Tuning Reactivity of Platinum(II) Complexes

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pKa1 values become smaller. In addition, the difference in the observed pKa values is also due to the σ-donor properties of the spacers. This is supported by the differences in the 195Pt NMR chemical shifts of Pt1 (-2303.9), Pt2 (-2304.2), Pt3 (-2284.7) and Pt4 (-2299 ppm), respectively. Since the position of the 195Pt resonance is influenced by the donor strength of the ligands attached to the platinum, 49 the results indicate that the σ-inductive effect of para-substituent on the pyridyl linker towards the Pt(II) centre differ in strength and as a result controls the bacisity of the aqua complexes. However, the difference of only 0.3 pKa1 units between pKa1 values of the complexes of shortest and longest spacer length shows the result is more of a charge effect than σ–donor effect by the bridging ligand. The pKa1 value of the diaqua Pt3 complex is in agreement with the recently published value for its trans- isomer. 34(c) Further observation shows that deprotonation of the second coordinated water molecule to the hydroxo/hydroxo species occurs at higher pH values than in the first step in all the three complexes. This results from a reduction of the overall charge to +3 after deprotonation of one coordinated water molecule. Hence, the Pt(II) centre of the aqua/hydroxo species is less electrophilicity compared to that of the diaqua complex, 25,31 leading to higher pKa2 values. As already mentioned for the first deprotonation step, the pKa2 values also depend on the nature and length of the spacer group. These σ–inductive effects on the ground-state properties of the Pt(II) complexes are supported by the computational data, which shows that the DFT calculated NBO charges at the Pt(II) centres decreased after deprotonation of the first water molecule as follows: Pt–OH (1.177): Pt–H2O (1.201) for Pt1, Pt–OH (1.173): Pt–H2O (1.201) for Pt2, and Pt– OH (1.169): Pt–H2O (1.201), respectively compared with values of the diaqua complexes in Table 6.2. The trend is also in the order of the magnitude of the dipole moments of the complexes, which is a measure of the electronegativiy of the complexes. 25
6.4.2 Ligand Substitution Based on the DFT calculated Pt---Pt distances between the complexes, one can conclude that the distances are long enough to prevent strong intramolecular “electronic communication” between the two Pt(II) centres. This makes the two Pt(II) centres kinetically indistinguishable from each other, and therefore, react independently. Analysis of the rate constants (Table 6.3) shows that the two metal centres could not be discriminated by the incoming nucleophiles, resulting in the simultaneous substitution of both aqua ligands as the first reaction step. From the values of the second-order rate constants (Table 6.3), the order of reactivity of the diaqua Pt(II) complexes for the direct attack pathway, k1, is Pt2 > Pt3 > Pt1. The difference in reactivity can be attributed to steric and electronic effects attributed to different structural or geometrical arrangement of the spacer atom(s) of the pyridyl linker. It is widely accepted that the pKa value of the coordinated water molecule is an indicator of the electron density around the metal centre and hence, of the electrophilicity of the Pt(II) centre. 19,45 Since the pKa1 value of the Pt1 complex is smaller than that of either Pt2 or Pt3, one would expect higher reactivity for Pt1. The data in Table 6.3 shows the contrary. In addition, enhanced reactivity due to the “entrapment effect” expected of complexes with C2v point group symmetry, 24 was also not observed in the first substitution step of Pt1. As seen from the optimised structure of the complex (Figure 6.8), the central cavity is blocked by the pyridine ring that protrudes into the cavity preventing the entrapment effect to the incoming nucleophiles. The DFT calculated C-S-C angles of 94.5 and 112.8° for the 4,4’-bis(pyridine)sulphide ligand and the Pt1 complex, respectively, show that the ligand has a perfect V-shaped planar structure (C2v), whereas Pt1 is highly distorted (Figure 6.8). The lone pairs on sp 3 hybridized S atom in Pt1 occupy less geometrical angles about the atom and cause greater repulsions, which forces the Pt coordination planes to sit in a twisted anti-conformation relative to each other as seen in Figure 6.8. The pyridine ring is inclined at an angle which is almost perpendicular to the Pt(II) centre, such that the ortho-Hydrogen atom on the aromatic ring (Hpy) poses steric influence to aerial approach of the nucleophile on each Pt(II) centre, leading to a slower nucleophilic attack. It can be presumed that an equal amount 26
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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
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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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Page 276 and 277: Table S5.22: Average observed rate
Page 278 and 279: k obs(3rd) / s -1 -5 8 .00 x 10 T U
Page 280 and 281: ln(k st 2(1 ) /T) -1.5 TU DMTU TMTU
Page 282 and 283: ln(k rd 2(3 ) /T) -8.5 -9.0 -9.5 -1
Page 284 and 285: SpinWorks 2.5: znPt(II)-OP4 in D2O
Page 286 and 287: Figure S5.31: Mass spectrum for com
Page 292 and 293: ln(k st 2(1 ) /T) -4 -5 -6 -7 -8 -9
Page 294 and 295: SpinWorks 2.5: phtPt(II)-OP2 in D2O
Page 296 and 297: Figure S5.41: Mass spectrum for com
Page 298 and 299: List of Figures Figure 6.1: Spectro
Page 300 and 301: Chapter 6 Tuning Reactivity of Plat
Page 302 and 303: Against this background, several re
Page 304 and 305: 6.2.2 Instruments Microanalyses wer
Page 306 and 307: Metal Complex Pt3 Yield: 52.5 mg (0
Page 308 and 309: 6.3 Results 6.3.1 Synthesis and Cha
Page 310 and 311: The pKa values obtained are summari
Page 312 and 313: Table 6.2: DFT-calculated parameter
Page 314 and 315: that of dinuclear Pt(II) complexes
Page 316 and 317: It can be concluded that substituti
Page 318 and 319: ate constants, kobs(1 st /2 nd ), w
Page 320 and 321: Table 6.3: Summary of rate constant
Page 322 and 323: 6.3.6 Activation Parameters The act
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Page 328 and 329: 6.5 Conclusion The present study ha
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Page 332 and 333: 51 Y. Iwadata, K. Kawamura, K. Igar
Page 334 and 335: Table S6.3: Average observed rate c
Page 336 and 337: Table S6.4(b): Average observed rat
Page 338 and 339: ln(k 2(2 nd ) /T) -4 -6 -8 -10 -12
Page 340 and 341: 45.0 40 35 30 25 20 %T 15 10 5 0 -5
Page 342 and 343: k st obs(1 ) in s-1 0.30 Br TU 0.25
Page 344 and 345: Table S6.9: Average observed rate c
Page 346 and 347: -2304.16 ppm H 3N PPM -2200.0 -2220
Page 352 and 353: Absorbance 1.6 1.4 1.2 1.0 0.8 0.6
Page 354 and 355: SH N SH + Mechanism Br N + CO 3 2-
Page 356 and 357: Figure 7.5: 195Pt NMR spectra of mi
Page 358 and 359: linker remained coordinated to the
Page 360 and 361: complexes, have a lower charge and
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Page 364 and 365: ButPt, HexPt, OctPt and DecPt, were
Page 366 and 367: 7.3 Results 7.3.1 DFT Calculations
Page 368 and 369: Structure HOMO LUMO EnPt (C2h) Prop
Page 370 and 371: Absorbance Table 7.2: Summary of pK
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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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