Research topics

We are currently pursuing several research directions, with more on the horizon. A unifying theme across these efforts is the search for strategies that enable the amplification of NMR signals in solution.

SABRE

SABRE (Signal Amplification By Reversible Exchange) is a hyperpolarization technique in which parahydrogen transfers its enhanced nuclear spin signal to target molecules through transient, reversible binding with an iridium-based catalyst. Our research focuses on designing and synthesizing new Ir-based catalysts to optimize this signal transfer and improve overall hyperpolarization efficiency. A key objective is to extend SABRE’s applicability to biologically relevant compounds, including pyruvate, acetate, amino acids, and pharmaceutical agents, in order to enhance the detection of clinically significant biomarkers.

PHIP

In PHIP-SAH (Side Arm Hydrogenation), parahydrogen transfers its spin polarization to target nuclei through a non-reversible hydrogenation process. Our research focuses on developing new rhodium-based catalysts and biologically relevant molecular precursors to enhance the efficiency of this method, improve the signal amplification of key biomarkers, and broaden its potential applications.

nhPHIP

Non-hydrogenative PHIP (nhPHIP) typically employs the same iridium-based catalysts used in SABRE. However, instead of transferring polarization to nuclei in their free form, nhPHIP focuses on the distinctive antiphase hydride signals that appear of the bound-to -catalyst species in the negative chemical shift region of the proton NMR spectrum. This fingerprint-like signature enables a wide range of applications, including the analysis of biological fluids such as urine to detect low-concentration metabolites of clinical relevance.

DNP

In Dynamic Nuclear Polarization (DNP), the source of signal enhancement is no longer parahydrogen but rather the electron spin. Our research explores new strategies to amplify nuclear spin signals in solution through electron-nuclear spin interactions. We aim to identify the key factors that govern this process in order to improve and further advance the capabilities of this technology.

Collaborations

Many great colleagues are helping us pursue different research endeavours. None of this would be possible without their active involvement.

Characterization of SABRE catalysts: Dr. Callum Gater and Prof. Simon Duckett, York University (UK)
Synthesis of Catalysts for SABRE and PHIP: Prof. Cristina Tubaro, Università di Padova (IT)
Theoretical modelling of SABRE: Dr. Salvatore Mamone, Università dell'Aquila (IT)
Radical characterization: Prof. Lorenzo Franco and Prof. Marco Ruzzi, Università di Padova (IT)

Instrumentation

Hardware development

Performing non-standard NMR experiments often requires custom-made instrumentation — from building probes, tuning/matching circuits and microcoils for fields below 0.5 T, to automated parahydrogen bubbling systems and rapid sample-transfer devices. We are interested in designing and refining these tools to enable new NMR experiments and broaden the scope of hyperpolarized NMR applications.

References:

1) A Controlled System for Parahydrogen Hyperpolarization Experiments L. Franco, F. Floreani, S. Mamone, A. M. Faramawy, M. Ruzzi, C. Tubaro and G. Stevanato *

Parahydrogen

Parahydrogen-based methods.

We work on PHIP-SAH trying to lead this technique to cellular metabolic investigations based on an established protocol that enables hyperpolarization experiments in acetone, followed by redissolution into aqueous buffered solutions containing living cells where it has been successfully demonstratedthe metabolic conversion of pyruvate to lactate.

References:

1) Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP J. Am. Chem. Soc. 2023, 145, 10, 5864–5871

2) Real-time cell metabolism assessed repeatedly on the same cells via para-hydrogen induced polarization, Chem. Sci., 2023, 14, 7642-7647

DNP

DNP-based methods.

We are setting up all is needed to make Dynamic Nuclear Polarization in solution and at ambient temperature.

References:

1) A factor two improvement in high-field dynamic nuclear polarization from Gd (iii) complexes by design, J. Am. Chem. Soc. 2019, 141, 22, 8746-8751

2) Open and Closed Radicals: Local Geometry Around Unpaired Electrons Governs MAS DNP Performance, J. Am. Chem. Soc. 2020, 142, 39, 16587–16599

Long-lived states

Long-lived nuclear spin states-based methods.

A rather exotic yet fascinating line of research focuses on molecular species in which thermalization mechanisms are in part suppressed, allowing them to persist for remarkably long times and give rise to long-lived NMR signals.

References:

1) A nuclear singlet lifetime of more than one hour in room‐temperature solution, Angew. Chem. Int. Ed. 2015, 54, 12, 3740-3743

2) Alternating Delays Achieve Polarization Transfer (ADAPT) to heteronuclei in PHIP experiments, J. Magn. Reson. 2017, 274, 148-162

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