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Molecular-Level Insights into the NMR Relaxivity of Gadobutrol Using Quantum and Classical Molecular Simulations

Thiago J Pinheiro Dos Santos1, Carla C Fraenza2,3, Giselle de Araujo Lima E Souza2

  • 1Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, United States.

Chemical & Biomedical Imaging
|September 26, 2025
PubMed

Insights

Molecular dynamics simulations reveal how Gadobutrol, an MRI contrast agent, affects water’s NMR relaxation. This parameter-free approach provides insights into developing more effective MRI contrast agents by understanding molecular-level processes.

Area of Science:

  • Computational Chemistry
  • Magnetic Resonance Imaging (MRI)
  • Molecular Dynamics

Background:

  • MRI is crucial for medical diagnostics, but understanding contrast agent molecular interactions is challenging.
  • Developing improved MRI contrast agents requires detailed knowledge of water's NMR relaxation processes.
  • Current understanding of molecular-level mechanisms governing relaxivity is limited.

Purpose of the Study:

  • To perform the first molecular dynamics simulations of Gadobutrol using quantum-based polarizable force fields.
  • To determine the 1H NMR longitudinal relaxivity (r1) of the aqueous phase without adjustable parameters.
  • To elucidate the molecular-level processes governing r1 dispersion and contrast agent effectiveness.

Main Methods:

  • Utilized quantum-based polarizable force fields for molecular dynamics (MD) simulations of Gadobutrol.
  • Calculated 1H NMR longitudinal relaxivity (r1) dispersion (frequency dependence) directly from MD trajectories.
  • Decomposed the NMR dipole-dipole autocorrelation function into molecular modes for mechanistic insights.

Main Results:

  • MD simulations of r1 dispersion showed good agreement with clinical MRI frequencies.
  • Outer-shell water contributed approximately 50% to Gadobutrol's total relaxivity, unlike gadolinium-aqua (15%).
  • Identified the crucial role of the second eigenmodal decay in governing r1 and its multiexponential nature.

Conclusions:

  • This parameter-free MD approach accurately simulates Gadobutrol's NMR relaxivity and its frequency dependence.
  • Outer-shell water dynamics significantly influence relaxivity, offering a key target for contrast agent design.
  • The study provides fundamental molecular insights crucial for developing next-generation MRI contrast agents.
Keywords:
GadobutrolMRI contrast agentsMolecular Dynamics SimulationsNMR dispersion

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