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A pyrido‐pyrimidinone heterocycle derived pH‐activated, hydrazone based molecular switch and its switching mechanism are reported here. The introduction of a new conjugated π electronic framework (enone part in the molecule) allowed the system to undergo hydrazone‐azo tautomerization, followed by E‐Z isomerization through rotation around the partial C−N single bond. Under acidic pH, protonation took place selectively on pyrimidinone nitrogen, and that turned the molecule to the corresponding ZH+ configuration. On the other hand, addition of triethylamine in the same solution reverted the molecule back to its original E‐configuration. Extensive proton‐NMR, and detailed X‐ray crystallography coupled with UV‐vis spectroscopy were carried out to establish the switching phenomena. Theoretical DFT calculations leading to free energy diagrams, transition states, and intermediates shed light on the mechanism behind the switching phenomenon. [ABSTRACT FROM AUTHOR]

Cyclic dipeptides (CDPs) are crucial building blocks for a range of functional nanomaterials due to their simple chemical structure and high molecular stability. In this investigation, we synthesized a set of S‐benzyl‐L‐cysteine‐based CDPs (designated as P1‐P6) and thoroughly examined their self‐assembly behavior in a methanol‐water solvent to elucidate the relationship between their structure and gelation properties. The hydrophobicity of the amino acids within the CDPs was gradually increased. The present study employed a comprehensive array of analytical techniques, including NMR, FT‐IR, AFM, thioflavin‐T, congo‐red CD, X‐ray crystallography, and biophysical calculations like Hirshfield Surface analysis and DFT analysis. These methods revealed that in addition to hydrogen bonding, the hydrophobic nature of the amino acid side chain significantly influences the propensity of CDPs to form hydrogels. Each CDP yielded distinct nanofibrillar networks rich in β‐sheet structures, showcasing unique morphological features. Moreover, we explored the practical application of these CDP‐based hydrogels in water purification by utilizing them to remove harmful organic dyes from contaminated water. This application underscores the potential of CDPs in addressing environmental challenges, offering a promising avenue for the future development of these materials in water treatment technologies. [ABSTRACT FROM AUTHOR]

Late‐stage functionalization of indoles can be a valuable strategy for modifying different existing indolyl‐drugs and natural products to get their new analogues. In this study, we report the photoredox‐metal catalyzed decarboxylative arylation strategy of indole‐3‐acetic acids with aryl halides. Here, photoredox‐catalysis was synergistically merged with nickel‐catalysis for the synthesis of biologically important 3‐benzyl indoles with good functional group tolerance. The merit of this methodology is demonstrated by the synthesis of amino acid derived substrates 3 p, 3 v and 3 x. [ABSTRACT FROM AUTHOR]

A Ruthenium(II) catalyzed additive‐free oxidative, dehydrogenative annulation of different malemides on 3,4‐disubstituted isoquinolone to afford fused and spiro‐cyclized isoquinolo‐isoquinolone and isoindolo‐isoquinolone derivatives is reported here. By simply changing solvent and oxidizing agents, under two different conditions, this methodology produced two different poly‐N‐heterocyclized products. Isoquinolone‐NH was strategically used as the internal directing group in the ortho C−H activation using Ru(II) catalyst. Mechanistically dehydrogenative, oxidative C−C followed by C−N cross‐coupling and aza‐michael reaction pathway led to the corresponding fused and spiro‐products respectively. A diversified library of eighty‐one (81) such two products were synthesized by employing this methodology. The fused and the spirocyclized polyheterocyclic compounds absorbed at λmax 240–270 nm range, however only spiro‐compounds produced blue fluorescence at λem 391–450 nm range. [ABSTRACT FROM AUTHOR]

Regioselective synthesis of N‐fused benzimidazo‐indolo‐isoquinoline heterocycles via Pd‐catalyzed domino coupling reaction of 1‐(1‐methyl‐1H‐indol‐2‐yl)‐1H‐benzimidazoles and aryl halides was developed. This one pot methodology proceeded via a five‐member carbopalladacycle intermediate and provided direct and facile route to access structurally complex polyheterocycles in moderate to good yields. These unique hybrid molecules resembled structural similarity with naturally isolated alkaloids. Notably, the present domino process occurred through activation of three C−H bonds and the simultaneous formation of two new C−C bonds in one‐shot. These molecules exhibited strong solid and solution phase fluorescence and their emission spectra in both the medium are reported here. [ABSTRACT FROM AUTHOR]

An environmentally benign, efficient, practically applicable and C(sp3)−H functionalization of primary amines for the synthesis of highly substituted oxazoles from easily available internal alkynes was developed. This synthesis is toxic chemicals, transition‐metal free as well as mild and regioselective. This one‐pot methodology with broad substrate scope unlocks a green avenue for the synthesis of highly functionalized oxazole derivatives with excellent yields. [ABSTRACT FROM AUTHOR]

Peptide‐based low molecular weight supramolecular hydrogels hold promising aspects in various fields of application especially in biomaterial and biomedical sciences such as drug delivery, wound healing, tissue engineering, cell proliferation, and so on due to their extreme biocompatibility. Unlike linear peptides, cyclic peptides have more structural rigidity and tolerance to enzymatic degradation and high environmental stability which make them even better candidates for the above‐said applications. Herein, a new small cyclic dipeptide (CDP) cyclo‐(Leu‐S‐Bzl‐Cys) (P1) consisting of L‐leucine and S‐benzyl protected L‐cysteine was reported which formed a hydrogel at physiological conditions (at 37°C and pH = 7.46). The hydrogel formed from the cyclic dipeptide P1 showed very good tolerance towards environmental parameters such as pH and temperature and was seen to be stable for more than a year without any deformation. The hydrogel was thermoreversible and stable in the pH range 6–12. Mechanical strength of P1 hydrogel was measured by rheology experiments. Atomic force microscopy (AFM) and field emission scanning electron microscopy (FE‐SEM) images revealed that, in aqueous solvents, P1 self‐assembled into a highly cross‐linked nanofibrillar network which immobilized water molecules inside the cages and formed the hydrogel. The self‐assembled cyclic dipeptide acquired the antiparallel β‐sheet secondary structure, which was evident from CD and Fourier transform infrared (FT‐IR) studies. The β‐sheet arrangement and formation of amyloid fibrils were further established by ThT binding assay. Furthermore, P1 was able to form a hydrogel in the presence of the anticancer drug 5‐fluorouracil (5FU), and sustainable release of the drug from the hydrogel was measured in vitro. The hydrogelator P1 showed almost no cytotoxicity towards the human colorectal cancer cell line HCT116 up to a considerably high concentration and showed potential application in sustainable drug delivery. The co‐assembly of 5FU and P1 hydrogel exhibited much better anticancer activity towards the HCT116 cancer cell line than 5FU alone and decreased the IC50 dose of 5FU to a much lower value. [ABSTRACT FROM AUTHOR]

Sulphonamide derived oxazoline hybrid compounds showed neuroprotective effects by inducing autophagy. In the present study, a series of sulphonamide containing oxazoline hybrids were synthesized and their neuroprotective efficacy in neuronal cell lines was explored. All the compounds showed moderate to good neuroprotection against adrenal medulla cell lines (PC 12). Compound 6 j had good neuroprotective activity against PC 12 cell lines showing increased expression of autophagy regulatory proteins (ATG7, LC 3B, p62, Beclin‐1) and anti‐apoptotic proteins (Bcl‐2) and also decreased expression of pro‐apoptotic proteins (Bax and Bad). This study demonstrated clearly that compound 6 j showed neuroprotective effect through the induction of autophagy and opens up new avenues for a new class of compounds as neuroprotective therapeutic agents. [ABSTRACT FROM AUTHOR]

This article, titled "Front Cover Picture: Ru(II) Catalyzed Oxidative Dehydrogenative Annulation and Spirocyclization of Isoquinolones with N-Substituted Maleimides," discusses the pursuit of scientific discovery and the symbolism of perseverance and dedication in the ancient Indian quest for spiritual liberation. The authors express gratitude to Dipomita Banerji for editing the cover art picture. The details of the research can be found in the Research Article by Kaushik Seal and Biswadip Banerji. [Extracted from the article]

Here in we report, rhodium(III)‐catalyzed decarboxylative acylation of arenes using α‐oxocarboxylic acids as acyl surrogate. In this strategy, O–NHAc group act as an autocleavable oxidizing directing group (ODGauto), thus giving rise to ortho‐acylated phenols in moderate to good yields. Mechanistic studies provided strong support for a kinetically relevant C–H bond activation. According to the best of our knowledge, this is the first report of Rhodium catalyzed decarboxylative acylation. [ABSTRACT FROM AUTHOR]

A 'green' methodology for the convenient synthesis of specific regioisomers of polysubstituted oxazoles through iodine catalyzed, water‐mediated, aerobic oxidative C(sp3)−H functionalization of primary amines has been developed. This mild and regioselective domino procedure does not require toxic peroxides, transition metals and organic solvents. The versatility of this methodology was demonstrated by preparing a natural product, texaline. It is also scalable and has a wide substrate scope. This methodology opens up a simple avenue for the synthesis of polyarylated oxazoles from various readily available amines as well as 1,2‐diketones and acyloins (α‐hydroxyl ketones) in moderate to excellent yields. Furthermore, these highly substituted oxazole molecules showed excellent fluorescence properties and thus have enormous potential to be a new type of fluorescent probe for use in medicinal applications and materials science. Green fields: An environmentally benign methodology was developed for the synthesis of polysubstituted oxazoles through an iodine‐catalyzed oxidative cyclization in water. The antimycobacterial natural product texaline was synthesized by using this protocol. These polyarylated oxazoles were prepared from readily available starting materials and the reaction can also be performed on gram scale. Some of the oxazole moieties showed good fluorescence response in solution as well as solid state. [ABSTRACT FROM AUTHOR]

A new turn‐on fluorescent probe 2‐((pyren‐3‐yl) methyl) isoindoline‐1,3‐dione was synthesized in a single step, high yielding reaction to detect hydrazine in solution. This ligand is highly sensitive to detect hydrazine in micromolar (1.1 μM) concentration in solution. It has high selectivity towards hydrazine compared to other analytes. Different biophysical experiments like hydrazine screening from both tap water and distilled water, vapour phase detection, anti‐interference studies with different analytes also corroborate the phenomenon of selective detection of hydrazine by our ligand. NMR titration and mass spectrum established the mechanism of hydrazine sensing. In addition, the probe was successfully used to trap exogenously added hydrazine inside the cell, which was further utilized to study insitu hydrazine released from an anti‐tubercular drug Isoniazid (INH), after its metabolism. A new turn on fluorescent probe was synthesized in a single step reaction in good yield to detect hydrazine in solution. It has high selectivity towards hydrazine compared to other relevant analytes. The probe was shown to detect exogenously added hydrazine inside the cell efficiently, which was further explored to study insitu hydrazine released from Isoniazid (INH), after its metabolism. Thus it was used as a protective reagent against hepatotoxicity induced by the release of hydrazine from the drug INH. [ABSTRACT FROM AUTHOR]

We report a palladium-catalyzed method for the direct synthesis of phenanthridones from benzamides in a single step. Unlike previous reports, the current protocol does not need any directing groups or any harsh conditions. This methodology has a wide functional group tolerance therefore a series of phenanthridones were synthesized with a yield up to 87 %. The efficacy of this protocol was further explored by synthesizing some important naturally occurring amaryllidaceae alkaloids in a single step with very good yields. [ABSTRACT FROM AUTHOR]

A new route for the expedient synthesis of specific regioisomer of quinazolinone- and phenanthridine-fused heterocycles through a palladium-catalyzed regioselective intramolecular oxidative C−H amination from cyclic strained amides of aromatic amido-amidine systems (quinazolinones) has been developed. The amine functionalization of an aromatic C−H bond from a strained amide nitrogen involved in aromaticity has been a challenging work so far. The fusion of two heterocyclic cores, quinazolinone and phenanthridine, can occur in two different ways (linear and angular), but under the conditions reported here, only linear type isomer is exclusively produced. This approach provides a variety of substituted quinazolinone- and phenanthridine-fused derivatives in moderate to excellent yields. Moreover, such fused molecules show excellent fluorescent properties and have great potential to be a new type of fluorophores for the use in medicinal and material science. [ABSTRACT FROM AUTHOR]

Cancer continues to be one of the biggest threats to the human civilization because there is no cure of it. Small heterocyclic molecule with low molecular weight and novel structural feature is therapeutically highly demanding. These molecules have the capability to disrupt signaling pathways leading to anticancer activities. Therefore, the search for new anticancer agents continues to draw attention to the research community. In this study, a small triazolo-benzoxazepine scaffolds was synthesized using a one-pot four-step synthetic methodology involving click reaction. Small libraries of 12 compounds were successfully synthesized and screened them against different cancer cell lines. Low micromolar anticancer activity was recorded using MTT assay, and further confirmation of cell death was obtained by phase contrast, fluorescent, and confocal images. [ABSTRACT FROM AUTHOR]

Under the reaction conditions only linear fused isomers are obtained. [ABSTRACT FROM AUTHOR]