Durham E-Theses X-ray structural studies of lanthanide macrocycles and biological molecules Moloney, Janet M. How to cite: Moloney, Janet M. (1999) X-ray structural studies of lanthanide macrocycles and biological molecules, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/4599/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk X-ray Structural Studies of Lanthanide Macrocycles and Biological Molecules by Janet M. Moloney, B.Sc. Thesis submitted in part fulfillment of the requirements for the degree of Doctor of Philosophy at the University of Durham Department of Chemistry September 1999 The copyright of this thesis rests with the author. No quotation from it should be published without die written consent of the author and information derived from it should be acknowledged. .12 APR 2000 X-ray {Structural Studies of Lanihanide Macrocycles and Biological Molecules Submitted for the degree of Doctor of Philosophy, September 1999, by Janet M. Moloney, University of Durham. ABSTRACT The work described in this thesis is broadly divided into two sections. The structural study on the lanthanide macrocyclic complexes was afforded by means of X-ray crystallography. In this chapter, the molecules dota, the cationic enantiopure tetraamide europium and dysprosium complexes, the sodium complexes of the tetranaphthylamide and quinoyl derivative, the enantiopure gadolinium and europium complexes of the tetraamide series with esteratic sidechains, the lanathanum and ytterbium complexes of the dota derivative with benzyl phosphinate sidechains, and the tetracarboxyethyl series both as three uncomplexed stereoisomer and complexes of the RRRR stereoisomer with europium, gadolinium and terbium. These complexes exhibit quite a lot of structural diversity. Chapter five deals with experiments carried out at ultra low temperatures. A phase transition that the molecule benzil undergoes is investigated on the Fddd diffractometer, - a study of the interesting 1,12-dicarbonyl borane was undertaken to obtain precise values for the carbonyl bond lengths and the unprecedented structure of its hydrate was revealed to be a carbene diol and not the expected carboxylic acid complex The standard for macromolecular tests for diffraction, chicken egg white lysozyme, was crystallised and used to optimise conditions for low-temperature data acquisition from macromolecular samples J. M. Moloney, 1999: ii The work described in this Thesis was carried out in the Department of Chemistry, Durham University from October 1995 to January 1999, under the supervision of Professor J.A.K. Howard. All of the work is my own, unless stated to the contrary, and it has not been submitted previously for a degree at this or any other university. J.M. Moloney, 1999 The copyright of this Thesis rests with the author. No quotation from it should be published without her prior written consent and information derived from it should be acknowledged: iii Acknowledgements I am eternally grateful and privileged to have had as a mentor Professor Judith Howard over the course of my Ph.D. Her dedication to science, to members of the group and hard-working attitude have been inspirational. Thank you also for your kindness to me, and constant words of encouragement during the writing of this thesis. I am extremely grateful to Dr. Andres Goeta for all the help he has given me over the past almost four years. I would like to thank Dr. Slimane Dahaoui, in particular, for being a brilliant teacher and for useful discussions and encouragement. It has been a pleasure to have collaborated with many chemists in this department, in particular the group of Professor David Parker in the field of lanthanide complexation chemistry. I am especially grateful to Dr. Gareth Williams for his help and ideas on the investigations of lanthanide complex binding to DNA. Thank you to Dr. Rachel Dickins, Dr. Morag Easson, Dr. Clive Foster, Dr. Linda Govenlock, Dr. Alvaro de Sousa and Dr. Mark Woods. I am very grateful to the chemist Dr. Mark Fox, whom I have enjoyed collaborating with on the boron cage project. Thank you to Dr. Simon Teat for much help and working long hours during visits to station 9.8 at Daresbury. Thank you to Dr. Harry Powell for advice on oligonucleotide crystallography. I am very indebted to many members of the crystallography group, past and present, for what they have taught me. I would like to sincerely thank Dr. Andrei Batsanov, Dr. Roy Copley, Dr. Phillippe Guinneou, Dr. Mike Leech, Dr. Christian Lehmann, Dr. Claire Wilson, and Dr. Dmitrii Yufit. Thank you also for your friendship and good humour to many crystallographers and visitors to the group over the three-and-a-half years: Charlie Broder, Dr. Brian Bridgewater, John Cowan, Dr. Jacqui Cole, Dr. Pete Ford, Richard Hampshire, Andrew Hamilton, Dr. Mark Roden and Dr. Jing-Wen Yao, Professor Lyudmila Kuz'mina, Professor Sasha Bagatur'yants. Elena Alekseveya,, Dr. Andrei Churakov, Dr. Olga Gladkikh and Dr. Dmitrii Naumov. It has been a pleasure to know you all. iv I must give a special mention to Andrew Johnson for genuine belief in me, extreme tolerance(!) and lots of good times inside and out of work, and to Jan Kelly for her friendship, support and for dragging me out of the lab. Outside of work, I would like to mention for making my time in Durham a happy one Adrian 0' Halloran, Kim McGarry, Julian Cherryman, Caroline Williamson, Marcela Goeta, Jane Vear, Faye Buxton, Linda Gibbons. To friends from Cork - Sarah Keating, Sinead Jacob, Darren McAdam-O' Connell and Entesar Al-Balushi thank you very much. Thank you to Dr. Yvonne Jones for understanding during the past few months, while I have finished writing. Thank you very much to Dr: Wai-Ching Hon for words of encouragement and ginseng tea, which kept me going And last but not least, thank you to Dr. Lesley Greene for good times in Oxford and especially for keeping me on a writing timetable - you're a good kid! To my parents, Thomas and Mary Moloney. Table of Contents Chapter 1: Introduction 1 Chapter 2 Theory and Practice of Crystal Growth 4 2.1 Historical Background 5 2.2 Stages in Crystal Growth 6 2.2.1 Nucleation 6 2.2.2 Growth 10 2.2.2.1 Factors Affecting Growth 11 2.2.3 Cessation of Growth 13 2.3 Crystallisation Conditions 14 2.4 Precipitants 16 2.4.1 Salts 16 2.4.2 Volatile and involatile organic solvents 18 2.4.3 Polyethylene Glycols 18 2.5 Crystal Growth Set-up and Experimental Conditions 19 2.5.1 Liquid Diffusion 19 2.5.2 Vapour Diffusion 19 2.6 Industrial Methods 20 2.7 References 22 Chapter 3 The X-ray Diffraction Experiment 23 3.1 Introduction 24 3.2 Background 24 3.3 Generation of X-radiation 26 3.4 Monochromation and Absorption 2 8 3.4.1 The analytical absorption correction 30 3.4.2 The semi-empirical absorption correction 31 3.4.3 The empirical absorption correction 31 3.5 Instrumentation 33 3.5.1 The four-circle goniostat 3 3 3.5.2 The single crystal Rigaku AFC6S four-circle diffractometer 36 vii 3.5.3 The Fddd four-circle diffractometer 39 3.5.4 The single crystal SMART three-circle diffiractometer 43 3.5.4.1 The charge-coupled device area detector 49 3.6 Crystal Evaluation and Mounting 52 3.7 Unit Cell Determination 54 3.8 Data Collection 57 3.9 Data Reduction 57 3.10 Structure Solution and Refinement 5 8 3.10.1 Space group assignment 59 3.10.2 Patterson methods 60 3.10.3 Direct methods 61 3.10.4 Refinement of the trial structure 63 3.11 Low temperature attachments 64 3.11.1 The N2 open flow cryostat 65 3.11.2 The closed cycle refrigerator 66 3.11.3 The open flow helium cryostat (Helix) 69 3.12 Synchrotron radiation at the Daresbury SRS 70 3.12.1 Background to synchrotron radiation crystallography 70 3.12.2 The Daresbury SRS 75 3.12.3 Station 9.8 75 3.13 Bibliography 79 3.14 References 80 Chapter 4 Structural Studies of Lanthanide Macrocytic Complexes 83 4.1 Introduction 84 4.2 Applications of lanthanide macrocyclic complexes 87 4.2.1 Luminescence 87 4.2.2. Spectroscopic applications 91 4.2.3 Tumour Imaging using Positron Imaging Tomography 94 4.3 Perspective 96 4.4 'DOTA' - The archetypal chelate 99 4.5 Characterisation of enantiopure lanthanide tetraamide compounds 110 4.5.1 Stereoisomers of lanthanide complexes of dota derivatives 110 viii 4.5.2 Structural investigations of enantiopure lanthanide complexes incorporating phenyl chromophores 112 4 .5 .3 Structural investigations of enantiopure lanthanide complexes incorporating naphthyl and quinoline chromophores 119 4.5.4 Enantiopure complexes of tetraamide dota bearing esteratic groups 125 4.5.5 The macrocycle DTMA in its free and complexed forms 130 4.6 Lanthanide complexes with benzylphosphinate pendant groups 137 4.7 Lanthanide complexes with carboxyethyl pendant groups 142 4.7.1 Structures of the all the isomers of the free ligand.