Tuning Reactivity of Platinum(II) Complexes

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However, because the highest occupied molecular orbitals (HOMO) on the metal atom are centred on the dz 2 orbitals whilst the lowest unoccupied molecular orbitals (LUMO) are located on the N-heterocyclic ligand that is lying perpendicular to the plane of the Pt(II) centre. Moreover, in the complexes qzn and pht, the HOMO orbitals are concentrated on the N-heterocyclic ligands and display a significantly higher energy HOMO level, which suggests that the extra aromatic ring on the benzodiazine ligand enables qzn and pht to possess better π-acceptor ability due to the extended π-system. This is supported by the smaller HOMO-LUMO (ΔE) energy gap (Table 5.1). Compared to that of pzn, the electron-acceptor properties of qzn and pht are only moderate since their LUMO is not as low in energy. It can also be seen from the DFT-calculations (Table 5.1) that the positive (NBO) charges at the Pt(II) centres are symmetrically distributed. Their values steadily increase as the (N1–N2) and Pt---Pt distances increase further along the series pht through pdn, to pzn, respectively. In addition, the corresponding Pt–N1/2 bond distances are also dependent on the structure of the diazine ligand, which also determines the average negative charge carried on the N1/2 atoms of the bridging ligands due to electronic charge transfer from the metal centre to the diazine ligand through the electronegative N atoms. This results in differential transfer of electron density from the metal centre to the diazine ligand, leading to variations in the positive charge on the metal centres and hence, in the electrophilicity of the Pt(II) centres. This simultaneously decreases or increases the lability of the aqua complexes as will be discussed further. 5.3.2 Acid Dissociation Constants (pKa) of the Diaqua Complexes Titrations of the diazine-bridged dinuclear Pt(II) complexes with NaOH show that deprotonation of the two aqua ligands occurred in two successive steps. Thus, the stepwise deprotonation steps for the pH dependence of the dinuclear system can be presented by Scheme 5.2. 12
[H 2 O -P t-(N N )-P t-O H 2 ] 4 + + O H - [H 2 O -P t-(N N )-O H ] 3 + + O H - K a1 K a2 13 [H 2 O -P t-(N N )-O H ] 3 + + H 2 O [H O -P t-(N N )-O H ] 2+ + H 2 O w here, N N = pzn, pmn, pdn, qzn, pht bridging ligand Scheme 5.2: Proposed stepwise deprotonation for the pH dependence of the dinuclear Pt(II) complexes. A typical plot of the UV-Visible spectra obtained during the pH titrations for qzn is given in Figure 5.2 (see also under Supplementary information Figure S5.2, for pmn). The pKa values of the aqua Pt(II) complexes were calculated from the pH profiles, an example is shown as an inset in Figure 5.2. Absorbance 2.0 1.5 1.0 0.5 0.0 Absorbance 0.45 0.40 0.35 0.30 0.25 0.20 2 4 6 8 10 Wavelength(nm) 200 300 400 500 Wavelength (nm) Figure 5.2: Variation of absorbance with pH for qzn complex in the pH range 2-10, I = 0.1 M HClO4, T = 25 °C. Inset: Titration curve at 305 nm for qzn complex. All the diaqua complexes exhibited two inflection points and a fit of the absorbance data to the standard Boltzmann equation, taken one at a time using the Origin 7.5 ®37 software, resulted in two pKa values which are presented in Table 5.2. λ = 305 nm
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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
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For the associative mechanism (A),
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the concentration of one of the rea
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k obs , s -1 0.00030 0.00025 0.0002
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k = Ae -Ea/RT 2.14 lnk = lnA - E a
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= 23.76 + R Hence, a plot of ln ⎛
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iii. # Δ V ≈ 10 cm3 mol-1 featur
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conventional methods are classical
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Figure 2.6: Schematic diagram of a
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The light transmitted from the samp
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c. Oxidizability: Ligands that are
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Table 2.1: A selection of n o pt va
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eaction with different nucleophiles
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eaction site from direct attack by
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PEt 3 PEt 3 R PEt 3 Pt Pt Y Y Cl R
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direct displacement of the leaving
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therefore, weaken the bond of the l
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σ-Donation According to classical
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References 1 (a) J. Reedijk, Chem.
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34 R. B. Jordan, Reaction Mechanism
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Table of Contents-3 Chapter 3.The
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Chapter 3 The π-Acceptor Effect in
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In order to extend our understandin
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after which water was added to quen
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O CH 3 + I + N O oH - N O O 7 CH 3
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84% (34.7 mg, 0.0618 mmol). 1 H NMR
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PhCN PhCN Pt Cl Cl + N N CH 3 N CH
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Complex Structure HOMO LUMO PtCl CH
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The geometry-optimised structures i
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against the concentration of the in
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Table 3.2: Summary of the second-or
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constants of CH3PhisoqPtCl decrease
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with π*-orbitals of the ligand. Th
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3.6 References 1 D. Rosenberg, L. V
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30 Microcal TM Origin TM Version 5.
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Figure S3.1: Kinetic trace at 448 n
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ln(k 2 /T) -6.0 -7.5 -9.0 -10.5 -12
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Table S3.3b: Average observed rate
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Table S3.5b: Temperature dependence
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Table S3.8: DFT calculated electros
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List of Figures Figure 4.1: Structu
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Table 4.2: Summary of pKa values fo
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4.1 Introduction Platinum compounds
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cis geometry, leading to dramatic c
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ligand was added to the [{cis-PtCl(
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spectra were measured in and refere
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4.3.1 DFT calculated Optimized Stru
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Table 4.1: A summary of the DFT cal
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H2O-Pt-L-Pt-OH2 H2O-Pt-L-Pt-OH2 H2O
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electrophilicity and acidity of the
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(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
Page 178 and 179: Table 4.5: DFT calculated (NBO) cha
Page 180 and 181: eaction proceeds via bimolecular pa
Page 182 and 183: References 1 T. Storr, K. H.Thomson
Page 184 and 185: 36 D. Jaganyi, D. Reddy, J.A. Gerte
Page 186 and 187: Appendix 4 THE INFLUENCE OF THE PYR
Page 188 and 189: Absorbance at 368. 0 nm 0. 0 8 0. 0
Page 190 and 191: Table S4.3: Average observed rate c
Page 192 and 193: k nd obs(2 ) , s-1 0.003 TU DMTU TM
Page 198 and 199: k obs2 , s -1 2.40x10 -4 2.20x10 -4
Page 200 and 201: Table S4.13: Average observed rate
Page 206 and 207: k obs(1 st ) , s -1 0.06 0.04 0.02
Page 210 and 211: ln(k 2(3 rd ) /T) -10.0 -10.5 -11.0
Page 212 and 213: SpinWorks 2.5: 2,6 pznClO4 in D2O N
Page 214 and 215: Table of Contents-5 Chapter 5 .....
Page 216 and 217: List of Tables Table 5.1: A summary
Page 218 and 219: 5.1 Introduction Multinuclear plati
Page 220 and 221: onding. For this reason, pKa titrat
Page 222 and 223: 400-300 cm -1): 3308, 3117, 3071 (N
Page 224 and 225: 5.2.6 Spectrophotometric pKa Titrat
Page 226 and 227: Table 5.1: A summary of DFT-calcula
Page 230 and 231: Table 5.2: Acid dissociation consta
Page 232 and 233: Table 5.3: A summary of DFT calcula
Page 234 and 235: H3N 6 eq TU 0 eq TU Ha NH3 Ha Cl TU
Page 236 and 237: third step due to the trans-effect
Page 238 and 239: [H 2 O-Pt-(NN)-Pt-OH 2 ] +4 [NU-Pt-
Page 240 and 241: k obs(1st) / s -1 0.20 TU DMTU TMTU
Page 242 and 243: thiourea nucleophile is large enoug
Page 244 and 245: ln(k st 2(1 ) /T) -3 -4 -5 -6 -7 -8
Page 246 and 247: is the same as the electron-withdra
Page 248 and 249: associative mode of substitution me
Page 250 and 251: 16 H. Ertürk, J. Maigut, R. Puchta
Page 252 and 253: 43 (a) D. Jaganyi, A. Hofmann and R
Page 254 and 255: 276 nm Absorbance 0 . 6 5 0 . 6 4 0
Page 256 and 257: k obs(1 st ) , s -1 0.4 0.3 0.2 0.1
Page 260 and 261: ln(k 2(2 nd ) /T) -8.0 TU -8.5 -9.0
Page 262 and 263: pzn PPM -1750.0 -1850.0 -1950.0 -20
Page 266 and 267: Figure S5.13: UV/Visible spectra fo
Page 268 and 269: k obs(1 st ) in s -1 0.030 0.025 0.
Page 272 and 273: ln(k 2(2 nd ) /T) -10 -11 -12 -13 -
Page 274 and 275: 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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Table S5.28: Average observed rate
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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 S6.3: Average observed rate c
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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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Table S6.9: Average observed rate c
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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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