Robust Hydrogen-Bonded Organic Framework for pH-Responsive Drug Delivery.

Hydrogen-bonded organic frameworks (HOFs), by virtue of their low toxicity, wide substrate tolerance, porosity, and regenerative and biocompatible traits, are an emerging class of porous polymeric materials that show great potential for intracellular delivery of chemotherapeutics. However, stability issues coupled with controlled release of a drug under desired stimuli have restricted their therapeutic potential. In the present study, based on density functional theory calculations predicting strong noncovalent interactions between the H-bonded 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid (HTATB) dimer and the chemotherapeutic drug doxorubicin (Dox), we prepared a robust and reticular nanoplatform Dox@nano-, which released Dox at low pH, making it an ideal carrier for targeted drug delivery to tumor sites sparing the normal tissues.

Structure-Activity Relationship of Ciprofloxacin towards S-Spike Protein of SARS-CoV-2: Synthesis and Evaluation.

The recent outbreak of the coronavirus (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has posed serious threats to global health systems. Although several directions have been put by the WHO for effective treatment, use of antibiotics, particularly ciprofloxacin, in suspected and acquired Covid-19 patients has raised an even more serious concern of antibiotic resistance. Ciprofloxacin has been reported to inhibit entry of SARS-CoV-2 into the host cells via interacting with the spike (S) protein.

Transition-metal-free decarbonylation-oxidation of 3-arylbenzofuran-2(3)-ones: access to 2-hydroxybenzophenones.

A transition-metal-free decarbonylation-oxidation protocol for the conversion of 3-arylbenzofuran-2(3)-ones to 2-hydroxybenzophenones under mild conditions has been developed. NMR studies confirmed the role of in-situ-generated hydroperoxide in the conversion. The protocol was applied to a diverse range of substrates to access the target products in good to excellent yields.

Experimental and theoretical validation for transmutation of palladium at electrochemical interfaces.

Electrolysis of DO may be used as a portable neutron source with numerous applications without the complexity of huge reactor operations. Herein, we report reproducible fast neutron generation by electrolysis of DO using palladium cathode and platinum anode, which was detected with diamond detector, gas filled He detectors after thermalisation with high density polythene, as well as novel epoxy resin and CR-39 detectors. Notably, a highly reproducible neutron generation at electrochemical surfaces of palladium electrode was observed and signature transmutation via Pd (d, n) Ag was corroborated.

N-rich carbon nanosphere as fluorescent nanoprobe for intracellular iron.

Nitrogen rich carbon nanoparticles are known to provide higher fluorescence stokes shift, and thereby are potential candidates for fluorescent sensors. Herein, a facile one-step hydrothermal synthesis is reported for N-rich carbon nanospheres (G-CNS) from caffeine and o-phenylenediamine as precursors. The as-synthesized G-CNS showed high fluorescence with λ at 509 nm, with a highly selective fluorescence turn-off response towards Fe/Fe, rendering these carbon nanospheres as potential candidates to detect intracellular labile iron pool in live cells.

Synthesis, Quality Control, and Bench-to-Bed Translation of a New [Ga]Ga-Labeled NOTA-Conjugated Bisphosphonate for Imaging Skeletal Metastases by Positron Emission Tomography.

: Early detection of skeletal metastasis is of great interest to determine the prognosis of cancer. Positron emission tomography-computed tomography (PET-CT) imaging provides a better temporal and spectral resolution than single photon emission computed tomography-computed tomography (SPECT-CT) imaging, and hence is more suitable to detect small metastatic lesions. Although [F]NaF has been approved by U.

Deep Eutectic Solvent-Based Highly Sensitive Turn-On Fluorescent Probe for DO.

Owing to the importance of heavy water in spectroscopy, nuclear energy generation, chemical characterization, and biological industry, a design of a robust, cheap, nontoxic, and sensitive DO sensor is very important. In this work, taking advantage of the singular emission fluorescence of the deep eutectic solvent prepared in our laboratory, we propose a first of its kind highly sensitive turn-on fluorescent sensor to effectively sense DO at an ultratrace level based on rapid exchange of the labile DES proton with deuterium. This method can be used as a full-range heavy water detection strategy with a limit of detection of 0.

Mechanistic Approach to Reveal Interaction of Uranyl Ions in Alkyltriphenylphosphonium Bromide-Based Deep Eutectic Solvent.

Speciation is known to control fundamental aspects of metal processing and electrochemical behavior such as solubility and redox potentials. Deep eutectic solvents (DESs) are an emerging class of green, low-cost and designer solvents and are being explored as alternatives for recycling nuclear fuel and critical materials. However, there is a lack of knowledge about the behavior of metals in them.

Multimodal Applications of Zinc Gallate-Based Persistent Luminescent Nanoparticles in Cancer Treatment: Tumor Margining, Diagnosis, and Boron Neutron Capture Therapy.

On the basis of the boron neutron capture therapy (BNCT) modality, we have designed and synthesized a zinc gallate (ZnGaO)-based nanoformulation for developing an innovative theranostic approach for cancer treatment. Initially, the (ZnGaCrO or ZnGaO:(0.5%)Cr persistent luminescence nanoparticles (PLNPs) embedded on silica matrix were synthesized.

Synthesis of Bioactive Diarylheptanoids from and Their Mechanism of Action for Anticancer Properties in Breast Cancer Cells.

An efficient synthesis of the -derived diarylheptanoids, viz., enantiomers of a β-hydroxyketone () and an α,β-unsaturated ketone () was developed starting from commercially available eugenol. Among these, compound showed a superior antiproliferative effect against human breast adenocarcinoma MCF-7 cells.

Binding Constant Determined from the Angstrom-Scale Change in Hydrodynamic Radius of Transferrin upon Binding with Europium Using Dual-Focus Fluorescence Correlation Spectroscopy.

Monitoring the binding of a large fluorescently tagged molecule to a small solute by fluorescence correlation spectroscopy (FCS) is rather uncommon because the binding-related change in diffusion coefficient is very small. Here, we use a high-precision variant of FCS, namely, dual-focus FCS (2fFCS), for measuring the angstrom-scale change of the hydrodynamic radius of the bilobal metal transport protein transferrin (Tf) upon binding europium ions. Applying a sequential 1:2 complexation model, we use these measurements for determining the binding constants ().

Determining Metal Ion Complexation Kinetics with Fluorescent Ligands by Using Fluorescence Correlation Spectroscopy.

Fluorescence correlation spectroscopy (FCS) has been extensively used to measure equilibrium binding constants (K) or association and dissociation rates in many reversible chemical reactions across chemistry and biology. For the majority of investigated reactions, the binding constant was on the order of ∼100 M , with dissociation constants faster or equal to 10  s , which ensured that enough association/dissociation events occur during the typical diffusion-determined transition time of molecules through the FCS detection volume. However, complexation reactions involving metal ions and chelating ligands exhibit equilibrium constants exceeding 10  M .

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12.

A chemoenzymatic synthesis of the title compound has been developed using an efficient and highly enantioselective lipase-catalyzed acylation in a hydrophobic ionic liquid, [bmim][PF], followed by a diastereoselective asymmetric dihydroxylation as the key steps for incorporating the stereogenic centers. The further conversion to the appropriate intermediates and subsequent acylation with lauric acid furnished the target compound.

Cell Permeable Imidazole-Desferrioxamine Conjugates: Synthesis and In Vitro Evaluation.

Desferrioxamine (DFO), a clinically approved iron chelator used for iron overload, is unable to chelate labile plasma iron (LPI) because of its limited cell permeability. Herein, alkyl chain modified imidazolium cations with varied hydrophobicities have been conjugated with DFO. The iron binding abilities and the antioxidant properties of the conjugates were found to be similar to DFO.

Remarkably enhanced direct dissolution of plutonium oxide in task-specific ionic liquid: insights from electrochemical and theoretical investigations.

The present work envisages an approach for direct dissolution of PuO2 in a task-specific ionic liquid (TSIL). An attractive possibility to electrodeposit plutonium from the mixture of TSIL and PuO2 has been explored further. The carboxyl functional group attached to the TSIL plays a key role in facilitating the dissolution of plutonium ions.

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation.

The inexpensive room temperature ionic liquid (RTIL), [bmim][Br] has been found to be a superior medium for the Bi-mediated Barbier-type allylation of aldehydes compared to other conventional solvents. It plays the dual role of a solvent and a metal activator enabling higher yields of the products in a shorter reaction time using stoichiometric/near-stoichiometric amounts of reagents. Plausibly, [bmim][Br] activates Bi metal by a charge transfer mechanism.

Syntheses and evaluation of Ga- and Sm-labeled DOTA-conjugated bisphosphonate ligand for potential use in detection of skeletal metastases and management of pain arising from skeletal metastases.

This article reports the syntheses and evaluation of Ga- and Sm-complexes of a new DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-conjugated geminal bisphosphonate, DOTA-Bn-SCN-BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeletal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three-step reaction scheme. Gallium-68- and Sm-complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate-buffered saline (PBS) and human serum.

Triphenylphosphonium-desferrioxamine as a candidate mitochondrial iron chelator.

Cell-impermeant iron chelator desferrioxamine (DFO) can have access to organelles if appended to suitable vectors. Mitochondria are important targets for the treatment of iron overload-related neurodegenerative diseases. Triphenylphosphonium (TPP) is a delocalized lipophilic cation used to ferry molecules to mitochondria.

syn-Selective crotylation of aldehydes using bismuth-crotyl bromide-(1-butyl-3-methylimidazolium bromide) combination: some synthetic applications.

The Bi-[bmim][Br] combination has been found to offer high syn-selectivity in the crotylation of aldehydes with crotyl bromide using practically stoichiometric amounts of the reagents. The room temperature ionic liquid (RTIL), [bmim][Br], activated Bi metal in the presence of oxygen to produce crotylbismuthdibromide, which reacted with the aldehydes at room temperature. The major anti-syn diastereomeric product obtained from the crotylation of (R)-cyclohexylideneglyceraldehyde was utilized for the synthesis of dictyostatin and cryptophycin segments, and (+)-cis-aerangis lactone, using standard synthetic protocols.

Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron.

Desferrioxamine (DFO) is a bacterial siderophore with a high affinity for iron, but low cell penetration. As part of our ongoing project focused on DFO-conjugates, we synthesized, purified, characterized and studied new mtDFOs (DFO conjugated to the Mitochondria Penetrating Peptides TAT49-57, 1A, SS02 and SS20) using a succinic linker. These new conjugates retained their strong iron binding ability and antioxidant capacity.

Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine.

Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47-57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood-brain barrier.

Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model.

Cell penetrating peptide (CPP)-conjugated desferrioxamine for enhanced neuroprotection: synthesis and in vitro evaluation.

Iron overload causes progressive and sometimes irreversible damage due to accelerated production of reactive oxygen species. Desferrioxamine (DFO), a siderophore, has been used clinically to remove excess iron. However, the applications of DFO are limited because of its inability to access intracellular labile iron.

Desferrioxamine-caffeine (DFCAF) as a cell permeant moderator of the oxidative stress caused by iron overload.

Desferrioxamine (DFO) is a potent iron chelator used in the treatment of iron overload (IO) disorders. However, due to its low cell permeability and fast clearance, DFO administration is usually prolonged and of limited use for the treatment of IO in tissues such as the brain. Caffeine is a safe, rapidly absorbable molecule that can be linked to other compounds to improve their cell permeability.