A quantitative and qualitative investigation of the impact of irradiation on the physico-chemical of pointed gourd during storage.

Irradiation effect on the physico-chemical characteristics and shelf stability of pointed gourd was investigated in research. It was estimated that moisture content, total phenol and total carotenoids was significantly (p≤0.05) decreased while physiological loss in weight, total soluble solids, lutein and α-cryptoxanthin were increased during the completion of study. The three carotenoid pigments (ß-carotene, lutein, α-cryptoxanthin) were identified by Thin Layer Chromatography (TLC) and spectrophotometric method and its changes reported during storage in control and irradiated sample. The principal component analysis showed that b* value, Physiological Loss Weight (PLW), adhesiveness and acidity have negative correlation with rest of the parameters during storage. The research will present a progressive strategy for increasing the storage stability of pointed gourd during transportation and storage in India's government and private mandis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05395-3.

Cyclic peptides nanospheres: A '2-in-1' self-assembled delivery system for targeting nucleus and cytoplasm.

Vascular endothelial growth factor (VEGF) is considered as one of the vital growth factors for angiogenesis, which is primarily responsible for the progress and maintenance of new vascular network in tumor. Numerous studies report that inhibition of VEGF-induced angiogenesis is a potent technique for cancer suppression. Recently, RNA interference, especially small interfering RNA (siRNA) signified a promising approach to suppress the gene expression. However, the clinical implementation of biological macromolecules such as siRNA is significantly limited because of stability and bioavailability issues. Herein, self-assembled peptide nanospheres have been generated from L,L-cyclic peptides using hydrophobic (Trp), positively charged (Arg) and cysteine (Cys) amino acid residues and demonstrated as vehicles for intracellular delivery of VEGF siRNA and VEGF antisense oligonucleotide. Formation of peptide nanostructures is confirmed by HR-TEM, AFM, SEM and DLS analysis. Possible mechanism of self-assembly of the cyclic peptides and their binding with macromolecules are demonstrated by in-silico analysis. Gel electrophoresis reveals that the newly generated peptide based organic materials exhibit strong binding affinity toward siRNAs / antisense oligonucleotides (ASOs) at optimum concentration. Flow cytometry and confocal microscopy results confirm the efficiency of the new biomaterials toward the intracellular delivery of fluorescent labeled siRNA / ASOs. Furthermore, VEGF expression evaluated by western blot and RT-PCR upon the delivery of functional VEGF siRNA/ASOs suggests that very low concentrations of VEGF siRNA/ASOs cause significant gene knockdown at protein and mRNA levels, respectively.

Carbon nano-dot for cancer studies as dual nano-sensor for imaging intracellular temperature or pH variation.

Cellular temperature and pH govern many cellular physiologies, especially of cancer cells. Besides, attaining higher cellular temperature plays key role in therapeutic efficacy of hyperthermia treatment of cancer. This requires bio-compatible, non-toxic and sensitive probe with dual sensing ability to detect temperature and pH variations. In this regard, fluorescence based nano-sensors for cancer studies play an important role. Therefore, a facile green synthesis of orange carbon nano-dots (CND) with high quantum yield of 90% was achieved and its application as dual nano-sensor for imaging intracellular temperature and pH was explored. CND was synthesized from readily available, bio-compatible citric acid and rhodamine 6G hydrazide using solvent-free and simple heating technique requiring purification by dialysis. Although the particle size of 19 nm (which is quite large for CND) was observed yet CND exhibits no surface defects leading to decrease in photoluminescence (PL). On the contrary, very high fluorescence was observed along with good photo-stability. Temperature and pH dependent fluorescence studies show linearity in fluorescence intensity which was replicated in breast cancer cells. In addition, molecular nature of PL of CND was established using pH dependent fluorescence study. Together, the current investigation showed synthesis of highly fluorescent orange CND, which acts as a sensitive bio-imaging probe: an optical nano-thermal or nano-pH sensor for cancer-related studies.

'BhAVI-23'-A spice-herb based dietary infusion possessing in-vitro anti-viral potential.

BACKGROUND: Viruses cause many life threatening human diseases. Recently, COVID-19 pandemic has challenged the health care systems worldwide. As a disease preventive approach and to bring relief to the severity of the symptoms, a infusion termed as Bhabha Anti-Viral Infusion-23 ('BhAVI-23') was conceptualized and formulated which comprised of 23 selected spices and herbals. OBJECTIVE: The present study was conducted to assess the in vitro antiviral potential of the formulation, BhaAVI-23. MATERIAL AND METHODS: The in-vitro anti-viral potential of BhAVI-23 was assessed through inhibition of HIV1 reverse transcriptase (RT) as well as through a novel P1 (virulent) bacteriphage based screening assay system. Anti-diabetic potential was assessed by non-enzymatic glycosylation of haemoglobin and the bioactive volatile components were detected through headspace gas chromatography followed by molecular docking analysis. RESULTS: The infusion displayed prominent anti-viral activity as evident from significant (57%) inhibition of the HIV1-RT as well as through reduction in the infectivity of P1 (virulent) bacteriophage. The infusion also exerted profound protection (∼64%) to non-enzymatic glycosylation of haemoglobin. Headspace gas chromatography and mass spectrometric analysis confirmed the presence of at least 47 major compounds. Docking analysis indicated possible interaction of α-pinene and eugenol with SARS-CoV spike protein. CONCLUSION: This 'BhAVI-23' infusion displayed prominent in-vitro anti-viral and anti-diabetic potential in different model systems. These attributes have relevance as diabetic patients are more prone to COVID-19 morbidity. 'BhAVI-23' opens the avenue for its potential inclusion as a supportive health care system upon due regulatory approval during the current pandemic.

Intussusception in children aged under two years in India: Retrospective surveillance at nineteen tertiary care hospitals.

OBJECTIVE: Intussusception has been linked with rotavirus vaccine (RVV) as a rare adverse reaction. In view of limited background data on intussusception in India and in preparation for RVV introduction, a surveillance network was established to document the epidemiology of intussusception cases in Indian children. METHODS: Intussusception in children 2-23 months were documented at 19 nationally representative sentinel hospitals through a retrospective surveillance for 69 months (July 2010 to March 2016). For each case clinical, hospital course, treatment and outcome data were collected. RESULTS: Among the 1588 intussusception cases, 54.5% were from South India and 66.3% were boys. The median age was 8 months (IQR 6, 12) with 34.6% aged 2-6 months. Seasonal variation with higher cases were documented during March-June period. The most common symptoms and signs were vomiting (63.4%), bloody stool (49.1%), abdominal pain (46.9%) and excessive crying (42.8%). The classical triad (vomiting, abdominal pain, and blood in stools) was observed in 25.6% cases. 96.4% cases were diagnosed by ultrasound with ileocolic location as the commonest (85.3%). Management was done by reduction (50.8%) and surgery (41.1%) and only 1% of the patients' died. 91.1% cases met Brighton criteria level 1 and 3.3% Level 2. Between 2010 and 2015, the case load and case ratio increased across all regions. CONCLUSION: Intussusception cases have occurred in children across all parts of the country, with low case fatality in the settings studied. The progressive rise cases could indicate an increasing awareness and availability of diagnostic facilities.

Ag(I)-Fesulphos-Catalyzed Enantioselective Synthesis of 3-Silylproline Derivatives.

An efficient catalytic asymmetric 1,3-dipolar cycloaddition of N-benzylidineiminoglycinate-derived azomethine ylides to ß-silylmethylene malonates catalyzed by a Ag(I)-Fesulphos complex has been developed, affording fully substituted 3-silylproline derivatives with an all carbon quaternary center. The silylproline derivatives were obtained in moderate-to-good yields (up to 81%) in high diastereoselectivities and enantioselectivities (dr up to 95:5; er up to 96:4). Tamao-Fleming oxidation of selected 3-silylproline derivatives provided not only an efficient route but also the shortest route to 3-hydroxyproline derivatives, which are not accessible by direct 1,3-dipolar cycloadditions of azomethine ylide with frequently used arylidene/alkylidene malonates.

First Report on the Separation of Trivalent Lanthanides from Trivalent Actinides Using an Aqueous Soluble Multiple N-Donor Ligand, 2,6-bis(1 H-tetrazol-5-yl)pyridine: Extraction, Spectroscopic, Structural, and Computational Studies.

A terdentate multiple N donor ligand, 2,6-bis(1 H-tetrazol-5-yl)pyridine (H2BTzP), was synthesized, and its complexation with trivalent americium, neodymium, and europium was studied using single-crystal X-ray diffraction, attenuated total reflectance-fourrier transform infrared spectroscopy, time-resolved fluorescence spectroscopy, UV-vis absorption spectrophotometry. Higher complexation strength of BTzP toward trivalent actinide over lanthanides as observed from UV-vis spectrophotometric study resulted in an effective separation of Am3+ and Eu3+ in liquid-liquid extraction studies employing N,N, N',N'-tetra- n-octyl diglycolamide in the presence of BTzP as the aqueous complexant. The selectivity of BTzP toward Am3+ over Eu3+ was further investigated by DFT computations, which indicated higher metal-ligand overlap in the Am3+ complex as indicated from the metal-nitrogen bond order and frontier molecular orbital analysis of the BTzP complexes of Am3+ and Eu3+.

Superparamagnetic graphene oxide-magnetite nanoparticle composites for uptake of actinide ions from mildly acidic feeds.

Super paramagnetic graphene oxide (GO) - Fe3O4 nanoparticle composites were prepared and characterized by conventional techniques such as XRD, SEM, EDX, FT-IR, Raman, XPS, DLS and zeta potential, etc. TEM studies have confirmed nanoparticle nature of the composites. The GO-magnetic nanoparticle composites can be dispersed in mildly acidic aqueous solutions and get concentrated in a small volume under application of an external magnetic field. The composites were evaluated for the uptake of actinide ions such as Am3+, UO22+, Th4+ and Pu4+ from mildly acidic aqueous solutions. Am3+ sorption sharply increased with pH as the Kd values increased from about 10 at pH 1 to 105 at pH 3 beyond which a plateau in the Kd values was seen. Eu3+ displayed nearly comparable uptake behaviour to that of Am3+ while the uptake of other metal ions followed the trend: Pu(IV)>Th(IV)>>UO22+. The adsorption behaviour of Am3+ onto the graphene oxide - Fe3O4 nanoparticle composites fitted very well to the Langmuir as well as Temkin isotherm models. The desorption rate (using 1M HNO3) was fast and reusability study results were highly encouraging. The very high uptake values suggest possible application of the magnetic nanoparticles in radioactive waste remediation in natural ground water.

Organocatalytic decarboxylative aldol reaction of ß-ketoacids with α-ketophosphonates en route to the enantioselective synthesis of tertiary α-hydroxyphosphonates.

The first example of an asymmetric organocatalyzed decarboxylative aldol reaction of ß-ketoacids (aroylacetic acids) with α-ketophosphonates that produces a quaternary chiral centre has been developed. A quinidine based bifunctional urea derivative was identified as the preferred catalyst affording γ-aroyl tertiary α-hydroxyphosphonates in good yield and enantioselectivity. The 31P NMR spectroscopic study was performed to shed light on the reaction mechanism.

Tuning the Stability and the Reactivity of Substituted [3]Dendralenes for Quick Access to Diverse Copiously Functionalized Fused Polycycles with Step and Atom Economy.

This is the first comprehensive study that details the synthesis of stable acyclic trisubstituted [3]dendralenes and deciphers their structural requisite for a successful diene transmissive Diels-Alder (DTDA) reaction by employing two different dienophiles and eventually generating a small repository of complex molecules, thus exemplifying how substituted [3]dendralenes could be deployed in diversity-oriented synthesis with high selectivities. A balance of reactivity and stability was struck by prudent selection of the position and nature of functional groups on these [3]dendralenes. Upon tandem Diels-Alder reactions with several symmetrical as well as unsymmetrical dienophiles, these dendralenes afforded diversity-oriented quick access to many polycyclic complex motifs possessing several functional groups and multiple stereogenic centers. Thus, the full potential of the dendralenes could be harnessed. The reactions proceeded under mild conditions with step and atom economy and were highly regio- and stereoselective besides being excellent yielding. The DTDA sequence resulted in the generation of four new carbon-carbon bonds, two new rings, and 3-7 stereogenic centers. The key feature of the method is that we could rapidly generate complexity along with functional and structural diversity from a trivial acyclic substrate with no stereogenic centers.

Organocatalyzed enantioselective Michael addition/cyclization cascade reaction of 3-isothiocyanato oxindoles with arylidene malonates.

An organocatalyzed Michael addition-cyclization reaction between 3-isothiocyanatooxindoles and arylidene malonates has been developed for the synthesis of highly functionalized 3,2'-pyrrolidinyl spirooxindole derivatives. The reaction was catalyzed by a quinine derived tertiary amino-thiourea based bifunctional catalyst or its pseudo-enantiomeric quinidine derived catalyst providing both the enantiomers of the desired product. The products were obtained in high yields and with excellent diastereo- (up to 99 : 1 dr) and enantioselectivities (up to >99% ee).

Synthesis and extraction studies with a rationally designed diamide ligand selective to actinide(iv) pertinent to the plutonium uranium redox extraction process.

A new class of conformationally constrained oxa-bridged tricyclo-dicarboxamide (OTDA) ligand was rationally designed for the selective extraction of tetravalent actinides pertinent to the Plutonium Uranium Redox EXtraction (PUREX) process. Two of the designed diamide ligands were synthesized and extraction studies were performed for Pu(iv) from HNO3 medium. The mechanism of extraction was investigated by studying various parameters such as feed HNO3, NaNO3 and OTDA concentrations. The nature of the extracted species was found to be [Pu(NO3)4(OTDA)]. One of the OTDA ligands was elaborately tested and showed the selective extraction of Pu(iv) and Np(iv) over other actinide species, viz., U(vi), Np(v), Am(iii), lanthanides and fission products contained in a nuclear waste from the PUREX process. DFT calculations predicted the charge density on each of the coordinating 'O' atoms of OTDA supporting its high Pu(iv) selectivity over other ions studied and also provided the energy optimized structure of OTDA and its Pu(iv) complex.

"On Water" Organocatalyzed [4 + 2] Cycloaddition of Enones and Nitro Dienes for the Enantioselective Synthesis of Densely Substituted Cyclohexanones.

An "on water" hydroquinine-based primary amine-benzoic acid organocatalyst system was found to be best suited to produce 3,4,5-trisubstituted cyclohexanones with a nitro group in the 4-position from enones and nitro dienes under ambient conditions in good yield, with good diastereoselectivity, and with excellent enantioselectivity. An appreciable rate enhancement by water was observed compared to organic solvents. Mechanistic analysis of the reaction suggests that it followed an endo [4 + 2] cycloaddition with enamine of enone as diene and nitro diene as dienophile.

Design, synthesis and extraction studies of a new class of conformationally constrained (N,N,N',N'-tetraalkyl)7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamides.

A new class of conformationally constrained 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamides (OBDA) of three secondary amines was synthesized, and their extraction behavior for trivalent and tetravalent actinides in HNO3 medium was studied. Amongst the diamides, N,N-bis-2-ethylhexyl substituted diamide showed the best results for actinide extraction. This diamide also exhibited a very low level of extraction for Sr(ii) and Ru(iii) which is desirable, thus providing higher selectivity for actinides. The stripping of extracted metal ions was achieved using 0.1 M oxalic acid for Pu(iv) or pH ∼ 2 solution for Am(iii). Third phase formation was not observed for the OBDA ligand even for a higher concentration of Eu up to 5 g L(-1) with retention of good DEu. The tridentate nature of the OBDA ligand was ascertained by studying the IR and NMR spectra of the Eu(iii) complex with the ligand. The OBDA showed the formation of a mixture of mono- and di-solvated species of Eu(iii) as indicated by the slope analysis method and ESI-MS. Density functional theoretical (DFT) study was carried out to determine the energy optimized structure of the free ligand and its Am(3+) complex.

Dialkylmethyl-2-(N,N-diisobutyl)acetamidoammonium iodide as a ruthenium selective ligand from nitric acid medium.

A new class of quaternary ammonium iodide based ligands with 2-(N,N-diisobutyl)acetamide as an alkyl appendage have been designed, synthesized and tested for their ability to extract ruthenium selectively from nitric acid medium. The 2-(N,N-diisobutyl)acetamido ammonium iodide with two propyl and a methyl substituents showed best results for the recovery of ruthenium. The optimized concentration of the solvent was found to be 0.2M in 30% isodecyl alcohol/n-dodecane. The stoichiometry of the complex was ascertained by slope analysis method and was found to be 1:1 with respect to ligand L(+)I(-) and Ru(NO)(NO3)3. Ruthenium formed an adduct of structure LRu(NO)(NO3)3 I in the extraction medium. Iodide ion played an important role in the formation of the stable and extractable complex of ruthenium. No extraction was observed when iodide was replaced by nitrate anion in the ligand. The ligand also showed good selectivity for ruthenium in the presence of other metal ions commonly found in nitric acid solutions of nuclear waste.

A remarkable enhancement in Am³âº/Eu³âº selectivity by an ionic liquid based solvent containing bis-1,2,4-triazinyl pyridine derivatives: DFT validation of experimental results.

Mutual separation of trivalent actinide (An(3+)) and lanthanide (Ln(3+)) using several soft (N) donor ligands (bis(5,6-dialkyl-1,2,4-triazinyl)pyridine (R-BTP)) is attempted for the first time in room temperature ionic liquid (RTIL) medium. The results indicate a spectacular enhancement in the selectivity as compared to that in molecular diluents with a separation factor (S.F.) of >3000 for Am(3+) over Eu(3+) using the methyl derivative (Me-BTP) in RTIL medium using [C(n)mim]·[NTf2] as the diluents (where n = 2, 3, 4, 6 or 8). Such a high S.F. value has never been reported before with any of the R-BTP derivatives in molecular diluents. An opposite trend in the distribution ratio values of both Am(3+) and Eu(3+) with the increasing size of the alkyl (R) group is observed in RTIL medium when compared with that in molecular diluents. The differences in the extraction behaviour of R-BTPs in RTILs vis-à-vis molecular diluents are explained on the basis of the difference in the nature of complexes extracted in these two distinctly different media as supported by the time resolved fluorescence (TRFS) study. An unusually high extractability and selectivity for Am(3+) over Eu(3+) with Me-BTP was attributed to the formation of a 1 : 4 complex for Am(3+), which was never reported earlier with any of the R-BTP derivatives in molecular diluents. DFT studies indicated higher metal 'd' and 'f' orbital participation (covalence) in the bonding with R-BTP in the case of Am(3+) complexes as compared to that in the case of Eu(3+) complexes, which resulted in the selectivity of these classes of ligands. The observed results may have a great significance in the radioactive waste management involving the partitioning and transmutation strategy.

Complexation of trivalent americium and lanthanides with terdentate 'N' donor ligands: the role of rigidity in the ligand structure.

A systematic study on the Ln(3+) complexation behaviour with two terdentate 'N' donor ligands of varying structural rigidity, viz. 5,6-dimethyl-(1,2,4)-triazinylbipyridine (Me2TBipy) and 5,6-dimethyl-(1,2,4)-triazinylphenanthroline (Me2TPhen), is performed in the present work by UV-Vis spectrophotometry, time resolved fluorescence spectroscopy (TRFS) and electrospray ionization mass spectrometric (ESI-MS) studies. These studies indicate the formation of a 1 : 1 complex of La(3+), 1 : 2 complexes of Eu(3+) and Er(3+) with both the ligands. Density functional theoretical (DFT) study is carried out to determine the solution phase structure of the Eu(3+) complex considering the species (from UV-Vis spectrophotometry) and C2v site symmetry around the Eu(3+) ion (from TRFS study). Me2TPhen is found to be a stronger complexing ligand as compared to Me2TBipy irrespective of the Ln(3+) ions. The solid state crystal structure of the La(3+) complex of Me2TPhen is determined using the single crystal X-ray diffraction (SCXRD) technique. The complexation of the trivalent Am(3+) ion is also studied with both these ligands using UV-Vis spectrophotometric titrations which show the formation of 1 : 2 complexes with higher complexation constant values as compared to all the Ln(3+) ions studied, indicating the selectivity of these ligands for the trivalent actinides over the lanthanides.

A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.

Deuterium-labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl-d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2 O combination with high yield and isotopic purity. The 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one was obtained from the adduct of methyl-d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran-2-one is the precursor for geminal (2) H2 -labeled (+)-4-hydroxy-6-undecyl-tetrahydropyran-2-one, an advanced intermediate for gem-dideutero (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide syntheses.

Synthesis of substituted [3]dendralenes and their unique cycloaddition reactions.

Dimethylsulfonium methylide mediated olefination of 2-phenylethenylidene phosphonoacetate followed by the Horner-Wadsworth-Emmons reaction with aromatic aldehydes provided access to reactive 1,5-diaryl-2-ethoxycarbonyl [3]dendralenes which in situ underwent Diels-Alder cyclodimerisation leading to highly functionalised cyclohexenes with very high regio- and stereoselectivity.

Developing a diastereoselective intramolecular [4+3] cycloaddition of nitrogen-stabilized oxyallyl cations derived from N-sulfonyl-substituted allenamides.

Efforts toward achieving a practical and diastereoselective intramolecular [4+3] cycloaddition of nitrogen-stabilized oxyallyl cations with tethered dienes are described. Epoxidation of N-sulfonyl substituted allenamides with dimethyldioxirane (DMDO) generates nitrogen-stabilized oxyallyl cations that readily undergo stereoselective [4+3] cycloaddition with dienes. Selectivity is found to depend on the tethering length as well as the stability of the oxyallyl cation intermediate, whether generated from N-carbamoyl- or N-sulfonyl-substituted allenamides. The use of chiral N-sulfonyl-substituted allenamides provided minimal diastereoselectivity in the cycloaddition, while high diastereoselectivity can be achieved with a stereocenter present on the tether. These studies provide further support for the synthetic utility of allenamides.