N-Heteroarilaminidas de pridinio: preparación de aminas y poliaminas ramificadas

Las N-heteroarilaminidas de piridinio han demostrado ser unos materiales de partida competitivos para la síntesis de compuestos heterocíclicos, debido a la gran variedad reacciones que se pueden llevar a cabo sobre ellas de manera regioselectiva. En el presente trabajo de investigación se enfoca la utilidad de diferentes N-azinilaminidas de piridinio halogenadas para la preparación de aminoazinas con elevada funcionalización. El trabajo se centra fundamentalmente en poner a punto un método de síntesis regioselectiva de 2-aminopirazinas 3,5-disustituidas y en prepararar poli?heteroarilaminas a partir de N-heteroarilaminidas de piridinio y sustratos poli?halogenados para finalmente explorar la posibilidad de obtener poliaminas ramificadas o dendriméricas. En el esquema siguiente se resume la síntesis de las 2-aminopirazinas a partir de la 3,5-dibromopirazinilaminida de piridinio en la que están implicados procesos de arilación mediados por paladio (reacción de Suzuki), alquilación y reducción sucesivamente y donde dos de ellos trascurren con una elevada regioselectividad: A partir de diversas N-heteroarilaminidas de piridinio adecuadamente funcionalizadas y derivados polihalogendos, empleado procesos análogos de alquilación regioselectiva se ha logrado la síntesis de polisales. El enlace N-N de estas sales se reduce satisfactoriamente originando poliaminas ramificadas Finalmente, se ha estudiado la viabilidad de aplicar estos procesos a la síntesis de estructuras de mayor complejidad y de naturaleza dendrimérica, lográndose la preparación de hexa-sales ramificadas sobre las que llevar a cabo procesos de reducción

N-Heteroarilaminidas de pridinio: preparación de aminas y poliaminas ramificadas

Las N-heteroarilaminidas de piridinio han demostrado ser unos materiales de partida competitivos para la síntesis de compuestos heterocíclicos, debido a la gran variedad reacciones que se pueden llevar a cabo sobre ellas de manera regioselectiva. En el presente trabajo de investigación se enfoca la utilidad de diferentes N-azinilaminidas de piridinio halogenadas para la preparación de aminoazinas con elevada funcionalización. El trabajo se centra fundamentalmente en poner a punto un método de síntesis regioselectiva de 2-aminopirazinas 3,5-disustituidas y en prepararar poli?heteroarilaminas a partir de N-heteroarilaminidas de piridinio y sustratos poli?halogenados para finalmente explorar la posibilidad de obtener poliaminas ramificadas o dendriméricas. En el esquema siguiente se resume la síntesis de las 2-aminopirazinas a partir de la 3,5-dibromopirazinilaminida de piridinio en la que están implicados procesos de arilación mediados por paladio (reacción de Suzuki), alquilación y reducción sucesivamente y donde dos de ellos trascurren con una elevada regioselectividad: A partir de diversas N-heteroarilaminidas de piridinio adecuadamente funcionalizadas y derivados polihalogendos, empleado procesos análogos de alquilación regioselectiva se ha logrado la síntesis de polisales. El enlace N-N de estas sales se reduce satisfactoriamente originando poliaminas ramificadas Finalmente, se ha estudiado la viabilidad de aplicar estos procesos a la síntesis de estructuras de mayor complejidad y de naturaleza dendrimérica, lográndose la preparación de hexa-sales ramificadas sobre las que llevar a cabo procesos de reducción

Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer

Introduction: Nanocarriers have emerged as a powerful alternative for cancer therapy.Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs – the so-called multidrug resistance (MDR) phenomenon – which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem. Areas covered: Herein we summarize the current efforts developed to provide MSNbased nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems’ killing capability towards particular cells by enhancing both recognition and specificity; ii)increasing the apoptotic effect throughout co-delivery of several drugs; or iii)combining drug delivery with apoptosis induced by physical methods. Expert Opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors

Recent applications on the combination of Mesoporous Silica Nanoparticles with Nucleic Acids: Development of Bioresponsive Devices, Carriers and Sensors

The discovery and control of the biological roles mediated by nucleic acids have turned them into a powerful tool for the development of advanced biotechnological materials. Much is the importance of those gene-keeping biomacromolecules that even nanomaterials have succumbed to the claimed benefits of DNA and RNA. Currently, there could be found in the literature a practically intractable number of examples which report the use in combination of nanoparticles with nucleic acids, which demands boundedness. Following this premise, this revision will only cover the most recent and powerful strategies developed to exploit the possibilities of nucleic acids as biotechnological materials when in combination with mesoporous silica nanoparticles. The extensive research done on nucleic acids has significantly incremented the technological possibilities for those biomacromolecules, which could be employed in many different applications; where substrate or sequence recognition or modulation of biological pathways due to its coding role in living cells are the most promising. In the present revision, the chosen counterpart, mesoporous silica nanoparticles, also with unique properties, became a reference material for drug delivery and biomedical applications due to their high biocompatibility and porous structure suitable for hosting and delivering small molecules. Although most of revisions deal with significant advances in the use of nucleic acid and mesoporous silica nanoparticles in biotechnological applications, a rationale classification of those new generation hybrid materials is still uncovered. Along this review there will be covered promising strategies for living cell and biological sensors, DNA-based molecular gates with targeting, transfection or silencing properties which could provide a significant advance of current nanomedicine

Sobre el origen de la vida

La biogénesis es, quizás, el tema más complejo de la Biología y, sin duda, una de las cuestiones pendientes de la ciencia. Este libro aborda el asunto desde los cuatro enfoques epistemológicos posibles: ascendente, descendente, sintético y analítico. El libro se divide en 11 capítulos con gran profusión de dibujos, tablas y cuadros explicativos. En la introducción se comenta la naturaleza física y química de la vida y los límites del conocimiento. En los nueve siguientes se hace uso, por razones didácticas, de las aitia del empirismo lógico. En el capítulo 2 (qué) se plantea el núcleo duro de la biogénesis, compatibilizándolo con el principio de continuidad y analizando las dificultades conceptuales suscitadas a lo largo de la historia. En los capítulos 3 y 4 (dónde y cuándo) se estudian los aspectos cosmológicos, astrofísicos y geológicos. Se habla de habitabilidad, exobiología, planetología y paleobiología. El capítulo 5 trata del cómo. Se exponen los principios científicos para la compresión de la biogénesis: información, cinética química, termodinámica, autoensamblaje, evolución y análisis filogénico. Los capítulos 6-9 abordan aspectos prácticos del cómo, tanto los modelos ascendentes (simulación prebiótica de micro y macromoléculas y sistemas biopoyéticos) como los descendentes (“mundos”, bioquímica comparada y biología sintética). El capítulo 10 trata brevemente el aitia más compleja de todas, el porqué. En él se vierten reflexiones filosóficas y opiniones personales. En el último capítulo, pese a la enorme dificultad del tema y al exiguo número de investigadores que le han dedicado sus esfuerzos, se recogen algunas conclusiones.The origin of life on Earth is probably the most complex problem in Biology and one of the main pending problems to be solved in science. This book poses the problem from the four epistemological approaches: bottom-up, top-down, synthetic and analytics. The book is divided into 11 chapters including many explanatory drawings and tables. The introduction addresses the physicochemical nature of living beings and the limits of knowledge. In the following 9 chapters the authors, for didactic reasons, make use of the different aitia of logical empiricism. In Chapter 2 (What) the hard core of the biogenesis is exposed in the context of the continuity principle analyzing some conceptual problems faced along the history. In Chapters 3 and 4 (Where and When) the cosmological, geological and astrophysical aspects of the biogenesis are treated. Habitability, exobiology and paleontology are also treated in these chapters. Chapters 5 treat the question, How? In this chapter the scientific principles to understand the biogenesis are exposed: Information, chemical kinetics, thermodynamics, auto-assembly, evolution and phylogenetic analysis. In chapters 6-9 the practical aspect of the same question (how) are addressed, using either “bottom-up” (prebiotic simulation of micro- and macromolecules and biopoyetic systems) and “top-down” (different “worlds”, comparative biochemistry and synthetic biology) models. In Chapter 10 the most difficult aitia of the biogenesis is treated: Why? Here some philosophical and personal opinion of the authors are exposed. In the last chapter some provisional conclusions are extracted from the relatively scarce bibliography, if compared to complexity of the problem

Pyridinium N-heteroarylaminides: synthesis of N-heteroaryltetramines based on 1,6-bis(phenoxy)hexane and 1,3-bis(phenoxymethyl)benzene

The synthesis of a set of new N-heteroaryltetramines is reported. A regioselective alkylation on the N-exo nitrogen of pyridinium N-(heteroaryl)aminide with the corresponding tetrabromo compounds, followed by a clean N–N bond reduction of the corresponding tetra-salts, allowed an easy and general method to obtain N,N′,N″,N‴-tetrakis(2-heteroaryl)tetramines.Ministerio de Educación y Cienci

Recent Advances Toward the Use of Mesoporous Silica Nanoparticles for the Treatment of Bacterial Infections.

It is a fact that the use of antibiotics is inducing a growing resistance on bacteria. This situation is not only the consequence of a drugs’ misuse, but a direct consequence of a widespread and continuous use. Current studies suggest that this effect could be reversed by using abandoned antibiotics to which bacteria have lost their resistance, but this is only a temporary solution that in near future would lead to new resistance problems. Fortunately, current nanotechnology offers a new life for old and new antibiotics, which could have significantly different pharmacokinetics when properly delivered; enabling new routes able to bypass acquired resistances. In this contribution, we will focus on the use of porous silica nanoparticles as functional carriers for the delivery of antibiotics and biocides in combination with additional features like membrane sensitizing and heavy metal-driven metabolicdisrupting therapies as two of the most interesting combination therapie

Suzuki reaction on pyridinium N-haloheteroarylaminides: regioselective synthesis of 3,5-disubstituted 2-aminopyrazines

An extensive study of Suzuki–Miyaura cross-coupling processes on N-pyridinium bromoazinyl aminides has been performed. Mono- and disubstitution on 5- and 3,5-bromo derivatives produced the corresponding aryl derivatives. In the disubstituted compounds regioselective substitution at the 3-position occurred, vicinal to the aminide nitrogen, and this was more evident in pyrazine derivatives. The commonly used strategy involving N-alkylation and reduction of the N–N bond gave rise to a series of 2-alkylamino-3,5-disubstituted-pyrazines.The authors wish to thank the Comisión Interministerial de Ciencia y Tecnología (CICYT-BQU2001-1508 and CTQ2005-08902) and the Universidad de Alcalá (UAH GC2005/006) for financial support and the Ministerio de Educación y Ciencia (MEC) for two studentships (M.J.R. and R.C.). We also thank Professor Mijail Galajov for his assistance in the NMR study

Regioselective suzuki coupling on pyridinium N-(3,5-dibromoheteroar-2-yl)aminides

A regioselective Suzuki-Miyaura cross-coupling reaction on 3',5'-dibromo pyridinium N-(2'-azinyl)aminides is reported. A series of 3'-aryl(or heteroaryl)-5-bromo-pyridinium N-(2'-pirazinyl)aminides were obtained in good yields. Two isomeric 3',5'-diaryl pyridinium N-(2-azinyl)aminides were also prepared.The authors wish to thank the Comisión Interministerial de Ciencia y Tecnología (CICYT-BQU2001-1508) and the Universidad de Alcalá (UAH GC2005/006) for financial support, and the Ministerio de Educación y Cultura (MEC) for two studentships (M.J.R. and R.C.)

Electron microscopy for inorganic-type drug delivery nanocarriers for antitumoral applications: What is possible to see?

The use of nanoparticles able to transport drugs, in a selective and controlable manner, directly to diseased tissues and cells have improved the therapeutic arsenal for addressing unmet clinical situations. In the recent years, a vast number of nanocarriers with inorganic, organic, hybrid and even biological nature have been developed, expecially for their application in oncology fied. The exponential growing in the nanomedicine field would not have been possible without the also rapid expansion of electron microscopy techniques, which allow a more precise observation of nanometric objects. The use of these techniques provides a better understanding of the key parameters which rule their synthesis and behavior. In this review, the recent advances performed in the application of inorganic nanoparticles for clinical uses and the role which has played electron microscopy will be presented