Introduction to NMR Spectroscopy and Imaging

Lecture 07 Basic Heteronuclear 2D Experiments

(Spring Term, 2011)

Department of ChemistryNational Sun Yat-sen University

核磁共振光譜與影像導論

Basic Heteronuclear 2D Experiments

Introduction

Heteronuclear correlation (HETCOR) and its variants (COLOC, HMBC etc)

Heteronuclear multiple-quantum coherence (HMQC)

Heteronuclear single-quantum coherence (HSQC)

Introduction

• The availability of other (“hetero”) nuclei than proton for multi-dimensional NMR spectroscopy is extremely useful, particularly, for macromolecules (of synthetic or biological origin) because the connectivity between protons and heteronuclear spins can be established in addition to the homonuclear multi-dimensional spectra.

• Like homonuclear 2D spectroscopy, the central task in heteronulcear 2D experiments is to select proper coherence pathways so that the desired interaction can be elucidated. Heteronuclear 2D experiments can be more diverse because, e.g., the data acquisition can be carried out on heteronuclei (C-13, N-15 etc) or on protons (inverse detection).

Heteronuclear correlation (HETCOR) and its variants

During t1, the carbons that are coupled to protons are selected so that only those carbons are “visible” in the detection period. The choice of two fixed delays Δ1 and Δ2 is determined by smallest J-coupling we want to observe, i.e., when long- range coupled carbons (in addition to directly bonded carbons) are also to be observed: Δ1=1/2Jmin, Δ2=1/3Jmin.

Enhanced Heteronuclear Correlation 0 0

, 1 x,S 1

1

0,

90 ( )t -180 ( )t

1

21 1 1 1

90

1sin sin

cos

( cos 2 )cos ( cos 2 )

2 sin

x I I S z z I S z z

z z z z

y I

JI S JI SI z S z I y S

x

z

y I y

JI S I SI y I S

z

z

I

z xy

z

I S

I S I S

I t S

I J t S JJ S I J

I S

0

,

1 1 1

901 1 1

cos 2 sin

2 sin cos 2 sinx S

I S x x

I z y I S x x

J t S I J

I S J t S I J

2

12

1 2 12 2 12sin sin co cos sins ( sin s n o) i c sz z z zJx I x S SI

I II

S SIS t S t tJ J J Jt

S(δI, δS)

ωI

ωS

COrrelation via LOng-range Coupling(COLOC)

The choice of two fixed delays Δ1 and Δ2 is determined by smallest J-coupling we want to observe, i.e., when long- range coupled carbons (in addition to directly bonded carbons) are also to be observed: Δ1=1/2Jmin, Δ2=1/3Jmin.

Heteronuclear Multi-Bond Correlation (HMBC)

Inverse Detection

HSQC

Points a-d (INEPT)

Points e-g (Reversed INEPT)

Phase Cycling

1 2 3, ; 8( ),8( ); 2( ), 2( ), 2( ), 2( );

2( , , , , , , , )rec

x x x x x y x y

x x x x x x x x

HMQC

Difference of HMQC and HSQC(I)

Difference of HMQC and HSQC(II)

2D J Spectroscopy2D methods that show coupling multipletsversus chemical shift. There is both ahomonuclear and a heteronuclear version.Both methods are useful for resolvingoverlapping multiplets. They are also used tomeasure coupling constants. These sequencesallow both J coupling and chemical shiftevolution but re-focus the chemical shifts like aspin echo sequence (90 - - 180 -- acq).

t1: J; t2: J+CS

t1: JIS, t2: JIS+CSS

,

0

0

0

I

I S

I

S

I z

z z z z

z z

z z

I

JI S JI S

JI S

JI S

Summary

HETCOR, COLOC

HSQC/HMQC

HMBC

J spectrosc.

HSQC is now a “platform” for many more complicated pulse sequences.