, several σ-gold, σ,π-gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X-ray diffraction, or MALDI spectrometry. The ligand control in the simultaneous or alternative π- and σ,π-activation modes is also supported by deuterium-labeling experiments.

NHC-stabilized gold(I) complexes: suitable catalysts for 6-exo-dig heterocyclization of 1-(o-ethynylaryl)ureas.

3-Substituted 1-(o-ethynylaryl)ureas 1 selectively undergo either 6-exo-dig or 5-endo-dig cyclization (to give 4-methylene-3,4-quinazolin-2-ones 2 or indoles 3, respectively) depending on the choice of the metal, ligand, and reaction conditions. The best results (up to 96% yield) in the preparation of the hydroamination products 2 are achieved with the highly bulky NHC-stabilized cationic gold(I) complex [Au(IPr)](+). Conversely, ureas bearing an internal alkyne lead to the 5-endo-dig cyclization mode regardless of the gold(I) complex employed. Whereas the nature of the substituent at N-3 does not have any influence on the regiochemistry observed, it does, in some cases, affect the efficiency of these transformations.

Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with α,β-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes

α,β-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with a suitable gold catalyst. The method, which represents the first application of N,N-dialkyl hydrazones in gold catalysis, is compatible with a wide variety of substituents at the alkenyl moiety of the hydrazone component, proceeds with excellent levels of regio- and diastereoselectivity, and provides densely substituted cyclobutanes with good to excellent yields.

Retinal Vein Occlusion: Current Treatment

Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management.

Insights on the interaction between transthyretin and Aβ in solution. A saturation transfer difference (STD) NMR analysis of the role of iododiflunisal

Several strategies against Alzheimer disease (AD) are directed to target Aβ-peptides. The ability of transthyretin (TTR) to bind Aβ-peptides and the positive effect exerted by some TTR stabilizers for modulating the TTR-Aβ interaction have been previously studied. Herein, key structural features of the interaction between TTR and the Aβ(12-28) peptide (3), the essential recognition element of Aβ, have been unravelled by STD-NMR spectroscopy methods in solution. Molecular aspects related to the role of the TTR stabilizer iododiflunisal (IDIF, 5) on the TTR-Aβ complex have been also examined. The NMR results, assisted by molecular modeling protocols, have provided a structural model for the TTR-Aβ interaction, as well as for the ternary complex formed in the presence of IDIF. This basic structural information could be relevant for providing light on the mechanisms involved in the ameliorating effects of AD symptoms observed in AD/TTR± animal models after IDIF treatment and eventually for designing new molecules toward AD therapeutic drugs.

Mechanistic Insight into the Binding of Multivalent Pyrrolidines to α‐Mannosidases

Novel pyrrolidine-based multivalent iminosugars, synthesized by a CuAAC approach, have shown remarkable multivalent effects towards jack bean α-mannosidase and a Golgi α-mannosidase from Drosophila melanogaster, as well as a good selectivity with respect to a lysosomal α-mannosidase, which is important for anticancer applications. STD NMR and molecular modeling studies supported a multivalent mechanism with specific interactions of the bioactive iminosugars with Jack bean α-mannosidase. TEM studies suggested a binding mode that involves the formation of aggregates, which result from the intermolecular cross-linked network of interactions between the multivalent inhibitors and two or more dimers of JBMan heterodimeric subunits.

Glycans in Infectious Diseases. A Molecular Recognition Perspective

BACKGROUND From the simplest bacteria to the highest complex mammals, including humans, every single cell is covered by a dense coat of glycans. Glycans are involved in almost every biological process that takes place in our body, playing a central role in the communication between cells and their environment. Glycans are also involved in infectious diseases, which arise from the specific interaction between glycans of the pathogen cell coat and specific receptors on the host cell or vice versa. OBJECTIVE The understanding of the mechanisms governing these specific carbohydrateprotein interactions, at atomic and molecular levels, is crucial to develop new drugs able to block the infection and to avoid the disease. METHODS Recent advances in biophysical techniques allow for a complete picture of the hostpathogen infection event, unveiling the key aspects of the molecular interaction and, thus, providing an opportunity to interfere with it. CONCLUSION In this general review, we discuss some recent contributions, providing a summary of what we consider the most innovative and inspiring research lines to the field.

Environmental Effects Determine the Structure of Potential β-Amino Acid Based Foldamers

This work shows that hybrid peptides formed by alternating trans-2-aminocyclopentanecarboxylic acid (trans-ACPC) and trans-2-aminocyclohexanecarboxylic acid (trans-ACHC) do not fold in the solvents typically used in the study of their homo-oligomers. Only when the peptides are assayed in SDS micelles are the predicted helical structures obtained. This indicates that the environment could play an equally important role (as the backbone stereochemistry) in determining their fold, possibly by providing a sequestered environment.

Recent advances in the application of NMR methods to uncover the conformation and recognition features of glycans

This chapter is dedicated to the presentation of different examples of the application of solution NMR to the study of conformation, dynamics of sugar molecules (oligo and polysaccharides, glycopeptides and glycomimetics) and to the investigation of glycan-related molecular recognition events. Selected examples since 2012 are presented depending on the chemical nature of the sugar molecule, on the environment (free or bound) and on the nature of the receptor.

Record Attendance at the 10th EURETINA Congress in Paris

NA/ESCRS Symposia and one Clinical Research Symposium anchored the meeting. Other new introductions for 2010 were the French-British and Eire Symposium (CFSR-BEAVRS) and the ARVO symposium on anti-VEGF therapy beyond AMD. The programme also included popular scientific contributions such as the Amsterdam Retina Debate, Eurolam, the Fan Club and the French-Israeli (AFIV SOFI) Symposium. The EURETINA Lecture 2010 was given by Prof. Anthony Moore, Moorfields Eye Hospital, London, who discussed the current state of research into retinovascular disorders of childhood. Dr. Martine Jager was the recipient of the Kreissig Award and made the presentation entitled ‘Immunology in uveal melanoma: friend or foe?’ Not only did the 10th Congress see an increase in attendance, but abstract submission numbers also showed a dramatic increase from previous years. Free paper submissions increased by 30% from the Nice 2009 Congress, while video submissions doubled since last year. While stressing that the organizing committee was extremely gratified in the record attendance and progress displayed in Paris this year, Bill Aylward said that the goal of EURETINA in the years ahead would be to continue to make progress and raise standards: ‘We don’t just want to be big – we also want to be the best.’ The 11th EURETINA Congress will take place in the Queen Elizabeth II Centre in London from the 26th to the 29th May 2011. A record number of medical and surgical retina specialists from all over the world converged on Paris this month to attend the 10th EURETINA Congress, which took place from the 2nd to the 5th September in the Palais des Congrès, Porte Maillot. A total of 2,700 delegates attended the Congress, making it not only the largest EURETINA meeting in the history of the Society, but also establishing it as the largest retina meeting ever convened. The 2010 Congress also saw EURETINA partner with the European Society of Cataract and Refractive Surgeons (ESCRS), drawing a total number of almost 9,000 ophthalmologists to the Palais des Congrès over a 6-day period. Addressing the audience at the official opening ceremony, EURETINA President Bill Aylward welcomed delegates to Paris for what he expected would prove to be the most stimulating and rewarding congress to date: ‘It is truly a great pleasure to welcome all of you to this wonderful city for the 10th EURETINA Congress. We are particularly excited as this is the first time that we have joined forces with the ESCRS for this joint meeting. The early signs of this collaboration are very good.’ At the core of the EURETINA programme were 13 main sessions, comprising presentations from invited speakers, all of whom are leaders in their field. There were also a total of 32 Instructional Courses and Surgical Skills Courses, the former including the daylong Retinal Detachment and Uveitis Courses. Two combined EURETIPublished online: February 3, 2011 Ophthalmologica