Tetrazo[1,2-b]indazoles: Straightforward Access to Nitrogen-Rich Polyaromatics from s-Tetrazines.

The straightforward access to a new class of aza-polyaromatics is reported. Starting from readily available fluorinated s-tetrazine, a cyclization process with azide leads to the formation of an unprecedented tetrazo[1,2-b]indazole or a bis-tetrazo[1,2-b]indazole (cis and trans conformers). Based on the new nitrogen core, further N-directed palladium-catalyzed ortho-C-H bond functionalization allows the introduction of halides or acetates. The physicochemical properties of these compounds were studied by a joint experimental/theoretical approach. The tetrazo[1,2-b]indazoles display solid-state π-stacking, low reduction potential, absorption in the visible range up to the near-infrared, and intense fluorescence, depending on the molecular structure.

Tetranuclear Dicationic Aurophilic Gold(I) Catalysts in Enyne Cycloisomerization: Cooperativity for a Dramatic Shift in Selectivity.

In comparison to mononuclear gold Lewis acid catalysts, digold complexes and dual-gold catalysis have illustrated a distinct and powerful potential for the activation of carbon-carbon multiple bonds. Herein, this concept is pushed further by designing novel tetranuclear gold(I) dicationic complexes structurally supported by strongly stabilizing constraint diphosphinoferrocenyl ligands and attractive closed-shell Au⋅⋅⋅Au aurophilic interactions. The use of a molecularly-defined tetranuclear dicationic aurophilic gold(I) precatalyst for the selectivity-challenging cycloisomerization of low-substituted 1,6-enynes favors the formation with high selectivity of strained azabicyclo[4.1.0]hept-4-enes - even in the complete absence of activating/orienting substituents on alkyne and olefin reactive functions. This selectivity is not achieved by the reported phosphine- and carbene-stabilized mono- and dinuclear cationic gold(I) complexes, including the ones formed from the same ligands. More importantly this selectivity differs also from nanoparticles and heterogeneous gold catalysts reported to date. DFT studies correlated to experimental mechanistic investigations support an unprecedented "cluster-like" reactivity from polynuclear cooperation at the origin of this peculiar selectivity where the aurophilic interactions preexist, and pre-organize, gold cluster reactive intermediates.

The Hydrogen-Storage Challenge: Nanoparticles for Metal-Catalyzed Ammonia Borane Dehydrogenation.

Dihydrogen is one of the sustainable energy vectors envisioned for the future. However, the rapidly reversible and secure storage of large quantities of hydrogen is still a technological and scientific challenge. In this context, this review proposes a recent state-of-the-art on H2 production capacities from the dehydrogenation reaction of ammonia borane (and selected related amine-boranes) as a safer solid source of H2 by hydrolysis (or solvolysis), catalyzed by nanoparticle-based systems. The review groups the results according to the transition metals constituting the catalyst with a mention to their current cost and availability. This includes the noble metals Rh, Pd, Pt, Ru, Ag, as well as cheaper Co, Ni, Cu, and Fe. For each element, the monometallic and polymetallic structures are presented and the performances are described in terms of turnover frequency and recyclability. The structure-property links are highlighted whenever possible. It appears from all these works that the mastery of the preparation of catalysts remains a crucial point both in terms of process, and control and understanding of the electronic structures of the elaborated nanomaterials. A particular effort of the scientific community remains to be made in this multidisciplinary field with major societal stakes.

C-H Bond Arylation of Pyrazoles at the ß-Position: General Conditions and Computational Elucidation for a High Regioselectivity.

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the α-position using classical palladium-catalysis. Conversely, regioselective functionalization of such heterocycles at the concurrent ß-position remains currently very challenging. Herein, we report general conditions for regioselective direct arylation at the ß-position of pyrazoles, while C-H α-position is free. By using aryl bromides as the aryl source and a judicious choice of solvent, the arylation reaction of variously N-substituted pyrazoles simply proceeds via ß-C-H bond functionalization. The ß-regioselectivity is promoted by a ligand-free palladium catalyst and a simple base without oxidant or further additive, and tolerates a variety of substituents on the bromoarene. DFT calculations revealed that a protic solvent such as 2-ethoxyethan-1-ol significantly enhances the acidity of the proton at ß-position of the pyrazoles and thus favors this direct ß-C-H bond arylation. This selective pyrazoles ß-C-H bond arylation was successfully applied for the straightforward building of π-extended poly(hetero)aromatic structures via further Pd-catalyzed combined α-C-H intermolecular and intramolecular C-H bond arylation in an overall highly atom-economical process.

Patellar component size effects patellar tilt in total knee arthroplasty with patellar resurfacing.

PURPOSE: Patellar component positioning and patellofemoral kinematics are of great importance in total knee arthroplasty (TKA). The factors influencing patellar tilt are femoral rotation and lateral patellar release. However, the effect of patellar component size remains unknown. The aim of this study was to evaluate the intra-operative risk factors for patellar tilt, particularly the effect of the patellar component size. The hypothesis was that increasing the patellar component size would reduce the risk of patellar tilt. METHODS: 878 primary TKAs with patellar resurfacing were included between January 2015 and October 2018. Analysis was performed at 1-year postoperatively on patients categorized into two groups: patellar tilt (PT) and no patellar tilt (NPT). A multivariate analysis was performed for the effect of patellar component size, femoral rotation, femoral overbuilding, patellar thickness and lateral release on patellar tilt risk. Secondary analysis was performed for any difference in clinical outcomes and revision rates between groups. RESULTS: Multivariate analysis showed that increasing the patellar component size decreased the risk of patellar tilt by 37% (p < 0.001). Placing the femoral component at 3° of external rotation decreased the risk of patellar tilt by 67% (p < 0.001). Secondary analysis showed better clinical outcomes in the NPT group, especially regarding global satisfaction, and KSS objective and subjective scores. The revision for any cause was less in the NPT group (p = 0.019). The cause for TKA revision was related to the patellar in 11% of cases in the NPT group and 65% in the PT group (p < 0.001). CONCLUSION: Increased patellar component size and positioning the femoral component in external rotation decreases the risk of patellar tilt, improves clinical outcomes and decreases the rate of surgical revision. LEVEL OF EVIDENCE: III.

Coordination Chemistry of a Bis(Tetrazine) Tweezer: A Case of Host-Guest Behavior with Silver Salts.

The carbon-carbon cross-coupling of phenyl s-tetrazine (Tz) units at their ortho-phenyl positions allows the formation of constrained bis(tetrazines) with original tweezer structures. In these compounds, the face-to-face positioning of the central tetrazine cores is reinforced by π-stacking of the electron-poor nitrogen-containing heteroaromatic moieties. The resulting tetra-aromatic structure can be used as a weak coordinating ligand with cationic silver. This coordination generates a set of bis(tetrazine)-silver(I) coordination complexes tolerating a large variety of counter anions of various geometries, namely, PF6-, BF4-, SbF6-, ClO4-, NTf2-, and OTf-. These compounds were characterized in the solid state by single-crystal X-ray diffraction (XRD) and diffuse reflectance spectroscopy, and in solution by 1H-NMR, mass spectrometry, electroanalysis, and UV-visible absorption spectrophotometry. The X-ray crystal structure of complexes {[Ag(3)][PF6]}∞ (4) and {[Ag(3)][SbF6]}∞ (6), where 3 is 3,3'-[(1,1'-biphenyl)-2,2'-diyl]-6,6'-bis(phenyl)-1,2,4,5-tetrazine, revealed the formation of 1D polymeric chains, characterized by an evolution to a large opening of the original tweezer and a coordination of silver(I) via two chelating nitrogen atom and some C=C π-interactions. Electrochemical and UV spectroscopic properties of the original tweezer and of the corresponding silver complexes are reported and compared. 1H-NMR titrations with AgNTf2 allowed the determination of the stoichiometry and apparent stability of two solution species, namely [Ag(3)]+ and [Ag(3)2]2+, that formed in CDCl3/CD3OD 2:1 v/v mixtures.

ACL reconstruction using a quadruple semitendinosus graft with cortical fixations gives suitable isokinetic and clinical outcomes after 2 years.

PURPOSE: The objective of this single-center randomized single-blinded trial was to assess the hypothesis that anterior cruciate ligament reconstruction (ACLR) using a four-strand semitendinosus (ST) graft with adjustable femoral and tibial cortical fixation produced good outcomes compared to an ST/gracilis (ST/G) graft with femoral pin transfixation and tibial bioscrew fixation. Follow-up was 2 years. METHODS: Patients older than 16 years who underwent primary isolated ACLR included for 1 year until August 2017 were eligible. The primary outcome measures were the subjective International Knee Documentation Committee (IKDC) score, isokinetic muscle strength recovery, and return to work within 2 years. The study was approved by the ethics committee. RESULTS: Of 66 eligible patients, 60 completed the study and were included, 33 in the 4ST group and 27 in the ST/G group. Mean age was 30.5 ± 8.9 years in the 4ST group and 30.3 ± 8.5 in the ST/G group (n.s.). No significant between-group differences were found for mean postoperative subjective IKDC (4ST group, 80.2 ± 12.5; ST/G group, 83.6 ± 13.6; n.s.), side-to-side percentage deficits in isokinetic hamstring strength (at 60°/s: ST group, 17% ± 16%; ST/G group, 14% ± 11%; n.s.) or quadriceps strength (at 60°/s: ST group, 14% ± 12%; ST/G group, 19% ± 17%; n.s.), return to work, pain during physical activities, side-to-side differential laxity, balance, loss of flexion/extension, or surgical complications. CONCLUSION: This trial demonstrates that functional outcomes after 4ST for ACLR with cortical fixations could be as good, although not better, than those obtained using ST/G. The 4ST technique spares the gracilis tendon, which thus preserves the medial sided muscle and thereby could improve function and limit donor-side morbidity. LEVEL OF EVIDENCE: Level I.

Bridge-Clamp Bis(tetrazine)s with [N]8 π-Stacking Interactions and Azido-s-Aryl Tetrazines: Two Classes of Doubly Clickable Tetrazines.

Click chemistry at a tetrazine core is useful for bioorthogonal labeling and crosslinking. Introduced here are two new classes of doubly clickable s-aryl tetrazines synthesized by Cu-catalyzed cross-coupling. Homocoupling of o-brominated s-aryl tetrazines leads to bis(tetrazine)s structurally characterized by tetrazine cores arranged face-to-face. [N]8 π-stacking interactions are essential to the conformation. Upon inverse electron demand Diels-Alder (iEDDA) cycloaddition, the bis(tetrazine)s produce a unique staple structure. The o-azidation of s-aryl tetrazines introduces a second proximal intermolecular clickable function that leads to double click chemistry opportunities. The stepwise introduction of fluorophores and then iEDDA cycloaddition, including bioconjugation to antibodies, was achieved on this class of tetrazines. This method extends to (thio)etherification, phosphination, trifluoromethylation and the introduction of various bioactive nitrogen-based heterocycles.

Solvent-free ruthenium-catalysed triflate coupling as a convenient method for selective azole-o-C-H monoarylation.

Metal-catalysed ortho-directed C-H functionalization usually faces selectivity issues in the competition between mono- and disubstitution processes. We report herein the ruthenium-catalysed N-directed C-H monoarylation of arylpyrazoles with a selectivity of up to 96% or that generally reaches values above 80%. This selectivity is an effect of solvent-free conditions associated with sulfonate reagents, in the absence of frequently used acidic additives.

Correction to: Short lateral posterior condyle is associated with trochlea dysplasia and patellar dislocation.

Unfortunately, the author name was incorrectly published in the original publication as Sébatien Lustig insted of Sébastien Lustig. The author name is corrected here by this Erratum. The original article has been corrected.

Short lateral posterior condyle is associated with trochlea dysplasia and patellar dislocation.

PURPOSE: Surgeons mainly consider the anterior anatomy of the distal femur in the treatment of patellar instability (PI) with trochlear dysplasia (TD). Through this research, the idea was to analyse the posterior femoral condyle length in TD. The research team posited the presence of morphological differences in the posterior part of the femoral epiphysis in TD compared to a control group. They also postulated that the posterior bicondylar angle (PCA), in the axial plane, was increased in TD. METHODS: This is a single-centre morphological study of 100 patients who had a computed tomography (CT) using the same protocol. 50 patients with PI (25 dysplasias A and 25 B-C-D according to the Dejour classification), and 50 controls were included. All patients presenting a clinical PI were considered for the study. None of these patients had undergone a surgical treatment prior to imaging. Demographic characteristics, BMI, and laterality were comparable in all patients. 20 pilot CT scans were used to establish the methodology. The following measurements were performed: anterior bicondylar angle, PCA, and condylar lengths with respect to the surgical transepicondylar axis. Ratios were calculated in relation to the femoral width. TD was classified according to the Dejour classification in grade A or grades B-C-D. An analysis of variance and a linear model were performed within some groups to investigate which parameters correlated with the classification's grade. RESULTS: This study showed a link between TD and the PCA: control group (1.4 ± 0.2°), type A group (1.6 ± 0.3°), and types B, C, D group (2.6 ± 0.3°) (p = 0.01). The difference between the control group and types B, C, D TD group was significant (p = 0.002). In groups B, C, D, the PCA was more important, which proves that in these groups the posterior part of the lateral condyle was relatively shorter compared to the medial condyle. The greater the dysplasia, the longer the medial condyle was in the anterior posterior (p = 0.02). CONCLUSIONS: This study shows not only an anterior but also a posterior anomaly in PI with TD. There is a correlation between the severity of the anterior deformation and the PCA: in other words, the knee is placed in valgus in flexure which promotes the external dislocation of the patella. This anatomical study could open a field of research on the development of surgical treatments based on the correction of posterior condylar femoral anomalies in PI. LEVEL OF EVIDENCE: III.

Gold(I) Complexes of Ferrocenyl Polyphosphines: Aurophilic Gold Chloride Formation and Phosphine-Concerted Shuttling of a Dinuclear [ClAu···AuCl] Fragment.

A smart steric control of the metallocene backbone in bis- and poly(phosphino)ferrocene ligands favors intramolecular aurophilic interactions between [AuCl] fragments in polynuclear gold(I) complexes. We synthesized and characterized by multinuclear NMR and X-ray diffraction analysis mono-, di-, and polynuclear gold complexes of constrained ferrocenyl diphosphines, which bear either bulky tert-butyl groups or more flexible siloxane substituents at the cyclopentadienyl rings. The complexes meso-1,1'-bis(diphenylphosphino)-3,3'-di-tert-butylferrocene (4-m), rac-1,1'-bis[bis(5-methyl-2-furyl)phosphino]-3,3'-di-tert-butylferrocene (5-r), and rac-1,1'-bis(diphenylphosphino)-3,3'-bis[(tri-iso-propylsilyl)oxy]ferrocene (6-r) were used to form dinuclear gold complexes. Coordination of tert-butylated ferrocenyl phosphines generated aurophilic interactions in the corresponding dinuclear gold complexes, contrary to gold(I) complexes reported with 1,1'-bis(diphenylphosphino)ferrocene. The structurally related tetraphosphine 1,1',2,2'-tetrakis(diphenylphosphino)-4,4'-di-tert-butylferrocene (11) also gave access to mononuclear, dinuclear, and the original trinuclear gold chloride aurophilic complexes in which 14e- to 16e- gold centers coexist. In such complexes, nonbonded ("through-space") 31P-31P' nuclear spin couplings were evidenced by high-resolution NMR. In these interactions nuclear spin information is transferred between the lone-pair electron of an uncoordinated phosphorus P and a phosphorus P' that is involved in a σ covalent bond Au-P'. The dinuclear aurophilic complex displayed a concerted shuttling of its [ClAu···AuCl] fragment between the four phosphorus donors of the tetraphosphine ligand. Thus, an aurophilic Au···Au bond, which is assumed to be a weak energy interaction, can be conserved within a dynamic shuttling process at high temperature involving an intramolecular coordination-decoordination process of digold(I) at phosphorus atoms.

HIV Nef promotes expression of B-lymphocyte stimulator by blood dendritic cells during HIV infection in humans.

Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]). We have recently shown that, in human immunodeficiency virus (HIV)-infected individuals with rapid and those with classic disease progression, B-cell dysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with slow disease progression (also known as "elite controllers"). In previous work with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant with altered mDCs and dependent on HIV negative factor (Nef). We now report that HIV Nef is detected early after infection and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic progressors, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1. Importantly, this is counteracted in the presence of all-trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individuals.

Ortho-Functionalized Aryltetrazines by Direct Palladium-Catalyzed C-H Halogenation: Application to Fast Electrophilic Fluorination Reactions.

A general catalyzed direct C-H functionalization of s-tetrazines is reported. Under mild reaction conditions, N-directed ortho-C-H activation of tetrazines allows the introduction of various functional groups, thus forming carbon-heteroatom bonds: C-X (X=I, Br, Cl) and C-O. Based on this methodology, we developed electrophilic mono- and poly-ortho-fluorination of tetrazines. Microwave irradiation was optimized to afford fluorinated s-aryltetrazines, with satisfactory selectivity, within only ten minutes. This work provides an efficient and practical entry for further accessing highly substituted tetrazine derivatives (iodo, bromo, chloro, fluoro, and acetate precursors). It gives access to ortho-functionalized aryltetrazines which are difficult to obtain by classical Pinner-like syntheses.

A general palladium-catalyzed method for alkylation of heteroarenes using secondary and tertiary alkyl halides.

A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.

Molecular engineering of 3-arylated tetrazo[1,2-b]indazoles: divergent synthesis and structure-property relationships.

The synthetic scope of 3-arylated tetrazo[1,2-b]indazoles is reported based on a Pd-catalyzed Liebeskind-Srogl cross-coupling reaction followed by an N-cyclisation process. The reactivity of the nitrogen atoms was used to further diversify these N-rich polyaromatic tetrazo[1,2-b]indazoles in a panel of reactions (protonation, selective oxidation, metallations). Selective ortho-C-H activation/functionalization on the heterocycle was also demonstrated with three transition metals (TM = Pd, Ir and Rh). The effects of all these molecular engineering strategies, particularly the N-modifications, on the optical and redox properties of the 3-arylated tetrazoindazoles were studied experimentally and theoretically. This study highlights the diversity of molecular structures and electronic properties offered by the tetrazo[1,2-b]indazole platform.

Talo-navicular and calcaneo-cuboid fusion with PEEK H-pode™ vs. Titanium Maxlock™ locking plates: Comparison of functional and radiographic outcomes.

BACKGROUND: Locking plates are increasingly used to achieve hindfoot fusion. The objective of this study was to compare hindfoot fusion outcomes with the PEEK H-pode™ (Biotech™) locking plate and the titanium Maxlock™ (Tornier-Wright™) locking plate. HYPOTHESIS: A polyetheretherketone (PEEK) H-pode™ locking plate provides similar fusion rates to a titanium Maxlock™ locking plate for talo-navicular and calcaneo-cuboid arthrodesis. METHODS: We conducted a retrospective comparative study in 39 patients (including 21 [54%] with pes planovalgus and 11 [28%] with neurological equinovarus deformities) who underwent talo-navicular and/or calcaneo-cuboid fusion, usually combined with subtalar fusion. The first 17 patients (January 2014-February 2016) were managed with Maxlock™ locking plates and the next 22 patients (March 2016-August 2018) with H-pode™ locking plates. These two cohorts of consecutive patients were comparable regarding age, sex distribution, body mass index, and comorbidities. At last follow-up more than 1year after surgery, we compared functional scores, pain intensity, and fusion assessed by radiographs and computed tomography (CT) (threshold set at 33%). RESULTS: Mean follow-up was 42months (range: 34-63months) in the Maxlock™ group and 25months (range: 12-36months) in the H-pode™ group. At last follow-up, the two groups were not significantly different for the mean values of the American Orthopedic Foot & Ankle Society score, European Foot & Ankle Society score, and visual analogue scale pain score. Neither were the two groups significantly different for talo-navicular and calcaneo-cuboid fusion by CT. In the Maxlock™ group, we found non-significant trends towards a higher proportion of patients with talo-navicular nonunion (18% vs. 5% in the H-pode™ group) and weaker talo-navicular fusion in patients with pes planovalgus (60.8% vs. 82.0%, respectively). Radiographic results overestimated the fusion rates. DISCUSSION: Talo-navicular and calcaneo-cuboid fusion was not significantly different with H-pode™ and Maxlock™ locking plates. CT was more accurate than standard radiography to assess fusion. These results underline the usefulness of PEEK locking plates for talo-navicular and calcaneo-cuboid fusion; moreover, the radiolucency of PEEK facilitates the interpretation of radiographs. LEVEL OF EVIDENCE: IV.

Hybrid Phosphine/Amino-Acid Ligands Built on Phenyl and Ferrocenyl Platforms: Application in the Suzuki Coupling of o-Dibromobenzene with Fluorophenylboronic Acid.

We describe the synthesis and characterization of two classes of hybrid phosphino ligands functionalized with amino ester or amino acid groups. These compounds are built either on a rigid planar phenyl platform or on a functionalized - conformationally controlled - rotational ferrocene backbone. Modifications at the -PR2 phosphino groups (R=aryl and alkyl, with various steric bulk, Ph, Mes, i-Pr, Cy) and at the amino acid/amino ester functions are reported, showing a valuable high modularity. The coordination chemistry of these compounds regarding palladium and gold was investigated, in particular with respect to the coordination mode of the phosphino groups and the preferred interaction with metals for the amino ester and amino acid functions. For all the hybrid ligands, based either on ferrocenyl or phenyl platforms, the (P,N)-chelating effect dominates in solution for coordination to Pd(II), while linear P-Au(I) complexes without interaction with the amino groups are assumed. The investigation of the catalytic activity of these new ligands in the demanding palladium-catalyzed Suzuki-Miyaura coupling of o-dibromoarenes with fluorophenylboronic acid underlined the importance of the amino ester dicyclohexylphosphinoferrocene for avoiding the deleterious homocoupling and arene oligomerization side-reactions that were otherwise observed with the other phosphine ligands.

Synthesis of meso,ß-Fused Thiazinamine-Porphyrins via Oxidative C-N Fusion of Pyrimidinyl-Substituted Porphyrins.

5,15-Bis(pyrimidin-2-ylthio)porphyrins have been synthesized. Their electrochemical oxidation leads to the formation of mono- and bis-C-N-fused thiopyrimidinium intermediates depending on the applied charge and potential. These latter undergo nucleophilic attack with water during workup that drives the ring opening of the pyrimidinium moiety. When piperidine is added before or after workup, the neutral fused porphyrinthiazin-2-amines are generated, and they exhibit a significant bathochromic shift of their Soret and Q bands.

Alkali halides as nucleophilic reagent sources for N-directed palladium-catalysed ortho-C-H halogenation of s-tetrazines and other heteroaromatics.

A general palladium-catalysed selective C-H halogenation reaction is reported, which was successfully achieved for a large variety of functionalized aromatic rings incorporating diverse N-directing groups. By using simple alkali halides of MX type as the nucleophilic reagent source (M = Li, Na, K, Cs and X = I, Br and Cl), and phenyliodanediacetate oxidant, clean C-H-iodination, bromination and chlorination reactions were performed. This general protocol of selective ortho-monohalogenation, which complements but contrasts with the classical methods using electrophilic reagents, is achievable in a short time (30 min) with microwave irradiation assistance. The reaction was extended to substrates bearing N-directing pyridine, pyrimidine, pyrazole, oxazoline, naphtho[1,2-d]thiazole, and azobenzene groups. Notably, the topical and selectivity-challenging s-tetrazine, as a nitrogen-rich heteroaromatic, was successfully halogenated by this protocol.