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A route is developed to (g,g',g''''-trifluoro)neopentyl (TFNP) aryl ethers to extend the methods for the introduction of the tert-butyl group, carrying a fluorine on each of the methyl substituents. The route combines neopentyltosylate 3 with phenols and thiophenols to give efficient substitution reactions to the corresponding TFNP aryl ethers. The three C-F bonds adopt a helical propeller conformation as revealed by computation and single crystal X-ray structure analysis. The LogPs of TFNP ethers are lower (more hydrophilic) than their tert-butyl analogues. The metabolism of selected TFNP ethers was explored in the fungus Cunninghamella elegans.
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The conformational equilibria of selectively halogenated cyclohexanes are explored both experimentally (VT-NMR) for 1,1,4,-trifluorocyclohexane 7 and by computational analysis (M06-2X/aug-cc-pVTZ level), with the latter approach extending to a wider range of more highly fluorinated cyclohexanes. Perhaps unexpectedly, 7ax is preferred over the 7eq conformation by ΔG = 1.06 kcal mol-1, contradicting the accepted norm for substituents on cyclohexanes. The axial preference is stronger again in 1,1,3,3,4,5,5,-heptafluorocyclohexane 9 (ΔG = 2.73 kcal mol-1) as the CF2 groups further polarize the isolated CH2 hydrogens. Theoretical decomposition of electrostatic and hyperconjugative effects by natural bond orbital analysis indicated that nonclassical hydrogen bonding (NCHB) between the C-4 fluorine and the diaxial hydrogens at C-2 and C-6 in cyclohexane 7 and 9 largely accounts for the observed bias. The study extended to changing fluorine (F) for chlorine (Cl) and bromine (Br) at the pseudoanomeric position in the cyclohexanes. Although these halogens do not become involved in NCHBs, they polarize the geminal -CHX- hydrogen at the pseudoanomeric position to a greater extent than fluorine, and consequent electrostatic interactions influence conformer stabilities.
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The (ß,ß',ßâ³-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.
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3'-O-ß-Glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 is identified as a natural product of Streptomyces calvus and Streptomyces virens. It is also generated in vitro by direct ß-glucosylation of 4',5'-didehydro-5'-deoxyadenosine 12 with the enzyme NucGT. The intact incorporation of oxygen-18 and deuterium isotopes from (±)[1-18O,1-2H2]-glycerol 14 into C-5' of nucleocidin 1 and its related metabolites precludes 3'-O-ß-glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 as a biosynthetic precursor to nucleocidin 1.
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Produtos BiológicosRESUMO
Background: Studies to date comparing biceps tenodesis methods in the setting of concomitant rotator cuff repair (RCR) have demonstrated relatively equivalent pain and functional outcomes. Purpose: To compare biceps tenodesis constructs, locations, and techniques in patients who underwent RCR using a large multicenter database. Study Design: Cohort study; Level of evidence, 3. Methods: A global outcome database was queried for patients with medium- and large-sized tears who underwent biceps tenodesis with RCR between 2015 and 2021. Patients ≥18 years of age with a minimum follow-up of 1 year were included. The American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, visual analog scale for pain, and Veterans RAND 12-Item Health Survey (VR-12) scores were compared at 1 and 2 years of follow-up based on construct (anchor, screw, or suture), location (subpectoral, suprapectoral, or top of groove), and technique (inlay or onlay). Nonparametric hypothesis testing was used to compare continuous outcomes at each time point. The proportion of patients achieving the minimal clinically important difference (MCID) at the 1- and 2-year follow-ups were compared between groups using chi-square tests. Results: A total of 1903 unique shoulder entries were analyzed. Improvement in VR-12 Mental score favored anchor and suture fixations at 1 year of follow-up (P = .042) and the onlay tenodesis technique at 2 years of follow-up (P = .029). No additional tenodesis comparisons demonstrated statistical significance. The proportion of patients with improvement exceeding the MCID did not differ based on tenodesis methods for any outcome score assessed at the 1- or 2-year follow-up. Conclusion: Biceps tenodesis with concomitant RCR led to improved outcomes regardless of tenodesis fixation construct, location, or technique. A clear optimal tenodesis method with RCR remains to be determined. Surgeon preference and experience with various tenodesis methods as well as patient clinical presentation should continue to guide surgical decision-making.
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A new isoxazole-based iodo-noium salt, C13H13INO5 +·C2F3O2 -, has been synthesized and structurally characterized. In the crystal, ions are linked by short Iâ¯O contacts to form a neutral tetra-ion aggregate. These combine with C-Hâ¯F and C-Hâ¯O inter-actions to form double-layered two-dimensional sheets in the (001) plane.
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This account describes the evolution of a research programme that started by linking fluoromethylene (-CHF-) groups along aliphatic chains and then progressing to alicyclic rings with contiguous fluorine atoms. Different stereoisomers of aliphatic chains tend to adopt low polarity conformations. In order to force polar conformations, the programme began to address ring systems and in particular cyclohexanes, to restrain conformational freedom and co-aligned C-F bonds. The flagship molecule, all-cis-1,2,3,4,5,6-hexafluorocyclohexane 7, emerged to be the most polar aliphatic compound recorded. The polarity arises because there are three co-aligned triaxial C-F bonds and the six fluorines occupy one face of the ring. Conversely the electropositive hydrogens occupy the other face. These have been termed Janus face cyclohexanes after the Roman god with two faces. The review outlines progress by our group and others in preparing derivatives of the parent cyclohexane 7, in order to explore properties and potential applications of these Janus cyclohexanes.
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PURPOSE: Accurate glenoid component placement in total shoulder arthroplasty (TSA) remains challenging even with preoperative planning, especially for variable glenoid erosion patterns in the coronal plane. METHODS: We retrospectively reviewed 170 primary TSAs in which preoperative planning software was used. After registration of intraoperative bony landmarks, surgeons were blinded to the navigation screen and attempted to implement their plan by simulating placement of a central-axis guide pin: 230 screenshots of simulated guide pin placement were included (aTSA = 66, rTSA = 164). Displacement, error in version and inclination, and overall malposition from the preoperatively-planned target point were stratified by the Favard classification describing superior-inferior glenoid wear: E0 (n = 89); E1 (n = 81); E2 (n = 29); E3(n = 29); E4(n = 2). Malposition was considered > 10° for version/inclination errors or > 4 mm displacement from the starting point. RESULTS: Mean displacement error was 3.5 ± 2.7 mm (aTSA = 2.7 ± 2.3 mm, rTSA = 3.8 ± 2.9 mm), version error was 5.7 ± 4.7° (aTSA = 5.8 ± 4.4°, rTSA = 5.7 ± 4.8°), inclination error was 7.1 ± 5.6 (aTSA = 4.8 ± 4.8°, rTSA = 8.1 ± 5.7°), and malposition rate was 53% (aTSA = 38%, rTSA = 59%). When compared by Favard classification, there were no differences in any measure; when stratified by TSA type, version error differed for rTSAs (P = .038), with E1 having the greatest version error (6.9 ± 5.2°) and E3 the least (4.2 ± 3.4°). When comparing glenoids without wear (E0) and glenoids with superior wear (E2 and E3), the only difference was greater version error in glenoids without wear (6.0 ± 4.9° vs. 4.6 ± 3.7°, P = .041). CONCLUSIONS: Glenoid malposition did not differ based on coronal glenoid morphology. Although, malposition was relatively high, suggesting surgeons should consider alternate techniques beyond preoperative planning and standard instrumentation in TSA. LEVEL OF EVIDENCE III: Retrospective Cohort Study.
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Artroplastia do Ombro , Cavidade Glenoide , Articulação do Ombro , Humanos , Articulação do Ombro/cirurgia , Artroplastia do Ombro/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Escápula/cirurgia , Cavidade Glenoide/diagnóstico por imagem , Cavidade Glenoide/cirurgiaRESUMO
PURPOSE: Various fixation techniques have been described for midshaft clavicle fractures in the literature. We hypothesized that use of the Rockwood pin for fixation of displaced midshaft clavicle fractures would result in favorable outcomes in a young active cohort. METHODS: Patients aged 10-35 years who underwent Rockwood clavicle pin fixation at a single institution were identified. Preoperative and postoperative radiographs were reviewed and assessed for fracture characteristics, postoperative alignment, and radiographic union. Postoperative outcome scores were obtained. RESULTS: A total of 39 patients (age 17.3 ± 3.9 years) with clavicle fracture treated with Rockwood pin were identified. Radiographic review demonstrated that 88% of fractures were 100%, or more, displaced, and surgery achieved near-anatomic reduction in 92% of cases. Average time to radiographic union was 2.3 ± 0.8 months, and average time to clinical union was 2.5 ± 0.3 months. One patient required revision for nonunion (3%). Complete outcome responses were obtained for 24 patients, with an average 40 ± 27.7 months of follow-up. Mean Total Clavicle Functional score was 2.75 ± 3.6 for minor patients. For adult patients, Nottingham Clavicle score was 90.7 ± 10.7, mean American Shoulder and Elbow Society score was 92.4 ± 11.2, and mean Single Assessment Numerical Evaluation score was 88.8 ± 21.5. 77% of adults reported no long-term functional limitation; 54% reported a bump at the prior fracture site, but 100% reported satisfaction with shoulder appearance. CONCLUSIONS: In our cohort of young active patients, treatment with Rockwood pin allowed for anatomic reduction, healing with a low nonunion rate, and favorable patient reported outcomes.
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Fixação Intramedular de Fraturas , Fraturas Ósseas , Adulto , Humanos , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Consolidação da Fratura/fisiologia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fraturas Ósseas/etiologia , Fixação Intramedular de Fraturas/efeitos adversos , Reoperação , Resultado do Tratamento , Fixação Interna de Fraturas , Estudos RetrospectivosRESUMO
The importance of electrostatic nonconventional hydrogen bonds (NCHBs) to the pseudo-anomeric effect of 4-substituted methoxycyclohexanes is evaluated using theory [natural bond orbital (NBO)] to deconvolute electrostatic from other contributing effects. There is an interesting interplay between σCH â σCX* hyperconjugation and the electropositive charge on 3,5-axial hydrogens (Hax). In essence, better σCX* (or πCO*) acceptors increase the charge on 3,5-CHax, which in turn strengthens Cδ+Hax···Î´-OMe NCHB interactions.
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The gene cluster in Streptomyces calvus associated with the biosynthesis of the fluoro- and sulfamyl-metabolite nucleocidin was interrogated by systematic gene knockouts. Out of the 26 gene deletions, most did not affect fluorometabolite production, nine abolished sulfamylation but not fluorination, and three precluded fluorination, but had no effect on sulfamylation. In addition to nucI, nucG, nucJ, nucK, nucL, nucN, nucO, nucQ and nucP, we identified two genes (nucW, nucA), belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster, as required for sulfamyl assembly. Three genes (orf(-3), orf2 and orf3) were found to be essential for fluorination, although the activities of their protein products are unknown. These genes as well as nucK, nucN, nucO and nucPNP, whose knockouts produced results differing from those described in a recent report, were also deleted in Streptomyces virens - with confirmatory outcomes. This genetic profile should inform biochemistry aimed at uncovering the enzymology behind nucleocidin biosynthesis.
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Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Família MultigênicaRESUMO
In the discussion about zoo elephant husbandry, the report of Clubb et al. (2008, Science 322: 1649) that zoo elephants had a "compromised survivorship" compared to certain non-zoo populations is a grave argument, and was possibly one of the triggers of a large variety of investigations into zoo elephant welfare, and changes in zoo elephant management. A side observation of that report was that whereas survivorship in African elephants (Loxodonta africana) improved since 1960, this was not the case in Asian elephants (Elephas maximus). We used historical data (based on the Species360 database) to revisit this aspect, including recent developments since 2008. Assessing the North American and European populations from 1910 until today, there were significant improvements of adult (≥10 years) survivorship in both species. For the period from 1960 until today, survivorship improvement was significant for African elephants and close to a significant improvement in Asian elephants; Asian elephants generally had a higher survivorship than Africans. Juvenile (<10 years) survivorship did not change significantly since 1960 and was higher in African elephants, most likely due to the effect of elephant herpes virus on Asian elephants. Current zoo elephant survivorship is higher than some, and lower than some other non-zoo populations. We discuss that in our view, the shape of the survivorship curve, and its change over time, are more relevant than comparisons with specific populations. Zoo elephant survivorship should be monitored continuously, and the expectation of a continuous trend towards improvement should be met.
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Elefantes , Animais , Sobrevivência , Bem-Estar do Animal , Animais de Zoológico , Criação de Animais DomésticosRESUMO
The history and development of 4'-fluoro-nucleosides is discussed in this review. This is a class of nucleosides which have their origin in the discovery of the rare fluorine containing natural product nucleocidin. Nucleocidin contains a fluorine atom located at the 4'-position of its ribose ring. From its early isolation as an unexpected natural product, to its total synthesis and bioactivity assessment, nucleocidin has played a role in inspiring the exploration of 4'-fluoro-nucleosides as a privileged motif for nucleoside-based therapeutics.
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Produtos Biológicos , Nucleosídeos , Nucleotídeos , FlúorRESUMO
Theory and solution NMR indicate that all-syn 1,3,5-trifluorocyclohexane 5 adopts the expected tri-equatorial conformation, however in the solid state the more polar triaxial conformation is observed. This and the favoured conformations of substituted (Me, OMe, NH(CO)Me, NHBoc) derivatives of 5 are investigated to explore triaxial C-F preferences.
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Conformação Molecular , Espectroscopia de Ressonância MagnéticaRESUMO
C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.
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Monoterpenos Acíclicos , Receptores Odorantes , Monoterpenos Acíclicos/química , Ésteres/química , Humanos , Ligação de Hidrogênio , Oxalatos , Receptores Odorantes/agonistasRESUMO
Concise and general synthesis protocols are reported to generate all-syn mono-, di- and tri-alkylated cyclohexanes where a single fluorine is located on the remaining carbons of the ring. The alkyl groups are positioned to lie equatorially and to have triaxial C-F bonds imparting polarity to these ring systems. Intermolecular electrostatic interactions in the solid-state structure of the trialkylated systems are explored and the resultant supramolecular order opens up prospects for design in soft materials.
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Cicloexanos , Flúor , Carbono , Cicloexanos/química , Fluoretos , Flúor/química , Eletricidade EstáticaRESUMO
The nature of linear photophysical and nonlinear optical properties of a new squaraine derivative 2,4-bis[4-(azetidyl)-2-hydroxyphenyl]squaraine (1) with efficient near-infrared (NIR) emission was comprehensively analyzed based on spectroscopic, photochemical, and two-photon absorption (2PA) measurements, along with quantum chemical analysis. The steady-state absorption, fluorescence, and excitation anisotropy spectra of 1 and its fluorescence emission lifetimes revealed the multiple aspects of the electronic structure of 1, including the relative orientations of the main transition dipoles, effective rotational volumes in solvents of different polarities, and a maximum molar extinction of 1.35 × 10-5 M-1·cm-1, which is unusually small for similar symmetric squaraines. The degenerate 2PA spectrum of 1 was obtained over a broad spectral range under femtosecond excitation, using standard open-aperture Z-scan and two-photon induced fluorescence methods, revealing maximum 2PA cross sections of â¼400 GM. Squaraine 1 exhibited efficient superluminescence emission in the polar solvent (dichloromethane) at room temperature under femtosecond pumping conditions. Quantum chemical analysis of the electronic structure of 1 was performed using the DFT/TD-DFT level of theory and found to be in good agreement with experimental data. The new squaraine derivative 1 displayed high fluorescence quantum yield, efficient NIR superluminescence, large 2PA cross sections, and high photostability with a photodecomposition quantum yield â¼4 × 10-6, suggesting its potential for applications in two-photon fluorescent bioimaging and lasing.
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Ciclobutanos , Corantes Fluorescentes , Ciclobutanos/química , Corantes Fluorescentes/química , Fenóis/química , Fótons , Solventes/químicaRESUMO
Space-time (ST) wave packets are a class of pulsed optical beams whose spatiotemporal spectral structure results in propagation invariance, tunable group velocity, and anomalous refractive phenomena. Here, we investigate the refraction of ST wave packets normally incident onto a planar interface between two dispersive, homogeneous, isotropic media. We formulate a new, to the best of our knowledge, refractive invariant for ST wave packets in this configuration, from which we obtain a law of refraction that determines the change in their group velocity across the interface. We verify this new refraction law in ZnSe and CdSe, both of which manifest large chromatic dispersion at near-infrared frequencies in the vicinity of their band edges. ST wave packets can thus be utilized in nonlinear optics for bridging large group-velocity mismatches in highly dispersive scenarios.
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Advances in low-cost sensors (LCS) for monitoring air quality have opened new opportunities to characterize air quality in finer spatial and temporal resolutions. In this study, we deployed LCS that measure both gas (CO, NO, NO2, and O3) and particle concentrations and co-located research-grade instruments in Atlanta, GA, to investigate the capability of LCS in resolving air pollutant sources using non-negative matrix factorization (NMF) in a moderately polluted urban area. We provide a comparison of applying the NMF technique to both normalized and non-normalized data sets. We identify four factors with different temporal trends and properties for both normalized and non-normalized data sets. Both normalized and non-normalized LCS data sets can resolve primary organic aerosol (POA) factors identified from research-grade instruments. However, applying normalization provides factors with more diverse compositions and can resolve secondary organic aerosol (SOA). Results from this study demonstrate that LCS not only can be used to provide basic mass concentration information but also can be used for in-depth source apportionment studies even in an urban setting with complex pollution mixtures and relatively low aerosol loadings.
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Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , Material Particulado/análiseRESUMO
The fast relaxation processes in the excited electronic states of functionalized aza-boron-dipyrromethene (aza-BODIPY) derivatives (1-4) were investigated in liquid media at room temperature, including the linear photophysical, photochemical, and nonlinear optical (NLO) properties. Optical gain was revealed for nonfluorescent derivatives 3 and 4 in the near infrared (NIR) spectral range under femtosecond excitation. The values of two-photon absorption (2PA) and excited-state absorption (ESA) cross-sections were obtained for 1-4 in dichloromethane using femtosecond Z-scans, and the role of bromine substituents in the molecular structures of 2 and 4 is discussed. The nature of the excited states involved in electronic transitions of these dyes was investigated using quantum-chemical TD-DFT calculations, and the obtained spectral parameters are in reasonable agreement with the experimental data. Significant 2PA (maxima cross-sections â¼2000â GM), and large ESA cross-sections â¼10-20 â m2 of these new aza-BODIPY derivatives 1-4 along with their measured high photostability reveal their potential for photonic applications in general and optical limiting in particular.