Unconventional Approaches in Coordination Chemistry and Organometallic Reactivity

This contribution highlights a number of approaches developed by coordination and organometallic chemists that go beyond mainstream inorganic reactivity. A few of these strategies have been known for decades and are fundamental tools in synthesis and catalysis, while others are more recent and still belong to a niche. Through selected examples, we show herein how transmetalation, metal exchange, metal cooperativity, and catalytic transformation of metal complexes provide unique new opportunities to expand the reactivity arsenal of inorganic systems for synthetic and technological applicationsL.S. acknowledges financial support from the Spanish State Research Agency for the grant PID2019-109111RB-I00 and the Spanish Multi-MetDrugs network (RED2018-102471-T) for fruitful discussions. This work was performed under the Severo Ochoa Centres of Excellence Program of the Spanish State Research Agency, Grant No. CEX2018-000867-S (DIPC)

The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo- and imino-pyridine anticancer complexes : control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway

Organometallic half-sandwich complexes [M(p-cymene)(azo/imino-pyridine)X]+ where M = RuII or OsII and X ═ Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido complexes more potent than the chlorido analogues, but they are not cross-resistant with the clinical platinum drugs cisplatin and oxaliplatin. They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes. They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. The iodido complexes retain potency in p53 mutant colon cells. All complexes activate caspase 3. In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor l-buthionine sulfoxime. The work illustrates how subtle changes to the design of low-spin d6 metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity

Nauczyciele, którzy nie uczą. Być nauczycielem w przygotowanym do uczenia się otoczeniu elementarnej szkoły Montessori

After a brief introduction to the Montessori model of education (psychological foundations, guiding principles, distinctive features), the Author’s contribution is aimed at giving a satisfactory representation of the Montessori teacher, in particular the one dealing with learners at the elementary school stage. The framework is developed using a selection of sources belonging to three different types: Montessori’s writings, visual materials, empirical data. Each section collects specific material with the intention of bringing it to the attention of the reader, allowing wider reflection from different points of view. The triangulation of the proposed contents and data is seen as a method for considering this complex but fascinating teacher profile both in its theoretical specificities and in its operational qualities in the context in which the teaching-learning process takes place. The desired overall results should allow a greater focus on the profile and role of the Montessori teacher in the elementary school as well as giving the reader himself the opportunity to elaborate further reflections and conclusions independently.Po krótkim omówieniu modelu edukacji Marii Montessori (podstawy psychologiczne, zasady postępowania, cechy wyróżniające) autorka stara się zaprezentować wyczerpujący opis roli nauczyciela Montessori, zwłaszcza na poziomie szkoły elementarnej. Opracowane w tym celu ramy opisu obejmują selekcję materiałów należących do trzech źródeł: oryginalnych pism M. Montessori, materiałów wizualnych (ikonograficznych) oraz danych empirycznych z badań własnych. Każdy z wymienionych działów zbiera materiały o wysokiej jakości z intencją skoncentrowania na nich uwagi czytelnika i poddania ich szerszej refleksji z różnych punktów widzenia. Triangulacja proponowanych treści i danych jest tu postrzegana jako metoda badania złożonej, lecz fascynującej charakterystyki profilu nauczyciela, zarówno w aspekcie jego teoretycznych właściwości, jak i operacyjnych cech działania ujawnianych w kontekście procesu nauczania-uczenia się. Głównym celem analizy jest głębsze skoncentrowanie się na profilu i roli nauczyciela Montessori w szkole elementarnej, a także umożliwienie czytelnikowi samodzielnej, pogłębionej refleksji nad zagadnieniem i niezależnego formułowania własnych wniosków

Design of photoactivatable metallodrugs : selective and rapid light-induced ligand dissociation from half-sandwich [Ru([9]aneS3)(N–N′)(py)]2+ complexes

The synthesis of the inert Ru(II) half-sandwich coordination compounds, [Ru([9]aneS3)(bpy)(py)][PF6]2 (1, [9]aneS3 = 1,4,7-trithiacyclononane, bpy = 2,2′-bipyridine, py = pyridine), [Ru([9]aneS3)(en)(py)][PF6]2 (2, en = 1,2-diaminoethane), and [Ru([9]aneN3)(en)(dmso-S)][PF6]2 (3, [9]aneN3 = 1,4,7-triazacyclononane), is reported along with the X-ray crystal structure of 1. We investigated whether these complexes have photochemical properties which might make them suitable for use as pro-drugs in photochemotherapy. Complexes 1 and 2 underwent rapid (minutes) aquation with dissociation of the pyridine ligand in aqueous solution when irradiated with blue light (λ = 420 or 467 nm). The photodecomposition of 3 was much slower. All complexes readily formed adducts with 9-ethylguanine (9-EtG) when this model nucleobase was present in the photolysis solution. Similarly, complex 1 formed adducts with the tripeptide glutathione (GSH), but only when photoactivated. HPLC and MS studies of 1 showed that irradiation promoted rapid formation of 1:1 (major) and 1:2 (minor) adducts of the oligonucleotide d(ATACATGCTACATA) with the fragment {Ru([9]aneS3)(bpy)}2+. Density functional theory (DFT) calculations and time-dependent DFT reproduced the major features of the absorption spectra and suggested that the lowest-lying triplet state with 3MLCT character, which is readily accessible via intersystem crossing, might be responsible for the observed dissociative behavior of the excited states. These complexes are promising for further study as potential photochemotherapeutic agents

Diazido mixed-amine platinum(IV) anticancer complexes activatable by visible-light form novel DNA adducts

Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side-effects. Photoactivatable PtIV prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X-ray crystallographic and spectroscopic properties of photoactivatable diazido complexes trans,trans,trans-[Pt(N3)2(OH)2(MA)(Py)] (1; MA=methylamine, Py=pyridine) and trans,trans,trans-[Pt(N3)2(OH)2(MA)(Tz)] (2; Tz=thiazole), and interpret their photophysical properties by TD-DFT modelling. The orientation of the azido groups is highly dependent on H bonding and crystal packing, as shown by polymorphs 1 p and 1 q. Complexes 1 and 2 are stable in the dark towards hydrolysis and glutathione reduction, but undergo rapid photoreduction with UVA or blue light with minimal amine photodissociation. They are over an order of magnitude more potent towards HaCaT keratinocytes, A2780 ovarian, and OE19 oesophageal carcinoma cells than cisplatin and show particular potency towards cisplatin-resistant human ovarian cancer cells (A2780cis). Analysis of binding to calf-thymus (CT), plasmids, oligonucleotide DNA and individual nucleotides reveals that photoactivated 1 and 2 form both mono- and bifunctional DNA lesions, with preference for G and C, similar to transplatin, but with significantly larger unwinding angles and a higher percentage of interstrand cross-links, with evidence for DNA strand cross-linking further supported by a comet assay. DNA lesions of 1 and 2 on a 50 bp duplex were not recognised by HMGB1 protein, in contrast to cisplatin-type lesions. The photo-induced platination reactions of DNA by 1 and 2 show similarities with the products of the dark reactions of the PtII compounds trans-[PtCl2(MA)(Py)] (5) and trans-[PtCl2(MA)(Tz)] (6). Following photoactivation, complex 2 reacted most rapidly with CT DNA, followed by 1, whereas the dark reactions of 5 and 6 with DNA were comparatively slow. Complexes 1 and 2 can therefore give rapid potent photocytotoxicity and novel DNA lesions in cancer cells, with no activity in the absence of irradiation

Modifications and grounds of new double taxation convention signed between Argentina and Spain (2013)

El presente trabajo se enfoca en el Convenio de doble imposición sobre la renta y el patrimonio suscrito entre Argentina y España en marzo de 2013, el cual vino a suceder a al Convenio que ambos países habían suscrito en 1992 que estuvo vigente hasta 2012. La finalidad de este estudio estriba en identificar cuáles son las modificaciones que el nuevo Acuerdo tiene respecto al Acuerdo de 1992 y en determinar a qué objetivos responden dichas reformas. Este análisis nos permitirá contar, por un lado, con una visión comparativa sobre los dos Convenios que se firmaron con España y, por otro lado, con ciertas herramientas para poder vislumbrar la estrategia que está adoptando nuestro país a la hora de firmar y denunciar Convenios de doble imposición.This paper focuses on Double Taxation Convention on Income and Capital signed between Argentina and Spain in March 2013, which it came to pass Convention that both countries had signed in 1992 which was in force until 2012. Objectives of this work are to identify the changes of new Agreement regarding the Agreement of 1992 and determine the targets of these reforms. This analysis will provide us, on the one hand, a comparison of the two Conventions signed between these countries and, on the other hand, tools in order to glimpse the strategy taking by our country when sign and report Double Taxation Conventions.Fil: Salassa Boix, Rodolfo Rubén. Universitat Rovira I Virgili; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A simple and effective algorithm for the maximum happy vertices problem

In a recent paper, a solution approach to the Maximum Happy Vertices Problem has been proposed. The approach is based on a constructive heuristic improved by a matheuristic local search phase. We propose a new procedure able to outperform the previous solution algorithm both in terms of solution quality and computational time. Our approach is based on simple ingredients implying as starting solution gen- erator an approximation algorithm and as an improving phase a new matheuristic local search. The procedure is then extended to a multi-start configuration, able to further improve the solution quality at the cost of an acceptable increase in compu- tational time

Synthesis, reactivity studies, and cytotoxicity of two trans-Iodidoplatinum(II) complexes. Does photoactivation work?

trans-Platinum complexes have been the landmark in unconventional drugs prompting the development of innovative structures that might exhibit chemical and biological profiles different to cisplatin. Iodido complexes signaled a new turning point in the platinum drug design field when their cytotoxicity was reevaluated and reported. In this new study, we have synthesized and evaluated diodidoplatinum complexes trans-[PtI2(amine)(pyridine)] bearing aliphatic amines (isopropylamine and methylamine) and pyridines in trans configuration. X-ray diffraction data support the structural characterization. Their cytotoxicity has been evaluated in tumor cell lines such as SAOS-2, A375, T-47D, and HCT116. Moreover, we report their solution behavior and reactivity with biological models. Ultraviolet-a (UVA) irradiation induces an increase in their reactivity towards model nucleobase 5′-GMP in early stages, and promotes the release of the pyridine ligand (spectator ligand) at longer reaction times. Density Functional calculations have been performed and the results are compared with our previous studies with other iodido derivatives.MINECO CTQ-2015-68779