Reseña de libro: Emergencias de lo poshumano. Desafíos arquitectónicos y pedagógicos desde un margen disciplinar. Universidad de Alicante. ISBN: 978-84-9717-769-6.
Slightly attractive: The attractive and anisotropic nature of the Cl···Cl interaction in C₆Cl₆ is experimentally demonstrated from an expansion of the electron density ρ(r) around the chlorine ...nuclei. The interaction is explained in a model in which there is a bonding attraction involving electron-deficient (see picture, blue) and electron-rich (red) regions of adjacent Cl atoms.
Activation of a deep electron‐deficient area on chalcogen atoms (Ch=Se, Te) is demonstrated in alkynyl chalcogen derivatives, in the prolongation of the (C≡)C−Ch bond. The solid‐state structures of ...1,4‐bis(methylselenoethynyl)perfluorobenzene (1Se) show the formation of recurrent chalcogen‐bonded (ChB) motifs. Association of 1Se and the tellurium analogue 1Te with 4,4′‐bipyridine and with the stronger Lewis base 1,4‐di(4‐pyridyl)piperazine gives 1:1 co‐crystals with 1D extended structures linked by short and directional ChB interactions, comparable to those observed with the corresponding halogen bond (XB) donor, 1,4‐bis(iodoethynyl)‐perfluorobenzene. This “alkynyl” approach for chalcogen activation provides the crystal‐engineering community with efficient, and neutral ChB donors for the elaboration of supramolecular 1D (and potentially 2D or 3D) architectures, with a degree of strength and predictability comparable to that of halogen bonding in iodoacetylene derivatives.
Chalcogen bond activation by alkynyl substitution is realized in bis(selenomethyl‐alkynyl) and bis(telluromethyl‐alkynyl) derivatives, as evidenced in co‐crystals with ditopic Lewis bases, such as 4,4′‐bipyridine and 1,4‐di(pyridin‐4‐yl)piperazine, with Te⋅⋅⋅N interactions as short as I⋅⋅⋅N halogen bonds with analogous iodo‐alkynyl derivatives.
Chalcogen bonding has been investigated in terms of the electron density distribution ρ(r) around chalcogen atoms. The evolution of ρ(r) along the series of chalcogen atoms is shown based on ab ...initio calculations on chalcogenophthalic anhydrides C8O2H4Chal (Chal = O, S, Se, and Te), where the Chal atom is in its sp 3 hybridization. From a detailed analysis of the experimental and theoretical electron density and the L(r) = −∇2ρ(r) function in the crystal phase of C8O2H4Se, we characterize directionality and strength of chalcogen bonding (Se···O and Se···Se) and hydrogen bonding (Se···H) interactions. In addition, several isolated dimers and a trimer of C8O2H4Se have been also studied at the X-ray geometry in order to compare interaction energies with those estimated from the measured electron density. Similarly to halogen atoms in halogen bonding interactions, the anisotropic distribution of ρ(r) around the Chal atoms was found to be at the origin of chalcogen bonding. Therefore, the concepts, developed earlier for halogen bonding, are extended here to chalcogen bonding interactions. From the results of this work, the L(r) function proves to be more precise than the σ-hole concept to identify electrophilic sites of Se-atoms in sp 3 hybridization.
The ability of alkylseleno/alkyltelluroacetylenes such as bis(selenomethylethynyl)-perfluorobenzene (4F-Se) to act as a ditopic chalcogen bond (ChB) donor in co-crystals with ditopic Lewis bases such ...as 4,4′-bipyridine is extended here to the octafluorobiphenylene analog, 4,4′-bis(selenomethylethynyl)-perfluorobiphenyl (8F-Se), with the more electron-rich 4,4′-bipyridylethane (bpe), showing in the 1:1 (8F-Se)•(bpe) co-crystal a shorter and more linear C−Se•••N ChB interaction than in (4F-Se)•(bpe), with Se•••N distances down to 2.958(2) Å at 150 K, i.e., a reduction ratio of 0.85 vs. the van der Waals contact distance.
Uveal melanoma is a rare neoplasm with poor prognosis in the metastatic setting. Unlike cutaneous melanoma, treatment with kinase inhibitors or immune checkpoint inhibitors is not effective. ...Glycoprotein 100 (Gp-100) is a protein highly expressed in melanocytes and melanoma that has recently been effectively targeted by tebentafusp, a first-in-class bispecific protein of the immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs) family. Tebentafusp targets tumor cells that express a peptide of Gp-100 presented by HLA*A0201, creating an immune synapse that kills targeted tumor cells. Recently, a randomized phase III trial reported an overall survival benefit for tebentafusp in patients with untreated metastatic uveal melanoma. The aim of this comprehensive review is to summarize evidence of Gp-100 as a therapeutic target in melanoma, and the preclinical and clinical development of tebentafusp as a novel therapeutic strategy for patients with uveal melanoma.
Professor Dunitz questions the usefulness of ascribing crystalline structural stability to individual atom-atom intermolecular interactions viewed as bonding (hence stabilizing) whenever linked by a ...bond path. An alternative view is expressed in the present essay that articulates the validity and usefulness of the bond path concept in a crystallographic and crystal engineering context.
Abstract Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain ...unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells.
Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Five-month-old ...B6.MRL-Faslpr/J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelve-week-old MRL/MpJ-Faslpr/J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.
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