Magnetization Lifetimes Prediction and Measurements Using Long-Lived Spin States in Endogenous Molecules

F Teleanu,P R Vasos,A Cucoanes,C Tuță,S Vasilca

doi:10.3390/molecules25235495

Abstract

Nuclear magnetization storage in biologically-relevant molecules opens new possibilities for the investigation of metabolic pathways, provided the lifetimes of magnetization are sufficiently long. Dissolution-dynamic nuclear polarization-based spin-order enhancement, sustained by long-lived states can measure the ratios between concentrations of endogenous molecules on a cellular pathway. These ratios can be used as meters of enzyme function. Biological states featuring intracellular amino-acid concentrations that are depleted or replenished in the course of in-cell or in-vivo tests of drugs or radiation treatments can be revealed. Progressing from already-established long-lived states, we investigated related spin order in the case of amino acids and other metabolites featuring networks of coupled spins counting up to eight nuclei. We detail a new integrated theoretical approach between quantum chemistry simulations, chemical shifts, J-couplings information from databanks, and spin dynamics calculations to deduce a priori magnetization lifetimes in biomarkers. The lifetimes of long-lived states for several amino acids were also measured experimentally in order to ascertain the approach. Experimental values were in fair agreement with the computed ones and prior data in the literature.

Highlights

Predictive modeling of cancer cell sensitivity to various therapies can be based on metabolomics [1].Equilibria of concentrations of endogenous small molecules can be both the motor and most sensitive diagnostic of biological transformations
We explore the lifetime of long-lived states in simple endogenous molecules that are suitable for in cells orfor in the vivo experiments as biomarkers of metabolic processes
Our investigations first addressed several of amino acids from experimental and molecules theoretical that are suitable in cells or ininsights vivo NMR

Summary

Introduction

Predictive modeling of cancer cell sensitivity to various therapies can be based on metabolomics [1]. Our investigations first addressed several of amino acids from experimental and molecules theoretical that are suitable in cells or ininsights vivo NMR actingofaslong-lived biomarkers of metabolic processes perspectives, infor order to gain intoexperiments the applicability states on coupled proton using theoretical approaches This analysis provides, via computational techniques, networks inside and theirexperimental structure, where such networks reached up to eight spins (in phenylalanine). These QISR states displayed improved lifetimes in low magnetic field B0 = 1 T, which makes them good candidates for studying biochemical transformations in vivo

Materials and Methods

Conclusions