Cristóbal Verdugo-Escamilla

CRISTALES: a world to discover. An exhibition for schools and universities

The exhibition CRISTALES: a world to discover is a teaching/outreach activity whose main goals are to increase awareness of the importance of crystallography and its role in everyday life in modern society, motivate young people, and promote education and research in crystallography. CRISTALES is designed to inspire the audience with a careful design and a view of crystallography that places the emphasis not only on the most important contributions of crystallography to societys welfare, including new materials and biomedical research, but also on those aspects of crystallography related to art and the mind. This article describes the simplest version of the exhibition, composed of 14 posters that have been created specifically for schools and universities. Each poster displays an image that is both aesthetically powerful and scientifically intriguing, so as to provoke the curiosity of the students. The posters also contain a brief text explaining the image and its relation to crystallography and a QR code that links the poster to a web page containing further information.

Luminescent biomimetic citrate-coated europium-doped carbonated apatite nanoparticles for use in bioimaging: physico-chemistry and cytocompatibility

Nanomedicine covers the application of nanotechnologies in medicine. Of particular interest is the setup of highly-cytocompatible nanoparticles for use as drug carriers and/or for medical imaging. In this context, luminescent nanoparticles are appealing nanodevices with great potential for imaging of tumor or other targetable cells, and several strategies are under investigation. Biomimetic apatite nanoparticles represent candidates of choice in nanomedicine due to their high intrinsic biocompatibility and to the highly accommodative properties of the apatite structure, allowing many ionic substitutions. In this work, the preparation of biomimetic (bone-like) citrate-coated carbonated apatite nanoparticles doped with europium ions is explored using the citrate-based thermal decomplexing approach. The technique allows the preparation of the single apatitic phase with nanosized dimensions only at Eu3+ doping concentrations ≤0.01 M at some timepoints. The presence of the citrate coating on the particle surface (as found in bone nanoapatites) and Eu3+ substituting Ca2+ is beneficial for the preparation of stable suspensions at physiological pH, as witnessed by the ζ-potential versus pH characterizations. The sensitized luminescence features of the solid particles, as a function of the Eu3+ doping concentrations and the maturation times, have been thoroughly investigated, while those of particles in suspensions have been investigated at different pHs, ionic strengths and temperatures. Their cytocompatibility is illustrated in vitro on two selected cell types, the GTL-16 human carcinoma cells and the m17.ASC murine mesenchymal stem cells. This contribution shows the potentiality of the thermal decomplexing method for the setup of luminescent biomimetic apatite nanoprobes with controlled features for use in bioimaging.

Vapour Diffusion Route to Mineralize Graphene and Polymer Surfaces with Calcium Phosphate Intended for Biomedical Applications

After successful application of the sitting drop vapour diffusion route to deposit calcium phosphate layers on mica muscovite sheets, in this work we have extended the method to mineralize polymer surfaces (OSTE+) and bidimensional materials (graphene), aimed to prepare implants or scaffolds for nonload bearing applications in the medical sector. Thin octacalcium phosphate/apatite layers have been deposited on mica muscovite sheets. Thin apatite/octacalcium phosphate layers deposited on OSTE+ polymer lames. When graphene nanoflakes where used as support, this technique yielded apatite/graphene nanocomposites.

Biotechnological application of enzyme crystals, from microfluidic to batch production

Biocatalysts make use of the versatility, selectivity and specificity of enzymes to catalyze a variety of processes for the production of relevant compounds under mild conditions. One of the most common strategies to extend the lifetime under extreme conditions and to increase the efficiency of enzymes is their immobilization in different materials or the autoimmobilization by cross-linking. In this context, cross-linked enzyme crystals (CLECs), yet proven to be a better solution to enhance catalyst lifetime, recoverability, etc. when compared with cross-linked enzyme aggregates (CLEAs), have been almost abandoned [1]. Cross-linked enzyme crystals (CLECs) have been neglected although they are proven to be a better solution to enhance catalyst lifetime, recoverability, etc. when compared with cross-linked enzyme aggregates (CLEAs) [1]. We have recently demonstrated that the use of CLECs-based microreactors, shows unprecedented self-storage capability and stability as compared to standard biosensors, which cannot be stored for long periods due to quick denaturation of the enzymes (with lifetimes of weeks in the best case) [2]. We have further extended this concept by combining an enzymatic (lipase) microreactor, operating in continuous mode, with an optofluidic detection system [3] (Figure 1.a). The use of enzymatic catalytic reactions under microfluidic flow conditions reveals a promising technology with a number of strategic advantages such as the dramatic improvement of surface/volume ratios or enhanced energy consumption and mass transport, which are fundamental for the fabrication of novel biosensor systems based on CLECs. In this work, we have explored the use of different gels in order to control nucleation and growth of lipase crystals while providing a diffusion mass transport environment for the incorporation of cross-linkers inside the crystals, thus avoiding any osmotic shock. The production of Reinforced Cross-linked Lipase Crystals (RCLLCs), recovery, and enzymatic characterization are shown in this communication. RCLLCs have been used to pack a 10 cm chromatographic column, a scale-up representation of the microfluidic approach that operates in continuous flow (Figure 1.b). The characteristics and main features of both systems, micro and macro scale flow systems, are shown and compared. [1] Brady, D. et al. (2009). J. Biotech. Letters, 31, 1639-1650. [2] Conejero-Muriel, M. et al. (2015). Lab Chip, 15, 4083-4089. [3] Conejero-Muriel, M. et al., (2016). Anal. Chem. 88, 11919−11923.

Novel solid forms of the analgesic drug ethenzamide

The interest in multicomponent solid forms has increased in the last years within the pharmaceutical industry and also the solid-state community due to the possibility of obtaining materials with new properties [1]. Crystallization strategies, supported by solventand solid-based techniques, have also received attention in the search and development of methodologies for the screening of multicomponent crystals. In this work, ethenzamide, an anti-inflammatory and analgesic drug, was selected as a model drug to develop cocrystals on the basis of the synthon types using a series of phenolic coformers. Ethenzamide cocrystals and cocrystal solvates have been reported recently [2,3]. Liquid Assisted Grinding (LAG) and solution methods were used as synthetic tools. Attempts to produce cocrystals by LAG and Reaction Crystallization led to the formation of polycrystalline material. The solids obtained were then characterized by powder X-ray diffraction (PXRD), FT-IR and Raman spectroscopy. Recrystallization by slow solvent evaporation was carried out when the above-referred techniques strongly suggest the formation of a new solid form. The structure of five new multicomponent solids has been determined by single crystal X-ray diffraction. Additional stability studies have been performed at controlled relative humidity conditions and followed by PXRD.

Pyrazinamide cocrystals with dicarboxylic acids by liquid-assisted grinding

Cocrystals have received much attention in recent years, especially in the pharmaceutical industry because they offer a way to alter the physical properties of a drug without affecting its therapeutic effects [1]. Furthermore, cocrystals offer an alternative to salts, hydrates and solvates, traditionally used by the pharmaceutical industry. In this work, pyrazinamide, a first-line antibacterial drug used in monotherapy and also in combination to treat tuberculosis [2], was selected as a model drug to develop cocrystals on the basis of the synthon types by liquid-assisted grinding (LAG), using a series of GRAS (Generally Regarded As Safe) coformers. Novel forms were synthesized and characterized by X-ray powder diffraction (XRPD) and Raman spectroscopy. Crystals suitable for single crystal X-ray diffraction were grown from the powder obtained by LAG method and the structures of these novel forms were solved.