Chitosan hydrophobic domains are favoured at low degree of acetylation and molecular weight

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 aggregatesThis work was financially supported by the Spanish Government (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037)S

PEG-dendritic block copolymers for biomedical applications

The incorporation of poly(ethylene glycol) (PEG) chains at the focal point of dendrimers results in customizable platforms where the careful selection of the PEG length, the nature of the peripheral groups, and the structure and generation of the dendritic block entail materials for specific applications in the biomedical field. In this focus article, the synthesis, properties, and biomedical applications of PEG-dendritic block copolymers are discussed with examples in drug and gene delivery, tissue repair, and diagnosisThis work was financially supported by the Spanish MICINN (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037).S

Disclosing an NMR-Invisible Fraction in Chitosan and PEGylated Copolymers and Its Role on the Determination of Degrees of Substitution

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 acidThis 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)S

Stepwise Filtering of the Internal Layers of Dendrimers by Transverse-Relaxation-Edited NMR

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)S

SEQUENTIAL INDUCTION OF CHIRALITY IN POLY(PHENYLACETYLENE)S

Several hierarchical levels of chirality have been detected in functionalized poly(phenylacetylene)s (PPA).1 In this work we have studied the chirality induction throughout these levels in PPA functionalized with phenylglycine methyl ester groups, Fig. 1.2 These pendant groups force the PPA chain to lose its planar all-transoid shape to form helical structures. The chiral seed of the pendants, [(R)- or (S)-], dictates the preferent handedness of the helices, both the internal polyacetylene helical covalent backbone and the external helix formed by the side pendants which forms a complementary helix or counter-helix. In this work, we afford a full assessment of the interconnection between stereocenter and helix sources of chirality and the action of these polymers as chiral templates of other supra-molecular structures with inherited chiral properties. We then used VCD spectroscoy to demonstrate the chiral induction from the stereogenic centers to the backbone helix and from this to the pendant helix, which are largely promoted by two mechanisms: steric effects and hydrogen bonding. In addition, the VCD spectra supported that the helical setup of the pendants induces the solvent DMSO molecules to adopt a solvation helix around the polymer, thus proving how an achiral solvent becomes chirally organized owing to the template effect of the covalent polymer helices. A similar effect was observed in DMSO solutions of the monomeric units. Interestingly, this resulted in opposite helical sense to the one observed in the polymer with identical enantiomeric form.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Chiral nanostructure in polymers under different deposition conditions observed using atomic force microscopy of monolayers: poly(phenylacetylene)s as a case study

Dynamic poly(phenylacetylene)s (PPAs) adopt helical structures with different elongation or helical senses depending on the types of pendants. Hence, a good knowledge of the parameters that define their structures becomes a key factor in the understanding of their properties and functions. Herein, the techniques used for the study of the secondary structure of PPAs using atomic-force microscopy (AFM) are presented, with special attention directed towards the methods used for the preparation of monolayers, and their consequences in the quality of the AFM images. Thus, monolayers formed by drop casting, spin coating followed by crystallization or annealing, Langmuir–Blodgett and Langmuir–Schaefer methods, onto highly oriented pyrolytic graphite (HOPG) or mica, are described, together with the AFM images and the resulting helical structure obtained for different PPAs. Furthermore, some conclusions are drawn both on the adequacy of the different techniques for the formation of monolayers and on the solid supports utilized to elucidate the secondary structure of different PPAsThis work was supported by grants from MEC (CTQ2014-61470-EXP, CTQ2015-70519-P), ERDF and Xunta de Galicia (GRC2014/040)S

Real-Time Evaluation of Binding Mechanisms in Multivalent Interactions: A Surface Plasmon Resonance Kinetic Approach

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 mechanismsThis 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 contractS

Predicting PSR Filters by Transverse Relaxation Enhancements

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 drugsThis 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)S

Peripheral Functionalization of Dendrimers Regulates Internalization and Intracellular Trafficking in Living Cells

GATG (gallic acid-triethylene glycol) dendrimers represent appealing nanostructures for biomedical applications. The incorporation of specific ligands and targeting and imaging agents on their surface has resulted in promising tools in diagnosis and drug delivery. With the aim to further explore the versatility of GATG dendrimers in the biomedical field, in this work we study the effect of peripheral substitution on their uptake and intracellular trafficking in living cells. To this end, peripheral groups with different physicochemical properties and biological relevance have been installed on the surface of GATG dendrimers, and their interactions, uptake efficacy, and specificity for certain cell populations studied by confocal microscopy. Finally, this information was used to design a pH-sensitive drug delivery system for the selective release of cargo molecules inside cells after lysosomal localization. These results along with the easy functionalization and modular architecture of GATG dendrimers reveal these systems as promising nanotools in biomedicineThis work was financially supported by the Spanish MICINN (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037). M.F.-V. thanks the Spanish Ministry of Education for a FPU fellowshipS

GATG Dendrimers and PEGylated Block Copolymers: from Synthesis to Bioapplications

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/s12248-014-9642-3Dendrimers 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 fieldsThe 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)S