Quantifying non-covalent interactions [Elektronische Ressource] : rational in-silico design of guanidinium-based carboxylate receptors / vorgelegt von Sebastian Schlund

Ak Engels

Informations

• Publié par: julius-maximilians-universitat_wurzburg
• Publié le: 01 janvier 2007
• Nombre de lectures: 22
• Langue: Deutsch
• Poids de l'ouvrage: 13 Mo

Extrait

Julius-Maximilians-
Universität
Würzburg

Fakultät für Chemie und Pharmazie



Quantifying Non-covalent Interactions –
Rational in-silico Design of Guanidinium-based
Carboxylate Receptors


Dissertation zur Erlangung des
naturwissenschaftlichen Doktorgrads
der Julius-Maximilians-Universität Würzburg



vorgelegt von

Sebastian Schlund

aus Würzburg



Würzburg 2007









Eingereicht am: _________________________________________________________
bei der Fakulät für Chemie und Pharmazie.



1. Gutachter: _________________________________________________________
2. Gutachter:
der Dissertation.




1. Prüfer: _________________________________________________________
2. Prüfer:
3. Prüfer:
des öffentlichen Promotionskolloquiums.



Tag des öffentlichen Promotionskolloquium: __________________________________



Doktorurkunde ausgehändigt am:


Die vorliegende Arbeit wurde unter Anleitung von Prof. Dr. Bernd Engels von Dezember
2003 bis Juli 2007 am Institut für Organische Chemie der Julius-Maximilians-Universität
Würzburg angefertigt.

Teilergebnisse dieser Arbeit waren Gegenstand von Publikationen sowie von Postern und
Kurzvorträgen.

Publikationen:
"Knock-out" Analogues as a Tool to Quantify Supramolecular Processes: A Theoretical Study
of Molecular Interactions in Guanidiniocarbonyl Pyrrole Carboxylate Dimers" S. Schlund, C.
Schmuck, B. Engels, JACS 2005, 127, 11115-11124.
"Geometry and Cooperativity Effects in Adenosine-carboxylic Acid Complexes" S. Schlund,
M. Mladenovic, E. M. Basilio Janke, B. Engels, K. Weisz, JACS 2005, 127, 16151-16158.
"How important is molecular rigidity for the complex-stability of artificial host-guest
systems? A theoretical study on Self-Assembly of Gas phase Arginine" S. Schlund, C.
Schmuck, B. Engels, Chem-Eur. J. 2007, 13 (23), 6644 – 6653.
"Conformational Analysis of Arginine in Gas Phase - A Strategy for Scanning the Potential
Energy Surface effectively" S. Schlund, R. Müller, C. Graßmann, J. Comp. Chem. 2007, DOI:
10.1002/jcc.20798

Poster und Vorträge:
S. Schlund, C. Schmuck, B. Engels; A Theoretical Study of Guanidiniocarbonyl Pyrrole
Complexes as Model Systems for Carboxylate Receptors, Posterbeitrag, Summer School
International University of Bremen:: Advanced Modelling of Biological Function –
Expression, Networks and Structure, Bremen, August 2004.
Schlund S., Engels B.; Theoretical Investigations of Non-covalent Interactions in
Guanidiniocarbonyl Pyrrole Carboxylate Dimers, Vortrag, Joint PhD Students Meeting of the
SFBs 544 and 630, Würzburg, November 2004.
Guanidiniocarbonyl Pyrrole Carboxylate Dimers, Posterbeitrag, Joint PhD Students Meeting
of the SFBs 544 and 630, Würzburg, November 2004. S. Schlund, C. Schmuck, B. Engels; “Knock-out” Analogues as a Tool to Quantify
Supramolecular Processes - Theoretical Investigations of Non-covalent Interactions in
Guanidiniocarbonyl Pyrrole Carboxylate Dimers, Posterbeitrag, 41. Symposium Theoretische
Chemie, Innsbruck, September 2005.
S. Schlund, C. Schmuck, B. Engels; “Knock-out” Analogues as a Tool to Quantify
Supramolecular Processes - Theoretical Investigations of Non-covalent Interactions in ers, Posterbeitrag, 1st International Symposium
the SFB 630 – Novel Agents against Infectious Deseases, Würzburg, Februar 2006.
Schlund S., Engels B.; How to Quantify Weak Molecular Interactions: Conformational
Analysis of Monomeric Arginine and the Zwitterionic Dimer in Gas Phase, Posterbeitrag, 42.
Symposium Theoretische Chemie, Berlin, September 2006. eakational
Analysis of Monomeric Arginine and the Zwitterionic Dimer in Gas Phase, Posterbeitrag,
Second Joint PhD Students Meeting of the SFBs 544 and 630, Heidelberg, November 2006. Chapter 1 Introduction – Binding of anions in artificial receptor systems I
Table of Contents
Chapter 1 Introduction – Binding of anions in artificial receptor systems................... 1
Chapter 2 How to Quantify Intermolecular Interactions? ............................................. 9
2.1 Experimentally............................................................................................................................ 9
2.1.1 Determination of association constants......................................................................... 9
2.1.2 Determination of entropy and enthalpy contributions................................................. 12
2.2 Theoretically ............................................................................................................................. 14
2.2.1 Calculation of dimerization energies .......................................................................... 14
2.2.2 entropy and enthalpy contributions ..................................................... 15
Chapter 3 Theoretical Methods....................................................................................... 19
3.1 Electronic structure methods..................................................................................................... 20
3.1.1 A short review on the self-consistent field (SCF) theory............................................ 20
3.1.2 Electron correlation methods ...................................................................................... 28
3.1.2.1 Møller-Plesset perturbation theory.............................................................. 29
3.1.2.2 Coupled-cluster theory ................................................................................ 37
3.1.3 Density functional theory............................................................................................ 39
3.1.4 Drawbacks and benefits of the electronic structure methods...................................... 47
3.2 Conformational analysis ........................................................................................................... 49
3.2.1 Brief introduction to molecular mechanics................................................................. 49
3.2.2 Conformational search algorithms .............................................................................. 51
3.3 From gas-phase to solution ....................................................................................................... 55
3.3.1 Continuum solvation................................................................................................... 56
3.3.1.1 The Apparent Surface Charge Method........................................................ 58
3.3.1.2 The Conductor-like Screening Model ......................................................... 59
3.3.2 Explicit solvation ........................................................................................................ 62
3.4 Molecular simulations – Accounting for the entropy................................................................ 63
3.4.1 Molecular Dynamics 63
3.4.2 Thermodynamic Integration........................................................................................ 69
3.5 The QM/MM Method ............................................................................................................... 71
II Chapter 1 Introduction – Binding of anions in artificial receptor systems
Chapter 4 Results and Discussion ................................................................................... 73
4.1 Quantifying Supramolecular Processes by Knock-out Analogues............................................ 73
4.1.1 Introduction................................................................................................................. 73
4.1.2 Computational Details ................................................................................................ 77
4.1.3 Geometries.................................................................................................................. 78
4.1.4 Energies ...................................................................................................................... 82
4.1.5 Conclusions 94
4.2 Arginine as Model System for Guanidinium-Carboxylate Interactions.................................... 95
4.2.1 Conformational Analysis in Gas Phase – The Quest for the Global Minimum .......... 96
4.2.1.1 Introduction................................................................................................. 96
4.2.1.2 Computational Details................................................................................. 97
4.2.1.3 Force-Field Validation ................................................................................ 99
4.2.1.4 Conformational Search Algorithms........................................................... 101
4.2.1.5 Electronic Structure Optimizations 104
4.2.1.6 Calculated Spectra..................................................................................... 113
4.2.1.7 Conclusions............................................................................................... 120
4.2.2 Self-Assembly of Gas Phase Arginine...