LR-HSQMBC: a sensitive NMR technique to probe very long-range heteronuclear coupling pathways

Area of Science:

• Nuclear Magnetic Resonance (NMR) Spectroscopy
• Organic Chemistry
• Structural Elucidation

Background:

• Heteronuclear Multiple Bond Correlation (HMBC) is a standard NMR experiment for structure determination.
• HMBC typically detects correlations across two or three bonds (2,3JCH).
• Limitations exist in HMBC for analyzing proton-deficient molecules.

Purpose of the Study:

• To develop a novel NMR pulse sequence with enhanced sensitivity.
• To extend the range of detectable heteronuclear couplings beyond the typical HMBC limitations.
• To provide a complementary technique for HMBC in structural analysis.

Main Methods:

• Development of a high-sensitivity NMR pulse sequence (LR-HSQMBC).
• Optimization of responses for very small long-range (n)JCH couplings.
• Utilizing Density Functional Theory (DFT) calculations to validate observed correlations.

Main Results:

• The LR-HSQMBC experiment visualizes long-range heteronuclear couplings up to 4-, 5-, and 6-bonds (nJCH).
• This technique overcomes the (2,3)JCH limitation of standard HMBC.
• LR-HSQMBC provides data comparable to 1,n-ADEQUATE, even in sample-limited scenarios.
• DFT calculations supported the observed long-range correlations in cervinomycin A2.

Conclusions:

• LR-HSQMBC is an effective NMR experiment for complementing HMBC.
• The technique is particularly useful for probing the structures of proton-deficient molecules.
• LR-HSQMBC offers extended range and sensitivity for structural elucidation in challenging samples.