Investigation of structural effects on the reactivity of heterocyclic bioactive compounds

Tese de dout., Química, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2008In the course of this investigation, structural effects on the reactivity of a series of heterocyclic compounds, in particular tetrazole and benzisothiazole derivatives, submitted to different chemical environments, were explored. The photochemistry of several representative tetrazoles was considered in solution and for the compounds trapped in a rigid matrix of solidified argon at cryogenic temperatures. UV-excitation resulted in photofragmentation of tetrazoles with a wide range of exit channels. Important mechanistic questions concerning the photodecomposition of allyl-tetrazolyl derivatives in different solvents were answered, and new synthetic methodologies for the preparation of heterocyclic compounds, such as pyrimidinones or oxazines, from allyl-tetrazoles, were developed. For the matrix-isolated compounds, since the obtained fragments in general stay in the matrix cage where they are formed, no subsequent cross-reactions involving species resulting from photolysis of different reactant molecules can occur. This fact introduced a useful simplification for the interpretation of the reaction mechanisms. FTIR spectroscopy provided experimental frequencies and intensities of characteristic absorptions of the matrix-isolated chemical species, both for reagents and photoproducts. The analysis of experimental data was assisted by their direct comparison with the vibrational spectra theoretically calculated for the single molecule in vacuum. Spectroscopic characterization of a number of relatively unusual or highly reactive molecules, formed from photolysis of matrix-isolated tetrazoles, is presented for the first time. Novel tetrazolyl and benzisothiazolyl naphthylmethylic ethers were synthesized and the development of experimental conditions for their palladium-catalysed hydrogenolysis, using a hydrogen donor or molecular hydrogen, was carried out successfully. Structural effects on the reactivity of the heteroaromatic ethers were investigated. Furthermore, new benzisothiazole-tetrazolyl derivatives differing on the spacer-group used for linkage of the two heterocyclic systems were designed, produced and tested as multidentate ligands in coordination reactions with transition-metal complexes

The current status of radiological clinical audit and feedback on the ESR Guide to Clinical Audit in Radiology and the ESR Clinical Audit Tool (Esperanto) – an ESR Survey of European Radiology Departments

Clinical audit “according to national procedures” is a legal requirement as defined within the recently implemented European Council Basic Safety Standards Directive (BSSD), 2013/59/Euratom. A survey was undertaken in 2019 to assess the current status of clinical audit in European radiology departments and for feedback on the recently published “ESR Guide to Clinical Audit in Radiology” and the “ESR Clinical Audit Tool (Esperanto)”. The survey was distributed within the European Society of Radiology (ESR) EuroSafe Imaging Star network and also to European national radiological societies which are institutional members of the ESR

In vitro assessment of antimicrobial, antioxidant, and cytotoxic properties of Saccharin-Tetrazolyl and-Thiadiazolyl derivatives: the simple dependence of the pH value on antimicrobial activity

The antimicrobial, antioxidant, and cytotoxic activities of a series of saccharin-tetrazolyl and -thiadiazolyl analogs were examined. The assessment of the antimicrobial properties of the referred-to molecules was completed through an evaluation of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against Gram-positive and Gram-negative bacteria and yeasts. Scrutiny of the MIC and MBC values of the compounds at pH 4.0, 7.0, and 9.0 against four Gram-positive strains revealed high values for both the MIC and MBC at pH 4.0 (ranging from 0.98 to 125 µg/mL) and moderate values at pH 7.0 and 9.0, exposing strong antimicrobial activities in an acidic medium. An antioxidant activity analysis of the molecules was performed by using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, which showed high activity for the TSMT (N-(1-methyl-2H-tetrazol-5-yl)-N-(1,1-dioxo-1,2-benzisothiazol-3-yl) amine, 7) derivative (90.29% compared to a butylated hydroxytoluene positive control of 61.96%). Besides, the general toxicity of the saccharin analogs was evaluated in an Artemia salina model, which displayed insignificant toxicity values. In turn, upon an assessment of cell viability, all of the compounds were found to be nontoxic in range concentrations of 0-100 µg/mL in H7PX glioma cells. The tested molecules have inspiring antimicrobial and antioxidant properties that represent potential core structures in the design of new drugs for the treatment of infectious diseases.Funding Agency Portuguese Foundation for Science and Technology UID/QUI/00100/2019 UID/MULTI/04326/2019 -CCMAR Portuguese Foundation for Science and Technology SFRH/BPD/99851/2014 IST-ID/115/2018info:eu-repo/semantics/publishedVersio

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

CGIAR modeling approaches for resource constrained scenarios: IV Models for analyzing socio‐economic factors to improve policy recommendations

International crop-related research as conducted by the CGIAR uses crop modelingfor a variety of purposes. By linking crop models with economic models andapproaches, crop model outputs can be effectively used as inputs into socioeco-nomic modeling efforts for priority setting and policy advice using ex-ante impactassessment of technologies and scenario analysis. This requires interdisciplinarycollaboration and very often collaboration across a variety of research organizations.This study highlights the key topics, purposes, and approaches of socioeconomicanalysis within the CGIAR related to cropping systems. Although each CGIARcenter has a different mission, all CGIAR centers share a common strategy of strivingtoward a world free of hunger, poverty, and environmental degradation. This meansresearch is mostly focused toward resource-constrained smallholder farmers. Thereview covers global modeling efforts using the IMPACT model to farm householdbio-economic models for assessing the potential impact of new technologies onfarming systems and livelihoods. Although the CGIAR addresses all aspects of foodsystems, the focus of this review is on crop commodities and the economic analysislinked to crop-growth model results. This study, while not a comprehensive review,provides insights into the richness of the socioeconomic modeling endeavors withinthe CGIAR. The study highlights the need for interdisciplinary approaches to addressthe challenges this type of modeling faces

Structural and functional insights into asymmetric enzymatic dehydration of alkenols

The asymmetric dehydration of alcohols is an important process for the direct synthesis of alkenes. We report the structure and substrate specificity of the bifunctional linalool dehydratase isomerase (LinD) from the bacterium Castellaniella defragrans that catalyzes in nature the hydration of β-myrcene to linalool and the subsequent isomerization to geraniol. Enzymatic kinetic resolutions of truncated and elongated aromatic and aliphatic tertiary alcohols (C5-C15) that contain a specific signature motif demonstrate the broad substrate specificity of LinD. The three-dimensional structure of LinD from Castellaniella defragrans revealed a pentamer with active sites at the protomer interfaces. Furthermore, the structure of LinD in complex with the product geraniol provides initial mechanistic insights into this bifunctional enzyme. Site-directed mutagenesis confirmed active site amino acid residues essential for its dehydration and isomerization activity. These structural and mechanistic insights facilitate the development of hydrating catalysts, enriching the toolbox for novel bond-forming biocatalysis

Photochemical Ring-Opening and Intramolecular Hydrogen Shift Reactions in Sulfur Analogues of α-Pyrone

A combined matrix isolation FTIR and theoretical DFT(B3LYP)/6-311++G(d,p) study of the photochemistry of sulfur analogues of α-pyrone [2H-thiopyran-2-one (TP) and 2H-pyran-2-thione (PT)] was carried out. The vibrational spectra of monomers of the compounds isolated in low-temperature argon matrixes were studied experimentally and assigned completely on the basis of theoretical calculations. UV irradiation (λ > 337 nm) of the studied compounds isolated in low-temperature matrixes results mainly in the ring-opening reaction by means of the cleavage of the α-bond. Other photoprocesses, not involving the α-bond-cleavage step (such as generation of Dewar valence isomer), correspond to the minor reaction channels in both studied compounds. The ring-opening photoreaction in PT represents the first reported case of an α-bond cleavage in a compound with a CS group attached to a six-membered ring, in which the internal strain practically does not exist, whereas the corresponding reaction in TP (a cleavage of a C−S bond in the α position with respect to a carbonyl group) is now reported for the first time. Following the ring-opening reactions, isomerization processes and intramolecular hydrogen shift reactions were observed, enabling production of TP from PT and vice versa. A detailed study of such processes was undertaken, and kinetical and mechanistical data are presented and discussed