Origin of Octafluorocyclopentene Polyelectrophilicity.

Octafluorocyclopentene (OFCP) has found utility as a polyelectrophile in substitution cascades that form complex macrocyclic compounds. The Harran group synthesis of macrocyclic polypeptides depends on OFCP as a linker, combining with four different nucleophilic units of a polypeptide. We report a computational investigation of the origins of OFCP reactivity and a rationale for controlled mono-, di-, tri-, and tetrasubstitution of fluoride ions by heteroatomic nucleophiles. The roles of inductive, negative hyperconjugative, and resonance electron-donation by fluoride substituents are explored for the reaction of OFCP, less-fluorinated analogues, and common electrophilic alkenes with several different nucleophiles.

Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds.

We synthesized six new camphor-derived homochiral thioureas 1-6, from commercially available (1R)-(-)-camphorquinone. These new compounds 1-6 were evaluated as asymmetric organocatalysts in the stereoselective formation of glycosidic bonds, with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl and 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates as donors, and several alcohols as glycosyl acceptors, such as methanol, ethanol, 1-propanol, 1-butanol, 1-octanol, iso-propanol, tert-butanol, cyclohexanol, phenol, 1-naphtol, and 2-naphtol. Optimization of the asymmetric glycosylation reaction was achieved by modifying reaction conditions such as solvent, additive, loading of catalyst, temperature, and time of reaction. The best result was obtained with 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates, using 15 mol% of organocatalyst 1, in the presence of 2 equiv of MeOH in solvent-free conditions at room temperature for 1.5 h, affording the glycosidic compound in a 99% yield and 1:73 α:ß stereoselectivity; under the same reaction conditions, without using a catalyst, the obtained stereoselectivity was 1:35 α:ß. Computational calculations prior to the formation of the products were modeled, using density functional theory, M06-2X/6-31G(d,p) and M06-2X/6-311++G(2d,2p) methods. We observed that the preference for ß glycoside formation, through a stereoselective inverted substitution, relies on steric effects and the formation of hydrogen bonds between thiourea 1 and methanol in the complex formed.

Cascade Synthesis of Fluorinated Spiroheterocyclic Scaffolding for Peptidic Macrobicycles.

Octafluorocyclopentene (OFCP) engages linear, unprotected peptides in polysubstitution cascades that generate complex fluorinated polycycles. The reactions occur in a single flask at 0-25 °C and require no catalysts or heavy metals. OFCP can directly polycyclize linear sequences using native functionality, or fluorospiroheterocyclic intermediates can be intercepted with exogenous nucleophiles. The latter tactic generates molecular hybrids composed of peptides, sugars, lipids, and heterocyclic components. The platform can create stereoisomers of both single- and double-looped macrocycles. Calculations indicate that the latter can mimic diverse protein surface loops. Subsets of the molecules have low energy conformers that shield the polar surface area through intramolecular hydrogen bonding. A significant fraction of OFCP-derived macrocycles tested show moderate to high passive permeability in parallel artificial membrane permeability assays.

Self-Assembled Monolayer of Monomercaptoundecahydro-closo-dodecaborate on a Polycrystalline Gold Surface.

In this work, we present an electrochemical study of the boron cage monomercaptoundecahydro-closo-dodecaborate [B12H11SH]2- in solution and in a self-assembled monolayer over a polycrystalline gold electrode. Cyclic voltammetry of the anion [B12H11SH]2- in solution showed a shift in the peak potentials related to the redox processes of gold hydroxides, which evidences the interaction between the boron cage and the gold surface. For an Au electrode modified with the anion [B12H11SH]2-, cyclic voltammetry response of the probe Fe(CN)63-/Fe(CN)64- showed a ΔEp value typical for a surface modification. Electrochemical impedance spectroscopy presented Rtc and Cdl values related to the formation of a self-assembled monolayer (SAM). A comparison of electrochemical responses of a modified electrode with thioglycolic acid (TGA) reveals that the boron cage [B12H11SH]2- diminishes the actives sites over the Au surface due to the steric effects. Differential capacitance measurements for bare gold electrode and those modified with [B12H11SH]2- and (TGA), indicate that bulky thiols enhance charge accumulation at the electrode-solution interface. In addition to electrochemical experiments, DFT calculations and surface plasmon resonance measurements (SPR) were carried out to obtain quantum chemical descriptors and to evaluate the molecular length and the dielectric constant of the Boron cage. From SPR experiments, the adsorption kinetics of [B12H11SH]2- were studied. The data fit for a Langmuir kinetic equation, typical for the formation of a monolayer.

How to adapt sexual and reproductive health services to the needs and circumstances of trans people- a qualitative study in Colombia.

BACKGROUND: People living a trans-life require access to equitable healthcare services, policies and research that address their needs. However, trans people have experienced different forms of violence, discrimination, stigma, and unfair access barriers when dealing with healthcare providers. Therefore, adapting sexual and reproductive health services with the purpose of providing more equitable, inclusive and discrimination-free healthcare services is an urgent need. The article presents an example of how operative research can be used in order to adjust sexual and reproductive healthcare services to trans people's needs, identities and circumstances. METHODS: This is a qualitative study written from a constructivist perspective, and it is based on the voices and experiences of trans people in four major cities in Colombia. The research used a combination of focus groups of discussion (n = 6) and in-depth interviews with trans people (n = 13) in Barranquilla, Bogota, Cali and Medellin. This research had two specific objectives: i) identifying the main sexual and reproductive health needs of people living a trans-life; and ii) generating new evidence in order to guide the adaptation of sexual and reproductive health services centered to trans people's needs, identities, and circumstances. Qualitative data codification and analysis was using NVivo. RESULTS: Once access barriers to sexual and reproductive health services, unmet sexual and reproductive health needs were identified, the research helped define strategies to adapt sexual and reproductive health services to the needs, identities, and circumstances of people living a trans-life in Colombia. Amongst the main barriers found were healthcare costs, lack of insurance, stigmatization, discrimination and abuse by health care providers. Perhaps among the most notable sexual and reproductive health needs presented were trans-specific services such as sensitive assistance for the transition process, endocrinology appointments, and sex reaffirmation surgeries. CONCLUSIONS: The evidence obtained from this research allowed Profamilia, a Colombian healthcare provider, to adapt the sexual and reproductive health services it provides to people living a trans-life in Colombia. Furthermore, it was possible for Profamilia to design and implement an inclusive sexual and reproductive health program that specifically addresses trans people's needs, identities, and circumstances.

Syntheses of Atypically Fluorinated Peptidyl Macrocycles through Sequential Vinylic Substitutions.

Small peptides containing combinations of cysteine, tyrosine, histidine, and serine residues react with octafluorocyclopentene (OFCP) to afford atypically structured macrocycles through successive vinylic substitutions. The reactions proceed rapidly in air at 0 °C and are tolerant of spectating tryptophan, asparagine, glutamine, and threonine residues. Hexapeptides of consensus sequence YXCXXC displace four fluorine atoms from OFCP to generate fluorinated macrobicyclic compounds that display dual-turn surfaces. The method provides facile access to a wide range of previously unknown heterocyclic structures.

Assessment of the nursing skill mix in Mozambique using a task analysis methodology.

BACKGROUND: The density of the nursing and maternal child health nursing workforce in Mozambique (0.32/1000) is well below the WHO minimum standard of 1 nurse per 1000. Two levels of education were being offered for both nurses and maternal child health nurses, in programmes ranging from 18 to 30 months in length. The health care workforce in Mozambique also includes Medical Technicians and Medical Agents, who are also educated at either basic or mid-level. The Ministry of Health determined the need to document the tasks that each of the six cadres was performing within various health facilities to identify gaps, and duplications, in order to identify strategies for streamlining workforce production, while retaining highest educational and competency standards. The methodology of task analysis (TA) was used to achieve this objective. This article provides information about the TA methodology, and selected outcomes of the very broad study. METHODS: A cross-sectional descriptive task analysis survey was conducted over a 15 month period (2008-2009). A stratified sample of 1295 individuals was recruited from every type of health facility in all of Mozambique's 10 provinces and in Maputo City. Respondents indicated how frequently they performed any of 233 patient care tasks. Data analysis focused on identifying areas where identical tasks were performed by the various cadres. Analyses addressed frequency of performance, grouped by level of educational preparation, within various types of health facilities. RESULTS: Task sharing ranged from 74% to 88% between basic and general nurse cadres and from 54% to 88% between maternal and child health nurse cadres, within various health facility types. Conversely, there was distinction between scope of practice for nursing and maternal/child health nursing cadres. CONCLUSION: The educational pathways to general nursing and maternal/child health nursing careers were consolidated into one 24 month programme for each career. The scopes of practice were affirmed based on task analysis survey data.

2,5-Bis{[(-)-(S)-1-(4-bromo-phen-yl)eth-yl]imino-meth-yl}thio-phene.

The title compound, C22H20Br2N2S, was synthesized under solvent-free conditions. The mol-ecule shows crystallographic C 2 symmetry, with the S atom of the central thio-phene ring lying on a twofold rotation axis. Furthermore, as a consequence of the (S,S) stereochemistry, the mol-ecule has a twisted conformation. The dihedral angle between the thio-phene and benzene rings is 72.7 (2)° and that between the two benzene rings is 55.9 (2)°. In the crystal, mol-ecules are arranged in a chevron-like pattern, without any significant inter-molecular inter-actions.

Bis{(S)-(-)-N-[(2-biphen-yl)methyl-idene]-1-(4-meth-oxy-phen-yl)ethyl-amine-κN}di-chlorido-palladium(II).

The PdII complex bis-{(S)-(-)-N-[(biphenyl-2-yl)methyl-idene]1-(4-meth-oxy-phen-yl)ethanamine-κN}di-chlorido-palladium(II), [PdCl2(C22H21NO)2], crystallizes in the monoclinic Sohncke space group P21 with a single mol-ecule in the asymmetric unit. The coordination environment around the palladium is slightly distorted square planar. The N-Pd-Cl bond angles are 91.85 (19), 88.10 (17), 89.96 (18), and 90.0 (2)°, while the Pd-Cl and Pd-N bond lengths are 2.310 (2) and 2.315 (2) Šand 2.015 (2) and 2.022 (6) Å, respectively. The crystal structure features inter-molecular N-H⋯Cl and intramolecular C-H⋯Pd inter-actions, which lead to the formation of a supramolecular framework structure.

(S)-(+)-1-(4-Bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine and bis-{(S)-(+)-1-(4-bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine-κN}di-chlorido-palladium(II).

The (S)-(+)-1-(4-bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine ligand, C16H16BrNO, (I), was synthesized through the reaction of 4-meth-oxy-anisaldehyde with (S)-(-)-1-(4-bromo-phen-yl)ethyl-amine. It crystallizes in the ortho-rhom-bic space group P212121 belonging to the Sohncke group, featuring a single mol-ecule in the asymmetric unit. The refinement converged successfully, achieving an R factor of 0.0508. The PdII com-plex bis-{(S)-(+)-1-(4-bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine-κN}di-chlorido-pal-ladium(II), [PdCl2(C16H16BrNO)2], (II), crystallizes in the monoclinic space group P21 belonging to the Sohncke group, with two mol-ecules in the asymmetric unit. The central atom is tetra-coordinated by two N atoms and two Cl atoms, resulting in a square-planar configuration. The imine moieties exhibit a trans configuration around the PdII centre, with average Cl-Pd-N angles of approximately 89.95 and 90°. The average distances within the palladium com-plex for the two mol-ecules are ∼2.031 Šfor Pd-N and ∼2.309 Šfor Pd-Cl.

L-Citrullinato-Bipyridine and L-Citrullinato-Phenanthroline Mixed Copper Complexes: Synthesis, Characterization and Potential Anticancer Activity.

Citrulline (C6H13N3O3) is an amino acid found in the body as a zwitterion. This means its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, citrulline possesses a terminal ureido group on its aliphatic chain, which also appears to coordinate. Here, two new mixed complexes of citrulline were made with 1,10-phenanthroline and 2,2'-bipyridine. These compounds, once dissolved in water, gave aquo-complexes that were subject to DFT studies and in vitro toxicity studies on cancer cell lines (HeLa, MDA-MB-231, HCT 15, and MCF7) showed promising results. Docking studies with DNA were also conducted, indicating potential anticancer properties.

The Relationship Between Gut Microbiome and Ophthalmologic Diseases: A Comprehensive Review.

The gut microbiome has been studied in recent years due to its association with various pathological pathways involved in different diseases, caused by its structure, function, and diversity alteration. The knowledge of this mechanism has generated interest in the investigation of its relationship with ophthalmologic diseases. Recent studies infer the existence of a gut-eye microbiota axis, influenced by the intestinal barrier, the blood-retina barrier, and the immune privilege of the eye. A common denominator among ophthalmologic diseases that have been related to this axis is inflammation, which is perpetuated by dysbiosis, causing an alteration of the intestinal barrier leading to increased permeability and, in turn, the release of components such as lipopolysaccharides (LPS), trimethylamine oxide (TMAO), and bacterial translocation. Some theories explain that depending on how the microbiome is composed, a different type of T cells will be activated, while others say that some bacteria can pre-activate T cells that mimic ocular structures and intestinal permeability that allow leakage of metabolites into the circulation. In addition, therapies such as probiotics, diet, and fecal microbiota transplantation (FMT) have been shown to favor the presence of a balanced population of microorganisms that limit inflammation and, in turn, generate a beneficial effect in these eye pathologies. This review aims to analyze how the intestinal microbiome influences various ocular pathologies based on microbial composition and pathological mechanisms, which may provide a better understanding of the diseases and their therapeutic potential.

6-[(4'-Ethoxycarbonyl-[1,1'-biphenyl]-4-yl)oxy]hexanoic acid.

In the title compound, C21H24O5, the dihedral angle between the benzene rings is 19.57 (15)°. In the crystal, the mol-ecular arrangement makes up head-to-head centrosymmetric dimers assembled by pairs of O-H⋯O bonds; this arrangement builds a graph-set ring motif of R (2) 2(8). The dimers are linked into a tape running along the b-axis direction through C-H⋯O inter-actions. The packing is further consolidated by C-H⋯π inter-actions, forming layers parallel to (10-2).

2,2-Dimethyl-5-(2-nitro-benzyl-idene)-1,3-dioxane-4,6-dione.

The asymmetric unit of the title compound, C13H11NO6, contains two mol-ecules in both of which the six-membered 1,3-dioxane-4,6-dione ring shows a screw-boat conformation. The dihedral angles between the best planes through the six-membered rings are 47.8 (2) and 49.8 (2)°. In the crystal, C-H⋯O inter-actions link the mol-ecules, building a supramolecular sheet parallel to the c axis.

(+)-(S)-N-[(1-Benzo-thio-phen-2-yl)methyl-idene]-1-(naphthalen-1-yl)ethyl-amine.

In the title compound, C21H17NS, the C=N double bond shows an E conformation. The dihedral angle between the mean planes of the naphthyl residue and the benzo-thio-phene residue is 89.14 (6)°. The crystal packing is stabilized by inter-molecular C-H⋯π inter-actions, building a ribbon structure along the a axis.

Second monoclinic form of (E)-3-(4-fluoro-phen-yl)-1-phenyl-prop-2-en-1-one.

The unit-cell dimensions and space group of the second monoclinic polymorph of the title compound, C15H11FO, differ from those of the previously reported form [Jing (2009 ▶). Acta Cryst. E65, o2515]. The title compound shows an E conformation of the C=C bond with the 4-fluoro-phenyl group opposite to the benzoyl group. The torsion angle of between the planes of the 4-fluoro-phenyl and benzoyl groups is 10.53 (6)°. In the crystal, weak C-H⋯O and C-H⋯F inter-actions form a cross-linked packing motif, building sheets parallel to (-102).

2-[3-(1H-Benzimidazol-2-yl)prop-yl]-1H-benzimidazol-3-ium 3,4,5-tri-hydroxy-benzoate-1,3-bis-(1H-benzimidazol-2-yl)propane-ethyl acetate (2/1/2.94): co-crystallization between a salt, a neutral mol-ecule and a solvent.

The chemical formula of the title compound, 2C17H17N4 +·2C7H5O5 -·C17H16N4·2.94C4H8O2, was established by X-ray diffraction of a single-crystal obtained by reacting 1,3-bis-(benzimidazol-2-yl)propane (L) and gallic acid (HGal) in ethyl acetate. The mol-ecular structure can be described as a salt (HL)+(Gal)- co-crystallized with a mol-ecule L, with a stoichiometric relation of 2:1. Moreover, large voids in the crystal are filled with ethyl acetate, the amount of which was estimated by using a solvent mask during structure refinement, affording the chemical formula (HL +·Gal-)2·L·(C4H8O2)2.94. The arrangement of components in the crystal is driven by O-H⋯O, N-H⋯O and O-H⋯N hydrogen bonds rather than by π-π or C-H⋯π inter-actions. In the crystal, mol-ecules and ions shape the boundary of cylindrical tunnels parallel to [100] via R (rings) and D (discrete) supra-molecular motifs. These voids, which account for about 28% of the unit-cell volume, contain disordered solvent mol-ecules.

Minimally Invasive Surgical Technique for the Management of Giant Dumbbell Spinal Schwannoma.

BACKGROUND: Completely extradural spinal schwannomas have a unique morphology (dumbbell tumors) with an intra- and extraspinal component. When they compromise two contiguous vertebral bodies or have an extraspinal extension >2.5 cm, they are classified as giant spinal schwannomas. The aim of this study is to present our experience in the surgical management of completely extradural giant spinal schwannomas with a minimally invasive approach. METHODS: This study is a case series of patients treated at the Neurosurgery Department of the University Clinical and Provincial Hospital of Barcelona, Spain, between January 2016 and December 2019. RESULTS: Fifteen patients met the inclusion criteria, with thoracic and lumbar spines being the most frequent locations. All patients underwent surgical treatment, with a mini-open interlaminar and far-lateral technique. Total gross resection was accomplished in all patients and spine instrumentation was not necessary. CONCLUSIONS: Microsurgery is the treatment of choice for spinal schwannomas, and gross total resection with low morbidity must be the surgical goal. Mini-open interlaminar and far-lateral access is a valid surgical option, with low morbidity in experienced hands, and there is no need for spinal instrumentation.

(E)-1-Benzyl-idene-2,2-diphenyl-hydrazine.

The asymmetric unit of the title compound, C(19)H(16)N(2), contains two independent mol-ecules, both of which show an E configuration with respect to the C=N bond. The dihedral angles between the phenyl rings bonded to the hydrazine group are 81.00 (10) and 88.34 (8)° in the two mol-ecules. Inter-molecular C-H⋯π inter-actions are observed in the crystal structure.

(S)-(-)-2-(1H-Indol-3-yl)-N-(1-phenyl-eth-yl)acetamide.

In the title compound, C(18)H(18)N(2)O, the dihedral angle between the indole system and the phenyl ring is 17.2 (2)°. The crystal packing features two N-H⋯O hydrogen bonds, which link the mol-ecules into layers parallel to (001). The absolute configuration was determined by the synthetic procedure and was set according to the starting material.