Research
We are firm believers on
the critical value of first level research and
advanced education as means to promote
the socio-economical, technological, and
cultural progress of our society
We strive to provide an appropriate environment
for performing creative and competitive research
at the frontier of knowledge, and to promote the formation
of people that should later lead relevant academic
and industrial projects.
Our Group
We are a multidisciplinary group that, leveraging in the power of catalysis and synthetic chemistry, aims to perform cutting-edge scientific discoveries at the interface of chemistry, chemical biology and biomedicine. Since the year 2000, we have published many high-level papers in top-notch journals (J. Am. Chem. Soc., Nature Communications, Angewandte Chemie, ACS Catal., Chem. Sci., etc,)
In recent years we have also increased our work to explore the tech transfer possibilities of some of our discoveries.
Please, for updated information check the publications section.
Research interests
Our current research program deals with two main topics:
Synthesis and catalysis (José Luis Mascareñas, Fernando López, Moisés Gulías):
discovery and development of innovative catalytic methodologies.
Chemical biology and biomedicine (José Luis Mascareñas, María Tomás):
- a) merging metal catalysis with cell biology;
- b) development of novel biomedical tools.
Synthesis and Catalysis
Modern organic synthesis should be more than just reaching the target at any cost. Therefore, part of our efforts focuses on developing innovative and creative methods for transforming simple, readily accessible substances into architecturally complex, target-relevant products.
The development of these methods, which may ultimately provide faster access to biologically and clinically relevant polycyclic products, should also adhere to the principles of minimal waste and maximum atom economy..
By leveraging the remarkable coordination and activation properties of transition metals, we aim to design unconventional strategies that transform simple substances into cyclic, target-relevant products, with a particular emphasis on reactions that activate otherwise inert C–C and C–H bonds. The development of enantioselective variants of these processes, based on novel chiral transition metal catalysts, is also a major focus of our research.
For example, under the direct supervision of Dr. Fernando López, we have demonstrated the potential of platinum and gold catalysts in promoting novel annulations using allenes as key reaction partners. This approach enables the synthesis of diverse and valuable scaffolds, including substituted piperidines and aza-bridged medium-sized carbocycles (e.g., tropanes).
We also applied one of these methods for a highly efficient, versatile and enantioselective synthesis of Englerin A, a complex natural product that has attracted great interest as antitumoral agent.
Additionally, we have discovered various metal-catalyzed cycloadditions and cycloisomerization reactions as key steps in the construction of highly relevant polycyclic and heterocyclic systems. Recent efforts have particularly focused on developing new palladium catalysts, as well as exploring catalysts based on earth-abundant metals such as cobalt.
We are also developing highly enantioselective hydrocarbonation reactions based on the initial activation of C–H bonds of heteroaromatic systems. These methods enable the efficient asymmetric synthesis of synthetically relevant alkaloid-based structures featuring quaternary carbon stereocenters. Thus far, iridium catalysts have proven to be the most effective choice.
We have also worked extensively in the development of C-H activation/cycloaddition processes enabled by rhodium or palladium catalysts, as a direct entry to a variety of heterocycles and carbocycles. Additionally, we develop enantioselective C-H functionalization methods to access chiral heterocycles and atropoisomers, expanding the toolbox for precision synthesis in organic chemistry.
A crucial aspect of our research, supervised by Prof. M. Gulías and Prof. J. L. Mascareñas, also involves design and development of new chiral ligands to enhance selectivity and efficiency in these transformations.
Future research in this program will be mainly focused on the invention of novel, unconventional catalytic annulation technologies based on C-C and C-H activation protocols, and the application of our methods to streamline the assembly of enantioenriched, biorelevant carbo- and heterocyclic scaffolds.
Chemical biology and biomedicine
We are synthetic chemists, and as such, we can imagine and make molecules. If such molecules are appropriately designed so that they can probe or alter specific biological processes, we might be in the condition of contributing to Cell Biology and Medicine from a different perspective of more Biology-focused groups.
Therefore, our research lies at the interface of organic and synthetic chemistry with chemical and cell biology and biomedicine. Our group welcomes students with backgrounds from chemistry to biology or biotechnology.
A) Organometallic bioorthogonal chemistry
Leaded by Dr. M. Tomás and Prof. J. L. Mascareñas, our group has been among the pioneers to develop organometallic catalytic transformations within biological settings and living contexts. Despite the general belief that metal promoted reactions are incompatible with the aqueous environments of biological habitats, and that the metal complexes can be highly cytotoxic, we have extensively demonstrated the viability of some organometallic processes in live mammalian cells.
1. Bond-forming processes:
2. Bond-breaking processes
B) Bioorthogonal synthetic photocatalysis
Under the direction of Dr. M. Tomás and Prof. J. L. Mascareñas we have recently initiated a new research endeavor, focused on the use of visible light photocatalysis for promoting bioorthogonal synthetic reactions.
These efforts culminated with the first example of an abiotic photocatalytic bond-forming reaction that can take place in live cells. Specifically, our group demonstrated that exogenous styryl azides can be converted into indoles inside living mammalian cells under photo-catalytic conditions. Moreover, we could develop cell-selective photocatalytic reactions. These exciting results let us to initiate the essentially unexplored area of “synthetic bioorthogonal photocatalysis”.
C) Nanoscaffolds for bioorthogonal metal-catalysis
Artificial metallopeptides: Profiting from the previous experience of the group in supramolecular chemistry of DNA-protein interactions and the results on designing short peptides that display metal-promoted cell internalization, we have recently shown how pallado-miniproteins work as effective metalloreactors to promote depropargylation reactions inside living mammalian cells. These results represent a first step towards the development of a “bottom-up” strategy for the generation of artificial catalytic metalloproteins capable of working in the native living environment of enzymes. This research is performed in collaboration with E. Vázquez group.
MOFs and nanocapsules: Furthermore, we are currently exploring the combination of transition metal catalysts with nanomaterials in order to build up heterogenous catalysts which are compatible with cellular media. This work is being developed in collaboration with experienced groups in the field of nanomaterials (P. del Pino, M Correa, M. Souto, D. Maspoch, etc.).
MetBioCat
ERC Advanced Grant Project
Our aim is to discover robust transition-metal catalyzed transformations that can take place in aqueous media and cellular lysates, and are susceptible of being exported to living cells, so that in some way we could mimic the mode of action of enzymes.
Our transversal expertise in synthesis, metal catalysis, molecular recognition and chemical biology places us in a unique position to tackle this interdisciplinary project. The results of the project might lead to the development of new diagnostic and therapeutic tools as well as new biotechnological techniques.