Visible/solar-light-driven thiyl-radical-triggered synthesis of multi-substituted pyridines.

A light-triggered synthesis of thio-functionalized pyridines is demonstrated using γ-ketodinitriles, thiols, and eosin Y as the photocatalyst. The reaction proceeds via the selective attack on one of the cyano groups by an in situ generated thiyl radical. The reaction also proceeds with nearly equal efficiency using direct sunlight. Large-scale synthesis and a few useful synthetic transformations of the substituted pyridines are also performed.

Surface Acoustic Wave Propagation of GaN/Sapphire Integrated with a Gold Guiding Layer.

Gallium nitride (GaN), widely known as a wide bandgap semiconductor material, has been mostly employed in high power devices, light emitting diodes (LED), and optoelectronic applications. However, it could be exploited differently due to its piezoelectric properties, such as its higher SAW velocity and strong electromechanical coupling. In this study, we investigated the affect of the presence of a guiding layer made from titanium/gold on the surface acoustic wave propagation of the GaN/sapphire substrate. By fixing the minimum thickness of the guiding layer at 200 nm, we could observe a slight frequency shift compared to the sample without a guiding layer, with the presence of different types of surface mode waves (Rayleigh and Sezawa). This thin guiding layer could be efficient in transforming the propagation modes, acting as a sensing layer for the binding of biomolecules to the gold layer, and influencing the output signal in terms of frequency or velocity. The proposed GaN/sapphire device integrated with a guiding layer could possibly be used as a biosensor and in wireless telecommunication applications.

Transformable Transient Directing Group-Assisted C(sp2)-H Activation: Synthesis and Late-Stage Functionalizations of o-Alkenylanilines.

The isocyanate group in aryl isocyanates serves as a transformable transient directing group in a Ru(II)-catalyzed ortho olefination leading to o-alkenylanilines. In alcoholic solvents, aryl isocyanates are transformed into carbamates, which initiate the insertion of acrylates via o-C-H activation. In particular, tAmOH serves the dual role of solvent-cum transient directing mediator. The o-alkenylanilines are converted into azacoumarins and subsequently into C-4 aryl-substituted azacoumarins using aryl iodides as coupling partners via Pd(II)-catalyzed C-H functionalizations.

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles.

Hypervalent iodine (HVI) chemistry is a rapidly growing subdomain of contemporary organic chemistry because of its enormous synthetic applications. The high nucleofugality of the phenyliodonio group (-I+Ph) and its radical nature, serving as a single-electron oxidant makes HVI compounds highly valuable in organic synthesis. Due to the feasibility and benignity, reactions that rely solely on HVI reagents as promoters have received particular interest. Considering their great influence and synthetic potential, we contribute a brief synopsis on this field with a specific emphasis on metal-free functionalisations of alkenes, alkynes and heterocycles. The discussion is divided according to the type of substrate and reaction type and elaborated with mechanism and representative examples.

Correction: Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles.

Correction for 'Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles' by Anjali Dahiya et al., Org. Biomol. Chem., 2022, DOI: 10.1039/d1ob02233d.

Visible-Light-Mediated Difunctionalization of Alkynes: Synthesis of ß-Substituted Vinylsulfones Using O- and S-Centered Nucleophiles.

An inimitable illustration of a green-light-induced, regioselective difunctionalization of terminal alkynes has been disclosed using sodium arylsulfinates and carboxylic acids in the presence of eosin Y as the photocatalyst. The present methodology is further demonstrated by employing NH4SCN as an S-centered nucleophile instead of carboxylic acid. The mechanistic investigation reveals a radical-induced iodosulfonylation followed by a base-mediated nucleophilic substitution. The mechanism is supported by various studies, viz., radical-trapping experiment, fluorescence quenching, and CV studies. In this protocol, (Z)-ß-substituted vinylsulfones are obtained, exclusively covering a broad range of alkynes and nucleophiles, which are often unaddressed. The present strategy can tolerate structurally discrete substrates with steric bulk and different electronic properties, which provides a straightforward and practical pathway for the synthesis of highly functionalized (Z)-ß-substituted vinylsulfones. Herein, C-O and C-S bonds are assembled simultaneously with the concomitant introduction of important functional groups, viz., ester, thiocyanate, and sulfone.

Cyano-Sacrificial (Arylthio)arylamination of Quinoline and Isoquinoline N-Oxides Using N-(2-(Arylthio)aryl)cyanamides.

A copper(I)-catalyzed regioselective arylthio-arylamination of quinoline and isoquinoline N-oxides has been achieved at the expense of a cyano (CN) group from N-(2-(arylthio)aryl)cyanamides. This reductive amination proceeds in one pot at 80 °C in the absence of any additives. This is a unique demonstration of aryl cyanamides serving as arylaminating agents on quinoline/isoquinoline N-oxides with concurrent autoreduction of N-oxide.

Visible-Light-Mediated Solvent-Switched Photosensitizer-Free Synthesis of Polyfunctionalized Quinolines and Pyridines.

A solvent (2,2,2-trifluoroethanol (TFE) vs ethyl alcohol (EtOH)) switched synthesis of quinolines and pyridines is illustrated from (E)-2-(1,3-diphenylallylidene)malononitriles via a Pd(II)-catalyzed photochemical process. The active catalyst [L2Pd(0)] generated serves as an exogenous photosensitizer. The process offers predominantly Z-alkenylated quinolines and pyridines in TFE and EtOH, respectively. Furthermore, large-scale synthesis and a few interesting post-synthetic modifications have been demonstrated.

Intranasal nanoparticulate delivery systems for neurodegenerative disorders: a review.

Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood-brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There are different pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradation and poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems show potential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.

Neurodegenerative diseases cause severe illness worldwide, over a sixth of the world's population suffer from these diseases in which 10­15% of the world's population lose their life. The presence of the blood­brain barrier (BBB) is one of the major drawbacks for the treatment. There are many ways to bypass the BBB, the intranasal route was found to be prominent among all routes. The drug is transported across epithelial cells by passive diffusion. Drawbacks, adverse reactions and physicochemical properties of the drug affect drug availability in the brain. These drawbacks can be solved by using novel nano formulations and intranasal drug-delivery devices. Nano formulations deliver drugs with negligible disadvantages; several nano formulations suitable for nose-to-brain targeting include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and niosomes. Delivery devices such as atomizers, nebulizers, pressurized olfactory devices metered-dose spray pumps and pressurized metered dose inhaler systems, dry powder inhalers, and powder devices have been used to deliver drugs to the brain through the intranasal route. The intranasal drug-delivery system could be a promising approach to treat neurodegenerative diseases, which could save the lives of a large patient population.

The Renaissance of Organo Nitriles in Organic Synthesis.

In the arena of functional group-oriented organic synthesis, nitrile or cyano functionality is of immense importance. The presence of nucleophilic N-atom, π-coordinating ability of the triple bond, and electrophilic C-center imparts unique and interesting reactivities. Owing to the ability of the nitrile to transform into various other functional groups or intermediates, the chemistry is very rich and diverse. In particular, the involvement of nitrile in numerous organic reactions such as inter- or intramolecular alkyne insertion, [2+2+2] cycloaddition with alkynes, [3+2] cycloaddition with azides, [4+2] cycloaddition with dienes allow the synthesis of many important carbo- and heterocycles. Furthermore, the nitrile serves as a directing group in many C-H bond functionalization reactions to introduce diverse functionalities and participate as a radical acceptor in radical cascade strategies to obtain a large variety of functional molecules. This review mainly focuses on the reactivity and diverse synthetic application of the nitrile including C-H bond functionalization, alkyne insertion, cycloaddition, and thermal or photochemical cascade strategy. The objective of the current review aims at bringing out the striking collection of various nitrile-triggered organic transformations.

Pd(II)-Catalyzed Synthesis of Furo[2,3-b]pyridines from ß-Ketodinitriles and Alkynes via Cyclization and N-H/C Annulation.

A Pd(II)-catalyzed synthesis of furopyridines has been developed from ß-ketodinitriles and alkynes via an unusual N-H/C annulation. The participation of both the nitrile groups and the concurrent construction of furan and pyridine rings through the formation of C-C, C═C, C-O, C-N, and C═N bonds are the important features. The synthetic applicability is further demonstrated through a series of postsynthetic alterations.

Visible-Light-Mediated Synthesis of Thio-Functionalized Pyrroles.

An inimitable illustration of the green-light-induced synthesis of thio-functionalized pyrroles has been established using ß-ketodinitriles and thiophenols as the reacting partners and eosin Y as the photocatalyst. Large-scale synthesis and some useful synthetic modifications of the thio-functionalized pyrroles are also demonstrated.

Posterior Belly of Digastric Muscle Transposition Flap in Preventing Frey's Syndrome after Superficial Parotidectomy- A Prospective Study.

Introduction: Superficial parotidectomy is an effective management for benign and malignant tumours of the superficial lobe of the parotid gland. Frey's syndrome is one of the most common complications observed after parotidectomy. The objective of our study was to find the incidence of Frey's syndrome 6 months and 1 year postoperatively after doing posterior belly of the digastric flap during superficial parotidectomy. Materials and Methods: This is an observational prospective study done in the Department of General Surgery of the Institute from November 2018 to December 2020. Thirty-eight patients with parotid swellings (both due to benign or malignant causes) were evaluated preoperatively and planned for superficial parotidectomy with a posterior belly of digastric muscle (PBDM) flap to prevent the occurrence of Frey's syndrome. They were followed up in 6 months and 1 year. Minor's test was done in each visit to look for the occurrence of Frey's syndrome. Results: Two patients (5.2%) out of 38 patients developed asymptomatic Frey's syndrome after 6 months postoperatively out of which one patient (2.6%) developed symptomatic Frey's syndrome after 9 months postoperatively with symptoms such as sweating, flushing, and redness over the parotid area during chewing. Discussion: PBDM flap following superficial parotidectomy in a single-stage surgery is an effective and easy method to prevent Frey's syndrome. This procedure is easy to perform and requires no complex dissection. There have not been many studies regarding the use of this flap; hence, this study may be considered as a pilot study.

Correction to Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.

[This corrects the article DOI: 10.1021/acsomega.0c04300.].

Effect of Perioperative Fluids on Serum Osmolality and Serum Sodium in Patients Undergoing Transcranial Excision of Craniopharyngioma: A Prospective Randomized Controlled Trial.

BACKGROUND: Electrolyte imbalance and acute diabetes insipidus (DI) are the most common complications in patients undergoing craniopharyngioma excision. Data are sparse regarding the choice of fluid in these patients. We compared the effects of balanced salt solution and 0.45% saline infused perioperatively on serum osmolality and serum sodium levels in these patients. METHODOLOGY: A prospective randomized double-blinded study was conducted in 30 patients undergoing transcranial excision of craniopharyngioma. The patients received either balanced salt solution or 0.45% sodium chloride solution perioperatively till they were allowed orally. Serum and urine osmolality, serum and urine sodium, urine specific gravity, and total dose of desmopressin required to treat DI were measured in the perioperative period. RESULTS: Demographic data were comparable. We observed that there was significantly higher serum osmolality in the intraoperative period at 2nd h (P = 0.04), 3rd h (P = 0.01), at end of the surgery (P = 0.034) and on postoperative day 0 (POD 0) with P = 0.03 in patients receiving balanced salt solution. We also observed that the difference in serum sodium levels were significantly higher in patients receiving balanced salt solution as compared to those receiving 0.45% sodium chloride solution intraoperatively, at 3rd h (P = 0.02) and at the end of surgery (P = 0.04) although the values were comparable in both the groups as measured on POD 0, 1 and 2. CONCLUSION: 0.45% sodium chloride solution has better effect on serum osmolality than balanced salt solution in patients undergoing transcranial resection of craniopharyngioma.

Laparoscopic Versus Open Rectopexy for Rectal Prolapse: A Randomized Controlled Trial.

Introduction Most of the patients with rectal prolapse complain of fecal incontinence followed by constipation. Surgery is the only definitive treatment option for rectal prolapse. There are two approaches: either transanal/perineal or transabdominal. The abdominal procedures can be done in the open laparotomy method or laparoscopically. Suture rectopexy is a very old and popular method of treating rectal prolapse. Nowadays, rectopexy by laparoscopic approach is considered the gold standard treatment for rectal prolapse. The study has been conducted to compare both the procedures and their outcomes in terms of conditions associated with rectal prolapse. Methods All consecutive patients with full-thickness rectal prolapse who had attended the surgery outpatient department were included in the study. The patients had undergone either open suture rectopexy or laparoscopic rectopexy after randomization. Assessment of postoperative pain, mean days of hospital stay, constipation, and incontinence score along with operative time, recurrence within six months of follow-up, and time to resume bowel activity were done. The patients were followed up for 18 months at regular intervals. Results A total of 58 patients were included in the study: 27 in the open group and 31 in the laparoscopic group. The operative time was 102 minutes versus 129 minutes (p=0.0001) in the open and laparoscopic groups, respectively. The laparoscopic group had an earlier resumption of bowel activity (3.1 days vs. 1.4 days [p=0.0001]); fewer days of hospital stay (6.8 days vs. 2.5 days [p=0.0001]), less postoperative pain (mean visual analogue scale score for pain on postoperative day one 4.0 versus 3.1 [p=0.0035] and on postoperative day two 3.8 versus 2.2 [p=0.0001]). There was no significant difference in postoperative constipation score and incontinence score between the two groups. Conclusion Laparoscopic rectopexy results in lesser postoperative pain, lesser hospital stay, and better patient satisfaction than open rectopexy.

Reinforcement of ball shaped MoS2 nanoparticles in epoxy resin.

The present work involves the synthesis of molybdenum disulfide (MoS2) nanoparticles by annealing the precursor obtained from simple reflux method. XRD, FESEM and HRTEM confirmed the formation of 2H-MoS2 with ball shaped particles, where some of them possess coalesced dumbbell morphology. The reinforcement of polysulphide modified epoxy resin (PSER) by MoS2 with varying amounts from 0.150 to 0.200 wt% provides unique combination of the improved thermal stability, tribological and mechanical properties. XRD studies indicate interaction between the sulphur containing nanoparticles and the epoxy resin. Maximum improvements in tensile strength (440%) and toughness (534%) are observed with ball shaped MoS2 nanoparticles (0.150 wt%)/PSER composite. Also the coefficient of friction and wear resistance show improvements of 60 and 78% respectively for 0.175 wt% loading in PSER compared to the neat resin matrix. Thermal stability is found to be improved maximum by 23 degrees C, when 5% weight loss is taken as a point of comparison. Similar studies on synthetic microcrystalline MoS2 filled PSER show that improvements in all these properties are very inferior.

Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.

Combination of drugs is extensively used to treat chronic inflammatory disease. Naringin (NAR), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC) are nutraceuticals with promising anti-inflammatory properties. However, their clinical effectiveness gets hindered because of low aqueous solubility and poor bioavailability. In the current study, two combinations of liposome (NAR + SFN and NAR + PEITC) were prepared and studied thoroughly in different in vivo models of acute and chronic models of inflammation. The encapsulation efficiency of NAR, SFN, and PEITC in the combination liposomal formulations (CLFs) prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine -020CN (15:4:1 M ratio) was determined to be 79.8 ± 4.2, 46.5 ± 3.6, and 78.5 ± 3.2%, respectively. The CLFs were characterized by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and Fourier transform infrared spectroscopy. The physicochemical results showed that the preparations were monodisperse (PDI 0.062-0.248) in water with an average size from 140.5 to 165.6 nm and a zeta potential of -47.3 to -53.3 mV. Dissolution studies in vitro showed a slower release of PEITC (>90%, 6 h) in comparison to that of SFN (3 h). Here, we are the first to report the antiarthritic activity of CLF of NAR + SFN and NAR + PEITC in the Freund's complete adjuvant (FCA)-induced arthritic model. At an intraperitoneal dose (375 + 375 µg/mL) for 3 weeks, the NAR + PEITC liposome significantly improves both % paw edema and arthritic score compared to their free drug combinations in FCA rats. Most importantly, hematological and biochemical results showed improved anemic conditions with significant changes in the SGOT, SGPT, and ALP levels. The ELISA results showed similar trends of increased cytokine (IL-10) and decreased inflammation markers (TNF-α, IL-6, IFN-γ). Histological evaluations showing reduction in cell infiltration, pannus formation, and bone and cartilage destruction further confirm and validate the antiarthritic activity of the CLF. This comprehensive study reveals the effectiveness of combination liposomes of poorly soluble anti-inflammatory molecules (NAR, SFN, PEITC) in the treatment of arthritis.

tert-Butyl Nitrite (TBN), a Multitasking Reagent in Organic Synthesis.

The upsurge interest in the development of efficient methodologies for the construction of nitrogen-containing frameworks via the use of expedient reagents have been creating a renaissance in contemporary organic chemistry. In this perspective, tertbutyl nitrite (TBN) is an emerging building block. Due to its unique structural features, it shows differential reactivity under different reaction conditions. These diverse reactivities have resulted in the construction of a diverse array of complex N-containing molecules. The primary objective of the present review is to bring the latest findings of TBN in terms of its applications in reactions (oxidation, diazotization, nitrosation, nitration, oximation, N-synthon, and miscellaneous reactions) into the limelight. For simplicity and brevity, reactions in each section are explained with the mechanism of formation and selected examples are given.