Reactivity of Glutaconamides Within [2]Rotaxanes: Mechanical Bond Controlled Chemoselective Synthesis of Highly Reactive α-Ketoamides and their Light-Triggered Cyclization

Glutaconamide-based [2]rotaxanes are efficiently oxidized to the respective interlocked α-ketoamides, whereas their non-interlocked threads afford hydroxycyclohexene tetraamides under similar reaction conditions. These results showcase the mechanically interlocking of highly reactive substrates as a powerful tool for controlling their chemical behavior. Inside the macrocycle and under irradiation with light, the α-ketoamide threads convert, in a divergent manner, into the corresponding interlocked hydroxy-β-lactams or oxazolidinones by two modes of Norrish/Yang type-II intramolecular cyclizations, processes that are efficiently chemocontrolled by the mechanical bond

Effects on Rotational Dynamics of Azo and Hydrazodicarboxamide-Based Rotaxanes

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This manuscript version is made available under the CC-BY 4.0 license https://creativecommons.org/licenses/by/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Molecules. To access the final edited and published work see https://doi.org/10.3390/molecules22071078The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent interactions between the interlocked components have an important effect on the dynamic behavior of these compounds. Having this in mind, the chemical interconversion between the azo and hydrazo forms of the [2]rotaxane was investigated to provide a chemically-driven interlocked system enable to switch its circumrotation rate as a function of the oxidation level of the binding site. Different structural modifications were carried out to further functionalize the nitrogen of the pyridine rings, including oxidation, alkylation or protonation reactions, affording interlocked azo-derivatives whose rotation dynamics were also analyzed

Mechanically Planar-to-Point Chirality Transmission in [2]Rotaxanes

© 2024. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the published version of a published work that appeared in final form in Journal of the American Chemical Society (JACS). To access the final work, see DOI: https://doi.org/10.1021/jacs.3c11611Herein we describe an effective transmission of chirality, from mechanically planar chirality to point chirality, in hydrogen-bonded [2]rotaxanes. A highly selective mono-N-methylation of one (out of four) amide N atom at the macrocyclic counterpart of starting achiral rotaxanes generates mechanically planar chirality. Followed by chiral resolution, both enantiomers were subjected to a base-promoted intramolecular cyclization, where their interlocked threads were transformed into new lactam moieties. As a matter of fact, the mechanically planar chiral information was effectively transferred to the resulting stereocenters (covalent chirality) of the newly formed heterocycles. Upon removing the entwined macrocycle, the final lactams were obtained with high enantiopurity

Ring-to-Thread Chirality Transfer in [2]Rotaxanes for the Synthesis of Enantioenriched Lactams

© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This manuscript version is made available under the CC-BY-NC 4.0 license https://creativecommons.org/licenses/by-nc/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Angewandte Chemie International Edition. To access the final edited and published work see https://doi.org/10.1002/anie.202209904The synthesis of chiral mechanically interlocked molecules has attracted a lot of attention in the last few years, with applications in different fields, such as asymmetric catalysis or sensing. Herein we describe the synthesis of orientational mechanostereoisomers, which include a benzylic amide macrocycle with a stereogenic center, and nonsymmetric N-(arylmethyl)fumaramides as the axis. The base-promoted cyclization of the initial fumaramide thread allows enantioenriched value-added compounds, such as lactams of different ring sizes and amino acids, to be obtained. The chiral information is effectively transmitted across the mechanical bond from the encircling ring to the interlocked lactam. High levels of enantioselectivity and full control of the regioselectivity of the final cyclic compounds are attained

Mechanically interlocked molecules in metal–organic frameworks

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Society Reviews, copyright © Royal Society of Chemistry after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.rsc.org/en/content/articlelanding/2022/CS/D2CS00167EMechanically interlocked molecules (MIMs) have great potential in the development of molecular machinery due to their intercomponent dynamics. The incorporation of these molecules in a condensed phase makes it possible to take advantage of the control of the motion of the components at the macroscopic level. Metal–organic frameworks (MOFs) are postulated as ideal supports for intertwined molecules. This review covers the chemistry of the mechanical bond incorporated into metal–organic frameworks from the seminal studies to the latest published advances. We first describe some fundamental concepts of MIMs and MOFs. Next, we summarize the advances in the incorporation of rotaxanes and catenanes inside MOF matrices. Finally, we conclude by showing the study of the rotaxane dynamics in MOFs and the operation of some stimuli-responsive MIMs within MOFs. In addition to emphasising some selected examples, we offer a critical opinion on the state of the art of this research field, remarking the key points on which the future of these systems should be focused

Inflammatory biomarkers in Alzheimer's disease plasma.

INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. RESULTS: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). DISCUSSION: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Mediated alkaline flow batteries: from fundamentals to application

Alkaline flow batteries are attracting increasing attention for stationary energy storage. Very promising candidates have been proposed as active species for the negative compartment, while potassium ferrocyanide (K4Fe(CN)6) has been the only choice for the positive one. The energy density of this family of batteries is limited by the low solubility of K4Fe(CN)6 in alkaline media. Herein, we propose a general strategy to increase the energy density of this family of alkaline flow batteries by storing energy in commercial Ni(OH)2 electrodes confined in the positive reservoir. In this way, K4Fe(CN)6 dissolved in the electrolyte acts not only as electroactive species but also as charge carrier between current collector and solid Ni(OH)2 particles located in an external reservoir. A storage capacities of 29 Ah L–1 for the positive compartment is demonstrated. The concept is implemented in three systems, Zn–K4Fe(CN)6, anthraquinone–K4Fe(CN)6, and phenazine–K4Fe(CN)6 alkaline flow battery, showing the versatility of the strategy. Challenges and future directions to exceed the 16 Wh Ltotal–1 demonstrated in this work are discussed

Enantioselective Formation of 2-Azetidinones by Ring-Assisted Cyclization of Interlocked N-(alpha-Methyl)benzyl Fumaramides

The synthesis of optically active interlocked and non-interlocked 2-azetidinones by intramolecular cyclization of N-(alpha-methyl)benzyl fumaramide [2]rotaxanes is described. Two different strategies of asymmetric induction were tested in which the chiral group was located either proximal or distal to the reacting center of the thread. During these experiments, an interesting equilibration process inside the macrocyclic void occurred, thus leading to the cyclization through the (alpha-methyl)benzyl carbon atom and giving rise to beta-lactams, with a quaternary carbon atom, in an enantio- and diastereocontrolled manner. This cyclization also proceeds in kinetically stable chiral pseudo[2]rotaxanes, thus allowing further de threading to provide enantioenriched 3,4-disubstituted trans-2-azetidinones. The stereochemical outcomes of the cyclization inside and outside the macrocycle demonstrated noticeabl