Does the degree of substitution on the cyclodextrin hosts impact their affinity towards guest binding?

Although cyclodextrins have been extensively utilized in various branches of supramolecular chemistry due to their numerous attractive attributes, however, to achieve even advanced applications, they often need structural modification through substitutions of suitable functional groups at their rims. A systematic investigation on how the degree of substitution on the cyclodextrin rims affects the binding affinity for a given guest molecule has however rarely been reported, especially from the perspective of photophysical studies. Herein, we report the non-covalent interaction of a styryl based dye, LDS-798, with three different sulfobutylether beta cyclodextrin (SBEnßCD) derivatives bearing varying degrees of substitution (n), using ground state absorption, steady-state emission, excited-state lifetime and time-resolved fluorescence anisotropy measurements. The dye-host binding constant values indicate that the strength of the interaction between LDS-798 and SBEnßCD derivatives follows an increasing trend with an increasing number of tethered sulfobutylether substituents on the cyclodextrin rims, which is attributed to the gradual increase of the electrostatic interaction between the negatively charged sulfobutylether groups and the positively charged LDS-798. Excited state lifetime measurements and ionic strength dependent studies on the dye-SBEnßCD complexes further support the increased affinity between the dye and the host in the supramolecular complexes, with an increasing number of sulfobutylether substituents on the ßCD rims. The obtained results suggest that the molecular recognition of LDS-798 with SBEnßCD derivatives can be tuned very effectively by varying the number of sulfobutylether substituents on the cyclodextrin rims. Considering that SBE7ßCD is one of the FDA approved agents for drug formulations, the obtained results with other SBEnßCD hosts may be useful in designing selective drug delivery applications, drug formulations, and effective fluorescence on-off switches.

A styryl based fluorogenic probe with high affinity for a cyclodextrin derivative.

Supramolecular host-guest pairs, with a very high association constant, represent excellent molecular recognition motifs, and serve as useful building blocks for numerous exciting supramolecular functional materials. Cyclodextrins, an important class of glucopyranose-based hosts, generally, suffer from low affinity for most guest molecules (102-104 M-1). Herein, we report a styryl-based fluorogenic probe which registers a very high association constant of 7.84 × 105 M-1 with sulfobutylether substituted ß-cyclodextrin in contrast to a low association constant of 1.89 × 102 M-1 with unmodified ß-cyclodextrin (ß-CD). This exceptionally high binding affinity of the fluorogenic probe with the sulfobutylether substituted ß-CD has been attributed to the strong electrostatic interactions between the cationic guest and the polyanionic host along with improved hydrophobic interactions due to the extended butylether groups present on the rims of the cyclodextrin cavity. The significant modulations in the photophysical properties of guest molecule, upon interaction with host molecule, have been investigated, in detail, using ground-state absorption, steady-state fluorescence and time-resolved emission measurements. The effect of temperature and ionic strength of the medium have been employed to investigate the nature of the underlying interactions in the present host-guest system. The possibility of indicator displacement assay involving the present host-guest system has also been demonstrated using a competitive binder.

Iron oxide labeling does not affect differentiation potential of human bone marrow mesenchymal stem cells exhibited by their differentiation into cardiac and neuronal cells.

Mesenchymal stem cells (MSCs) have shown promising outcomes in cardiac and neuronal diseases. Efficient and noninvasive tracking of MSCs is essential to harness their therapeutic potential. Iron oxide nanoparticles (IONPs) have emerged as effective means to label stem cells and visualize them using magnetic resonance imaging (MRI). It is known that IONPs do not affect viability and cell proliferation of stem cells. However, very few studies have demonstrated differentiation potential of iron oxide-labeled MSCs and their differentiation into specific lineages that can contribute to cellular therapies. The differentiation of IONP-labeled human bone marrow mesenchymal stem cells (hBM-MSCs) into cardiac and neuronal lineages has never been studied. In this study, we have shown that IONP-labeled hBM-MSCs retain their differentiation potential to cardiac and neuronal cell lineages. We also confirmed that labeling hBM-MSCs with IONP does not affect their characteristic properties such as viability, cellular proliferation rate, surface marker profiling, and trilineage differentiation capacity. This study shows that IONP can be efficiently tracked, and its labeling does not alter stemness and differentiation potential of hBM-MSCs. Thus, the labeled hBM-MSCs can be used in clinical therapies and regenerative medicine.

Modulation of the Photophysical Properties of ß-substituted BODIPY Dyes.

Photophysical properties of BODIPY dyes containing acetyl acetone and benzoyl acetone BF2 unit as an electron accepting substituent at beta position linked via double bond have been investigated using a wide range of solvents of different polarities. The substitution effect at beta position of the BODIPY dyes on their absorption, emission and quantum yield of fluorescence have been the aim of present study. For the synthesized BODIPY dyes fluorescence quantum yields and lifetimes show very sharp decrease with an increase in the solvent polarity, suggesting the involvement of highly polar ICT state de-excitation mechanism along with the local excitation process. The polarity dependent changes in average fluorescence life time and quantum yield values rationalize the formation of ICT states.

Enhanced fluorescence of aqueous BODIPY by interaction with cavitand cucurbit[7]uril.

One cationic BODIPY chromophore was synthesized and its complexation behaviour with the macrocyclic host cucurbit[7]uril (CB[7]) was studied using different spectroscopy techniques such as UV-vis absorption, steady-state and time-resolved fluorescence, 1H NMR as well as DFT based quantum calculations. The dye showed formation of a 1 : 1 dye-CB[7] complex with improvement in the fluorescence intensity. These new results of the formation of moderate association of aqueous BODIPYs with the nontoxic host CB[7] may lead to promising applications of the dye molecule as a sensitive and efficient off-on mode fluorescent probe in chemical and biological studies.

Proton Induced Modulation of ICT and PET Processes in an Imidazo-phenanthroline Based BODIPY Fluorophores.

BODIPY fluorophores linked with an imidazo-phenanthroline donor at α and ß positions have been synthesized. Intriguing intramolecular charge transfer phenomenon is observed in both the dyes which has been extensively investigated using UV-vis absorption, steady-state and time-resolved fluorescence measurements. H-bonding and intrinsic polarity of the solvents has modulated the absorption and emission bands of these fluorophores strongly causing significant increase in the Stokes shifts. In spite of having difference only in terms of the position of donor subunit, the photophysics of these dyes are not only significantly different from each other, but contradictory too. Interestingly, acidochromic studies revealed the shuttling mechanism between ICT and PET processes for BDP 2. Quantum chemical calculations have been employed further to support experimental findings. DFT and TD-DFT method of analysis have been used to optimize ground and excited state geometries of the synthesized dyes.

Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß activities.

Solvent-Driven Conformational Exchange for Amide-Linked Bichromophoric BODIPY Derivatives.

The fluorescence lifetime and quantum yield are seen to depend in an unexpected manner on the nature of the solvent for a pair of tripartite molecules composed of two identical boron dipyrromethene (BODIPY) residues attached to a 1,10-phenanthroline core. A key feature of these molecular architectures concerns the presence of an amide linkage that connects the BODIPY dye to the heterocyclic platform. The secondary amide derivative is more sensitive to environmental change than is the corresponding tertiary amide. In general, increasing solvent polarity, as measured by the static dielectric constant, above a critical threshold tends to reduce fluorescence but certain hydrogen bond accepting solvents exhibit anomolous behaviour. Fluorescence quenching is believed to arise from light-induced charge transfer between the two BODIPY dyes, but thermodynamic arguments alone do not explain the experimental findings. Molecular modelling is used to argue that the conformation changes in strongly polar media in such a way as to facilitate improved rates of light-induced charge transfer. These solvent-induced changes, however, differ remarkably for the two types of amide.

Cytotoxic evaluation of hydroxyapatite-filled and silica/hydroxyapatite-filled acrylate-based restorative composite resins: An in vitro study.

STATEMENT OF PROBLEM: Although the physical and mechanical properties of hydroxyapatite-filled dental restorative composite resins have been examined, the biocompatibility of these materials has not been studied in detail. PURPOSE: The purpose of this in vitro study was to analyze the toxicity of acrylate-based restorative composite resins filled with hydroxyapatite and a silica/hydroxyapatite combination. MATERIAL AND METHODS: Five different restorative materials based on bisphenol A-glycidyl methacrylate (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) were developed: unfilled (H0), hydroxyapatite-filled (H30, H50), and silica/hydroxyapatite-filled (SH30, SH50) composite resins. These were tested for in vitro cytotoxicity by using human bone marrow mesenchymal stromal cells. Surface morphology, elemental composition, and functional groups were determined by scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The spectra normalization, baseline corrections, and peak integration were carried out by OPUS v4.0 software. RESULTS: Both in vitro cytotoxicity results and SEM analysis indicated that the composite resins developed were nontoxic and supported cell adherence. Elemental analysis with EDX revealed the presence of carbon, oxygen, calcium, silicon, and gold, while the presence of methacrylate, hydroxyl, and methylene functional groups was confirmed through FTIR analysis. CONCLUSIONS: The characterization and compatibility studies showed that these hydroxyapatite-filled and silica/hydroxyapatite-filled bis-GMA/TEGDMA-based restorative composite resins are nontoxic to human bone marrow mesenchymal stromal cells and show a favorable biologic response, making them potential biomaterials.

Congeners of Pyrromethene-567 Dye: Perspectives from Synthesis, Photophysics, Photostability, Laser, and TD-DFT Theory.

In an attempt to develop photostable and efficient BODIPY (PM) dyes for use in liquid dye lasers, three new congeners of widely used laser dye, PM567, were synthesized and their photophysical properties in various organic solvents, laser performances, and photostabilities in a selected solvent, 1,4-dioxane, have been investigated using a frequency doubled Q-switched (10 Hz) Nd:YAG laser at 532 nm. The results of photostability study in nonpolar 1,4-dioxane revealed the remarkable enhancement in stability of the novel dyes compared to that of PM567 as well as improved laser performances. Cyclic voltammetry study strongly supports the observed enhancement in photostability of the novel dyes compared to that of PM567. The observed properties of the novel dyes in relation to those of PM567 have been rationalized by extensive use of DFT and TD-DFT using the B3LYP/6-31G(d) method of theory.

Novel pyrromethene dyes with N-ethyl carbazole at the meso position: a comprehensive photophysical, lasing, photostability and TD-DFT study.

Two novel BODIPY (pyrromethene, PM) dyes containing N-ethyl carbazole at the meso position are synthesized and their photophysical properties in different solvents and the photochemical stabilities and laser performances in n-heptane are investigated. The n-heptane solution of the dyes was used as a gain medium in a constructed narrow band dye laser, pumped by a Q-switched (10 Hz) frequency-doubled (532 nm) Nd:YAG laser and the results gave enhanced photo stabilities and similar peak efficiencies of the synthesized dyes as compared to parent dye PM567. When substituted at the meso position with N-alkyl carbazole, photostability is found to be increased in comparison to PM567, and also when substituted at 2- and 6-positions with a benzyl group instead of an ethyl group along with N-ethyl carbazole at the meso position, the photo stability is further increased in n-heptane. A comprehensive study on structural, photophysical and electronic properties of dyes by means of DFT and TD-DFT in the solvents of various polarities has revealed remarkable characteristics of the BODIPY chromophore.

High laser efficiency and photostability of pyrromethene dyes mediated by nonpolar solvent.

Many pyrromethene (PM) dyes have been shown to outperform established rhodamine dyes in terms of laser efficiency in the green-yellow spectral region, but their rapid photochemical degradation in commonly used ethanol or methanol solvents continues to limit its use in high average power liquid dye lasers. A comparative study on narrowband laser efficiency and photostability of commercially available PM567 and PM597 dyes, using nonpolar n-heptane and 1,4-dioxane and polar ethanol solvents, was carried out by a constructed pulsed dye laser, pumped by the second harmonic (532 nm) radiation of a Q-switched Nd:YAG laser. Interestingly, both nonpolar solvents showed a significantly higher laser photostability (∼100 times) as well as peak efficiency (∼5%) of these PM dyes in comparison to ethanol. The different photostability of the PM dyes was rationalized by determining their triplet-state spectra and capability to generate reactive singlet oxygen (O21) by energy transfer to dissolved oxygen in these solvents using pulse radiolysis. Heptane is identified as a promising solvent for these PM dyes for use in high average power dye lasers, pumped by copper vapor lasers or diode-pumped solid-state green lasers.

Culture & differentiation of mesenchymal stem cell into osteoblast on degradable biomedical composite scaffold: In vitro study.

BACKGROUND & OBJECTIVES: There is a significant bone tissue loss in patients from diseases and traumatic injury. The current autograft transplantation gold standard treatment has drawbacks, namely donor site morbidity and limited supply. The field of tissue engineering has emerged with a goal to provide alternative sources for transplantations to bridge this gap between the need and lack of bone graft. The aim of this study was to prepare biocomposite scaffolds based on chitosan (CHT), polycaprolactone (PCL) and hydroxyapatite (HAP) by freeze drying method and to assess the role of scaffolds in spatial organization, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, in order to achieve bone graft substitutes with improved physical-chemical and biological properties. METHODS: Pure chitosan (100CHT) and composites (40CHT/HAP, 30CHT/HAP/PCL and 25CHT/HAP/PCL scaffolds containing 40, 30, 25 parts per hundred resin (phr) filler, respectively) in acetic acid were freeze dried and the porous foams were studied for physicochemical and in vitro biological properties. RESULTS: Scanning electron microscope (SEM) images of the scaffolds showed porous microstructure (20-300 µm) with uniform pore distribution in all compositions. Materials were tested under compressive load in wet condition (using phosphate buffered saline at pH 7.4). The in vitro studies showed that all the scaffold compositions supported mesenchymal stem cell attachment, proliferation and differentiation as visible from SEM images, [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, alkaline phosphatase (ALP) assay and quantitative reverse transcription (qRT)-PCR. INTERPRETATION & CONCLUSIONS: Scaffold composition 25CHT/HAP/PCL showed better biomechanical and osteoinductive properties as evident by mechanical test and alkaline phosphatase activity and osteoblast specific gene expression studies. This study suggests that this novel degradable 3D composite may have great potential to be used as scaffold in bone tissue engineering.

Masking and demasking strategies for the BF2-BODIPYs as a tool for BODIPY fluorophores.

An efficient and chemoselective route for transforming BF2-BODIPYs to Et2B-BODIPYs (masking) was developed using Et2AlCl. The Et groups can be easily replaced with F atoms using BF3·Et2O in moist CH2Cl2 to regenerate the BF2-BODIPYs (demasking). The masking-demasking strategy is very useful for synthesizing functionalized BODIPYs via nucleophilic and reductive reactions. The masking strategy was used to synthesize a BODIPY dimer by McMurry coupling of a formyl Et2B-BODIPY, while a new BODIPY with an asymmetrically substituted B-center was synthesized using the demasking strategy.

Rational design of boradiazaindacene (BODIPY)-based functional molecules.

Three boradiazaindacene (BODIPY) dyes with different-coloured (greenish-yellow, orange and red) fluorescence and good Stokes shifts were synthesised starting from the greenish-yellow BODIPY dye PM546. The high Stokes shifts of the dyes are due to the release of the steric strain in their excited states relative to that in the highly twisted ground states. One of these compounds might be a useful water-soluble fluorophore, whereas the other two are promising H(+) sensors.

Change of boron substitution improves the lasing performance of Bodipy dyes: a mechanistic rationalisation.

Bodipy laser dyes are highly efficient but degrade rapidly in solution by reacting with in situ generated singlet oxygen ((1)O(2)). To increase the lasing lifetimes of these dyes, we have designed and synthesised two different congeners of the widely studied Pyrromethene 567 (PM567) by substitution at the boron centre and/or at both the boron centre and the meso position. The two new dyes showed high lasing efficiencies with increased photostability. The results of theoretical and pulse radiolysis studies revealed that the substitution at the boron centre reduced the (1)O(2) generation capacity of these dyes as well as their rate of reaction with (1)O(2), thereby enhancing their lifetimes even under lasing conditions.

Enhanced redifferentiation of chondrocytes on microperiodic silk/gelatin scaffolds: toward tailor-made tissue engineering.

Direct-write assembly allows rapid fabrication of complex three-dimensional (3D) architectures, such as scaffolds simulating anatomical shapes, avoiding the need for expensive lithographic masks. However, proper selection of polymeric ink composition and tailor-made viscoelastic properties are critically important for smooth deposition of ink and shape retention. Deposition of only silk solution leads to frequent clogging due to shear-induced ß-sheet crystallization, whereas optimized viscoelastic property of silk-gelatin blends facilitate the flow of these blends through microcapillary nozzles of varying diameter. This study demonstrates that induction of controlled changes in scaffold surface chemistry, by optimizing silk-gelatin ratio, can govern cell proliferation and maintenance of chondrocyte morphology. Microperiodic silk-gelatin scaffolds can influence postexpansion redifferentiation of goat chondrocytes by enhancing Sox-9 gene expression, aggregation, and driving cartilage matrix production, as evidenced by upregulation of collagen type II and aggrecan expression. The strategy for optimizing redifferentiation of chondrocytes can offer valuable consideration in scaffold-based cartilage repair strategies.

Soluplus--solubilized citrated camptothecin--a potential drug delivery strategy in colon cancer.

Camptothecin (CPT), a potent antitumor drug, exhibits poor aqueous solubility and rapid conversion from the pharmacologically active lactone form to inactive carboxylate form at physiological pH. Solid dispersion of CPT in Soluplus®, an amphiphilic polymeric solubilizer, was prepared to increase the aqueous solubility of CPT and the resultant solid dispersion along with citric acid was formulated as hard gelatin capsules that were subsequently coated with Eudragit S100 polymer for colonic delivery. FTIR spectrum of the solid dispersion confirmed the presence of CPT. PXRD and DSC revealed the semicrystalline nature of solid dispersion. The solubility of the drug was found to increase ~40 times in the presence of Soluplus and ~75 times in solid dispersion. The capsules showed no drug release in 0.01 N HCl but released 86.4% drug in lactone form in phosphate buffer (pH 7.4) and the result appears to be due to citric acid-induced lowering of pH of buffer from 7.4 to 6.0. Thus the presence of citric acid in the formulation led to stabilization of the drug in its pharmacologically active lactone form. Cytotoxicity studies conducted with the formulation of solid dispersion with citric acid, utilizing cell cytotoxicity test (MTT test) on Caco-2 cells, confirmed cytotoxic nature of the formulation.

Waste derived approach towards wealthy fluorescent N-doped graphene quantum dots for cell imaging and H2O2 sensing applications.

Herein, we report the synthesis of a highly fluorescent nitrogen doped graphene quantum dots (N-GQDs) from waste precursors such as melamine sponge and arjuna bark via a microwave treatment and its functional and morphological characterization using various spectroscopy techniques such as optical, FTIR, XPS and TEM. The as-prepared aqueous N-GQD (dia. 2-3 nm) was used for the bio-imaging application using breast carcinoma cell line (MDA-MB-231) as a model, and the locations of all cells in the cytoplasm as well as nuclei were observed to stain brightly in blue fluorescent color successfully. In addition to that, the aqueous N-GQD showed fluorescence quenching behavior in the presence of hydrogen peroxide, which was exploited to sense H2O2, a probable toxin generated in the diseased cells. Importantly, the cell cytotoxicity was measured and found to be non-toxic (70% survival) to the MDA-MB-231 cells even at very high concentration (∼1.8 mg/ml) of the synthesized N-GQD. This study revealing excellent biocompatibility and imaging of the model cancer cells, and sensing of H2O2 by fluorescent quenching, indicates potential in-vivo cell culture applications of the prepared fluorescent N-GQD.

Stimuli Responsive Confinement of a Molecular Rotor Based BODIPY Dye inside a Cucurbit[7]uril Nanocavity.

Present study reports the interaction of a molecular rotor based BODIPY dye, 8-anilino-BODIPY (ABP), with a versatile macrocyclic molecule, cucurbit[7]uril (CB7), investigated through various techniques such as ground-state absorption, steady-state fluorescence, time-resolve emission, proton NMR, and quantum chemical studies. Although BODIPY dyes have widespread applications due to their intriguing photochemical properties, studies on their noncovalent interactions with different macrocyclic hosts, especially regarding their supramolecularly induced modulations in photophysical properties are very limited. The investigated BODIPY dye, especially its protonated ABPH+ form (pH ∼ 1), shows a large fluorescence enhancement on its interaction with the CB7 host, due to large reduction in the structural flexibility for the bound dye, causing a suppression in its nonradiative de-excitation process in the excited state. Unlike ABPH+, the neutral ABP form (pH ∼ 7) shows considerably weaker interaction with CB7. For ABPH+-CB7 system, observed photophysical results indicate formation of both 1:1 and 1:2 dye-to-host complexes. Plausible geometries of these complexes are obtained from quantum chemical studies which are substantiated nicely from 1H NMR results. The response of the ABPH+-CB7 system toward changing temperature of the solution have also been investigated elaborately to understand the potential of the system in different stimuli-responsive sensor applications.