About Helices and Solvents: VCD and more

Intermolecular forces drive self-organization of molecules, which is ultimately the origin of most the physical and chemical phenomena in Nature. Molecules able to interact themselves by non-covalent forces, as hydrogen bonding and/or hydrophobic attractions, usually form macrostructures in condensed phases (solid, solution). The properties of these aggregates depend of three main factors: the structural and chemical features of the molecules, the nature of intermolecular forces and the environment. The first two drive aggregation in solid state, while in solution the role of the solvent become determinant as it can induce a variety of structural effects on the aggregation behaviour of the solute. In the case of chiral molecules, this property is transferred to the aggregates and supramolecular chirality appears. Here we present our research on chiral molecules that self-organize in solution forming helical structures. We use VCD as the main chiroptical tool, but also supported by other chiroptical spectroscopies (ECD, ROA) and theoretical modelling. In our first steps, we studied the effect of modulating the environmental settings on the helices. Thus, helix handedness was proved highly and reversibly dependent on factors as pH or ionic strength in peptide-mimetic hydrogelators. We also observe how the initial conditions (concentration, temperature) were capable of controlling the helix structure of oligo-p-phenylene-based polymers towards kinetic or thermodynamics pathways. Besides, the structure of the helices can also be the consequence of direct solvent-solute interactions. In this way, we have demonstrated that an achiral solvent can act as a template for chiral organization of N-heterotriangulenes-based organogelators, thus showing the different levels of complexity of the hierarchical organization of supramolecular polymers. But the solvent-helix interactions can be bidirectional. As a nice example, we recorded chiral signals which can be only assigned to the organization of the solvent molecules around helical aggregates of phenylglycine functionalized poly(phenylacetylene)s. The solvent molecules thus form a first solvation shell to which the helix chirality is transferred. The helices would act therefore as a template of the solvent molecules, and the chirality of this external helix would be fully controlled by the solute.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Quiralidad en Estructuras Supramoleculares: Espectroscopías de Dicroísmo Circular (ECD, VCD y ROA)

El término quiral procede de la palabra griega Kheir (χείρ) cuya traducción al castellano es mano. En la actualidad usamos la palabra quiral para definir aquellos objetos que, como la mano derecha y la mano izquierda, no son superponibles a su imagen especular. La utilización de la palabra quiralidad en el mundo molecular se la debemos a Lord Kelvin, (1824-1907) que la introdujo en 1884: “Llamo a cualquier figura geométrica, o grupo de puntos, quirales, y digo que tiene quiralidad, si su imagen en un espejo plano, diseñado idealmente, no puede coincidir consigo mismo." Hasta finales del siglo pasado el interés de las moléculas quirales se centraba en la industria y en investigaciones farmacológicas. En la actualidad otros campos de investigación, como la electrónica orgánica, tratan de aprovechar los beneficios estructurales y ópticos que pueden presentar los materiales quirales. Las propiedades de un material molecular dependen tanto de la naturaleza de sus constituyentes como de las interacciones entre ellos. La presencia de quiralidad en las moléculas orgánicas puede mejorar ambas características. Por un lado aporta una nueva propiedad al material, haciéndolo más selectivo (reconocimiento enantiomérico) y con nuevas propiedades ópticas, y por otro lado, la quiralidad influye en la conformación molecular, modificando sus interacciones con otras moléculas. Son precisamente estas interacciones intermoleculares las que promueven procesos de ensamblaje, desmontaje e intercambio entre los sistemas, es decir, son las que generan materiales dinámicos. Si conseguimos controlar, mediante estímulos externos, las interacciones moleculares conseguiremos almacenar, recuperar y transferir información a nivel molecular. Por ello, la combinación de quiralidad e interacciones intermoleculares es actualmente un tema de gran interés en la comunidad científica. Por tanto, existe un creciente interés sobre estos materiales y sus aplicaciones que justifican una Tesis destinada a estudiar la relación existente entre la estructura de estos materiales quirales y sus posibles aplicaciones. En la presente Tesis presentamos el estudio de cuatro familias de sistemas quirales en orden creciente de complejidad molecular, desde la molécula más pequeña al sistema supramolecular más elaborado. En primer lugar, nos centramos en estudiar la molécula más pequeña posible que presenta quiralidad axial, el difluoroaleno, y su posterior incorporación como ladrillo constitutivo de estructuras macrocíclicas. De este modo conseguimos moléculas discretas de diferente simetría cuya principal característica es su intensa respuesta dicroica. El estudio de esta familia de moléculas constituye el capítulo 3. En el capítulo siguiente nos introducimos en el concepto de estructuras supramoleculares quirales, realizando un estudio teórico del origen de la señal dicroica en sistemas agregados quirales. El análisis lo realizamos utilizando como modelo una molécula aquiral de simetría C3. Las conclusiones del capítulo anterior servirán como base para comprender los resultados presentados en el capítulo quinto, dedicado a la agregación en geles formados por moléculas quirales. Estudiaremos dos familias de compuestos quirales, porfirinas y oligo-para-fenilenos, cuyas propiedades como materiales moleculares van a variar en función del número de centros quirales presentes en su estructura. El último capítulo de esta Tesis se dedica a la quiralidad en el mundo biológico, en concreto en sistemas peptidomiméticos y proteínas, caracterizados por la estrecha relación que existe entre la estructura tridimensional y su funcionalidad. En resumen, en la presente Tesis hemos abordado el estudio de cuatro familias de sistemas quirales que encuentran aplicaciones en el campo de la electrónica orgánica y de la bioquímica

Chiroptical Spectroscopy of C3 Molecules

The relevance of molecules with C3 symmetry comes from the fact of many of them, upon assembling as columnar helical macromolecules, are ideal platform for electro-optical devices, for example as liquid crystals. The properties of these devices are highly dependent of the structure of the bulk aggregates, and consequently they can be controlled by modifying the position and nature of the stereocenters in the molecular building blocks. In this work we present an electronic and vibrational chiroptical study on a series of star-shaped molecules based on the octopolar C3-symmetric 1,3,5-(phenylene-ethynylene)-benzene block.Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tec

Variations in the Thickness of the Plantar Fascia After Training Based in Training Race. A Pilot Study

Plantar fascia (PF) is a connective tissue made up of mostly type 1 collagen that is subjected to constant loads. This study evaluated the effect of continuous running on tissue stress in the PF by measuring changes in the thickness of the PF using ultrasound scans. It was a cross-sectional study involving 24 runners from the University of Valen- cia, recruited as volunteers between December 2018 and February 2019. A variety of data was recorded: (age, body mass index, type of footwear, number of workouts per week, KM run per week, sports injuries in the last year, pre and postrace ultrasound PF measurements). There were significant differences in the 3 postrace meas- urements of the left foot (<0.001). PF thicknesses were measured before and after running, with a minimal average difference of 0.4 mm in the medial and central fascicles, and 0.3 mm in the lateral fascicle. We observed PF thick- nesses above 4mm in asymptomatic patients with no signs of vascularisation, proving that increased PF thickness is not the only criterion for diagnosis of plantar fasciitis.Funding for open access charge: Universidad de Málaga / CBU

Hospitalisation cost of patients with diabetic foot ulcers in Valencia (Spain) in the period 2009-2013 : a retrospective descriptive analysis

Ulcers are the main cause of hospitalisation and clinical complications in patients with diabetes. We analyse the length and cost of hospital stay of patients with diabetic foot ulcers, taking into consideration that hospitalisation and, if necessary, amputation represent the greatest area of expense to the healthcare system for such patients. This analysis focuses on the treatment provided to these patients in public hospitals in the region of Valencia (Spain), registered in the Spanish Minimum Basic Data Set, during the period 2009-2013. The number of acute hospital admissions in this respect is increasing and has a high socioeconomic cost. During the study period, there were over 2700 hospital admissions, an average of nearly 550 per year. The total hospital stay for these patients was 30,886 days, with an average of 11.4 days and a cost of 7633 per admission. Preventive policies and the deployment of multidisciplinary teams are essential to reduce these costs and avoid future complications such as amputation

A Systematic review to identify the effects of biologics in the feet of patients with rheumatoid arthritis

Background and objective: Ninety percent of patients with rheumatoid arthritis (RA) feel foot pain during the disease process. Pharmacological treatment of RA has a systematic effect on the body and includes: Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. The objective of our review was to examine the impact of biologics on patients with RA 'foot. Methods and material: A systematic review of randomized control trials and observational studies that evaluated the efficacy of biologics against other pharmacological treatment, and included a foot outcome measure. The search covered MEDLINE Ovid, Pubmed, CINAHL, Cochrane Library, Evidence Search, and Web of Science. Risk of bias was evaluated using Cochrane guidance and the Newcastle Ottawa Scale adapted version. Results: A total of eight studies fully met the inclusion criteria: Three randomized control trials, and five observational studies were the basis of our review. A total sample of 1856 RA patients with RA treatment participated. The use of biologics was not associated as a risk factor for post-operative surgical site infection or delayed wound healing. The benefits of biologics, in terms of the disease evolution, were assessed using Xray. Conclusion: Evidence suggests that the use of biologics is not a risk factor for post-operative surgical site infection or delayed wound healing. The use of biologics presents benefits in terms of the disease evolution assessed through X-ray

Raman Optical Activity Monitoring the Interaction of Globular Proteins with Surfactants

Protein denaturation by surfactants is related with topic as pharmaceutics, cosmetics, paints or biotechnology. This phenomenon is highly dependent on the physico-chemical properties of the denaturing agents. In this communication we report the ROA spectra of bovine serum albumin in the presence of different surfactants, which share a common hydrophobic tail, with the objerctive of correlating the structural specificities of the surfactant-protein interaction with the ROA signatures by following the protein unfolding process.In our work we propose two new groups of ROA marker bands related with the protein unfolding induced by surfactants. This work represents one of the first applications of ROA to study the interaction of a protein with surfactants, and a new proof of the ability of this chiroptical technique to see beyond that can be seen with conventional Raman spectroscopy.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sequential Induction of Chirality in Helical Polymers: From the Stereocenter to the Achiral Solvent

This is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of the Physical Chemistry Letters, Copyright © 2018 American Chemical Society after peer review and technical edityng by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/10.1021/acs.jpclett.8b00519Several steps of chiral induction have been detected in poly(phenylacetylene)s among their different hierarchical levels of chirality by vibrational circular dichroism, namely, (i) from the stereogenic centers to the innermost polyacetylene helical covalent backbone (helixint), (ii) from this to the external helix (helixext) formed by the side phenyl pendants that form a complementary helix or counter-helix, and (iii) from this pendant helix to the helical solvation sphere (helixsolv.), the last one being observed along this work. The pendant to polyene backbone chiral induction determines the helical structure adopted by the polymer and therefore the solvation helix. This helical structure is promoted by two mechanisms: steric effects and hydrogen bonding. An important finding concerns the demonstration by VCD of how an achiral solvent becomes chirally organized owing to the template effect of the covalent polymer helices, an effect that is silent to other structural techniques such as ECD or AFM and that hence significantly broadens the scope of these previous analysesFinancial support from Ministerio de Ciencia e Innovación [CTQ2014-61470-EXP, CTQ2015- 69391-P, FPI (R. Rodríguez), FPU (S. Medina), Juan de la Cierva postdoctoral Fellowship FJCI- 2015-23531 (B.Nieto-Ortega)], Xunta de Galicia (GRC2014/040, Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09) and the European Regional Development Fund (ERDF) is gratefully acknowledgedS

Tuning Proton Conductivity in Alkali Metal Phosphonocarboxylates by Cation Size-Induced and Water-Facilitated Proton Transfer Pathways

The structural and functional chemistry of a family of alkali-metal ions with racemic R,S-hydroxyphosphonoacetate (M-HPAA; M = Li, Na, K, Cs) are reported. Crystal structures were determined by X-ray data (Li+, powder diffraction following an ab initio methodology; Na+, K+, Cs+, single crystal). A gradual increase in dimensionality directly proportional to the alkali ionic radius was observed. [Li3(OOCCH(OH)PO3)-(H2O)4]·H2O (Li-HPAA) shows a 1D framework built up by Li-ligand “slabs” with Li+ in three different coordination environments (4-, 5-, and 6-coordinated). Na-HPAA, Na2(OOCCH(OH)PO3H)(H2O)4, exhibits a pillared layered “house of cards” structure, while K-HPAA, K2(OOCCH(OH)PO3H)(H2O)2, and Cs-HPAA, Cs(HOOCCH(OH)-PO3H), typically present intricate 3D frameworks. Strong hydrogen-bonded networks are created even if no water is present, as is the case in Cs-HPAA. As a result, all compounds show proton conductivity in the range 3.5 × 10−5 S cm−1 (Cs-HPAA) to 5.6 × 10−3 S cm−1 (Na-HPAA) at 98% RH and T = 24 °C. Differences in proton conduction mechanisms, Grothuss (Na+ and Cs+) or vehicular (Li+ and K+), are attributed to the different roles played by water molecules and/or proton transfer pathways between phosphonate and carboxylate groups of the ligand HPAA. Upon slow crystallization, partial enrichment in the S enantiomer of the ligand is observed for Na-HPAA, while the Cs-HPAA is a chiral compound containing only the S enantiomer.Proyectos nacionales MAT2010-15175 y MAT2013-41836-

Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease

Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum