Photodegradation of nimodipine and felodipine in microheterogeneous systems

Indexación: Web of Science; ScieloThe photochemical behavior of nimodipine (NIMO) and felodipine (FELO), photolabile drugs widely used as antihypertensive calcium channel blockers, is studied in constrained media. Specifically, we are interested in the kinetic analysis of 4-aryl-1,4-dihydropyridine photodegradation processes when they are incorporated in biological-mimicking systems like micelles or liposomes. In order to establish if the nature of the head of surfactant (ionic or nonionic) could be important modulating the photo-reactivity of these drugs, we studied the photodegradation of NIMO and FELO incorporated in micelles formed with sodium dodecyl sulfate (SDS, anionic), dodecyl-pyridinium chloride (DPC, cationic) and mono lauryl sucrose ester (MLS, nonionic) as surfactants. Additionally, the results of the photodegradation of these compounds in liposomes were also included. The results clearly indicate that both dihydropyridines studied, NIMO and FELO, are located near to the interface, but the surface charge of micelles does not affect neither, the photodegradation rate constant nor the photodegradation products profile. The absence of singlet oxygen generation in micellar media is consistent with the proposition of these 4-aryl-1,4-dihidropyridines located near to the interface of the micelle, where a polar environment is sensed. In addition, the ethanol preferential location on membranes and dihydropyridine enhanced photodegradation by alcohol presence are interesting results to consider in future research.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072012000300025&nrm=is

Radiolysis of Amino Acids by Heavy and Energetic Cosmic Ray Analogs in Simulated Space Environments: α\alpha-Glycine Zwitterion Form

In this work, we studied the stability of the glycine molecule in the crystalline zwitterion form, known as {\alpha}-glycine ($^{+}$NH$_{3}$CH$_{2}$COO$^{-}$) under action of heavy cosmic ray analogs. The experiments were conducted in a high vacuum chamber at heavy ions accelerator GANIL, in Caen, France. The samples were bombarded at two temperatures (14 K and 300 K) by $^{58}$Ni$^{11+}$ ions of 46 MeV until the final fluence of $10^{13}$ ions cm$^{-2}$. The chemical evolution of the sample was evaluated in-situ using Fourrier Transformed Infrared (FTIR) spectrometer. The bombardment at 14 K produced several daughter species such as OCN$^-$, CO, CO$_2$, and CN$^-$. The results also suggest the appearing of peptide bonds during irradiation but this must be confirmed by further experiments. The halflives of glycine in Interstellar Medium were estimated to be 7.8 $\times 10^3$ years (300 K) and 2.8 $\times 10^3$ years (14 K). In the Solar System the values were 8.4 $\times 10^2$ years (300 K) and 3.6 $\times 10^3$ years (14 K). It is believed that glycine could be present in space environments that suffered aqueous changes such as the interior of comets, meteorites and planetesimals. This molecule is present in proteins of all alive beings. So, studying its stability in these environments provides further understanding about the role of this specie in the prebiotic chemistry on Earth.Comment: 28 pages, 12 figures, 9 tables. Accepted to be published at Monthly Notices of the Royal Astronomical Society (MNRAS

A comparative study of the electrochemical properties of vitamin B-6 related compounds at physiological pH

A comparative study of vitamin B6 group and related compounds in buffered solutions using electrochemical techniques has been performed at neutral pH. Irreversible bi- or tetra-electronic processes are observed for these substances, and the electron transfer coefficient (αn) calculated. It was concluded that either the first or second electron transfer were the rate determining step of the electrode process. The diffusion coefficient of these substances was calculated and the values given follow an inverse tendency to the molecular size. For aldehydes the values obtained were corrected of the hydration reaction. It is important to remark that catalytic waves were reported for the first time for these compounds. Using a model involving the nitrogen of the basic structure the kinetic constants were calculated for most of them

Photon Correlation Spectroscopy and Applications

Contains report on one research project.National Science Foundation (Grant PCM81-11534

Photon Correlation Spectroscopy and Applications

Contains reports on two research projects.National Science Foundation (Grant DMR-84- 18718)Wan-Yuan Company, Beijing, Peoples Republic of China Contrac

Actividad inmunosupresora de derivados de Rapamicina, síntesis de indolizidinas con centros cuaternarios y nanodetección de células tumorales

179 p.Una eficiente vía enantioselectiva para la preparación de centros cuaternarios en unidades de prolina es a través del reordenamiento sigmatrópico [2,3] de Stevens. Los rendimientos del reordenamiento sigmatrópico podrían ser mejores con el uso de 1-butil-3- metilimidazolium hexafluorofosfato, clave en la evaluación de los rendimientos en el reordenamiento de Stevens debido a una posible estabilización y/o activación de especies zwiteriónicas en solución por el líquido iónico. Varios derivados indolizidínicos serán sintetizadas a partir del derivado cuaternario de (S)-α-alil-prolina. Los quantum dots (QDs) son nanopartículas que poseen la característica de ser agentes de contraste y ofrecen ser la nueva generación como pruebas de fluorescencia para estudios de imagen en procesos biológicos. Debido a sus elevadas propiedades ópticas, los QDs son un promisorio método aplicable en la biotecnología, industria alimentaría, biomedicina, específicamente el monitorear células vivas en el seguimiento de procesos citoplasmáticos que permanecen limitados a los métodos disponibles en la actualidad, además en el diagnóstico (marcaje celular) por ejemplo de células tumorales y también como método terapéutico. Existen otros tipos de macromoléculas, los polímeros dendríticos que componen una nueva generación de “nano-sistemas” que han despertado un gran interés en los últimos años entre otras cosas, por su alto potencial como agentes transportadores de fármacos y su prácticamente nula citotóxicidad que provoca en los sistemas biológicos. Desde un punto de vista químico, los dendrímeros son macromoléculas poliméricas sintéticas que pueden ser de distinta naturaleza (peptídicos, lipídicos, polisacarídicos, etc.). Un dendrímero típico está formado por una molécula central de la que salen varias «ramas», que a su vez se ramifican, originando así una estructura tridimensional globular de capas concéntricas. Cada paso de la síntesis química está perfectamente controlado, dando lugar a una estructura organizada, de tamaño concreto presentando en la superficie un número definido de grupos funcionales. La presencia de esos grupos funcionales (amino, carboxilo, hidroxilo, etc.) en la superficie de los dendrímeros confiere a estos agentes gran parte de su utilidad en terapéutica por su permeabilidad celular. Estudios de encapsulación de QDs en dendrímeros y la evaluación de su aplicación en nanotecnología no se ha llevado a cabo, por lo tanto este estudio sería pionero en sintetizar y evaluar su aplicabilidad en los sistemas biológicos específicamente en estudios de imagenología, diagnóstico y terapia tumoral./ ABSTRACT: Immunosuppressants are a class of drugs capable of inhibiting the immune response. They are often used in the treatment of autoimmune disorders. The most frequent diseases are systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis (RA), inflammatory myopathies, and systemic vasculites. Immunosuppressant are also prescribed to prevent rejection of transplanted tissues and organs. The use of these agents has allowed the increase of the number of transplants in the world. The most studied representatives of this class of therapeutic agents are Cyclosporin-A, FK506, and Rapamicin. Through molecular modelling studies it has been established that analogues of rapamycin and FK506 possess molecular structures simplest can have major immunosuppressive activity. For the construction of such analogous ones a hydrogenation proposes an efficient enantioselective asymmetric transfer-hydrogenation of α,β-unsaturated ketones to the corresponding chiral secondary alcohols using Ru (II)-TsDPEN catalyst is pursued. The obtained alcohols will be couplae with proline and pipecolic acid derivates to produce FK506 analogues. Immunosuppressive activity of these synthesized compounds will be is evaluated. Furtheremore, an efficient enantioselective approach for preparation of quaternary centers from proline 5 building block will be developed through [2,3]-sigmatropic Stevens’s rearrangement co-catalyzed by ionic liquid. The sigmatropic rearrangement was stereospecific because the [2,3]-migrations will be restricted to the same face, and the stereoselectivity arose from the previous N-alkylation step in 8. The approach will show better yields than described in literature. The use of 1-butyl-3-methylimidazolium hexafluorophosphate is expected to improve the yields of the Stevens rearrangement due to a possible stabilization and/or activatation of zwiterionic species in solution by the ionic liquid. Several indolizidine moieties will be synthesized from quaternary proline derivative (S). The quantum dots (QDs) are nanoparticles that have the characteristic of being contrast agents and offer to be the new generation of tests for fluorescence imaging studies in biological processes. Due to their high optical properties of QDs are promising methods in BIotechnology, food industry, biomedicine, specifically to monitor live cells in the followcytoplasmic processes that are limited to the methods currently available, in addition to the diagnosis (Marking cell) such as tumor cells and also as a therapeutic method. In nanotechnology, there are also other types of macromolecules, the dendritic polymers that comprise a new generation of nano-systems "which have attracted interest in recent years among other things, its high potential as agents of drug transporters and its virtually no cytotoxicity resulting in biological systems. From a chemical point of view, the macromolecules dendrimers are synthetic polymers that may be of different nature (peptide, lipid, polysaccharide, etc.). Dendrimers a typical molecule is composed of a central post of the various "branches", which in turn branch, creating a globular three-dimensional structure of concentric layers. Each step of the synthesis chemistry is well controlled, resulting in an organized structure, size of concrete surface in a defined number of functional groups. The presence of these functional groups (amino, carboxyl, hydroxyl, etc.) on the surface of these agents dendrimers gives much of its usefulness in therapy for their cell permeability.Studies in dendrimers encapsulating QDs and evaluate its application in biotechnology is not performed therefore a pioneer in the study would be to synthesize and evaluate its applicability in biological systems specifically on imaging studies, tumor diagnosis and therap

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio

Radiolysis of ammonia-containing ices by energetic, heavy and highly charged ions inside dense astrophysical environments

Deeply inside dense molecular clouds and protostellar disks, the interstellar ices are protected from stellar energetic UV photons. However, X-rays and energetic cosmic rays can penetrate inside these regions triggering chemical reactions, molecular dissociation and evaporation processes. We present experimental studies on the interaction of heavy, highly charged and energetic ions (46 MeV Ni^13+) with ammonia-containing ices in an attempt to simulate the physical chemistry induced by heavy ion cosmic rays inside dense astrophysical environments. The measurements were performed inside a high vacuum chamber coupled to the heavy ion accelerator GANIL (Grand Accelerateur National d'Ions Lourds) in Caen, France.\textit{In-situ} analysis is performed by a Fourier transform infrared spectrometer (FTIR) at different fluences. The averaged values for the dissociation cross section of water, ammonia and carbon monoxide due to heavy cosmic ray ion analogs are ~2x10^{-13}, 1.4x10^{-13} and 1.9x10^{-13} cm$^2$, respectively. In the presence of a typical heavy cosmic ray field, the estimated half life for the studied species is 2-3x10^6 years. The ice compaction (micropore collapse) due to heavy cosmic rays seems to be at least 3 orders of magnitude higher than the one promoted by (0.8 MeV) protons . In the case of the irradiated H2O:NH3:CO ice, the infrared spectrum at room temperature reveals five bands that were tentatively assigned to vibration modes of the zwitterionic glycine (+NH3CH2COO-).Comment: Accepted to be published in Astronomy and Astrophysics; Number of pages: 12; Number of Figures: 7; Number of Tables: