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Diverse DNA-encoded libraries of complex and novel sp3-rich spirocycles were achieved using a versatile and operationally simple visible light-mediated intermolecular [2 + 2] cycloaddition.

DNA-encoded libraries have proven their tremendous value in the identification of new lead compounds for drug discovery. To access libraries in new chemical space, many methods have emerged to transpose traditional mol-scale reactivity to nmol-scale, on-DNA chemistry. However, procedures to access libraries with a greater fraction of C(sp

Recent advances in synthetic chemistry have seen a resurgence in the development of methods for visible light-mediated radical generation. Herein, we report the development of a photoactive ester based on a quinoline

Electron donor–acceptor (EDA) complexes can controllably generate radicals under mild conditions through selective photoexcitation events. However, unproductive reactivity from fast deactivation of...

This paper describes the one-electron interconversions of isolable NiIII and NiIV complexes through their reactions with carbon-centered radicals (R•). First, model NiIII complexes are shown to react with alkyl and aryl radicals to afford NiIV products. Preliminary mechanistic studies implicate a pathway involving direct addition of a carbon-centered radical to the NiIII center. This is directly analogous to the known reactivity of NiII complexes with R•, a step that is commonly implicated in catalysis. Second, a NiIV-CH3 complex is shown to react with aryl and alkyl radicals to afford C-C bonds via a proposed SH2-type mechanism. This pathway is leveraged to enable challenging H3C-CF3 bond formation under mild conditions. Overall, these investigations suggest that NiII/III/IV sequences may be viable redox pathways in high-oxidation-state nickel catalysis.

Over the past decade, photoredox catalysis has risen to the forefront of synthetic organic chemistry as an indispensable tool for selective small-molecule activation and chemical-bond formation. This cutting-edge platform allows photosensitizers to convert visible light into chemical energy, prompting generation of reactive radical intermediates. In this review, we highlight some of the recent key contributions in the field, including elucidating the impact of the chosen light arrays, promoting fundamental cross-coupling steps, selectively functionalizing aliphatic amines, engaging complementary mechanistic paradigms, and applications in industry. With such a wide breadth of reactivity already realized, the presence of photoredox catalysis in all sectors of organic chemistry is expected for years to come.

Electron donor-acceptor (EDA) complexes can controllably generate radicals under mild conditions through selective photoexcitation events. However, unproductive reactivity from fast deactivation of the photoexcited complexes through back electron transfer has slowed the development of EDA complexes in synthetic methodology. Here, we disclose the study of EDA complexes derived from 2-methoxynaphthalene donor and acylated ethyl isonicotinate N-oxide acceptor that undergo a fast N–O bond fragmentation event upon photoexcitation. This reaction design not only overcomes the limitations of back electron transfer but also enables the regeneration of the donor species, representing a rare example EDA photochemistry in a catalytic regime. The synthetic utility is demonstrated through visible light-driven radical trifluoromethylation and Minisci alkylation reactions. The scalability of the EDA complex promoted reaction evidenced by the successful multigram-scale trifluoromethylation of methyl N-Boc pyrrole-2-carboxylate in a continuous flow manifold.

A net redox-neutral method for the decarboxylative alkylation of heteroarenes using photoredox catalysis is reported. Additionally, this method features the use of simple, commercially available carboxylic acid derivatives as alkylating agents, enabling the facile alkylation of a variety of biologically-relevant heterocyclic scaffolds under mild conditions.

Several series of novel 1,4-disubstituted 1,2,3-triazoles were prepared using the Huisgen cycloaddition reaction and evaluated as inhibitors against caspase-3/-7. The 1,2-benzisothiazol-3-one-derived 1,4-disubstituted 1,2,3-triazoles containing an urea group had dramatically increased inhibitory activity in vitro compared to the others, and the most potent caspase-3 inhibitor was found to be N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-3-oxobenzoisothiazole-2(3H)-carboxamide 14c with IC50-values of 11.0 ± 1.2 nM. Meanwhile, the compound 14c showed significant protection against apoptosis in human Jurkat T cells, as determined by annexin V-FITC/7-AAD. Moreover, in order to better rationalize the action and the binding mode of these compounds, docking studies were carried out.

Regioselective copper-catalyzed boracarboxylation of vinyl arenes with bis(pinacolato)diboron and carbon dioxide has been achieved. New boron-functionalized α-aryl carboxylic acids, including nonsteroidal anti-inflammatory drugs (NSAIDs), are obtained in moderate to excellent yields. The synthetic utility of the transformation was shown through subsequent derivatization of the carbon–boron bond yielding formal hydroxy- and fluorocarboxylation products as well as anionic difluoroboralactones.

Geratric patients who are treated operatively or nonoperatively for acetabular fractures may develop posttraumatic arthritis. Performing delayed total hip arthroplasties (THAs) in this patient population may be more technically challenging. Previous operative reports, radiographs, and computed tomography scans may help with preoperative planning. Scarring of the sciatic nerve from previous surgeries may warrant the use of nerve monitoring. Special surgical considerations include choosing a surgical approach, especially through preexisting incisions; deciding whether or not to remove hardware; and removing heterotopic ossification (HO). Multiple fixation options should be available in light of possible acetabular deficiency, including autograft, allograft, structural augments, and acetabular cups offering different fixation options. The postoperative management may differ from primary THAs performed for osteoarthritis because these patients may require protection of weight-bearing status and may require HO prophylaxis. By using the techniques described in this article, delayed THAs after acetabular fractures have demonstrated good outcomes in the geriatric patient population.

A gold-catalyst with an electron-deficient phosphite as the ancillary ligand is found to exclusively promote the carbophilic chemoselective addition of arenes, hetarenes and 1,3-diketones to α-aryldiazoesters.

The first gold-catalyzed Markovnikov addition of sulfinic acids to terminal alkynes is presented.

The chemoselective addition of arenes and 1,3-diketones to α-aryldiazoesters was achieved through ligand-controlled gold catalysis. Unlike a dirhodium catalyst (which promotes C(sp3)-H insertion and cyclopropanation) and a copper catalyst (which catalyzes O-H and N-H insertions), the gold catalyst with an electron-deficient phosphite as the ancillary ligand exclusively gave the carbophilic addition product, thus representing a new and efficient approach to form "carbophilic carbocations", which selectively react with carbon nucleophiles.

This restrospective study compared plate fixation versus pin fixation in 57 patients with rheumatoid arthritis who underwent wrist arthrodesis. Fixation was achieved by using plates in 32 patients and longitudinal pins in 25 patients. Clinical follow-up averaged 29 months (range: 12-57 months) and radiographic follow-up averaged 16 months (range: 12-39 months). Union occurred in 97% of the wrists fixed with plates and in 96% of the wrists fixed with pins. There were 6 (19%) complications in the plate group and 7 (28%) complications in the pin group. Three (12%) wrists fixed with pins moved from the immediate postoperative position to a position of relative volar flexion, while radiographs showed no changes in wrist position in the plate group. With both methods, successful arthrodesis stabilized the wrist in a high percentage of patients. Plate fixation offers an excellent alternative method for arthrodesis of the rheumatoid wrist.

A general method for the synthesis of α-substituted vinyl sulfones makes use of a combination of a triazole gold complex and gallium triflate. This efficient CS bond formation between simple terminal alkynes and sulfinic acids provides access to various α-substituted vinyl sulfones.

Treatment of chronic periprosthetic joint infections (PJIs) after TKA is limited to fusions, above-the-knee amputations (AKAs), revision TKA, and antibiotic suppression and is often based on the patient's medical condition. However, when both fusion and AKA are options, it is important to compare these two procedures with regard to function.Do patients receiving a knee fusion for PJI after TKA have better function compared to patients receiving an AKA?We retrospectively reviewed patients who were eligible for either fusion or AKA after PJI TKA. Thirty-seven patients underwent a fusion for PJIs after TKA between 1999 and 2010. Nine patients died postoperatively and eight patients were lost to followup, leaving 20 patients. Patients completed a specialized questionnaire about their fusion, and functional capability was assessed by the SF-12. We compared fusions to a previously published group of six patients who underwent AKA for recurrent PJI after TKA.For patients with fusion, community ambulators increased from five to 10 and nonambulators decreased from three to one. For patients with AKA, nonambulatory patients increased from zero to two, and community ambulators decreased from four to one. The SF-12 physical component summary measurements were higher for fusions (51) than for AKAs (26). The mental component summary was also higher in fusions (60) than in AKAs (44). Seventy percent of patients indicated they would undergo a fusion again instead of undergoing an amputation if they were presented with both options after undergoing their operation.Patients receiving knee fusions for treating recurrent PJIs after TKA have better function and ambulatory status compared to patients receiving AKA.Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Thirty-two total knee arthroplasties (TKAs) in patellectomized patients were evaluated with recent clinical and radiographic examinations. Eighteen patients had a primary TKA with a mean follow-up period of 49 months, and 14 patients had a revision TKA with a mean follow-up period of 36 months. A control group of 13 TKA patients with intact patellae were randomly generated but matched for age, sex, follow-up data, diagnosis, and prosthesis. Posterior cruciate ligament-retaining types of prostheses were used in the primary knees, while the revision knees underwent arthroplasties with the more constrained, posterior cruciate ligament-substituting prostheses. All knees were evaluated based on the Knee Society's clinical and radiographic scoring system. In addition, 18 patients (9 primary, 9 revision) underwent isokinetic dynamometer testing for quantitation of peak quadriceps and hamstring torque. The knee score, indicative of pain relief, averaged 82.5 in the primary group (16 good/excellent, 1 fair, 1 poor), 86.5 in the revision group (12 good/excellent, 1 fair, 1 poor), and 93.9 in the control group (13/13 excellent). The function score averaged 59.7 in the primary group (6 good/excellent, 6 fair, 6 poor), 60.0 in the revision group (5 good/excellent, 2 fair, 7 poor), and 80.9 in the control group (12 good/excellent, 1 fair). The lower function scores predominantly reflected the patients' difficulty in independently climbing or descending stairs. This was also reflected in their higher flexion to extension peak torque ratios. There was one failure in the primary group requiring a revision and one failure in the revision group requiring a knee fusion. There was no radiographic evidence of impending failure in any of the remaining knees. No clinical or radiographic differences were found between the patients with osteoarthritis or rheumatoid arthritis. Although the knee and function scores were lower in the patellectomized patients, the overall results were generally satisfactory without a high incidence of failures. Satisfactory results were obtained in the primary TKAs using the minimally constrained prostheses when the posterior cruciate ligament was intact. Revision TKAs, in which the posterior cruciate ligament was absent, also demonstrated satisfactory results with the more constrained, posterior cruciate ligament-substituting prostheses.

Surgical management of supraspinatus compartment syndrome has not been previously reported. A high index of suspicion for severe shoulder pain of unclear etiology coupled with MRI is necessary for diagnosis. Prompt decompression to avoid irreversible ischemia is warranted. Perhaps mild ischemia of the supraspinatus muscle is an unrecognized cause of recurrent shoulder pain.

Thirty-one patients with unstable displaced pelvic or acetabular fractures were admitted and underwent an open reduction and internal fixation of their fracture. All patients were studied prospectively for the incidence of proximal deep vein thrombosis (DVT) utilizing venous duplex ultrasound. Duplex scans were repeated at 1 week postoperatively in all patients. Additional scans were performed when clinically indicated. A total of 61 scans were completed. DVT developed in three patients (approximately 10%). Two of the three positive scans were noted only on postoperative examination. The third scan was positive on the preoperative phase. Duplex ultrasound was easily applied and well tolerated by the multiply injured patient.

Four cases of fracture of the volar aspect of the greater multangular are presented. The correct diagnosis was missed initially due to the lack of proper roentgenographic views.

The clinical picture, pathogenesis, gross appearance, and pathological changes of an ossifying hematoma of the fingers called turret exostosis have been described, as well as the results of treatment in eight cases. It must be emphasized that the end result of the excision of the turret exostosis is dependent upon the timing and technical quality of the surgical excision.

Carrageenan, a sulfated polyanionic polysaccharide, is commonly used to induce inflammation in experimental animals, and this model is used to screen for the effectiveness of antiinflammatory drugs. Carrageenan-induced inflammation has been attributed to a variety of autocoids including histamine, bradykinin, complement, Superoxide, and prostaglandins. This study examines the effects of carrageenan on human PMN in a serum-free system. Carrageenan was found to stimulate the reduction of NBT by PMNs without stimulating membrane depolarization, oxygen consumption, H2O2 production, or myeloperoxidase secretion. Carrageenan stimulates a heat-labile, NBT-reducing system which is unassociated with the usual stimulus-response coupling seen with other PMN activators such as PMA, FMLP, and zymosan.

A comparative statistical analysis was performed weighing the relative merits of two surgical approaches for total hip arthroplasty--the Watson-Jones anterolateral approach and the gluteus maximus splitting posterolateral approach. Intraoperative and clinical records were evaluated for 175 patients undergoing total hip arthroplasty between 1975 and 1979--100 by a posterolateral approach and 75 by an anterolateral approach. Minimum follow-up period was two years. Mean operative times for the posterolateral and anterolateral approaches were 62 minutes and 140 minutes, respectively. The posterolateral group had a mean blood loss of 433 ml, with 35% requiring an average transfusion of 2.5 units. The anterolateral group had a mean blood loss of 767 ml, with 78% requiring an average transfusion of 2.5 units. The average lengths of hospitalization for posterolateral and anterolateral groups were 13 and 15 days, respectively. The time to independent cane ambulation was significantly less in the posterolateral group. The rate of post-operative complications was similar in each group. However, in the posterolateral group there were four dislocations, three loosened femoral components, one deep-wound infection, and one pulmonary embolus, while the anterolateral group suffered one dislocation, no prosthesis loosening, no deep-wound infections, and three pulmonary emboli. Although the posterolateral approach was associated with a lower perioperative morbidity than the anterolateral approach, the latter exhibited fewer dislocations and loosened acetabular components.