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.

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.

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.

(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.

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.

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.

Electrochemical and CD-spectroelectrochemical studies of the interaction between BSA and the complex [Cu(Bztpen)]2+, (Bztpen = (N-benzyl-N, N', N'-tris (pyridin-2-ylmethyl) ethylenediamine).

In this work we report the electrochemical, spectroscopical and spectro-electrochemical studies of a model complex [CuΙΙ(Bztpen)]2+, (Bztpen = (N-benzyl-N,N',N'-tris(pyridin-2-ylmethyl)ethylenediamine) in order to propose a methodology to evaluate the interaction of potential metal based anticancer agents during electron transfer processes, with transport proteins such as Bovine Serum Albumin (BSA). It was possible to establish a reversible electron transfer [CuΙΙ(Bztpen)]2+ +1e â†’ [CuΙ(Bztpen)]+ and a weak interaction energy between BSA and [CuΙΙ(Bztpen)] and [CuΙ(Bztpen)] species, with no adsorption of protein over the electrode surface. Circular Dichroism (CD) Spectroelectrochemistry, not reported before, reveals no significant changes in BSA structure during the electron transfer [CuΙΙ(Bztpen)]2+ + 1e â†’ [CuΙ(Bztpen)]+. CD experiments at variable temperature for BSA denaturalization in the absence and in the presence of [CuΙΙ(Bztpen)]2+, shown no change in thermodynamic parameters due to low interaction between the transport protein and copper complex.

Clinical and Radiological Outcome in a Series of Patients Treated by Anterior Cervical Discectomy and Fusion: Retrospective Controlled Study With 2 Different Stand-Alone Cages.

BACKGROUND: Cervical spine balance and alignment targets after cervical spine surgery are poorly established in patients with cervical spine degenerative disease surgically treated by anterior cervical discectomy and fusion (ACDF). The objective of the study is to determine the correlation between radiological and clinical outcomes in patients surgically treated by ACDF with 2 different stand-alone cervical cages. METHODS: Clinical outcomes were evaluated using visual analog scale (VAS), Neck Disability Index (NDI), Nurick Scale, and Japanese Orthopedic Association score for myelopathy. Radiological evaluation included cervical and segmental Cobb angles, cervical sagittal vertical axis (cSVA), T1 slope (T1s), C0-C2 angle, fusion rates, adjacent segment degeneration, and cage subsidence. RESULTS: A total of 80 patients were included with an average age of 53 years. There was a statistically significant improvement in both clinical and radiological evaluations. There was a statistical significant correlation between cervical pain on cervical VAS and cSVA. There was a significant correlation between postoperative T1s and cSVA, related to the improvement in cervical angles. There was no significant difference in rates of fusion, adjacent segment changes, or reoperation between both cervical cages, and there was a higher rate of subsidence in the Aleutian group. There were significant differences between both groups on postoperative NDI and VAS, but this difference is not maintained during follow-up. CONCLUSIONS: Cervical sagittal balance is directly related to clinical outcome in patients with cervical spine degenerative disease. Both cervical implants analyzed were comparable in clinical and radiological outcomes. CLINICAL RELEVANCE: There are important clinical and radiological parameters that should be taken into account for the analysis of the surgical outcome of patients treated by ACDF; this is one of the few studies that report the results with 2 different cervical cage designs.

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.

Crystal structure of r-1,c-2-dibenzoyl-t-3,t-4-bis-(2-nitro-phen-yl)cyclo-butane.

The condensation reaction of aceto-phenone (1-phenyl-ethan-1-one) with 2-nitro-benzaldehyde in the molten state yielded the expected chalcone, (E)-3-(2-nitro-phen-yl)-1-phenyl-prop-2-en-1-one, and, unexpectedly, the title compound, C30H22N2O6, which results from the syn head-to-head [2 + 2] cyclo-addition of the chalcone. The mol-ecular structure of the dimer shows that the four benzene rings of the substituents are oriented in such a way that potential steric hindrance is minimized, whilst allowing some degree of inter-molecular π-π inter-actions for crystal stabilization. In the mol-ecule, one nitro group is disordered over two positions, with occupancies for each part of 0.876 (7) and 0.127 (7).

Novel synthesis of steroidal oximes and lactams and their biological evaluation as antiproliferative agents.

A novel three-step methodology to obtain 6a-aza-B-homo steroidal lactams has been developed starting from the easily available cholesterol and pregnenolone. In addition, a new procedure for the synthesis of a 6a-aza-B-homo steroidal lactam analog of vespertilin, starting from diosgenin has been established. In both synthetic pathways, the key intermediate is a hydroxyimino derivative obtained in a one- or two-step sequence from the starting materials. These methods avoid the use of hazardous oxidant agents in the process. The new steroidal oximes and lactams were examined for their antiproliferative activities against several tumor cell lines. The 6,23-dihydroxyimino derivative exhibited the highest activity with GI50 values of 11-22µM.

Crystal structures of ten enanti-opure Schiff bases bearing a naphthyl group.

Using a general solvent-free procedure for the synthesis of chiral Schiff bases, the following compounds were synthesized and their crystal structures determined: (S)-(+)-2-{[(1-phenyl-eth-yl)imino]-meth-yl}naphthalene, C19H17N, (1), (S)-(+)-2-({[(4-methyl-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C20H19N, (2), (R)-(-)-2-({[(4-meth-oxy-lphen-yl)eth-yl]imino}-meth-yl)naphthalene, C20H19NO, (3), (R)-(-)-2-({[(4-fluoro-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16FN, (4), (S)-(+)-2-({[(4-chloro-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16ClN, (5), (S)-(+)-2-({[(4-bromo-phen-yl)eth-yl]imino}-meth-yl)naphthalene, C19H16BrN, (6), (S)-(+)-2-({[1-(naphthalen-1-yl)eth-yl]imino}-meth-yl)naph-thalene, C23H19N, (7), (S)-(+)-2-{[(1-cyclo-hexyl-eth-yl)imino]-meth-yl}naph-tha-lene, C19H23N, (8), (S)-(-)-2-{[(1,2,3,4-tetra-hydro-naphthalen-1-yl)imino]meth-yl}naphthalene, C21H19N, (9), and (+)-2-({[(1S,2S,3S,5R)-2,6,6-tri-methylbi-cyclo-[3.1.1]hept-3-yl]imino}-meth-yl}naphthalene, C21H25N, (10). The moiety provided by the amine generates conformational flexibility for these imines. In the crystals, no strong inter-molecular contacts are observed, in spite of the presence of aromatic groups.

Design of a protocol for obtaining genomic DNA from saliva using mouthwash: Samples taken from patients with periodontal disease.

BACKGROUND: Obtaining high quality genomic DNA safely and economically is vital for diverse studies of large populations aimed at evaluating the role of genetic factors in susceptibility to disease. AIM: This study was to test a protocol for the extraction of high quality genomic DNA from saliva samples obtained with mouthwash and taken from patients with periodontal disease. METHODS: Saliva samples were taken from 60 patients and then stored at room temperature. DNA extraction was carried out at distinct post-sampling times (10, 20 and 30 days). Evaluation of genomic DNA was performed with spectrophotometry, electrophoresis, and PCR genotyping and sequencing. RESULTS: The greatest concentration of DNA obtained was 352 µg at 10 days post-sampling, followed by 121.025 µg and 19.59 µg at 20 and 30 days, respectively. When determining the purity of DNA with the spectrophotometric ratio of 260/230, the relations of 1.20, 1.40 and 0.781 were obtained for 10, 20 and 30 days, respectively. In all samples, it was possible to amplify the product of 485 bp and the sequence of the amplicons showed 95% similarity to the reference sequence. CONCLUSION: The present protocol represents an easy, safe and economical technique for obtaining high quality genomic DNA.

Crystal structures of four chiral imine-substituted thio-phene derivatives.

A series of thio-phenes substituted in positions 2 and 5 by imine groups have been synthesized using a solvent-free approach, and their crystal structures determined. The substituents are chiral groups, and the expected absolute configuration for each mol-ecule was confirmed by refinement of the Flack parameter. The compounds are 2,5-bis-[(S)-(+)-(1,2,3,4-tetra-hydro-naphthalen-1-yl)imino]-thio-phene, C26H26N2S, (I), 2,5-bis-{[(R)-(-)-1-(4-meth-oxy-phen-yl)eth-yl]imino-meth-yl}thio-phene, C24H26N2O2S, (II), 2,5-bis-{[(R)-(-)-1-(4-fluoro-phen-yl)eth-yl]imino-meth-yl}thio-phene, C22H20F2N2S, (III), and 2,5-bis-{[(S)-(+)-1-(4-chloro-phen-yl)eth-yl]imino-meth-yl}thio-phene, C22H20Cl2N2S, (IV). A common feature of all four mol-ecules is the presence of twofold symmetry. For (I), which crystallizes in the triclinic space group P1, this symmetry is non-crystallographic, but for (II) in C2 and the isomorphous structures (III) and (IV) that crystallize in P21212, the twofold symmetry is crystallographically imposed with one half of each mol-ecule in the asymmetric unit. The comparable mol-ecular symmetry in the four structures is also reflected in similar packing, with mol-ecules aggregated to form chains through weak C-H⋯S inter-actions.

Crystal structure of (2S,4R)-ethyl 4-nitro-methyl-1-[(S)-1-phenyl-eth-yl]-6-sulfanyl-idene-piperidine-2-carboxyl-ate.

In the title compound, C17H22N2O4S, a thio-piperidine derivative, the piperidine ring has an envelope conformation with the methyl-ene C atom opposite to the C=S bond as the flap. The nitro-methyl substituent is equatorial while the eth-oxy-carbonyl group is axial. The mean planes of the nitro-methyl group, the carb-oxy group and phenyl ring are inclined to the mean plane through the five planar atoms of the piperidine ring [maximum deviation = 0.070 (4) Å] by 56.8 (2), 83.8 (5) and 87.1 (2)°, respectively. There is an intra-molecular C-H⋯O hydrogen bond involving an H atom of the eth-oxy-carbonyl group and a nitro O atom. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming chains along [100]. The chains are linked by further C-H⋯O hydrogen bonds, forming corrugated layers lying parallel to (001).

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.

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.