Abstract
Time is a critical dimension in chemistry and biology. Studying the composition of chemical systems as they evolve, including the effects of processing, use, and wear, provides access to the mechanisms underlying the transfor-mations, either wanted or unwanted, as they occur. If monitoring of molecular events can occur in real-time, it can allow for adjusting the reaction conditions to maximize the wanted transformation and minimize the unwanted ones. In biological systems, which are constantly out of equilibrium, real-time monitoring provides precious in-sights into the kinetics of the underlying molecular events. Therefore, real-time approaches can radically change the approach to studying chemical and biological processes, paving the way to increased sustainability and a better understanding of living systems. However, selectively observing molecular events which take place within mixtures of high complexity is a challenging task. Commonly-used spectroscopies (UV-VIS, IR) are defeated by the fact that reactants, intermediates, and products have largely superimposable structures, which in turn are reflected in spec-tra that are difficult to disentangle, and the relation between the spectral response and concentrations must be identified (absorption coefficients). On the contrary, NMR is uniquely suited for characterizing the complex re-sponses of these systems. It is intrinsically quantitative, as all the active nuclei provide a signal proportional to their concentration regardless of the chemical environment they are found in, and it is also perfectly selective as even the smallest structural perturbation is reflected in detectable shifts. Finally, its non-destructive nature makes it ideal for application to biological samples. Historically, however, NMR has not been included in online reaction monitoring applications because of its intrinsic low sensitivity, which in turn yields long measurement times, and the application to real-time monitoring of living cells is still in its infancy. In this project, we will develop new acquisition and processing schemes with the aim of reducing the time burden of the NMR experiments while preserving the level of attainable information, thereby pushing the usability of real-time NMR methodologies for real-time monitoring of chemical reactions and biological processes. In particular, we will focus on the development and implementation of blind-source-separation (BSS) methods and fast NMR exper-iments, and to apply them to a number of biotechnologically-relevant test cases including target-based drug screening in-cell, food processing, and biotransformations. We expect that the methods we propose will lead to a quick maturation of the application for real-time monitoring and that, in the longer run, they might become a standard for time-resolved NMR investigations.
Project details
Unibo Team Leader: Elena Babini
Unibo involved Department/s:
Dipartimento di Scienze e Tecnologie Agro-Alimentari
Coordinator:
Università degli Studi di FIRENZE(Italy)
Total Unibo Contribution: Euro (EUR) 69.400,00
Project Duration in months: 24
Start Date:
28/09/2023
End Date:
28/02/2026
