Tuning Reactivity of Platinum(II) Complexes

More documents

Recommendations

Info

Table 5.2: Acid dissociation constants of platinum(II) complexes determined pKa1 pKa2 ΔpKa spectrophotometrically at 25 °C (Ionic strength, I = 0.1 M NaClO4/ HClO4). pzn pmn pdn qzn pht 3.29 ± 0.06 5.55 ± 0.09 2.32 3.27 ± 0.20 5.92 ± 0.23 2.65 4.87 ± 0.07 5.96 ± 0.08 14 1.09 3.27 ± 0.05 8.62 ± 0.12 5.35 3.59 ± 0.12 9.61 ± 0.06 The results shown in Table 5.2 indicate a correlation between pKa values and the properties of the linkers, and the DFT calculations of the complexes. The pKa1 values for the first deprotonation of the aqua ligand coordinated to Pt(II) centre fall in the range qzn (pKa1 = 3.27) to pdn (pKa1 = 4.87) and increases in the order: qzn ≈ pmn < pzn < pht < pdn. This is attributed to the π-acceptor properties of the linker and the difference in the distance separating the two Pt(II) centres, which has an influence on the overall charge observed on the Pt(II) atoms (Table 5.1). Previous studies have established that a short distance between the Pt atoms results in the addition of single charges to the Pt(II) centres, 16–18,42 which enables each metal centre to become more electrophilic and more acidic, leading to lower pKa values. As a consequence of the short distance coupled with extended π-conjugation in the benzodiazine ligands, good electronic communication between the ligand and the Pt centres is present. 30,43 This results in additional charge increments on the Pt(II) centres and is the reason for the significantly lower pKa1 values of qzn and pht in comparison to pmn and pdn, respectively. This trend is in line with the π-acceptor properties of the ligand and DFT calculations. The results also show that when the number of aromatic rings is increased the complex becomes more acidic, showing that the electron density on the Pt(II) centre and on the hydroxo ligand are stabilised better by extended π-conjugation of the 6.02
enzodiazine ring. This is supported by the lower energy gap (ΔE) values for qzn and pht complexes. It is also noted that the pKa2 values for deprotonation of the second water molecule from the aqua/hydroxo complex species to form hydroxo/hydroxo species occurred at higher pH. Following deprotonation of the first aqua ligand the overall charge of the complexes decreases to +3 on forming the hydroxo species on the first Pt(II) centre. 14,18 Because of this, the electrophilicity of the second Pt(II) centre is decreased, resulting in higher pKa2 values in all cases. However, in the case of pht and qzn, the pKa2 values are exceptionally high. After deprotonation of the first aqua ligand, the second nitrogen atom bound to Pt(II) centre bearing the aqua ligand causes a destabilising effect on the metal centre, due to the excess negative charges carried by adjacent N atoms. This results in elongation of the Pt–OH2 bond as observed from the DFT calculations (Table 5.3). Also, the π-donor character is significantly increased in the benzodiazines which have higher energy HOMOs compared with their monocyclic analogues (Table 5.3). Thus, phthalazine ligand is the strongest heterocyclic π-donor in the series, quite consistent with its electron-rich structure that is supported by the bigger value of the HOMO-LUMO energy gap and lowest NBO charges for the aqua/Hydroxo derivative of the pht complex. These factors collectively are responsible for the remarkable high pKa2 values in qzn and pht, respectively. 15
Page 1 and 2:
Tuning Reactivity of Platinum(II) C
Page 3 and 4:
Declaration This thesis report is b
Page 5 and 6:
Abstract Systematic kinetic and the
Page 7 and 8:
Table of contents Acknowledgements
Page 9 and 10:
2.5.5 Effect of Non-participating G
Page 11 and 12:
5.2.1 Chemical and Solutions ......
Page 13 and 14:
7.2 Experimental Section ..........
Page 15 and 16:
procurements, Messers P. Forder and
Page 17 and 18:
Figure 2.2 Potential energy profile
Page 19 and 20:
Figure 4.6 Concentration dependence
Page 21 and 22:
Figure 6.1 Spectrophotometric titra
Page 23 and 24:
List of Tables Table 2.1 A selectio
Page 25 and 26:
Table 6.4 Summary of rate constants
Page 27 and 28:
TU thiourea DMTU 1,3-dimethyl-2-thi
Page 30 and 31:
Table of Contents-1 Chapter 1 .....
Page 32 and 33:
1.0 Introduction 1.1 Cancer Disease
Page 34 and 35:
toxic potential. The most well-know
Page 36 and 37:
1.3.2.2 Cellular Uptake Cisplatin i
Page 38 and 39:
H 3N OH 2 Pt H 3N OH 2 Active Pt(II
Page 40 and 41:
transformational pathways that comp
Page 42 and 43:
the hydrolysis of the complex, wher
Page 44 and 45:
1.3.4 Terpyridine Platinum(II) Comp
Page 46 and 47:
H 3 N Cl Pt NH 3 H 3 N NH 2 (CH 2 )
Page 48 and 49:
1.4 Kinetic Interest The platinum-b
Page 50 and 51:
3. The effect of varying the positi
Page 52 and 53:
17 R. A. Henderson, The Mechanism o
Page 54 and 55:
Altona J. H. van Boom, G. A. van de
Page 56 and 57:
76 (a)J. Kašpárková, J. Zehnulov
Page 58 and 59:
Table of Contents-2 Chapter Two ...
Page 60 and 61:
List of Tables Table 2.1: A selecti
Page 62 and 63:
The mononuclear Pt(II) complexes 1-
Page 64 and 65:
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 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 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.
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
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 228 and 229: However, because the highest occupi
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
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 288 and 289:
Table S5.28: Average observed rate
Page 290 and 291:
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
Page 324 and 325:
pKa1 values become smaller. In addi
Page 326 and 327:
of steric influence is felt by the
Page 328 and 329:
6.5 Conclusion The present study ha
Page 330 and 331:
17 O. F. Wendt and L. I. Elding, 19
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 348 and 349:
Page 350 and 351:
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
Page 362 and 363:
ange 326-400 cm -1 (weak) for Pt-Cl
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
Page 372 and 373:
coordination to the soft Pt(II) cen
Page 374 and 375:
observed at -2962.4 and -3024.1 ppm
Page 376 and 377:
H 3N NH 3 Pt NH 2 OH 2 n NH 3 NH 2
Page 378 and 379:
k obs2 , in s -1 -3 TU 1.2x10 DMTU
Page 380 and 381:
7.3.4 Activation Parameters The tem
Page 382 and 383:
density is located on the metal cen
Page 384 and 385:
acetylmethionine, which reported th
Page 386 and 387:
References 1 (a) B. Rosenberg, L. V
Page 388 and 389:
32 N. Summa, J. Maigut, R. Puchta a
Page 390 and 391:
Appendix 7 Table S7.1: Summary of s
Page 392 and 393:
k obs(2 nd ) , in s -1 0.00020 0.00
Page 394 and 395:
ln(k 2(2 nd ) /T) -8.5 -9.0 -9.5 -1
Page 396 and 397:
k obs(1 st ) , in s -1 0.06 TU DMTU
Page 398 and 399:
ln(k 2(1 st ) /T) -3.2 TU DMTU TMTU
Page 400 and 401:
Table S7.11: Summary of kobs(2 nd )
Page 402 and 403:
Page 404 and 405:
%T 22.0 20 18 16 14 12 10 8 6 4 2 0
Page 406 and 407:
k st obs(1 ) , in s-1 0.10 0.08 0.0
Page 408 and 409:
ln(k st 2(1 ) /T) -4.0 TU DMTU TMTU
Page 410 and 411:
Figure S7.23: Mass spectra for HexP
Page 412 and 413:
Table S21: Average observed rate co
Page 414 and 415:
Table S7.23: Summary of kobs(2 nd )
Page 416 and 417:
Page 418 and 419:
90.0 80 70 60 50 40 30 20 %T 10 0 -
Page 420 and 421:
Figure S7.37: Mass spectrum for Hex
Page 422 and 423:
Chapter 8 Tuning Reactivity of plat
Page 424 and 425:
dinuclear Pt(II) complexes to relea
Page 426 and 427:
finally Pt2. The order of reactivit
Page 428:
• prolonged survival in the cell
show all

Tuning Reactivity of Platinum(II) Complexes

Create successful ePaper yourself

Delete template?

Save as template?