Metal-Organic Framework-Based Selective Sensing of Biothiols via Chemidosimetric Approach in Water.

Selective detection of biothiols holds prime importance owing to the role of varied concentrations of biothiols in various diseases, thus demanding extensive research for developing materials toward selective sensing. In this study, we targeted postsynthetic modification (PSM) approach for imparting desired functionality to chemically stable UiO-66-NH metal-organic framework, which exhibits highly selective sensing toward biothiols. The appended dinitrobenzenesulfonyl group reacts with biothiols via chemidosimetric approach.

Guest-Responsive Metal-Organic Frameworks as Scaffolds for Separation and Sensing Applications.

Metal-organic frameworks (MOFs) have evolved to be next-generation utility materials because of their serviceability in a wide variety of applications. Built from organic ligands with multiple binding sites in conjunction with metal ions/clusters, these materials have found profound advantages over their other congeners in the domain of porous materials. The plethora of applications that these materials encompass has motivated material chemists to develop such novel materials, and the catalogue of MOFs is thus ever-escalating.

Cisplatin-Stitched Polysaccharide Vesicles for Synergistic Cancer Therapy of Triple Antagonistic Drugs.

New cisplatin-stitched polysaccharide vesicular nanocarrier is developed for combination therapy of three clinical important antagonistic drugs together to accomplish synergistic cancer therapy in breast cancer treatment. Carboxylic functionalized dextran was tailor-made for the chemical conjugation of cisplatin, and a renewable hydrophobic unit was anchored in the backbone to interdigitize the chains to self-assemble as cisplatin-stitched polysaccharide nanovesicles. Water-soluble DNA-intercalating drug doxorubicin·HCl (DOX) and water insoluble topoisomerase type I inhibitor drug camptothecin (CPT) were encapsulated in these vesicles to produce dual or triple drug-loaded vesicular nanocarrier.

Development of l-Tyrosine-Based Enzyme-Responsive Amphiphilic Poly(ester-urethane) Nanocarriers for Multiple Drug Delivery to Cancer Cells.

New classes of enzymatic-biodegradable amphiphilic poly(ester-urethane)s were designed and developed from l-tyrosine amino acid resources and their self-assembled nanoparticles were employed as multiple drug delivery vehicles in cancer therapy. The amine and carboxylic acid functional groups in l-tyrosine were converted into dual functional ester-urethane monomers and they were subjected to solvent free melt polycondensation with hydrophilic polyethylene glycols to produce comb-type poly(ester-urethane)s. The phenolic unit in the l-tyrosine was anchored with hydrophobic alkyl side chain to bring appropriate amphiphilicity in the polymer geometry to self-assemble them as stable nanoscaffolds in aqueous medium.

Hydroxy-functionalized hyper-cross-linked ultra-microporous organic polymers for selective CO capture at room temperature.

Two hydroxy-functionalized hyper-cross-linked ultra-microporous compounds have been synthesized by Friedel-Crafts alkylation reaction and characterised with different spectroscopic techniques. Both compounds exhibit an efficient carbon dioxide uptake over other gases like N, H and O at room temperature. A high isosteric heat of adsorption () has been obtained for both materials because of strong interactions between polar -OH groups and CO molecules.

Bacterial Actins and Their Interactors.

Bacterial actins polymerize in the presence of nucleotide (preferably ATP), form a common arrangement of monomeric interfaces within a protofilament, and undergo ATP hydrolysis-dependent change in stability of the filament-all of which contribute to performing their respective functions. The relative stability of the filament in the ADP-bound form compared to that of ATP and the rate of addition of monomers at the two ends decide the filament dynamics. One of the major differences between eukaryotic actin and bacterial actins is the variety in protofilament arrangements and dynamics exhibited by the latter.

Hydrogen-Bonded Organic Frameworks (HOFs): A New Class of Porous Crystalline Proton-Conducting Materials.

Two porous hydrogen-bonded organic frameworks (HOFs) based on arene sulfonates and guanidinium ions are reported. As a result of the presence of ionic backbones appended with protonic source, the compounds exhibit ultra-high proton conduction values (σ) 0.75× 10(-2)  S cm(-1) and 1.

High hydroxide conductivity in a chemically stable crystalline metal-organic framework containing a water-hydroxide supramolecular chain.

A chemically stable cationic MOF encapsulating an in situ formed water-hydroxide supramolecular anionic chain is realized for high hydroxide (OH(-)) ion conductivity in the solid-state (Type A). High OH(-) ion conductivity and low activation energy of the MOF demonstrate the advantage of the in situ incorporation of OH(-) ions to achieve efficient OH(-) ion conduction in the solid-state.

Nanoparticle-Mediated Mitochondrial Damage Induces Apoptosis in Cancer.

Detouring of conventional DNA damaging anticancer drugs into mitochondria to damage mitochondrial DNA is evolving as a promising strategy in chemotherapy. Inhibiting single target in mitochondria would eventually lead to the emergence of drug resistance. Moreover, targeting mitochondria selectively in cancer cells, keeping them intact in healthy cells, remains a major challenge.

Fluorescence Up-Conversion Studies of [2,2'-Bipyridyl]-3,3'-diol in Octyl-β-d-glucoside and Other Micellar Aggregates.

In this present work, excited state double proton transfer dynamics (ESIDPT) of 2,2'-bipyridyl-3,3'-diol (BP(OH)2) molecules has been probed in a nontoxic, biocompatible sugar surfactant assembly, namely, octyl-β-d-glucoside (OBG) micelle with the help of steady state and fluorescence up-conversion techniques. Moreover, the ultrafast double proton transfer dynamics in conventional micelles (SDS, CTAB) and bile salts aggregates have been probed and compared. Interestingly, in all these supramolecular aggregates, the ESIDPT dynamics is found to follow sequential pathway; however, the time-scale of proton transfer dynamics varies from 11 to 30 ps.

Core-shell polymer nanoparticles for prevention of GSH drug detoxification and cisplatin delivery to breast cancer cells.

Platinum drug delivery against the detoxification of cytoplasmic thiols is urgently required for achieving efficacy in breast cancer treatment that is over expressed by glutathione (GSH, thiol-oligopeptide). GSH-resistant polymer-cisplatin core-shell nanoparticles were custom designed based on biodegradable carboxylic functional polycaprolactone (PCL)-block-poly(ethylene glycol) diblock copolymers. The core of the nanoparticle was fixed as 100 carboxylic units and the shell part was varied using various molecular weight poly(ethylene glycol) monomethyl ethers (MW of PEGs = 100-5000 g mol(-1)) as initiator in the ring-opening polymerization.

Chimeric Nanoparticle: A Platform for Simultaneous Targeting of Phosphatidylinositol-3-Kinase Signaling and Damaging DNA in Cancer Cells.

Phosphatidylinositol-3-kinase (PI3K) signaling has been hijacked in different types of cancers. Hence, PI3K inhibitors have emerged as novel targeted therapeutics in cancer treatment as mono and combination therapy along with other DNA damaging drugs. However, targeting PI3K signaling with small molecules leads to the emergence of drug resistance and severe side effects to the cancer patients.

Real-Time Drug Release Analysis of Enzyme and pH Responsive Polysaccharide Nanovesicles.

The accurate estimation of drug release kinetics of polymeric vehicles is an indispensable prerequisite for the developments of successful drug carriers for cancer therapy. The present investigation reports the development of time-resolved fluorescence spectroscopic approach for the real-time release kinetics of fluorophore loaded polysaccharide vesicles that are potential vectors in cancer treatment. The polysaccharide vesicles were custom designed with appropriate enzyme and pH responsiveness and loaded with water-soluble biocompatible fluorophore Rhodamine B (Rh-B).

Dual drug conjugated nanoparticle for simultaneous targeting of mitochondria and nucleus in cancer cells.

Effective targeting of mitochondria has emerged as an alternative strategy in cancer chemotherapy. However, considering mitochondria's crucial role in cellular energetics, metabolism and signaling, targeting mitochondria with small molecules would lead to severe side effects in cancer patients. Moreover, mitochondrial functions are highly dependent on other cellular organelles like nucleus.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells.

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 ± 10 nm diameter nano-vesicles in water.

Amyloid-like hierarchical helical fibrils and conformational reversibility in functional polyesters based on L-amino acids.

The present investigation reports one of the first examples of synthetic polymers that capable of undergoing reversible conformation transformation and also self-assembled to hierarchical helical amyloid-like fibrils. A new temperature selective melt polycondensation reaction was developed for amino acid monomers L-aspartic acid and L-glutamic acid to produce high molecular weight linear functional polyesters. These new polyesters have hydrogen bonded urethane (or carbamate) units that are in-built in each repeating unit.

Spectroscopic and thermodynamic insights into the interaction between proflavine and human telomeric G-quadruplex DNA.

The G-quadruplex (GQ-DNA), an alternative structure motif of DNA, has emerged as a novel and exciting target for anticancer drug discovery. GQ-DNA formed in the presence of monovalent cations (Na(+)/K(+)) by human telomeric DNA is a point of interest due to their direct relevance for cellular aging and abnormal cell growths. Small molecules that selectively target and stabilize G-quadruplex structures are considered to be potential therapeutic anticancer agents.

Role of Mg²⁺ ions in flavin recognition by RNA aptamer.

The role of Mg(2+) ion in flavin (flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)) recognition by RNA aptamer has been explored through steady state and time-resolved fluorescence, circular dichroism (CD), thermal melting (TM) and isothermal titration calorimetry (ITC) studies. A strong quenching of flavin emission is detected due to stacking interaction with the nucleobases in the mismatched region of aptamer, and it enhances manifold with increasing Mg(2+) concentrations. A comparatively lower binding affinity toward FAD compared to FMN is attributed to the presence of intramolecular 'stack' conformer of FAD, which cannot participate in the intermolecular stacking interactions with the nucleobases.

Polysaccharide nano-vesicular multidrug carriers for synergistic killing of cancer cells.

Multi-drug delivery based on polymer nano-scaffolds is an essential protocol to be developed for better administration of anticancer drugs to enhance their therapeutic efficacies against cancer cells. Here, we report dual delivery polysaccharide nano-vesicles that are capable of loading and delivering both water soluble and water insoluble drugs together in a single polymer scaffold. The selective rupture of the nano-vesicular assembly under intracellular enzyme conditions allowed the simultaneous delivery of a hydrophobic drug camptothecin (CPT) and hydrophilic drug doxorubicin (DOX) supporting their synergistic killing of breast and colon cancer cells.

Urea induced unfolding dynamics of flavin adenine dinucleotide (FAD): spectroscopic and molecular dynamics simulation studies from femto-second to nanosecond regime.

Here, we investigate the effect of urea in the unfolding dynamics of flavin adenine dinucleotide (FAD), an important enzymatic cofactor, through steady state, time-resolved fluorescence spectroscopic and molecular dynamics (MD) simulation studies. Steady state results indicate the possibility of urea induced unfolding of FAD, inferred from increasing emission intensity of FAD with urea. The TCSPC and up-conversion results suggest that the stack-unstack dynamics of FAD severely gets affected in the presence of urea and leads to an increase in the unstack conformation population from 15% in pure water to 40% in 12 M urea.

Synthesis, characterization and in vitro evaluation of novel vitamin D3 nanoparticles as a versatile platform for drug delivery in cancer therapy.

Development of novel nanotechnology based platforms can impact cancer therapeutics in a paradigm shifting manner. The major concerns in drug delivery in cancer therapy are the biocompatibility, biodegradability, non-toxic nature, easy and short synthesis and versatility of the nanovectors. Herein we report the engineering of versatile nanoparticles from biocompatible, biodegradable and non-toxic lipid soluble vitamin D3.

Amphiphilic diblocks sorting into multivesicular bodies and their fluorophore encapsulation capabilities.

Synthetic macromolecular diblocks sorting into mutivesicular bodies (MVBs) and their fluorophore encapsulation pathways were reported. Renewable resource based diblocks having hydrophobic units and flexible hydrophilic polyethylene glycols (PEG) were custom designed for the above purpose. Single crystal structure was resolved to prove the existence of the strong intermolecular interactions and the formation of unilamellar layer-like self-assemblies.

Polymers from amino acids: development of dual ester-urethane melt condensation approach and mechanistic aspects.

A new dual ester-urethane melt condensation methodology for biological monomers-amino acids was developed to synthesize new classes of thermoplastic polymers under eco-friendly and solvent-free polymerization approach. Naturally abundant L-amino acids were converted into dual functional ester-urethane monomers by tailor-made synthetic approach. Direct polycondensation of these amino acid monomers with commercial diols under melt condition produced high molecular weight poly(ester-urethane)s.

Probing the role of chain length on the diffusion dynamics of π-conjugated polymers by fluorescence correlation spectroscopy.

We investigate the role of the chain length and molecular weight distribution on the diffusion dynamics of freshly synthesized MEH-PPV polymer chains. For the above purpose, a new technique based on combination of size exclusion chromatography (SEC) with fluorescence correlation spectroscopy (FCS) is developed to probe the diffusion dynamics of a narrow molecular weight distribution of fractionated samples of 20-500 kDa. The narrow dispersed samples were characterized by absorbance, emission, and time-resolved fluorescence decay techniques.

Supramolecular liquid crystalline π-conjugates: the role of aromatic π-stacking and van der Waals forces on the molecular self-assembly of oligophenylenevinylenes.

Here, we report a unique design strategy to trace the role of aromatic π-stacking and van der Waals interactions on the molecular self-organization of π-conjugated building blocks in a single system. A new series of bulky oligophenylenevinylenes (OPVs) bearing a tricyclodecanemethylene (TCD) unit in the aromatic π-core with flexible long methylene chains (n = 0-12 and 16) in the longitudinal position were designed and synthesized. The OPVs were found to be liquid crystalline, and their enthalpies of phase transitions (also entropies) showed odd-even oscillation with respect to the number of carbon atoms in alkyl chains.