Multi-component supramolecular gels for the controlled crystallization of drugs : Synergistic and antagonistic effects

The applicability of multi-component gels, based on the combination of Lys-based dendrons and alkyl amines, for the crystallization of common drugs is presented. The results presented herein demonstrate that active pharmaceutical ingredients (APIs) with no carboxylic acid in their structure readily crystallize inside the organogels formed by a second generation lysine-based dendron (G2-Lys) and aliphatic amines. The thermodynamic parameters (ΔHdiss, ΔSdiss and ΔGdiss) of the corresponding three-component mixture (API + G2-Lys dendron + amine) have been calculated by using VT 1H NMR. Interestingly, the presence of carbamazepine (CBZ) in the mixture of G2-Lys and decylamine allows efficient gelation at room temperature in contrast with the behaviour observed for an unmodified G2-Lys dendron and decylamine mixture that only forms toluene gels at -20 °C-a synergistic effect in which the API enhances gelation. On the other hand, aspirin (ASP) or indomethacine (IND), that possess a carboxylic acid in their structure, do not crystallize inside the organogel formed by G2-Lys dendron and the amine-indeed they prevent formation of the gel. The Ka values of the complexes G2-Lys⋯decylamine and IND⋯decylamine have been calculated by 1H NMR titrations in toluene-d8. The higher Ka value for the complex IND⋯decylamine justifies that this pair is thermodynamically favoured thus preventing the formation of the complex between the Lys-based dendron and the amine, which underpins gel fibre assembly, and also preventing effective crystallization of the API-an antagonistic effect. Overall, these results demonstrate the active roles played by all components when multi-component gels are used for API crystallisation

Synchrotron Radiation Pair Distribution Function Analysis of Gels in Cements

The analysis of atomic ordering in a nanocrystalline phase with small particle sizes, below 5 nm, is intrinsically complicated because of the lack of long-range order. Furthermore, the presence of additional crystalline phase(s) may exacerbate the problem, as is the case in cement pastes. Here, we use the synchrotron pair distribution function (PDF) chiefly to characterize the local atomic order of the nanocrystalline phases, gels, in cement pastes. We have used a multi r-range analysis approach, where the ~4–7 nm r-range allows determining the crystalline phase contents; the ~1–2.5 nm r-range is used to characterize the atomic ordering in the nanocrystalline component; and the ~0.2–1.0 nm r-range gives insights about additional amorphous components. Specifically, we have prepared four alite pastes with variable water contents, and the analyses showed that a defective tobermorite, Ca11Si9O28(OH)2 8.5H2O, gave the best fit. Furthermore, the PDF analyses suggest that the calcium silicate hydrate gel is composed of this tobermorite and amorphous calcium hydroxide. Finally, this approach has been used to study alternative cements. The hydration of monocalcium aluminate and ye’elimite pastes yield aluminum hydroxide gels. PDF analyses show that these gels are constituted of nanocrystalline gibbsite, and the particle size can be as small as 2.5 nmThis work has been supported by Spanish MINECO through BIA2014-57658-C2-2-R, which is co-funded by FEDER, BIA2014-57658-C2-1-R and I3 (IEDI-2016-0079) grants. We also thank CELLS-ALBA (Barcelona, Spain) for providing synchrotron beam time at BL04-MSPD beamline. Finally, we thank Prof. Simon Billinge, Long Yang and Monica Dapiaggi for their help with the PDF script and simulations for Ca(OH)2 scattering dat

Electrochemically-triggered spatially and temporally resolved multi-component gels

Spatial control over gelation with low molecular weight gelators is possible using an electrochemically-driven pH triggering method. Gelation occurs at the electrode surface. We show here that composition control in multi-component low molecular weight hydrogels can also be achieved, allowing simultaneous spatial, temporal and compositional control

Multistep kinetic self-assembly of DNA-coated colloids

Self-assembly is traditionally described as the process through which an initially disordered system relaxes towards an equilibrium ordered phase only driven by local interactions between its building blocks. However, This definition is too restrictive. Nature itself provides examples of amorphous, yet functional, materials assembled upon kinetically arresting the pathway towards the ground state. Kinetic self-assembly is intrinsically more flexible and reliable than its equilibrium counterpart, allowing control over the morphology of the final phase by tuning both the interactions and the thermodynamic pathway leading to kinetic arrest. Here we propose strategies to direct the gelation of two-component colloidal mixtures by sequentially activating selective interspecies and intra-species interactions. We investigate morphological changes in the structure of the arrested phases by means of event driven molecular dynamics (MD) simulations and experimentally using DNA-coated colloids (DNACCs). Our approach can be exploited to finely tune the morphology of multicomponent nano- or micro-porous materials with possible applications in hybrid photovoltaics, photonics and drug delivery.Comment: Please email for Supplementary Information

Synchrotron x-ray pair distribution function: A tool to characterize cement gels

Cement matrices contain large amounts of crystalline phases jointly with amorphous and/or nanocrystalline phases. Consequently, their analyses are very challenging. Synchrotron powder diffraction in combination with the pair distribution function (PDF) methodology is very useful to characterize such complex cement pastes. This work is focused on the study of the short and medium range atomic arrangement(s) in the different nanocrystalline gels which are present in the cement pastes through total scattering Pair Distribution Function quantitative phase analyses.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Acknowledgments: We thank CELLS-ALBA (Barcelona, Spain) for providing synchrotron beam time and the financial support by BIA2014-57658-C2-1-R and BIA2014-57658-C2-2-R, which is co-funded by FEDER. We also thank Dr. Monica Dapiaggi for her contribution with the PDF study of Ca(OH)2 monolayer

A simple method for the production of large volume 3D macroporous hydrogels for advanced biotechnological, medical and environmental applications

The development of bulk, three-dimensional (3D), macroporous polymers with high permeability, large surface area and large volume is highly desirable for a range of applications in the biomedical, biotechnological and environmental areas. The experimental techniques currently used are limited to the production of small size and volume cryogel material. In this work we propose a novel, versatile, simple and reproducible method for the synthesis of large volume porous polymer hydrogels by cryogelation. By controlling the freezing process of the reagent/polymer solution, large-scale 3D macroporous gels with wide interconnected pores (up to 200??m in diameter) and large accessible surface area have been synthesized. For the first time, macroporous gels (of up to 400?ml bulk volume) with controlled porous structure were manufactured, with potential for scale up to much larger gel dimensions. This method can be used for production of novel 3D multi-component macroporous composite materials with a uniform distribution of embedded particles. The proposed method provides better control of freezing conditions and thus overcomes existing drawbacks limiting production of large gel-based devices and matrices. The proposed method could serve as a new design concept for functional 3D macroporous gels and composites preparation for biomedical, biotechnological and environmental applications

Self-Sorting Microscale Compartmentalized Block Copolypeptide Hydrogels

Multicomponent interpenetrating network hydrogels possessing enhanced mechanical stiffness compared to their individual components were prepared via physical mixing of diblock copolypeptides that assemble by either hydrophobic association or polyion complexation in aqueous media. Optical microscopy analysis of fluorescent-probe-labeled multicomponent hydrogels revealed that the diblock copolypeptide components rapidly and spontaneously self-sort to form distinct hydrogel networks that interpenetrate at micron length scales. These materials represent a class of microscale compartmentalized hydrogels composed of degradable, cell-compatible components, which possess rapid self-healing properties and independently tunable domains for downstream applications in biology and additive manufacturing

Supercomplex-Associated Cox26 Protein Binds to Cytochrome \u3cem\u3ec\u3c/em\u3e Oxidase

Here we identified a hydrophobic 6.4 kDa protein, Cox26, as a novel component of yeast mitochondrial supercomplex comprising respiratory complexes III and IV. Multi-dimensional native and denaturing electrophoretic techniques were used to identify proteins interacting with Cox26. The majority of the Cox26 protein was found non-covalently bound to the complex IV moiety of the III–IV supercomplexes. A population of Cox26 was observed to exist in a disulfide bond partnership with the Cox2 subunit of complex IV. No pronounced growth phenotype for Cox26 deficiency was observed, indicating that Cox26 may not play a critical role in the COX enzymology, and we speculate that Cox26 may serve to regulate or support the Cox2 protein. Respiratory supercomplexes are assembled in the absence of the Cox26 protein, however their pattern slightly differs to the wild type III–IV supercomplex appearance. The catalytic activities of complexes III and IV were observed to be normal and respiration was comparable to wild type as long as cells were cultivated under normal growth conditions. Stress conditions, such as elevated temperatures resulted in mild decrease of respiration in non-fermentative media when the Cox26 protein was absent