Responsabile Scientifico

• CARNIATO Fabio (DiSIT)

Titolo del progetto

• Exploring Spin Dynamics of Earth Abundant Transition Metal Ion Complexes as MRI Diagnostic Probes - STARS

Ente finanziatore

• MUR - Ministero dell'Università e Ricerca

Programma di finanziamento

• PRIN - Progetti di Ricerca di Rilevante Interesse Nazionale (dal 2020)

Bando di riferimento

• PRIN 2022 PNRR

Anno di presentazione del progetto

• 2022

Anno di approvazione del progetto

• 2023

Acronimo del progetto

• STARS

Project ID / numero contratto

• P20224R8YZ

Durata del progetto

• 24 mesi

Inizio del progetto

• 30/11/2023

Fine del progetto

• 29/11/2025

Ente capofila

• UNITO - Università degli studi di Torino

Progetto approvato - Contributo unità di ricerca del Dipartimento

• €105.708,00

Aree tematiche

• Salute

Keyword

• Spin dynamics
• NMR relaxometry
• medical diagnostic
• Paramagnetic relaxation
• EPR Spectroscopy
• transition metal ion chelates

Stato del progetto

• Approvato

Abstract

• The progress and innovation of the EU health industry as well as the development of inclusive and safe health policies rely on the development of breakthrough technologies, which in turn are based on the gain of fundamental knowledge. STARS is a curiosity-driven project aiming at advancing our understanding on the spin dynamics of paramagnetic complexes of earth abundant and essential transition metal ion complexes for the design of new and safer magnetic resonance imaging (MRI) contrast agents. Metal containing contrast agents have contributed to the success of MRI as a diagnostic procedure in biomedicine. At present contrast agents are almost exclusively Gd(III) based chelates and 8% of the Gd market share is absorbed by the manufacture of pharmaceutical products for MRI applications. However, criticalities related to Gd supply risks, as well as concerns on its long-term safety, call for possible alternatives. The overarching objective of STARS is to explore Gd substitutes based on abundant and well biologically tolerated paramagnetic first-row transition-metal ions (TMI) such as Cu(II) and V(IV). We plan to combine advanced electron and nuclear magnetic resonance techniques and computational modelling to provide a new and deep understanding of the factors governing the spin dynamics and the relaxivity of a library of Cu and V chelates under different experimental conditions (pH, redox environment, etc). In addition, their potential as a switchable redox sensing contrast agents will be also investigated, exploiting the redox conversion between paramagnetic (Cu(II) and V(IV)) and diamagnetic (Cu(I) and V(V)) redox states. Building upon the partners’ different and complementary competences, STARS will converge towards the following objectives: (O1): To develop an integrated general Magnetic Resonance approach based on the complementary use of advanced EPR and 1H NMR relaxometric techniques for the characterization of paramagnetic relaxivity. (O2): To understand the mechanism of proton relaxation of V(IV) and Cu(II) complexes, assess the role of contact contributions, optimize water interactions, proton exchange and field strength dependence of electronic relaxation of complexes of differing geometry. (O3): To develop a general methodology to translate the analytical results in new advances of health technologies, including optimization of redox responses for the development of activatable compounds, capable of responding to external stimuli such as pH changes. The results are expected to provide the first comprehensive characterization of the relaxivity properties of V and Cu complexes, developing a new holistic approach for the determination of spin dynamic properties of paramagnetic TMI in solution. This knew knowledge will provide guidelines to tune and engineer the relaxation properties of paramagnetic complexes enabling the replacement of critical elements such as Gd and improving the accuracy of existing diagnostic processes.