Advanced NMR Techniques for the Investigation of Small Molecules in Solution

Table of Contents

ABBREVIATIONS ... x

1 INTRODUCTION ... 1

2 OUTLINE ... 22

3 APPLICATIONS OF SLICE-SELECTIVE NMRSPECTROSCOPY ... 23

4 ANISOTROPIC NMRSPECTROSCOPY IN POLYMERIC GELS ... 45

5 EXPERIMENTAL PART ... 81

6 APPENDIX ... 94

7 REFERENCES ... 125

DANKSAGUNG ... 135

CURRICULUM VITAE ... 136

A BBREVIATIONS

1 I NTRODUCTION

1.1 Lithium Organic Compounds

1.1.1 Applications

1.1.2 Structure Determination

Structure Determination in Solid State

Structure Determination in Solution

1.2 Slice-Selective Excitation

1.2.1 Principles

⃗⃗⃗

⃗⃗⃗

⃗⃗⃗

𝜈_z =𝛾 ∙ 𝐺_z∙ 𝑧′

2π

∆𝑧 =2𝜋 ∙ ∆𝜈_BW 𝛾𝐺_z

1.2.2 Applications

1.3 Anisotropic NMR Spectroscopy

1.3.1 Residual Dipolar Couplings

Theoretical Basics of (Residual) Dipolar Couplings

𝐷 = − 3

8π²𝑅³𝛾_T𝛾_S𝜇₀ℏ (cos² 𝜃 −1 3)

⃗⃗⃗

⃗⃗⃗

𝐀 = (

𝐴_xx 𝐴_xy 𝐴_xz 𝐴_yx 𝐴_yy 𝐴_yz 𝐴_zx 𝐴_zy 𝐴_zz

) (1-4)

𝐀 = 𝐏 −1

3𝟏 (1-5)

𝑃_x̃ 𝑃_ỹ 𝑃_z̃

⃗⃗⃗

𝐏_PAS= (

𝑃_x̃ 0 0 0 𝑃_ỹ 0 0 0 𝑃_z̃

) (1-6)

𝐷̅ = − 3

8𝜋²𝑅³𝛾_T𝛾_S𝜇₀ℏ (𝑟 ^𝑇𝐀𝑟 ) (1-7)

⃗⃗ ⃗⃗

Experimental Determination of RDCs

𝑇_CH

1 = 𝐽¹_CH+ 𝐷¹ _CH (1-8)

Applications of Residual Dipolar Couplings

1.3.2 Residual Quadrupolar Couplings

Theoretical Basics of (Residual) Quadrupolar Couplings

𝐕 = (

𝑉_xx 𝑉_xy 𝑉_xz 𝑉_yx 𝑉_yy 𝑉_yz 𝑉_zx 𝑉_zy 𝑉_zz

) (1-9)

̃ ̃ ̃

𝜂 =𝑉_x̃− 𝑉_ỹ

𝑉_z̃ (1-10)

𝜈_q = ^3𝜒

4𝐼(2𝐼−1)(3cos²𝛽 − 1 + 𝜂sin²𝛽cos 2𝛼) (1-11)

𝜒 =𝑒²𝑞𝑄

ℎ (1-12)

̃

𝜈_rq = 3𝑒𝑄

2𝐼(2𝐼 − 1)ℎ ∑ 𝑉_ij𝐴_ij

i,j=x,y,z

(1-13)

Applications of (Residual) Quadrupolar Couplings

1.3.3 Alignment Techniques

2 O UTLINE

Slice-Selective Excitation

Anisotropic NMR Spectroscopy

3 A PPLICATIONS OF S LICE -S ELECTIVE NMR S PECTROSCOPY

3.1 Preparation of the SSE Experiments

Determination of the magnetic field gradient strength

𝜈_z=𝛾 ∙ 𝐺_z∙ 𝑧

2𝜋 (1-1)

𝐺_z = 𝑔_IG∙ 𝐼_a (3-1)

𝐺_z =2𝜋 ∙ ∆𝜈_z

𝛾 ∙ 𝛥𝑧_z (3-2)

Setting of the pulse duration and power

Determination of the spatial detection sensitivity

3.2 Observation of Reactions

Reaction between nBuLi and PMDTA

3.3 Single-Shot Titration

Titration of Li⁺ with 12-crown-4

3.4 Qualitative Chromatography

Separation of amino acids L-aspartic acid, L-histidine, L-tyrosine and L-valine in agarose

𝑐

𝑐_𝑜= erfc ( 𝑧

2√𝐷_SSE𝑡) (3-3)

̅

̅ ̅ ̅

1

𝑇₂ = 1

𝑇_2,bulk+ 𝛿𝑆

𝑉 (3-4)

𝐼_cpmg

𝐼_cpmg,0= exp (− 𝑡

𝑇₂) (3-5)

̅

̅

̅

̅

̅

̅ ̅

3.5 Summary and Outlook Slice-Selective Excitation

4 A NISOTROPIC NMR S PECTROSCOPY IN P OLYMERIC G ELS

4.1 Alignment of Small Symmetric Molecules



〈𝐷〉 = 𝐷_||3 cos²𝜙 − 1

2 (4-1)

〈 〉

𝐀_PAS= (

𝐴_𝑥̃ 0 0 0 𝐴_𝑦̃ 0 0 0 𝐴_𝑧̃

) (4-2)

𝐷 = 𝑘(𝐴_x̃sin²𝜗cos²𝜑 + 𝐴_ỹsin²𝜗sin²𝜑 + 𝐴_z̃cos²𝜗) (4-3)

𝐴_x̃ 𝐴_ỹ 𝐴_𝑧̃

𝐴_x̃ 𝐴_ỹ 𝐴_z̃

̃ ̃ ̃

𝑨_𝐱̃

𝑨_𝐲̃

𝑨_𝐳̃

𝐴_x̃ 𝐴_ỹ 𝐴_z̃

𝐴_𝑧̃

̃ ̃ ̃

𝑨_𝐱̃

𝑨_𝐲̃

𝑨_𝐳̃

4.1.1 Molecular Dynamics Simulations

4.2 Structure Elucidation of Synthetic Indanes

𝑄 = √∑(𝐷_calc,i− 𝐷_exp,i)²

∑ 𝐷_exp,i (4-4)

4.2.1 Structural Error Analysis

4.3 Quantitative Analysis of Residual Quadrupolar Couplings

𝜈_rq = 3𝑒𝑄

2𝐼(2𝐼 − 1)ℎ ∑ 𝑉_ij𝐴_ij

i,j=x,y,z

(1-13)

〈 〉

𝐴_x̃ 𝐴_ỹ 𝐴_z̃

̃

̃

̃

̃

| _̃|

̃

̃

̃

̃

̃

̃

̃

̃ ̃

𝜈_rq =3𝑒𝑄

4ℎ 𝐴_z̃𝑉_z̃ (4-5)

̃ ̃

̃ ̃

̃

̃ ̃

4.4 Summary and Outlook Anisotropic NMR Spectroscopy

5 E XPERIMENTAL P ART

5.1 Sample Preparation

5.2 NMR Experiments

5.3 Processing of NMR Data

5.4 Computational Techniques

6 A PPENDIX

A Applications of Slice-Selective NMR Spectroscopy ... 95

B Anisotropic NMR Spectroscopy in Polymeric Gels ... 99

A Applications of Slice-Selective NMR Spectroscopy

Preparation of SSE Experiment Data

Imaging Pulse Sequence

SSE Pulse Sequence

Observation of Reactions Data

Single-Shot Titration Data

Qualitative Chromatography Data

Relaxation Data

B Anisotropic NMR Spectroscopy in Polymeric Gels

Alignment of Small Molecules Data

Least-Square Solution Script

MD Energy Optimization Run File

Exemplary MD Simulation Run File

Exemplary OPLS Topologies

Structural Elucidation of Synthetic Indanes Data

Exemplary ORCA input files geometry optimization and numerical frequencies

Structure Data β-aa-H*

Structure Data β-aa-Me*

RDC Data β-aa-H*

RDC Data β-aa-Me*

Exemplary MSpin Input and Output

Structural Noise Script

Extended NMR Spectroscopy of Synthetic Indanes

Quantitative Analysis of Residual Quadrupolar Couplings Data

Exemplary ORCA input files EFG tensor calculation

Structure Data of [CpLi(OMe

)], [CpLi(OMe

)

], [CpLi(OMe

)

] and [Cp

Li]

7 R EFERENCES

‐

‐

D ANKSAGUNG

C URRICULUM V ITAE

EDUCATION

SCHOLARSHIPS AND AWARDS

TEACHING ACTIVITY

VARIOUS WORKING EXPERIENCES

VOLUNTARY SERVICES

PERSONAL SKILLS

CONFERENCES AND WORKSHOPS

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