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.

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.

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.

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.

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.

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.

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.

Predictive Factors of Detectable Viral Load in HIV-Infected Patients.

Despite availability of effective antiretroviral therapy (ART), many HIV patients still have a detectable viral load (VL). Predictive factors of detectable VL are not well documented. This study was done at two large multidisciplinary HIV outpatient clinics at the Centre hospitalier de l'Université de Montréal (CHUM) and the McGill University Health Centre (MUHC). This is a retrospective case-control study of patients treated between 2016 and 2018. Cases had a VL ≥50 copies/mL in 2018. Controls had an undetectable VL from 2016 to 2018. Matching was based on gender and year of HIV diagnosis. Primary objective was to identify predictive factors of detectable VL. Secondary objectives included to identify predictive factors of virologic failure, low persistent viremia, and viral blip. A forward stepwise model selection by the Akaike Information Criterion of the conditional logistic regression was used to identify predictive factors. Two hundred cases were identified and matched with 200 controls. The cohort was mostly male (68.0%) with a median age of 54 years (21-83 years). Among cases, viral blip was the most common type of detectable VL (43.0%). The strong predictive factors for a detectable VL were adherence to ART and seeking health care services. Asylum seekers were less at risk of detectable VL. Adherence to ART was the only strong predictive factor for virologic failure. Three main predictive factors of detectable VL were identified in two ambulatory clinic hospitals in Montreal. Ascertaining these factors will allow for identification of patients more at risk of detectable VL.

Nanocatalysts for High Selectivity Enyne Cyclization: Oxidative Surface Reorganization of Gold Sub-2-nm Nanoparticle Networks.

Ultrasmall gold nanoparticles (NPs) stabilized in networks by polymantane ligands (diamondoids) were successfully used as precatalysts for highly selective heterogeneous gold-catalyzed dimethyl allyl(propargyl)malonate cyclization to 5-membered conjugated diene. Such reaction usually suffers from selectivity issues with homogeneous catalysts. This control over selectivity further opened the way to one-pot cascade reaction, as illustrated by the 1,6-enyne cycloisomerization-Diels-Alder reaction of dimethyl allyl propargyl malonate with maleic anhydride. The ability to assemble nanoparticles with controllable sizes and shapes within networks concerns research in sensors, medical diagnostics, information storage, and catalysis applications. Herein, the control of the synthesis of sub-2-nm gold NPs is achieved by the formation of dense networks, which are assembled in a single step reaction by employing ditopic polymantanethiols. By using 1,1'-bisadamantane-3,3'-dithiol (BAd-SH) and diamantane-4,9-dithiol (DAd-SH), serving both as bulky surface stabilizers and short-sized linkers, we provide a simple method to form uniformly small gold NPs (1.3 ± 0.2 nm to 1.6 ± 0.3 nm) embedded in rigid frameworks. These NP arrays are organized alongside short interparticular distances ranging from 1.9 to 2.7 nm. The analysis of gold NP surfaces and their modification were achieved in joint experimental and theoretical studies, using notably XPS, NMR, and DFT modeling. Our experimental studies and DFT analyses highlighted the necessary oxidative surface reorganization of individual nanoparticles for an effective enyne cycloisomerization. The modifications at bulky stabilizing ligands allow surface steric decongestion for the alkyne moiety activation but also result in network alteration by overoxidation of sulfurs. Thus, sub-2-nm nanoparticles originating from networks building create convenient conditions for generating reactive Au(I) surface single-sites-in the absence of silver additives-useful for heterogeneous gold-catalyzed enyne cyclization. These nanocatalysts, which as such ease organic products separation, also provide a convenient access for building further polycyclic complexity, owing to their high reactivity and selectivity.

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.

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.

Arthroscopic "Debridement and Implant Retention" With Local Administration of Exebacase (Lysin CF-301) Followed by Suppressive Tedizolid as Salvage Therapy in Elderly Patients for Relapsing Multidrug-Resistant S. epidermidis Prosthetic Knee Infection.

Exebacase, a recombinantly produced lysin has recently (i) reported proof-of-concept data from a phase II study in S. aureus bacteremia and (ii) demonstrated antibiofilm activity in vitro against S. epidermidis. In patients with relapsing multidrug-resistant (MDR) S. epidermidis prosthetic knee infection (PKI), the only surgical option is prosthesis exchange. In elderly patients who have undergone several revisions, prosthesis explantation could be associated with definitive loss of function and mortality. In our BJI reference regional center, arthroscopic debridement and implant retention with local administration of exebacase (LysinDAIR) followed by suppressive tedizolid as salvage therapy is proposed for elderly patients with recurrent MDR S. epidermidis PKI with no therapeutic option or therapeutic dead end (for whom revision or transfemoral amputation is not feasible and no other oral option is available). Each use was decided in agreement with the French health authority and in accordance with the local ethics committee. A written consent was obtained for each patient. Exebacase (75 mg/mL; 30 mL) was administered directly into the joint during arthroscopy. Four patients (79-89 years old) were treated with the LysinDAIR procedure. All had several previous prosthetic knee revisions without prosthesis loosening. Three had relapsing PKI despite suppressive antibiotics following open DAIR. Two had clinical signs of septic arthritis; the two others had sinus tract. After the LysinDAIR procedure, no adverse events occurred during arthroscopy; all patients received daptomycin 8 mg/kg and linezolid 600 mg bid (4-6 weeks) as primary therapy, followed by tedizolid 200 mg/day as suppressive therapy. At 6 months, recurrence of the sinus tract occurred in the two patients with sinus tract at baseline. After >1 year follow up, the clinical outcome was favorable in the last two patients with total disappearance of clinical signs of septic arthritis even if microbiological persistence was detected in one of them. Exebacase has the potential to be used in patients with staphylococci PKI during arthroscopic DAIR as salvage therapy to improve the efficacy of suppressive antibiotics and to prevent major loss of function.

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.

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.

Gold(I) Complexes Nuclearity in Constrained Ferrocenyl Diphosphines: Dramatic Effect in Gold-Catalyzed Enyne Cycloisomerization.

Di-tert-butylated-bis(phosphino)ferrocene ligands bearing phosphino substituents R (R=phenyl, cyclohexyl, iso-propyl, mesityl, or furyl) allow tuning the selective formation of Au(I) halide complexes. Thus, dinuclear linear two-coordinate, but also rare mononuclear trigonal three-coordinate and tetrahedral four-coordinate complexes were formed upon tuning of the conditions. Both Au(I) chloride and rarer Au(I) iodide complexes were synthesized, and their X-ray diffraction analysis are reported. The significance of the control of structure and nuclearity in Au(I) complexes is further illustrated herein by its strong effect on the efficiency and selectivity of gold-catalysed cycloisomerization. Cationic linear digold(I) bis(dicyclohexylphosphino) ferrocenes outperform other catalysts in the demanding regioselective cycloisomerization of enyne sulphonamides into cyclohexadienes. Conversely, tetrahedral and trigonal cationic monogold(I) complexes were found incompetent for enyne cycloaddition. We used the two-coordinate linear electron-rich Au(I) complex 2 b (R=Cy) to extend the scope of selective intramolecular cycloaddition of different 1,6-enyne sulfonylamines with high activity and excellent selectivity to the endo cyclohexadiene products.

Factors lead to return to sports and recreational activity after total knee replacement - A retrospective study.

INTRODUCTION: The number of total knee replacements performed (TKR) is increasing and so are patient expectations and functional demands. The mean age at which orthopedic surgeons may indicate TKR is decreasing, and therefore return to sport (RTS) after TKR is often an important expectation for patients. The aim of this study was to analyze the mid-term RTS, recreational activities, satisfaction level, and forgotten joint level after TKR. METHODS: Between January 2015 and December 2016, 536 TKR (same implant design, same technique) were performed in our center. The mean age at survey was 69 years with a mean follow-up of 43 months. All patients who did not have a follow-up in the last 6 months were called. Finally, 443 TKR were analyzed. RTS was assessed using the University of California Los Angeles Scale (UCLA), forgotten joint score (FJS), and Satisfaction Score. RESULTS: In this study, 85% of patients had RTS after TKR with a mean UCLA score increasing from 4.48 to 5.92 and a high satisfaction rate. Satisfaction with activity level was 93% (satisfied and very satisfied patients). The RTS is more important for people with a higher preoperative UCLA score and a lower American Society of Anesthesiologist score (ASA). Each point increase in ASA score is associated with reduced probability to RTS by 52%. DISCUSSION: RTS and recreational activity were likely after TKR with a high satisfaction score. Preoperative condition and activity are the two most significant predictive factors for RTS. LEVEL OF EVIDENCE: Retrospective case series, level IV.

How Does Isolated Medial Patellofemoral Ligament Reconstruction Influence Patellar Height?

BACKGROUND: Reconstruction of the medial patellofemoral ligament (MPFL) is the gold standard treatment for recurrent patellar dislocation. Patella alta has been reported in about half of patients with recurrent patellofemoral instability. HYPOTHESIS: MPFL reconstruction (MPFLr) has a beneficial role in the correction of patellar height in patients with mild patella alta (Caton-Deschamps index [CDI] between 1.20 and 1.40). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Skeletally mature patients, with no history of previous or concomitant knee surgical procedures, who underwent isolated MPFLr using hamstring autograft for recurrent patellar instability between 2005 and 2018, were included in this study. The authors calculated CDI, modified Insall-Salvati index (MISI), and Blackburne-Peel index (BPI) ratios. Measurements done by 2 independent observers were calculated and used to compare pre- and postoperative patellar height (patella alta: CDI >1.20). RESULTS: A total of 89 patients (95 knees) were included in the study, with a mean age of 25.0 years (range, 15.0-45.0 years). There were 70% women and 30% men. We found patella alta in 35.8% of cases preoperatively. Among them, 79.4% had reduced patellar height indices, within normal limits, postoperatively (mean follow-up, 18.4 ± 12.0 months). All the ratios showed a significant reduction in patellar height after surgery (CDI: 0.19 [range, -0.05, 0.60]; MISI: 0.22 [-0.14, 0.76]; BPI: 0.18 [-0.08, 0.59]; P < .00001). The CDI of 79.4% of the study knees was reduced to within normal limits postoperatively. The CDI was maintained within normal limits postoperatively in 93.4% of the knees with normal patellar height and reduced to normal in 50% of the knees with severe patella alta before surgery . No patient reported patella infera before surgery, whereas this condition was found in 8.2% of study patients postoperatively. A moderate correlation was reported between preoperative radiographic indices and their reduction after surgery (CDI: P < .001, ρ = 0.39; MISI: P < .001, ρ = 0.39; BPI: P < .001, ρ = 0.48). CONCLUSION: The higher the preoperative patellar height, the more important is the lowering effect of MPFLr using the hamstring for patellar instability. Bony procedures should not be indicated in patients with patellar instability and a CDI between 1.20 and 1.40.

Influence of solvent mixture on nucleophilicity parameters: the case of pyrrolidine in methanol-acetonitrile.

The course of organic chemical reactions is efficiently modelled through the concepts of "electrophiles" and "nucleophiles" (meaning electron-seeking and nucleus-seeking reactive species). On the one hand, an advanced approach of the correlation of the nucleophilicity parameters N and electrophilicity E has been delivered from the linear free energy relationship log k (20 °C) = s(N + E). On the other hand, the general influence of the solvent mixtures, which are very often employed in preparative synthetic chemistry, has been poorly explored theoretically and experimentally, to date. Herein, we combined experimental and theoretical studies of the solvent influence on pyrrolidine nucleophilicity. We determined the nucleophilicity parameters N and s of pyrrolidine at 20 °C in CH3OH/CH3CN mixtures containing 0, 20, 40, 60, 80 and 100% CH3CN by kinetic investigations of their nucleophilic substitution reactions to a series of 2-methoxy-3-X-5-nitrothiophenes 1a-e (X = NO2, CN, COCH3, CO2CH3, CONH2). Depending on the resulting solvation medium, the N parameters range from 15.72 to 18.32 on the empirical nucleophilicity scale of Mayr. The nucleophilicity parameters N first evolve linearly with the content of acetonitrile up to 60% CH3CN by volume, but is non linear for higher amounts. We designed a general computation protocol to investigate the solvent effect at the atomistic scale. The nucleophilicity in solvent mixtures was evaluated by combining classical molecular dynamic (MD) simulations of solvated pyrrolidine and a few density functional theory (DFT) calculations of Parr nucleophilicity. The pyrrolidine theoretical nucleophilicity 1/ω obtained in various CH3OH/CH3CN mixtures are in excellent agreement with Mayr's nucleophilicity (N) parameters measured. Analyses of the molecular dynamic trajectories reveal that the decrease of the nucleophilicity in methanol rich mixtures arises predominantly from the solvation of the pyrrolidine by methanol molecules through strong hydrogen bonds. Last, we proposed a simple model to predict and accurately reproduce the experimentally obtained nucleophilicity values.

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.