This page describes my Ph.D. thesis with the title:

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

• Thesis - Table of Contents

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

Computer Simulation of Chemical and Biological Properties of Saccharides: Sucrose, Fructose, Cyclodextrins, and Starch			Page
Title + Remarks + Contents
Chapter 1 - Computersimulation chemischer und biologischer Eigenschaften von Sacchariden			1
	Das Molekulare Elektrostatische Potential (MEP) der Saccharose		3
	Das Molekulare Lipophilie-Profil (MLP) der Saccharose		5
	Struktur-Süßkraftbeziehungen der Fructose		8
	Nicht-Kohlenhydrat Süßstoffe		9
	Hydrophobie-Profile von Cyclodextrinen		10
	Kleinere Cyclodextrine, Cyclomannine, Cyclogalactine und Cyclofructine		11
	Die Hydrophobie-Charakteristika von Stärke		13
	Abschließende Bemerkungen		14
	Literaturzitate		14
Chapter 2 - Sucrose, Sucralose, Fructose, and some Non-Carbohydrate High-Potency Sweeteners: Correlations Between Hydrophobicity Patterns and AH-B-X Assignments			17
	The Electrostatic Potential Profiles and Hydrophobicity Patterns of Sucrose		20
	The Tripartite AH-B-X Glucophore in Sucrose Derivatives		25
	Deoxy-Halo-Sucroses		30
	β-D-Fructopyranose: Conformations and Molecular Lipophilicity Profiles		38
	Molecular Lipophilicity Profiles of Non-Carbohydrate, High-Potency Sweeteners		44
Chapter 3 - Sucrose: Generation of Molecular Electrostatic and Lipophilic Profiles and their Implications on Hydroxyl Group Reactivities and Sweetness Elicitation			51
	Solid-State and Solution Conformation of Sucrose		52
	Conformational Properties of the Isolated Sucrose Molecule		53
	Molecular Dynamics of Sucrose in Aqueous Solution		58
	Relative Stabilities of Sucrose Solution Conformations		61
	Umbrella Sampling Procedure		62
	Free Energy Profile of Sucrose in Aqueous Solution		63
	The Molecular Electrostatic Potential (MEP) Profile of Sucrose		68
	Computational Basics		68
	Visualization of Data		68
	Chemical Implications of the MEP Profiles		70
	MEP Pattern of Sucrose and Hydrogen Bonding		73
	The Molecular Lipophilicity Pattern (MLP) of Sucrose		73
	Localization of Hydrophobicity		74
	Application of the Hydrophobicity Mapping		75
	Biological Significance of the Molecular Lipophilicity Profiles		76
	The Modified AH-B-X-Concept of Structure-Sweetness-Relationships		77
	Assessment of the Modified AH-B-X-Concept with Sucrose Derivatives		79
	Hydrophobicity Pattern of Sucralose		81
	Quantitative Sweetness-Hydrophobicity Relationships for Halo-Sucroses		84
	Conclusions		87
	Appendix - Computational Methods		87
	I. F / Y-Energy Potential Surfaces and Contour Plots		87
	II. Molecular Dynamics Simulations		88
	III. Free Energy Calculations using Umbrella Sampling		88
Chapter 4 - Fructose: Structure-Sweetness Relationships on the Basis of Electrostatic and Lipophilicity Potential Profiles			91
	Molecular Geometry of β-D-Fructopyranose		93
	Molecular Electrostatic Potential (MEP) Profile of β-D-Fructopyranose		95
	Molecular Lipophilicity Pattern (MLP) of β-D-Fructopyranose		98
	Experimental Corroboration of AH-B-X-Assignments		99
	Comparison of β-D-Fructopyranose and α-L-Sorbopyranose		102
	Conclusions		106
	Appendix - Computational Methods		107
Chapter 5 - Fructose: Conformational Properties of all Different Tautomers and Implications of their Lipophilicity Patterns on Sweetness			109
	Pyranoid Fructose Tautomers - β- and α-D-Fructopyranose		110
	Furanoid Fructose Tautomers - β- and α-D-Fructofuranose		112
	Conformations of Five-Membered Ring Systems		112
	Conformational Properties of Cyclopentanol and Tetrahydro-2-furanol in Relation to the Anomeric Effect		114
	Energy Potential Surfaces of β- and α-D-Fructofuranose		120
	Statistical Crystal Structure Analysis		121
	NMR-Data in Relation to Molecular Conformation		128
	Acyclic keto-D-Fructose		136
	Structure-Sweetness Relationships		139
	Molecular Contact Surfaces		140
	Molecular Lipophilicity Profiles		141
	Conclusions		144
	Appendix - Computational Methods		145
	I. Energy Potential Surfaces and Contour Plots		145
	II. Molecular Surfaces and Hydrophobicity Potential Profiles		146
Chapter 6 - A New Look at the Hydrophobic Characteristics of Cyclodextrins and Their Inclusion Complexes			147
	Molecular Geometry of Cyclodextrins		148
	Solid-State Structures of Cyclodextrin Hydrates as Models for "Empty" Solution Conformations		155
	The Contact Surfaces of α-, β-, γ-, and δ-Cyclodextrin		158
	Molecular Lipophilicity Profiles of Non-Complexed Cyclodextrins		161
	The Thermodynamic Fundamentals of Inclusion Complex Formation		164
	Enthalpy-Entropy Compensation		166
	The Hydrophobic Topographies of Cyclodextrin Inclusion Complexes		170
	The Hydrophobic Guest-Host Relationship as Exemplified for α-Cyclodextrin Inclusion Complexes		172
	α-Cyclodextrin Complexes as Models for the Blue Starch-Iodine Adduct		176
	Flexible Guest Molecules in the β-Cyclodextrin Cavity		177
	γ-CD 12-Crown-4 Ether as an Example for a Capped Cyclodextrin Inclusion Complex		179
	Some General Remarks on the Hydrophobic Guest-Host Relationship and the Molecular Recognition of Cyclodextrins		182
	Cyclodextrins with Inverse Hydrophobicity		184
	Epilogue		189
	Appendix - Computational Methods		191
	I. Molecular Structures		191
	II. Geometry of δ-Cyclodextrin		191
	III. Molecular Surfaces and Hydrophobicity Patterns		191
Chapter 7 - Some Reflections on the Multitude of Cyclodextrin Isomers: Astronomic Numbers as a Justification for Computational Studies prior to Synthesis			193
	Cyclodextrin Isomers from Chemical Modification of Hydroxyl Groups		194
	Cyclooligosaccharide Isomers from Exchange of Sugar Units		198
	Selecting Relevant Isomers prior to Synthesis		201
Chapter 8 - Small Ring Cyclodextrins: their Geometries and Hydrophobic Topographies			203
	Conformational Features of Small Ring Cyclodextrins in Relation to α-CD		204
	High Temperature Annealing of α-CD and Cycloglucopentaoside		212
	Small Ring Cyclodextrin Contact Surfaces and Cavity Dimensions		216
	Molecular Lipophilicity Pattern (MLP) of Small Ring Cyclodextrins		219
	Conclusions		222
	Appendix - Computational Methods		223
	I. Glucose Tilt Angle Variations		223
	II. HTA Calculations		223
	III. Energy Potential Surfaces and Contour Plots		224
	IV. Molecular Surfaces and Lipophilicity Profiles		224
Chapter 9 - Cyclodextrins, Cyclomannins, and Cyclogalactins with five and six (1→4)-linked Sugar Units: an Assessment of their Conformations and Hydrophobicity Patterns			225
	Nomenclature		226
	Conformational Features		227
	Contact Surfaces and Cavity Proportions		232
	Molecular Lipophilicity Profiles		234
	Appendix - Computational Methods		240
	I. Monosaccharide Tilt Angle Variations		240
	II. Contact Surfaces and Molecular Lipophilicity Profiles		240
Chapter 10 - Cyclofructohexaoside: Molecular Electrostatic and Lipophilic Potential Profiles			241
	Molecular Lipophilicity Patterns		243
	Molecular Electrostatic Potential Profiles		244
	Conclusions		247
Chapter 11 - The Hydrophobic Topography of Amylose			249
	Crystalline Polymorphism of Amylose		249
	Molecular Geometries and H-Bonding Patterns of A- and Vh-type Amylose		251
	Contact Surfaces and Molecular Dimensions of A- and Vh-type Amylose		255
	Molecular Lipophilicity Pattern (MLP) of A- and Vh-type Amylose		256
	The Amylose-Iodine-Iodide Complex		259
Chapter 12 - References and Notes			263