Reductions of Arenes using a Magnesium-Dinitrogen Complex.

In this contribution, we present "Birch-type", and other reductions of simple arenes by the potassium salt of an anionic magnesium dinitrogen complex, [{K(TCHPNON)Mg}2(µ-N2)] (TCHPNON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene), which acts as a masked dimagnesium(I) diradical in these reactions. This reagent is non-hazardous, easy-to-handle, and in some cases provides access to 1,4-cyclohexadiene reduction products under relatively mild reaction conditions. This system works effectively to reduce benzene, naphthalene and anthracene through magnesium-bound "Birch-type" reduction intermediates. Cyclohexadiene products can be subsequently released from the magnesium centres by protonolysis with methanol. In contrast, the reduction of substituted arenes is less selective and involves competing reaction pathways. For toluene and 1,3,5-triphenylbenzene, the structural authentication of "Birch-type" reduction intermediates is conclusive, although the formation of corresponding 1,4-cyclohexadiene derivatives was low yielding. Reduction of anisole did not yield an isolable "Birch-type" intermediate, but instead gave a C-O activation product. Treating triphenylphosphine with [{K(TCHPNON)Mg}2(µ-N2)] resulted in the extrusion of both biphenyl and dinitrogen to afford a magnesium(II) phosphanide [{K(TCHPNON)Mg(µ-PPh2)}2]. Reduction of fluorobenzene proceeded via C-F activation of the arene, and isolation of the magnesium(II) fluoride [{K(TCHPNON)Mg(µ-F)}2]. Finally, the two-electron reduction of 1,3,5,7-cyclooctatetraene (COT) with [{K(TCHPNON)Mg}2(µ-N2)] yielded a complex, [{K(TCHPNON)Mg}2(µ-COT)], incorporating the aromatic dianion (COT2-).

Decision tree learning in Neo4j on homogeneous and unconnected graph nodes from biological and clinical datasets.

BACKGROUND: Graph databases enable efficient storage of heterogeneous, highly-interlinked data, such as clinical data. Subsequently, researchers can extract relevant features from these datasets and apply machine learning for diagnosis, biomarker discovery, or understanding pathogenesis. METHODS: To facilitate machine learning and save time for extracting data from the graph database, we developed and optimized Decision Tree Plug-in (DTP) containing 24 procedures to generate and evaluate decision trees directly in the graph database Neo4j on homogeneous and unconnected nodes. RESULTS: Creation of the decision tree for three clinical datasets directly in the graph database from the nodes required between 0.059 and 0.099 s, while calculating the decision tree with the same algorithm in Java from CSV files took 0.085-0.112 s. Furthermore, our approach was faster than the standard decision tree implementations in R (0.62 s) and equal to Python (0.08 s), also using CSV files as input for small datasets. In addition, we have explored the strengths of DTP by evaluating a large dataset (approx. 250,000 instances) to predict patients with diabetes and compared the performance against algorithms generated by state-of-the-art packages in R and Python. By doing so, we have been able to show competitive results on the performance of Neo4j, in terms of quality of predictions as well as time efficiency. Furthermore, we could show that high body-mass index and high blood pressure are the main risk factors for diabetes. CONCLUSION: Overall, our work shows that integrating machine learning into graph databases saves time for additional processes as well as external memory, and could be applied to a variety of use cases, including clinical applications. This provides user with the advantages of high scalability, visualization and complex querying.

Coordination and Activation of N2 at Low-Valent Magnesium using a Heterobimetallic Approach: Synthesis and Reactivity of a Masked Dimagnesium Diradical.

The activation of dinitrogen (N2 ) by transition metals is central to the highly energy intensive, heterogeneous Haber-Bosch process. Considerable progress has been made towards more sustainable homogeneous activations of N2 with d- and f-block metals, though little success has been had with main group metals. Here we report that the reduction of a bulky magnesium(II) amide [(TCHP NON)Mg] (TCHP NON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5 % w/w K/KI yields the magnesium-N2 complex [{K(TCHP NON)Mg}2 (µ-N2 )]. DFT calculations and experimental data show that the dinitrogen unit in the complex has been reduced to the N2 2- dianion, via a transient anionic magnesium(I) radical. The compound readily reductively activates CO, H2 and C2 H4 , in reactions in which it acts as a masked dimagnesium(I) diradical.

Ni-Catalyzed Reductive Dicarbofunctionalization of Nonactivated Alkenes: Scope and Mechanistic Insights.

Olefins devoid of directing or activating groups have been dicarbofunctionalized here with two electrophilic carbon sources under reductive conditions. Simultaneous formation of one C(sp3)-C(sp3) and one C(sp3)-C(sp2) bond across a variety of unbiased π-systems proceeds with exquisite selectivity by the combination of a Ni catalyst with TDAE as sacrificial reductant. Control experiments and computational studies revealed the feasibility of a radical-based mechanism involving, formally, two interconnected Ni(I)/Ni(III) processes and demonstrated the different ability of Ni(I) species (Ni(I)I vs PhNi(I)) to reduce the C(sp3)-I bond. The role of the reductant was also investigated in depth, suggesting that a one-electron reduction of Ni(II) species to Ni(I) is thermodynamically favored. Further, the preferential activation of alkyl vs aryl halides by ArNi(I) complexes as well as the high affinity of ArNi(II) for secondary over tertiary C-centered radicals explains the lack of undesired homo- and direct coupling products (Ar-Ar, Ar-Alk) in these transformations.

Dual Photoredox/Nickel-Catalyzed Three-Component Carbofunctionalization of Alkenes.

The potential of merging photoredox and nickel catalysis to perform multicomponent alkene difunctionalizations under visible-light irradiation is demonstrated here. Secondary and tertiary alkyl groups, as well as sulfonyl moieties can be added to the terminal position of the double bond with simultaneous arylation of the internal carbon atom in a single step under mild reaction conditions. The process, devoid of stoichiometric additives, benefits from the use of bench-stable and easy-to-handle reagents, is operationally simple, and tolerates a wide variety of functional groups.

Palladium-Catalyzed Directed meta-Selective C-H Allylation of Arenes: Unactivated Internal Olefins as Allyl Surrogates.

Palladium(II)-catalyzed meta-selective C-H allylation of arenes has been developed utilizing synthetically inert unactivated acyclic internal olefins as allylic surrogates. The strong σ-donating and π-accepting ability of pyrimidine-based directing group facilitates the olefin insertion by overcoming inertness of the typical unactivated internal olefins. Exclusive allyl over styrenyl product selectivity as well as E stereoselectivity were achieved with broad substrate scope, wide functional-group tolerance, and good to excellent yields. Late-stage functionalisations of pharmaceuticals were demonstrated. Experimental and computational studies shed light on the mechanism and point to key steric control in the palladacycle, thus determining product selectivities.

Persistence of acetamiprid in paddy and soil under West Bengal agro-climatic conditions.

Acetamiprid insecticide has been widely used to control paddy insects. In order to find out the dissipation of acetamiprid residues in paddy (variety: Satabdi), field studies were conducted in Nadia, West Bengal. Acetamiprid (20% SP) was applied twice at 10 g (T1), 20 g (T2) and 40 g (T3) a.i. ha-1 with three replications along with untreated control (T4). Residue analysis of acetamiprid in paddy (leaf, grain, husk and straw) and soil was conducted utilizing high-pressure liquid chromatograph (HPLC) with UV detector at LOQ of 0.05 mg kg-1. The recoveries of acetamiprid from fortified paddy sample were obtained in the range of 81.8 to 93.1% (for leaf, grain, husk and straw), and for soil, it was 87.2 to 94.3% at the LOQ level and upper two levels of LOQ. The initial residue of acetamiprid (0.11-0.99 mg kg-1) dissipated following the first-order reaction kinetics with the half-life of 1.5 to 1.8 days in paddy leaf and 1.3 to 1.4 days in soil. In harvested samples of paddy straw, grain and soil, the residue was found below LOQ. Because of the rapid dissipation, acetamiprid may be considered to have low risk to the ecosystem. Therefore, the use of acetamiprid for plant protection in paddy may be considered safe for food and environmental health.

Template-Assisted meta-C-H Alkylation and Alkenylation of Arenes.

To expand the scope of meta-functionalization, a pyrimidine-based template effective for the formation of ß-aryl aldehydes and ketones, using allyl alcohols, by meta-C-H activation of benzylsulfonyl esters is described. In addition, α,ß-unsaturated aldehydes were generated by in situ olefination and deprotection of allyl benzyl ethers. These new functionalizations at the meta-position of an arene have also been successfully implemented in benzylphosphonate, phenethyl carbonyl, and phenethylsulfonyl ester scaffolds. Key to these successful new functionalizations is the creation of an electropositive palladium center by accepting the electron cloud from the metal to the energetically low-lying π-orbitals of pyrimidine ring, and it favors coordination of allyl alcohol to the metal center.

Remote meta-C-H Cyanation of Arenes Enabled by a Pyrimidine-Based Auxiliary.

An easily removable pyrimidine-based auxiliary has been employed for the remote meta-C-H cyanation of arenes. The scope of this Pd-catalyzed cyanation reaction using copper(I) cyanide as the cyanating agent was demonstrated with benzylsilanes, benzylsulfonates, benzylphophonates, phenethylsulfonates, and phenethyl ether derivatives. The method was utilized for the synthesis of pharmaceutically valuable precursors.

Rhodium-Catalyzed meta-C-H Functionalization of Arenes.

Rhodium-catalyzed ortho-C-H functionalization is well known in the literature. Described herein is the Xphos-supported rhodium catalysis of meta-C-H olefination of benzylsulfonic acid and phenyl acetic acid frameworks with the assistance of a para-methoxy-substituted cyano phenol as the directing group. Complete mono-selectivity is observed for both scaffolds. A wide range of olefins and functional groups attached to arene are tolerated in this protocol.

Steric control of Mg-Mg bond formation vs. N2 activation in the reduction of bulky magnesium diamide complexes.

Reduction of the magnesium(II) diamide [Mg(TripNON)] (TripNON = 4,5-bis(2,4,6-triisopropylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) with 5% w/w K/KI leads to a good yield of a dianionic dimagnesium(I) species, as its potassium salt, [{K(TripNON)Mg}2]. An X-ray crystallographic analysis shows the molecule to contain a very long Mg-Mg bond (3.137(2) Å). The formation of [{K(TripNON)Mg}2] contrasts with a previously reported reduction of a magnesium(II) complex incorporating a bulkier diamide ligand, which instead afforded a magnesium-dinitrogen complex. In the current study, [{K(TripNON)Mg}2] has been shown to be a viable reagent for the reductive activation of CO, H2 and N2O.

Synthesis of α-Seleno Boronates via Diboration of Carbonyl Compounds.

A method has been described for accessing α-seleno alkyl boronates. The selenoboration was achieved via the diboration of carbonyl compounds to give α-oxyl boronates, which then undergo 1,2-metalate rearrangement in the presence of lithium selenolates and trifluoroacetic anhydride (TFAA). A variety of structurally diverse substrates were compatible with this protocol and efficiently provides difunctionalized products from simple starting materials. The presence of the boronic ester in the resulting organoselenium compounds serves as a versatile synthetic handle for various functionalizations. Mechanistic studies revealed that the binding of selenium nucleophile to both the boron centers in α-oxyl boronate esters.

Approach to the Synthesis of gem-Thiolated Alkylboronates via Cobalt-Catalyzed Diboration of Aldehydes.

A new method has been developed for the sequential gem-thioborylation of readily available aldehydes via the cobalt-catalyzed diboration reaction. The N-heterocyclic carbene (NHC)-cobalt complex has been used as a catalyst for the diboration of aldehydes to generate α-oxyl boronic esters, which react with lithium thiolates to form a tetracoordinate boronate species, which undergoes 1,2-metalate rearrangement in the presence of trifluoroacetic anhydride. The stepwise functionalization of the boryl and thiol moiety of the products enriches the chemical toolbox of diverse organic synthesis.

Reductive activation of N2 using a calcium/potassium bimetallic system supported by an extremely bulky diamide ligand.

An extremely bulky xanthene bridged diamide ligand (TCHPNON = 4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene) has been developed and used to prepare two monomeric diamido-calcium complexes [(TCHPNON)Ca(D)n] (D = THF, n = 2, 3; D = toluene, n = 1, 4). Reduction of 4 with 5% w/w K/KI under an N2 atmosphere gave the first well-defined, hetero-bimetallic s-block complex of activated dinitrogen, [{K(TCHPNON)Ca}2(µ-η2:η2-N2)] 5, presumably via a transient calcium(I) intermediate.

Dissipation behaviour and risk assessment of fipronil and its metabolites in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS.

Fipronil -a broad spectrum phenylpyrazole insecticide has high level of toxicity towards environment. Therefore, an easy and reliable analytical method was developed for residue estimation of fipronil to ensure food and environmental safety. A modified QuEChERS technique was followed for estimation of fipronil (5% SC) in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS. The initial residues (0.168-0.794 µg g-1) of total fipronil i.e., sum of fipronil and its metabolites (viz., desulfinyl and sulfone) in leaf and soil were dissipated following first order kinetics. About 92-96% of fipronil residues were degraded after 15 days with half-life of 3.4-4.1 days and pre-harvest interval of 19.4-25.7 days in plant. Residues were below level of quantification (<0.005 µg g-1) in plant and soil at harvest. The fipronil residues in rice grain present low dietary risk (RQd < 1) to human health. However, high risk (RQd > 1) was predicted for cattle health due to fipronil residues in paddy leaf up to 10 days. The residual level in soil was also at highrisk (RQs > 1) for soil ecological health.

Evaluation of Functional Outcome of Elbows after Resection Arthroplasty of Failed Total Elbow Replacement.

BACKGROUND: Recovery of elbow function is a challenging problem following resection arthroplasty after failure of total elbow prosthesis. The objective of this study is to evaluate long term functional outcome in a series of such patients. MATERIALS AND METHODS: Nineteen patients with twenty elbows who had failed total elbow arthroplasty (TEA) following the use of Baksi total elbow prosthesis needed removal of prosthesis during the period from 1978 to 2003. As two patients were lost to followup, 17 patients with 18 elbows (bilateral in one) were included in this study with a mean age of 44.3 years. Nine cases had uncontrolled infection, seven cases of aseptic loosening including one occurred after TEA for bilateral postburns ankylosis, and two had broken humeral stems. After removal of the prosthesis and its adjacent surrounding bone cement, the cut ends of humerus and ulna were approximated with number 5 Ethibond suture. Postoperatively, the elbow was immobilized in a plaster slab in 110° elbow flexion for 6 weeks followed by physiotherapy. The patients were evaluated for 15-19.4 (mean 16.3) years where functional results were compared at 10 years and 15 years following resection arthroplasty. RESULTS: The resected elbow initially remained flail but gradually regained stability, especially in the sagittal plane. Both the groups showed overall improvement from preoperative Mayo Elbow Performance Score (MEPS) 26.5 to postoperative mean MEPS at 10 years (69.6) and at 15 years (70) (P = 0.001). Postoperative mean DASH score was 36.62 at 10 years' and 36.38 at 15 years' followup, suggesting persistence of function of resected elbow in the passage of time. The results were good in 9 (50%), fair in 7 (38.8%), and poor in 2 (11.1%) patients. None had recurrence of infection. Transient ulnar nerve palsy was seen in three patients. Postoperatively, power of Biceps recovered up to Medical Research Council grade 4 and Triceps 2-3. CONCLUSION: Resection arthroplasty of elbow provided acceptable functional recovery in our series of patients with failed elbow prosthesis.

Simultaneous determination and risk assessment of fipronil and its metabolites in sugarcane, using GC-ECD and confirmation by GC-MS/MS.

A sensitive gas chromatographic method using a modified QuEChERS technique is reported for simultaneous determination, dissipation and risk assessment of fipronil and its metabolites in sugarcane and soil. Recoveries were 80.7-98.5% with precision within 1.4-16.5% estimated at the limits of detection (LOD) 0.0015-0.002 µg g-1 and limits of quantification (LOQ) 0.005 µg g-1. Fipronil dissipated with half-life (T1/2) of 2.8-4.3 days while for total fipronil it was 3.7-6.0 days following application of fipronil (5% SC) in sugarcane fields at recommended (100 g a.i. ha-1) and double the recommended (200 g a.i. ha-1) doses. Estimated pre-harvest intervals (PHI) for fipronil were 20.3-27.0 days in sugarcane plants, and for total fipronil the corresponding values were 28.2-37.8 days. No dietary risk was observed due to fipronil (RQd < 1) 5 days after application. Potential risk exists towards algae and soil macro-organism (RQs > 1), but for earthworms it was safe (RQs < 1).

GC-MS/MS determination and ecological risk assessment of pesticides in aquatic system: A case study in Hooghly River basin in West Bengal, India.

A liquid-liquid extraction (LLE) for water and modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method for sediment combined with gas chromatography-tandem mass spectrometry (GC-MS/MS) detection in multiple reaction monitoring (MRM) mode was standardized for determination of 31 pesticides. Performance characteristics for the selected pesticides were acceptable according to European Commission's (EC) guidelines for method validation (recovery 70-120%, RSD <20% and R2 value ≥ 0.99). River, pond and tubewell water and river sediment samples (64 nos.) were collected from Hooghly River basin in West Bengal, India during 2014-2016. About 42% of the samples showed the presence of 19 pesticides with the highest loading of total pesticides (T-pesticides) in river water (3.01 ng mL-1) followed by sediment (1.25 ng g-1), pond (0.40 ng mL-1) and tubewell (0.02 ng mL-1) water. The non-agricultural OC (organochlorine) insecticides were detected in all river water and sediment samples mainly due to HCHs (hexachlorocyclohexane) from old source and fresh use of DDTs (dichlorodiphenyltrichloroethane) in local areas. No OC insecticides were detected in pond and tubewell water. Maximum residues of some recommended pesticides in agriculture were obtained in pond water. Most of the river water samples (93.7%) were in excess of EC limit (0.50 ng mL-1) of T-pesticides for drinking followed by pond water samples (56.2%). Tubewell water samples were free from T-pesticide threat but exceeded the EC limit (0.10 ng mL-1) for single pesticide in case of chlorpyrifos only. Ecological risk on aquatic animals was observed for OCs in river and chlorpyrifos in pond aquatic ecosystem.

A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy.

BACKGROUND: Vitamin B12 deficiency has been associated with peripheral neuropathy, loss of sensation in the peripheral nerves, and weakness in the lower extremities. Methylcobalamin is the most effective analogue of vitamin B12 used to treat or prevent the complications associated with vitamin B12 deficiency. The current study aimed to compare the serum cobalamin levels after administration of two different regimes of methylcobalamin in peripheral neuropathy patients. METHODS: The present study was a prospective, randomized, comparative study. The study consisted of two parallel groups, group A (methylcobalamin 500 µg injection intramuscularly three times a week) and group B (methylcobalamin 1500 µg injection intramuscularly once a week). A control group of healthy volunteers was also included. RESULTS: A total of 24 patients (12 in each group) were included in the study. Five healthy volunteers were also included as a control in each group. At the end of treatment, serum cobalamin levels were significantly (P = 0.028) higher in group A (1892.08 ± 234.50) as compared with group B (1438.5 ± 460.32). The serum cobalamin levels in Group A healthy volunteers were also two times higher than that of group B (P = 0.056). Both the LANSS scale and DN4 questionnaire reported similar results at end of treatment. CONCLUSIONS: The 500 µg methylcobalamin thrice weekly regime is more effective in increasing the serum cobalamin levels as compared to the 1500 µg methylcobalamin once weekly regime.

Validation of Multiresidue Method for Analysis of 31 Pesticides in Rice Using Gas Chromatography-Tandem Mass Spectrometry.

Five modified QuEChERS were tested for the multiresidue analysis of 31 pesticides in rice. Rice was spiked with mixture solution of pesticides at 10 ng/g. Method selection was based on the LODs (sensitivity) and recovery tests (accuracy) of the pesticides. Analysis was done in GC-tandem MS in multiple reaction monitoring mode with a total run time of approximately 37 min. The selected method was validated after spiking rice at 20 and 100 ng/g in rice. The performance characteristics of the method impacted for all selected pesticides were acceptable according to the guidelines for method validation (recovery of 70-120% with an RSD of <20% and r2 value of ≥0.99). For rice, matrix effect on the signals of the compounds was corrected by using matrix-matched calibration standards. The LOQs met the requirements of the maximum residue limits for pesticides in rice. The developed method allowed for the simultaneous determination and confirmation of a large number of different groups of pesticides and was fast, simple, inexpensive, and useful for the routine analysis of rice.