Tuning Reactivity of Platinum(II) Complexes

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PhCN PhCN Pt Cl Cl + N N CH 3 N CH 3 CN 40-50 o C [Pt(PhCN) 2 Cl 2 ] [4'-(2"'-CH 3 -Ph)-2,2': 6',2"-terpy] CH 3 PhPtCl Scheme 3.9: Synthesis of the complex CH3PhPtCl 11 N N Pt Cl CH 3 N CF 3 SO 3 To a solution of 1.0 mol of [Pt(PhCN)2Cl2] in acetonitrile was added slowly and with constant stirring an equimolar amount of AgCF3SO3. The contents were refluxed for 16 h under nitrogen. The precipitated AgCl was filtered off, and one equiv. of 4’–(2’’’–CH3– phenyl)–2,2’:6’,2’’–terpyridine ligand was added to the filtrate and refluxed for a further 24 h. The solution was allowed to cool down, which resulted in the separation of a red solid that was filtered, washed with small amounts of diethyl ether, acetonitrile and dried in vacuo. The required product, [CH3PhPtCl], was characterised by elemental analysis, IR (KBr disc), 1H and 13C NMR and UV-Vis spectroscopy. 18 [CH3PhPtCl]: Anal. Calcd for C23H17ClF3N3PtS: C, 39.24; H, 2.58; N, 5.97. Found: C, 38.96; H, 2.94; N, 5.68%. 3.2.2 Physical Measurements and Instrumentation Kinetic Analyses All kinetic measurements were performed under pseudo first-order conditions using at least a 10-fold excess of the entering nucleophile. The wavelengths chosen for the kinetic investigations were determined from UV/Visible absorption spectra obtained from measurements on a Varian Cary 100 Bio UV/Visible spectrophotometer. The wavelengths at which there was greatest absorbance change were used for the subsequent kinetic analyses. These are summarised in Table SI 3.1 (appendix). An Applied Photophysics SX.18MV (v 4.33) stopped-flow analyzer coupled to an online data acquisition system was used to determine the observed rate constants, kobs. All measurements were carried out in a thermostated environment to within ± 0.1 o C using
a coupled temperature control unit. All data were graphically analysed using the Origin 5.0 ® 30 graphical analysis software package. 3.2.3 Computational Modelling Ground-state electronic structures calculations of CH3PhPtCl, CH3PhisoqPtCl, pyPhenPtCl as well as PtCl were optimized, as cations of +1 charge in gas phase, by the density functional theory (DFT) method using Spartan `04 for Windows ® . The functional used throughout this study was the B3LYP, 31 a non-local hybrid exchange functional defined by Becke’s three parameter equation, utilizing LACVP** (Los Alamos Core Valence Potentials) 32 pseudo-potential basis set. 3.3 Results 3.3.1 Computational Analysis Computational modelling of the Pt(II) complexes, in gaseous phase, were determined in order to help explain the kinetic trends observed and the influence of the molecular structures as well as the electronic properties of the complexes on the observed reactivity. An extract of the geometry optimized structures of the complexes CH3PhPtCl, pyPhenPtCl, CH3PhisoqPtCl and PtCl are shown in Figure 3.1. A summary of corresponding properties of the frontier molecular orbitals: HOMO-LUMO energies, NBO atomic charges, and bond lengths and angles are presented in Table 3.1 12
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Tuning Reactivity of Platinum(II) C
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Declaration This thesis report is b
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Abstract Systematic kinetic and the
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Table of contents Acknowledgements
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2.5.5 Effect of Non-participating G
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5.2.1 Chemical and Solutions ......
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7.2 Experimental Section ..........
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procurements, Messers P. Forder and
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Figure 2.2 Potential energy profile
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Figure 4.6 Concentration dependence
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Figure 6.1 Spectrophotometric titra
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List of Tables Table 2.1 A selectio
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Table 6.4 Summary of rate constants
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TU thiourea DMTU 1,3-dimethyl-2-thi
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Table of Contents-1 Chapter 1 .....
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1.0 Introduction 1.1 Cancer Disease
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toxic potential. The most well-know
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1.3.2.2 Cellular Uptake Cisplatin i
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H 3N OH 2 Pt H 3N OH 2 Active Pt(II
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transformational pathways that comp
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the hydrolysis of the complex, wher
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1.3.4 Terpyridine Platinum(II) Comp
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H 3 N Cl Pt NH 3 H 3 N NH 2 (CH 2 )
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1.4 Kinetic Interest The platinum-b
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3. The effect of varying the positi
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17 R. A. Henderson, The Mechanism o
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Altona J. H. van Boom, G. A. van de
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76 (a)J. Kašpárková, J. Zehnulov
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Table of Contents-2 Chapter Two ...
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List of Tables Table 2.1: A selecti
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The mononuclear Pt(II) complexes 1-
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Potential Energy R + X RX 1 transit
Page 66 and 67: For the associative mechanism (A),
Page 68 and 69: the concentration of one of the rea
Page 70 and 71: k obs , s -1 0.00030 0.00025 0.0002
Page 72 and 73: k = Ae -Ea/RT 2.14 lnk = lnA - E a
Page 74 and 75: = 23.76 + R Hence, a plot of ln ⎛
Page 76 and 77: iii. # Δ V ≈ 10 cm3 mol-1 featur
Page 78 and 79: conventional methods are classical
Page 80 and 81: Figure 2.6: Schematic diagram of a
Page 82 and 83: The light transmitted from the samp
Page 84 and 85: c. Oxidizability: Ligands that are
Page 86 and 87: Table 2.1: A selection of n o pt va
Page 88 and 89: eaction with different nucleophiles
Page 90 and 91: eaction site from direct attack by
Page 92 and 93: PEt 3 PEt 3 R PEt 3 Pt Pt Y Y Cl R
Page 94 and 95: direct displacement of the leaving
Page 96 and 97: therefore, weaken the bond of the l
Page 98 and 99: σ-Donation According to classical
Page 100 and 101: References 1 (a) J. Reedijk, Chem.
Page 102 and 103: 34 R. B. Jordan, Reaction Mechanism
Page 104 and 105: Table of Contents-3 Chapter 3.The
Page 106 and 107: Chapter 3 The π-Acceptor Effect in
Page 108 and 109: In order to extend our understandin
Page 110 and 111: after which water was added to quen
Page 112 and 113: O CH 3 + I + N O oH - N O O 7 CH 3
Page 114 and 115: 84% (34.7 mg, 0.0618 mmol). 1 H NMR
Page 118 and 119: Complex Structure HOMO LUMO PtCl CH
Page 120 and 121: The geometry-optimised structures i
Page 122 and 123: against the concentration of the in
Page 124 and 125: Table 3.2: Summary of the second-or
Page 126 and 127: constants of CH3PhisoqPtCl decrease
Page 128 and 129: with π*-orbitals of the ligand. Th
Page 130 and 131: 3.6 References 1 D. Rosenberg, L. V
Page 132 and 133: 30 Microcal TM Origin TM Version 5.
Page 134 and 135: Figure S3.1: Kinetic trace at 448 n
Page 136 and 137: ln(k 2 /T) -6.0 -7.5 -9.0 -10.5 -12
Page 138 and 139: Table S3.3b: Average observed rate
Page 140 and 141: Table S3.5b: Temperature dependence
Page 142 and 143: Table S3.8: DFT calculated electros
Page 144 and 145: List of Figures Figure 4.1: Structu
Page 146 and 147: Table 4.2: Summary of pKa values fo
Page 148 and 149: 4.1 Introduction Platinum compounds
Page 150 and 151: cis geometry, leading to dramatic c
Page 152 and 153: ligand was added to the [{cis-PtCl(
Page 154 and 155: spectra were measured in and refere
Page 156 and 157: 4.3.1 DFT calculated Optimized Stru
Page 158 and 159: Table 4.1: A summary of the DFT cal
Page 160 and 161: H2O-Pt-L-Pt-OH2 H2O-Pt-L-Pt-OH2 H2O
Page 162 and 163: electrophilicity and acidity of the
Page 164 and 165: (A) 18 Absorbance 0.08 0.07 0.06 0.
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k obs(3 rd ) , s -1 -5 6.00x10 TMTU
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4.3.4 Kinetics with NMR The substit
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ln([ML] t ) 4.0 3.5 3.0 2.5 2.0 1.5
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ln(k 2(1 st ) /T) -3.5 -4.0 -4.5 -5
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Comple x Table 4.4: Summary of Acti
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The decrease in reactivity of 2,6pz
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Table 4.5: DFT calculated (NBO) cha
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eaction proceeds via bimolecular pa
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References 1 T. Storr, K. H.Thomson
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36 D. Jaganyi, D. Reddy, J.A. Gerte
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Appendix 4 THE INFLUENCE OF THE PYR
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Absorbance at 368. 0 nm 0. 0 8 0. 0
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Table S4.3: Average observed rate c
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k nd obs(2 ) , s-1 0.003 TU DMTU TM
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k obs2 , s -1 2.40x10 -4 2.20x10 -4
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Table S4.13: Average observed rate
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k obs(1 st ) , s -1 0.06 0.04 0.02
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ln(k 2(3 rd ) /T) -10.0 -10.5 -11.0
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SpinWorks 2.5: 2,6 pznClO4 in D2O N
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Table of Contents-5 Chapter 5 .....
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List of Tables Table 5.1: A summary
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5.1 Introduction Multinuclear plati
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onding. For this reason, pKa titrat
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400-300 cm -1): 3308, 3117, 3071 (N
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5.2.6 Spectrophotometric pKa Titrat
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Table 5.1: A summary of DFT-calcula
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However, because the highest occupi
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Table 5.2: Acid dissociation consta
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Table 5.3: A summary of DFT calcula
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H3N 6 eq TU 0 eq TU Ha NH3 Ha Cl TU
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third step due to the trans-effect
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[H 2 O-Pt-(NN)-Pt-OH 2 ] +4 [NU-Pt-
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k obs(1st) / s -1 0.20 TU DMTU TMTU
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thiourea nucleophile is large enoug
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ln(k st 2(1 ) /T) -3 -4 -5 -6 -7 -8
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is the same as the electron-withdra
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associative mode of substitution me
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16 H. Ertürk, J. Maigut, R. Puchta
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43 (a) D. Jaganyi, A. Hofmann and R
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276 nm Absorbance 0 . 6 5 0 . 6 4 0
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k obs(1 st ) , s -1 0.4 0.3 0.2 0.1
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ln(k 2(2 nd ) /T) -8.0 TU -8.5 -9.0
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pzn PPM -1750.0 -1850.0 -1950.0 -20
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Figure S5.13: UV/Visible spectra fo
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k obs(1 st ) in s -1 0.030 0.025 0.
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ln(k 2(2 nd ) /T) -10 -11 -12 -13 -
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9.61 ppm Ha PPM 9.8 9.6 9.4 9.2 9.0
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k obs(3rd) / s -1 -5 8 .00 x 10 T U
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ln(k st 2(1 ) /T) -1.5 TU DMTU TMTU
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ln(k rd 2(3 ) /T) -8.5 -9.0 -9.5 -1
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SpinWorks 2.5: znPt(II)-OP4 in D2O
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Figure S5.31: Mass spectrum for com
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ln(k st 2(1 ) /T) -4 -5 -6 -7 -8 -9
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SpinWorks 2.5: phtPt(II)-OP2 in D2O
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Figure S5.41: Mass spectrum for com
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List of Figures Figure 6.1: Spectro
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Chapter 6 Tuning Reactivity of Plat
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Against this background, several re
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6.2.2 Instruments Microanalyses wer
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Metal Complex Pt3 Yield: 52.5 mg (0
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6.3 Results 6.3.1 Synthesis and Cha
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The pKa values obtained are summari
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Table 6.2: DFT-calculated parameter
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that of dinuclear Pt(II) complexes
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It can be concluded that substituti
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ate constants, kobs(1 st /2 nd ), w
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Table 6.3: Summary of rate constant
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6.3.6 Activation Parameters The act
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pKa1 values become smaller. In addi
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of steric influence is felt by the
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6.5 Conclusion The present study ha
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17 O. F. Wendt and L. I. Elding, 19
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51 Y. Iwadata, K. Kawamura, K. Igar
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Table S6.4(b): Average observed rat
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ln(k 2(2 nd ) /T) -4 -6 -8 -10 -12
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45.0 40 35 30 25 20 %T 15 10 5 0 -5
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k st obs(1 ) in s-1 0.30 Br TU 0.25
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-2304.16 ppm H 3N PPM -2200.0 -2220
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Absorbance 1.6 1.4 1.2 1.0 0.8 0.6
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SH N SH + Mechanism Br N + CO 3 2-
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Figure 7.5: 195Pt NMR spectra of mi
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linker remained coordinated to the
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complexes, have a lower charge and
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ange 326-400 cm -1 (weak) for Pt-Cl
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ButPt, HexPt, OctPt and DecPt, were
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7.3 Results 7.3.1 DFT Calculations
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Structure HOMO LUMO EnPt (C2h) Prop
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Absorbance Table 7.2: Summary of pK
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coordination to the soft Pt(II) cen
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observed at -2962.4 and -3024.1 ppm
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H 3N NH 3 Pt NH 2 OH 2 n NH 3 NH 2
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k obs2 , in s -1 -3 TU 1.2x10 DMTU
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7.3.4 Activation Parameters The tem
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density is located on the metal cen
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acetylmethionine, which reported th
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References 1 (a) B. Rosenberg, L. V
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32 N. Summa, J. Maigut, R. Puchta a
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Appendix 7 Table S7.1: Summary of s
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k obs(2 nd ) , in s -1 0.00020 0.00
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ln(k 2(2 nd ) /T) -8.5 -9.0 -9.5 -1
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k obs(1 st ) , in s -1 0.06 TU DMTU
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ln(k 2(1 st ) /T) -3.2 TU DMTU TMTU
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Table S7.11: Summary of kobs(2 nd )
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%T 22.0 20 18 16 14 12 10 8 6 4 2 0
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k st obs(1 ) , in s-1 0.10 0.08 0.0
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ln(k st 2(1 ) /T) -4.0 TU DMTU TMTU
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Figure S7.23: Mass spectra for HexP
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Table S21: Average observed rate co
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Table S7.23: Summary of kobs(2 nd )
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90.0 80 70 60 50 40 30 20 %T 10 0 -
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Figure S7.37: Mass spectrum for Hex
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Chapter 8 Tuning Reactivity of plat
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dinuclear Pt(II) complexes to relea
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finally Pt2. The order of reactivit
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• prolonged survival in the cell
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Tuning Reactivity of Platinum(II) Complexes

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