The search of new therapies for cancer is a primary EU mission. In-cell redox catalysis promoted by organometallic complexes of precious metals as Ru(II), Os(II), Rh(III) and Ir(III) is a novel promising concept to access more efficient, safer, and less invasive medicines. Co-CaReD aims to design new in-cell catalytic systems based on half-sandwich Co(III) complexes. Cobalt combines effective catalytic performances for biomedical applications and high catalytic versatility. Moreover, it is a cheap, sustainable, and biocompatible metal whose peculiar chemical properties can access unique reactivity pathways. The project will focus on the development of new synthetic catalysts, on their applications in redox reactions of therapeutic interest, involving known examples and unprecedent cases of study, and on the unveiling of their biological mechanism of action in cancer cells. Co-CaReD will be implemented in a vibrant and stimulating research environment at IMDEA Nanociencia, in Dr. Ana Pizarro research group. The project will benefit of the complementary expertise of the ER in organometallic chemistry and redox catalysis and of the supervisor in studying the intracellular reactivity at the molecular level of metal-based drugs. An intense training plan is designed to equip the researcher with the necessary skills to study the biological activity of the Co(III) catalysts – including single-cell studies – and to design proof-of-concept experiments that confirm the occurrence of a metal-based catalytic reactivity inside the human cells. The main goal of Co-CaReD is to generate novel redox catalytic systems based on more biocompatible, less toxic, and cheaper cobalt drug candidates, as complementary tools to noble metal complexes.

Photoinduced electron transfer (ET) and charge transfer (CT) processes occurring in organic materials are the cornerstone of technologies aiming at the conversion of solar energy into electrical energy and at its efficient transport. Thus, investigations of ET/CT induced by visible (VIS) and ultraviolet (UV) light are fundamental for the development of more efficient organic opto-electronic materials. The usual strategy to improve efficiency is chemical modification, which is based on chemical intuition and try-and-error approaches, with no control on the ultrafast electron dynamics induced by light. Achieving the latter is not easy, as the natural time scale for electronic motion is the attosecond (10-18 seconds), which is much shorter than the duration of laser pulses produced in femtochemistry laboratories. With femtosecond pulses, one can image and control “slower” processes, such as isomerization, nuclear vibrations, hydrogen migration, etc., which certainly affect ET and CT at “longer” time scales. However, real-time imaging of electronic motion is possibly the only way to fully understand and control the early stages of ET and CT, and by extension the coupled electron-nuclear dynamics that come later and lead (or not) to an efficient electric current. In this project we propose to overcome the fs time-scale bottleneck and get direct information on the early stages of ET/CT generated by VIS and UV light absorption on organic opto-electronic systems by extending the tools of attosecond science beyond the state of the art and combining them with the most advanced methods of organic synthesis and computational modelling. The objective is to provide clear-cut movies of ET/CT with unprecedented time resolution and with the ultimate goal of engineering the molecular response to optimize the light driven processes leading to the desired opto-electronic behavior. To this end, synergic efforts between laser physicists, organic chemists and theoreticians is compulsory.

Almost all biological processes, involving molecular trafficking, signal-transduction, cell-to-cell interactions, hinge on precisely orchestrated electrostatic interactions, arising from electrical charges on biomolecules and membranes. Yet, our understanding of the role of electrostatics in these fundamental processes remains elusive due to the absence of quantitative methods to measure the electrical charges of biomolecules and to map the surface charge distribution of membranes. This challenge is further compounded by the requirement of capturing molecular and membrane dynamics that take place at the nanometre length scales and nano- to sub-millisecond time scales. The overall objective of this project is to bridge this technological gap by introducing Metal-Induced Energy Transfer based Electrometry and Nanometry (MIETEN), a groundbreaking technology that will quantify the electrical charge of biomolecules or membranes while capturing their dynamics with nanometre spatial and microsecond temporal resolutions. We will demonstrate MIETEN for measuring: (i) the charges and sizes of individual membrane proteins, (ii) membrane protein structural changes, conformational dynamics, and spatial organization in response to changes in membrane potential, (iii) reaction-diffusion kinetics at a charged membrane, (iv) mechanical properties and dynamics of membranes containing charged inclusions and (v) interactions between two charged membranes. The ability to measure biomolecular and membrane electrical charges and to elucidate the role of electrostatics in structure, organization, and interactions of proteins, as well as in membrane dynamics and intermembrane interactions, will be crucial for our understanding of fundamental biology and for advancing biomedical research. MIETEN will open new frontiers in studying protein and membrane dynamics and impact drug development, early diagnostics, and therapeutic interventions.