Tuning Reactivity of Platinum(II) Complexes

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ligand was added to the [{cis-PtCl(NH3)2(DMF)]ClO4 solution slowly, in order to have constantly excess of [{cis-PtCl(NH3)2(DMF)]ClO4 in the solution and stirred for 12 h and after cooling at 5-10 °C for 1h, was filtered to remove any undissolved material. The solvent was evaporated under vacuum. The residue was washed with diethyl ether, re- dissolved in warm water (40-50 °C) and the water evaporated under vacuum to dryness. The light yellow solid was washed with a minimal amount of ethanol followed by concomitant amounts of diethyl ether and dried over potassium hydroxide (KOH) in a desiccator. This process was repeated for 2,3pzn and 2,5pzn, using stoichiometric amounts (0.279 mmol, 30.21 mg 2,3pzn; and 0.289 mmol, 31.22 mg 2,5pzn, respectively) of the appropriate nitrogen ligand. cis- [{PtCl(NH3)2}2–μ–2, 6 pzn]Cl2 (2,6pzn) Literature procedure was used for the synthesis of the platinum complex, [{cis– PtCl(NH3)2}2–μ–2,6pzn]Cl2 (2,6pzn). 25 A solution (5 mL) of 2,6pzn ligand (18.3 mg, 0.170 mmol) in water was added to a solution (10 mL) of cis–[Pt(NH3)2Cl2] (101.5 mg, 0.338 mmol) in water. The mixture was stirred for 3 days at 40 °C in the dark, filtered to remove any unreacted material and concentrated to 1-2 mL under vacuum. The compound formed, [{cis–Pt(NH3)2Cl}2–µ–2,6–pzn]Cl2, was filtered off, washed with a small amount of ethanol, diethyl ether and dried under vacuum. Their purity was confirmed by micro-elemental analysis, infrared (IR), 1 H and 195 Pt NMR. The IR spectra of all the complexes exhibited common characteristic peaks in the range 326-400 cm -1 (weak) for Pt–Cl and 1090-1100 cm -1 (broad, strong) for Cl–O (perchlorate counter ion) vibration stretches, respectively. The results obtained from the analysis of the complexes are given below. (pzn) Yield: 382.8 mg (45.5%). 1 H NMR (500 MHz, D2O), δ /ppm: 8.99, s (4H). 195 Pt NMR (107 MHz, D2O) δ/ppm: -2302.2. IR (KBr, 4000-300 cm -1): 3305, 3224, 3107 (N–H stretch); 1090-1100 (perchlorate counter ion); 340 (Pt–Cl stretch). Anal. Calc. for C4H16N6Cl4O8Pt2: H, 2.00; C, 5.94; N, 10.40; Found H, 2.23; C, 5.50; N, 9.90 %. 6
(2,3pzn) Yield: 137.2 mg (58.8 %). 1 H NMR (500 MHz, D2O), δ /ppm: 8.80 (d, 2H); 3.2 (s. 6H). 195Pt NMR (107 MHz, D2O) δ /ppm: -2312.2. IR (KBr, 4000-300 cm -1): 3303, 3227, 3057 (N–H stretch); 1090-1100 (Perchlorate counter ion); 338 (Pt–Cl stretch). TOF MS/ES +. (m/z, M 2+): 318 (C3H10N3PtCl species). Anal. Calc. for C6H20N6Cl4O8Pt2: H, 2.39; C, 8.61; N, 10.05; Found H, 2.17; C, 8.23; N, 10.28%. (2,5pzn) Yield: 179.9 mg (74.4%). 1 H NMR (500 MHz, D2O) δ / ppm: 9.05 (s, 2H); 3.04 (s, 6H). 195Pt NMR (107 MHz, D2O) δ / ppm: -2344.34. IR (KBr, 4000-300 cm -1): 3300, 3228, 3057 (N–H stretch); 1090-1100 (perchlorate counter ion); 338 (Pt–Cl stretch). TOF MS/ES + . (m/z, M 2+ ): 318 (C3H10N3PtCl species). Anal. Calc. for C6H20N6Cl4O8Pt2: H, 2.39; C, 8.61; N, 10.05; Found H, 2.21; C, 8.11; N, 9.87%. (2,6pzn) Yield: 103.0mg (44.8%). 1H NMR (500 MHz, D2O) δ /ppm: 8.95 (s, 2H); 3.05 (s, 6H). 195 Pt NMR (107 MHz, D2O) δ /ppm: -2320.36, -2461.82. IR (KBr, 4000-300 cm -1 ): 3285, 3207, 3075 (N–H stretch); 1090-1100 cm -1 (perchlorate counter ion); 326 (Pt–Cl stretch). TOF MS/ES + . (m/z, M 2+ ): 318 (C3H10N3PtCl species). Anal. Calc. for C6H20N6Cl4Pt2: H, 2.82; C, 10.17; N, 11.80; Found H, 2.78; C, 9.99; N, 11.27%. 4.2.4 Preparation of the dinuclear Pt(II) diaqua aqueous complexes The solutions of the diaqua complexes pzn, 2,3pzn, 2,5pzn and 2,6pzn were prepared as described in the literature, 26 by addition of appropriate amount of AgClO4 to each of corresponding chloro complexes. The chloro Pt(II) complex and AgClO4 (1: 1.98 molar ratio) were dissolved in 0.1M HClO4 and the mixture stirred vigorously at 50 °C for 24 h in the dark. The precipitated AgCl was removed by filtration through a 0.45 μm nylon membrane using Millipore filtration unit. The filtrate was diluted with 0.1 M HClO4 solution to give the required complex concentrations which were 3.52 x 10 -4, 1.0 x 10 -3, 1.06 x 10 -3 , and 1.0 x 10 -3 M for 2,6pzn, 2,3pzn, 2,5pzn and pzn, respectively. 4.2.5 Instrumentation and Physical measurements Elemental analyses of the complexes were performed on a Carlo Erba Elemental Analyzer 1106. The infrared spectra in the range 4000-300 cm -1 were recorded in the solid state (KBr pellets) using Perkin Elmer Spectrum One FT-IR spectrometer. The NMR 7
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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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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 116 and 117: PhCN PhCN Pt Cl Cl + N N CH 3 N CH
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 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.
Page 166 and 167: k obs(3 rd ) , s -1 -5 6.00x10 TMTU
Page 168 and 169: 4.3.4 Kinetics with NMR The substit
Page 170 and 171: ln([ML] t ) 4.0 3.5 3.0 2.5 2.0 1.5
Page 172 and 173: ln(k 2(1 st ) /T) -3.5 -4.0 -4.5 -5
Page 174 and 175: Comple x Table 4.4: Summary of Acti
Page 176 and 177: 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
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Table S4.14: 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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Table S5.5: Average observed rate c
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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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