Solid-phase dendrimer synthesis: a promising approach to transform dendrimer construction

Dendrimers, by virtue of their unique well-defined dendritic structure and multivalent cooperativity, hold great promise for a wide variety of applications, ranging from healthcare to energy production and environmental sustainability. However, dendrimer synthesis suffers from two inherent problems which greatly handicap their development and limit their application: the formation of structural defects caused by incomplete or side reactions, and difficulties associated with purification. Solid-phase synthesis may overcome both these problems, firstly by enabling complete chemical reactions through the use of a large excess of reagents, secondly by facilitating purification through simple washing and filtering steps. The end result is the speeded up reactions producing the desired product in high yield, with simultaneous suppression of by-products. In this review, we present the challenges and current state of research in solid-phase dendrimer synthesis, and provide our perspectives on its future development. We start with a short introduction to solid-phase synthesis and specific considerations for dendrimer construction. We then present exemplary studies to highlight the potential of, and challenges faced by, solid-phase dendrimer synthesis. Finally, we describe efforts to deliver more effective and reliable methods that will transform the synthesis of dendrimers and permit exploitation of their full potential.     

Molecular modeling as a tool to discriminate between enantiomers resolved by derivatized cyclodextrins in gas chromatography

The elution order of a series of enantiomers, determined by gas chromatography using permethylated and trifluoroacetylated- and-cyclodextrins as stationary phases, was tentatively correlated with the lowest energies of the host-guest complex models resulting by including the enantiomers into the cyclodextrin cavity by means of the molecular mechanics method using standard software packagesSybyl andSpartan. The modeling data of cyclic isomers such as proline derivatives and-lactones correlate with the gas chromatographic data. Those of open isomers such as other aliphaticd,l-amino acids and alcohols, give contradictory results.     

Methylprednisolone release from agar-Carbomer-based hydrogel: a promising tool for local drug delivery

A number of studies and works in drug delivery literature are focused on the understanding and modelling of transport phenomena, the pivotal point of a good scaffold design for tissue engineering. Accurate knowledge of the diffusion coefficient of an active drug plays a key role in the analysis, prediction of their kinetics and formulation of efficient drug delivery systems. In this work, the kinetics of the release of methylprednisolone from agar-Carbomer hydrogel were studied taking into consideration the different drug concentrations and clearances typically achieved in in vitro or in vivo tests. Starting from the experiments it is possible to model the transport phenomenon and to calculate the diffusion coefficient through the hydrogel matrix.     

Core-shell lipid-polymer nanoparticles as a promising ocular drug delivery system to treat glaucoma

Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer nanoparticles.In this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic effect.The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the core.Brz-LPNs were prepared by a modified thin-film dispersion method.With the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs.Brz-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and Brz-LPs.Furthermore,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in vitro.Moreover,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in vivo.In conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.     

Hierarchically structured nanocrystalline hydroxyapatite assembled hollow fibers as a promising protein delivery system

Nanocrystalline hydroxyapatite assembled hollow fibers (NHAHF) in the membrane form were fabricated by combining the electrospinning technique and the hydrothermal method. This novel hierarchical tubular structure of hydroxyapatite exhibited excellent protein loading capacity and long-term sustained release property.     

Variable connectivity index as a tool for modeling structure-property relationships

We report on the calculation of normal boiling points for a series of n = 58 aliphatic alcohols using the variable connectivity index in which variables x and y are used to modify the weights on carbon (x) and oxygen atoms (y) in molecular graphs, respectively. The optimal regressions are found for x = 0.80 and y = -0.90. Comparison is made with available regressions on the same data reported previously in the literature. A refinement of the model was considered by introducing different weights for primary, secondary, tertiary, and quaternary carbon atoms. The standard error in the case of the normal boiling points of alcohols was slightly reduced with optimal weights for different carbon atoms from s = 4.1 degrees C (when all carbon atoms were treated as alike) to s = 3.9 degrees C.     

Experimentally available kinetic codes as a tool for promising data extraction in thermal analysis

By the study of 3000 kinetic runs for all homogeneous two-step models under variation of activation and signal parameters, it has been stated that the generated Mechanistic Concentration Code (=MCC) is the best vehicle for data extraction in Thermal Analysis. It summarises the rate-controlling steps and their molecularities, independently of their activation data and (to 80–90%) of their method-specific signal parameters. Hence, an optimum evaluation needs the internal (best-fitted) reference step, the initial concentration of a reference reactant, and equal weight of theoretical and experimental results, reached using the same algorithms. Thus, the MCC of any series measured in general allows for a reliable model determination via the distribution into all two-step models, using the tools of probability and decision theory. A transfer of the strategy to heterogeneous reactions is discussed.

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Zusammenfassung Durch die Untersuchung von über 3000 kinetischen Abläufen für alle homogenkinetischen Zweistufen-Modelle wurde festgestellt, da\ der Mechanistische Konzentrations-Code (= MCC) ein optimaler Datenträger in der Thermischen Analyse ist: Er beschreibt die geschwindigkeitsbestimmenden Schritte und ihre Molekularität, unab- hängig von deren Aktivierungsdaten und, zu 80–90%, von ihren methodenspezifischen Signalparametern. Ein optimales Auswerteverfahren benötigt einen internen (optimal angepa\ten) Referenzschritt, die Startkonzentration eines Referenz-Reaktanten und Gleichberechtigung theoretischer und experimenteller Befunde, erreicht, durch Verwendung derselben Algorithmen. Allgemein ermöglicht der MCC aus einer Reihe von Experimenten dann eine Modellbestimmung über eine Verteilung, die durch entscheidungstheoretische Kriterien die Wahrscheinlichkeiten aller Zweistufenmodelle auflistet.Eine übertragung des Verfahrens auf heterogene Prozesse wird diskutiert.

     

Chemical conjugation with cyclodextrins as a versatile tool for drug delivery

A pillar[5]arene-based N-heterocyclic carbene ligand was prepared by reaction of bromoethoxy pillar[5]arene with excess 1-methylimidazole at 130 °C in the absence of solvent and used as a catalyst for the Suzuki coupling reaction. Excellent yields were obtained when the Suzuki reactions were carried out under ambient atmosphere in ethanol, employing 0.2 mol% ligand, 1 mol% PdCl₂(CH₃CN)₂ and 1.5 mmol of K₂CO₃. The novel pillar[5]arene-based imidazolium salt is a promising material for the construction of highly active supramolecular catalytic systems.     

Stimuli-responsive chitosan-graft-poly(N-vinylcaprolactam) as a promising material for controlled hydrophobic drug delivery

A novel type of pH- and thermo-responsive copolymer, chitosan-graft-poly(N-vinylcaprolactam) (chitosan-g-PNVCL), was prepared by grafting carboxyl-terminated poly(N-vinylcaprolactam) (PNVCL-COOH) chains onto a chitosan backbone as a drug-delivery carrier. The formation of chitosan-g-PNVCL was confirmed by FT-IR and 1H NMR techniques. Chitosan-g-PNVCL showed a definite phase transition at 32 degrees C as occurs in pure PNVCL. The swelling degree of the chitosan-g-PNVCL beads was found to be higher at pH 2.2 than at pH 7.4. Moreover, the swelling degree of the beads decreased with increased environmental temperature. Compared to the chitosan beads, the release profile of chitosan-g-PNVCL beads showed a slower and more controlled release of the entrapped ketoprofen. The release behavior of the chitosan-g-PNVCL beads was influenced by both the pH and temperature of the medium. The MTT assay showed no obvious cytotoxicity of chitosan-g-PNVCL against a human endothelial cell line over a concentration range of 0-400 microg x mL(-1). These results suggest that chitosan-g-PNVCL could be a potential stimuli-responsive material for controlled drug delivery, and it may improve the bioavailability, efficacy, and compliance of the encapsulated drugs. [Reaction: see text].     

Dilatometry as a tool to study a new synthesis for calcium hexaluminate

By using a wet chemical route, pure calcium hexaluminate (CA₆) was yielded, significantly lowering the reaction temperature and shortening the synthesis time if compared to usual industrial procedures. owever, dilatometric studies performed on compacts made of the as-prepared powder, just after pre-heating at 450°C, has shown a superposition between sintering shrinkage and expansion related to CA₂ formation, an intermediate phase formed during calcination and phase evolution to CA₆. oupling of such opposite phenomena led to microcracking of the material, mainly if the heating rates (10°C min^-1) were high. However, lower heating rates (1-5°C min^-1) could quite avoid microcracking but also limit densification. This revised version was published online in July 2006 with corrections to the Cover Date.     

Nanoconfinement as a tool to study early stages of polymer crystallization

This article promotes the idea that crystallization experiments under confinement can be an interesting tool to learn more about the early stages of polymer crystallization in bulk systems. Based on various results from the recent literature, it is demonstrated that crystalline forms that are metastable, transient, or inaccessible in bulk samples can be easily obtained and studied in nanoscopic compartments. This is interesting in the light of the recent discussion about thermodynamic reasons for the temporary occurrence of a mesophase at the growth front of crystals in bulk polymers, in particular, about a hexagonally packed mesophase in polyethylene. The experimental findings for nanoconfined methylene sequences seem to support indirectly thermodynamic approaches explaining the occurrence of a mesophase based on the small thickness of the crystal at the growth front. A first estimate for the critical crystal thickness d_mc defining the transition from hexagonal to orthorhombic packing in case of confined methylene sequences is provided based on results for side chain polymers. Further perspectives of crystallization experiments on confined systems are discussed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1556–1561, 2008     

Preparative isotachophoresis with surface enhanced Raman scattering as a promising tool for clinical samples analysis

A surface enhanced Raman scattering (SERS) spectrometry is an interesting alternative for a rapid molecular recognition of analytes at very low concentration levels. The hyphenation of this technique with advanced separation methods enhances its potential as a detection technique. Until now, it has been hyphenated mainly with common chromatographic and electrophoretic techniques. This work demonstrates for a first time a power of preparative isotachophoresis-surface enhanced Raman scattering spectrometry (pITP-SERS) combination on the analysis of model analyte (buserelin) in a complex biological sample (urine). An off-line identification of target analyte was performed using a comparison of Raman spectra of buserelin standard with spectra obtained by the analyses of the fractions from preparative isotachophoretic runs. SERS determination of buserelin was based on the method of standard addition to minimize the matrix effects. The linearity of developed method was obtained in the concentration range from 0.2 to 1.5 nmol L(-1) with coefficient of determination 0.991. The calculated limit of detection is in tens of pico mols per liter.     

Product ion mobility as a promising tool for assignment of positional isomers of drug metabolites

Travelling wave ion mobility spectrometry - mass spectrometry (TWIMS-MS) was evaluated as a tool for structural identification of metabolites of small molecule drugs in cases where the exact position of the biotransformation could not be identified by conventional tandem mass spectrometry. Test sets of compounds containing biotransformations at aromatic positions were analyzed. These present a problem for traditional MS methods since an atomic level localization of the biotransformation cannot normally be determined from MS(n) spectra. In addition to ion mobility measurements of the intact metabolite ions, ion mobility measurements of product ions were also made and the results compared with calculated values. This approach reduces the complexity of the problem, making theoretical calculations easier and more predictable when a modeled collision cross section (CCS) is required. A good relative correspondence between theoretical and measured CCSs was obtained allowing the identification of the exact position of the biotransformation. It was also demonstrated that authentic standards with substructures identical to those in the unknown can be used to assign the exact position of the biotransformation. In this approach the identification was based on the comparison of the drift times or CCSs for product ions of the standard, with those of the same product ions in the unknown.     

Molecular imprinting of proteins emerging as a tool for protein recognition

This article gives the recent developments in molecular imprinting for proteins. Currently bio-macromolecules such as antibodies and enzymes are mainly employed for protein recognition purposes. However, such bio-macromolecules are sometimes difficult to find and/or produce, therefore, receptor-like synthetic materials such as protein-imprinted polymers have been intensively studied as substitutes for natural receptors. Recent advances in protein imprinting shown here demonstrate the possibility of this technique as a future technology of protein recognition.     

Scanning tunneling microscopy as a tool to study catalytically relevant model systems

The surface science approach to catalysis, pioneered by 2007 Nobel Laureate in chemistry Gerhard Ertl, has helped revolutionize our understanding of heterogeneous catalysis at the atomic level. In this tutorial review we show how the scanning tunnelling microscope (STM), in combination with this surface science approach, is a very important tool for the study of catalytically relevant model systems. We illustrate how the high spatial and temporal resolution of the STM can be used to obtain quantitative information on elementary processes involved in surface catalyzed reactions. Furthermore, we show that the STM is an outstanding surface science tool to bridge the materials gap and the pressure gap between surface science experiments and real catalysis. Finally, we show that we are approaching an era where the atomic-scale insight gained from fundamental STM surface science studies can be used for the rational design of new catalysts from first principles.     

Molecular rotation as a tool for exploring specific solute-solvent interactions.

Solute-solvent interactions play an important role in determining the physicochemical properties of liquids and solutions. As a consequence, understanding these interactions has been one of the long-standing problems in physical chemistry. This Minireview describes our approach towards attaining this goal, which is to investigate rotational relaxation of a pair of closely related, medium-sized nondipolar solutes in a set of appropriately chosen solvents. Our studies indicate that solute-solvent hydrogen bonding significantly hinders solute rotation. We have also examined the role of solvent size both in the absence and presence of specific interactions and it has been observed that the size of the solvent has a bearing on solute rotation especially in the absence of specific interactions. Our results point to the fact that only strong solute-solvent hydrogen bonds have the ability to impede the rotation of the solute molecule because, in such a scenario, hydrogen-bonding dynamics and rotational dynamics transpire on comparable time scales. This aspect has been substantiated by measuring the reorientation times of the chosen solutes in solvents such as ethanol and trifluoroethanol, which have distinct hydrogen-bond donating and accepting abilities, and correlating them with solute-solvent interaction strengths. As an alternative treatment, it has been shown that specific interactions between the solute and the solvent can be modeled as dielectric friction with the extended charge distribution model. This approach is not unrealistic considering the fact that specific as well as non-specific interactions are electrostatic by nature and the differences between them are subtle.     

Isotope pattern deconvolution as a tool to study iron metabolism in plants

Isotope pattern deconvolution is a mathematical technique for isolating distinct isotope signatures from mixtures of natural abundance and enriched tracers. In iron metabolism studies measurement of all four isotopes of the element by high-resolution multicollector or collision cell ICP–MS allows the determination of the tracer/tracee ratio with simultaneous internal mass bias correction and lower uncertainties. This technique was applied here for the first time to study iron uptake by cucumber plants using ⁵⁷Fe-enriched iron chelates of the o,o and o,p isomers of ethylenediaminedi(o-hydroxyphenylacetic) acid (EDDHA) and ethylenediamine tetraacetic acid (EDTA). Samples of root, stem, leaves, and xylem sap, after exposure of the cucumber plants to the mentioned ⁵⁷Fe chelates, were collected, dried, and digested using nitric acid. The isotopic composition of iron in the samples was measured by ICP–MS using a high-resolution multicollector instrument. Mass bias correction was computed using both a natural abundance iron standard and by internal correction using isotope pattern deconvolution. It was observed that, for plants with low ⁵⁷Fe enrichment, isotope pattern deconvolution provided lower tracer/tracee ratio uncertainties than the traditional method applying external mass bias correction. The total amount of the element in the plants was determined by isotope dilution analysis, using a collision cell quadrupole ICP–MS instrument, after addition of ⁵⁷Fe or natural abundance Fe in a known amount which depended on the isotopic composition of the sample.     

Sequential extraction as a tool to study the foliar uptake of radionuclides

In order to study the foliar uptake of radionuclides deposited from an aerosol released in an accidental situation, lettuce plants were contaminated with an aerosol containing⁸⁵Sr,¹³⁴Cs and^110mAg isotopes. The methodology chosen to carry out this study is based on a sequential extraction scheme using water, to evaluate the fraction possibly removed by rain or by washing, and an organic solvent, to distinguish between the fraction adhering to the cuticle and the one incorporated in the leaves. Two procedures are compared. Moreover, the different behavior of the radionuclides in their incorporation into the leaves is deduced from the results obtained.     

Layer-by-layer coated emulsion microparticles as storage and delivery tool

Microencapsulation is an imperative technology in pharmacy, food industry and medicine. However, the current level of the development requires not only the fabrication of the emulsion systems, but also their functionalization in order to impart it multifunctional properties. One of the most perspective approaches to attain additional functionality to the emulsion particles is the use of the layer-by-layer modification of their surface. This technique permits the step-wise adsorption of various components (polyelectrolytes, nanoparticles, proteins, enzymes, etc.) as the layer growth is governed by their electrostatic, hydrogen bonding, hydrophobic, etc. forces and allows the formation of multilayer shells with nanometer (thickness) precision. The proposed review surveys the layer-by-layer approach for modification of both polymer and Pickering emulsions with polyelectrolyte or nanoparticle multilayers together with the demonstration of the application examples of the modified emulsion systems, where the emulsion particles play simultaneously the role of the template for layer-by-layer assembly as well as of the inner load.