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Top of Page Ph.D. Thesis
This page describes my Ph.D. thesis with the title:

Computer Simulation of Chemical and Biological Properties of Saccharides:
Sucrose, Fructose, Cyclodextrins, and Starch

PD Dr. S. Immel, Ph.D. Thesis, Darmstadt University of Technology, 1995.

The Ph.D. Thesis was carried out from Oct.1990 till Nov.1994 under the supervision of Prof. Dr. Dr. h.c. F. W. Lichtenthaler at the Institute of Organic Chemistry at the Darmstadt University of Technology. This work is divided into several independent English-written chapters and a German introduction. References and Notes are given in the last chapter.
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Structure of Sucrose
Structure of Sucrose
Top of Page Ph.D. Thesis - Table of Contents
Computer Simulation of Chemical and Biological Properties of Saccharides: Sucrose, Fructose, Cyclodextrins, and StarchPage
Title + Remarks + Contents
Chapter 1 - Computersimulation chemischer und biologischer Eigenschaften von Sacchariden1
Das Molekulare Elektrostatische Potential (MEP) der Saccharose3
Das Molekulare Lipophilie-Profil (MLP) der Saccharose5
Struktur-Süßkraftbeziehungen der Fructose8
Nicht-Kohlenhydrat Süßstoffe9
Hydrophobie-Profile von Cyclodextrinen10
Kleinere Cyclodextrine, Cyclomannine, Cyclogalactine und Cyclofructine11
Die Hydrophobie-Charakteristika von Stärke13
Abschließende Bemerkungen14
Chapter 2 - Sucrose, Sucralose, Fructose, and some Non-Carbohydrate High-Potency Sweeteners: Correlations Between Hydrophobicity Patterns and AH-B-X Assignments17
The Electrostatic Potential Profiles and Hydrophobicity Patterns of Sucrose20
The Tripartite AH-B-X Glucophore in Sucrose Derivatives25
β-D-Fructopyranose: Conformations and Molecular Lipophilicity Profiles38
Molecular Lipophilicity Profiles of Non-Carbohydrate, High-Potency Sweeteners44
Chapter 3 - Sucrose: Generation of Molecular Electrostatic and Lipophilic Profiles and their Implications on Hydroxyl Group Reactivities and Sweetness Elicitation51
Solid-State and Solution Conformation of Sucrose52
Conformational Properties of the Isolated Sucrose Molecule53
Molecular Dynamics of Sucrose in Aqueous Solution58
Relative Stabilities of Sucrose Solution Conformations61
Umbrella Sampling Procedure62
Free Energy Profile of Sucrose in Aqueous Solution63
The Molecular Electrostatic Potential (MEP) Profile of Sucrose68
Computational Basics68
Visualization of Data68
Chemical Implications of the MEP Profiles70
MEP Pattern of Sucrose and Hydrogen Bonding73
The Molecular Lipophilicity Pattern (MLP) of Sucrose73
Localization of Hydrophobicity74
Application of the Hydrophobicity Mapping75
Biological Significance of the Molecular Lipophilicity Profiles76
The Modified AH-B-X-Concept of Structure-Sweetness-Relationships77
Assessment of the Modified AH-B-X-Concept with Sucrose Derivatives79
Hydrophobicity Pattern of Sucralose81
Quantitative Sweetness-Hydrophobicity Relationships for Halo-Sucroses84
Appendix - Computational Methods87
I. F / Y-Energy Potential Surfaces and Contour Plots87
II. Molecular Dynamics Simulations88
III. Free Energy Calculations using Umbrella Sampling88
Chapter 4 - Fructose: Structure-Sweetness Relationships on the Basis of Electrostatic and Lipophilicity Potential Profiles91
Molecular Geometry of β-D-Fructopyranose93
Molecular Electrostatic Potential (MEP) Profile of β-D-Fructopyranose95
Molecular Lipophilicity Pattern (MLP) of β-D-Fructopyranose98
Experimental Corroboration of AH-B-X-Assignments99
Comparison of β-D-Fructopyranose and α-L-Sorbopyranose102
Appendix - Computational Methods107
Chapter 5 - Fructose: Conformational Properties of all Different Tautomers and Implications of their Lipophilicity Patterns on Sweetness109
Pyranoid Fructose Tautomers - β- and α-D-Fructopyranose110
Furanoid Fructose Tautomers - β- and α-D-Fructofuranose112
Conformations of Five-Membered Ring Systems112
Conformational Properties of Cyclopentanol and Tetrahydro-2-furanol in Relation to the Anomeric Effect114
Energy Potential Surfaces of β- and α-D-Fructofuranose120
Statistical Crystal Structure Analysis121
NMR-Data in Relation to Molecular Conformation128
Acyclic keto-D-Fructose136
Structure-Sweetness Relationships139
Molecular Contact Surfaces140
Molecular Lipophilicity Profiles141
Appendix - Computational Methods145
I. Energy Potential Surfaces and Contour Plots145
II. Molecular Surfaces and Hydrophobicity Potential Profiles146
Chapter 6 - A New Look at the Hydrophobic Characteristics of Cyclodextrins and Their Inclusion Complexes147
Molecular Geometry of Cyclodextrins148
Solid-State Structures of Cyclodextrin Hydrates as Models for "Empty" Solution Conformations155
The Contact Surfaces of α-, β-, γ-, and δ-Cyclodextrin158
Molecular Lipophilicity Profiles of Non-Complexed Cyclodextrins161
The Thermodynamic Fundamentals of Inclusion Complex Formation164
Enthalpy-Entropy Compensation166
The Hydrophobic Topographies of Cyclodextrin Inclusion Complexes170
The Hydrophobic Guest-Host Relationship as Exemplified for α-Cyclodextrin Inclusion Complexes172
α-Cyclodextrin Complexes as Models for the Blue Starch-Iodine Adduct176
Flexible Guest Molecules in the β-Cyclodextrin Cavity177
γ-CD 12-Crown-4 Ether as an Example for a Capped Cyclodextrin Inclusion Complex179
Some General Remarks on the Hydrophobic Guest-Host Relationship and the Molecular Recognition of Cyclodextrins182
Cyclodextrins with Inverse Hydrophobicity184
Appendix - Computational Methods191
I. Molecular Structures191
II. Geometry of δ-Cyclodextrin191
III. Molecular Surfaces and Hydrophobicity Patterns191
Chapter 7 - Some Reflections on the Multitude of Cyclodextrin Isomers: Astronomic Numbers as a Justification for Computational Studies prior to Synthesis193
Cyclodextrin Isomers from Chemical Modification of Hydroxyl Groups194
Cyclooligosaccharide Isomers from Exchange of Sugar Units198
Selecting Relevant Isomers prior to Synthesis201
Chapter 8 - Small Ring Cyclodextrins: their Geometries and Hydrophobic Topographies203
Conformational Features of Small Ring Cyclodextrins in Relation to α-CD204
High Temperature Annealing of α-CD and Cycloglucopentaoside212
Small Ring Cyclodextrin Contact Surfaces and Cavity Dimensions216
Molecular Lipophilicity Pattern (MLP) of Small Ring Cyclodextrins219
Appendix - Computational Methods223
I. Glucose Tilt Angle Variations223
II. HTA Calculations223
III. Energy Potential Surfaces and Contour Plots224
IV. Molecular Surfaces and Lipophilicity Profiles224
Chapter 9 - Cyclodextrins, Cyclomannins, and Cyclogalactins with five and six (1→4)-linked Sugar Units: an Assessment of their Conformations and Hydrophobicity Patterns225
Conformational Features227
Contact Surfaces and Cavity Proportions232
Molecular Lipophilicity Profiles234
Appendix - Computational Methods240
I. Monosaccharide Tilt Angle Variations240
II. Contact Surfaces and Molecular Lipophilicity Profiles240
Chapter 10 - Cyclofructohexaoside: Molecular Electrostatic and Lipophilic Potential Profiles241
Molecular Lipophilicity Patterns243
Molecular Electrostatic Potential Profiles244
Chapter 11 - The Hydrophobic Topography of Amylose249
Crystalline Polymorphism of Amylose249
Molecular Geometries and H-Bonding Patterns of A- and Vh-type Amylose251
Contact Surfaces and Molecular Dimensions of A- and Vh-type Amylose255
Molecular Lipophilicity Pattern (MLP) of A- and Vh-type Amylose256
The Amylose-Iodine-Iodide Complex259
Chapter 12 - References and Notes263

Computer Simulation of Chemical and Biological Properties of Saccharides: Sucrose, Fructose, Cyclodextrins, and Starch

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