Fundacion Fraunhofer Chile Research

Santiago, Chile

Fundacion Fraunhofer Chile Research

Santiago, Chile
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Ratjen L.,University of Strasbourg | Ratjen L.,Fundacion Fraunhofer Chile Research | Ratjen L.,Andrés Bello University | Vantomme G.,University of Strasbourg | Lehn J.-M.,University of Strasbourg
Chemistry - A European Journal | Year: 2015

The displacement of molecular structures from their thermodynamically most stable state by imposition of various types of electronic and conformational constraints generates highly strained entities that tend to release the accumulated strain energy by undergoing either structural changes or chemical reactions. The latter case amounts to strain-induced reactivity (SIR) that may enforce specific chemical transformations. A particular case concerns dynamic covalent chemistry which may present SIR, whereby reversible reactions are activated by coupling to a high-energy state. We herewith describe such a dynamic covalent chemical (DCC) system involving the reversible imine formation reaction. It is based on the formation of strained macrocyclic bis-imine metal complexes in which the macrocyclic ligand is in a high energy form enforced by the coordination of the metal cation. Subsequent demetallation generates a highly strained free macrocycle that releases its accumulated strain energy by hydrolysis and reassembly into a resting state. Specifically, the metal-templated condensation of a dialdehyde with a linear diamine leads to a bis-imine [1+1]-macrocyclic complex in which the macrocyclic ligand is in a coordination-enforced strained conformation. Removal of the metal cation by a competing ligand yields a highly reactive [1+1]-macrocycle, which then undergoes hydrolysis to transient non-cyclic aminoaldehyde species, which then recondense to a strain-free [2+2]-macrocyclic resting state. The process can be monitored by 1H NMR spectroscopy. Energy differences between different conformational states have been evaluated by Hartree-Fock (HF) computations. One may note that the stabilisation of high-energy molecular forms by metal ion coordination followed by removal of the latter, offers a general procedure for producing out-of-equilibrium molecular states, the fate of which may then be examined, in particular when coupled to dynamic covalent chemical processes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Encina C.,University of Chile | Vergara C.,Fundacion Fraunhofer Chile Research | Gimenez B.,University of Santiago de Chile | Oyarzun-Ampuero F.,University of Chile | Robert P.,University of Chile
Trends in Food Science and Technology | Year: 2016

Polyunsaturated fatty acids, especially long-chain polyunsaturated omega-3 fatty acids (LCω3-PUFA), are essential in human nutrition because they play an important role in humans and prevent several diseases. Fish oil is a natural source of LCω3-PUFA that can be incorporated into food products. One of the major drawbacks of oils containing a high amount of LCω3-PUFA, such as fish oils, is their high susceptibility to oxidation and unpleasant flavours. Microencapsulation of fish oil by spray-drying has been proposed as a strategy to retard lipid auto-oxidation, improving oil stability, prolonging its shelf life, limiting the development of off-flavours and controlling the release into food. The encapsulation of fish oil by conventional spray-drying has been performed by preparing fish oil-in-water emulsions (micro- or nano-sized) by applying high shearing forces. The objective of this review is to compile the scientific research on the encapsulation of fish oil to discuss the main formulation and process variables that affect the physicochemical properties of the fish oil microparticles obtained by conventional spray-drying, the stability of fish oil during storage and the application of fish oil microparticles in food systems. An alternative strategy to conventional spray-drying (water-free spray-drying) is also proposed. © 2016 Elsevier Ltd

Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.3.1-01 | Award Amount: 8.64M | Year: 2013

Plant natural products have been utilised by human civilisation for millennia, providing vital medicines and essential dietary components. More recently bioactive compounds from plant sources have been used in cosmetics, as health supplements and are important components of feedstuffs. Despite significant investments new activities and new sustainable biosources are required to alleviate our reliance on chemical synthesis. In the DISCO project we aim to address these issues and create a framework that can act as a generic pipeline capable of taking discovery through application and validation, to translation and industrial valorisation. Key aspects of the project will be concerned with (i) translating discovery into industrial feasibility and/or commercialisation, (ii) transfer our knowledge gained optimising isoprenoid/terpenoid production to other important terpenoids and different classes of natural products, (iii) maintaining and incorporating the very latest technologies into both the discovery and translational pipelines and (iv) develop green factories with integrated biorefining pipelines to reduce or eliminate chemical refining and thus environmental impact. The bioactive molecules and their biochemical pathways targeted include, carotenoids (including apo-carotenoids), terpenoids and tropane alkaloid. For example; ketocarotenoids which are used as colorants in feedstuffs especially aquaculture; colourless carotenes such as phytoene and phytofluene, which are important bioactive ingredients of cosmetics; apo-carotenoids from saffron which are colorants and potent bioactives; the terpenoid solanesol which is used in the production of Coenzyme Q10 and the alkaloid scopolamine which is used as analgesic. The project will have real-life impacts reducing environmental impact, provide new material to benefit human activities and stimulate economic development.

Salvador-Morales C.,George Mason University | Brahmbhatt B.,George Mason University | Marquez-Miranda V.,Andrés Bello University | Araya-Duran I.,Andrés Bello University | And 9 more authors.
Langmuir | Year: 2016

Currently, several challenges prevent poly(lactic-co-glycolic acid) (PLGA) particles from reaching clinical settings. Among these is a lack of understanding of the molecular mechanisms involved in the formation of these particles. We have been studying in depth the formation of patchy polymeric particles. These particles are made of PLGA and lipid-polymer functional groups. They have unique patch-core-shell structural features: hollow or solid hydrophobic cores and a patchy surface. Previously, we identified the shear stress as the most important parameter in a patchy particle's formation. Here, we investigated in detail the role of shear stress in the patchy particle's internal and external structure using an integrative experimental and computational approach. By cross-sectioning the multipatch particles, we found lipid-based structures embedded in the entire PLGA matrix, which represents a unique finding in the PLGA field. By developing novel computational fluid dynamics and molecular dynamics simulations, we found that the shear stress determines the internal structure of the patchy particles. Equally important, we discovered that these particles emit a photoacoustic (PA) signal in the optical clinical imaging window. Our results show that particles with multiple patches emit a higher PA signal than single-patch particles. This phenomenon most likely is due to the fact that multipatchy particles absorb more heat than single-patchy particles as shown by differential scanning calorimetry analysis. Furthermore, we demonstrated the use of patchy polymeric particles as photoacoustic molecular probes both in vitro and in vivo studies. The fundamental studies described here will help us to design more effective PLGA carriers for a number of medical applications as well as to accelerate their medical translation. © 2016 American Chemical Society.

PubMed | University for Development, Bernardo O'Higgins University, Andrés Bello University and Fundacion Fraunhofer Chile Research
Type: Journal Article | Journal: Nanoscale research letters | Year: 2016

Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino-terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes.

Camarada M.B.,University of Santiago de Chile | Marquez-Miranda V.,Andrés Bello University | Marquez-Miranda V.,Fundacion Fraunhofer Chile Research | Araya-Duran I.,Andrés Bello University | And 5 more authors.
Physical Chemistry Chemical Physics | Year: 2015

Cationic dendrimers, such as PAMAM, are known to be positively charged at neutral pH allowing their unspecific interaction with proteins and other cellular components. Especially, ferritin, which has an important role in iron homeostasis, presents a negative electrostatic potential at the 3-fold channel. This channel is important in the functionality of ferritin because it allows the iron entry into its inner cavity. In this way, the interaction between the protonated terminal amines of the dendrimer and the negatively charged 3-fold channels of ferritin is expected. Experimental measurements demonstrated that PAMAM G4 inhibits the iron storage properties of L-chain human ferritin (L-Ftn). Molecular dynamics simulations have been used to analyze the specific interaction between PAMAM G4 and L-Ftn. Results show that PAMAM G4 effectively interacts with the 3-fold channels of L-Ftn, suggesting that this interaction is responsible for the inhibition of the iron storage properties of L-Ftn. This journal is © the Owner Societies.

Vilos C.,Andrés Bello University | Vilos C.,University of Santiago de Chile | Morales F.A.,Andrés Bello University | Solar P.A.,Andrés Bello University | And 16 more authors.
Biomaterials | Year: 2013

This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded. The Fourier transform infrared spectroscopy suggests the formation of a short-lived crystalline phase, also observed in the CG simulations, and transmission electron microscopy revealed branched structures on the surface of particles, which disappeared after 4 days. Biological analyses indicated that these particles have a 48-h window of toxicity protection, allowing for the endocytosis of the particle by the cells; this finding was corroborated by confocal microscopy and flow cytometry. The low cost to synthesize PHBV using microorganisms and the potential chemical modifications of the polymer make it attractive for inexpensive, large-scale pharmaceutical production. © 2013 Elsevier Ltd.

Camarada M.B.,Fundacion Fraunhofer Chile Research | Camarada M.B.,Andrés Bello University | Zuniga M.,Fundacion Fraunhofer Chile Research | Zuniga M.,University of Talca | And 3 more authors.
Chemical Physics Letters | Year: 2014

In this study, a structural and thermodynamical characterization of the complexation process of amine-terminated PAMAM G0 dendrimer with metal ions, commonly present in wastewater, was carried out using computational chemistry approaches. Relevant information about the geometry, charge distribution and affinity of metal cations confirmed that, in a tetragonal field, the most stable coordination site corresponds to the core of the dendrimer. This interaction is established via the tertiary nitrogen of the ethylenediamine core and oxygen atoms belonging to the carbonyl site of the amide groups. Independently of the PAMAM G0 fragment or coordination site, the binding energy of the metal ions exhibited the following trend Cu(II) > Ni(II) > Zn(II), which is in agreement with previous experimental studies. © 2014 Elsevier B.V. All rights reserved.

Marquez-Miranda V.,Andrés Bello University | Marquez-Miranda V.,Fundacion Fraunhofer Chile Research | Camarada M.B.,University of Santiago de Chile | Araya-Duran I.,Andrés Bello University | And 7 more authors.
PLoS ONE | Year: 2015

Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as nonviral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. Copyright: © 2015 Márquez-Miranda et al.

Fundacion Fraunhofer Chile Research and University of Talca | Date: 2013-11-22

The present invention considers derivatized nanomolecules with proven effectiveness to bind to actinides, more specifically uranium, during in vivo, ex vivo, in vitro or in situ assays. When assayed in vivo, the invention showed a reduction in at least kidney damage due to exposition to uranium.

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