Chemical Biology Metal Catalysis

Our Aims

Generation, training and transfer of knowledge

Development of creative and groundbreaking
research at the interface of Chemistry, Biology and Medicine.

Education of researchers in order they become
future leaders of academic or industrial projects.

Transferring of knowledge to Society in order
to propel economical and social progress

European Research Council Santiago de Compostela University Campus Vida CIQUS - Centro Singular de Investigación en Química Biológica y Materiales Moleculares
Latest News
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Another collaborative paper for 2024, and our first JACS Au, is already available on-line

06/23/2024
We're extremely happy to share our first JACS Au manuscript has been accepted, and it's now available as Open Access through the publisher website

We are so proud to announce here that our collaborative research article at JACS Au, entitled "De Novo Engineering of Pd-Metalloproteins and Their Use as Intracellular Catalysts" and authored by S. Learte-Aymamí, L. Martínez-Castro, C. González-González, M. Condeminas, P. Martin-Malpartida, M. Tomás-Gamasa, S. Baúlde, J. R. Couceiro, J.-D. Maréchal, M. J. Macias, J. L. Mascareñas and M. E. Vázquez, has been accepted and it's already on-line (gold Open Access) also being selected as "Editors' Choice".


Abstract: The development of transition metal-based catalytic platforms that promote bioorthogonal reactions inside living cells remains a major challenge in chemical biology. This is particularly true for palladium-based catalysts, which are very powerful in organic synthesis but perform poorly in the cellular environment, mainly due to their rapid deactivation. We now demonstrate that grafting Pd(II) complexes into engineered β-sheets of a model WW domain results in cell-compatible palladominiproteins that effectively catalyze depropargylation reactions inside HeLa cells. The concave shape of the WW domain β-sheet proved particularly suitable for accommodating the metal center and protecting it from rapid deactivation in the cellular environment. A thorough NMR and computational study confirmed the formation of the metal-stapled peptides and allowed us to propose a three-dimensional structure for this novel metalloprotein motif.








External link: https://pubs.acs.org/doi/10.1021/jacsau.4c00379

Second in a row: another Angew. Chem. Int. Ed. paper is already available on-line

06/17/2024
Once again, in just two weeks, we are sharing another manuscript in the Synthesis and Catalysis field, also published at ACIE journal

We are really glad to announce here another research article at Angew. Chem. Int Ed., entitled "Skeletal and Mechanistic Diversity  in Ir-Catalyzed Cycloisomerizations of Allene-Tethered Pyrroles and Indoles" and authored by A. Arribas, M. Calvelo, A. Rey, J. L. Mascareñas and F. López, has been accepted and it's already on-line (gold Open Access).


Abstract: Pyrroles and indoles bearing N-allenyl tethers participate in a variety of iridium-catalyzed cycloisomerization processes initiated by a C-H activation step, to deliver a diversity of synthetically relevant azaheterocyclic products. By appropriate selection of the ancillary ligand and the substitution pattern of the allene, the reactions can diverge from simple intramolecular hydrocarbonations to tandem processes involving intriguing mechanistic issues. Accordingly, a wide range of heterocyclic structures ranging from dihydro-indolizines and pyridoindoles to tetrahydroindolizines, as well as cyclopropane-fused tetrahydroindolizines can be obtained. Moreover, by using chiral ligands, these cascade processes can be carried out in an enantioselective manner. DFT studies provide insights into the underlying mechanisms and justify the observed chemo- regio- and stereoselectivities.



Our first Angew. Chem. Int. Ed. for 2024, and second collaborative paper of the year, is already available on-line

06/03/2024
We're really pleased to share our most recent ACIE manuscript has been accepted, and it's now available as Open Access through the publisher website

We are so happy to announce here that our collaborative research article at Angew. Chem. Int Ed., entitled "Gold(III) Auracycles featuring C(sp3)−Au−C(sp2) Bonds: Synthesis and Mechanistic Insights into the Cycloauration Step" and authored by J. A. González, A. Arribas, P. Tian, S. Díaz-Alonso, J. L. Mascareñas, F. López and C. Nevado, has been accepted and it's already on-line (gold Open Access).


Abstract: The direct auration of arenes is a key step in numerous gold-catalyzed reactions. Although reported more than 100 years ago, understanding of its underlying mechanism has been hampered by the difficulties in the isolation of relevant intermediates given the propensity of gold(III) species to undergo reductive elimination. Here, we report the synthesis and isolation of a new family of intriguing zwitterionic [C(sp3)^C(sp2)]-auracyclopentanes, as well as of their alkyl-gold(III) precursors and demonstrate their value as mechanistic probes to study the Csp2-Au bond-forming event. Experimental investigations employing Kinetic Isotope Effects (KIE), Hammett plot, and Eyring analysis provided important insights into the formation of the auracycle. The data suggest a SEAr mechanism wherein the slowest step might be the p-coordination between the arene and the gold(III) center, en route to the Wheland intermediate. We also show that these auracyclopentanes can work as catalysts in several gold-promoted transformations.






External link: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202402798

Starting February... first ACS Catalysis of 2024 year is hot off the press. And it's OA, have a look at it!

02/09/2024
Happy to share our brand new ACS Catal. manuscript has been accepted, and it's available as Open Access through the publisher website

We are really pleased to announce here that our research article at ACS catal., entitled "Iridium-Catalyzed Tandem Dehydrogenation/Hydroarylation Approach to Synthetically Versatile C2-Alkenyl N–H Indoles" and authored by C. Lázaro-Milla, J. L. Mascareñas and F. López, has been accepted and it's already on-line (gold Open Access).


This work is also dedicated, in memoriam, to Dr. Alejandro Gutiérrez González.

Abstract: Readily available N-carbamoyl indolines can be converted into highly valuable 2-alkenyl and 2-alkyl indoles in a one-pot reaction, through an autotandem catalytic cascade promoted by an iridium complex. The process entails a dehydrogenation reaction initiated by an iridium-promoted C(sp3)–H activation, the addition of the resulting indole to an alkyne -or alkene-partner, and a spontaneous loss of the carbamoyl directing group. Interestingly, the resulting C2-alkenyl indoles can participate in a variety of metal-catalyzed annulations initiated by C–H activation, including formal [4 + 1] and [4 + 2] cycloadditions, as well as cross-dehydrogenative cyclizations, thus enabling a divergent access to a collection of functionally rich nitrogen-containing heterocycles.


External link: https://pubs.acs.org/doi/10.1021/acscatal.3c05841

Synthetic models in Chemical Biology

07/18/2024
Workshop on Nanomedicine 2012. Prof. Mascareñas, ERC - Advanced Grant METBIOCAT, explains his research lines in the chemical biology field.
DNA is the key macromolecule used by nature to store the genetic information, therefore containing all the instructions that control the day-to-day function of cells. As such, it has been a traditional target for the development of different type of drugs, particularly anticancer agents. These drugs include alkylating agents, like cis-platinum and derivatives, and non-covalent binders like the anthracyclines, which interact to DNA by intercalation between base pairs. There are other types of cytotoxic non-covalent DNA binders, like distamycin or propamidine, which interact to DNA by insertion in the minor groove.

We have been interested in this latter type of molecules, because they are sequence selective and therefore provide for molecular engineering of site-specific DNA-promoted processes. In particular, we have designed and synthesized a number of variants of propamidine that work as sequence specific DNA optical sensors, or as light-activated prodrugs.

Some of the knowledge acquired in the studies of light-promoted processes has been extended to area of DNA-protein interactions. In particular, we have developed a chemical approach to control the DNA interaction of synthetic mimics of transcription factors, and expect that the tactic can be used in the future to regulate processes of gene expression.
Part of our work in this area is also focused to the construction of optical sensors that can detect minute amounts of transcription factors considered as oncogenic biomarkers, like the bZIP protein Jun.

Meet our team

José Luis Mascareñas, PhD leads this team of researchers. Find out more about him and the rest of the team in our Group members section.

Group Members

Join Us

We are always looking forward to welcoming exceptional candidates into our research Group. Please visit our Opportunities section or send us your cv.

Opportunities

Living and working in
Santiago de Compostela

Are you new to the city and its University?
We have gathered some facts and figures you may find interesting.

15ºC

Annual mean temperature. The humid oceanic climate guarantees mild weather throughout the year.

33,000

Students attend the University. With the city population around 100,000.

500

Year old University. Currently imparting more than 60 degrees.

Connected

Santiago is well connected, having its own international airport, train station, etc.

Heritage

Amongst many awards, Santiago was declared World Heritage City by UNESCO in 1985.

Galicia

Santiago de Compostela is the capital of Galicia de most Nortwestern region of Spain.

Transport

Public transport is available in order to get around the city, which is also conveniently located to visit other sites in Galicia.

Language

Spanish and Galician are the two official languages of Galicia. Your work will be carried out in English.

Resources

Official websites:
University of Santiago
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