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Organic Chemistry, High energy, Organic chemist, Intellectual development, Spin chemistry, Physical organic chemistry, History of science, Photochemistry, Chemistry, Supramolecular chemistry, and Electronic spin

This Perspective presents a review and survey of the science and philosophy of my research career over the past five decades at Columbia as a physical organic chemist and photochemist. I explore the role of paradigms, structure, and geometric thinking in my own cognitive and intellectual development. The Perspective describes my investigations of high energy content molecules in electronically excited states and the development of electronic spin and supramolecular photochemistry chemistry. Current research dealing with the nuclear spin chemistry of H2 incarcerated in buckyballs is illustrated. In the second part of this Perspective, I recount a personal role of the philosophy and history of science and the scientific communities’ use of paradigms in their every day research and intellectual activities. Examples are given of the crucial role of geometry and structure in the rapid development of organic chemistry and physical organic chemistry over the past century.

Library and Information Sciences, Computer Science Applications, General Chemical Engineering, General Chemistry, Computational chemistry, Combinatorial Chemistry Techniques, Combinatorial chemistry, Medicinal chemistry, and Drug discovery

As part of a large medicinal chemistry program, we wish to develop novel selective estrogen receptor modulators (SERMs) as potential breast cancer treatments using a combination of experimental and computational approaches. However, one of the remaining difficulties nowadays is to fully integrate computational (i.e., virtual, theoretical) and medicinal (i.e., experimental, intuitive) chemistry to take advantage of the full potential of both. For this purpose, we have developed a Web-based platform, Forecaster, and a number of programs (e.g., Prepare, React, Select) with the aim of combining computational chemistry and medicinal chemistry expertise to facilitate drug discovery and development and more specifically to integrate synthesis into computer-aided drug design. In our quest for potent SERMs, this platform was used to build virtual combinatorial libraries, filter and extract a highly diverse library from the NCI database, and dock them to the estrogen receptor (ER), with all of these steps being ful...

Physical and Theoretical Chemistry, General Physics and Astronomy, General Chemistry, Chemical kinetics, Chemical reaction, Photochemistry, Standard enthalpy of formation, Chemical nomenclature, Atmospheric chemistry, Kinetic energy, Chemistry, Experimental data, and Quantum yield

This paper updates and extends part of the previous data base of critical evaluations of the kinetics and photochemistry of gas-phase chemical reactions of neutral species involved in atmospheric chemistry [J. Phys. Chem. Ref. Data 9, 295 (1980); 11, 327 (1982); 13, 1259 (1984); 18, 881 (1989); 21, 1125 (1992); 26, 521 (1997); 26, 1329 (1997)]. The present evaluation is limited to the organic family of atmospherically important reactions. The work has been carried out by the authors under the auspices of the IUPAC Subcommittee on Gas Phase Kinetic Data Evaluation for Atmospheric Chemistry. Data sheets have been prepared for 171 thermal and photochemical reactions, containing summaries of the available experimental data with notes giving details of the experimental procedures. For each thermal reaction, a preferred value of the rate coefficient at 298 K is given together with a temperature dependence where possible. The selection of the preferred value is discussed and estimates of the accuracies of the rate coefficients and temperature coefficients have been made for each reaction. For each photochemical reaction the data sheets list the preferred values of the photoabsorption cross sections and the quantum yields of the photochemical reactions together with comments on how they were selected. The data sheets are intended to provide the basic physical chemical data needed as input for calculations which model atmospheric chemistry. A table summarizing the preferred rate data is provided, together with an Appendix listing the available values of enthalpies of formation of the reactant and product species.

General Chemistry, Catalysis, Organic Chemistry, Dioxomolybdenum, N-heterocycles, Nitroaromatics, Photophysical properties, Reuse of waste, Química orgánica, Chemistry, Organic, Full Paper, Full Papers, Hot Paper, dioxomolybdenum, nitroaromatics, photophysical properties, and reuse of waste

A catalytic domino reduction–imine formation–intramolecular cyclization–oxidation for the general synthesis of a wide variety of biologically relevant N‐polyheterocycles, such as quinoxaline‐ and quinoline‐fused derivatives, and phenanthridines, is reported. A simple, easily available, and environmentally friendly dioxomolybdenum(VI) complex has proven to be a highly efficient and versatile catalyst for transforming a broad range of starting nitroarenes involving several redox processes. Not only is this a sustainable, step‐economical as well as air‐ and moisture‐tolerant method, but also it is worth highlighting that the waste byproduct generated in the first step of the sequence is recycled and incorporated in the final target molecule, improving the overall synthetic efficiency. Moreover, selected indoloquinoxalines have been photophysically characterized in cyclohexane and toluene with exceptional fluorescence quantum yields above 0.7 for the alkyl derivatives.
A catalytic domino reduction / imine formation / intramolecular cyclization / oxidation allows the synthesis of a wide variety of biologically relevant N‐polyheterocycles. The reported process employs an inexpensive and nontoxic dioxomolybdenum(VI) complex as catalyst, easily available nitroarenes as starting materials and different glycols as reducing agents with reuse of the waste reduction carbonyl byproduct, which is embodied into the final compounds.

Article, Sulfides, Alcohols, Column chromatography, Cyclization, Propargyls, Química orgánica, Chemistry, Organic, and Organic Chemistry

This work describes the 6-endo-dig cyclization of Saryl propargyl sulfides to afford 2H-thiochromenes. The substitution at the propargylic position plays a crucial role in allowing intramolecular silver-catalyzed alkyne hydroarylation and Niodosuccinimide-promoted iodoarylation. Additionally, a PTSAcatalyzed thiolation reaction of propargylic alcohols was developed to synthesize the required tertiary S-aryl propargyl ethers. The applicability of merging these two methods is demonstrated by synthesizing the retinoic acid receptor antagonist AGN194310.
Junta de Castilla y León and FEDER (BU291P18 and BU049P20) and Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P) for financial support. The project leading to these results has received funding from “la Caixa” Foundation, under Agreement LCF/PR/PR18/51130007> (CAIXA-UBU001). N.V., F.M.-L., and S.S.-P. thank Junta de Castilla y León and FSE and FEDER for predoctoral (N.V. and F.M.-L.) and postdoctoral (S.S.-P.) contracts, respectively.

General Chemical Engineering, General Chemistry, Química orgánica, and Chemistry, Organic

Thioamide groups represent useful hydrogen-bonding motifs for the development of active transmembrane anion transporters. Using a 1,8-di(thioamido)carbazole scaffold the superior performance of thioamides compared with the parent amides has been demonstrated.
Polish National Science Centre for grant OPUS (2011/01/B/ST5/03900) and Consejer´ıa de Educaci´on de la Junta de Castilla y Le´on (project BU067P20)

Organic Chemistry, Physical and Theoretical Chemistry, Chemistry, Organic chemistry, Amorfrutin C, Science & Technology, Physical Sciences, Chemistry, Organic, Aromatization, Biomimetic synthesis, Cyclization, Ketenes, Natural products, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

Amorfrutin C, a C-5 prenyl amorfrutin, its allyl analog and an amorfrutin C-5 aldehyde have been synthesized using a biomimetic strategy from non-aromatic precursors. In this approach, a dioxinone derived β,δ-diketo ester underwent a decarboxylative Pd(0) catalyzed prenyl migration to give a β,δ-diketo dioxinone, which readily aromatized giving the amorfrutin core. The introduction of prenyl and allyl moieties at the C-5 position of the scaffold was accomplished using a Claisen rearrangement. Alternatively, iodination, lithium-iodine exchange and trapping with DMF gave the amorfrutin aldehyde and an amorfrutin alcohol when excess n-BuLi was used.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Chemistry, Catalysis, Phenanthrenes, Combinatorial chemistry, Biphenyl, chemistry.chemical_compound, Cycloisomerization, Hydrocarbons, Catalysts, Isomerization, Aromatic compounds, Solvents, Química orgánica, and Chemistry, Organic

Readily available o′-alkenyl-o-alkynylbiaryls, a particular type of 1,7-enynes, undergo a selective cycloisomerization reaction in the presence of a gold(I) catalyst to give interesting phenanthrene and dihydrophenanthrene derivatives in high yields. The solvent used provokes a switch in the evolution of the gold intermediate and plays a key role in the reaction outcome.
Ministerio de Economıá y Competitividad (MINECO), AEI and FEDER (projects CTQ2017- 85263-R and CTQ2016-75023-C2-1-P), Instituto de Salud Carlos III (FEDER funds, ISCIII RETIC REDINREN RD16/ 0009/0015), Junta de Castilla y León and FEDER (BU291P18), and University of Alcalá (projects CCGP2017- EXP/016 and CCG2018/EXP-008

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Reaction conditions, Chemistry, Combinatorial chemistry, Catalysis, Ethyl lactate, chemistry.chemical_compound, Tandem, Hydrocarbons, Cyclization, Mixtures, Catalysts, Selectivity, Química orgánica, and Chemistry, Organic

Skipped diynones, efficiently prepared from biomass-derived ethyl lactate, undergo a tandem hydration− oxacyclization reaction under gold(I) catalysis. Reaction conditions have been developed for a switchable process that allows selective access to 4-pyrones or 3(2H)-furanones from the same starting diynones. Further application of this methodology in the total synthesis of polyporapyranone B was demonstrated.
Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P) and Junta de Castilla y León and FEDER (BU291P18)

microwave-assisted synthesis, catecholated rosamines, 9-aminopyronins, photophysical properties, biogenic amines detection, Article, Microwave-assisted synthesis, Catecholated rosamines, Photophysical properties, Biogenic amines detection, Química orgánica, Chemistry, Organic, Organic chemistry, QD241-441, Chemistry (miscellaneous), Analytical Chemistry, Physical and Theoretical Chemistry, Molecular Medicine, Drug Discovery, and Pharmaceutical Science

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9−aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.
Financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the project PTDC/QUI-QOR/29426/2017. The research team would like to thank the projects UIDB/50006/2020, PTDC/QUI-QIN/28142/2017 and Grant BU263P18 (from the Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo). F. M. -S. gratefully acknowledges FCT (Portugal’s Foundation for Science and Technology) within grant DFA/BD/9136/2020. A.M.G.S. and A.L. thank FCT for the program DL 57/2016 – Norma transitória.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Microbiology, Chemistry, Antibiotics, medicine.drug_class, medicine, Total synthesis, Multiple drug resistance, BrisSynBio, Bristol BioDesign Institute, Science & Technology, Physical Sciences, Chemistry, Organic, ALCALIGENES SP YL-02632S, METHYLENATION, ELUCIDATION, ANTIBIOTICS, and RULES

The kalimantacins make up a family of hybrid polyketide-nonribosomal peptide-derived natural products that display potent and selective antibiotic activity against multidrug resistant strains of Staphylococcus aureus. Herein, we report the first total synthesis of kalimantacin A, in which three fragments are prepared and then united via Sonogashira and amide couplings. The enantioselective synthetic approach is convergent, unlocking routes to further kalimantacins and analogues for structure-activity relationship studies and clinical evaluation. ispartof: ORGANIC LETTERS vol:22 issue:16 pages:6349-6353 ispartof: location:United States status: published

Organic Chemistry, Adamantane derivatives, Chemistry, Computational chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Adamantane, 4-directional synthesis, enantioselective cyclopropanation, alpha-diazo-beta-keto-esters, KETO-ESTERS, CONVERSION, MOLECULE, SYMMETRY, C-13, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

1-Adamantanemethanol, 1,3-adamantanedimethanol and 1,3,5,7-adamantanetetramethanol were converted into adamantanes functionalized with one or four (2R,1S)-2-formyl-1-cyclopropyl residues using Charette enantioselective cyclopropanation reactions and with one, two or four 4-ethoxy- (or 4-t-butoxy)-3-diazo-2,4- dioxobutyl residues from aldehyde and diazo-acetate ester condensation reactions by 1-directional, 2- directional or 4-directional syntheses. The synthesis of adamantane fused to cyclopentadiene is also reported.

Organic Chemistry, Physical and Theoretical Chemistry, Batch processing, Flow (psychology), Catalysis, Continuous flow, Residence time distribution, Photoredox catalysis, Materials science, Continuous reactor, Plug flow, Chemical engineering, Science & Technology, Physical Sciences, Chemistry, Applied, Chemistry, Organic, Chemistry, HANU reactor, plug flow, oscillatory flow, photoredox catalysis, dual catalysis, slurry handling, and REACTOR

Continuous flow reactor technology has a proven track record in enabling photochemical transformations. However, transfer of a photochemical batch process to a flow protocol often remains elusive, ...

cellular prion protein, GSK3β, microtubule-associated protein tau, alternative splicing, Alzheimer’s disease, tauopathies, Malalties neurodegeneratives, Malaltia d'Alzheimer, Malalties per prions, Neurodegenerative Diseases, Alzheimer's disease, Prion diseases, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Article, Institute of Neuropathology, 570 Life sciences, biology, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, Microtúbuls, Microtubules, mental disorders, nervous system diseases, and animal diseases

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrPC), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrPC and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrPC and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrPC ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrPC expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrPC levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrPC in this phenomenon. Our results indicate that PrPC plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.

Geology, Halite, engineering.material, engineering, Biosphere, Extremophile, Biomass, Archaea, biology.organism_classification, biology, Earth science, Total organic carbon, Extreme environment, Heterotroph, [SDU]Sciences of the Universe [physics], [SDE]Environmental Sciences, [CHIM]Chemical Sciences, bepress|Physical Sciences and Mathematics, bepress|Physical Sciences and Mathematics|Chemistry, bepress|Physical Sciences and Mathematics|Chemistry|Organic Chemistry, bepress|Physical Sciences and Mathematics|Earth Sciences, bepress|Physical Sciences and Mathematics|Earth Sciences|Biogeochemistry, EarthArXiv|Physical Sciences and Mathematics, EarthArXiv|Physical Sciences and Mathematics|Chemistry, EarthArXiv|Physical Sciences and Mathematics|Chemistry|Organic Chemistry, EarthArXiv|Physical Sciences and Mathematics|Earth Sciences, EarthArXiv|Physical Sciences and Mathematics|Earth Sciences|Biogeochemistry, ddc:550, Geomicrobiology, Dead Sea, and Extremophiles

Archaea and Bacteria that inhabit the deep subsurface (known as the deep biosphere) play a prevalent role in the recycling of sedimentary organic carbon. In such environments, this process can occur over millions of years and requires microbial communities to cope with extremely limited sources of energy. Because of this scarcity, metabolic processes come at a high energetic cost, but the ways heterotrophic microbial communities develop to minimize energy expenses for a maximized yield remain unclear. Here, we report molecular biomarker evidence for the recycling of archaeal cell wall constituents in extreme evaporitic facies of Dead Sea deep sediments. Wax esters derived from the recombination of hydrolyzed products of archaeal membrane lipids were observed in gypsum and/or halite sedimentary deposits down to 243 m below the lake floor, implying the reutilization of archaeal necromass possibly by deep subsurface bacteria. By recycling the building blocks of putatively better-adapted archaea, heterotrophic bacteria may build up intracellular carbon stocks and mitigate osmotic stress in this energy-deprived environment. This mechanism illustrates a new pathway of carbon transformation in the subsurface and demonstrates how life can be maintained in extreme environments characterized by long-term isolation and minimal energetic resources.

psychosocial stress, bone pathologies, osteoporosis, bone mineral density, childhood, neuroendocrine, Bone remodeling, Bone mineral, Bone disease, medicine.disease, medicine, Endocrinology, medicine.medical_specialty, VIPR1, Internal medicine, business.industry, business, Bone pathology, Homeostasis, Osteocalcin, biology.protein, biology, Risk factor, ddc:540, ddc:570, Strukturbereich Kognitionswissenschaften, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Osteoporosis, 540 Chemie und zugeordnete Wissenschaften, 570 Biowissenschaften, Biologie, Article, Brain Research Institute, 570 Life sciences, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, and lcsh:QD1-999

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (��CT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
Postprints der Universit��t Potsdam : Humanwissenschaftliche Reihe; 670

Organic Chemistry, Catalysis, Stereoselectivity, C h bond, Heteroatom, Photoredox catalysis, Regioselectivity, Surface modification, Combinatorial chemistry, Chemistry, Transition metal, Science & Technology, Physical Sciences, Chemistry, Organic, C-H functionalization, saturated heterocycles, transition metal catalysis, stereoselectivity, regioselectivity, C-H BOND, ALPHA-AMINO-ACIDS, UNACTIVATED C(SP(3))-H, STEREOSELECTIVE-SYNTHESIS, ALIPHATIC-AMINES, DIRECT ARYLATION, NITROGEN ATOM, REMOTE FUNCTIONALIZATION, INTRAMOLECULAR AMINATION, PHOTOREDOX CATALYSIS, 0305 Organic Chemistry, and 0301 Analytical Chemistry

Synthetic methods that can readily access saturated heterocycles with different substitution patterns and with control of stereo- and regiochemistry are of huge potential value in the development of new medicinal compounds. Directed C–H functionalization of simple and commercially available precursors offers the potential to prepare diverse collections of such valuable compounds that can probe the different available exit vectors from a ring system. Nonetheless, the presence of the Lewis basic heteroatoms makes this a significant challenge. This review covers recent advances in the catalytic C–H functionalization of saturated heterocycles, with a view to different heterocycles (N, O, S), substitution patterns and transformations.1 Introduction2 α-C–H Functionalization with Directing Group on Nitrogen3 C–H Functionalization at Unactivated C(3), C(4), and C(5) Positions3.1 C–H Functionalization at C(3) with Directing Groups at C(2)3.2 C–H Functionalization at C(3), C(4), and C(5): Directing Groups at C(4) and C(3)4 Transannular C–H Functionalization5 Conclusion

Organic Chemistry, Radical, Chemistry, Oxidative phosphorylation, Cleavage (embryo), Alkoxy radical, Alkoxy group, Combinatorial chemistry, Amination, Ketone, chemistry.chemical_classification, Synthon, Science & Technology, Physical Sciences, Chemistry, Organic, O BOND-CLEAVAGE, ONE-POT, AMINATION, CYCLOALKANOLS, RADICALS, FACILE, FUNCTIONALIZATION, REARRANGEMENT, VERSATILE, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

A silver-mediated synthesis of α-amino ketones via the oxidative deconstruction of azetidinols has been developed using a readily scalable protocol with isolated yields up to 80%. The azetidinols are easily synthesized in one step and can act as protecting groups for these pharmaceutically relevant synthons. Furthermore, mechanistic insights are presented and these data have revealed that the transformation is likely to proceed through the β-scission of an alkoxy radical, followed by oxidation and C–N cleavage of the resulting α-amido radical.

Organic Chemistry, Catalysis, Hydrosilylation, chemistry.chemical_compound, chemistry, Organic synthesis, Organic chemistry, Deoxygenation, Boranes, Ligand, Lewis acids and bases, Silanes, dioxomolybdenum(VI) complexes, reduction, oxidation, deoxygenation, Lewis acid, nitroaromatics, Química orgánica, and Chemistry, Organic

Molybdenum(VI) dichloride dioxide (MoO2Cl2), and its addition complexes [MoO2Cl2(L)n; L = neutral ligand], are commercially or easily available and inexpensive transition-metal complexes based on a non-noble metal that can be applied as catalysts for various organic transformations. This short review aims to present the most significant breakthroughs in this field.
Ministerio de Economía y Competitividad (MINECO) (CTQ2016-48937-C2-1-P) and Junta de Castilla y León and FEDER (BU076U16)

Organic Chemistry, Catalysis, Cycloaddition, Stereoselectivity, Natural product, chemistry.chemical_compound, chemistry, Quinone methide, Total synthesis, Biomimetic synthesis, Addition reaction, Organic synthesis, Organic chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, ortho-quinone methide, ortho-quinone methide imine, total synthesis, review, INTRAMOLECULAR 4+2 CYCLOADDITION, ENANTIOSELECTIVE TOTAL-SYNTHESIS, OXONIUM-PRINS CYCLIZATION, BRONSTED ACID CATALYSIS, AZA-ORTHO-XYLYLENES, BIOMIMETIC SYNTHESIS, ORGANIC-SYNTHESIS, BETA-DICARBONYLS, FORMAL SYNTHESIS, RING-SYSTEM, and 0305 Organic Chemistry

Herein presented is a review of the reactivity and synthetic utility of ortho-quinone methides and ortho-quinone methide imines. These versatile intermediates have received significant attention in the literature and new methods for their preparation and reaction as well as recent applications in total synthesis are discussed.1 Introduction2 Conjugate Addition Reactions3 Concerted Cycloaddition Reactions4 Stepwise Addition Reactions5 Applications in Total Synthesis6 Conclusion

Organic Chemistry, Drug Discovery, Biochemistry, Catalytic cycle, Organic chemistry, Ether, chemistry.chemical_compound, chemistry, Oxetane, Friedel–Crafts reaction, Nucleophile, Polar effect, Catalysis, Phenol, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, Oxetanes, Dihydrobenzofurans, O-Alkylation, Lithium, MEDICINAL CHEMISTRY, PHASE ALKYLATION, ALCOHOLS, FUNCTIONALIZATION, BIOISOSTERES, DERIVATIVES, STABILITY, FRAGMENTS, PEPTIDES, 0305 Organic Chemistry, and 0304 Medicinal And Biomolecular Chemistry

Studies on the mechanism and intermediate products in the Friedel–Crafts reaction between oxetanols and phenols are presented. The formation of O-alkylated intermediates is identified using 1H NMR spectroscopy, in a reversible formation of the kinetic oxetane ether products. An interesting relationship between the electronic nature of the nucleophile and the degree of O-alkylation is uncovered. For phenols substituted with an electron withdrawing group such as CN, oxetane ethers are the only products isolated regardless of reaction time. Increasing the electron rich nature of the phenol leads to an increased proportion of the thermodynamic C-alkylated Friedel–Crafts products after just 1 h and as the sole product/s after extended reaction times. These studies have enabled a more complete catalytic cycle to be proposed. Using the same lithium catalyst and carefully selected reaction times, several examples of oxetane ethers are successfully isolated as novel bioisosteres for ester groups.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Article, Herpes Simplex Virus Type-1, viral transcription factor, ICP4, intrinsically disordered proteins, liquid–liquid phase separation, viral replication compartments, Biology (General), QH301-705.5, Chemistry, QD1-999, Institute of Anatomy, Institute of Molecular Life Sciences, Institute of Virology, 570 Life sciences, biology, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, and viruses

Herpes Simplex Virus Type-1 (HSV-1) forms progeny in the nucleus within distinct membrane-less inclusions, the viral replication compartments (VRCs), where viral gene expression, DNA replication, and packaging occur. The way in which the VRCs maintain spatial integrity remains unresolved. Here, we demonstrate that the essential viral transcription factor ICP4 is an intrinsically disordered protein (IDP) capable of driving protein condensation and liquid–liquid phase separation (LLPS) in transfected cells. Particularly, ICP4 forms nuclear liquid-like condensates in a dose- and time-dependent manner. Fluorescence recovery after photobleaching (FRAP) assays revealed rapid exchange rates of EYFP-ICP4 between phase-separated condensates and the surroundings, akin to other viral IDPs that drive LLPS. Likewise, HSV-1 VRCs revealed by EYFP-tagged ICP4 retained their liquid-like nature, suggesting that they are phase-separated condensates. Individual VRCs homotypically fused when reaching close proximity and grew over the course of infection. Together, the results of this study demonstrate that the HSV-1 transcription factor ICP4 has characteristics of a viral IDP, forms condensates in the cell nucleus by LLPS, and can be used as a proxy for HSV-1 VRCs with characteristics of liquid–liquid phase-separated condensates.

Chemistry (miscellaneous), Analytical Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Molecular Medicine, Drug Discovery, Pharmaceutical Science, Communication, glycosyl furans, singlet oxygen, [4+2] cycloaddition, C-nucleosides, photooxygenation, pyridazines, reduction, QD241-441, Glycosyl furans, Photooxygenation, Pyridazines, Reduction, Singlet oxygen, Chemistry, Organic, Furans, Glycosides, Nucleosides, and Terpenes

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside.

General Chemistry, Catalysis, Organic Chemistry, Cis–trans isomerism, Alkene, chemistry.chemical_classification, chemistry, Stereochemistry, Carbocation, Carbene, chemistry.chemical_compound, Well differentiated, Stereoselectivity, Química orgánica, and Chemistry, Organic

The first general regio‐ and stereoselective 5‐exo gold(I)‐catalyzed alkoxycyclization of a specific class of 1,5‐enynes such as 1,3‐dien‐5‐ynes has been described, despite 1,5‐enynes being known to almost invariably proceed via endo cyclizations under gold‐catalysis. The configuration of the terminal alkene in the starting 1,3‐dien‐5‐yne plays a crucial role on the regiochemical outcome of the reaction. A wide variety of interesting alkoxy‐functionalized alkylidenecyclopentenes have been synthesized from 1‐monosubstituted (E)‐1,3‐dien‐5‐ynes. On the contrary, the corresponding Z isomers evolve affording formal 6‐endo cyclization products. In addition, mechanistic exploration supports a highly stabilized carbocation as a key intermediate instead of a highly constrained cyclopropyl gold carbene from E isomers, and also accounts for the well differentiated reactivity observed between both E/Z geometrical isomers as well as for the stereochemical outcome of the reaction.
Ministerio de Ciencia eInnovacinand FEDER (CTQ2016-75023-C2-1-P and 2-P), Junta de Castilla yLenand FEDER (BU291P18) and Xunta de Galiza (ED431C2017/70and ED431E 2018/07)

General Chemistry, Solvent effects, Crystal structure, Chemistry, Electron, Cycloaddition, Eutectic system, Photochemistry, 1,3-Dipolar cycloaddition, Efficient catalyst, Science & Technology, Physical Sciences, Chemistry, Applied, Chemistry, Organic, Alkenes, Azides, Heterocycles, Solvent Effects, 1,3-DIPOLAR CYCLOADDITION, EFFICIENT CATALYST, CRYSTAL-STRUCTURE, ARYL AZIDES, ACID, DELTA-2-1,2,3-TRIAZOLINES, HYDRAZINE, CUAAC, Organic Chemistry, 0302 Inorganic Chemistry, 0305 Organic Chemistry, and 0904 Chemical Engineering

The reaction of organic azides and electron‐deficient alkenes was investigated in a deep eutectic solvent. A series of highly substituted 2‐pyrazolines was successfully isolated and their formation rationalised by DFT calculations. The critical effect of substitution was also explored; even relatively small changes in the cycloaddition partners led to completely different reaction outcomes and triazolines, triazoles or enaminones can be formed as major products depending on the alkene employed.

Organic Chemistry, Physical and Theoretical Chemistry, Passerini reaction, Four component, Aldol reaction, Chemistry, Transesterification, Organic chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Aldol addition, Multicomponent reactions, Molecular diversity, 3-COMPONENT REACTION, AMINE DEPROTECTION, TROST STRATEGY, UGI ADDUCTS, ISOCYANIDES, EFFICIENT, TRANSFORMATIONS, HETEROCYCLES, and ACCESS

ispartof: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY vol:2020 issue:23 pages:3378-3389 status: published

Multidisciplinary

Multidisciplinary and Environmental chemistry

Multidisciplinary

Multidisciplinary, Organic chemistry, and Chemistry

Multidisciplinary

Multidisciplinary, Organic chemistry, and Chemistry

Multidisciplinary

Multidisciplinary

Organic Chemistry, Physical and Theoretical Chemistry, Acetic acid, chemistry.chemical_compound, chemistry, Derivatization, Ketene, Organic chemistry, Biomimetic synthesis, Aromatization, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, Cyclization, Synthetic methods, POTENT, 0305 Organic Chemistry, and 0304 Medicinal and Biomolecular Chemistry

A series of natural product inspired piperidines spiro‐fused with resorcylic, chromenic and chromanic amides were prepared from a general derivative of a N ‐Boc‐4‐oxo‐4 H ‐spiro[benzo[ d ][1,3]dioxinone‐2,4‐piperidine], which was prepared via biomimetic aromatization of a b , d ‐diketo‐dioxinone, in turn synthesized from N ‐Boc‐4‐piperidone and geraniol using ketene coupling reagents.

Article, simulated microgravity, vector-averaged gravity, 2D clinostat, immune cells, gene expression, microarray, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Institute of Anatomy, Institute of Physiology, Center for Integrative Human Physiology, 570 Life sciences, biology, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Hypergravity, Physics, Regulation of gene expression, Transduction (genetics), Centrifuge, Cell culture, Clinostat, Jurkat cells, Cell biology, and Gene expression

Cellular processes are influenced in many ways by changes in gravitational force. In previous studies, we were able to demonstrate, in various cellular systems and research platforms that reactions and adaptation processes occur very rapidly after the onset of altered gravity. In this study we systematically compared differentially expressed gene transcript clusters (TCs) in human Jurkat T cells in microgravity provided by a suborbital ballistic rocket with vector-averaged gravity (vag) provided by a 2D clinostat. Additionally, we included 9×
g centrifuge experiments and rigorous controls for excluding other factors of influence than gravity. We found that 11 TCs were significantly altered in 5 min of flight-induced and vector-averaged gravity. Among the annotated clusters were G3BP1, KPNB1, NUDT3, SFT2D2, and POMK. Our results revealed that less than 1% of all examined TCs show the same response in vag and flight-induced microgravity, while 38% of differentially regulated TCs identified during the hypergravity phase of the suborbital ballistic rocket flight could be verified with a 9×
g ground centrifuge. In the 2D clinostat system, doing one full rotation per second, vector effects of the gravitational force are only nullified if the sensing mechanism requires 1 s or longer. Due to the fact that vag with an integration period of 1 s was not able to reproduce the results obtained in flight-induced microgravity, we conclude that the initial trigger of gene expression response to microgravity requires less than 1 s reaction time. Additionally, we discovered extensive gene expression differences caused by simple handling of the cell suspension in control experiments, which underlines the need for rigorous standardization regarding mechanical forces during cell culture experiments in general.

Organic Chemistry, Clinical Biochemistry, Drug Discovery, Pharmaceutical Science, Molecular Biology, Molecular Medicine, Biochemistry, Pyridine, chemistry.chemical_compound, chemistry, Ligand (biochemistry), Cyclin, Kinase, Stereochemistry, Pyridine moiety, Structure–activity relationship, Dengue virus, medicine.disease_cause, medicine, Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Cyclin G-associated kinase, Isothiazolo[4,3-b]pyridine, Kinase inhibitor, Antiviral drugs, CLATHRIN COAT, INHIBITORS, IDENTIFICATION, OPTIMIZATION, and BINDING

Previously, we reported the discovery of 3,6-disubstituted isothiazolo[4,3-b]pyridines as potent and selective cyclin G-associated kinase (GAK) inhibitors with promising antiviral activity. In this manuscript, the structure-activity relationship study was expanded to synthesis of isothiazolo[4,3-b]pyridines with modifications of the pyridine moiety. This effort led to the discovery of an isothiazolo[4,3-b]pyridine derivative with a 3,4-dimethoxyphenyl residue at position 5 that displayed low nanomolar GAK binding affinity and antiviral activity against dengue virus. ispartof: BIOORGANIC & MEDICINAL CHEMISTRY vol:28 issue:1 ispartof: location:England status: published

Organic Chemistry, Chemistry, User Friendly, Combinatorial chemistry, Copper, chemistry.chemical_element, Science & Technology, Physical Sciences, Chemistry, Organic, Amines, Azides, Reduction, Pyridyldi(imine) Ligands, TRANSITION-METAL-COMPLEXES, ARYL HALIDES, SCHIFF-BASE, DERIVATIVES, FUNCTIONALIZATION, REACTIVITY, AMINATION, DIOXYGEN, LIGANDS, and 0305 Organic Chemistry

Three homoleptic copper(I) complexes have been prepared and applied to the reduction of organic azides. Under optimised conditions, complex [Cu(HPDIDMA)2]BF4 3 ( HPDIDMA = 2,6-bis[N-(4-dimethylaminophenyl)carbaldimino]pyridine) could reduce a range of electron-poor azides in a mixture of DMSO and water without the need of an additional Hsource.

Organic Chemistry, Alkali metal, Organic chemistry, Environmentally friendly, Catalysis, Chemistry, 1,2,3-Triazole, chemistry.chemical_compound, Bicyclic molecule, Science & Technology, Physical Sciences, Chemistry, Organic, 4,5-FUNCTIONALIZED 1,2,3-THIADIAZOLES, POTENT INHIBITORS, DERIVATIVES, 1,2,3-TRIAZOLES, THIOAMIDES, DESIGN, TRANSANNULATION, REARRANGEMENT, and ACID

The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides 1 with various types of azides 2 in water in the presence of alkali presents an efficient, general, one-step, atom-economic, and eco-friendly method for the synthesis of 1,2,3-thiadiazol-4-carbimidamides 5 and 1,2,3-triazole-4-carbothioamides 4. This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines 2'o with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides. The method was furthermore applied to the reaction of N,N'-bis-(2-cyanothiocarbonyl)pyrazine 1h with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles 8 and 1,2,3-triazoles 9 connected via a 1,1'-piperazinyl linker. 2-Cyanothioacetamides 1 were also shown to react with aromatic azides in water in the presence of alkali to afford 1-aryl-5-amino-1,2,3-triazole-4-carbothioamides 11. In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones 2o-q react with cyanothioacetamides to form N-pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4-N-l-carbimidamides 12. A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides. ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:84 issue:21 pages:13430-13446 ispartof: location:United States status: published

Multidisciplinary

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, DNA methylation, Brachypodium distachyon, biology.organism_classification, biology, Brachypodium, Genetic diversity, Niche, Genome, DNA sequencing, Drought tolerance, Evolutionary biology, Article, drought, flowering, genome, phenomics, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Department of Plant and Microbial Biology, Zurich-Basel Plant Science Center, From Genomes to Ecosystems [Evolution in Action], 580 Plants (Botany), Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, food and beverages, and fungi

Brachypodium distachyon (Brachypodium) is a non-domesticated model grass species that can be used to test if variation in genetic sequence or methylation are linked to environmental differences. To assess this, we collected seeds from 12 sites within five climatically distinct regions of Turkey. Seeds from each region were grown under standardized growth conditions in the UK to preserve methylated sequence variation. At six weeks following germination, leaves were sampled and assessed for genomic and DNA methylation variation. In a follow-up experiment, phenomic approaches were used to describe plant growth and drought responses. Genome sequencing and population structure analysis suggested three ancestral clusters across the Mediterranean, two of which were geographically separated in Turkey into coastal and central subpopulations. Phenotypic analyses showed that the coastal subpopulation tended to exhibit relatively delayed flowering and the central, increased drought tolerance as indicated by reduced yellowing. Genome-wide methylation analyses in GpC, CHG and CHH contexts also showed variation which aligned with the separation into coastal and central subpopulations. The climate niche modelling of both subpopulations showed a significant influence from the &ldquo
Precipitation in the Driest Quarter&rdquo
on the central subpopulation and &ldquo
Temperature of the Coldest Month&rdquo
on the coastal subpopulation. Our work demonstrates genetic diversity and variation in DNA methylation in Turkish accessions of Brachypodium that may be associated with climate variables and the molecular basis of which will feature in ongoing analyses.

Article, Blood Vessels, Humans, Polymers, Contrast Media, Spectroscopy, Near-Infrared, Semiconductors, Nanoparticles, Molecular Imaging, Photoacoustic Techniques, Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemical Research Methods, Biochemistry & Molecular Biology, Chemistry, Multidisciplinary, Chemistry, Organic, Chemistry, BIOLOGICAL APPLICATIONS, CONTRAST AGENTS, 0305 Organic Chemistry, 0601 Biochemistry And Cell Biology, 0304 Medicinal And Biomolecular Chemistry, Organic Chemistry, Pharmaceutical Science, Pharmacology, Biomedical Engineering, Bioengineering, Biotechnology, Organic semiconductor, Biocompatibility, Absorbance, Conjugated system, Nanoparticle, Polymer, chemistry.chemical_classification, Nanotechnology, and Molecular imaging

Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

General Chemistry, Catalysis, Chemistry, Reducing agent, Pinacol, chemistry.chemical_compound, Molybdenum, chemistry.chemical_element, Microwave heating, Organic chemistry, Deoxygenation, amine N-oxides, deoxygenation, molyb-denum, microwave heating, N-hydroxybenzotria-zoles, Química orgánica, and Chemistry, Organic

A molybdenum-catalyzed deoxygenationof pyridine N -oxides and N-hydroxybenzotriazoles,as well as other azole N-oxides, has been developedusing pinacol as an environmentally friendly oxo-acceptor. The only by-products are acetone andwater making the process a convenient alternativeto established protocols in terms of waste gener-ation. The reaction is highly chemose lective and avariety of functional groups are tolerated. Theprocesses are usually very clean allowing theisolation of the pure deoxygenated products after asimple extraction in most cases.
Ministerio de Economı´ayCompetitividad (MINECO) (CTQ2013-48937-C2-1-P,CTQ2015-70371-REDT, and CTQ2016-75023-C2-1-P) andJunta de Castilla y Leo´n and FEDER (BU076U16)
This is the peer reviewed version of the following article: R. Rubio-Presa, M. A. Fernández-Rodríguez, M. R. Pedrosa, F. J. Arnáiz, R. Sanz, Adv. Synth. Catal. 2017, 359, 1752. doi: 10.1002/adsc.201700071, which has been published in final form at 10.1002/adsc.201700071. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

Materials Chemistry, Polymers and Plastics, Organic Chemistry, Swelling capacity, Superabsorbent polymer, Hydrolysis, Polymer chemistry, Self-healing hydrogels, Chitosan, chemistry.chemical_compound, chemistry, Acrylic acid, Calcium alginate, Chemical engineering, Drug delivery, Science & Technology, Physical Sciences, Chemistry, Applied, Chemistry, Organic, Polymer Science, Chemistry, Superabsorbent polymers, Alginate, Acrylates, Substitution degree, Swelling, Moisture uptake, MECHANICAL-PROPERTIES, ACID, HYDROGELS, HYDROLYSIS, CHITOSAN, BEHAVIOR, MORTAR, ESTERS, and AMIDES

Superabsorbent polymers (SAPs) based on polysaccharides, especially alginate, could offer a valuable solution in a plethora of applications going from drug delivery to self-healing concrete. This has already been proven with both calcium alginate and methacrylated alginate combined with acrylic acid. In this manuscript, the effect of varying the degree of methacrylation and use of a combination of acrylic acid and acrylamide is investigated to explore the effects on the relevant SAP characteristics. The materials showed high gel fractions and a strong swelling capacity up to 630gwater/gSAP, especially for superabsorbent polymers with a low degree of substitution. The SAPs also showed only a limited hydrolysis in aqueous and cement filtrate solutions. ispartof: CARBOHYDRATE POLYMERS vol:168 pages:44-51 ispartof: location:England status: published

Multidisciplinary

Multidisciplinary, Polymer science, and Philosophy

Multidisciplinary, Philosophy, Spacetime, and Art history

Multidisciplinary

Multidisciplinary

Multidisciplinary

Multidisciplinary

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Psychology, Treatment strategy, Scientific evidence, Curcumin, chemistry.chemical_compound, chemistry, Incurable diseases, Internet privacy, business.industry, business, n/a, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Institute of Complementary Medicine, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, and Editorial

The efficacy of the plant-derived polyphenol curcumin, in various aspects of health and wellbeing, is matter of public interest. An internet search of the term “Curcumin” displays about 12 million hits. Among the multitudinous information presented on partly doubtful websites, there are reports attracting the reader with promises ranging from eternal youth to cures for incurable diseases. Unfortunately, many of these reports are not based on scientific evidence, but they feed the desideratum of the reader for a “miracle cure”. This circumstance makes it very difficult for researchers, who work in a scientifically sound and evidence-based manner on the therapeutic benefits (or side effects) of curcumin, to demarcate their results from sensational reports that circulate in the web and in other media. This is only one of many obstacles making it difficult to pave curcumin’s way into clinical application; others are its nonpatentability and low economic usability. A further impediment comes from scientists who never worked with curcumin or any other natural plant-derived compound in their own labs. They have never tested these compounds in any scientific assay, neither in vitro nor in vivo; however, they claim, in a sometimes polemic manner, that everything that has so far been published on curcumin’s molecular effects is based on artefacts. The here presented Special Issue comprises a collection of five scientifically sound articles and nine reviews reporting on the therapeutic benefits and the molecular mechanisms of curcumin or of chemically modified curcumin in various diseases ranging from malignant tumors to chronic diseases, microbial infection, and even neurodegenerative diseases. The excellent results of the scientific projects that underlie the five original papers give reason to hope that curcumin will be part of novel treatment strategies in the near future—either as monotherapy or in combination with other drugs or therapeutic applications.

Organic Chemistry, Transition metal, Moiety, Free access, Oxidative phosphorylation, Tetralones, Cycloaddition, Chemistry, Combinatorial chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, HYPOIODITE REACTION, REGIOSELECTIVE SYNTHESIS, C-C, CYCLOADDITION, CYCLOALKANOLS, HETEROCYCLES, MECHANISM, ALKENES, PROBES, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

Advances in the transition-metal-free cyclobutanol ring expansion to 4-tetralones under N-bromosuccinimide mediation are described. We have expanded the scope of this ring expansion methodology and investigated the effect substituents on the aromatic ring, and the cyclobutanol moiety, have on the outcome of the reaction. Limitations with certain substituents on the cyclobutanol moiety are also described. Further experimental evidence to support our mechanistic understanding is disclosed, and we now preclude the suggested involvement of a primary radical for this transformation.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Allocolchicine, Coupling, Reagent, Aromaticity, Oxidative phosphorylation, Intramolecular force, Chemistry, Combinatorial chemistry, Oxidative coupling of methane, Science & Technology, Physical Sciences, Chemistry, Organic, HYPERVALENT IODINE(III) REAGENT, ANTITUBULIN ACTIVITY, SCHOLL REACTION, STEGANACIN, CONGENERS, EFFICIENT, LIGNANS, TUBULIN, AGENTS, and RING

A novel series of 1,2,3-triazolo-fused allocolchicine analogs is described. The strategy to prepare these analogs involves two steps: The first step is the synthesis of 1,2,3-triazole derivatives using our previously reported triazolization method, and in the second step, cyclization between two aromatic rings occurs by using the combination of PIFA and BF3·Et2O as an oxidative coupling reagent. Furthermore, the diversity of aromatic rings and functional groups is explored in order to obtain seven- and eight-membered ring systems with medicinal chemistry interest. ispartof: ORGANIC LETTERS vol:21 issue:13 pages:5002-5005 ispartof: location:United States status: published

Article, live cell imaging, suborbital rocket, microgravity, immune cells, cytoskeleton, nucleus, Institute of Anatomy, Center for Integrative Human Physiology, 570 Life sciences, biology, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Fluorescence microscope, Calcein, chemistry.chemical_compound, chemistry, Actin cytoskeleton, Cytoplasm, Cytoskeleton, Live cell imaging, Confocal, Biophysics, Microscope, law.invention, law, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, and lcsh:QD1-999

The FLUMIAS (Fluorescence-Microscopic Analyses System for Life-Cell-Imaging in Space) confocal laser spinning disk fluorescence microscope represents a new imaging capability for live cell imaging experiments on suborbital ballistic rocket missions. During the second pioneer mission of this microscope system on the TEXUS-54 suborbital rocket flight, we developed and performed a live imaging experiment with primary human macrophages. We simultaneously imaged four different cellular structures (nucleus, cytoplasm, lysosomes, actin cytoskeleton) by using four different live cell dyes (Nuclear Violet, Calcein, LysoBrite, SiR-actin) and laser wavelengths (405, 488, 561, and 642 nm), and investigated the cellular morphology in microgravity (10&minus
4 to 10&minus
5 g) over a period of about six minutes compared to 1 g controls. For live imaging of the cytoskeleton during spaceflight, we combined confocal laser microscopy with the SiR-actin probe, a fluorogenic silicon-rhodamine (SiR) conjugated jasplakinolide probe that binds to F-actin and displays minimal toxicity. We determined changes in 3D cell volume and surface, nuclear volume and in the actin cytoskeleton, which responded rapidly to the microgravity environment with a significant reduction of SiR-actin fluorescence after 4&ndash
19 s microgravity, and adapted subsequently until 126&ndash
151 s microgravity. We conclude that microgravity induces geometric cellular changes and rapid response and adaptation of the potential gravity-transducing cytoskeleton in primary human macrophages.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Catalysis, Engineering, business.industry, business, Paradigm shift, Nanotechnology, Informatics, Department of Chemistry, 540 Chemistry, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Catalysis, Software_GENERAL, ComputingMilieux_COMPUTERSANDEDUCATION, ComputingMilieux_PERSONALCOMPUTING, ComputerSystemsOrganization_COMPUTERSYSTEMIMPLEMENTATION, and ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS

Catalysis research is on the verge of experiencing a paradigm shift regarding how catalysts are designed and characterized due to the rise of catalyst informatics. The details of catalyst informatics are reviewed where the following three key concepts are proposed: catalyst data, catalyst data to catalyst design via data science, and catalyst platform. Additionally, progress and opportunities within catalyst informatics are explored and introduced. If the field of catalyst informatics grows in the appropriate manner, the methods and approaches taken for catalyst design would be fundamentally altered, leading towards great advancement within catalysis research.

General Chemistry, Catalysis, Halide, Amination, Organic chemistry, Chemistry, Triphenylphosphine, chemistry.chemical_compound, Molybdenum, chemistry.chemical_element, Nitro, Aryl, Aromatic amine, chemistry.chemical_classification, amination, boronic acids, molybdenum, nitro compounds, reduction, Química orgánica, Chemistry, Organic, and General Medicine

The synthesis of aromatic amines is of utmost importance in a wide range of chemical contexts. We report a direct amination of boronic acids with nitro compounds to yield (hetero)aryl amines. The novel combination of a dioxomolybdenum(VI) catalyst and triphenylphosphine as inexpensive reductant has revealed to be decisive to achieve this new C-N coupling. Our methodology has proven to be scalable, air and moisture tolerant, highly chemoselective and engages both aliphatic and aromatic nitro compounds. More-over, this general and step-economical synthesis of aromatic secondary amines show cases orthogonality to other aromatic secondary amines show cases orthogonality to other aromatic amine syntheses as it tolerates aryl halides and carbonyl compounds.
Junta de Castilla y León (BU022G18),Junta de Castilla y León and FEDER (BU076U16 and BU291P18) and Ministerio de Economía y Competitividad (MINECO) (CTQ2016-75023-C2-1-P)

Organic Chemistry, Ruthenium, chemistry.chemical_element, chemistry, Transition metal, Organic chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, REGIOSELECTIVE SYNTHESIS, RUTHENIUM, and KETONES

A novel, transition metal-free and one-pot methodology to synthesize various substituted NH-pyrroles from readily available building blocks such as secondary alcohols and 2-aminoalcohols is described. The process is based on the venerable Oppenauer-Woodward oxidation, which uses benzophenone as an inexpensive reagent to achieve oxidation of secondary alcohols under mild condition to ketones, further in situ condensation with aminoalcohol, and oxidative cyclization to the target pyrrole ring. The reaction occurs under basic conditions, and features a broad substrate scope combined with very good tolerance for sensitive functional groups. This method can be used to synthesize various substituted pyrroles useful as a starting material for broad applications. ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:84 issue:9 pages:5027-5034 ispartof: location:United States status: published

Organic Chemistry, Catalysis, Combinatorial chemistry, Chemistry, Extramural, One-Step, Trifluoromethylation, Reagent, Molecule, Article, Science & Technology, Physical Sciences, Chemistry, Organic, DECARBOXYLATIVE TRIFLUOROMETHYLATION, TEBUFENPYRAD ANALOGS, ORGANIC HALIDES, DIFLUOROCARBENE, and FLUORINATION

A new bench-stable trifluoromethylation reagent, phenyl bromodifluoroacetate, converts readily available alcohols to trifluoromethanes in a Cu-catalyzed deoxytrifluoromethylation reaction. This reaction streamlines access to target biologically active molecules, and should be useful for a variety of medicinal, agricultural, and materials chemists. doi: 10.1021/acs.joc.8b03072 ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:84 issue:4 pages:2061-2071 ispartof: location:United States status: published

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Membrane, Protein stabilization, Chemistry, Amphiphile, G protein-coupled receptor, Biophysics, Trehalose, chemistry.chemical_compound, Micelle, Membrane protein, Bacterial Leucine Transporter, Journal Article, Research Support, Non-U.S. Gov't, Science & Technology, Physical Sciences, Chemistry, Organic, GLYCOL GNG AMPHIPHILES, BETA(2)-ADRENERGIC RECEPTOR, ALLOSTERIC MODULATION, FACIAL AMPHIPHILES, CRYSTAL-STRUCTURE, SOLUBILIZATION, CRYSTALLIZATION, GLYCOSIDES, INSIGHTS, ANALOGS, Detergents, Glucosides, Humans, Micelles, Molecular Structure, Particle Size, Protein Stability, Receptors, G-Protein-Coupled, Surface-Active Agents, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

A novel class of non-chromophoric trehalose-cored amphiphiles was developed and some of the detergents displayed favorable behavior in stabilizing membrane proteins.
Despite their importance in biology and medicinal chemistry, structural and functional studies of membrane proteins present major challenges. To study diverse membrane proteins, it is crucial to have the correct detergent to efficiently extract and stabilize the proteins from the native membranes for biochemical/biophysical downstream analyses. But many membrane proteins, particularly eukaryotic ones, are recalcitrant to stabilization and/or crystallization with currently available detergents and thus there are major efforts to develop novel detergents with enhanced properties. Here, a novel class of trehalose-cored amphiphiles are introduced, with multiple alkyl chains and carbohydrates projecting from the trehalose core unit are introduced. A few members displayed enhanced protein stabilization behavior compared to the benchmark conventional detergent, -dodecyl-β- -maltoside (DDM), for multiple tested membrane proteins: (i) a bacterial leucine transporter (LeuT), (ii) the photosynthetic superassembly, and (iii) the human β 2 adrenergic receptor (β 2 AR). Due to synthetic convenience and their favourable behaviors for a range of membrane proteins, these agents have potential for membrane protein research. In addition, the detergent property–efficacy relationship discussed here will guide future design of novel detergents.

Materials Chemistry, Metals and Alloys, Surfaces, Coatings and Films, General Chemistry, Ceramics and Composites, Electronic, Optical and Magnetic Materials, Catalysis, Klebsiella pneumoniae, biology.organism_classification, biology, Antimicrobial, Microbiology, Small molecule, Transmembrane protein, Chemistry, Enterococcus faecium, Pseudomonas aeruginosa, medicine.disease_cause, medicine, Acinetobacter baumannii, In vitro, Química orgánica, and Chemistry, Organic

Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains.
Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains. This type of compound offers promise as a strategy to develop novel antibacterial agents.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Fluorescence, Stokes shift, symbols.namesake, symbols, Biomolecule, chemistry.chemical_classification, chemistry, Combinatorial chemistry, Suzuki reaction, Chromophore, Biocompatibility, Hyperpolarizability, Fluorophore, chemistry.chemical_compound, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, HYPER-RAYLEIGH SCATTERING, EXCITATION CROSS-SECTIONS, ETHIDIUM-BROMIDE, MULTIPHOTON FLUORESCENCE, 2-PHOTON FLUORESCENCE, BORONIC ACIDS, HYPERPOLARIZABILITY, ABSORPTION, BINDING, and PRODAN

DANPY-1 is a prototype for a family of NLO-active, low-toxicity fluorescent dyes for biological imaging and biophotonics.
Dyes with nonlinear optical (NLO) properties enable new imaging techniques and photonic systems. We have developed a dye (DANPY-1) for photonics applications in biological substrates such as nucleic acids; however, the design specification also enables it to be used for visualizing biomolecules. It is a prototype dye demonstrating a water-soluble, NLO-active fluorophore with high photostability, a large Stokes shift, and a favorable toxicity profile. A practical and scalable synthetic route to DANPY salts has been optimized featuring: (1) convergent Pd-catalyzed Suzuki coupling with pyridine 4-boronic acid, (2) site-selective pyridyl -methylation, and (3) direct recovery of crystalline intermediates without chromatography. We characterize the optical properties, biocompatibility, and biological staining behavior of DANPY-1. In addition to stability and solubility across a range of polar media, the DANPY-1 chromophore shows a first hyperpolarizability similar to common NLO dyes such as Disperse Red 1 and DAST, a large two-photon absorption cross section for its size, substantial affinity to nucleic acids , an ability to stain a variety of cellular components, and strong sensitivity of its fluorescence properties to its dielectric environment.

Organic Chemistry, Clinical Biochemistry, Drug Discovery, Pharmaceutical Science, Molecular Biology, Molecular Medicine, Biochemistry, In vitro, Chemistry, Amine gas treating, Catalysis, Palladium, chemistry.chemical_element, Two-dimensional nuclear magnetic resonance spectroscopy, Epimer, C nucleosides, Stereochemistry, Nucleobase, Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Nucleoside analogues, C-nucleosides, Xylo-nucleosides, Antitumor agents, PRACTICAL SYNTHESIS, BENZYL ETHERS, METABOLISM, and ANALOG

The synthesis of a xylo-C-nucleoside containing pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase along with that of its 1'-cyano analogue is described. Among different experimental conditions explored in order to optimize a key debenzylation step in the presented synthetic route, it was found that palladium catalyzed hydrogen transfer allowed for obtaining the target compounds in good yields. The resulting mixture of epimers was separated and each was characterized by NOESY NMR experiments. In vitro antiproliferative assays showed that the 1'-unsubstituted analogue was active against a panel of tumor cell lines such as the human leukemia HL-60 (IC50 = 1.9 µM) and lung cancer NCI-H460 (IC50 = 2.0 µM) cells. ispartof: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS vol:29 issue:12 pages:1450-1453 ispartof: location:England status: published

Pollution, Environmental Chemistry, Ethyl lactate, chemistry.chemical_compound, chemistry, Conjugated system, Raw material, Renewable energy, business.industry, business, Organic chemistry, Química orgánica, Chemistry, Organic, and complex mixtures

Ethyl lactate, a sustainable feedstock, serves as a highly attractive building block for the synthesis of value-added chemicals such as skipped diynones and, after gold-catalyzed transposition, conjugated diynones. Green solvents are involved in all steps and high yields are obtained for the final diynones which, in several cases, are isolated in a pure form without any purification.
Junta de Castilla y León and FEDER (BU076U16) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P)

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Medicinal chemistry, Stereospecificity, Catalysis, Carbene, chemistry.chemical_compound, chemistry, Nucleophile, Química orgánica, and Chemistry, Organic

The stereospecific gold(I)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes to produce C-1 functionalized 1H-indenes including challenging substrates and nucleophiles, such as β-(cyclo)alkyl-substituted o-(alkynyl)styrenes and a variety of alcohols as well as selected electron-rich aromatics, is reported. DFT calculations support the stereochemical outcome of the process that involves the formation of a key cyclopropyl gold carbene intermediate through a regiospecific 5-endo cyclization.
Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P and 2-P), and Junta de Castilla y León and FEDER (BU291P18) and Xunta de Galicia (ED431C 2017/70 and ED431E 2018/07)

General Medicine, Extracellular matrix, Molecular interactions, Chemistry, Regenerative medicine, Biological studies, Nanotechnology, Polysaccharide, chemistry.chemical_classification, Tissue engineering, Science & Technology, Physical Sciences, Chemistry, Applied, Chemistry, Organic, Polymer Science, Polysaccharides, Biomaterials, Biopolymers, Topochemical engineering, REGENERATIVE MEDICINE APPLICATIONS, BIOMATERIAL SURFACE-PROPERTIES, EMBRYONIC STEM-CELLS, PROTEIN DATA-BANK, EXTRACELLULAR-MATRIX, BIOMEDICAL APPLICATIONS, MECHANICAL-PROPERTIES, CRYSTAL-STRUCTURE, BACTERIAL CELLULOSE, and CROSS-LINKING

Biological studies on the importance of carbohydrate moieties in tissue engineering have incited a growing interest in the application of polysaccharides as scaffolds over the past two decades. This review provides a perspective of the recent approaches in developing polysaccharide scaffolds, with a focus on their chemical modification, structural versatility, and biological applicability. The current major limitations are assessed, including structural reproducibility, the narrow scope of polysaccharide modifications being applied, and the effective replication of the extracellular environment. Areas with opportunities for further development are addressed with an emphasis on the application of rationally designed polysaccharides and their importance in elucidating the molecular interactions necessary to properly design tissue engineering materials. ispartof: CARBOHYDRATE POLYMERS vol:205 pages:601-625 ispartof: location:England status: published

Polymers and Plastics, Materials Chemistry, Organic Chemistry, Polymer, chemistry.chemical_classification, chemistry, Microporous material, Saturation (chemistry), Micrometre, Ionic liquid, chemistry.chemical_compound, Supercritical fluid, Materials science, Tensile testing, Fabrication, Chemical engineering, ScCO2, Microporous film, PMMA, Química orgánica, and Chemistry, Organic

The use of supercritical CO2 (ScCO2) has been established as a standard technique to produce micro- and nanocellular polymers with controlled morphologies and cell sizes between 500 nm and several microns. However, overcoming the gap between micro and nanocellular polymers implies the use of long saturation times (up to several days) and low temperatures (below 0 °C) combined with high saturation pressures (above 30 MPa). This work presents a different approach to obtain microporous poly (methyl methacrylate) (PMMA) structures with controlled morphologies using a physical procedure employing ionic liquids that are mixed in solution with PMMA. The ionic liquid can produce interesting fine microporous materials simply by being removed with distilled water. The work compares the two fabrication methods previously mentioned to critically analyze the benefits and drawbacks of each preparation route. The method in this paper opens the possibility to obtain microporous polymers by employing ionic liquids, thus reducing the time of processing, avoiding specific foaming equipment and broadening the applicability of crosslinked and semi crystalline polymers. Low velocity tensile test results are also presented to point out the improvement in the mechanical parameters of microporous films obtained from ionic liquids compared to those of films foamed using ScCO2.

Organic Chemistry, Physical and Theoretical Chemistry, Stereochemistry, Phosphonate, chemistry.chemical_compound, chemistry, Epimer, Glycosylation, Moiety, C nucleosides, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, C-Nucleosides, Epimerization, Phosphonates, Nucleoside mimics, ACYCLIC NUCLEOSIDE PHOSPHONATES, ANALOGS, VIRUS, and ACIDS

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Herein, the synthesis of the first example of a 3′-deoxy-5′-phosphonate 2′[R] C-nucleoside and its corresponding prodrug is presented. The developed route involves a reductive debromination at the 2′-position of a suitably substituted 9-deazaadenosine intermediate, followed by a stereoselective glycosylation at the 5′-anomeric position to achieve the installation of the phosphonomethoxy functionality. The target compound with the desired configuration is formed upon base-promoted epimerization at the 2′[S]-position of the sugar moiety. ispartof: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY vol:2018 issue:47 pages:6657-6664 status: published

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Gene, Acetylation, Chromatin, Epigenetics, Epigenome, Transcriptional regulation, Biology, Cell biology, Regulation of gene expression, Metabolic pathway, epigenetics, metabolic signaling, chromatin, obesity, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Review, Department of Molecular Mechanisms of Disease, 570 Life sciences, biology, and Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, chromatin

The regulation of cellular metabolism is coordinated through a tissue cross-talk by hormonal control. This leads to the establishment of specific transcriptional gene programs which adapt to environmental stimuli. On the other hand, recent advances suggest that metabolic pathways could directly signal into chromatin modifications and impact on specific gene programs. The key metabolites acetyl-CoA or S-adenosyl-methionine (SAM) are examples of important metabolic hubs which play in addition a role in chromatin acetylation and methylation. In this review, we will discuss how intermediary metabolism impacts on transcription regulation and the epigenome with a particular focus in metabolic disorders.

Organic Chemistry, Acetic acid, chemistry.chemical_compound, chemistry, Morpholine, D-1, Medicinal chemistry, Nitrogen, chemistry.chemical_element, Dissolution, Cyclopentane, Cyclopentene, Methanol, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, amidines, imidazoles, pyrimidinediones, triazines, triazolines, ring transformations, 1,3-DIPOLAR CYCLOADDITION, SULFONYL AMIDINES, FACILE SYNTHESIS, AZIDES, ENAMINES, REARRANGEMENT, DECOMPOSITION, and REACTIVITY

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. [Figure not available: see fulltext.] It was found that brief refluxing of N-hetarylcyclopentano[d][1,2,3]triazolines in methanol resulted in the elimination of nitrogen, accompanied by cyclopentane ring opening with the formation of N-hetarylvaleramidines. Amidines containing pyrimidine-2,4-dione ring were synthesized by a one-step procedure – the reaction of 5-azidopyrimidine-2,4-diones with endocyclic enamines containing a cyclopentene ring proceeded through an N-pyrimidyl-1,2,3-triazoline intermediate. Triazolines containing a 1,3,5-triazine ring at position 1 did not form valeramidines upon refluxing in methanol. N-(1,3,5-triazin-2-yl)cyclopenta[d][1,2,3]triazoline containing a morpholine ring at position 6a underwent a different type of transformation upon dissolving in acetic acid, resulting in the formation of N-(1,3,5-triazin-2-yl)diaminoalkene. Mechanisms for these transformations are proposed. ispartof: CHEMISTRY OF HETEROCYCLIC COMPOUNDS vol:54 issue:11 pages:1050-1055 status: published

Organic Chemistry, Oligonucleotide synthesis, Chemistry, Combinatorial chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, D-ALTRITOL NUCLEOSIDES, NUCLEIC-ACIDS, HYBRIDIZATION, THERAPIES, and lipids (amino acids, peptides, and proteins)

A new synthesis protocol for the preparation of hitherto unknown 1',5'-anhydro-4'-amino-trityl/MMTr hexitol nucleosides has been developed. Key steps in the synthesis of the pyrimidine analogues (U and C) include the regioselective d- allo-hexitol oxirane and 2',4'-anhydronucleoside ring opening by uracil and azide, respectively. A different strategy using a regioselective epoxide ring opening of d- gulo-oxirane, followed by a SN2 type of azidation reaction, has been adopted for the purine analogues (A and G). These compounds can be easily converted to 6'-phosphoramidites for the solid-phase synthesis of N4' → P6' phosphoramidates of amino hexitol nucleic acids (AHNA). ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:83 issue:24 pages:15155-15169 ispartof: location:United States status: published

Drug Discovery, Pharmacology, Molecular Medicine, Medicine, business.industry, business, Survivin, Tumor progression, Radiation therapy, medicine.medical_treatment, Cancer, medicine.disease, Inhibitor of apoptosis, Downregulation and upregulation, Programmed cell death, Cancer cell, Cancer research, anticancer therapy, apoptosis, chemoresistance, inhibitor ofapoptosis proteins, SMAC mimetics, survivin inhibitors, Química orgánica, Chemistry, Organic, Patologia molecular, Càncer, Transducció de senyal cel·lular, Inhibició, Molecular pathology, Cellular signal transduction, Inhibition, and neoplasms

Survivin is a small protein that belongs to the inhibitor of apoptosis protein family. It is abundantly expressed in tumors compared with adult differentiated tissues, being associated with poor prognosis in many human neoplasms. This apoptotic inhibitor has a relevant role in both the promotion of cancer cell survival and in the inhibition of cell death. Consequently, aberrant survivin expression stimulates tumor progression and confers resistance to several therapeutic strategies in a variety of tumors. In fact, efficient survivin downregulation or inhibition results in spontaneous apoptosis or sensitization to chemotherapy and radiotherapy. Therefore, all these features make survivin an attractive therapeutic target to treat cancer. Currently, there are several survivin inhibitors under clinical evaluation, although more specific and efficient survivin inhibitors are being developed. Moreover, novel combination regimens targeting survivin together with other therapeutic approaches are currently being designed and assessed. In this review, recent progress in the therapeutic options targeting survivin for cancer treatment is analyzed. Direct survivin inhibitors and their current development status are explored. Besides, the major signaling pathways implicated in survivin regulation are described and different therapeutic approaches involving survivin indirect inhibition are evaluated. Finally, promising novel inhibitors under preclinical or clinical evaluation as well as challenges of developing survivin inhibitors as a new therapy for cancer treatment are discussed.
Consejería de Educación, Junta de Castilla y León. Grant Number: BU092U16 Instituto de Salud Carlos III. Grant Number: FIS PI18/00441

Article, innate immunity, adaptive immunity, spaceflight, microgravity, gravisensitivity, microarray, Institute of Anatomy, Center for Integrative Human Physiology, 570 Life sciences, biology, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Oxidative stress, medicine.disease_cause, medicine, Chemistry, Hypergravity, Jurkat cells, Reactive oxygen species, chemistry.chemical_classification, Acquired immune system, Innate immune system, Cell biology, Cellular homeostasis, Reactive nitrogen species, and chemistry.chemical_compound

Whereby several types of cultured cells are sensitive to gravity, the immune system belongs to the most affected systems during spaceflight. Since reactive oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of cellular homeostasis, particularly in the cells of the immune system, we investigated the immediate effect of altered gravity on the transcription of 86 genes involved in reactive oxygen species metabolism, antioxidative systems, and cellular response to oxidative stress, using parabolic flight and suborbital ballistic rocket experiments and microarray analysis. In human myelomonocytic U937 cells, we detected a rapid response of 19.8% of all of the investigated oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted after 5 min of microgravity. After the almost complete adaptation of initially altered transcripts, a significant second pool of differentially expressed transcripts appeared. In contrast, we detected nearly no response of oxidative stress-related transcripts in human Jurkat T cells to altered gravity. In conclusion, we assume a very well-regulated homeostasis and transcriptional stability of oxidative stress-related pathways in altered gravity in cells of the human immune system.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Ruthenium, chemistry.chemical_element, chemistry, Molecular orbital, Hydrogen bond, Metal, visual_art.visual_art_medium, visual_art, Electronegativity, Ionic bonding, Hydride, Crystallography, Ligand, Science & Technology, Physical Sciences, Chemistry, Inorganic & Nuclear, Chemistry, Organic, Chemistry, BASIS-SETS, SIGMA-COMPLEXES, HYDROGEN BOND, ALUMINUM, ZINC, MAGNESIUM, ELEMENTS, METAL, PSEUDOPOTENTIALS, COORDINATION, 0302 Inorganic Chemistry, 0305 Organic Chemistry, and 0399 Other Chemical Sciences

The reaction of [Ru(H)2(N2)2(PCy3)2] (1) with β-diketiminate stabilized hydrides of Al, Zn, and Mg generates a series of new heterobimetallic complexes with either H2 or N2 ligated to the ruthenium center. Changing the main-group fragment of the M·Ru-N2 (M = Al, Zn, Mg) complexes can subtly alter the degree of binding, and therefore activation, of the diatomic ligand, as evidenced by the νN≡N absorptions in the infrared data. Experimental and computational data rationalize this tunable binding; decreasing the electronegativity of the main group in the order Al > Zn > Mg infers greater ionic character of these M·Ru-N2 complexes, and this in turn results in greater destabilization of the frontier molecular orbitals of ruthenium and therefore greater Ru(4d) → π*(N2) back-donation.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Medicinal chemistry, Phenylacetylene, chemistry.chemical_compound, chemistry, Carboxylate, Ruthenium, chemistry.chemical_element, Ligand, Chemoselectivity, Alkyne, chemistry.chemical_classification, Kinetics, Catalysis, Science & Technology, Physical Sciences, Chemistry, Inorganic & Nuclear, Chemistry, Organic, Chemistry, MOLECULAR-ORBITAL METHODS, RUTHENIUM-CATALYZED HYDROSILYLATION, C-H ACTIVATION, INSERTION REACTIONS, ALKYNYL COMPLEXES, DIRECT ARYLATION, BASIS-SETS, BOND, MECHANISM, ALKENYL, 0302 Inorganic Chemistry, 0305 Organic Chemistry, and 0399 Other Chemical Sciences

This work addresses a counterintuitive observation in the reactivity of the well-known ruthenium complexes [Ru(X)H(CO)(PiPr3)2], according to which the 5-coordinate chloro complex (X = Cl, 1) is less reactive toward phenylacetylene than its 6-coordinate acetate analogue (X = κO2-OC(O)Me, 3), since 3 undergoes a hydride-to-alkenyl-to-alkynyl transformation, whereas the reaction of 1 stops at the alkenyl derivative. The experimental kinetics of the key alkenyl-to-alkynyl step in the acetate complex are compared to the results of DFT calculations, which disclose the ability of the acetate not only to assist the alkyne C–H activation step via a CMD mechanism but also to subsequently deliver the proton to the alkenyl ligand. Possible consequences of this mechanistic resource connecting mutually trans ligands are briefly discussed on the basis of reported chemoselectivity changes induced by carboxylate ligands in 1-alkyne hydrosilylations catalyzed by this type of ruthenium complexes.
The authors are thankful for financial support from Ministerio de Economía, Industria y Competitividad (MINECO)/Fondo Europeo de Desarrollo Regional (FEDER) (Grants CTQ2015- 64486-R and CTQ2017-87792-R), MINECO-Severo Ochoa Excellence Accreditation 2014-2018 (Grant SEV-2013-0319), and Gobierno de Aragon/FEDER (E08_17R). A. de A. thanks MINECO for a FPI fellowship (BES-2015-073012).

Organic Chemistry, Solvent, Beta-lactam, chemistry.chemical_compound, chemistry, Combinatorial chemistry, Diastereomer, One-pot synthesis, Catalysis, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, MICHAEL CASCADE REACTION, N-ARYL ALKYNAMIDES, ONE-POT SYNTHESIS, INTRAMOLECULAR HYDROARYLATION, SELECTIVE SYNTHESIS, PASSERINI REACTIONS, DOMINO CYCLIZATION, BETA-LACTAMS, ALKYNES, and DEAROMATIZATION

A gold-catalyzed post-Ugi ipso-cyclization for the diastereoselective synthesis of spirocyclic pyrrol-2-one-dienone system is described. Tuning the catalytic system, solvent, and temperature allowed selectively attaining two sets of diastereoisomers. The scope of the process has been evaluated, and a putative mechanistic model was proposed. ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:83 issue:15 pages:8170-8182 ispartof: location:United States status: published

Organic Chemistry, Organic chemistry, Cycloisomerization, Amide, chemistry.chemical_compound, chemistry, Chloride, medicine.drug, medicine, Catalysis, Allylic rearrangement, Coumarin, Overman rearrangement, Pyridinium, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, POLYCYCLIC SCAFFOLDS, TANDEM PROCESS, DERIVATIVES, CYCLIZATION, COMPLEXES, 1,2-DIHYDROQUINOLINES, FLUORESCENCE, CHROMENES, MECHANISM, ACCESS, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

A four-step synthesis of allylic trichloroacetimidates bearing a 2-proparyloxyaryl group has been developed from readily available 2-hydroxybenzaldehydes, and these have been used for the preparation of allylic amide derived 2H-chromenes using an Overman rearrangement and a 6-endo-dig hydroarylation. High yields of the 2H-chromenes were achieved using a stepwise approach involving an Overman rearrangement under thermal conditions followed by a hydroarylation reaction with a gold(I) triflimide catalyst. An alternative method where both reactions were performed as a one-pot process was also developed and instead used a gold(I) chloride catalyst activated by silver(I) hexafluoroantimonate for the cycloisomerization step. The allylic amide derived 2H-chromenes were converted to the corresponding coumarin analogues by a pyridinium dichromate (PDC)-mediated chemoselective allylic oxidation.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Drug Discovery, Biochemistry, Catalysis, Algal bloom, Botany, Iron Chelator, Chemical ecology, Allelopathy, Chemistry, Siderophore, Cyanobacteria, biology.organism_classification, biology, Green algae, Nutrient, Department of Chemistry, Department of Plant and Microbial Biology, 540 Chemistry, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Biochemistry, Drug Discovery, Catalysis, fungi, bacteria, biochemical phenomena, metabolism, and nutrition, and inorganic chemicals

One of the compounds suggested to be responsible for the cyanobacterial dominance over competing green algae is identified. Evidence is provided on the molecular, chemical level that the iron chelator anachelin from the cyanobacterium Anabaena cylindrica promotes both the growth of cyanobacteria and reduces the growth of competing chlorophytes. These results illustrate a molecular strategy of addressing two challenges (nutrient availability and algal competition) by one molecule. Such strategies could be implied in harmful algal blooms in marine and freshwater environments.

Organic Chemistry, Clinical Biochemistry, Drug Discovery, Pharmaceutical Science, Molecular Biology, Molecular Medicine, Biochemistry, Histone methyltransferase, Small Molecule Libraries, Structure–activity relationship, Halogen, Nitrile, chemistry.chemical_compound, chemistry, Stereochemistry, Small molecule, Nucleoside, Bioisostere, and Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Protein methyltransferase, DOT1L inhibitors, Toyocamycin, Bioisostere, Cyano-deaza-SAH, H3K79 Methylation, Potent, Leukemia, Derivatives, Toyocamycin

A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L activity. SARs established that DOT1L inhibition could be achieved through incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12) or by the application of alternative nitrogenous bases (18). Based on these results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L activity where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms.

General Chemical Engineering, General Chemistry, Thermogravimetry, Photopolymer, Propargyl, Curing (chemistry), Materials science, Bisphenol A, chemistry.chemical_compound, chemistry, Thermosetting polymer, Epoxy, visual_art.visual_art_medium, visual_art, Ethyleneimine, Polymer chemistry, Organic chemistry, Enginyeria química::Química orgànica [Àrees temàtiques de la UPC], Enginyeria dels materials::Assaig de materials::Assaig de fractura [Àrees temàtiques de la UPC], Enginyeria dels materials::Materials plàstics i polímers [Àrees temàtiques de la UPC], Composite materials, Chemistry, Organic, Michael addition, Yne chemistry, Networks, Thermosets, Polymers, Photopolymerization, Polymerization, Alkynes, Amine, Materials compostos, and Química orgànica

A novel curing methodology based on the combination of thiol-yne and thiol-epoxy click reactions has been developed. The curing process consists of a first photoinitiated thiol-yne reaction, followed by a thermal thiol-epoxy process. As alkyne substrate a new propargyl terminated hyperbranched poly(ethyleneimine) (PEIyne) has been synthesized from the reaction of commercial poly(ethylenimine) (PEI) and glycidyl propargyl ether. The evolution of the curing of different mixtures of PEIyne and diglycidylether of bisphenol A (DGEBA) with the stoichiometric amount of tetrathiol (PETMP) has been monitored by DSC. The new hybrid materials have been characterized by thermomechanical analysis, thermogravimetry and by electronic microscopy inspection and compared with neat thiol-yne and thiol-epoxy materials. The T(g)s of the complete cured materials increase with the proportion of epoxide in the formulation. The thiol-yne network improves the plasticity of the fracture of the materials.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Epithelium, medicine.anatomical_structure, medicine, Trichostatin A, medicine.drug, Tumor necrosis factor alpha, Histone deacetylase inhibitor, medicine.drug_class, Chemistry, Cell culture, Squamous carcinoma, Butyrate, Cell adhesion molecule, Molecular biology, Clinic of Reconstructive Dentistry, 610 Medicine & health, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, butyric acid, periodontium, intercellular adhesion molecule-1, oral biology, epithelial cells, in vitro, Article, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, and lcsh:QD1-999

Short-chain fatty acids (SCFA) are bacterial metabolites that can be found in periodontal pockets. The expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) within the epithelium pocket is considered to be a key event for the selective transmigration of leucocytes towards the gingival sulcus. However, the impact of SCFA on ICAM-1 expression by oral epithelial cells remains unclear. We therefore exposed the oral squamous carcinoma cell line HSC-2, primary oral epithelial cells and human gingival fibroblasts to SCFA, namely acetate, propionate and butyrate, and stimulated with known inducers of ICAM-1 such as interleukin-1-beta (IL1&beta
) and tumor necrosis factor-alfa (TNF&alpha
). We report here that butyrate but not acetate or propionate significantly suppressed the cytokine-induced ICAM-1 expression in HSC-2 epithelial cells and primary epithelial cells. The G-protein coupled receptor-43 (GPR43/ FFAR2) agonist but not the histone deacetylase inhibitor, trichostatin A, mimicked the butyrate effects. Butyrate also attenuated the nuclear translocation of p65 into the nucleus on HSC-2 cells. The decrease of ICAM-1 was independent of Nrf2/HO-1 signaling and phosphorylation of JNK and p38. Nevertheless, butyrate could not reverse an ongoing cytokine-induced ICAM-1 expression in HSC-2 cells. Overall, these observations suggest that butyrate can attenuate cytokine-induced ICAM-1 expression in cells with epithelial origin.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, 0304 Medicinal and Biomolecular Chemistry, and 0305 Organic Chemistry

Correction for ‘Trehalose-cored amphiphiles for membrane protein stabilization: importance of the detergent micelle size in GPCR stability’ by Manabendra Das et al., Org. Biomol. Chem., 2019, 17, 3249–3257.

Article, 19F-MRI, Bisphosphonates (BPs), Magnetic resonance imaging (MRI), Preclinical imaging, Fluorinated bisphosphonate, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Environmental Chemistry, Biochemistry, MRI contrast agent, Magnetic resonance imaging, medicine.diagnostic_test, medicine, In vivo, Calcium, chemistry.chemical_element, chemistry, Biodistribution, Nuclear magnetic resonance, Bisphosphonate, medicine.medical_treatment, In vitro, Science & Technology, Physical Sciences, Chemistry, Inorganic & Nuclear, Chemistry, Organic, Chemistry, F-19-MRI, F-19 MAGNETIC-RESONANCE, BONE METASTASES, 19F MRI, NANOPARTICLES, ANGIOGENESIS, INFLAMMATION, NANOBEACONS, COMPLEXES, DESIGN, BRAIN, 0302 Inorganic Chemistry, and 0305 Organic Chemistry

Graphical abstract A water-soluble 1,1-geminal fluorinated bisphosphonate showing a single and narrow 19F resonance was synthesised and characterised. Its properties as contrast agent for 19F-MRI were evaluated in vitro and in vivo.
Highlights • A trifluoromethyl-bisphosphonate for 19F-MRI was synthesised and characterised. • In vitro studies showed its potential with properties comparable to previous probes. • In vivo 19F/1H-MRI studies showed fast renal excretion and liver uptake.
19F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate (19F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow 19F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of 19F-BP to provide contrast was analysed in vitro and in vivo using 19F-MRI. In vitro studies demonstrated the potential of 19F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of 19F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, 19F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing 19F MRI probes with the highest signal intensity achievable.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Monoclonal antibody, medicine.drug_class, medicine, Ceramide, chemistry.chemical_compound, chemistry, Gene chip analysis, Glycan, biology.protein, biology, Stereochemistry, Glycosphingolipid, Microarray analysis techniques, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, 1ST TOTAL-SYNTHESIS, HUMAN HEPATOCELLULAR-CARCINOMA, CERAMIDE CASSETTE APPROACH, LE(X) GANGLIOSIDE ANALOGS, REAL CARBOHYDRATE LIGAND, RAT-KIDNEY, SULFATED GLYCOSPHINGOLIPIDS, L-SELECTIN, MONOCLONAL-ANTIBODIES, ISOGLOBO-SERIES, Carcinoma, Ceramides, Glycosphingolipids, Humans, Microarray Analysis, Polysaccharides, Sulfur Compounds, 0304 Medicinal And Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology And Pharmaceutical Sciences, Article, and carbohydrates (lipids)

Total syntheses of two natural sulphoglycolipids, disulphated glycosphingolipid SB1a and the structurally related monosulphated SM1a, are described. They have common glycan sequences and ceramide moieties and are associated with human epithelial carcinomas. The syntheses featured efficient glycan assembly and the glucosyl ceramide cassette as a versatile building block. The binding of the synthetic sulphoglycolipids by the carcinoma-specific monoclonal antibody AE3 was investigated using carbohydrate microarray technology.

Organic Chemistry, Physical and Theoretical Chemistry, Pheromone, Bioassay, Olfactometer, Acanthoscelides obtectus, ved/biology.organism_classification_rank.species, ved/biology, Octadecanal, chemistry.chemical_compound, chemistry, Acanthoscelides, biology.organism_classification, biology, Botany, Sex pheromone, and Chemistry, Organic

Male-specific volatile components, released by the dried bean beetle, Acanthoscelides obtectus, were identified as methyl (E,R)-2,4,5-tetradecatrienoate, methyl (2E,4Z,7Z)-2,4,7-decatrienoate, methyl (2E,4Z)-2,4-decadienoate, octadecanal and the sesquiterpenes (3Z,6E)- and (3E,6E)-alpha-farnesene. In olfactometer bioassays, pure methyl (E, R)-2,4,5-tetradecatrienoate was only weakly attractive to unmated females. However, a blend of the six identified compounds released in physiologically relevant ratios and doses proved to be as active as headspace odours collected from live males.

photoactivatable complexes, ruthenium, ruthenium arene, PDT, DFT, photochemistry, lcsh:Organic chemistry, lcsh:QD241-441, density-functional theory, molecula calculations, excitation-energies, ruthenium(II), cancer, potentials, mechanism, continuum, ligands, atoms, CHEMISTRY, ORGANIC, Photoactivatable complexes, Photochemistry, Ruthenium, Ruthenium arene, Organic Chemistry, Article, Chemistry (miscellaneous), Analytical Chemistry, Physical and Theoretical Chemistry, Molecular Medicine, Drug Discovery, Pharmaceutical Science, Triplet state, Aqueous solution, Medicinal chemistry, Singlet state, Ligand, Stereochemistry, Denticity, Chemistry, Bipyridine, chemistry.chemical_compound, Molecule, and chemistry.chemical_element

New Ru(II) arene complexes of formula [((6)-p-cym)Ru(N-N)(X)](2+) (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 1-4) were synthesised and characterized, including the molecular structure of complexes [((6)-p-cym)Ru(bpy)(m-COOMe-Py)](2+) (3) and [((6)-p-cym)Ru(bpy)(p-COOMe-Py)](2+) (4) by single-crystal X-ray diffraction. Complexes 1-4 are stable in the dark in aqueous solution over 48 h and photolysis studies indicate that they can photodissociate the monodentate m/p-COOMe-Py ligands selectively with yields lower than 1%. DFT and TD-DFT calculations (B3LYP/LanL2DZ/6-31G**) performed on singlet and triplet states pinpoint a low-energy triplet state as the reactive state responsible for the selective dissociation of the monodentate pyridyl ligands. Our work in this area was supported by Spanish Ministry of Economy and Competitiveness (grant CTQ2012-39315), the Department of Industry of the Basque Country (grant ETORTEK), L.S. and E.R. are supported by the MICINN of Spain with the Ramon y Cajal Fellowship RYC-2011-07787 and by the MC CIG fellowship UCnanomat4iPACT (grant n. 321791). We thank IKERBASQUE for the Visiting Professor Fellowship to A.H. and members of the European COST Action CM1105 for stimulating discussions. The SGI/IZO-SGIker UPV/EHU is gratefully acknowledged for generous allocation of computational resources. S.A.C. thanks the Spanish Ministry of Economy and Competitiveness for her PhD fellowship (BES-2013-065642). L.S. is also grateful to J.M. Ugalde, T. Mercero and E. Ogando for their support. Technical and human support provided by SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is gratefully acknowledged.

Article, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, POLYMER SOLAR-CELLS, COPOLYMER, ANTHRADITHIOPHENE, BENZOTHIADIAZOLE, EFFICIENCY, Organic Chemistry, 0304 Medicinal And Biomolecular Chemistry, 0305 Organic Chemistry, 0302 Inorganic Chemistry, Potential impact, Polymer solar cell, Solid-state, Electronic properties, Moiety, Copolymer, Polymer chemistry, Intermolecular force, Organic electronics, and Photochemistry

The 4,7-dithieno-2,1,3-benzothiadiazole (DTBT) moiety and its fluorinated counterpart are important π-conjugated building blocks in the field of organic electronics. Here we present a combined experimental and theoretical investigation into fundamental properties relating to these two molecular entities and discuss the potential impact on extended π-conjugated materials and their electronic properties. While the fluorinated derivative, in the solid state, packs with a cofacial overlap smaller than that of DTBT, we report experimental evidence of stronger optical absorption as well as stronger intra- and intermolecular contacts upon fluorination.

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Cancer, medicine.disease, medicine, Aquaporin 1, Asbestos, medicine.disease_cause, Pathology, medicine.medical_specialty, Biomarker (medicine), business.industry, business, Lung, medicine.anatomical_structure, Mesothelioma, Staining, Immunohistochemistry, Asbestiform, Asbestos, Biancavilla, Biomarker, Cancer, Fluoro-edenite, Lung, Malignant pleural mesothelioma, NOA, Catalysis, Molecular Biology, Spectroscopy, Computer Science Applications1707 Computer Vision and Pattern Recognition, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry, fluoro-edenite, Biancavilla, malignant pleural mesothelioma, cancer, asbestos, asbestiform, lung, NOA, biomarker, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, and Communication

Background: The immunohistochemical expression of aquaporin-1 (AQP1) in asbestos-related malignant pleural mesothelioma (MPM) is emerging as a useful prognostic indicator of improved survival. A significantly increased incidence of MPM in a small town in southern Italy was ascribed to exposure to fluoro-edenite (FE), a naturally occurring asbestos fiber. We investigated the immunohistochemical expression of AQP1 in patients affected by FE-related MPM; taking into consideration its suggested independent prognostic role, its possible correlation with clinicopathological parameters and patient outcome was also evaluated. Methods: Ten patients were selected for this study, as neoplastic tissue blocks, clinical and follow-up data were available. The immunohistochemical overexpression of AQP1 was defined as ≥50% of tumor cells showing membranous staining. Results: Six cases showed AQP1 expression in ≥50% of tumor cells; in this group, a significant association of AQP1 overexpression with an increased median overall survival (OS) of 26.3 months was observed. By contrast, four patients exhibited an AQP1 score of

Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis, Fas receptor, Medicine, business.industry, business, Inflammation, medicine.symptom, Programmed cell death, Cancer research, Caspase, biology.protein, biology, Fas ligand, Necroptosis, BH3 interacting-domain death agonist, Apoptosis, Article, neutrophil, FAS/CD95, BID, apoptosis, RIPK3, necroptosis, caspases, inflammation, colitis, mouse model, 610 Medicine & health, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, Institute of Experimental Immunology, 570 Life sciences, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications, and biological phenomena, cell phenomena, and immunity

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Silylation, Reagent, Amide, chemistry.chemical_compound, chemistry, Tetramethyl orthosilicate, Organic chemistry, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, AMIDE BOND FORMATION, CATALYZED DIRECT AMIDATION, ROOM-TEMPERATURE, MESOPOROUS SILICA, PEPTIDE-SYNTHESIS, COUPLING REAGENT, CONVENIENT METHOD, AMINO-ACIDS, IN-SITU, CARBOXAMIDES, and 03 Chemical Sciences

Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods. Amidations on a 1 mol scale are demonstrated with a favorable process mass intensity.

Organic Chemistry, Physical and Theoretical Chemistry, Biochemistry, Denticity, Metal catalyst, Hydrolysis, Imine, chemistry.chemical_compound, chemistry, Covalent bond, Combinatorial chemistry, Catalysis, Carbon, chemistry.chemical_element, Transition metal, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, UNACTIVATED C(SP(3))-H BONDS, CARBON-HYDROGEN BONDS, FREE PRIMARY AMINES, INTERMOLECULAR HYDROACYLATION, ALIPHATIC-AMINES, AROMATIC KETONES, DIRECT ARYLATION, ORTHO-ALKYLATION, DUAL ACTIVATION, ALDEHYDES, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, and 1115 Pharmacology and Pharmaceutical Sciences

This review describes recent developments in the use of catalytic transient directing groups, through imine linkages, which in combination with transition metal catalysts provide streamlined C–H functionalisation processes.
C–H functionalisation promises a paradigm shift in synthetic planning. However, the additional steps often required to install and remove directing groups currently detract from the efficiency. The strategy of reversible installation of a directing group an imine linkage has recently emerged, with the imine formed and hydrolysed . Such transient directing groups can promote transition metal catalysed functionalisation of unactivated C–H bonds of aldehydes, ketones and amines. This approach removes additional steps usually required for covalent directing groups and can use catalytic quantities of the imine forming component. This review updates the rapidly developing field of transient directing groups for C–H functionalisation on sp 2 and sp 3 carbon centres, to form new C–C and C–X bonds. We focus on the structures of the transient directing groups as mono or bidentate coordinating groups for various metal catalysts.

Article, Department of Chemistry, 540 Chemistry, Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Biochemistry, Environmental Chemistry, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Environmental Chemistry, Biochemistry, Mass spectrometry, Chemical purity, Chemistry, Quadrupole mass analyzer, Molecular imaging, Trace Amounts, Radiochemistry, Molecule, Volume concentration, Positron emission tomography, medicine.diagnostic_test, and medicine

Mass spectrometry (MS) has longstanding applications in radiochemistry laboratories, stemming from carbon-dating. However, research on the development of radiotracers for molecular imaging with either positron emission tomography (PET) or single photon emission computed tomography has yet to take full advantage of MS. This inertia has been attributed to the relatively low concentrations of radiopharmaceutical formulations and lack of access to the required MS equipment due to the high costs for purchase and maintenance of specialized MS systems. To date, single quadrupole (SQ)-MS coupled to liquid chromatography (LC) systems is the main form of MS that has been used in radiochemistry laboratories. These LC/MS systems are primarily used for assessing the chemical purity of radiolabeling precursor or standard molecules but also have applications in the determination of metabolites. Herein, we highlight personal experiences using a compact SQ-MS in our PET radiochemistry laboratories, to monitor the small amounts of carrier observed in most radiotracer preparations, even at high molar activities. The use of a SQ-MS in the observation of the low mass associated with non-radioactive species which are formed along with the radiotracer from the trace amounts of carrier found is demonstrated. Herein, we describe a pre-concentration system to detect dilute radiopharmaceutical formulations and metabolite analyses by SQ-MS. Selected examples where SQ-MS was critical for optimization of radiochemical reactions and for unequivocal characterization of radiotracers are showcased. We also illustrate examples where SQ-MS can be applied in identification of radiometal complexes and development of a new purification methodology for Pd-catalyzed radiofluorination reactions, shedding light on the identity of metal complexes present in the labelling solution.

cellulose, ionic liquid, polymerized ionic liquid, composite, lcsh:Biology (General), lcsh:QH301-705.5, lcsh:Chemistry, lcsh:QD1-999, drug-delivery, polysaccharides, solvent, functionalization, polymers, chloride, fibers, gels, polymerization, CATALYSIS, SPECTROSCOPY, MOLECULAR BIOLOGY, COMPUTER SCIENCE APPLICATIONS, CHEMISTRY, PHYSICAL, CHEMISTRY, ORGANIC, CHEMISTRY, INORGANIC AND NUCLEAR, Review, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, General Medicine, Polymer, chemistry.chemical_classification, chemistry, Cellulosic ethanol, Dissolution, Surface modification, Materials science, Chemical engineering, Chemical modification, Polysaccharide, Ionic liquid, chemistry.chemical_compound, Cellulose, and Organic chemistry

Due to its abundance and a wide range of beneficial physical and chemical properties, cellulose has become very popular in order to produce materials for various applications. This review summarizes the recent advances in the development of new cellulose materials and technologies using ionic liquids. Dissolution of cellulose in ionic liquids has been used to develop new processing technologies, cellulose functionalization methods and new cellulose materials including blends, composites, fibers and ion gels. The financial support of the European Commission through Project RENAISSANCE-ITN 289347 is acknowledged.