University of Ghana http://ugspace.ug.edu.gh UNIVERSITY OF GHANA LEGON SYNTHESIS, CHARACTERIZATION AND LUMINESCENT PROPERTIES OF BIPODAL AND TRIPODAL PYRAZOLE AND TRIAZOLE LANTHANIDE COORDINATION COMPLEXES BY TOFAH KWASI PASCAL (10417798) THIS THESIS IS SUBMITTED TO THE UNIVERSITY OF GHANA, LEGON IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF MPHIL IN CHEMISTRY DEGREE. JULY 2019. i University of Ghana http://ugspace.ug.edu.gh DECLARATION I, Tofah Kwasi Pascal, hereby declare that this project work is of my findings towards the attainment of my degree and references to other people’s work have been properly acknowledged and no part of this work has been formally offered for another degree anywhere else. SIGN . . . . . . . . . . . . . . . . . . . . . . DATE . . . . . . . . . . . . . . . . . . .. . . TOFAH KWASI PASCAL (10417798) STUDENT SIGN . . . . . . . . . . . . . . . . . . . . . SIGN . . . . . . . . . . . . . . . . . . . . . . . . . DATE . . . . . . . . . . . . . . . . . . . . . . DATE. . . . . . . . . . . . . . . . . . . . . . . . . DR. MICHAEL .K. AINOOSON DR COLLINS OBUAH (SUPERVISOR) (SUPERVISOR) ii University of Ghana http://ugspace.ug.edu.gh Dedicated To the Tofah Family, Thank You All for the Support and Prayers. iii University of Ghana http://ugspace.ug.edu.gh ACKNOWLEDGEMENTS I would not have made it this far had it not been the grace of God Almighty. My first and foremost thanks go to God Almighty for giving me the strength and good health throughout my academic pursuit. I am highly indebted to my supervisors Dr. Michael K. Ainooson and Dr. Collins Obuah for their time, patience, encouragement, and direction they gave me. Big thanks to all members of my family for their prayers and financial support. I thank my friends Richard, Peter, Eric, Emmanuella and Cephas who were there during tiring times. I extend a hand of gratitude to Mr. Samuel Attuah for his assistance and Mr. Bob Essien for supplying me with laboratory equipment and chemicals. I appreciate you all and I am most grateful for your efforts that have shaped this project. I thank you for sharing your time and knowledge with me. God richly bless you. v University of Ghana http://ugspace.ug.edu.gh ABSTRACT Lanthanide complexes have been established as promising agents in their application as catalysts and photo-luminescent materials. Recent research has been geared towards the optical application of these lanthanide complexes, especially as organic light-emitting diodes (OLED) for TV screens, phones and other portable electronic devices. The luminescent ability of these complexes is largely dependent on the choice of ligand environment. We report here for the first time lanthanide complexes bearing three classes of ligands, mainly a heteroscorpionate R (N^N^O) ligand of the form Pz2 (CHPhOH) (Figure 1.0-A), (N^N) 1-(2-Picolyl)-4-phenyl-1H- 1,2,3-triazole (Figure 1.0-B) and (N^N) 3,6-(dipyridyl)-1,2,4,5-tetrazine (Figure 1.0-C). The coordination complex of the lanthanum salts (Pr, Dy, Gd and Tb), have been synthesized and 1 13 characterized by H-NMR, C-NMR and FT-IR. The electronic and luminescence property of the ligands and complexes have been studied using Cyclic Voltammetry, UV-vis and spectro- fluorophotometric studies. Figure 1.0: Synthesized lanthanide complexes vi University of Ghana http://ugspace.ug.edu.gh TABLE OF CONTENTS DECLARATION ....................................................................................................................... ii ACKNOWLEDGEMENTS.........................................................................................................v ABSTRACT ............................................................................................................................. vi LIST OF FIGURES .................................................................................................................. ix LIST OF SCHEMES ................................................................................................................ xii LIST OF TABLES .................................................................................................................. xiii THESIS STRUCTURE ...............................................................................................................1 CHAPTER ONE .........................................................................................................................2 GENERAL INTRODUCTION....................................................................................................2 1.0 BACKGROUND ..........................................................................................................2 1.1 PROJECT AIM .........................................................................................................5 CHAPTER TWO ........................................................................................................................6 2.0 LITERATURE SURVEY .............................................................................................6 2.1 CHEMISTRY OF LANTHANIDES ..........................................................................6 2.2 ELECTRONIC PROPERTIES OF LANTHANIDES ................................................7 2.3 COORDINATION CHEMISTRY OF LANTHANIDES ...........................................8 2.4 LUMINESCENCE ....................................................................................................9 2.5 LANTHANIDE LUMINESCENES SENSITIZATION ........................................... 10 2.5.1 MECHANISM OF LANTHANIDE LUMINESCENCE ................................... 11 2.5.2 QUENCHING OF LANTHANIDE LUMINESCENCE ................................... 12 2.6 APPLICATIONS OF LANTHANIDE COMPLEXES ............................................. 14 vii University of Ghana http://ugspace.ug.edu.gh 2.6.1 LASERs (Light Amplification by Stimulated Emission of Radiation) ............... 14 2.6.2 LANTHANIDE SHIFT REAGENTS ............................................................... 14 2.6.3 MAGNETIC RESONANCE IMAGING (MRI) ................................................ 15 CHAPTER THREE ................................................................................................................... 17 LANTHANIDE COMPLEXES BASED ON SUBSTITUTED TRIAZOLE LIGANDS ............ 17 3.0 INTRODUCTION AND LITERATURE REVIEW .................................................... 17 3.1 GENERAL OVERVIEW OF TRIAZOLES ............................................................. 17 3.1.1 COORDINATION OF 1,2,3-TRIAZOLES. ...................................................... 17 3.2 SYNTHESIS OF TRIAZOLES ............................................................................... 18 3.3 EXPERIMENTAL .................................................................................................. 23 3.3.1 Synthesis of 1-(2-Picolyl)-4-phenyl-1H-1,2,3-triazole (L1). ............................. 23 3.3.2 PREPARATION OF LANTHANIDE COMPLEXES. ...................................... 23 3.3.2.1 Synthesis of (L1Pr(acac)3). ........................................................................... 23 3.3.2.2 Synthesis of (L1Dy(acac)3). .......................................................................... 24 3.3.2.3 Synthesis of (L1Gd(acac)3). .......................................................................... 25 3.4 RESULTS AND DISCUSSION .............................................................................. 27 3.4.1 CHARACTERIZATION OF COMPLEXES. ................................................... 27 3.4.2 FT-IR ANALYSIS ........................................................................................... 27 1 3.4.3 H-NMR STUDIES .......................................................................................... 30 3.4.4 ELECTRONIC PROPERTIES OF LIGAND AND COMPLEXES. .................. 33 viii University of Ghana http://ugspace.ug.edu.gh 3.4.5 LUMINESCENT STUDIES ............................................................................. 34 3.4.6 QUANTUM YIELD MEASUREMENTS ........................................................ 36 3.4.7 CYCLIC VOLTAMMETRY MEASUREMENTS ........................................... 38 3.5 CONCLUSION ....................................................................................................... 40 CHAPTER FOUR ..................................................................................................................... 41 LANTHANIDE COMPLEXES BASED ON PYRAZOLE HETEROSCORPIONATES ........... 41 4.0 INTRODUCTION AND LITERATURE REVIEW .................................................... 41 4.1 GENERAL OVERVIEW OF PYRAZOLES ........................................................... 41 4.1.1 COORDINATION CHEMISTRY OF 1H-PYRAZOLE. .................................. 41 4.1.2 SYNTHESIS OF PYRAZOLES ....................................................................... 43 4.2 SCORPIONATES ................................................................................................... 45 4.2.1 COORDINATION OF SCORPIONATES ........................................................ 46 4.2.2 SYNTHESIS OF SCORPIONATES................................................................. 49 4.2.3 MECHANISM OF REACTION ....................................................................... 50 4.2.4 APPLICATIONS OF POLYPYRAZOLYL-SCORPIONATES ........................ 51 4.3 EXPERIMENTAL METHODS ............................................................................... 53 4.3.1 Synthesis of (2-hydroxyphenyl)bis(3,5-dimethyl-pyrazol-1-yl) methane (L2). .. 53 4.3.2 Synthesis of (2-hydroxyphenyl)bis(3,5-di-tert-butyl-pyrazol-1-yl)methane (L3). 53 4.3.3 PREPARATION OF COMPLEXES. ................................................................ 55 ix University of Ghana http://ugspace.ug.edu.gh 4.3.3.1 Synthesis of [L2Pr(diphenyl acac)2] 2A. ....................................................... 55 4.3.3.2 Synthesis of [L2Dy(diphenyl acac)2] 2B ....................................................... 56 4.4 RESULTS AND DISCUSSION. ............................................................................. 57 4.4.1 CHARACTERIZATION OF LIGAND AND COMPLEXES. .......................... 57 4.4.2 FT-IR ANALYSIS ........................................................................................... 57 4.4.3 NMR ANALYSIS ............................................................................................ 60 4.4.4 CHARACTERIZATION OF LANTHANIDE COMPLEXES .......................... 65 4.4.5 ELECTRONIC PROPERTIES OF LIGAND AND COMPLEXES. .................. 66 4.4.6 LUMINESCENT STUDIES ............................................................................. 68 4.5 CONCLUSION ....................................................................................................... 70 CHAPTER FIVE ...................................................................................................................... 71 LANTHANIDE COMPLEXES BASED ON TETRAZINE LIGANDS ..................................... 71 5.0 INTRODUCTION AND LITERATURE REVIEW .................................................... 71 5.1 TETRAZINE AS LIGANDS ................................................................................... 71 5.2 SYNTHESIS OF 1,2,4,5-TETRAZINES ................................................................ 72 5.2.1 COORDINATION CHEMISTRY OF 3,6-DISUBSTITUTED 1,2,4,5- TETRAZINES................................................................................................................ 74 5.2.2 APPLICATIONS OF TETRAZINE COMPOUNDS ........................................ 75 5.3 EXPERIMENTAL METHODS ............................................................................... 76 5.3.1 SYNTHESIS OF COMPLEX 4A. .................................................................... 76 x University of Ghana http://ugspace.ug.edu.gh 5.3.2 SYNTHESIS OF COMPLEX 4B. .................................................................... 77 5.3.3 SYNTHESIS OF COMPLEX 4C. .................................................................... 77 5.3.4 SYNTHESIS OF COMPLEX 4D. .................................................................... 78 5.4 RESULTS AND DISCUSSION .............................................................................. 79 5.4.1 FT-IR ANALYSIS ........................................................................................... 79 5.4.2 NMR STUDIES ............................................................................................... 80 5.4.3 ELECTRONIC PROPERTIES OF LIGAND AND PROPERTIES ................... 81 5.4.4 UV-VIS STUDIES ........................................................................................... 81 5.4.5 LUMINESCENT STUDIES ............................................................................. 82 5.5 CONCLUSION ....................................................................................................... 85 CONCLUSION AND RECOMMENDATIONS ....................................................................... 86 REFERENCES ......................................................................................................................... 87 APPENDIX I ............................................................................................................................ 98 APPENDIX II ......................................................................................................................... 101 APPENDIX III ........................................................................................................................ 108 xi University of Ghana http://ugspace.ug.edu.gh LIST OF FIGURES Figure 1.1: Target Ligands ; triazole ligand( L1), pyrazole ligand (L2 and L3) and tetrazine ligand (L4). .................................................................................................................................4 3+ Figure 2.2: Partial energy diagram of Ln ions. .........................................................................8 Figure 2.3: Some coordination modes of lanthanide complexes reproduced from (Cotton, 2006) .9 Figure 2.4: The emission spectra of some lanthanide complexes (Bünzli, 2009) ........................ 10 Figure 2.5: Lanthanide luminescence sensitization. Image obtained from (Reddy et al., 2013) . 11 Figure 2.6: Mechanism of luminescence in lanthanide complexes adopted from (Cable et al., 2011)......................................................................................................................................... 12 Figure 2.7: Quenching of lanthanide luminescence .................................................................... 13 Figure 2.8: A chiral shift reagent reproduced from (Cotton, 2006) ............................................. 15 Figure 2.9: MRI scanner (left) and head scan image (right) ...................................................... 16 Figure 2.10: Some common gadolinium complexes used as contrast agents............................... 16 Figure 3.1: Structure of 1,2,3-triazole ........................................................................................ 17 Figure 3.2: Coordination modes of triazole ligand reproduced from (Aromí et al., 2011)........... 18 Figure 3.3: Iridium(III) complex of triazole ligand reproduced from (Connell et al., 2016) ........ 21 Figure 3.4: Au(III) complex of substituted triazole ligand reproduced from (Bortoluzzi et al., 2013)......................................................................................................................................... 22 Figure 3.5: FT-IR of L1 ............................................................................................................ 28 Figure 3.6: Stacked IR of L1 and (L1Pr(acac)3). ....................................................................... 28 Figure 3.7:Stacked IR of L1 and (L1Dy(acac)3). ....................................................................... 29 Figure 3.8: Stacked IR of L1 and (L1Gd(acac)3). ...................................................................... 29 1 Figure 3.9: H- NMR OF (L1Pr(acac)) ..................................................................................... 31 ix University of Ghana http://ugspace.ug.edu.gh 1 Figure 3.10: H- NMR OF (L1Dy(acac)) ................................................................................... 31 1 Figure 3.11: H- NMR OF (L1Gd(acac)) .................................................................................. 32 1 Figure 3.12: Stacked H-NMR of L1 and complexes ................................................................. 32 Figure 3.13: Absorption of L1 and complexes ........................................................................... 33 Figure 3.14: Comparison of absorption A and emission B of complexes in methanol, acetone and dichloromethane ................................................................................................................. 35 Figure 3.15: Comparison of absorption C and emission D of ligand and complexes in methanol solution ..................................................................................................................................... 35 Figure 3.16: Cyclic voltamogram of ligand L1 .......................................................................... 39 Figure 3.17: Cyclic voltamogram of gadolinium complex ......................................................... 39 Figure 3.18: Cyclic voltamogram of praseodymium complex .................................................... 39 Figure 4.1 :Various coordination modes of 1H-pyrazole with metals (M) reproduced from (M. A. Halcrow, 2009) ......................................................................................................................... 42 Figure 4.2: Depiction of a scorpionate attack (Martins & Pombeiro, 2017). ............................... 45 Figure 4.3 Target ligands ........................................................................................................... 52 Figure 4.4: FT-IR of L2 ............................................................................................................ 59 Figure 4.5: FT-IR of L3 ............................................................................................................ 59 1 Figure 4.6: H-NMR OF L3 ...................................................................................................... 61 1 Figure 4.7: H-NMR OF L3 EXPANDED ................................................................................. 61 13 Figure 4.8 C-NMR of L3 ........................................................................................................ 62 13 Figure 4.9: C-NMR of L3 (expanded) ..................................................................................... 63 13 Figure 4.10: C-NMR of L3 (expanded) ................................................................................... 63 1 Figure 4.11: H-NMR spectra of L2 .......................................................................................... 64 x University of Ghana http://ugspace.ug.edu.gh 1 Figure 4.12: Stacked H-NMR of L2 and complexes ................................................................ 65 Figure 4.13: Absorption of L2 ................................................................................................... 66 Figure 4.14: Absorption of praseodymium complex recorded at 1µM in methanol .................... 67 Figure 4.15: Absorption of dysprosium complex recorded at 1µM in methanol ......................... 67 Figure 4.16: Excitation of praseodymium complex .................................................................... 69 Figure 4.17: Excitation of dysprosium comple........................................................................... 69 Figure 5.1: Isomers of tetrazines (Saracoglu, 2007) .................................................................. 71 Figure 5.2: Coordination of 3,6-disubstituted pyridyl-1,2,4,5-tetrazine to a metal center. Reproduced from (Kaim, 2002) ................................................................................................. 74 Figure 5.3: Platinum complex of tetrazine reproduced from (Gudat et al., 2004) ....................... 74 Figure 5.4: Structures of explosive tetrazine compounds ........................................................... 75 1 Figure 5.5: Stacked H-NMR of 4A-4D ..................................................................................... 80 Figure 5.6: Absorption spectra of L4 and complexes ................................................................. 82 Figure 5.7: Excitation (350 nm) and emission spectrum of L4 ................................................... 84 Figure 5.8: Excitation (290 nm) and emission spectra of 4A ...................................................... 84 Figure 5.9: Excitation (290 nm) and emission spectra of 4C ...................................................... 84 Figure 5.10: Excitation (290 nm) and emission spectra of 4D .................................................... 84 xi University of Ghana http://ugspace.ug.edu.gh LIST OF SCHEMES Scheme 3.1: Regioselectivity of azide-alkyne cycloaddition reaction. Reproduced from (Totobenazara & Burke, 2015). ................................................................................................. 20 Scheme 3.2: Proposed mechanism for the CuAAC click reaction for triazoles based on DFT calculations by (Hein & Fokin, 2010). ....................................................................................... 20 Scheme 3.3: Synthesis of (L1). .................................................................................................. 23 Scheme 3.4: Synthesis of (L1Pr(acac)3)..................................................................................... 24 Scheme 3.5 Synthesis of (L1Dy(acac)3). .................................................................................. 25 Scheme 3.6 Synthesis of (L1Gd(acac)3). .................................................................................. 26 Scheme 4.1: Amphoteric nature of (1H)-pyrazole ...................................................................... 41 Scheme 4.2: Knorr synthesis of pyrazoles ................................................................................. 43 Scheme 4.3: Preparation of 3,5-disubstituted pyrazoles reproduced from(Fustero et al., 2009) .. 44 Scheme 4.4: Solventless synthesis of pyrazoles reproduced from (Wang & Qin, 2004) ............. 44 Scheme 4.5: Zn and Cu complexes of N, N, O heteroscorpionate ligand reproduced from (S. Milione et al., 2009) .................................................................................................................. 47 Scheme 4.6: Zn and Mg complexes of N,N,O heteroscorpionate reproduced from (Schofield et al., 2009) ................................................................................................................................... 48 Scheme 4.7: Synthetic schemes for the synthesis of bis-pyrazolyl scorpionates reproduced from(S. Milione et al., 2009; Otero et al., 2013; Schofield et al., 2009) ..................................... 49 Scheme 4.8: Proposed mechanism for the preparation of N,N,O heteroscorpionate ligand reproduced from (S. Milione et al., 2009) .................................................................................. 50 Scheme 4.9: Synthetic scheme for preparation of (L3). ............................................................ 54 Scheme 4.10: Synthesis of [L2Pr(diphenyl acac)2] 2A .............................................................. 55 xii University of Ghana http://ugspace.ug.edu.gh Scheme 4.11: Synthesis of [L2Dy(diphenyl acac)2] 2B ............................................................. 56 Scheme 5.1: Synthesis of substituted 1,2,4,5-tetrazine .............................................................. 72 Scheme 5.2: Synthesis of 3,6-disubstituted 1,2,4,5-tetrazines.reproduced from(Yang et al., 2012) ................................................................................................................................................. 73 Scheme 5.3: Preparation of`4,4’-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic acid. Reproduced from (Calahorro et al., 2015; Savastano et al., 2016) ......................................................................... 73 Scheme 5.4: Preparation of complex 4A. ................................................................................... 76 Scheme 5.5: Synthesis of complex 4B. ...................................................................................... 77 Scheme 5.6: Preparation of complex 4C. ................................................................................... 78 Scheme 5.7: Preparation of complex 4D. .................................................................................. 78 LIST OF TABLES Table 3.1: Quantum yield data of L1 and complexes ................................................................. 37 Table 4.1: Comparison of IR main stretching vibrations (cm-1) of L2 and complexes ............... 58 Table 5.1: Comparison of IR streching vibrations (cm-1) of L4 and complexes (4A-4D) ........... 79 xiii University of Ghana http://ugspace.ug.edu.gh THESIS STRUCTURE This study is presented in five different chapters to help distinguish the various experiments undertaken. It is also intended to help in the structuring of manuscripts for journal publication to the international community. CHAPTER ONE: This chapter introduces the research work and also outlines the specific aim and objectives for the research work. CHAPTER TWO: This chapter delves into reported literature mainly on lanthanide metals. The various physical and chemical properties of the lanthanides are reviewed with more focus on their luminescence properties. CHAPTER THREE: This section gives a brief overview of the choice of ligand (triazole based ligand), their synthetic approaches and applications. Sub-sections on this chapter reports on the experimental methods used for the synthesis of the complexes and further discusses the findings from the work. CHAPTER FOUR: This chapter also gives an overview of the heteroscorpionate ligand used for the complex preparation as well as a discussion on the findings. CHAPTER FIVE: An overview of the choice of ligand (3,6-(dipyridyl)-1,2,4,5-tetrazine) is reported, the preparation method employed in the synthesis of the ligands and discussion on the various experiments analyzed with the compounds. 1 University of Ghana http://ugspace.ug.edu.gh CHAPTER ONE GENERAL INTRODUCTION 1.0 BACKGROUND Lanthanide metal-organic frameworks (LnMOFs) have recently been an interesting study area for many researchers due to their useful applications in a wide variety of fields. Lanthanide complexes have been applied as catalysts, luminescent probes, biomedical analyzers, and organic light-emitting diodes (OLED) (Bünzli, 2016; Bünzli et al., 2007; Priya & Sharma, 2017). Lanthanide metals have high coordination numbers and flexible coordination geometry and as 3+ such their complexes show some interesting structural motifs. The lanthanide ions (Ln ) absorb -1 -1 light weakly and therefore have less than 3 M cm molar absorption coefficients, resulting in their low luminescence (Lin et al., 2018). The characteristic f-f transition of the lanthanide ions is due to the shielding of the 4f orbital by the outer shells of the 5s and 5p orbitals (Malta, 2008). The f-f transition of lanthanides which is spin and parity forbidden usually occurs by the help of organic sensitizers which acts as energy transfer medium for the lanthanides through a process known as the “antenna effect”(Li et al., 2012; Lin et al., 2018; Zhao et al., 2017). Now, a typical luminescent lanthanide ligand (antenna) should consist of a chelating part for binding to the lanthanide ion, thereby prevents the coordination of H2O molecules to it which destroys the luminescence and also an aromatic part “antenna” which absorbs light energy and transfers to the excited state of the lanthanide ions and thereby emitting the characteristic fluorescence upon returning to the ground state (Krinochkin et al., 2018; Lin et al., 2018). The choice of organic sensitizer (ligand) used determines the effectiveness and stability of the luminescent lanthanide complex. Research has shown that the presence of a highly conjugated π- 2 University of Ghana http://ugspace.ug.edu.gh system and multiple coordination sites of the ligand improve the luminescent properties of the lanthanide complex(Filho et al., 2018). N-heterocyclic ligands have also been reported to influence the luminescent abilities of lanthanides and also make their complexes exhibit higher thermal stability (Biswas et al., 2011; Zhao et al., 2017). The chemistry of ligands bearing the nitrogen motif such as pyrazoles, triazoles and tetrazines has been the subject of research and several reviews. Their ease of synthesis and ability to substitute different groups on these heterocycle makes them interesting candidates for coordination chemistry. For instance, they have the ability to incorporate alkyl groups, aromatic rings and polydentate groups on the heterocyclic ring (Malcolm A. Halcrow, 2014). It is on this basis that this research work will focus on the synthesis of a highly conjugated π- system of pyrazole, triazole and tetrazine multidentate ligands bearing the N^N and O^N^N motifs and whose lanthanide complexes has not been fully explored from literature as shown in figure 1.1. The coordination, electronic and luminescent behaviour of the various ligands with some lanthanide salts was also investigated. 3 University of Ghana http://ugspace.ug.edu.gh Figure 1.1: Target Ligands ; triazole ligand( L1), pyrazole ligand (L2 and L3) and tetrazine ligand (L4). 4 University of Ghana http://ugspace.ug.edu.gh 1.1 PROJECT AIM The aim of this project is to synthesize and characterize some lanthanide metal (Pr, Gd, Dy, Tb) complexes of multidentate N-heterocyclic ligands {1-(2-Picolyl)-4-phenyl-1H-1,2,3-triazole (L1), [(2-hydroxyphenyl)bis(3,5-dimethyl-pyrazol-1-yl)]methane (L2) and 3,6-(dipyridyl)- 1,2,4,5-tetrazine} (L4) and study their luminescent properties. OBJECTIVES The objectives of this study are to:  Synthesize and fully characterize bis-pyrazolyl heteroscorpionates, triazole and tetrazine substituted ligands.  Complex the synthesized ligands to selected lanthanide metal salts.  Study the coordination modes of the synthesized lanthanide complexes.  Study the electronic and luminescent properties of the lanthanide complexes. 5 University of Ghana http://ugspace.ug.edu.gh CHAPTER TWO 2.0 LITERATURE SURVEY 2.1 CHEMISTRY OF LANTHANIDES The lanthanides which are also classified as rare earth elements, comprises of 15 elements, from 3+ lanthanum (57) to lutetium (71) on the periodic table. The lanthanides form trivalent ions Ln (where Ln is the general representation of lanthanide elements) which is the most stable oxidation state. However, a few other oxidation states have been observed, examples are 2+ 4+ europium (Eu ) and cerium (Ce ) ions. The lanthanide ions are paramagnetic due to the 3+ 3+ unpaired 4f electrons except in the case of lanthanum (La )and lutetium( Lu ) ions which are diamagnetic. (Bunzli & Eliseeva, 2010). The 4f electrons of the lanthanides are shielded by the low energy outer 5s and 5p electrons. As a result of this, the 4f electrons do have little or no interaction with their chemical environment. This phenomenon makes the lanthanides exhibit similar chemical properties. The lanthanides are found together in nature and require difficult and critical processes to separate them into their respective metal forms (Faridbod et al., 2018). However, they have their own unique physical properties such as colour, luminescent behaviour and nuclear magnetic properties. 6 University of Ghana http://ugspace.ug.edu.gh 2.2 ELECTRONIC PROPERTIES OF LANTHANIDES 3+ Lanthanide ions (Ln ) absorbs radiations mainly in the visible region of the electromagnetic spectrum. This causes excitation of the lanthanide ions from the ground state to an excited higher energy state, as a result of the availability of the partly filled 4f subshell. The 4f electrons are shielded by the 5s and 5p electrons and hence the 4f electrons have little interaction with their surrounding chemical environment of the metal ion (Werts, 2005). The f–f transitions of the lanthanide ions are possible by excitation by both electric dipole and magnetic dipole radiation. Electric dipole transition results from the interaction of an electron in an atom with the electromagnetic field while magnetic dipole transition results from the coupling of an electron to the magnetic part of the electromagnetic wave. The magnetic dipole transitions of the lanthanides are parity allowed whiles the electric dipole transitions are parity forbidden. Normally, the magnetic dipole transitions would not be perceived for transition metals, nevertheless, the lanthanides magnetic dipole transitions can often be seen, particularly in fluorescence spectra (Cotton, 2006). However, when the lanthanide ion is complexed to a ligand, the interactions causes relaxation of the selection rules, and electric dipole transition becomes partially allowed resulting in long-lasting emission as shown in figure 2.1 below. The lanthanide ions have 3+ 7 3+ 7 multiple excited states with Tb having Fn (where n= 0-6) and Eu having Fn (where n= 0-4) excited states. The excited states of the lanthanide ions should lie below the excited triplet state of the ligand for energy transfer. 3+ 5 7 From the diagram, the europium ion (Eu ) can emit light by the transition from D0 → F0 with -1 3+ 5 an energy of about 18 000 cm . Likewise, Tb can also emit light by the transition from D4 → 7 -1 F6 with an energy of about 20 000 cm . 7 University of Ghana http://ugspace.ug.edu.gh 3+ Figure 2.1: Partial energy diagram of Ln ions . Image obtained from Wang et al (2018). 2.3 COORDINATION CHEMISTRY OF LANTHANIDES Across the period of the lanthanides series, the atomic number increases and the ionic radius decreases as a result of the poor shielding ability of the f-orbital electrons. This leads to an increase of the effective nuclear charge which causes the shrinking of the 5s and 5p outer 3+ orbitals. Due to the emphasis on the ionic character of the lanthanides, Ln ions have a weak stereochemical preference and hence readily coordinates giving rise to variable coordination numbers and geometries as shown in figure 2.2. Lanthanides usually have coordination numbers between 3 and 14 with 8 being the most common coordination numbers observed (Cotton, 2006). However, coordination of the lanthanides are not easy to predict in solution. The lanthanides - - - usually complete their coordination with solvent molecules and anions (Cl , Br , OH ) if the 8 University of Ghana http://ugspace.ug.edu.gh denticity of the ligand is small or subsequently if their electronic density is low. Lanthanide ions also show hard acid behaviour as a result of their relatively small size and high charge states according to Pearson acid-base concept and hence prefer to bind with hard bases. As a result, they form stronger bonds with negatively charged N or O as donor atoms. Figure 2.2: Some coordination modes of lanthanide complexes reproduced from (Cotton, 2006) 2.4 LUMINESCENCE Luminescence is defined as the emission of light from an electronically excited state usually produced by excitation with either light (photoluminescence), electric current (electroluminescence) or by a chemical reaction (chemiluminescence). The lanthanides are luminescent with the exception of lanthanum (La) and lutetium (Lu). Their emission lines 9 University of Ghana http://ugspace.ug.edu.gh 3+ 3+ cover the entire electromagnetic spectrum from Ultraviolet (Gd ) to visible (orange Sm , 3+ 3+ 3+ 3+ 3+ red Eu , green Tb , yellow Dy ) and near-Infrared (Nd , Yb ) as shown in figure 2.3 Figure 2.3: The emission spectra of some lanthanide complexes (Bünzli, 2009) 2.5 LANTHANIDE LUMINESCENES SENSITIZATION The f-f transition of lanthanides which is spin and parity forbidden causes the lanthanides to have low absorption coefficients hence transition of the lanthanide ions by directly exciting them is usually not efficient. Therefore to avoid this setback, effective organic sensitizers (ligands) must be used. The organic sensitizers act as an energy transfer medium for the lanthanides through a process known as the “antenna effect” (Li et al., 2012; Lin et al., 2018; Zhao et al., 2017) as illustrated in figure 2.4. 10 University of Ghana http://ugspace.ug.edu.gh Figure 2.4: Lanthanide luminescence sensitization. Image obtained from “Reddy et al. (2013)” The ligand (antenna) transports energy to the lanthanide ions thereby exciting the lanthanide ion indirectly. This process causes excitation of the lanthanide ions at wavelengths which would usually not display absorption (Reddy et al., 2013; H. P. Santos et al., 2019). 2.5.1 MECHANISM OF LANTHANIDE LUMINESCENCE Firstly, an electron from the ligand absorbs energy which causes excitation to a higher energy level of the singlet state (S0 → S2). The excited electron undergoes internal conversion (IC) by falling to the lowest state of the excited singlet state (S1). At the lowest state of the excited singlet, two transitions take place. The excited electron can either move to the ground state (S0) causing fluorescence or transverse a non-radiative pathway to the ligand triplet state (T1). At the triplet state, the excited electron can either move to the ground state resulting in phosphorescence or transport energy to the lanthanide ion excited state. Here the excited lanthanide ion can return to the ground state causing fluorescence through an f-f transition as illustrated in figure 2.5 (Cable et al., 2011; Cotton, 2006). 11 University of Ghana http://ugspace.ug.edu.gh Figure 2.5: Mechanism of luminescence in lanthanide complexes adopted from “Cable et al. (2011)”. 2.5.2 QUENCHING OF LANTHANIDE LUMINESCENCE 3+ A typical luminescent lanthanide ligand should consist of a chelating part for binding to the Ln ion thereby avoiding the coordination of H2O molecules to it which destroys the luminescence and also an aromatic part “antenna” which absorbs light energy and transfers to the excited state of the lanthanide ions and in so doing emits the characteristic fluorescence upon returning to the ground state (Krinochkin et al., 2018; Lin et al., 2018). The organic sensitizer which will bind to the lanthanide ions must be capable of absorbing and transferring energy efficiently to the lanthanide metal. It must also be able to guard the lanthanide ion from solvent molecules which kills off the luminescence as shown in figure 2.6 below. 12 University of Ghana http://ugspace.ug.edu.gh Figure 2.6: Quenching of lanthanide luminescence The type and structure of the ligand affect the fluorescence properties (quantum yield, excitation wavelength, emission lifetime and molar extinction coefficient) of the lanthanide complex 3+ 3+ (Ajlouni et al., 2016). The excited states of terbium (Tb ) and europium (Eu ) complexes from literature have been known to have large stokes’ shifts, strong fluorescence emission, narrow emission profiles and long fluorescence lifetimes (Yan et al., 2015). A research by Bortoluzzi et al (2011) synthesized a europium complex of hydrotris(pyrazolyl)borate. When the complex was irradiated with UV of wavelength lower than 380 nm, it showed luminescence with the most prominent emission peak corresponding to the 5 7 D0→ F4 transition which fell from 690 nm to 700 nm (Bortoluzzi et al., 2011). 13 University of Ghana http://ugspace.ug.edu.gh 2.6 APPLICATIONS OF LANTHANIDE COMPLEXES The lanthanide ions which are known for their narrow emission lines as a result of the f-f transition have found numerous applications. The f-f transitions are sharp due to their large stokes shift, hence high colour purity is observed. As a result of their distinctive photophysical properties, lanthanide metal complexes have been used as emitters in OLED displays, lasers, cathode-ray, plasma displays (Armelao et al., 2010; Monteiro & de Bettencourt-Dias, 2018). They are also applied in the field of medicine as contrast agents in MRI and CT scans. 2.6.1 LASERs (Light Amplification by Stimulated Emission of Radiation) Lasers are widely used as laser pointers, military target designation and in medicine (oncology, ophthalmology or thermotherapy). Various lanthanide ions such as Nyodenium, Erbium, Thulium, Ytterbium and Cerium can be used in LASERs as a doping material in pure YAG (yttrium Aluminium garnet). Neodymium YAG (yttrium Aluminium garnet) is the most common laser of all (Bünzli, 2015). 2.6.2 LANTHANIDE SHIFT REAGENTS Before the use of high-frequency NMR spectrometers, paramagnetic lanthanide complexes such as (tris(2,2,6,6-tetramethylhepta-3,5-dionato)europium(III)) [Eu(dpm)3] was used to produce shifts in the NMR spectra. This technique helped in the spreading out of the spectrum thereby removing degeneracies and overlaps in the spectrum which helped in the interpretation of the data. Also, chiral shift reagents such as europium camphorato complex as shown in figure 2.7 is used to differentiate two diastereomers by producing different peaks in the NMR spectrum when it binds to the racemic mixture. 14 University of Ghana http://ugspace.ug.edu.gh Figure 2.7: A chiral shift reagent reproduced from (Cotton, 2006) 2.6.3 MAGNETIC RESONANCE IMAGING (MRI) MRI is a suitable technique for the diagnosis of cerebral abnormalities, lesions, tumors, and infarcted artery. The MRI scanner is basically a pulsed FT-NMR spectrometer that depends on the detection of NMR signals from hydrogen atoms in water molecules (Bottrill et al., 2006). The MRI scanner is able to distinguish water molecules in a healthy tissue from a cancerous tissue due to the longer relaxation times of water molecules in cancerous tissues as shown in figure 2.8. However, this technique faces low sensitivity challenges and hence MRI contrast agents are used to enhance sensitivity. The contrast agents are usually paramagnetic or superparamagnetic compounds that shortens the relaxation time of water protons catalytically and thereby generate contrast between healthy and cancer tissues (Cotton, 2006; Rashid et al., 2013). Gadolinium (III) complexes have been the preferred choice of contrast agent due to the large number of unpaired electrons of the gadolinium ion because it lies mid-way through the lanthanide series. Also, it has fairly long electron spin relaxation time over the other 15 University of Ghana http://ugspace.ug.edu.gh 3+ 3+ 3+ paramagnetic ions (Eu , Dy , Yb ). Some structures of common gadaolinium complexes used as contrast agents are shown in figure 2.9. Figure 2.8: MRI scanner (left) and head scan image (right) Figure 2.1: Some common gadolinium complexes used as contrast agents. Fig 2.10-A ® ® (gadoterate meglumine; Dotarem ) and fig 2.10-B (ProHance ) reproduced from Cotton (2006). 16 University of Ghana http://ugspace.ug.edu.gh CHAPTER THREE LANTHANIDE COMPLEXES BASED ON SUBSTITUTED TRIAZOLE LIGANDS 3.0 INTRODUCTION AND LITERATURE REVIEW 3.1 GENERAL OVERVIEW OF TRIAZOLES Triazoles are five-membered nitrogen heterocycles consisting of three atoms of nitrogen and two atoms of carbon. There are two isomeric forms of triazoles which are (1,2,3)-triazole and (1,2,4)- triazole (Dheer et al., 2017). The 1,2,3-triazoles are a biologically important group of compounds. The triazole ring is stable due to its aromatic nature and also has a large dipole moment along with hydrogen bonding aptitude and this makes them a good moiety for organic compounds. Figure 3.1: Structure of 1,2,3-triazole (A) and 1,2,4-triazole (B) 3.1.1 COORDINATION OF 1,2,3-TRIAZOLES. The 1,2,3-triazole molecule can bind metal ions in five distinct coordination modes shown in figure 3.2. Structures A and B show the protonated triazole ligand acting as a di-nucleating 17 University of Ghana http://ugspace.ug.edu.gh ligand and exhibiting a (µ2,3- and µ1,3-) coordination mode. Structures C, D and E show the triazolate ring exhibiting (µ1,2- and µ1,3-) coordination modes or acting as a tri-nucleating ligand( µ1,2,3-) coordination mode (Aromí et al., 2011). Figure 3.2: Coordination modes of triazole ligand reproduced from (Aromí et al., 2011) 3.2 SYNTHESIS OF TRIAZOLES Preparation of 1,2,3-triazolyl compounds is mainly through a 1,3-dipolar cycloaddition reaction involving an alkyne and azide and the process is well known as the azide-alkyne Huisgen cycloaddition (Aromí et al., 2011). However, this reaction is slow, required high heat and had poor regioselectivity (Yamada et al., 2017). Sharpless et al (2002) reported the Cu(I)-catalyzed 18 University of Ghana http://ugspace.ug.edu.gh form of the azide-alkyne Huisgen cycloaddition (CuAAC) which is an improvement on both the rate and regioselectivity of the synthesis and thereby improving the yield of the 1,2,3-triazoles under mild and environmentally benign conditions as shown in scheme 3.1. This reaction was termed “click chemistry” and it has been used extensively in various research works (Kolb et al., 2001; Ogden et al., 2011; V.V. Rostovtsev et al., 2002). A report by Hein and Fokin (2010) investigated the mechanism for the copper-catalyzed click reaction based on Discrete Fourier Transform (DFT) calculations and proposed a mechanistic scheme for the reaction as shown in scheme 3.2. The mechanism involved firstly the formation of a copper (I) acetylide which then coordinates to the azide to form an intermediate. The electrophilic azide terminal is then attacked by the nucleophilic acetylide to for a C-N bond. The unstable copper metallacycle rearranges to form a stable copper triazolide which gets protonated to form the triazole molecule. Ruthenium catalyzed-azide alkyne “click” reaction (Ru-AAC) has been reported in some works by Krasinski et al for the synthesis of regio-specific 1,5-disubstituted-1,2,3-triazoles (Krasinski et al., 2004; Rasmussen et al., 2007). 19 University of Ghana http://ugspace.ug.edu.gh Scheme 3.1: Regioselectivity of azide-alkyne cycloaddition reaction. Reproduced from (Totobenazara & Burke, 2015). Scheme 3.2: Proposed mechanism for the CuAAC click reaction for triazoles based on DFT calculations by (Hein & Fokin, 2010). 20 University of Ghana http://ugspace.ug.edu.gh A survey of literature reveals quite a number of research work done on the synthesis and applications of substituted triazole ligands. A research work by Jiang et al synthesized copper complexes of triazole ligand from CuAAc click reactions. Their work revealed that both ligand and complexes were photoluminescence active. The complexes also showed catalytic activity towards azide-alkyne cycloaddition (Jiang et al., 2013). Other works done by Gu et al (2016) have synthesized a library of substituted triazole ligands with yields up to 96% using a phenanthroline-based N-heterocyclic carbene tetranuclear copper (I) complex as catalyst for click reaction(S. Gu et al., 2016; Shaojin Gu et al., 2012). A one-pot synthesis of triazole ligands reported by Xie et al involves benzyl halides and alkynes in nonionic nanomicelles with water as the preferred solvent (Xie et al., 2014). Connel and co- workers synthesized iridium(III) complexes of (2-pyridyl)-1,2,3-triazole with the ligand acting as a bidentate ligand. They also observed a C2N4 distorted octahedral geometry around the metal as shown in figure 3.3. Also, the complex showed good luminescent properties (Connell et al., 2016). Figure 3.3: Iridium(III) complex of triazole ligand reproduced from “Connell et al. (2016)” 21 University of Ghana http://ugspace.ug.edu.gh Bortoluzzi and co-workers also synthesized a novel gold complex of the substituted triazole ligand as illustrated in figure 3.4 (Bortoluzzi et al., 2013). Figure 3.4: Au(III) complex of substituted triazole ligand reproduced from (Bortoluzzi et al., 2013). A literature survey on the choice of substituted triazole ligand reveals extensive studies on the synthesis of the ligand. The coordination chemistry of the triazole ligand particularly with the transition metals have been widely investigated. However, there is a knowledge gap on the chemistry of lanthanide complexes for the choice of ligand. This chapter shows the chemistry of lanthanide complexes based on substituted triazole ligand particularly Praseodymium (Pr), Dysprosium (Dy), Terbium (Tb) and Gadolinium (Gd). 22 University of Ghana http://ugspace.ug.edu.gh 3.3 EXPERIMENTAL METHODS All reagents used in this experiment were of analytical grade obtained from Sigma-Aldrich. 3.3.1 Synthesis of 1-(2-Picolyl)-4-phenyl-1H-1,2,3-triazole (L1). Synthesis of the ligand L1 followed the procedure adopted by Connell et al, (2016). Scheme 3.3: Synthesis of (L1). 3.3.2 PREPARATION OF LANTHANIDE COMPLEXES. 3.3.2.1 Synthesis of (L1Pr(acac)3). (0.18 mL, 0.96 mmol, 3 mol eqv) 2,2,6,6-tetramethyl-3,5-heptanedione in 30 mL methanol acting as an ancillary ligand was deprotonated with potassium hydroxide solution. (110 mg, 0.32 mmol, 1 mol eqv) praseodymium chloride monohydrate (PrCl3.H2O) and (75 mg,0.32 mmol, 1 mol eqv) L1 ligand were added with stirring for 12 Hrs. After, it was allowed to stand in a fume hood and solvent slowly evaporated to afford yellow crystals. Yield (70%), 23 University of Ghana http://ugspace.ug.edu.gh -1 IR (cm ): 3128 (m), 2965 (s), 1595 (s), 1585 (s) , 1437(s), 1236 (m), 1148 (m), 1077 (w), 994 (m), 754 (s), 693 (s) 1 H-NMR(500 MHz, Chloroform-d) δ 0.78(s, 3H),1.18 (s, 5H), 5.72 (d,J = 12.7Hz, 2H),7.27 (d, J=8.6Hz, 3H),7.31 –7.34 (m, 1H),7.41 (t,J =7.5 Hz,2H),7.70 (t,J =7.6 Hz,1H),7.83 (d, J = 7.6 Hz, 2H),7.93 (s, 1H), 8.62 (s, 1H). Scheme 3.4: Synthesis of (L1Pr(acac)3). 3.3.2.2 Synthesis of (L1Dy(acac)3). (0.18 mL, 0.96 mmol, 3 mol eqv) 2,2,6,6-tetramethyl-3,5-heptanedione in 30 mL methanol acting as an ancillary ligand was deprotonated with potassium hydroxide solution. (120 mg, 0.32 mmol, 1 mol eqv) dysprosium chloride hexahydrate (DyCl3.6H2O) and (75 mg, 0.32 mmol, 1 mol eqv) L1 ligand were added with stirring for 12 Hrs. After, it was allowed to stand in a fume -1 hood and solvent slowly evaporated to afford pale yellow crystals. Yield (70%), IR (cm ): 3130 (m), 2925 (s), 1597 (s), 1571 (s), 1465 (m), 1437 (m), 1237 (m), 1148 (m), 994 (m), 754 (s), 693(s). 24 University of Ghana http://ugspace.ug.edu.gh 1 H-NMR (500 MHz, Chloroform-d) δ 1.51 – 1.63(m, 17H), 5.71(s,2H), 7.32 (s,1H), 7.41 (s, 3H), 7.70 (s, 1H),7.83(s,2H),7.93(s,1H),8.62 (s, 1H). Scheme 3.5 Synthesis of (L1Dy(acac)3). 3.3.2.3 Synthesis of (L1Gd(acac)3). (0.18 mL, 0.96 mmol, 3 mol eqv) 2,2,6,6-tetramethyl-3,5-heptanedione in 30 mL methanol acting as an ancillary ligand was deprotonated with potassium hydroxide solution. (126 mg, 0.32 mmol, 1 mol eqv) gadolinium chloride hexahydrate (GdCl3.6H2O) and (75 mg, 0.32 mmol, 1 mol eqv) L1 ligand were added and stirred for 12 Hrs. After, it was allowed to stand in a fume -1 hood and solvent slowly evaporated to afford creamy crystals. Yield(70%), IR (cm ): 3130 (m), 2957 (s), 2924 (s), 1597 (s), 1571 (s), 1438 (m), 1226 (s), 1049 (w), 754 (s), 693 (s). 25 University of Ghana http://ugspace.ug.edu.gh 1 H-NMR (500 MHz, Chloroform-d) δ 0.88 (s,1H), 1.18 (s, 2H), 5.71 (s, 5H), 7.27 (d,J = 9.3Hz, 8H),7.33 (d, J =7.1 Hz,2H),7.41 (t,J =7.5 Hz, 5H),7.70 (s,2H),7.83 (d, J =7.3 Hz, 5H), 7.94 (s, 2H), 8.62 (s, 2H). Scheme 3.6 Synthesis of (L1Gd(acac)3). 26 University of Ghana http://ugspace.ug.edu.gh 3.4 RESULTS AND DISCUSSION 3.4.1 CHARACTERIZATION OF COMPLEXES. 1 The complexes have been formed in good yields (70%), and characterized by H-1NMR, and FT-IR spectroscopy. The complexes were highly soluble in chloroform and methanol solution but insoluble in petroleum ether and water. 3.4.2 FT-IR ANALYSIS FT-IR spectroscopy was applied to confirm the functional groups present in the synthesized complexes. The study also examined the influence of the lanthanide metals on the absorption peaks. The spectrum of the synthesized ligand L1 presented in figure 3.5 was in accordance with literature values (Connell et al., 2016). Figure 3.6 presents a stacked spectra of ligand and praseodymium complex which outlines the 3 differences in vibrational bands observed. The sp -CH stretch was observed as an intense peak at -1 -1 2 2965 cm in comparison to the ligand at 2923 cm . Likewise, the sp -CH stretch showed at 3126 -1 -1 cm and that of L1 at 3129 cm . This differences in absorption was surrely due to coordination -1 L1 to the lanthanide. In addition, the C=O stretch at 1595 cm as compared to that of the -1 ancillary ligand C=O stretch at 1606 cm confirms coordination of the oxygen to the praseodymium metal and therefore justifies the observed change in absorption number. -1 Furthermore, the observed medium peak at 1236 cm for a C-N stretch as compared to that of -1 the ligand at 1227 cm also suggests coordination of the pyridine nitrogen to praseodymium. Similar observations were made for dysprosium and gadolinium complexes presented in figure 3.7 and figure 3.8 and therefore points out the formation of the complex. 27 University of Ghana http://ugspace.ug.edu.gh Figure 3.5: FT-IR of L1 Figure 3.6: Stacked IR of L1 and (L1Pr(acac)3). 28 University of Ghana http://ugspace.ug.edu.gh Figure 3.7:Stacked IR of L1 and (L1Dy(acac)3). Figure 3.8: Stacked IR of L1 and (L1Gd(acac)3). 29 University of Ghana http://ugspace.ug.edu.gh 13.4.3 H-NMR STUDIES Proton NMR spectrum of the synthesized complexes illustrated in figure 3.9 to figure 3.11 generally showed peaks likened to the ligand L1 and 2,2,6,6-tetramethylheptanedione(acac). However, the peaks are poorly resolved as a result of the paramagnetic nature of the lanthanide metals influencing the complex formed. Also, slight changes in the chemical shift values of the protons to a higher chemical shift value was observed due to the nature of the lanthanide complex, which is known and applied as shift reagents in NMR spectroscopy. For instance, the proton peak H7 observed at 5.68 ppm for the ligand was observed at 5.72 ppm for praseodymium complex and 5.71 ppm for both dysprosium and gadolinium complexes. Also, the proton peak H6 at 8.57 ppm for ligand was observed at 8.62 ppm for all the complexes. Furthermore, the presence of methyl protons of the tert-butyl from the ancillary ligand (acac) was detected in the proton NMR spectra for all the complexes at 1.18 ppm for praseodymium and gadolinium complexes and 1.56 ppm for dysprosium complexes. Also the intensity ratio of the methyl peaks to the proton peaks of the ligand is about 3:1 which is an indication that only one molecule of the ligand as compared to the ancillary ligand (acac) is involved in the complex formed. A stacked spectrum of the proton NMR of the synthesized complexes compares the intensities of the ligand peaks and the complex peaks. As seen from figure 3.12, the intensities of the ligand peaks are a thousand times more than the intensities of the synthesized lanthanide complex peaks which is an indication of the influence of the paramagnetic metal. Also, the stacked spectrum reveals shifts in the chemical shift values of the complexes to a more downfield region as compared to the ligand, which is expected since lanthanides are known to cause paramagnetic shifts in an NMR spectrum. 30 University of Ghana http://ugspace.ug.edu.gh 1 Figure 3.9: H- NMR OF (L1Pr(acac)) 1 Figure 3.10: H- NMR OF (L1Dy(acac)) 31 University of Ghana http://ugspace.ug.edu.gh 1 Figure 3.11: H- NMR OF (L1Gd(acac)) 1 Figure 3.12: Stacked H-NMR of L1 and complexes 32 University of Ghana http://ugspace.ug.edu.gh 3.4.4 ELECTRONIC PROPERTIES OF LIGAND AND COMPLEXES. The electronic behaviour of the synthesized ligand and complexes were examined using a Shimadzu UV-1800 spectrophotometer. Prior to the experiment, 1 µM methanolic solutions of L1 and complex was prepared. The absorption spectra of L1 and complexes in methanol is presented in figure 3.13. L1 presents absorption from 308nm to 235 nm with maximum * absorption at 244 nm and can be ascribed to π-π transition. The deprotonated 2,2,6,6- tetramethyl-3,5-heptanedione labelled as (acac) exhibited a broad absorption band between 315 * nm and 240 nm with a maximum absorption peak at 274 nm attributed to the π-π transition of enolate ion. The absorption maxima of the synthesized complexes are 245 nm and 248 nm for praseodymium and gadolinium complexes correspondingly indicating a bathochromic shift from the ligand absorption maximum. Figure 3.13: Absorption of L1 and complexes 33 University of Ghana http://ugspace.ug.edu.gh 3.4.5 LUMINESCENT STUDIES The excitation and emission spectrum of the ligand and complexes have been measured using a SHIMADZU RF-6000 SPECTROFLUOROPHOTOMETER. 1.0 mM solutions of ligand and complexes in methanol, acetone and dichloromethane was prepared for the experiment and measurement was done at room temperature condition. This fluorescent experiment was conducted in different solvents in other to determine the appropriate solvent that will give the maximum emission. As illustrated in figure 3.14, the graphs clearly indicate that methanol was a suitable solvent as it showed higher excitation and emission peaks as compared to acetone and dichloromethane. It can then be said that emission of the synthesized complexes increases in polar solvents. The absorption and emission spectra of the synthesized ligand and complexes in methanol solution are illustrated in figure 3.15 C and D respectively. Maximum excitation was achieved at -1 350 nm which resulted in a broad emission peak at 701 nm (14 265 cm ) and 703 nm (14 224 -1 3+ 3+ cm ) for Pr and Gd complex respectively. The praseodymium complex exhibited a higher emission intensity than that of the gadolinium complex. Nonetheless, the emission intensities of both the ligand and ancillary ligand were relatively low as compared to the emission intensities of the complexes. This observation was expected and indicates the effect of the ligand as a suitable sensitizer in improving the luminescence of complexes. 34 University of Ghana http://ugspace.ug.edu.gh Figure 3.14: Comparison of absorption A and emission B of complexes in methanol, acetone and dichloromethane Figure 3.15: Comparison of absorption C and emission D of ligand and complexes in methanol solution 35 University of Ghana http://ugspace.ug.edu.gh 3.4.6 QUANTUM YIELD MEASUREMENTS Quantum yield measures the efficiency of light emission of luminescent compounds. It is known as the ratio of the amount of photons emitted to the amount of photons absorbed and is given by the equation ŋ2 I A ref QY=QYref ŋ2 ref A I ref where QY= quantum yield of analyte QYref = quantum yield of reference compound 2 2 Ŋ and Ŋ ref = refractive index of solvent of analyte and reference respectively I and Iref = fluorescence intensity of the analyte and reference respectively A and Aref =absorbance of analyte and reference at excitation wavelength respectively The compound fluorescein was chosen as the reference compound which has a quantum yield of 92% in 0.1 M NaOH solution (Brouwer, 2011; Porres et al., 2006). 1 mM solution of fluorescein was prepared in 0.1 M NaOH for the experiment. The calculated quantum yield of ligand and complexes are presented in table 3.1. The quantum yield for both the ligand and the ancillary ligand could not be computed by the spectrofluorophotometer as a result of their extremely low emission properties. Praseodymium complex recorded the highest quantum yield value of 0.87% with dysprosium and gadolinium complexes recording 0.54% and 0.51% respectively. In general, the quantum yield values obtained for the complexes were relatively low. This observation could be due to the inefficiency of the ligand to act as a suitable sensitizer and also the possibility of water and solvent molecules in the coordination sphere of the complexes and 36 University of Ghana http://ugspace.ug.edu.gh thereby quenching the luminescence. This setback could be eliminated when solid-state luminescence measurements are done to eliminate the possibility of luminescence quenching from the oscillation of solvent molecules. Table 3.1: Quantum yield data of L1 and complexes COMPOUND QUANTUM YIELD % Pr-complex 0.87 Gd-complex 0.51 Dy-complex 0.54 Ligand L1 ----- Ancillary ligand(acac) ----- 37 University of Ghana http://ugspace.ug.edu.gh 3.4.7 CYCLIC VOLTAMMETRY MEASUREMENTS The reduction-oxidation properties of the synthesized ligand and complexes were observed using cyclic voltammetry experiments. 1mM solutions of both ligand and complexes were prepared in methanol at room temperature . A supporting electrolyte solution of 0.1 M tetrabutylammonium tetrafluoroborate in methanol was also prepared prior to the experiment. The experiment was performed as a three-electrode cell system comprising of Ag/AgCl reference electrode, glassy carbon working electrode and a platinum counter electrode. A ratio of 1:100 ( analyte to supporting electrolyte) in terms of the amount was adopted before the voltage sweep. The graph in figure 3.16 presents the cyclic voltammogram of the ligand L1. The graph reveals no cathodic and anodic peaks which indicates that the ligand is probably not redox active. Oxidation basically should involve the removal of an electron from the metal f- orbital. In the case of the complexes, the cyclic voltammograms shown in figure 3.17 and figure 3.18 both indicate an irreversible oxidation taking place at a scan rate of 80 mV/s. This observation could be due to the phenomenon of adsorption and desorption taking place in the reaction at the electrodes. The difference in the cyclic voltammetry graphs of the complex are an indication of the presence of a metal coordinated to the ligand. 38 University of Ghana http://ugspace.ug.edu.gh Figure 3.16: Cyclic voltamogram of ligand L1 Figure 3.17: Cyclic voltamogram of gadolinium complex Figure 3.18: Cyclic voltamogram of praseodymium complex 39 University of Ghana http://ugspace.ug.edu.gh 3.5 CONCLUSION This chapter reports on the preparation of three new lanthanides (Pr, Dy, and Gd) complexes of a CuAAC ligand in appreciable yields. The characterization techniques (FT-IR, 1H-NMR) employed helped to identify and confirm the coordination of the ligands to the lanthanide metal center. Absorption measurement helped identify the major electronic transition which was * ascribed to the π-π from the ligands. The prepared complexes exhibited fluorescent properties with the praseodymium complex having the highest quantum yield of 0.87% in methanol as compared to dysprosium and gadolinium complexes 0.51% and 0.54% respectively. Cyclic voltammetry measurements on the complexes also reveal coordination of the lanthanides to the ligand and also showed an irreversible oxidation of the complexes. 40 University of Ghana http://ugspace.ug.edu.gh CHAPTER FOUR LANTHANIDE COMPLEXES BASED ON PYRAZOLE HETEROSCORPIONATES 4.0 INTRODUCTION AND LITERATURE REVIEW 4.1 GENERAL OVERVIEW OF PYRAZOLES Pyrazoles are nitrogen heterocyclic five-membered aromatic ring bearing three carbons and two neighboring nitrogen atoms. Pyrazoles owing to the presence of two neighboring nitrogen atoms are also known as 1, 2-diazoles and they have good electron donor capabilities due to the two chemically distinct nitrogen atoms. Nitrogen atom (N1) is ‘‘pyrrole-like” because its unshared electrons are conjugated with the aromatic system. Nitrogen atom (N2) is ‘‘pyridine-like” since the unshared electrons are not affected by resonance, analogous to pyridine structures (Faria et al., 2017; M. A. Halcrow, 2009). Due to the different nitrogen atoms, pyrazoles can react with both acids and bases as shown in scheme 4.1. Scheme 4.1: Amphoteric nature of (1H)-pyrazole 4.1.1 COORDINATION CHEMISTRY OF 1H-PYRAZOLE. 1 Pyrazoles typically bind with metal in simple κ fashion through nitrogen atom (N2), leaving the N–H group to bind with anions and other hydrogen bond acceptors (T.C Higgs & Carrano., 1998). Figure 4.1 illustrates some coordination modes of pyrazole reported in literature. 41 University of Ghana http://ugspace.ug.edu.gh Figure 4.1 :Various coordination modes of 1H-pyrazole with metals (M) reproduced from (M. A. Halcrow, 2009) 42 University of Ghana http://ugspace.ug.edu.gh 4.1.2 SYNTHESIS OF PYRAZOLES The synthesis of pyrazoles has been extensively reported in literature (Brown, 2018). Pyrazole derived compounds were firstly synthesized in 1883 by Knorr through the condensation of 1,3- dicarbonyl with hydrazine presented in scheme 4.2. Scheme 4.2: Knorr synthesis of pyrazoles Several other methods have also been employed in the synthesis of pyrazole moiety. The widely used synthetic scheme for the synthesis of pyrazoles with substitution at the 3 and 5 position involves, cyclo-condensation of either α,β-unsaturated carbonyl or 1,3-dicarbonyl with a suitable hydrazine molecule, which acts as a nucleophile as shown in scheme 4.3 (Fustero et al., 2009). 43 University of Ghana http://ugspace.ug.edu.gh Scheme 4.3: Preparation of 3,5-disubstituted pyrazoles reproduced from(Fustero et al., 2009) Wang et al. also reported on a solventless preparation of pyrazole in a mortar by the combination of an appropriate hydrazine monohydrate and diketone using concentrated sulphuric acid as a catalyst is shown in sScheme 4.4 (Wang & Qin, 2004) Scheme 4.4: Solventless synthesis of pyrazoles reproduced from (Wang & Qin, 2004) 44 University of Ghana http://ugspace.ug.edu.gh The pyrazole moiety has been discovered to be suitable for comprehensive and wide-ranging applications. In the pharmaceutical sector, there is a long history of success with the pyrazole as the central structure in a variety of drugs. Latest achievements have seen interesting advances in metal-organic frameworks and electroluminescence, not to mention a few. This has driven some synthetic chemists to build larger structures from the pyrazole ring. One of the larger structures of pyrazole worked on in this work is the pyrazole scorpionate compounds. 4.2 SCORPIONATES The term scorpionates was first reported by Trofimenko in 1999 as tripodal ligands that contain nitrogen donor heterocycles (pyrazole, triazole, imidazole and others) that are linked to a bridging carbon. The scorpionate ligands tend to mimic the comparable position of a scorpion that uses its three stings (2 pincers and a claw) to attack its prey as shown in figure 4.2. If the bridging groups are of the same group, a C3V symmetry is obtained and the ligand is termed as a homoscorpionate. However, when one of the bridging groups is of more than one binding group, the ligand is termed as heteroscorpionate. Figure 4.2: Depiction of a scorpionate attack (Martins & Pombeiro, 2017). 45 University of Ghana http://ugspace.ug.edu.gh 4.2.1 COORDINATION OF SCORPIONATES The scorpionate ligands are highly versatile in the sense that they are able to swap between a bidentate and tridentate coordination manner to the metal center thereby giving rise to either an N, N or N, N, X (where X= N, O, S) coordination modes. The coordination properties of scorpionate ligands are also dependent on the electronic and steric properties of the substituents on the pyrazole at position C3 and C5 as reported by Trofimenko (1999). Strianese and co-workers synthesized (3,5-tert-butyl-2-phenol)bis(3,5-dimethylpyrazol-1- yl)methane and 2-phenol)bis(3,5-dimethylpyrazol-1-yl) methane complexes of CoCl2, ZnCl2 and 2 CuCl2. Their research showed that the ligand L2-H formed a κ -coordinated tetrahedral complex 2 with ZnCl2 and a κ -coordinated square complex with CuCl2.2H2O (Strianese et al., 2011). A similar research by Milione et al (2009) also synthesized zinc complexes of (3,5-di-tert-butyl-2- methoxyphenyl)bis(3,5-dimethylpyrazol-1-yl)methane and 2,4-di-tert-butyl-6-[bis(3,5- 2 dimethylpyrazol-1-yl)methyl]phenol. Their findings showed that the ligand was κ -coordinated to the zinc via the imino nitrogens of the two pyrazolyl rings. Their research also pointed out that the hydroxyl (OH) group did not coordinate to the zinc metal but was instead engaged in intermolecular hydrogen bonding that helped in the stability of the complex as demonstrated in scheme 4.5 (S. Milione et al., 2009). 46 University of Ghana http://ugspace.ug.edu.gh Scheme 4.5: Zn and Cu complexes of N, N, O heteroscorpionate ligand reproduced from (S. Milione et al., 2009) Warthen and Carrano synthesized Cu (II) acetate complex of (2-hydroxy-3-tertbutyl- methylphenyl)bis(3,5-dimethylpyrazolyl)methane. They observed that the Cu adopted a 5- coordinate geometry comprising a bidentate acetate, two pyrazole nitrogen and phenoxy oxygen in an apical position (Warthen & Carrano, 2003). A research by Schofield et al (2009) synthesized N,N,O 2,4-di-tert-butyl-6-bis(3,5- dimethylpyrazolyl)methyl)phenol complexes of sodium, magnesium and zinc (Schofield et al., 2009). In every case of the formation of the complex, they observed monomeric coordination of 47 University of Ghana http://ugspace.ug.edu.gh the ligand with the metals in an N, N, O coordination mode with the metal as shown in scheme 4.6. Scheme 4.6: Zn and Mg complexes of N,N,O heteroscorpionate reproduced from (Schofield et al., 2009) 48 University of Ghana http://ugspace.ug.edu.gh 4.2.2 SYNTHESIS OF SCORPIONATES The preparation of bis-pyrazolyl methane scorpionates has been described in literature as illustrated in scheme 4.7 (S. Milione et al., 2009; Otero et al., 2013; Paolucci et al., 2009; Schofield et al., 2009; Zhang et al., 2009). Scheme 4.7: Synthetic schemes for the synthesis of bis-pyrazolyl scorpionates reproduced from (S. Milione et al., 2009; Otero et al., 2013; Schofield et al., 2009) 49 University of Ghana http://ugspace.ug.edu.gh 4.2.3 MECHANISM OF REACTION Millione and co-workers in 2006 proposed a mechanism for the synthesis of the heteroscorpionate ligand which is presented in scheme 4.8. The mechanism relies on the cobalt catalyst which coordinates to the two pyridine-like nitrogen of the carbonyl-dipyrazole to form a ring. A heterolytic cleavage of the carbonyl-nitrogen then occurs to form a carbo-cation. The introduced salicylaldehyde gets attached to the carbanion to form a carbamate intermediate. The intermediate formed undergoes decarboxylation which is followed by dissociation of the cobalt metal to yield N, N, O heteroscorpionate ligand (Stefano Milione et al., 2006). Scheme 4.8: Proposed mechanism for the preparation of N,N,O heteroscorpionate ligand reproduced from (S. Milione et al., 2009) 50 University of Ghana http://ugspace.ug.edu.gh 4.2.4 APPLICATIONS OF POLYPYRAZOLYL-SCORPIONATES The most studied property of pyrazoles is their bioactivity and as such, they are widely used in the field of medicinal chemistry as pharmacological agents (Santos et al., 2012). Also, pyrazole ligands have also been applied as dyes and catalysts. Metal complexes of most pyrazole ligands have been studied as homogenous or supported catalysts. A research by Silvestri et al (2010) synthesized 2,4-di-tert-butyl-6-bid-(3,5-dimethylpyrazol-1- yl)methyl pheno-aluminium complexes for polymerization of L-lactide (Silvestri et al., 2010). Likewise, a research by Paolucci et al (2009) synthesized scandium and yttrium complexes of the scorpionate ligand (3,5-di-tert-butyl-2-phenoxo)bis(3,5-dimethyl-pyrazol-1-yl)methane and were applied in ethylene polymerization reactions (Paolucci et al., 2009). 51 University of Ghana http://ugspace.ug.edu.gh All though the coordination chemistry involving (2-phenoxo)bis(3,5-dimethyl-pyrazol-1- yl)methane ligand has been extensively studied, no reports to date have been made on analogues containing the more bulky tert-butyl (L3) substituted on the 3,5 positions of the pyrazole, as shown in figure 4.3. Figure 4.3 Target ligands Even more intriguing is the fact not no coordination complex of this ligand system with lanthanide metals have been reported in literature up to date. This chapter focuses on the synthesis of 2-hydroxyphenyl-bis-pyrazolyl methane ligands with more bulky substituents on the 3 and 5 positions of the pyrazole ring and their coordination complexes with selected lanthanide metal salts. 52 University of Ghana http://ugspace.ug.edu.gh 4.3 EXPERIMENTAL METHODS 4.3.1 Synthesis of (2-hydroxyphenyl)bis(3,5-dimethyl-pyrazol-1-yl) methane (L2). Synthesis of L2 followed a similar methodology adopted by (Alesso et al., 2012). Yield (50%) 4.3.2 Synthesis of (2-hydroxyphenyl)bis(3,5-di-tert-butyl-pyrazol-1-yl)methane (L3). (0.2 g, 1.11 mmol) 3,5-di-tert-butyl-1H-pyrazol was dissolved in 50 mL pre-dried tetrahydrofuran solution with excess metallic sodium. The solution was chilled to 0 °C and (0.05 mL, 0.055 mmol) phosgene solution added dropwise and stirred for 4 hrs. Approximately (0.07 mL, 0.055 mmol) 2-hydroxybenzaldehyde and catalytic amounts of CoCl2.6H2O were both added and the resulting solution was refluxed for two days. The reaction was stopped by adding 30 mL distilled water which changed the colour from turquoise green to yellow. 30 mL portions of chloroform were used to extract the product into the chloroform layer. The organic solvent was reduced to give the crude product. The compound was cleaned on a column using petroleum ether and hexane fractions. -1 Yield (50%), IR (cm ): 2959, 2923, 2869, 1738, 1560, 1459, 1343, 1245, 1270, 1218, 1121, 978, 1 893, 831, 807, 760. H NMR (500 MHz, Chloroform-d) δ 7.30(dd, J =7.6,1.7 Hz,1H),7.26(d,J = 1.1Hz,1H),7.25 –7.21(m, 1H), 6.96 (td, J =7.5,1.2Hz,1H),6.87(dd, J =8.4, 1.1Hz,1H),6.34 (s, 13 1H),6.06(s,2H),1.43(s, 18H), 1.21 (s, 18H). C NMR (126 MHz, Chloroform-d) δ 30.01, 30.03, 32.34, 32.73, 74.53, 76.91, 77.16, 77.41, 104.61, 116.76, 121.67, 127.63, 131.11, 151.71, 156.83, 162.25. 53 University of Ghana http://ugspace.ug.edu.gh Scheme 4.9: Synthetic scheme for preparation of (L3). 54 University of Ghana http://ugspace.ug.edu.gh 4.3.3 PREPARATION OF COMPLEXES. 4.3.3.1 Synthesis of [L2Pr(diphenyl acac)2] 2A. The lanthanide precursor was first synthesized by deprotonating (75 mg, 0.33 mmol, 2 mol eqv) 1,3-diphenyl-1,3-propanedione with 1 M KOH solution in methanol. (63 mg, 0.17 mmol, 1mol eqv) TbCl3.6H2O was added to the methanolic solution and stirred. (50 mg, 0.17 mmol, 1 mol eqv) L2 ligand dissolved in methanol was also deprotonated with 1 M KOH. Both solutions were combined with stirring for 18 Hrs. The solution was slowly evaporated to yield pale yellow crystals. Scheme 4.10: Synthesis of [L2Pr(diphenyl acac)2] 2A 55 University of Ghana http://ugspace.ug.edu.gh 4.3.3.2 Synthesis of [L2Dy(diphenyl acac)2] 2B The lanthanide precursor was first synthesized by deprotonating (75 mg, 0.33 mmol, 2 mol eqv,) 1,3-diphenyl-1,3-propanedione with 1M KOH solution inmethanol. (0.64 mg, 0.17 mmol, 1 mol eqv) DyCl3.6H2O was added to the methanolic solution and stirred. (50 mg, 0.17 mmol. 1 mol eqv) L2 ligand dissolved in methanol was also deprotonated with 1 M KOH. Both solutions were combined with stirring for 18 Hrs. The solution was slowly evaporated to yield pale yellow crystals. Yield (80%), Scheme 4.11: Synthesis of [L2Dy(diphenyl acac)2] 2B 56 University of Ghana http://ugspace.ug.edu.gh 4.4 RESULTS AND DISCUSSION. 4.4.1 CHARACTERIZATION OF LIGAND AND COMPLEXES. L2 and L3 have been formed in fairly good yields (50% and 60%) respectively and 1 13 characterized by H-1NMR, C-NMR and FT-IR spectroscopy. The ligands were soluble in both methanol and chloroform but insoluble in water and partially soluble in petroleum ether. 4.4.2 FT-IR ANALYSIS FT-IR spectroscopy was adopted to identify the various functional groups of the synthesized compounds. This technique can help detect the structural composition and variations in absorption bands of the ligands and complexes. IR spectrum of L2 in figure 4.4 and FT-IR spectrum of ligand L3 is shown in figure 4.5. The spectrum for L3 shows a medium peak at 3410 -1 -1 cm which signifies the hydroxyl (OH) group of the ligand. The two peaks at 2959 cm and -1 2 3 2923cm are sp -CH stretch and sp -CH stretch of the ligand respectively. The aromatic C-H -1 -1 -1 bending (overtones) are detected from 2000 cm to 1600 cm . The peak at 1560 cm confirms -1 aromatic C-C stretch and the aromatic C-N stretch is observed as a strong peak at 1343 cm . The IR stretching vibration of the synthesized ligand and complexes are tabulated in table 4.1. The absence of C=O stretching vibration in L2 and appearance in 2A and 2B indicates the introduction of the ancillary ligand (diphenyl acac)2. Also the reduction in wavenumber for C=O -1 -1 expected at 1606 cm to 1593 cm reveals that there is coordination of the oxygen atom to the lanthanide metal. In addition, the change in stretching vibration of aromatic C-N to higher wavenumber for the complexes gives a strong indication of coordination of the nitrogen to the lanthanide metal (Iftikhar & Bhat, 2019). 57 University of Ghana http://ugspace.ug.edu.gh Table 4.1: Comparison of IR main stretching vibrations (cm-1) of L2 and complexes Compound L2 2A 2B sp2-CH stretch 2922 2923 2922 sp3-CH stretch 2854 2850 2850 overtones 2000-1700 2000-1700 2000-1700 C-C stretch 1557 1546, 1520 1545, 1522 C-N stretch 1345 1372 1370 C=O stretch ---- 1593 1592 58 University of Ghana http://ugspace.ug.edu.gh Figure 4.4: FT-IR of L2 Figure 4.5: FT-IR of L3 59 University of Ghana http://ugspace.ug.edu.gh 4.4.3 NMR ANALYSIS The synthesized complexes were subjected to proton NMR studies to identify the various protons present in the compounds. The proton NMR of L3 recorded in deuterated chloroform is presented in figure 4.6 and expanded spectrum in figure 4.7. The spectrum showed two singlets at 1.21 ppm and 1.43 ppm both of which integrates for 18 protons each and represents the methyl groups of the two pyrazole groups. Further downfield, the singlet peak at 6.06 ppm integrates for 2H, which represents the anticipated pyrazolyl hydrogen E expected in that region. The singlet peak at 6.34 ppm corresponds to the OH peak G which integrates for 1H. Further downfield, multiple splitting patterns are observed for the aromatic protons of the compound. The peak at 6.87 ppm with multiplicity of doublet of doublets and coupling constant of 8.4 Hz and 1.1 Hz integrates for 1H and correspond to proton D. The triplet of doublet peak at 6.96 ppm corresponds to proton C with coupling constant 7.5 Hz while the peak at 7.24 ppm represents proton B. Proton F is observed at a higher chemical shift which is expected due to the deshielding by neighbouring nitrogen groups and hence appears at 7.26 ppm. The peak at 7.30 ppm corresponds to proton A with coupling constant 7.6 Hz. 60 University of Ghana http://ugspace.ug.edu.gh 1 Figure 4.6: H-NMR OF L3 1 Figure 4.7: H-NMR OF L3 (expanded) 61 University of Ghana http://ugspace.ug.edu.gh 13 C-NMR spectrum of L3 shows twelve distinct peaks as shown in figure 4.8 and expanded spectra in figure 4.9 and figure 4.10 for clarity. The peak at 30 ppm corresponds to the nine primary carbons of ter-butyl substituted on the pyrazole ring labelled as M and N. At 32 ppm shows two peaks which corresponds to the quaternary carbons labelled K and L. Further downfield at 74 ppm, a short peak which corresponds to the tertiary carbon J and this is due to the neighbouring nitrogen groups deshielding the carbon. The intense peak at 77 ppm corresponds to the solvent peak CDCl3. The intense single peak at 104 ppm corresponds to the IH-pyrazolyl carbon labelled H. A litle further downfield shows the aromatic carbons D,E,F,G. Carbon D which is meta to the OH group occurs at a higher ppm than the para carbon E at 127 ppm and ortho carbons F and G at 121 ppm and 116 ppm respectively. Carbon C appears at a higher chemical shift of 151 ppm due to the electron-donating nature of the OH group. The heteroaromatic carbon A and B were detected at 162 ppm and 157 ppm respectively. 13 Figure 4.8 C-NMR of L3 62 University of Ghana http://ugspace.ug.edu.gh 13 Figure 4.9: C-NMR of L3 (expanded) 13 Figure 4.10: C-NMR of L3 (expanded) 63 University of Ghana http://ugspace.ug.edu.gh 1 Figure 4.11: H-NMR spectra of L2 The proton NMR of the synthesized ligand L2 is presented in figure 4.11. The alkyl protons labelled H and I appeared at 2.18 ppm and 2.15 ppm indicates the methyl protons on the pyrazole ring. Proton G appeared at 4.02 ppm and represents the phenol OH group. Further downfield, proton F which showed singlet at 5.84 ppm and integrates for 2H which is expected for 1H- pyrazolyl heteroatom. The aromatic protons A,C,D,E all appeared at the expected chemical shift values. Proton B which represents the methane proton neighboured by two nitrogens occur as a singlet at 7.24 ppm. The spectrum is in accordance with literature values (Alesso et al., 2012). 64 University of Ghana http://ugspace.ug.edu.gh 4.4.4 CHARACTERIZATION OF LANTHANIDE COMPLEXES The proton NMR spectrum of the isolated complex was obtained in solution. As expected, the spectrum showed poorly resolved peaks and multiplicities with slight changes in the chemical shift values (downfield shift) due to the paramagnetic nature of lanthanides. Also, a stacked spectra of the ligand and complexes in figure 4.12 compares the relative intensity of the peaks of the ligand and complexes ascribed to the paramagnetic nature of the lanthanide complex. 1 Figure 4.12: Stacked H-NMR of L2 and complexes 65 University of Ghana http://ugspace.ug.edu.gh 4.4.5 ELECTRONIC PROPERTIES OF LIGAND AND COMPLEXES. The absorption spectra of 1 mM methanolic solutions of ligand and complex were measured using a Shimadzu UV-1800 spectrophotometer. Absorption spectra of L2 presented in figure 4.13 shows a broad absorption from 300 nm to 240 nm with maximum absorption attained at * 280 nm and 287 nm. The absorptions in this range could be ascribed to the π-π transitions of the aromatic phenol and pyrazole of the ligand. The UV-vis absorption spectrum of the praseodymium complex is given in figure 4.14 and shows two main absorption maxima, a broad absorption between 400 nm and 305 nm with a * maximum absorption intensity of 2.0116 at 348 nm which is ascribed to the π-π transition of the phenyl groups and an absorption maxima between 268 nm and 235 nm with absorbance of * 0.7545 ascribed to the π-π of the aromatic groups of the ligand. A critical observation of the absorption peaks reveals a blue shift for the complexes compared to the ligand. Also, an absorption minimum is observed at 285 nm with intensity of 0.3789 for the praseodymium complex. Similar observation occurs for the dysprosium complex given in figure 4.15 which shows two absorption maxima between 400 nm and 295 nm with absorbance of 2.2690 and the second absorption maxima between 260 nm and 228 nm with an absorption intensity of 1.1864. Figure 4.13: Absorption of L2 66 University of Ghana http://ugspace.ug.edu.gh Figure 4.14: Absorption of praseodymium complex recorded at 1µM in methanol Figure 4.15: Absorption of dysprosium complex recorded at 1µM in methanol 67 University of Ghana http://ugspace.ug.edu.gh 4.4.6 LUMINESCENT STUDIES The absorption and luminescent spectrum of the L2 and complexes in methanol solution were recorded using a SHIMADZU RF-6000 SPECTRO FLUOROPHOTOMETER. 1.0 mM solutions of L2 and complexes in methanol solution were prepared for the experiment and measurement was done at room temperature. Maximum excitation was achieved at 450 nm and hence the solution was excited at 450 nm which resulted in no observable photoluminescent emissions in the measurement range as shown in figure 4.16 and figure 4.17. This result could be due to a few factors including the complex formed not fluorescent or the fluorescence being quenched by surrounding solvent molecules. Secondly, the complex could be emitting the absorbed light in the near-infrared (NIR) range and was not detected since the spectrofluorophotometer used in this experiment could only measure emission peaks up to 900 nm. 68 University of Ghana http://ugspace.ug.edu.gh Figure 4.16: Excitation of praseodymium complex Figure 4.17: Excitation of dysprosium comple 69 University of Ghana http://ugspace.ug.edu.gh 4.5 CONCLUSION 1 Ligands L2 and L3 have been prepared in fairly good yields and characterized using FT-IR, H 13 and C NMR. To the best of our knowledge, ligand L3 is a new compound and has not been reported in any literature. The (Pr, Dy and Tb) complexes of L2 have been synthesized and 1 characterized using H-NMR and FT-IR which confirmed the coordination of the ligand to the complex. The complexes did not show any emission peak when excited at 450 nm suggesting that the ligand triplet state energy could not match the excited state energy of the trivalent lanthanide ion. 70 University of Ghana http://ugspace.ug.edu.gh CHAPTER FIVE LANTHANIDE COMPLEXES BASED ON TETRAZINE LIGANDS 5.0 INTRODUCTION AND LITERATURE REVIEW 5.1 TETRAZINE AS LIGANDS Tetrazines are aromatic heterocyclic six-membered rings comprising of four nitrogen atoms. There are three isomeric forms of the tetrazine molecule (1,2,3,4-tetrazines, 1,2,3,5-tetrazines and 1,2,4,5-tetrazines) as illustrated in figure 5.1(Saracoglu, 2007). Tetrazines are primarily coloured compounds with the 1,2,4,5-tetrazine isomer characteristically pink in colour. Tetrazines basically are not stable, nonetheless the most stable among the three isomers is the 1,2,4,5-tetrazine. The parent tetrazine molecule has a low melting point of 99°C and as such easily sublimes as such stability of tetrazine is generally achieved when the parent molecule is derivatized with bulky substituents (Kaim, 2002). Figure 5.1: Isomers of tetrazines (Saracoglu, 2007) 71 University of Ghana http://ugspace.ug.edu.gh 5.2 SYNTHESIS OF 1,2,4,5-TETRAZINES th 1,2,4,5-tetrazine was first synthesized by Pinner in the 19 century and the synthetic procedure involved the reaction of a nitrile with excess hydrazine in the presence of a catalyst ( S8 or lewis acid) to yield a dihydrotetrazine intermediate. Oxidation of the intermediate yields the aromatic 1,2,4,5-tetrazine ligand as shown in scheme 5.1. Scheme 5.1: Synthesis of substituted 1,2,4,5-tetrazine Several synthetic procedures for the synthesis of substituted 1,2,4,5-tetrazines have been reported in several literatures. A research by Yang et al reported on the synthesis of substituted 1,2,4,5- tetrazine using 2-phenylacetonitrile as starting material. Unlike conventional activated nitriles widely used in pinner synthesis, their research focused on the use of unactivated nitriles and the reaction only occurred with the help of a catalyst as shown in scheme 5.2. They reported a 95% yield when Ni(OTf)2 was used as a catalyst, 93% with NiI2, 63% with MgCl2, 59% with Cu(OAc)2 and 0% with no catalyst (H. Wu & Devaraj, 2018; Yang et al., 2012). A similar method was adopted by Calahorro and co-workers who synthesize 4,4’-(1,2,4,5-tetrazine-3,6- diyl)dibenzoic acid using excess hydrazine and N-acetyl-L-cysteine as a catalyst as shown in scheme 5.3 (Calahorro et al., 2015; Savastano et al., 2016). 72 University of Ghana http://ugspace.ug.edu.gh Scheme 5.2: Synthesis of 3,6-disubstituted 1,2,4,5-tetrazines.reproduced from(Yang et al., 2012) Scheme 5.3: Preparation of`4,4’-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic acid. Reproduced from (Calahorro et al., 2015; Savastano et al., 2016) 73 University of Ghana http://ugspace.ug.edu.gh 5.2.1 COORDINATION CHEMISTRY OF 3,6-DISUBSTITUTED 1,2,4,5-TETRAZINES The rich nitrogen composition of tetrazines makes them exhibit diverse coordination chemistry. Particularly 3,6-disubstituted pyridyl-1,2,4,5-tetrazines tend to exhibit either a cisoid or transoid coordination as shown in figure 5.2 by twisting one of the pyridyl ring around the C-C single bond (Kaim, 2002). Figure 5.2: Coordination of 3,6-disubstituted pyridyl-1,2,4,5-tetrazine to a metal center. Reproduced from (Kaim, 2002) Gudat and co-workers reported on the coordination of 3,6-dipyridyl-1,2,4,5-tetrazine with platinum as shown in figure 5.3. They observed a bidentate coordination to the platinum metal through the nitrogen of the pyridine ring and a nitrogen of the tetrazine (Gudat et al., 2004). Similar chemistry was observed by (EL-Qisairi & Qaseer, 2007) for the coordination of 3,6-(2- pyridyl)-1,2,4,5-tetrazine with Au(III). Figure 5.3: Platinum complex of tetrazine reproduced from (Gudat et al., 2004) 74 University of Ghana http://ugspace.ug.edu.gh 5.2.2 APPLICATIONS OF TETRAZINE COMPOUNDS Tetrazine compounds have found useful applications. The tetrazines are a rich source of nitrogen-containing compounds and as such have been found useful in various fields. They have been applied as biological labelling agents (Devaraj & Weissleder, 2011; H. Wu et al., 2014). Tetrazines are used as propellants and explosives with the popular among them being the LAX- 112 explosive as shown in figure 5.4 (Clavier & Audebert, 2010). Figure 5.4: Structures of explosive tetrazine compounds 75 University of Ghana http://ugspace.ug.edu.gh 5.3 EXPERIMENTAL METHODS The ligand L4 was synthesized using the procedure adopted by (Khistiaeva et al., 2018). 5.3.1 SYNTHESIS OF COMPLEX 4A. To a dichloromethane solution of the ligand L4 (75.5 mg, 0.32 mmol) was added with stirring 1 mol equivalent of Pr(PhAcac)3 (0.259 g, 0.32 mmol). After an hour, 1 mol equivalent Dy(acac)3 was added and stirred overnight. The mixture was allowed to stand for an hour and then filtered. Hexane was added dropwise to the filtrate, which led to the formation of an orange solid. 1 Yield (61%), H-NMR (500 MHz, Chloroform-d)δ 7.89(s,1H),7.57 –7.30(m, 2H), 6.76 (s,1H), 1.19 (s, 10H), 0.78 (s, 5H). Scheme 5.4: Preparation of complex 4A. 76 University of Ghana http://ugspace.ug.edu.gh 5.3.2 SYNTHESIS OF COMPLEX 4B. Complex 4B was prepared using the same procedure for complex 4A. Dy(PhAcac)3 (0.2662 g, 1 0.32 mmol) , Gd(acac)3 (0.1453 g, 0.32 mmol).Yield (60%), H NMR (500 MHz, Chloroform- d)δ 8.00(d, J=7.7 Hz,1H),7.53(d, J =29.1Hz,1H), 6.87(s,1H), 1.27 (s, 12H), 0.97 – 0.77 (m, 6H). Scheme 5.5: Synthesis of complex 4B. 5.3.3 SYNTHESIS OF COMPLEX 4C. Same procedure was employed using Tb(PhAcac)3 (0.2650 g, 0.32 mmol) , Pr(acac)3 (0.1402 g, 1 0.32 mmol).Yield (60%), H-NMR (500 MHz, Chloroform-d)δ 7.91 (d,J =7.6Hz,1H), 7.46 (s,1H), 7.41 (d, J=9.2Hz,1H), 1.18(s, 18H), 0.79 (d, J = 16.9 Hz, 8H). 77 University of Ghana http://ugspace.ug.edu.gh Scheme 5.6: Preparation of complex 4C. 5.3.4 SYNTHESIS OF COMPLEX 4D. Same procedure was applied using Gd(PhAcac)3 (0.2643 g, 0.32 mmol) , Tb(acac)3 (0.1459 g, 1 0.32 mmol). Yield (60%) , H NMR (500 MHz, Chloroform-d) δ 16.77 (s,1H),7.91 (s, 4H), 7.46 (s, 7H),6.78 (s,1H), 1.11 (d,J = 79.2Hz, 11H), 0.79 (s, 5H). Scheme 5.7: Preparation of complex 4D. 78 University of Ghana http://ugspace.ug.edu.gh 5.4 RESULTS AND DISCUSSION 1 13 The ligand L4 has been synthesized in good yield (80%) and characterized by H-1NMR, C- NMR and FT-IR spectroscopy. The ligand was highly soluble in methanol and chloroform solution. 5.4.1 FT-IR ANALYSIS The IR stretching vibration of the prepared ligand and complexes are tabulated and compared in table 5.1. The spectral data obtained indicates changes in the stretching vibrations particularly C- N stretch of the pyridine ring. The positions of the C-N stretching bands of the complexes are shifted to higher wavenumbers in comparison to the ligand. This is a clear indication of the coordination of the nitrogen to the lanthanide metals. Likewise, the reduction in wavenumber for C=O stretch indicates the coordination through the oxygen atoms. Also, the vibrational bands in the fingerprint region for the complexes are almost identical and that is a clear indication that the complexes adopted similar coordination modes. Table 5.1: Comparison of IR streching vibrations (cm-1) of L4 and complexes (4A-4D) compound L4 4A 4B 4C 4D C-C stretch 1560 1546, 1548, 1548, 1550, (aromatic) 1516 1515 1516 1515 2 sp -CH stretch 3058 3064 3060 3062 3060 C-N stretch 1388 1395 1393 1393 1403 C=O stretch ---- 1593 1594 1594 1594 3 sp -CH stretch ---- 2963 2964 2964 2964 79 University of Ghana http://ugspace.ug.edu.gh 5.4.2 NMR STUDIES The synthesized compounds were subjected to NMR solution studies to account for the protons for the compounds. The spectrum obtained for the ligand L4 was in accordance with reported literature values (Khistiaeva et al., 2018). Proton NMR spectra of the complexes were scanned multiple times with the intention of obtaining well resolved peaks to gain some structural 1 information for the complexes prepared. However, the H-NMR spectrum for the complexes generally showed peaks both in the aromatic and alkyl regions. A stacked spectrum of the complexes is presented in figure 5.5. 1 Figure 5.5: Stacked H-NMR of 4A-4D 80 University of Ghana http://ugspace.ug.edu.gh 5.4.3 ELECTRONIC PROPERTIES OF LIGAND AND PROPERTIES 5.4.4 UV-VIS STUDIES The absorption spectra of L4 and complexes 4A-4D were measured to determine the main transitions the compounds undertake. Ethanolic solutions (1 mM) of the compounds were prepared for the experiment using Shimadzu UV-1800 spectrophotometer. The main absorptions of the compounds are presented in figure 5.6. The ligand L4 presents mainly two absorption bands from 340 nm to 280 nm with maximum absorption at 294 nm and from 270 nm to 240 nm * with maximum absorption at 253 nm. The absorption at 294 nm could be ascribed to π-π electronic transition of the pyridine ring. The ancillary ligands, acetylacetone (acac) and 1,3- diphenyl-1,3-propanedione (Ph(acac)) has maximum absorptions at 273 nm and 340 nm * respectively. The absorption for acac at 273 is ascribed to n-π electronic transition and the * absorption for Ph(acac) at 340 nm is ascribed to π-π due to the benzene rings. The complexes 4A-4D generally showed similar absorption spectrum. Two main absorptions are * observed around 400 nm to320 nm and 270 nm to 230 nm which could be ascribed to π-π and n- * * π transition correspondingly. This shows a remarkable bathochromic shift for the π-π electronic transition of the complexes as compared to the ligands to a lower energy which clearly indicates the influence of the lanthanide metals coordinated to the ligands. Likewise, a hypsochromic shift * is also observed for the n-π transition of the complexes to a higher energy indicating the perturbation through coordination to the lanthanide metal. 81 University of Ghana http://ugspace.ug.edu.gh Figure 5.6: Absorption spectra of L4 and complexes 5.4.5 LUMINESCENT STUDIES The absorption and emission spectra of ligand L4 and complexes 4A-4D was recorded using the SHIMADZU RF-6000 SPECTROFLUOROPHOTOMETER. The compounds were prepared in ethanol solution for measurements. The excitation and emission spectrum of the synthesized ligand L4 is presented in figure 5.7. Maximum excitation of L4 was observed at 350 nm which resulted in a broad emission band from 380 nm to 540 nm. The emission observed is as a result of the extra conjugation of the pyridyl rings on the 1,2,4,5-tetrazine parent compound which are generally known to be pink in colour (Kaim, 2002). 82 University of Ghana http://ugspace.ug.edu.gh The shielding of the 4f orbitals by the 5s and 5p orbitals makes the lanthanides exhibit large stoke shifts in their excitation and emission spectrum (Aulsebrook et al., 2018). This is evident in the spectra obtained for the various complexes 4A-4D as compared to the spectrum of the ligand L4 which did not show large stoke shift. The luminescence spectra for the synthesized complex 4A showed maximum absorption at 290 nm and gave rise to poorly resolved multiple emission peaks as illustrated in figure 5.8 and this could be attributed to the transitions of both -1 4 praseodymium and dysprosium ions. The peak at 420nm (23 809 cm ) could be attributed to F9 2 6 -1 4 6 → H15 of the Dy ion and the peak at 500 nm (20 000 cm ) could also be assigned to F9 → H13 2 2 2 transition of Dy ion. The complex 4C upon excitation at 290 nm produced three main sharp emission peaks shown in -1 figure 5.9. The peak at 485 nm (20 618 cm ) is due to the radiative transition of the terbium ion 5 7 -1 from D4 → F5 state while the most intense emissive peak at 540 nm (18 518 cm ) is also due to 5 7 -1 5 7 the transition from D4 → F4 and finally the peak at 580 nm (17 241 cm ) is due to D4 → F3 transition. Similar emission peaks were observed for the complex 4D as shown in Figure 5.10. The emission peaks observed are a characteristic of terbium complexes as shown by (Zheng et -1 al., 2018). The emission peak at 410 nm with energy of 24 390 cm corresponds to transition 5 7 -1 5 7 from D4 → F6 and the peak at 485 nm (20 618 cm ) is attributed to D4 → F5 transition. The -1 5 most intense peak at 545 nm with energy of 18 348 cm corresponds to the transition from D4 7 3+ → F4. The transitions of Gd was not observed since their excited state energies are higher than the ligand triplet state (T1) energy and hence cannot accept energy from the ligand (Filho et al., 3+ 2018). However, the ligand generally showed good sensitization (energy transfer) to the Tb 3+ and Gd ions. 83 University of Ghana http://ugspace.ug.edu.gh Figure 5.7: Excitation (350 nm) and emission Figure 5.8: Excitation (290 nm) and emission spectrum of L4 spectra of 4A Figure 5.9: Excitation (290 nm) and emission Figure 5.10: Excitation (290 nm) and emission spectra of 4C spectra of 4D 84 University of Ghana http://ugspace.ug.edu.gh 5.5 CONCLUSION This chapter has reported on the synthesis of four new lanthanides (Pr, Tb, Gd and Dy) complexes of 3,6-(dipyridyl)-1,2,4,5-tetrazine ligand in good yields. The complexes have been 1 characterized using FT-IR and H-NMR spectroscopy. The main electronic transition observed * for the complexes is as a result of π-π transitions of the aromatic rings. Luminescence measurement for the complexes reveals good emitting properties for complex 4C and 4D which is an indication of the ligand triplet states ability to transfer energy to the excited state of terbium ions. 85 University of Ghana http://ugspace.ug.edu.gh CONCLUSION AND RECOMMENDATIONS This research work has synthesized nine new lanthanide complexes of three classes of ligands namely [(2-hydroxyphenyl)bis(3,5-dimethylpyrazole) methane] (L2), [3,6-(dipyridyl)-1,2,4,5- tetrazine] (L4) and [1-(2-Picolyl)-4-phenyl-1H-1,2,3-triazole] (L1). This work also reports for the first time the synthesis of the ligand [(2-hydroxyphenyl)bis(3,5-di-tert-butylpyrazole) methane] (L3). The synthesized complexes were subjected to luminescence studies and revealed some luminescent properties for L1 complexes with quantum yield values ranging from 0.87% to 0.51%. 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Dalton Trans(42), 9327-9333. doi:10.1039/b909685j Zhao, Q.-Q., Zhu, M.-M., Ren, N., & Zhang, J.-J. (2017). A series of novel lanthanide complexes with 2-bromine-5-methoxybenzoic acid and 2,2′-bipyridine: Syntheses, crystal structures, and luminescent properties. Journal of Molecular Structure, 1149, 171-182. doi:10.1016/j.molstruc.2017.07.080 Zheng, K., Ding, L.-W., & Zeng, C.-H. (2018). Highly luminescent lanthanide complexes constructed by Bis-tridentate ligand and as sensor for Et 2 O. Inorganic Chemistry Communications, 95, 95-99. doi:10.1016/j.inoche.2018.07.016 97 University of Ghana http://ugspace.ug.edu.gh APPENDIX I Synthesis of 2-(azidomethyl) pyridine (100 mg, 0.61 mmol) 2-chloromethylpyridine hydrochloride was dissolved in acetonitrile. (159 mg, 2.44 mmol) sodium azide was added to (45 mg, 0.3 mmol) sodium iodide in 30 mL water. A combination of the two solutions was refluxed for 12 Hrs. The resulting mixture was allowed to stand and cool down. 20 mL water and 20 mL portions of chloroform was then added. The washing was done twice to separate the compound into the organic layer, which was evaporated to yield yellow oil.. -1 IR (cm ); 2095(intense), 1713, 1592, 1436, 1270, 752 Synthesis of 2-(azidomethyl) pyridine Synthesis of 1-(2-Picolyl)-4-phenyl-1H-1,2,3-triazole (L1). (0.07 mL, 0.61 mmol) phenylacetylene was added to 100 mg of synthesized 2-(azidomethyl) pyridine in 30 mL tetrahydrofuran . 10 mg copper sulphate and 10mg sodium ascorbate was added and stirred overnight. The mixture was separated into organic and aqueous fractions using a separating funnel by washing with water and chloroform to give a greenish-black precipitate. -1 The pure pale yellow crystals were obtained after cleaning on a column. Yield (70%) IR (cm ): 3129, 2923, 2852, 1586, 1465, 1437, 1227, 1201, 1148, 994, 768, 754, 727, 694 98 University of Ghana http://ugspace.ug.edu.gh 13 C-NMR (126 MHz, Chloroform-d) δ 55.27, 76.81, 77.07, 77.32, 120.34, 125.75, 128.22, 128.83, 130.48, 138.04, 148.28, 149.14, 154.18. Synthesis of (L1) The spectrum in below shows 12 distinct carbon atom peaks with some being equivalent and is in correlation with literature values. A single peak in the upfield region is observed at 55 ppm for a secondary carbon C7. This high value in chemical shift value for a secondary 2° carbon is due to it’s connection to an aromatic pyridine and a triazole ring. At higher chemical shift we observe the peaks of the aromatic carbons C3 and C5 at 120.3 ppm 11 11 11 11 and 123.7 ppm respectively. Identical carbons C2 / C6 and C3 / C5 of the phenyl are 11 observed as intense peaks at 125.7 ppm and 128.8 ppm respectively and the para-carbon C4 is 11 observed between them at 128.2 ppm. C1 was observed at 130.4 ppm. 99 University of Ghana http://ugspace.ug.edu.gh 1 1 The two carbons of the triazole heterocycle C5 and C4 was observed at 130.4 ppm and 148.3 ppm correspondingly with the latter having a bigger chemical shift due to it’s attachment to an aromatic phenyl ring. C2 and C6 of the pyridine ring were detected at 154 ppm and 149 ppm respectively. 13 C-NMR of L1 ligand The spectrum below represents the proton NMR spectrum of the synthesized ligand. The spectrum obtained is in correlation with literature values and shows a singlet peak of the protons H7 at 5.68 ppm and integrates for 2H. The peaks further downfield shows the aromatic protons 100 University of Ghana http://ugspace.ug.edu.gh 11 11 11 of the ligand. At 7.26 ppm shows a multiplet peak for protons H3,3 ,5,5 ,4a which integrates 11 for 5 protons. Proton H4 was detected as a triplet peak at 7.68 ppm. Proton H2’’ and H6 which are both identical protons was detected as a doublet at 7.73 ppm and integrates for two protons .proton H5’ of the triazole ring was detected at a chemical shift value of 7.93 ppm as a singlet peak. Further downfield, a doublet peak is observed at 8.57 ppm which relates to proton H6 and this is due to its proximity to the nitrogen of the pyridine ring. 1 H-NMR spectrum of L1 APPENDIX II Synthesis of 3,5-diphenyl-1H-pyrazole 101 University of Ghana http://ugspace.ug.edu.gh 3,5-diphenyl-1H-pyrazole was synthesized using the methodology employed by (F. Wu et al., 2016). (2.0g, 8.92mmol) 1,3-diphenyl-1,3-propanedione in 50mL ethanol was added to (1.33 mL, 17.8 mmol, 2 mol eqv) hydrazine monohydrate. The solution was refluxed for 16 Hrs which yielded white crystals. -1 Yield (90%), IR (cm ): 3356(br), 2924, 2852, 1495, 1460, 1272, 1074, 1023, 974, 750, 684 Synthetic scheme for preparation of 3,5-diphenyl-1H-pyrazole(F. Wu et al., 2016) Synthesis of 3,5-di-tertbutyl-1H-pyrazole `3,5-di-tertbutyl-1H-pyrazolee was also synthesized using the methodology employed by (F. Wu et al., 2016). (0.285 mL, 1.34 mmol) 2,2,6,6-tetramethyl-3,5-heptanedione in 30 mL ethanol was added to (0.4 mL, 2.68 mmol) hydrazine monohydrate . The resulting solution was refluxed overnight which yielded yellow crystals.. -1 Yield (95%), IR (cm ): 3226, 3109, 2959, 2867, 1459,1362,1284, 1249, 1128, 1003, 804, 515 102 University of Ghana http://ugspace.ug.edu.gh Synthetic scheme for synthesis of 3,5-di-tertbutyl-1H-pyrazol (F. Wu et al., 2016) Synthesis of (2-hydroxyphenyl)bis(3,5-dimethyl-pyrazol-1-yl) methane (L2) Synthesis of L2 followed a related methodology adopted by (Alesso et al., 2012).. (0.5g, 5.2 mmol) 3,5-dimethylpyrazole was dissolved in a pre-dried tetrahydrofuran solution and a few chunks of sodium metal added.. To the solution at 0 °C was added with stirring (0.18 mL, 2.6 mmol) phosgene for 4hrs to form a white cloudy solution. (0.5 mL, 5.2 mmol) salicylaldehyde was added to the solution and catalytic amounts of CoCl2.6H2O was also added. A pale blue solution was observed and was refluxed for 2 days. 30 mL distilled water was added to quench the reaction, which changed the colour of the solution to yellow upon shaking. The product was obtained by washing the mixture with 50 mL chloroform twice and the organic solvent removed. The compound was cleaned to obtain a white powder. -1 IR (cm ): 2922, 2854, 2579, 1605, 1557, 1458, 1373, 1322, 1297, 1263, 1097, 1043, 886, 854, 13 756, 701.. C NMR (126 MHz, Chloroform-d) δ 11.39, 13.80, 74.00, 107.21, 119.36, 119.85, 122.03, 130.39, 131.18, 140.47, 148.55, 155.87. 103 University of Ghana http://ugspace.ug.edu.gh Synthetic scheme for preparation of (L2) The proton NMR of the synthesized ligand L2 is shown in figures below and the expanded spectra also presented for clarity. The alkyl protons labelled H and I appeared at 2.18 ppm and 2.15 ppm indicates the methyl protons on the pyrazole ring. Proton G appeared at 4.02 ppm and represents the phenol OH group. Further downfield, proton F which showed singlet at 5.84 ppm and integrates for 2H which is expected for 1H-pyrazolyl heteroatom. The aromatic protons A,C,D,E all appeared at the expected chemical shift values. Proton B which represents the methane proton neighboured by two nitrogens occur as a singlet at 7.24 ppm. 104 University of Ghana http://ugspace.ug.edu.gh 1 H-NMR of L2 1 H-NMR of L2 (expanded) 105 University of Ghana http://ugspace.ug.edu.gh 1 H-NMR of L2 (expanded) C-13 NMR spectrum of L1 showed 12 distinct carbon atoms as shown in the figure below. C-4 was observed at the highest chemical shift at 155ppm which is expected for aromatic carbon bearing a hydroxyl group. Aromatic carbons 1,2,3,5 and 6 are all accounted for with distinct peaks at 122 ppm, 130 ppm, 119.85 ppm , 119.36ppm and 131.18 ppm respectively. Quartenary carbons 12, 15, 10 and 17 of the heteroaromatic pyrazole showed peak at 148 ppm and 140 ppm at a higher chemical shift. Likewise the quartenary carbons 11 and 16 showed a singlet peak at 107 ppm. Tertiary carbon 7 which is neighboured by two nitrogen groups appeared at a higher chemical shift at 74 ppm. Methyl carbons 18, 19, 21 and 22 appeared at 13 ppm. 106 University of Ghana http://ugspace.ug.edu.gh 13 C-NMR spectrum of L1 107 University of Ghana http://ugspace.ug.edu.gh APPENDIX III 1 H-NMR of 4A 1 H-NMR of 4B 108 University of Ghana http://ugspace.ug.edu.gh 1 H-NMR of 4C 1 H-NMR of 4D 109 University of Ghana http://ugspace.ug.edu.gh 110