Stepping strong!!

Our young Sandra Ardevines has received the award “Casañal Poza” for the best academic record of the Degree in Chemistry 2019-20.

Congratulations!!!!

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Chemical reviews just published!

Main Avenues in Gold Coordination Chemistry, Herrera, R. P.; Gimeno, M. C. Chem. Rev. 2021, https://doi.org/10.1021/acs.chemrev.0c00930.

Hard, but gratifying work! Congratulations!!

Abstract. In this contribution, we provide an overview of the main avenues that have emerged in gold coordination chemistry during the last years. The unique properties of gold have motivated research in gold chemistry, and especially regarding the properties and applications of gold compounds in catalysis, medicine, and materials chemistry. The advances in the synthesis and knowledge of gold coordination compounds have been possible with the design of novel ligands becoming relevant motifs that have allowed the preparation of elusive complexes in this area of research. Strong donor ligands with easily modulable electronic and steric properties, such as stable singlet carbenes or cyclometalated ligands, have been decisive in the stabilization of gold(0) species, gold fluoride complexes, gold hydrides, unprecedented π complexes, or cluster derivatives. These new ligands have been important not only from the fundamental structure and bonding studies but also for the synthesis of sophisticated catalysts to improve activity and selectivity of organic transformations. Moreover, they have enabled the facile oxidative addition from gold(I) to gold(III) and the design of a plethora of complexes with specific properties.

Key words. Anions, Reaction products, Metals, Gold, Ligands

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Fer already “Doc”

Today, February 1st, Fernando defended his PhD thesis with great honors.

You got it! Congratulations, Fer!

THANKSSSS and good luck!

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Happy birthday Juanvi!!

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Happy birthday Guillermo!

Last December 28th, Guillermo blew out twenty-odd candles 😉

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Happy birthday Eduardo!

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Happy birthday Conchita and Alberto!

Thousands kisses from HOCAs!

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HOCA (aza-Henry reaction) in The 24th International Electronic Conference on Synthetic Organic Chemistry (Nov 2020)

Asymmetric aza-Henry reaction of hydrazones

I. G. Sonsona, J. V. Alegre-Requena,* E. Marqués-López, M. C. Gimeno, R. P. Herrera*

10.3390/ecsoc-24-08411 (registering DOI)

Abstract: In this work, the enantioselective organocatalyzed addition of nitroalkanes to N-benzoyl hydrazones has been developed for the first time. In order to find a chiral organocatalyst suitable to promote the reaction under high stereo-control and reaction rates, the catalytic activity of several cinchone-derived Brønsted bases was evaluated. As a result of the study, simple quinine alkaloid was able to catalyze, in the optimal reaction conditions, the synthesis of alkyl substituted betha-nitroalkylhydrazides with good yields (up to 91%) and enantiomeric excesses (up to 77%), while quinidine alkaloid was used to obtain the opposite enantiomer with similar catalytic results. Moreover, the further recrystallization of the corresponding enantio-enriched mixtures led to the obtainment of each enantiomer with ee up to 94%. The scope of the catalytic method was explored (14 examples), and the effect of substitutients present in the substrates was evaluated in terms of activity and selectivity. Additionally, the catalyzed reaction pathway was study ab initio in order to understand the successful chiral induction by the catalyst. Hence, in the transition state of the rate limiting step (RLS), quinine is acting as bifunctional catalyst activating both substrates simultaneously. This step involves the protonation of the hydrazone and the attack of the nitronate anion to the sp2 prochiral center in a concerted process. Experimental kinetic studies support this reaction mechanism.

Keywords: Organocatalysis; Asymmetric catalysis; aza-Henry reaction

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DHPs in 6th International Electronic Conference on Medicinal Chemistry (Nov 2020)

Novel ureido-dihydropyridine scaffolds as theranostic agents

F. Auria-Luna,* S. Ardevines, E. Marqués-López, E. Romanos, V. Fernández-Moreira, M. C. Gimeno, I. Marzo, R. P. Herrera

10.3390/ECMC2020-07419 (registering DOI)

Abstract: The potential as anticancer agents of 1,4-dihydropyridines (1,4-DHPs) and their pioneering urea derivatives have been evaluated in HeLa (cervix), Jurkat (leukaemia) and A549 (lung) cancer cell lines as well as on healthy mice. 1,4-DHPs show moderate cytotoxicity. However, when the urea moiety is introduced, an extraordinary increase in their antiproliferative activity is observed, proving an interesting synergy between these two scaffolds. Remarkably, when enantiomerically enriched samples are examined, they result to be in almost all cases less to equally active. This effect could be caused by a complex amalgam of physical and chemical contributions. The studied compounds present luminescent properties and a biodistribution study in cancer cells has been performed. Fluorescence microscopy showed that some of the 1,4-DHP derivatives accumulated in the lysosomes, whilst their urea counterparts targeted the cell membrane, which can be key to explain the different cytotoxic activity and imply a different mechanism of action. Finally, a preliminary in vivo study regarding the acute toxicity of some of these compounds on healthy mice has been conducted, using a concentration up to 7200 times higher than the corresponding IC50 value. No downgrade in the welfare of the test subjects was observed, which could support their use in preclinical tumour models. Recently, we have been exploring the biological properties of 1-benzamido-1,4-dihydropyridine derivatives and the preliminary results on cytotoxicity will be commented.

Keywords: cancer, 1,4-dihydropyridine, fluorescence, mice, theranosis, urea

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Further knowledge on DHP just published!

We did it again! Congratulations guys!

Novel ureido-dihydropyridine scaffolds as theranostic agents, Auria-Luna, F.; Marqués-López, E.; Romanos, E.; Fernández-Moreira, V.; Gimeno, M. C.; Marzo, I.; Herrera, R. P. Bioorg. Chem. 2020https://doi.org/10.1016/j.bioorg.2020.104364.

Abstract. In this work, the synthesis of interesting urea derivatives 5 based on 1,4-dihydropyridines 3 is described for the first time. Considering that both families exhibit potential as drugs to treat various diseases, their activity as anticancer agents has been evaluated in HeLa (cervix), Jurkat (leukaemia) and A549 (lung) cancer cell lines as well as on healthy mice in vivo.

In general, whereas 1,4-dihydropyridines show a moderate cytotoxic activity, their urea analogues cause an extraordinary increase in their antiproliferative activity, specially towards HeLa cells. Because of the chiral nature of these compounds, enantiomerically enriched samples were also tested, showing different cytotoxic activity than the racemic mixture. Although the reason is not clear, it could be caused by a complex amalgam of physical and chemical contributions.

The studied compounds also exhibit luminescent properties, which allow performing a biodistribution study in cancer cells. They have emission maxima between 420 and 471 nm, being the urea derivatives in general red shifted. Emission quenching was observed for those compounds containing a nitro group (3e,f and 5e,f). Fluorescence microscopy showed that 1,4-dihydropyridines 3a and 3g localised in the lysosomes, in contrast to the urea derivatives 5h that accumulated in the cell membrane. This different distribution could be key to explain the differences found in the cytotoxic activity and in the mechanism of action. Interestingly, a preliminary in vivo study regarding the acute toxicity of some of these compounds on healthy mice has been conducted, using a concentration up to 7200 times higher than the corresponding IC50 value. No downgrade in the welfare of the tested mice was observed, which could support their use in preclinical tumour models.

Keywords. Cancer; 1,4-dihydropyridine; fluorescence; mice; theranostic agent; urea

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