Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

¹H NMR: Complex Splitting

¹H NMR: Complex Splitting

A proton M that is coupled to a proton X results in doublet signals for M. However, NMR-active nuclei can be simultaneously coupled to more than one nonequivalent nucleus. When M is coupled to a second proton A, such as in styrene oxide, each peak in the doublet is split into another doublet.
Splitting diagrams or splitting tree diagrams are routinely used to depict such complex couplings. While drawing splitting diagrams, the splitting with the larger coupling constant is usually applied first.

¹H NMR: Interpreting Distorted and Overlapping Signals

¹H NMR: Interpreting Distorted and Overlapping Signals

Spin systems where the difference in chemical shifts of the coupled nuclei is greater than ten times J are called first-order spin systems. These nuclei are weakly coupled, and their chemical shifts and coupling constant can generally be estimated from the well-separated signals in the spectrum.
As Δν decreases and the signals move closer, the doublets appear increasingly distorted. The intensities of the inner lines increase at the cost of those of the outer lines as the signals are slanted or...

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...

NMR and Mass Spectroscopy of Carboxylic Acids

NMR and Mass Spectroscopy of Carboxylic Acids

In ¹H NMR spectroscopy, acidic protons (–COOH) of carboxylic acids are highly deshielded and absorb far downfield, at around 9–12 ppm. The chemical shift value depends on the concentration and solvent used.
While α protons of carboxylic acids absorb at 2–2.5 ppm, β protons absorb further upfield.
Carboxylic acids are easily identified by dissolving them in deuterium oxide, which results in a rapid exchange of the acidic protons with deuterium. This leads to the disappearance of the acidic...

NMR Spectroscopy: Spin–Spin Coupling

NMR Spectroscopy: Spin–Spin Coupling

The spin state of an NMR-active nucleus can have a slight effect on its immediate electronic environment. This effect propagates through the intervening bonds and affects the electronic environments of NMR-active nuclei up to three bonds away; occasionally, even farther. This phenomenon is called spin–spin coupling or J-coupling. Coupling interactions are mutual and result in small changes in the absorption frequencies of both nuclei involved. While nuclei of the same element are involved in...

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Silicone oil in protein drug products and its implications for formulation stability.

Advanced drug delivery reviews·2026

Same author

Call For Papers: Molecular Understanding and Formulation Design for Peptide Delivery.

Molecular pharmaceutics·2026

Same author

Force Distribution and Contact Mechanics in Mini-Tablet Compaction: A Discrete Element Method Study.

Pharmaceutical research·2026

Same author

Long-term outcomes with emicizumab prophylaxis for haemophilia A in China: A multicentre, large-cohort retrospective study.

British journal of haematology·2026

Same author

Adipocyte Enhancer Binding Protein 1 (AEBP1) Inhibition as a Potential Anti-Fibrotic Therapy in Heart Failure.

Research square·2026

Same author

Extracellular matrix and cytoskeletal reverse remodeling pathways are key drivers of myocardial recovery following left ventricular assist device therapy.

bioRxiv : the preprint server for biology·2026

Search research articles

Related Experiment Video

Updated: Jun 23, 2026

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

Published on: February 19, 2016

Molecular Insight into Lipid Nanoparticle Assembly from NMR Spectroscopy and Molecular Dynamics Simulation.

Mingyue Li^1,2, Ryan Schroder², Umut Ozuguzel³

¹Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., Rahway, New Jersey 07065, United States.

Molecular Pharmaceutics

|March 26, 2025

Summary

This summary is machine-generated.

Lipid nanoparticles (LNPs) assembly remains poorly understood. This study reveals how formulation components like phospholipids, PEG lipids, and cholesterol influence LNP structure and dynamics, impacting stability and potency.

Keywords:

cationic and ionizable lipid lipid assembly lipid nanoparticles molecular dynamics molecular dynamics simulation solid-state NMR solution NMR structural packing

More Related Videos

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Published on: September 1, 2023

Author Spotlight: Enhancing Lipid Nanoparticle Formation Through Turbulent Mixing in Confined Geometries

Author Spotlight: Enhancing Lipid Nanoparticle Formation Through Turbulent Mixing in Confined Geometries

Published on: August 23, 2024

Related Experiment Videos

Last Updated: Jun 23, 2026

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

Published on: February 19, 2016

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches

Published on: September 1, 2023

Author Spotlight: Enhancing Lipid Nanoparticle Formation Through Turbulent Mixing in Confined Geometries

Author Spotlight: Enhancing Lipid Nanoparticle Formation Through Turbulent Mixing in Confined Geometries

Published on: August 23, 2024

Area of Science:

Biophysics
Materials Science
Pharmaceutical Sciences

Background:

Lipid nanoparticles (LNPs) are crucial for oligonucleotide delivery.
A mechanistic understanding of LNP assembly at the molecular level is lacking.
LNP formulation and engineering significantly impact therapeutic efficacy.

Purpose of the Study:

To elucidate the molecular-level structure and interactions of LNP components.
To investigate the impact of formulation and engineering on LNP assembly and properties.
To provide a structural basis for LNP stability and potency.

Main Methods:

Solution and solid-state Nuclear Magnetic Resonance (NMR) spectroscopy.
Molecular dynamics (MD) simulations.
Advanced NMR techniques including ³¹P NMR, ¹H-¹³C CP-MAS, ¹H relaxation, and 2D ¹H-¹H correlation.

Main Results:

Identified the interplay of phospholipids (DSPC), PEG lipid conjugates, and cholesterol in governing LNP size and dynamics.
Revealed intermolecular contacts among lipid components, providing a structural basis for LNP assembly.
Found cationic/ionizable lipids interacting with PEG lipids in the outer LNP layer, challenging conventional models.

Conclusions:

LNP structure is influenced by formulation components and engineering processes.
Molecular interactions and compositional distribution are critical for LNP engineering, stability, and potency.
LNPs possess an outer layer of lipid components surrounding a core, with specific lipid interactions dictating particle properties.