Suchergebnisse

The characteristic distribution of transverse relaxation times (T2) within dendrimers (shorter values at the core than the periphery) can be exploited in T2-edited 1D and 2D NMR experiments for the stepwise filtering of internal nuclei according to their topology within the dendritic structure. The resulting filtered spectra, which can be conceived as corresponding to virtual hollow dendrimers, benefit from reduced signal overlap, thus facilitating signal assignment and characterization. The generality of the method as a powerful tool in structural and end-group analysis has been confirmed with various dendritic families and nuclei (1H, 13C, 31P) ; This work was financially supported by the Spanish Government (CTQ2009-10963, CTQ2012-34790, CTQ2009-14146-C02-02, CTQ2012-33436) and the Xunta de Galicia (10CSA209021PR and CN2011/037). L.F.P. thanks the Portuguese Foundation for Science and Technology (FCT MCTES) for a Ph.D. grant (SFRH/BD/37341/2007) ; SI

An unexpected 1H NMR invisible fraction (IF) for chitosan (CS) and CS-g-PEG is reported. The presence of this IF is remarkable considering that solution NMR is recognized as the method of choice for studying structural modifications in CS, including the degrees of acetylation (DA) and substitution (DS). In spite of IF figures as high as 50%, this IF does not interfere in the correct determination of the DA by 1H NMR, pointing to a homogeneous distribution of acetyl groups along the visible and invisible fractions. Quite in contrast, the IF negatively biases the determination of the DS in CS-g-PEG, with relative errors as high as 150% in a broad range of temperatures, pH values, and concentrations. This fact raises concerns about the accuracy of previously reported DS data for CS-g-PEG and many other CS copolymers. Efficient user-friendly conditions have been developed for the correct determination of the DS of CS-g-PEG by depolymerization by nitrous acid ; This work was financially supported by the Spanish Government (CTQ2009-10963, CTQ2012-34790, CTQ2009-14146-C02-02, and CTQ2012-33436) and the Xunta de Galicia (10CSA209021PR and CN2011/037) ; SI

The aggregation of chitosan (CS) has been studied as a function of concentration, degree of acetylation (DA), and degree of polymerization (DP) by means of pyrene fluorescence and rheology. Fluorescence experiments show that aggregation of CS involves hydrophobic domains (HD) which are more favoured as lower the DA and DP. Consistent with these results, the viscosity of CS solutions decreases continuously on increasing DA, in the whole range of DP. These results, which rule out the participation of the acetyl groups in the HD, have been interpreted by the theory of hydrophobic polyelectrolytes in terms of the electrostatic energy of the aggregates ; This work was financially supported by the Spanish Government (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037) ; SI

The paramagnetic spin relaxation (PSR) filter allows the suppression of the NMR resonances of individual components in mixtures according to their Gd3+-complexing ability. The difficulty in predicting this property hampers, however, the widespread application of this filter. Herein we describe that the PSR filter is dominated by the transverse relaxation enhancement (R2p) experienced by nuclei in the presence of Gd3+, so that R2p represents a reliable predictive tool of suppression in the 1D and 2D PSR filter of complex mixtures. The robustness of R2p as a predictive tool in PSR filters has been demonstrated at different magnetic fields and for the 1H, 13C, COSY, and HMQC filtering of commercial multicomponent compositions, including beverages and drugs ; This work was financially supported by the Spanish Government (CTQ2012-34790, CTQ2012-33436) and the Xunta de Galicia (CN2011/037). L.F.P. thanks the Portuguese Foundation for Science and Technology (FCT MCTES) for a Ph.D. grant (SFRH/BD/37341/2007) ; SI

Multivalency is a key, ubiquitous phenomenon in nature characterized by a complex combination of binding mechanisms, with special relevance in carbohydrate–lectin recognition. Herein we introduce an original surface plasmon resonance kinetic approach to analyze multivalent interactions that has been validated with dendrimers as monodisperse multivalent analytes binding to lectin clusters. The method, based on the analysis of early association and late dissociation phases of the sensorgrams provides robust information of the glycoconjugate binding efficiency and real-time structural data of the binding events under the complex scenario of the glyco-cluster effect. Notably, it reveals the dynamic nature of the interaction and offers experimental evidence on the contribution of binding mechanisms ; This work was financially supported by the Spanish Government (CTQ2009-10963, CTQ2012-34790, CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037). E.M.M. thanks the Xunta de Galicia for a "Parga Pondal" research contract ; SI

This is a post-peer-review, pre-copyedit version of an article published in The AAPS Journal. The final authenticated version is available online at: https://doi.org/10.1208/s12248-014-9642-3 ; Dendrimers are synthetic macromolecules composed of repetitive layers of branching units that emerge from a central core. They are characterized by a tunable size and precise number of peripheral groups which determine their physicochemical properties and function. Their high multivalency, functional surface, and globular architecture with diameters in the nanometer scale makes them ideal candidates for a wide range of applications. Gallic acid-triethylene glycol (GATG) dendrimers have attracted our attention as a promising platform in the biomedical field because of their high tunability and versatility. The presence of terminal azides in GATG dendrimers and poly(ethylene glycol) (PEG)-dendritic block copolymers allows their efficient functionalization with a variety of ligands of biomedical relevance including anionic and cationic groups, carbohydrates, peptides, or imaging agents. The resulting functionalized dendrimers have found application in drug and gene delivery, as antiviral agents and for the treatment of neurodegenerative diseases, in diagnosis and as tools to study multivalent carbohydrate recognition and dendrimer dynamics. Herein, we present an account on the preparation and recent applications of GATG dendrimers in these fields ; The authors wish to acknowledge past and present lab members who have contributed to the development of dendrimers in our group. This work was financially supported by the Spanish Government (CTQ2009-10963, CTQ2012-34790, CTQ2009-14146-C02-02, CTQ2012-33436) and the Xunta de Galicia (10CSA209021PR and CN2011/037) ; SI

The paramagnetic spin relaxation filter is described for the rapid NMR screening of intermolecular interactions between ligands and macromolecular anionic receptors with large transverse relaxation enhancements (R2p). The addition of micromolar concentrations of Gd3+ to the mixture produces the immediate broadening/suppression of the NMR signals of interacting species while leaving unaffected those of noncompetitive binders (one-dimensional and two-dimensional experiments). The method is highly sensitive, unveiling interactions that are too weak to generate changes in chemical shifts or relaxation times. It is operationally very simple and hence, it is amenable to ready implementation by nonspecialists. Examples of application such as detecting the formation of interpolymer complexes, cyclodextrin host–guest interactions, and the screening of DNA ligands are included that demonstrate the reliability and broad applicability of the method ; This work was financially supported by the Spanish Ministry of Economy, Industry, and Competitiveness (MINECO)(CTQ2015-69021-R), the Xunta de Galicia (GRC2014/040 and Centro Singular de Investigacion de Galicia Accreditation 2016-2019, ED431G/09), and the European Union (European Regional Development Fund-ERDF) ; SI

NMR is a powerful tool to study the dynamics of dendrimers. By analogy to linear polymers, shorter T1 relaxation times have been traditionally associated to less mobile nuclei and hence, dendrimers described with reduced local motions at either the core or the periphery. Herein we report a NMR relaxation study [1H and 13C T1, T2; 13C{1H}NOE; various fields and temperatures] which reveals profound differences between the relaxation behavior of dendrimers and linear polymers. Dendrimers show slower dynamics at internal layers and on increasing generation and may display internal nuclei in the slow motional regime with larger T1 values than the periphery. In contrast to the relaxation properties of linear polymers, these T1 increments should not be interpreted as resulting from faster dynamics. Only the recording of T1 data at various temperatures (alternatively, T2 or NOE at one temperature) ensures the correct interpretation of dendrimer dynamics ; This work was financially supported by the Spanish Government (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037). L.F.P. thanks the Portuguese Foundation for Science and Technology (FCT MCTES) for a Ph.D. grant (SFRH/BD/37341/2007) ; SI

A general method for the conversion of a polyphenylacetylene into its P or M helically oriented polymer, and into their corresponding P/M helical nanoparticles via dynamic metal coordination is presented. Addition of Mn+ ions ( e.g., Ca2+, Zn2+, Ag+, among others) to poly(phenylacetylene)s (poly-2 to poly-6), bearing OMe protected amino acids, produce complex I (chelation of the two carbonyl groups; sp conformation) associated to a helix inversion of the polymer. Ulterior addition of a small amount of MeOH, transforms complex I into complex II (metal ion coordinated only to the ester group; ap conformation), where a second helix inversion is produced. This dynamic coordination proccess between complex I and complex II works also at the nanoscale level, and therefore chiral nanoparticles with either P or M helices can be generated or transformed into each other by controlling the polymer/metal/methanol ratio in the helical polymer metal complex (HPMC) ; We thank Servicio de Microscopía Electrónica (RIAIDT, USC), Ministerio de Economía y Competitividad [CTQ2015-70519-P, CTQ2014-61470-EXP, FPI contract (M. Núñez)], Fundación Gil Dávila fellowship (S. Arias.), Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016-2019, GRC2014/040) and the European Union (European Regional Development Fund - ERDF) for financial support ; SI

The great importance of the secondary structure (compressed/stretched) of helical poly(phenylacetylene)s (PPAs) in the formation of nanostructures (nanospheres and nanotoroids) by complexation with metal ions of diverse valences is demonstrated. PPAs bearing the same chelating units [anilide of (R)-methoxyphenylacetic acid] but displaying different helical scaffolds show great differences in their nanostructuration due to the different secondary structures of their helices despite the analogous ways in which their mono- and divalent metal ions form complexes. This key 3-D structural feature has not been taken into account previously when studying the nanostructuration of helical polymer–metal complexes (HPMCs) ; We thank Ministerio de Economía y Competitividad [CTQ2015-70519-P, CTQ2014-61470-EXP], FPI (R. Rodríguez), Fundación Gil Dávila (S. Arias), Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016-2019, GRC2014/040) and European Union (European Regional Development FundERDF) for financial support ; SI

A precise tuning of the four possible states of a helix (P/M helical sense and stretched/compressed helical backbone) is attained by controlling the complexation between Li+ and a poly(phenylacetylene) that bears amide, ester and phenyl ring functionalities at the pendant group. Depending on the MeOH ratio that is present as a cosolvent, different coordination sites are involved in interactions leading to complexes I–III, each one with a characteristic structure (tri-, bi-, and unipodal) and an associated helical state. This dynamic coordination allows the selective modification of the helical sense or the stretching/compression backbone of a helical polymer ; We thank Ministerio de Economía y Competitividad [CTQ2015-70519-P and CTQ2014-61470-EXP], Erasmus Mundus (M. Alzubi), Fundación Gil Dávila (S. Arias), Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016–2019, GRC2014/040) and European Union (European Regional Development Fund –ERDF) for financial support ; SI

This is the peer reviewed version of the following article: Freire, F., Cobos, K., Rodríguez, R., Quiñoá, E. and Riguera, R. (2020), From Sergeants and Soldiers to Chiral Conflict Effects in Helical Polymers by Acting on the Conformational Composition of the Comonomers. Angew. Chem. Int. Ed. Accepted Author Manuscript. doi:10.1002/anie.202009215, which has been published in final form at https://doi.org/10.1002/anie.202009215. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions ; Different communication mechanisms can be switched within a copolymer by acting on the conformational composition of the components and their chirality. Thus, a Sergeant and Soldiers effect is produced in two diastereomeric copolymer series —poly[( S )‐ 1 r ‐ co ‐( S )‐ 2 ( 1‐r ) ] and poly[( R )‐ 1 r ‐ co ‐( S )‐ 2 ( 1‐r ) ]— due to the presence in chloroform of a preferred conformation in ( S )‐ 2 , and a conformational equilibrium in 1 , where a P helix is induced independently of the absolute configuration of the Soldier. In THF, the presence of a conformational equilibrium at the pendants of the two components produces a reciprocal chiral enhancement effect by copolymerization of the two monomers, while in DMF, a third chiral to chiral communication switch is produced due to the presence of a single conformer at the pendant group of the two components. In such case, a Chiral Conflict or Chiral Accord effect is produced depending if the two components induce the same or the opposite helical sense ; Financial support from MINECO (CTQ2015-70519-P), Xunta de Galicia (ED431C 2018/30, Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03, and postdoctoral fellowship to R. R.) and the European Union (European Regional Development Fund - ERDF) is gratefully acknowledged ; SI

This is the peer reviewed version of the following article: B. Fernández, R. Rodríguez, A. Rizzo, E. Quiñoá, R. Riguera, F. Freire, Angew. Chem. Int. Ed. 2018, 57, 3666, which has been published in final form at https://doi.org/10.1002/anie.201713164. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ; The calculated ECD spectrum (time‐dependent density functional theory TD‐DFT) for small oligomers of polyphenylacetylenes (PPAs) show a very good match with the experimental spectra of the PPA polymers, particularly with the first Cotton band associated to the helical sense of the internal polyenic backbone. This has been proven with a series of PPAs representative of cis‐cisoidal, cis‐transoidal, compressed and stretched polyene backbones, with identical or opposite internal/external rotational senses and allows the prediction of the helical sense of the internal helix of a PPA directly from its CD spectra ; We also thank the MEIyC [CTQ2014- 61470-EXP, CTQ2015-70519-P, FPI (R. Rodríguez)], XUGA (GRC2014/040, Centro singular de investigación de Galicia acreditation 2016-2019, GRC2014/040, and Axuda para Consolidación e Estruturación de Unidades de Investigación Competitivas do SUG, ED431C 2017/17) and the European Union (ERDF) for financial support ; SI

This is the peer-reviewed version of the following article: Fernandez-Villamarin, M., Sousa-Herves, A., Correa, J., Munoz, E., Taboada, P., Riguera, R., & Fernandez-Megia, E. (2016). The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG-Dendritic GATG Copolymers. Chemnanomat, 2(5), 437-446, which has been published in final form at https://doi.org/10.1002/cnma.201600008. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-Archiving ; A general synthetic strategy to polyethylene glycol (PEG)‐dendritic block copolymers of the GATG (gallic acid–triethylene glycol) family is described from commercially available PEG of different molecular weights and architectures. Glycosylation of the resulting azide‐terminated copolymers with fucose by copper‐catalyzed azide–alkyne cycloaddition (CuAAC) afforded a toolbox to study the effect of PEG on the multivalent binding with the lectin UEA‐I by surface plasmon resonance (SPR, on surface) and isothermal titration calorimetry (ITC, in solution). Our results indicate that PEG reduces the affinity of glycodendrimers towards lectins by steric hindrance in a molecular‐weight‐dependent fashion. Great differences were observed as a function of the PEG architecture, with diblock PEG‐dendritic copolymers benefiting from a positive entropic contribution (PEG folding), not seen in the dendritic‐PEG‐dendritic systems. The self‐inflicted steric stabilization of the PEGylated copolymers onto lectin clusters reveals the necessity of additional competitive experiments to fully assess the antiadhesive properties of PEG in biological environments ; Spanish Government. Grant Numbers: CTQ2015-69021-R, CTQ2012-34790, CTQ2014-61470-EXP Xunta de Galicia. Grant Number: GRC2014/040 ; SI

This work was financially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTQ2015‐ 69021‐R), the Consellería de Cultura, Educación e Ordenación Universitaria (GRC2014/040 and Centro Singular de Investigación de Galicia Accreditation 2016‐2019, ED431G/09), and the European Regional Development Fund (ERDF). M.F.‐V. thanks the Spanish Government for a FPU Fellowship ; Polyion complex (PIC) micelles incorporating PEG-dendritic copolymers display an unprecedented stability towards ionic strength that is amplified via hydrophobic interactions. The tridimensional orientation of peripheral hydrophobic linkers between charged groups and the globular/rigid dendritic scaffold maximizes this stabilization compared to PIC micelles from linear polymers. As a result, micelles stable at concentrations higher than 3 M NaCl are obtained, which represents the highest saline concentration attained with PIC micelles. Advantages of this stabilizing dendritic effect have been taken for the design of a robust, pH-sensitive micelle for the controlled intracellular release of the anticancer drug doxorubicin. This micelle displays a slightly higher toxicity, and distinctive mechanisms of cell uptake and intracellular trafficking relative to the free drug. The preparation of mixed PIC micelles by combining differently functionalized PEG-dendritic block copolymers has allowed the fine-tuning of their stability, paving the way towards the facile modulation of properties like biodegradability, drug loading, or the response to external stimuli ; SI