Tandem dehydrogenation-olefination-decarboxylation of cycloalkyl carboxylic acids via multifold C-H activation.

Dehydrogenation chemistry has long been established as a fundamental aspect of organic synthesis, commonly encountered in carbonyl compounds. Transition metal catalysis revolutionized it, with strategies like transfer-dehydrogenation, single electron transfer and C-H activation. These approaches, extended to multiple dehydrogenations, can lead to aromatization. Dehydrogenative transformations of aliphatic carboxylic acids pose challenges, yet engineered ligands and metal catalysis can initiate dehydrogenation via C-H activation, though outcomes vary based on substrate structures. Herein, we have developed a catalytic system enabling cyclohexane carboxylic acids to undergo multifold C-H activation to furnish olefinated arenes, bypassing lactone formation. This showcases unique reactivity in aliphatic carboxylic acids, involving tandem dehydrogenation-olefination-decarboxylation-aromatization sequences, validated by control experiments and key intermediate isolation. For cyclopentane carboxylic acids, reluctant to aromatization, the catalytic system facilitates controlled dehydrogenation, providing difunctionalized cyclopentenes through tandem dehydrogenation-olefination-decarboxylation-allylic acyloxylation sequences. This transformation expands carboxylic acids into diverse molecular entities with wide applications, underscoring its importance.

Access to unsaturated bicyclic lactones by overriding conventional C(sp3)-H site selectivity.

Transition metal catalysis plays a pivotal role in transforming unreactive C-H bonds. However, regioselective activation of distal aliphatic C-H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C-H bond in the presence of methyl C-H is underexplored. Here we show activation of a methylene C-H bond in the presence of methyl C-H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C-H bond activation. Computational studies suggest that reversible C-H activation is followed by ß-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C-O cyclization, and subsequent ß-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C-H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.

Electropotential-Inspired Star-Shaped Gold Nanoconfined Multiwalled Carbon Nanotubes: A Proof-of-Concept Electrosensoring Interface for Lung Metastasis Biomarkers.

Herein, an innovative way of designing a star-shaped gold nanoconfined multiwalled carbon nanotube-engineered sensoring interface (AuNS@MWCNT//GCE) is demonstrated for quantification of methionine (MTH); a proof of concept for lung metastasis. The customization of the AuNS@MWCNT is assisted by surface electrochemistry and thoroughly discussed using state-of-the-art analytical advances. Micrograph analysis proves the protrusion of nanotips on the surface of potentiostatically synthesized AuNPs and validates the hypothesis of Turkevich seed (AuNP)-mediated formation of AuNSs. In addition, a facile synthesis of electropotential-assisted transformation of MWCNTs to luminescent nitrogen-doped graphene quantum dots (Nd-GQDs avg. ∼4.3 nm) is unveiled. The sensor elucidates two dynamic responses as a function of CMTH ranging from 2 to 250 µM and from 250 to 3000 µM with a detection limit (DL) of ∼0.20 µM, and is robust to interferents except for tiny response of a similar -SH group bearing Cys (<9.00%). The high sensitivity (0.44 µA·µM-1·cm-2) and selectivity of the sensor can be attributed to the strong hybridization of the Au nanoparticle with the sp2 C atom of the MWCNTs, which makes them a powerful electron acceptor for Au-SH-MTH interaction as evidenced by density functional theory (DFT) calculations. The validation of the acceptable recovery of MTH in real serum and pharma samples by standard McCarthy-Sullivan assay reveals the holding of great promise to provide valuable information for early diagnosis as well as assessing the therapeutic consequence of lung metastasis.

Ligand-promoted palladium-catalyzed ß-methylene C-H arylation of primary aldehydes.

The transient directing group (TDG) strategy allowed long awaited access to the direct ß-C(sp3)-H functionalization of unmasked aliphatic aldehydes via palladium catalysis. However, the current techniques are restricted to terminal methyl functionalization, limiting their structural scopes and applicability. Herein, we report the development of a direct Pd-catalyzed methylene ß-C-H arylation of linear unmasked aldehydes by using 3-amino-3-methylbutanoic acid as a TDG and 2-pyridone as an external ligand. Density functional theory calculations provided insights into the reaction mechanism and shed light on the roles of the external and transient directing ligands in the catalytic transformation.

Design of poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres for pH-stimulated chemotherapeutic drug delivery and antibacterial susceptibility.

In this research, a core-shell type pH-responsive poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres (MBAG/PLGA) was designed via aminosilane functionalization of MBAG using 3-aminopropyltriethoxysilane (APTES). The formation of MBAG/PLGA was well dispersed in an aqueous medium and demonstrated high drug loading efficacy and enhanced drug delivery rate. Daunomycin (DAN) was considered as a model chemotherapeutic drug for loading and release study. The cumulative in vitro release of DAN from DAN loaded MBAG/PLGA (MBAG/PLGA@DAN) was observed to be pH-dependent and, the DAN release rate was much higher at pH ∼ 5.5 compared to pH at 7.4. The modified Kirby-Bauer microbial assay results showed that the MBAG is a potential antimicrobial agent and susceptibility for Gram-negative bacteria is observed to be much higher than Gram-positive ones. Advanced characterization studies such as SEM coupled with EDX, HRTEM, FTIR, XPS, TGA, XRD, and BET analysis were performed to support the findings of this research. Overall, these results demonstrated that MBAG/PLGA is a promising candidate for a pH-responsive localized drug delivery system in bioconjugate science.

A direct route to six and seven membered lactones via γ-C(sp3)-H activation: a simple protocol to build molecular complexity.

Lactones comprise a class of valuable compounds having biological as well as industrial importance. Development of a methodology to synthesize such molecules directly from readily available materials such as aliphatic carboxylic acid is highly desirable. Herein, we have reported synthesis of δ-lactones and ε-lactones via selective γ-C(sp3)-H activation. The γ-C-H bond containing aliphatic carboxylic acids provide six or seven membered lactones depending on the olefin partner in the presence of a palladium catalyst. A mechanistic investigation suggests that C-H activation is the rate-determining step. Further transformations of the lactones have been carried out to showcase the applicability of the present strategy.

Diverse strategies for transition metal catalyzed distal C(sp3)-H functionalizations.

Transition metal catalyzed C(sp3)-H functionalization is a rapidly growing field. Despite severe challenges, distal C-H functionalizations of aliphatic molecules by overriding proximal positions have witnessed tremendous progress. While usage of stoichiometric directing groups played a crucial role, reactions with catalytic transient directing groups or methods without any directing groups are gaining more attention due to their practicality. Various innovative strategies, slowly but steadily, circumvented issues related to remote functionalizations of aliphatic molecules. A systematic compilation has been presented here to provide insights into the recent developments and future challenges in the field. The Present perspective is expected to open up a new dimension and provide an avenue for deep insights into the distal C(sp3)-H functionalizations that could be applied routinely in various pharmaceutical and agrochemical industries.

Ligand-Enabled PdII -Catalyzed Iterative γ-C(sp3)-H Arylation of Free Aliphatic Acid.

C-H functionalization of aliphatic carboxylic acids without attaching exogenous auxiliary has been so far limited at the proximal ß-position. In this work, we demonstrate a ligand enabled palladium catalyzed first regioselective distal γ-C(sp3)-H functionalization of aliphatic carboxylic acids without incorporating an exogenous directing group. Aryl iodides containing versatile functional groups including complex organic molecules are well tolerated with good to excellent yields during the γ-C(sp3)-H arylation reaction. Interestingly, weak coordination of carboxylate group can be further extended for sequential hetero di-arylation. Application of the protocol has been showcased by synthesizing substituted α-tetralone. Mechanistic investigations have been carried out to shed light on the reaction pathway.

Direct electrochemical reduction of hematite decorated graphene oxide (α-Fe2O3@erGO) nanocomposite for selective detection of Parkinson's disease biomarker.

An unusual approach is reported herein to fabricate magnetic hematite (α-Fe2O3) decorated electrochemically reduced graphene oxide (α-Fe2O3@erGO) nanocomposite. The method utilizes direct electrochemical reduction of self-assembled, ex-situ synthesized α-Fe2O3 anchored GO to erGO (α-Fe2O3@erGO) on glassy carbon electrode (GCE) for selective detection dopamine (DA), an important biomarker of Parkinson's disease. The formation of α-Fe2O3@erGO/GCE has been confirmed by XPS and Raman spectroscopy. α-Fe2O3@erGO modified GCE exhibits synergistic catalytic activity nearly 2.2 and 5 fold higher than α-Fe2O3@GO and other modified electrodes, respectively towards oxidation of DA. The fabricated sensor exhibited linear dynamic ranges over 0.25 - 100 µM in response to DA with a LOD of 0.024 µM (S/N = 3), LOQ of 0.08 µM (S/N = 10), and a sensitivity of 12.56 µA µM-1 cm-2. Finally, the practical analytical application of the proposed α-Fe2O3@erGO/GCE was investigated for the determination of DA in commercially available pharmaceutical formulation and human serum samples, and showed satisfactory recovery results towards DA.

Diverse meta-C-H Functionalization of Arenes across Different Linker Lengths.

Arenes containing conformationally flexible long alkyl chains have been successfully functionalized at the meta-position. Good to excellent meta selectivity is achieved for systems with up to 20 atoms between the target C-H bond and the coordinating heteroatom of the directing group. The palladium-catalyzed functionalization reactions include alkylation, cyanation, olefination, and acetoxylation. The meta selectivity is exclusively governed by the design of flexible pyrimidine-based scaffolds.

Exploration of Wedelia chinensis leaf-assisted silver nanoparticles for antioxidant, antibacterial and in vitro cytotoxic applications.

Green synthetic route of silver nanoparticles (AgNPs) has already been proved to be an advantageous over other physico-chemical approaches due to its simplicity, cost effectiveness, ecofriendly and nontoxicity. In this finding, aqueous Wedelia chinensis leaf extract (WLE) mediated synthesis of AgNPs was approached. Surface plasmon resonance (SPR) band at 408 nm preliminary indicated the formation of AgNPs, while TEM and XRD characterization confirmed the formation of spherically shaped and crystalline AgNPs with an average size of 31.68 nm, respectively. The plausible biomolecules in the aqueous leaf extract responsible for the reduction and stabilization of AgNPs were identified by FTIR analysis and found to be polyphenolic groups in flavonoid. Further, synthesized AgNPs was explored for different biological applications. Biosynthesized AgNPs showed significant free radical scavenging activity as compared to Wedelia leaf extract and antibacterial activity against clinically isolated test pathogens where Gram-negative bacteria were found more susceptible to AgNPs than Gram-positive one. In addition, in vitro cytotoxic response was also evaluated on hepatocellular carcinoma Hep G2 cell lines and showed a dose-dependent cytotoxic response with an IC50 value of 25 µg/mL.

Bio-Inspired Green Nanoparticles: Synthesis, Mechanism, and Antibacterial Application.

In the recent years, noble nanoparticles have attracted and emerged in the field of biology, medicine and electronics due to their incredible applications. There were several methods have been used for synthesis of nanoparticles such as toxic chemicals and high energy physical procedures. To overcome these, biological method has been used for the synthesis of various metal nanoparticles. Among the nanoparticles, silver nanoparticles (AgNPs) have received much attention in various fields, such as antimicrobial activity, therapeutics, bio-molecular detection, silver nanocoated medical devices and optical receptor. Moreover, the biological approach, in particular the usage of natural organisms has offered a reliable, simple, nontoxic and environmental friendly method. Hence, the current article is focused on the biological synthesis of silver nanoparticles and their application in the biomedical field.