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application/pdf, Biomaterials Science. 2021, 9 (8), P.3076-3089

A unique property of 2,4,6-trichloro-1,3,5-triazine (TCT) is its ability to undergoes a nucleophilic aromatic substitution reaction (SNAr) under temperature-controlled conditions. Using a convenient and biologically friendly protocol, mono-substituted s-triazines were treated with excess nucleophiles to obtain tri-substituted triazines in 1 + 2 mode (one nucleophile as the first substitution followed by another nucleophile for the other two positions). The nucleophiles used for this study were phenol, thiol and amine, and the best order of incorporation was phenol or thiol for the first position followed by amine for the last two positions., The work was funded by: Researchers Supporting Project at King Saud University (RSP-2020/50) (Saudi Arabia); National Research Foundation (NRF) and the University of KwaZulu-Natal (South Africa); the Spanish Ministry of Economy, Industry, and Competitiveness (MINECO) (RTI2018-093831-B-100), CIBER-BBN, and the Generalitat de Catalunya (2017 SGR 1439) (Spain). Rotimi Sheyi thanks to MINTEK for a predoctoral fellowship.

Antibiotic resistance and biofilm-related infections, persistent in conventional antimicrobial treatment, are continuously increasing and represent a major health problem worldwide. Therefore, the development of new effective treatments to prevent and treat biofilm-related infections represents a crucial challenge. Unfortunately, the extensive use of antibiotics has led to an increase of resistant bacteria with the subsequent loss of effectivity of commercial antibiotics, mainly due to antibiotic resistance and the ability of some bacteria to form microbial communities in biotic or abiotic surfaces (biofilms). In some cases, these biofilms are resistant to high concentrations of antibiotics that lead to treatment failure and recurrence of the associated infections. In the fight against microbial resistance, the combination of traditional antibiotics with new compounds (combination therapy) is an alternative that is becoming more extensive in the medical field. In this work, we studied the cooperative effects between levofloxacin, an approved antibiotic, and peptides or cationic dendritic molecules, compounds that are emerging as a feasible solution to overcome the problem of microbial resistance caused by pathogenic biofilms. We studied a new therapeutic approach that involves the use of levofloxacin in combination with a cationic carbosilane dendron, called MalG2(SNHMe2Cl)4, or a synthetic cell-penetrating peptide, called gH625, conjugated to the aforementioned dendron. To carry out the study, we used two combinations (1) levofloxacin/dendron and (2) levofloxacin/dendron-peptide nanoconjugate. The results showed the synergistic effect of the combination therapy to treat Staphylococcus aureus biofilms. In addition, we generated a fluorescein labeled peptide that allowed us to observe the conjugate (dendron-peptide) localization throughout the bacterial biofilm by confocal laser scanning microscopy.

A series of first-, second-, and third-generation dendronic triazolo-pyridazinones were synthesized in good yields via the CuI-catalyzed azide–alkyne cycloaddition reactions of 4,6-diphenyl-2-(prop-2-yn-1-yl)pyridazin-3(2H)-one, possessing a terminal alkyne functional group with aromatic mono- and diazides with long alkyl and chiral glycol side-chain substituents. The chemical structures of the new compounds were characterized using different spectroscopic methods. The morphology of the dendrons was examined using the scanning electron microscope (SEM) analysis, which revealed the formation of highly ordered nanofiber and nanorod aggregations, directed by π-stacking interactions and van der Waals forces. Graphical abstract

International audience; AB5 compounds issued from the reactivity of hexachlorocyclotriphosphazene are relatively easy to obtain using two ways: either first the reaction of one chloride with one reagent, followed by the reaction of the five remaining Cl with another reagent, or first the reaction of five chlorides with one reagent, followed by the reaction of the single remaining Cl with another reagent. This particular property led to the use of such compounds as core for the synthesis of dendrons (dendritic wedges), using the five functions for growing the dendritic branches. The single function can be used for the synthesis of diverse types of dendrimers (onion peel, dumbbell-shape, Janus), for covalent or non-covalent grafting to solid surfaces, providing nanomaterials, for grafting a fluorophore, especially for studying biological mechanisms, or for self-associations to get micelles. All these properties are reviewed in this paper.

Organic-inorganic layered materials, such as organotalcs, are a promising alternative as gelling agent for liquid electrolytes in dye-sensitized solar cells. Talcs could provide an abundant, low cost and environmentally friendly option for solidifying the electrolyte. This work focuses on generation 5 polyamideamino dendron-modified talc with emphasis is on how it affects the performance and stability of the DSSC. The talc was shown to improve the initial photocurrent by up to 39% by acting as a light scatterer and/or a recombination barrier compared to reference solar cells with liquid electrolyte. Non-destructive analysis based on photographic image technique revealed that during the aging the additive absorbed charge carriers, tri-iodide, from the electrolyte reducing the performance of the solar cells. The degradation could, however, be prevented by intercalating polyiodides into interlamellar space of the talc as the resulting dendron chains did not absorb tri-iodide charge carriers from the electrolyte. These quasi-solid solar cells maintained 95% of their initial efficiency under light-soaking at 1 Sun for about 1000 h. The cells with a quasi-solid electrolyte showed up to 5% higher efficiency than those with liquid electrolyte.

International audience; The explosive growth of nanotechnology has brought challenging innovations in the synthesis of multifunctional nano-objects able to revolutionize the field of diagnosis and therapy in medicine. Furthermore, one important input of today's nanotechnology in biology is that their design will also allow real progress to achieve temporal and spatial site local therapy and imaging. Such a breakthrough is made possible by the development of multifunctional biocompatible nanosystems resulting from cutting-edge researches based on pluridisciplinary approaches. Among the challenges are the design of the organic coating and its grafting at the surface of NPs while preserving the properties of both NPs and molecules. The molecules should ensure the colloidal stability of NPs in physiological media, their biocompatibility and biodistribution, and may bear functions to couple bioactive groups. This paper aims at providing challenges in functionalization of iron oxide nanoparticles for biomedical applications. © 2015 by De Gruyter 2015.

Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species&mdash, triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.

Background: Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this study, both light-responsive and temperature-responsive synthetic gene vectors were designed for spatiotemporal control of a transfection system. Methods: 11-Mercaptoundecanoic acid-coated gold nanorods were mixed with polyamidoamine dendron-bearing lipids of two types having amino-terminus or ethoxydiethylene glycol-terminus to obtain hybrid vectors. Hybrid vectors were mixed further with pDNA. Then we investigated their physicochemical properties and transfection efficacy with or without near infrared laser irradiation. Results: Hybrid vectors formed complexes with pDNA and exhibited enhanced photothermal property under near infrared laser irradiation compared with parent gold nanorods. Transfection efficacy of complexes was promoted considerably by brief laser irradiation soon after complex application to the cells. Analysis of intracellular distribution revealed that laser irradiation promoted the adsorption of complexes to the cells and cytosolic release of pDNA, which is derived from the change in surface hydrophobicity of complexes through dehydration of temperature-responsive groups. Conclusions: Hybrid vector is promising as a light-activatable transfection system.

The lack of an appropriate intracellular delivery system for therapeutic nucleic acids (TNAs) is a major problem in molecular biology, biotechnology, and medicine. A relatively new class of highly symmetrical hyperbranched polymers, called dendrimers, shows promise for transporting small TNAs into both cells and target tissues. Dendrimers have intrinsic advantages for this purpose: their physico-chemical and biological properties can be controlled during synthesis, and they are able to transport large numbers of TNA molecules that can specifically suppress the expression of single or multiple targeted genes. Numerous chemical modifications of dendrimers extend the biocompatibility of synthetic materials and allow targeted vectors to be designed for particular therapeutic purposes. This review summarizes the latest experimental data and trends in the medical application of various types of dendrimers and dendrimer-based nanoconstructions as delivery systems for short small interfering RNAs (siRNAs) and microRNAs at the cell and organism levels. It provides an overview of the structural features of dendrimers, indicating their advantages over other types of TNA transporters.

Dendrimers are monodisperse polymers grown in a fractal manner from a central point. They are poised to become the cornerstone of nanoscale devices in several fields, ranging from biomedicine to light-harvesting. Technical difficulties in obtaining these molecules has slowed their transfer from academia to industry. In 2001, the arrival of the “click chemistry” concept gave the field a major boost. The flagship reaction, a modified Hüisgen cycloaddition, allowed researchers greater freedom in designing and building dendrimers. In the last five years, advances in click chemistry saw a wider use of other click reactions and a notable increase in the complexity of the reported structures. This review covers key developments in the click chemistry field applied to dendrimer synthesis from 2010 to 2015. Even though this is an expert review, basic notions and references have been included to help newcomers to the field.

Synthetic macromolecules that can bind and co-assemble with proteins are important for the future development of biohybrid materials. Active systems are further required to create materials that can respond and change their behavior in response to external stimuli. Here we report that stimuli-responsive linear-branched diblock copolymers consisting of a cationic multivalent dendron with a linear thermoresponsive polymer tail at the focal point, can bind and complex Pyrococcus furiosus ferritin protein cages into crystalline arrays. The multivalent dendron structure utilizes cationic spermine units to bind electrostatically on the surface of the negatively charged ferritin cage and the in situ polymerized poly(di(ethylene glycol) methyl ether methacrylate) linear block enables control with temperature. Cloud point of the final product was determined with dynamic light scattering (DLS), and it was shown to be approximately 31 °C at a concentration of 150 mg/L. Complexation of the polymer binder and apoferritin was studied with DLS, small-angle X-ray scattering, and transmission electron microscopy, which showed the presence of crystalline arrays of ferritin cages with a face-centered cubic (fcc, \( Fm\overline{3}m \)) Bravais lattice where lattice parameter a = 18.6 nm. The complexation process was not temperature dependent but the final complexes had thermoresponsive characteristics with negative thermal expansion.

Organic–inorganic hybrid layered materials are proposed as additives in a quasi-solid gel electrolyte for dye-sensitized solar cells. Talcs could provide a low-cost and environmentally friendly, as well as abundant, option as gelators. Here, talcs were prepared by functionalizing an organotalc with three polyamidopyridine dendron generations, PAMPy-talc-Gn (n = 1, 2 and 3). PAMPy dendrons grow parallel to the lamellae plane and form an organized structure by intermolecular interactions. In addition, polyiodide–dendron charge-transfer complexes were prepared onto the organotalc by adsorption of iodine. In this work, the effect of the dendron generation of PAMPy-talc and the influence of polyiodide intercalation on solar cell performance and stability were investigated. The best results were reached with the use of lowest-generation PAMPy-talc (η = 4.5 ± 0.3%, VOC = 710 ± 19 mV, Jsc = 10.4 ± 0.9 mA cm–2, and FF = 61 ± 2%): 15% higher efficiency compared to similar liquid devices. While some previously studi...

Damage of non-vascularised tissues such as cartilage and cornea can result in healing processes accompanied by a non-physiological angiogenesis. Peptidic aptamers have recently been reported to block the vascular endothelial growth factor (VEGF). However, the therapeutic applications of these aptamers is limited due to their short half-life in vivo. In this work, an enhanced stability and bioavailability of a known VEGF blocker aptamer sequence (WHLPFKC) was pursued through its tethering of molecular scaffolds based on hyperbranched peptides, the poly(É -lysine) dendrons, bearing three branching generations. The proposed design allowed simultaneous and orderly-spaced exposure of sixteen aptamers per dendrimer to the surrounding biological microenvironent, as well as a relatively hydrophobic core based on di-phenylalanine aiming to promote an hydrophobic interaction with the hydrophobic moieties of ionically-crosslinked metacrylated gellan gum (iGG-MA) hydrogels. The VEGF blocker dendrons were entrapped in iGG-MA hydrogels and their capacity to prevent endothelial cell sprouting was assessed qualitatively and quantitatively using 3D in vitro models and the in vivo chick chorioallantoic membrane (CAM) assay. The data demonstrate that at nanoscale concentrations, the dendronised structures were able to enhance control of the biological actvity of WHLPFKC at the material/tissue interface and hence the anti-angiogenic capacity of iGG-MA hydrogels not only preventing blood vessel invasion, but also inducing their regression at the tissue/iGG-MA interface. The in ovo study confirmed that iGG-MA functionalised with the dendron VEGF blockers do inhibit angiogenesis by controlling both size and ramifications of blood vessels in proximity of the implanted gel surface., This work was mainly supported by the EC FP7 project Disc Regeneration (Contract No NMP3-LA-2008-213904). This study was also funded by the EC FP7 Programme contract agreement no REGPOT-CT2012-316331-POLARIS.

The synthesis of new dendrons of the generations 0, 1 and 2 with a double bond at the focal point and a carbonyl group at the termini has been carried out. The carbonyl group has been exploited for the multivalent conjugation to a sample saccharide by reductive amination and alkoxyamine conjugation. © 2014 Bini et al; licensee Beilstein-Institut.

International audience; Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron–lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron–lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties. Self-assembly in water through a solvent exchange process resulted in vesicles for the 0 through 2nd generation systems and micelles for the 3rd and 4th generation systems. The critical aggregation concentrations decreased with increasing dendron generation, suggesting that the effects of increasing molar mass dominated over the effects of increasing the hydrophilic weight fraction. The binding of the assemblies to Griffonia simplicifolia Lectin I (GSL 1), a protein with specificity for α-Gal was studied by quantifying the binding of fluorescently labeled assemblies to GSL 1-coated beads. It was found that binding was enhanced for amphiphiles containing higher generation dendrons. Despite their substantial structural differences with the natural ligands for the CD1d receptor, the glycodendron–lipid hybrids were capable of stimulating invariant natural killer T (iNKT) cells, a class of innate-like T cells that recognize lipid and glycolipid antigens presented by CD1d and that are implicated in a wide range of diseases and conditions including but not limited to infectious diseases, diabetes and cancer.

Molecular recognition of glycans plays an important role in glycomic and glycobiology studies. For example, pathogens have a number of different types of lectin for targeting host sugars. In bacteria, lectins exist sometimes as domains of bacterial toxins and exploit adhesion to glycoconjugates as a means of entering host cells. Herein, we describe the synthesis of three glycodendrons with the aim to dissect the fine structural details involved in the multivalent carbohydrate-protein interactions. LecA, from the pathogen Pseudomonas aeruginosa, has been used to characterize galactose dendrons interaction using one of the most widespread NMR technique for the elucidation of receptor-ligand binding in solution, the saturation transfer difference (STD) NMR. Furthermore, the effective hydrodynamic radius of each dendrimer recognized by LecA was estimated from the diffusion coefficients determined by pulsed-field-gradient stimulated echo (PFG-STE) NMR experiments.

Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron’s focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron’s azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization.

Functionalized phenols based on tyramine were synthesized in order to be selectively grafted on to hexachlorocyclotriphosphazene, affording a variety of functionalized dendrons of type AB5. The B functions comprised fluorescent groups (dansyl) or dyes (dabsyl), whereas the A function was provided by either an aldehyde or an amine. The characterization of these dendrons is reported. An unexpected behaviour of a fluorescent and water-soluble dendron based on dansyl groups in mixtures of dioxane/water was observed.

This review highlights the utilization of dendron-polymer conjugates as building blocks for the fabrication of nanosized drug delivery vehicles. The examples given provide an overview of the evolution of these delivery platforms, from simple micellar containers to smart stimuli- responsive drug delivery systems through their design at the macromolecular level. Variations in chemical composition and connectivity of the dendritic and polymeric segments provide a variety of self-assembled micellar nanostructures that embody desirable attributes of viable drug delivery systems.

Surface immobilization of dendrons and dendrimers presents an exciting opportunity for creating a wide variety of functionalized polymeric architectures suitable for the immobilization of biomolecules. Dendritic molecules contain multifunctional groups that can be efficiently modified to control the properties of the resulting polymers. We are developing strategies to generate a highly functionalized surface using multifunctional and rigid dendrons immobilized onto different substrates. In this paper, electrochemical methods and scanning probe microscopy were used to explore the immobilization of a dendritic macromolecule (3,5-bis(3,5-dinitrobenzoylamino)benzoic acid) or (D-NO2) onto gold electrodes. D-NO2 adsorbs spontaneously by dipping the metal surface in dendron solution and also via grafting of cystamine covalent attached to gold electrode. Reduction of this layer generates the hydroxylamine product. The resulting redox-active layer exhibits a well-behaved redox response for the adsorbed nitroso/hydroxylamine couple. Fil: Paez, Julieta Irene. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Froimowicz, Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnología En Polimeros y Nanotecnología. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnología En Polimeros y Nanotecnología; Argentina Fil: Baruzzi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Brunetti, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

We describe the design, synthesis, and "stimuli-responsive" study of ferrocene-linked Fr�chet-type [poly(aryl ether)]-dendron-based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low-molecular-weight gelators (LMWGs) form robust gels in both polar and non-polar solvent/solvent mixtures. The organometallic gels undergo stimuli-responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb2+ ions (detection limit ?10-8 M). The metal ion-sensing results in a gel-sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal-ligand binding nature has been analyzed by using 1H NMR spectroscopy, mass spectrometry, and DFT calculations. Receptive dendritic gelators: Ferrocene-containing poly(aryl ether) dendron based low-molecular-weight organometallic gels exhibit multi-stimuli-responsive behavior under thermal, chemical, and electrochemical conditions, and in also presence of Pb2+ ions. Results suggest the reversible thermal and redox switching of the gel, in addition to its ability to sense Pb2+ ions with restorable tendency (see figure). � 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A nano-handling technique based on atomic force microscopy (AFM) is presented that allows reliable measuring of force–extension profiles of single-polymer molecules. The basis of the method is a properly functionalized solid substrate, to which a small amount of the polymers in question is adsorbed. The sample is first imaged in amplitude modulation mode in solution with a functionalized AFM cantilever, and a polymer chain is picked up with the AFM tip at one of the ends of the polymer molecule. Force curves are recorded by stretching the attached polymer molecule many times. After the force experiments, the molecule is imaged again. In this fashion, one can ascertain that the force experiments are truly carried out with one individual molecule. With this technique, the force response of amino-functionalized dendronized polymers was studied and it could be accurately described by the freely jointed chain model with chain elasticity. A monotonic dependence of the mechanical properties of these polymers up to generation 4 was found. The elastic constant was independent of the generation and solution composition. On the other hand, the effective Kuhn length increased with the generation at higher salt concentrations. The mechanical response of dendronized polymers can be tuned with solution composition., ACS Nano, 8 (3), ISSN:1936-0851, ISSN:1936-086X

Surface topography and work function maps were simultaneously obtained for carbon surfaces modified by a dendritic molecule: 3,5-Bis (3,5-dinitrobenzoylamino) benzoic acid. The dendrons were spontaneously assembled onto highly ordered pyrolytic graphite samples, exhibiting an increase in the surface potential. This fact is consistent with the incorporation of an electron-acceptor functional group that remains electroactive on the surface. Fil: Farias, Eliana Desiree. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones en Físicoquímica de Córdoba; Argentina Fil: Brunetti, Veronica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Investigaciones en Físicoquímica de Córdoba; Argentina Fil: Paez, Julieta Irene. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina Fil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina Fil: Passeggi, Mario Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Física del Litoral; Argentina. Universidad Nacional del Litoral; Argentina Fil: Ferron, Julio. Universidad Nacional del Litoral. Facultad de Ingenieria Quimica. Departamento de Materiales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Física del Litoral; Argentina

A reversal in solvatochromic behaviour was observed in second and third generation glycerol based dansylated polyether dendrons in water on addition of a second solvent like methanol or acetonitrile. Below a certain percentage of the nonaqueous solvent there is a negative-solvatochromism observed and above that there is a switch to positive-solvatochromism. The negative-solvatochromism is attributed to the progressive disaggregation of the dendron aggregates by the nonaqueous solvent component. Once the disaggregation process is complete, positive-solvatochromism is exhibited by the dendron monomers. Higher the hydrophobicity of the dendron more is the amount of the second solvent required for disaggregation. � 2014 Elsevier B.V. All rights reserved.

In this work, we report the synthesis and characterization of a novel series of first and second generation Fréchet type dendrons bearing amino-nitro substituted azobenzene units and tetra(ethylene glycol) spacers. These compounds were fully characterized by FTIR, 1H and 13C-NMR spectroscopies, and their molecular weights were determined by MALDI-TOF-MS. The thermal properties of the obtained dendrons were studied by TGA and DSC and their optical properties by absorption spectroscopy in solution and cast film. Molecular calculations were performed in order to determine the optimized geometries of these molecules in different environments. Besides, Langmuir and Langmuir Blodgett films were prepared with the first generation dendrons that were shown to be amphiphilic. Finally, some of the dendrons showed a liquid crystalline behaviour, which was studied by light polarized microscopy as a function of the temperature in order to determine the transition temperatures and the structure of the mesophase.

Bu çalışmada; (Trimetilpropan tris [poli (propilen glikol) tri-amin ve 4,4'-bis(klorometil)bifenil) polimerik ve araomatik çekirdeğe sahip pamam tipi dendrimerler sentezlendi. Sentezlenen dendrimerler üç fonksiyonel grup (ester, asit ve amin) içermektedir. Yüzeyinde ester grupları olan dendrimer formik asit ile karboksilik asite dönüştürüldü. Bu karboksilik asitli dendrimerler tiyonil kloridle klorlanarak açil klorürler elde edildi. Öbür taraftan mikrodalga yardımıyla sentezlenen nitrotriester ve nitrodiester Al-Ni katalizörü ile indirgendi, bu dendronlar dendritik açil klorürler ile başarı ile bağlandı ve FT-IR/ATR ve NMR gibi spektroskopi teknikleri ile karakterize edildi. In this study pamam type of dendrimers, have polymeric and aromatic core (trimethylolpropane tris[poly(propylene glycol), three-amine) and 4,4'-bis(chloromethyl)biphenyl), were synthesized. Synthesized dendrimers bears three functional groups (ester, acid and amine). Ester group on the surface of the dendrimers converted to carboxylic acid with formic acid. This carboxylic acid dendrimers converted to acyl chloride with thionyl chloride. Then Microwave assisted synthesized nitro tri and diesters were successively reduced by Al-Ni catalyst, these dendrons were coupled to the dendritic acylchloride and characterized via FT-IR/ATR and NMR spectroscopic techniques. 68

Polimerik misel yapılar, hidrofobik çekirdek kısmına istenilen hidrofobik molekülü yükleme kapasitesinin çokluğu ve polimer iskeletinden kaynaklanan biyouyumluluk özellikleri nedeniyle ilaç salım sistemleri için ideal olan bir araçtır.Amfifilik kopolimer yapısındaki miseller su içerisinde herhangi bir dış etken olmaksızın oluşabilme özelliğine sahiptir. Hidrofilik/ hidrofobik bloklardaki çözünürlük farkı sebebi ile oluşan misel yapılar belli bir ölçekte büyüklük dağılımına ve hidrofobik bloğun iç çekirdeği, hidrofilik bloğunsa dış katmanı oluşturduğu eşsiz bir yapıya sahiptir.Bu tez çalışmasında, dendron-polimer-dendron konjugeleri poliester dendronlar ve PEG polimeri kullanılarak Huisgen tipi `klik' reaksiyonu ile elde edilmiş, sonraki aşamada ise dendron yüzeylerine hidrofobik fonksiyonel gruplar bağlanmıştır. Bu sistem ile, sulu ortamda polimerik misel oluşumu için gerekli olan hidrofobik-hidrofilik-hidrofobik denge sağlanır. Dendron yüzeyleri ilaç molekülleri ile bezenerek, ilaç salım sistemi potansiyeli olan misel yapılar elde edilmiştir. Polymeric micelles are known to be good candidates for drug release systems due to their high loading capacities of inner hydrophobic core as well as unique compatibility in the body.Micelles from amphiphilic copolymers can be formed in water via self-assembly according to the solubility difference of the hydrophilic and hydrophobic blocks. This kind of polymeric micelles have a narrow size distribution and unique architectured core, where hydrophobic segment forms the inner core and hydrophilic segment of the block copolymer surrounds the core and form the sphere of micelle.In our study, dendron-polymer-dendron conjugates are prepared via Huisgen type `click? reaction using polyester dendrons and PEG, followed by functionalization of the dendron surface with hydrophobic moiety. This system provides the hydrophobic-hydrophilic-hydrophobic balance neccessary to form the polymeric micelles in aqueous media. Dendron surface was further ornamented with drug molecules to yield the micellar drug delivery system. 99

This edge article reports the multiscale modelling of spermine-functionalised dendrons designed to bind DNA and deliver it into cells. The modelling provides an insight into the mode of self-assembly of the dendrons, in particular aggregate charge density and shape, and hence suggests explanations for some of the unexpected experimental observations. In particular, the self-assembly model helps explain why the first generation dendron is more effective in binding DNA than the second generation analogue, even though the second generation system has a greater number of surface spermine ligands. Effective self assembly of the first generation dendron leads to a high charge density assembled structure – more effective than the larger number of ligands on the second generation dendron – i.e., less is more. The modelling also suggests an alternative shape of self-assembly for the system with two hydrophobic cholesterol units (rather than one) at the dendron focal point – this may help explain why this system shows much enhanced gene delivery in vitro.

Dendritic molecules contain multifunctional groups that can be used to efficiently control the properties of an electrode surface. We are developing strategies to generate a highly functionalized surface using multifunctional and rigid dendrons immobilized onto different substrates. In the present work, we explore the immobilization of a dendritic molecule: 3,5-bis(3,5-dinitrobenzoylamino) benzoic acid (D-NO2) onto carbon surfaces showing a simple and rapid way to produce conductive surfaces with electroactive chemical functions. The immobilized D-NO2 layer has been characterized using atomic force microscopy and cyclic voltammetry. D-NO2 adsorbs onto carbon surfaces spontaneously by dipping the electrode in dendron solutions. Reduction of this layer generates the hydroxylamine product. The resulting redox-active layer exhibits a well-behaved redox response for the adsorbed nitroso/hydroxylamine couple. The film permeability of the derivatized surface has been analyzed employing the electrochemical response of redox probes: Ru(NH3)6 3+/Ru(NH3)6 2+ and Fe(CN)6 3-/Fe(CN)6 4-. Electrocatalytic oxidation of nicotinamide adenine dinucleotide onto a modified carbon surface was also observed. Fil: Paez, Julieta Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Passeggi, Mario Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Ferron, Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Baruzzi, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Brunetti, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

Dendrimerler bir çekirdek etrafinda yapılanan, yüksek derecede dallanmış, tek dağılımlı moleküllerdir. Dendrimeri oluşturan parçalar dendron olarak adlandırılırlar. Genel kanı olarak dendrimerlerin, bütün dendronların tek bir çekirdek etrafında büyüyerek sentezlendiği düşünülür. Alternatif bir yol olarak dendronların ayrı ayrı sentezlenip daha sonra çok değerli bir çekirdek etrafinda birleştirilmesiyle de sentezlenebilirler. Çekirdekteki değerlik sayısı dendrimerdeki parçacık sayısını belirler. Dendronların çekirdeğe bağlanma biçimleri hem kovalent bir yolla hem de kovalent olmayan etkileşimler ile olabilir.Hidrofobik etkileşimlere dayalı kovalent olmayan etkileşimlerden faydalanarak supramoleküler dendrimer oluşumu sağlamak mümkündür. Sulu ortamda dendronların bu oluşumu sağlamaları, dendronların odak noktalarına biri diğerinin içine girebilecek fonksiyonel gruplarin bağlanmasıyla başarılabilir. Hidrofobik iç boşluğa sahip olan siklodekstrinler bahsi geçen kompleksi uygun moleküller ile yapabilme yetisine sahiptirler.Bu çesit kompleksleşme alanında en bilinen örnek ß-siklodekstrin ve adamantanın yaptığıdır.İki farklı dendron sentezlenmiş ve sırasıyla ß-siklodekstrin ve adamantan ile fonksiyonelleştirilmiştir. Adamantan barındıran poliester dendronları içten dışa sentez metoduyla sentezlenmiştir. Özgün bir metot olan bakır katalizörlü Huisgen tipi Klik kimyası kullanılarak, ß-siklodekstrin barındıran poliaril eter dendronları sentezlenmiştir. Sulu ortamda, parça bloklu dendrimerlerin, oluşumunun dendronların kendiliğinden bir araya gelmesi yolu ile gerçekleştiği başarı ile gösterilmiştir. Dendrimers are monodisperse and highly branched macromolecules which are built around a core. The segments that combine to form a dendrimer are called dendrons. The synthesis of dendrimers can be undertaken in a manner that all dendrons are grown from the core molecule. As an alternative, dendrons can be synthesized separately and later combined with a multivalent core molecule to obtain the dendrimer. The number of multivalency of the core determines the number of segments in the dendrimer. The attachment of the dendron segments to the core unit can be via a covalent or non-covalent interaction.Non-covalent interactions based on hydrophobic effect can be exploited to yield a supramolecular dendrimer assembly. Assembly of dendrons in aqueous environment can be achieved by attachment of functional groups capable of forming host-guest complex at the focal point of the dendrons. Cyclodextrins having a hydrophobic interior cavity are capable of making supramolecular host-guest interactions with appropriate guests. A well known example is the inclusion complex of ß-cyclodextrin and adamantane.Two different types of dendrons were synthesized and functionalized with ß-cyclodextrin and adamantane respectively. The adamantane containing polyester dendrons were synthesized using divergent synthesis. Novel methodology involving copper catalyzed Huisgen type Click chemistry was utilized to obtain the cyclodextrin containing polyether dendrons. Self-assembly of dendrons to provide segment-block dendrimers in aqueous environment was successfully demonstrated. 84

Förfrågan efter nya och mer avancerade applikationer är en pågående process vilket leder till en konstant utveckling av nya material. För att förstå relationen mellan en applikations egenskaper och dess sammansättning krävs full förståelse och kontroll över materialets uppbyggnad. En sådan kontroll över uppbyggnaden hos material hittas i en undergrupp till dendritiska polymerer som kallas dendrimerer. I den här doktorsavhandlingen belyses nya metoder för att framställa dendrimer med hjälp av selektiva kemiska reaktioner. Sådana selektiva reaktioner kan hittas inom konceptet klickkemi och har i detta arbete kombinerats med traditionell anhydrid- och karbodiimidmedierad kemi. Denna avhandling diskuterar en accelererad tillväxtmetod, dendrimerer med inre och yttre reaktiva grupper, simultana reaktioner och applikationer baserade på dessa dendritiska material. En accelererad tillväxtmetod har utvecklats baserad på AB2- och CD2-monomerer. Dessa monomerer tillåter tillväxt av dendrimerer utan att använda sig av skyddsgruppkemi eller aktivering av ändgrupper. Detta gjordes genom att kombinera kemoselektiviteten hos klickkemi tillsammans med traditionell syraklorid kopplingar. Dendrimerer med inre alkyn- eller azidfunktionalitet syntetiserades genom att använda AB2C-monomerer. Den dendritiska tillväxten skedde med hjälp av karbodiimidmedierad kemi. Monomererna som användes bär på en C-funktionalitet, alkyn eller azid, och på så sätt byggs får interiören i de syntetiserade dendrimeren en inneburen aktiv funktionell grupp. Ortogonaliteten hos klickkemi användes för att sammanfoga monomerer till en dendritisk struktur. Traditionell anhydridkemi- och klickemireaktioner utfördes samtidigt och på så sätt kunde dendritiska strukturer erhållas med färre antal uppreningssteg. En ljusemitterande dendrimer syntetiserades genom att koppla azidfunktionella dendroner till en alkynfunktionell cyclenkärna. Europiumjoner inkorporerades i kärnan varpå dendrimerens fotofysiska egenskaper analyserades. Mätningarna visade att den bildade triazolen hade en sensibiliserande effekt på europiumjonen. Termiska studier på några av de syntetiserade dendrimerer utfördes för att se om några av dem kunde fungera som templat vid framställning av isoporösa filmer. The need for new improved materials in cutting edge applications is constantly inspiring researchers to developing novel advanced macromolecular structures. A research area within advanced and complex macromolecular structures is dendrimers and their synthesis. Dendrimers consist of highly dense and branched structures that have promising properties suitable for biomedical and electrical applications and as templating materials. Dendrimers provide full control over the structure and property relationship since they are synthesized with unprecedented control over each reaction step. In this doctoral thesis, new methodologies for dendrimer synthesis are based on the concept of click chemistry in combination with traditional chemical reactions for dendrimer synthesis. This thesis discusses an accelerated growth approach, dendrimers with internal functionality, concurrent reactions and their applications. An accelerated growth approach for dendrimers was developed based on AB2- and CD2-monomers. These allow dendritic growth without the use of activation or deprotection of the peripheral end-groups. This was achieved by combining the chemoselective nature of click chemistry and traditional acid chloride reactions. Dendrimers with internal azide/alkyne functionality were prepared by adding AB2C monomers to a multifunctional core. Dendritic growth was obtained by employing carbodiimide mediated chemistry. The monomers carry a pendant C-functionality (alkyne or azide) that remains available in the dendritic interior resulting in dendrimers with internal and peripheral functionalities. The orthogonal nature of click chemistry was utilized for the simultaneous assembly of monomers into dendritic structures. Traditional anhydride chemistry and click chemistry were carried out concurrently to obtain dendritic structures. This procedure allows synthesis of dendritic structures using fewer purification steps. Thermal analyses on selected dendrimers were carried out to verify their use as templates for the formation of honeycomb membranes. Additionally, a light emitting dendrimer was prepared by coupling of azide functional dendrons to an alkyne functional cyclen core. A Europium ion was incorporated into the dendrimer core, and photophysical measurements on the metal containing dendrimer revealed that the formed triazole linkage possesses a sensitizing effect. QC 20100629

An accessible pathway to synthesize dendronized MDI oligomers was studied. Two dendrons bearing –CN and –t-butyl functional groups on the periphery were obtained following the synthetic strategy proposed by Newkome et al. Dendrons with one focal point were converted from nitro into amino precursors and used as modifiers in the preparation of new functionalized materials. The coupling reaction of dendrons on oligomers with isocyanate groups was carried out through an easy and quick procedure. The dendronized oligomers showed conformation changes according to the polarity of the solvents, allowing a prediction of a “stimuli-responsive” behavior. Fil: Martinelli, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina Fil: Calderon, Marcelo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina Fil: Rodríguez, Esteban. Universidad Nacional de Educacion a Distancia; España Fil: Freire, Juan J.. Universidad Nacional de Educacion a Distancia; España Fil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina

ÖZET KROMOFOR UÇ GRUP TAŞIYAN POLİ(ARİL ETER) DENDRİTİK HİPERDALLI YAPILARIN SENTEZİ VE FLORESANS ÖZELIİKLERİNİN İNCELENMESİ Meltem AYDINLI Doktora Tezi, Kimya Anabilim Da lı Danışman : Prof.Dr. Mehmet TUTAŞ Arahk2003, 112 sayfa Bu çalışmada, konverjent (yüzeyden çekirdeğe doğru) sentez metodu kullanılarak yüzeyinde 4-metil-7-hidroksikumarin (3) ve odak noktasında 3-siyano-7- Hdroksikumarin (6) taşıyan sıfırıncı (G-0), birinci (G-l) ve ikinci (G-2) jenerasyon sayılarında poli(aril eter) dendritik yapılar Williamson eter sentezi yöntemiyle sentezlenmiştir. Sentezlenen dendritik yapıların doğruluğu; kromatografik tekniklerle saflaştırıldıktan sonra elementel analiz ve spektroskopik yöntemler (FTIR, *H-NMR, 13C-NMR, MS(FAB) kullanılarak kanıtlanmıştır. Sentezlenen dendritik yapıların absorpsiyon ve emisyon özelliklerine jenerasyon sayışırım etkisi incelenmiştir. Jenerasyon sayısı arttıkça dendritik yapının yüzeyindeki kromofor grup sayısı arttığından söz konusu yapıların molar absoptivite katsayıları ve emisyon şiddetlerinin de orantılı olarak arttığı tespit edilmiştir. Anahtar Kelimden Dendrimer, dendron, enerji transferi, ışık hasat etme, kromofor, moleküler aletler. Jüri: Prof. Dr. Mehmet TUTAŞ (Danışman) Prof. Dr. Ertuğrul ARPAÇ Prof. Dr. Basri ATASOY Prof. Dr. Güler AYRANCI Yrd. Doç. Dr. Birsen Ş. BÜYÜKTAŞ ABSTRACT SYNTHESIS OF POLY(ARYL ETHER) DENDRITIC HYPERBRANCHED STRUCTURES CARRYING CHROMOPHOR END GROUP AND INVESTIGATION OF FLUORESCENCE PROPERTEES Meltem AYDINLI Ph.D. in Chemistry Adviser. Prof.Dr. Mehmet TUTAS December 2003, 112 pages In this study, by using convergent (from the surface to the nucleus) synthesis method, poly(aryl ether) dendritic structures carrying 4-methyl-7-hydroxycoıımarin (3) on the surface and 3-cyano-7-hydroxycoumarin (6) at the focal point with zeroth (G-0), first (G-l) and second (G-2) generation number were synthesized by Williamson emer synthesis method. Synthesized dendritic structures, after being purified by chromatographic techniques, were proved by spectroscopic methods (aH-NMR, 13C-NMR, FTIR, MS(FAB) and elemental analysis. The effect of the generation number on the absorption and emission properties of the synthesized dendritic structures was investigated. Because of the fact that chromophor group number or the surface of the dendritic structure increased molar absorptivity coefficients and emission intensities of the structure mentioned were determined to increase. Key words: Dendrimer, dendron, energy transfer, light harvesting, chromophor, molecular devices. Committee: Prof. Dr. Mehmet TUTAŞ Prof. Dr. Ertuğrul ARPAÇ Prof Dr. Basri ATASOY Prof Dr. Güler AYRANCI Yrd. Doç. Dr. Birsen Ş. BÜYÜKTAŞ ii 112

Novel chitosan films dendronized on one side were prepared by reaction between a cross-linked biopolymer and weisocyanate dendron. According to ATR-FTIR analysis, it can be concluded that the dendronization took place on only one of the faces of the films. The highlight of this work is that the modification grants different hydrophilic and hydrophobic properties on both sides of the system. Interactions between the dendron-polymer network and the hydrophobic characteristics of the dendron modify the physical properties of the films. As the thermal stability of the films increases, the degree of swelling and WVP values decrease, and the elastic modulus increases, turning the network more rigid. The dendronized films were swollen at pH 3.4 and 6.8 which are the pHs of the different wound healing stages. The films remained stable for an extended period. The films obtained can be potentially applied as wound dressings able to maintain a moist environment at the wound interface and act as a barrier to microorganisms, removing excess exudates. The product is made from a readily available biomaterial that requires minimal processing, possesses antimicrobial properties and could promote wound healing. Fil: Aldana, Ana Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Toselli, Ricardo Javier. Universidad Nacional de Cordoba. Facultad de Cs.quimicas. Centro de Quimica Aplicada; Argentina Fil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Martinelli, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina