Intermolecular interactions determined by NOE build-up in macromolecules from hyperpolarized small molecules

Area of Science:

• Nuclear Magnetic Resonance (NMR) Spectroscopy
• Biophysical Chemistry
• Chemical Physics

Background:

• Nuclear Overhauser effect (NOE) is crucial for characterizing intermolecular interactions via NMR.
• Conventional multi-dimensional NMR methods for NOE analysis are time-consuming.
• Hyperpolarization techniques offer significant signal enhancement.

Purpose of the Study:

• To demonstrate the application of dissolution dynamic nuclear polarization (D-DNP) for real-time NOE buildup measurements.
• To investigate intermolecular interactions between small molecules and macromolecules using D-DNP enhanced NMR.
• To showcase the potential of D-DNP for rapid characterization of host-guest systems.

Main Methods:

• Utilized dissolution dynamic nuclear polarization (D-DNP) to hyperpolarize 1H phenylbutazone (PBZ).
• Mixed hyperpolarized PBZ with the G3 polyamidoamine dendrimer (PAMAM) host.
• Acquired series of 1D NMR spectra to observe NOE buildup in real-time.
• Determined cross-relaxation rates from NOE buildup curves.

Main Results:

• Successfully observed real-time NOE buildup at various sites of the G3 PAMAM dendrimer.
• Quantified site-specific cross-relaxation rates between PBZ and PAMAM.
• Achieved signal-to-noise ratios sufficient to detect cross-peaks absent in conventional 2D-NOESY spectra.
• Demonstrated the applicability of D-DNP for studying small molecule-macromolecule interactions.

Conclusions:

• D-DNP significantly accelerates the characterization of intermolecular interactions using NOE measurements.
• Hyperpolarized NMR enables near-instantaneous analysis, overcoming limitations of conventional NMR techniques.
• This approach holds promise for applications in macromolecular and biomacromolecular NMR studies.