A Spectroscopic study of colchicine in the solid state and in solution by multinuclear magnetic resonance and vibrational circular dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.Peer Reviewe

Simulation of electron transport and secondary emission in a photomultiplier tube and experimental validation

[EN] The electron amplification and transport within a photomultiplier tube (PMT) has been investigated by developing an in-house Monte Carlo simulation code. The secondary electron emission in the dynodes is implemented via an effective electron model and the Modified Vaughan¿s model, whereas the transport is computed with the Boris leapfrog algorithm. The PMT gain, rise time and transit time have been studied as a function of supply voltage and external magnetostatic field. A good agreement with experimental measurements using a Hamamatsu R13408-100 PMT was obtained. The simulations have been conducted following different treatments of the underlying geometry: three-dimensional, two-dimensional and intermediate (2.5D). The validity of these approaches is compared. The developed framework will help in understanding the behavior of PMTs under highly intense and irregular illumination or varying external magnetic fields, as in the case of prompt gamma-ray measurements during pencil-beam proton therapy; and aid in optimizing the design of voltage dividers with behavioral circuit models.This work was supported by Conselleria de Educación, Investigación, Cultura y Deporte (Generalitat Valenciana) under grant numbers CDEIGENT/2019/011 and CDEIGENT/2021/012. P. Martín-Luna is supported by the Ministerio de Universidades (Gobierno de España), Spain under Grant Number FPU20/04958. We thank Hamamatsu (V. Sánchez, D. Castrillo) for technical support and guidance; R. Carrasco (IFIC) and P. Wohlfahrt (Siemens Healthineers) for the CT scanning; D. Calvo and D. Real (KM3net-IFIC) for their LED test platform, the electronics and maintenance services at IFIC for excellent support; and K. Albiol, J. V. Casaña-Copado, A. Gallas Torreira, E. Lemos Cid, G. Pausch, A. Pazos Álvarez, E. Pérez Trigo, S. Rit, A. Ros, J. Roser, J. Stein, J. L. Taín and R. Viegas for useful discussions.Martín-Luna, P.; Esperante, D.; Fernández Prieto, A.; Fuster-Martínez, N.; García Rivas, I.; Gimeno, B.; Ginestar Peiro, D.... (2024). Simulation of electron transport and secondary emission in a photomultiplier tube and experimental validation. Sensors and Actuators A Physical. 365:1-10. https://doi.org/10.1016/j.sna.2023.11485911036

Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2–12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated

Evaluation of Poly(N-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.This research was supported by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) and Co-financed by the European Union (FEDER) “A way to make Europe” (project references SBPLY/17/000376 and SBPLY/21/180501/000097) and by the Ministerio de Ciencia, Innovación y Universidades (RTI2018-096328-B-I00). Altea Soto was funded by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) M. Asunción Barreda-Manso is funded by the Council of Health of the Regional Government of Castilla La Mancha (Spain), through: “Convocatoria de Ayudas Regionales a la Investigación en Biomedicina y Ciencias de la Salud” (II-2020_05). Irene Novillo Algaba is funded by the Next Generation Funds of the European Union through the “Programa Investigo”.Peer reviewe

Desmotropy in reduced plumbagins: α- and β-Dihydroplumbagins

A report of 1933 about the desmotropy of dihydroplumbagin was examined using both DFT calculations and high field NMR experiments. It was concluded that the report was essentially correct because both tautomers were isolated and characterized. © 2008 Elsevier B.V. All rights reserved.Peer Reviewe

A new macrocyclic dipyrazolate salt of diazatetraester structure able to efficiently and selectively interact with psychotropic phenethylammonium salts: Influence of the amine substituents on the stability of the ammonium dipyrazolate complexes

The equilibrium stability constants (Ks) of a series of ammonium pyrazolate complexes [L22−]2RN(R′)H2+ (7, R′=H and 8, R′=Me) formed from a new macrocyclic disodium dipyrazolate salt of diazatetraester structure 6[L22−] 2Na+ and ammonium salts [RNH3+X− or RN(Me)H2+X−] of psychotropic drugs and neurotransmitter catecholamines has been evaluated by electrochemical methods in DMSO solution. The resulting Ks values demonstrate that in general, the diazatetraester crown-derived dipyrazolate salt 6 exerts a stronger complexing effect over phenethylammonium ions than that of the dioxatetraester crown-derived disodium dipyrazolate salt 2 previously reported. Interestingly, complexes formed by secondary ammonium salts of psychotropic amines [(±)-methamphetamine, (+)-methamphetamine and (±)-3,4-methylenedioxymethamphetamine (MDMA ‘ecstasy’)] are much more stable than those formed by primary ammonium salts of dopamine and norepinephrine. A study of the stability constants of ammonium pyrazolate complexes in terms of the contributions of substituent groups on the common phenethylamine unit is reported.Financial support by the Comunidad de Madrid (project CM-08.8/0015/1998) and by the Spanish Comision Interministerial de Ciencia y Tecnologı́a (CICYT, SAF 99-0063 and BQU-2000-1424) is gratefully acknowledged