Phosphine Ligand-Free Bimetallic Ni(0)Pd(0) Nanoparticles as a Catalyst for Facile, General, Sustainable, and Highly Selective 1,4-Reductions in Aqueous Micelles.

Phosphine ligand-free bimetallic nanoparticles (NPs) composed of Ni(0)Pd(0) catalyze highly selective 1,4-reductions of enones, enamides, enenitriles, and ketoamides under aqueous micellar conditions. A minimal amount of Pd (Ni/Pd = 25:1) is needed to prepare these NPs, which results in reductions without impacting N- and O-benzyl, aldehyde, nitrile, and nitro functional groups. A broad range of substrates has been studied, including a gram-scale reaction. The metal-micelle binding is supported by surface-enhanced Raman spectroscopy data on both the NPs and their individual components. Optical imaging, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy analyses reveal the formation of NP-containing micelles or vesicles, NP morphology, particle size distribution, and chemical composition. X-ray photoelectron spectroscopy measurements indicate the oxidation state of each metal within these bimetallic NPs.

Domino Michael/Michael reaction catalyzed by switchable modularly designed organocatalysts.

The domino Michael/Michael reaction between (E)-7-aryl-7-oxohept-5-enals and trans-cinnamaldehydes was investigated by using modularly designed organocatalysts (MDOs). It was found that both the enamine and iminium catalytic modes of the MDOs are switchable and can be individually switched on and off by using appropriate combinations of the precatalyst modules and the reaction conditions. When both the enamine and iminium catalysis modes of the MDOs are switched on, the desired domino reaction products can be obtained in good yields and stereoselectivities under optimized conditions.

Photoassisted Charge Transfer Between DMF and Substrate: Facile and Selective N,N-Dimethylamination of Fluoroarenes.

A reversible Van der Waals complex formation between the electron-deficient fluorinated aromatic ring and N,N-dimethylformamide (DMF) molecules followed by light irradiation resulted in charge transfer (CT) process. The complex was stabilized by ammonium formate and further decomposed to form the C-N bond. Control experiments revealed that the simultaneous SN Ar pathway also contributes to product formation. This methodology is mild, metal-free, and effective for the amination of a variety of substrates. The reproducibility of this methodology was also verified on gram-scale reactions. The CT states were supported by control UV/Vis spectroscopy and computational studies.

Diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes by using the modularly designed organocatalysts upon switching on their iminium catalysis.

The cinchona thiourea moiety in the self-assembled modularly designed organocatalysts (MDOs) switches off the iminium catalysis of these catalysts. In this study, it was found that the inhibited iminium catalysis could be switched on by using an appropriate weak acid and that, once the iminium catalysis was switched on, these catalysts could be applied for the highly stereoselective and diastereodivergent synthesis of 4-oxocyclohexanecarbaldehydes via a domino reaction between ketones and α,ß-unsaturated aldehydes.

Clonidine as an Adjuvant to Bupivacaine for Suprazygomatic Maxillary Nerve Blocks in Cleft lip and Palate Repair: A Randomized, Prospective, Double-Blind Study.

OBJECTIVES: Does clonidine, as adjuvant to bupivacaine for suprazygomatic maxillary nerve blocks, reduce emergence agitation in patients undergoing cleft lip and cleft palate surgery? DESIGN: Randomized, controlled, and double-blind study. SETTING: Guwahati Comprehensive Cleft Care Center, Guwahati (Assam, India). PARTICIPANTS: A total of 124 patients; with a median age of 5 years in the clonidine group (CLG) and 7 years in the control group (CG), who underwent cleft lip or cleft palate surgery were included. Exclusion criteria included lack of consent from patients or their guardians, allergy to local anesthetics, coagulation disorders, local infection at the puncture site before performing the block, and language difficulties or cognitive disorders. INTERVENTIONS: Patients were randomized into 2 groups to receive bilateral suprazygomatic maxillary nerve blocks with either a bupivacaine/clonidine mixture for the CLG or bupivacaine alone in the CG. MAIN OUTCOME MEASURE: The primary end point was the incidence of emergence agitation. RESULTS: There was a statistically significant difference in the incidence of emergence agitation (30.2% in the CG compared to 15.2% in the CLG; difference of incidences: 15%, 95% CI: 0.1-30.1). The percentage of patients requiring intraoperative Fentanyl was lower in the CLG (10.6% compared to 26.4%; difference of incidences: 15.8%, 95% CI: 1.8-29). No other differences were observed. Further research in a more typically aged children population undergoing cleft surgery is needed. CONCLUSIONS: The use of clonidine as an adjuvant to bupivacaine in maxillary nerve block reduces the incidence of emergence agitation and intraoperative opioid consumption without hemodynamic or sedative side effects in patients undergoing cleft lip and palate surgery.

Shielding Effect of Micelle for Highly Effective and Selective Monofluorination of Indoles in Water.

Highly selective direct monofluorination of indoles and arenes was developed through an approach that allows site-specific solubility of substrate and fluorine source in the micelle. This approach was highly selective for a broad range of substrates with excellent functional group tolerance. Differences in binding constant and solubility of indoles and arenes in the micelle allowed the fine-tuning of selectivity. Control experiments suggested a radical pathway and provided insight into the role of micelles of the environmentally benign amphiphile PS-750-M. Dynamic light scattering experiments strongly indicated the site-specific solubility of the substrate and fluorine source. The methodology was successfully adapted to gram scale, and the E-factor established from a recycle study indicated that the process is environmentally responsible and sustainable.

Bilateral suprazygomatic maxillary nerve blocks vs. infraorbital and palatine nerve blocks in cleft lip and palate repair: A double-blind, randomised study.

BACKGROUND: Cleft defects are common craniofacial malformations which require early surgical repair. These patients are at high risk of postoperative airway obstruction and respiratory failure. Cleft surgery may require high doses of opioids which may contribute to these complications. OBJECTIVES: To compare the effectiveness of proximal and distal approaches to blocking the maxillary nerve in patients undergoing cleft lip or cleft palate surgery. DESIGN: Randomised, controlled and double-blind study. SETTING: The current study was carried out in Guwahati (Assam, India) between April 2014 and June 2014. PATIENTS: A total of 114 patients older than 6 months who underwent cleft lip or cleft palate surgery were included. Exclusion criteria included coagulation disorders, peripheral neuropathy or chronic pain syndrome, infection in the puncture site, allergy to local anaesthetics, lack of consent and language problems or other barriers that could impede the assessment of postoperative pain. INTERVENTIONS: Patients were randomly assigned to one of two groups: proximal group (bilateral suprazygomatic maxillary nerve blocks) and distal group (bilateral infraorbital nerve blocks for cleft lip repair and bilateral greater and lesser palatine nerve blocks and nasopalatine nerve block for cleft palate surgery). MAIN OUTCOME MEASURE: The primary endpoint was the percentage of patients requiring extra doses of opioids. Secondary endpoints included pain scores, respiratory and nerve block-related complications during the first 24 h. RESULTS: In the intra-operative period, there was a significant reduction of nalbuphine consumption in the proximal group (9.1 vs. 25.4%, P = 0.02). The percentage of patients requiring intra-operative fentanyl was lower in the proximal group (16.4 vs. 30.5%, P = 0.07). There were no differences in either postoperative pain scores or in postoperative complications. No technical failure or block-related complications were reported. CONCLUSION: Bilateral suprazygomatic maxillary nerve block is an effective and safe alternative to the traditional peripheral nerve blocks for cleft lip and cleft palate surgery, in a mixed paediatric and adult population.

Rhodium-Catalyzed Regio- and Stereoselective [2 + 2] Cycloaddition of Allenamides.

A highly regio- and stereoselective Rh-catalyzed intermolecular head-to-head [2 + 2] cycloaddition of allenamides was developed. The intermolecular cycloadducts, trans-dimethylenecyclobutane-1,2-diamine derivatives, were achieved in good yields with high regioselectivity and stereoselectivity.

PPL catalyzed four-component PASE synthesis of 5-monosubstituted barbiturates: Structure and pharmacological properties.

Enzymatic four-component reactions are very rare although three-component enzymatic promiscuous reactions are widely reported. Herein, we report an efficient PASE protocol for the synthesis of potentially lipophilic zwitterionic 5-monosubstituted barbiturates by four component reaction of mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde and barbituric acid in ethanol at room temperature. Seven different lipases were screened for their promiscuous activity towards the synthesis of 5-monosubstituted barbiturates and the lipase from porcine pancreas (PPL) found to give optimum efficiency. The zwitterionic 5-monosubstituted barbiturates with pyrazolyl ring showed promising pharmacological activity upon screening for antibacterial and apoptotic properties.

A green four-component synthesis of zwitterionic alkyl/benzyl pyrazolyl barbiturates and their photophysical studies.

A novel series of unsymmetrically substituted alkyl/benzyl pyrazolyl barbiturates incorporating highly biologically active pyrazolone and barbiturate moieties was synthesized by four-component reactions of a mixture of ethyl acetoacetate, hydrazine hydrate, aldehydes and barbituric acid/thiobarbituric acid in ethanol without using a catalyst. The photophysical properties of the newly designed alkyl/benzyl pyrazolyl barbiturates were studied, and good quantum yield of some products indicated a definitive scope in the field of biochemical applications. Single-crystal X-ray crystallographic studies revealed that the newly synthesized compounds exist in zwitterionic form. The zwitterionic nature of the new chimera makes them interesting candidates for drug delivery as zwitterionic drugs are known to have highly water soluble properties, specific protein absorption, slow recognition by immune system, slow blood clearance from body and can constantly diffuse and deposit throughout the physiological pH.