Tuning Reactivity of Platinum(II) Complexes
Tuning Reactivity of Platinum(II) Complexes Tuning Reactivity of Platinum(II) Complexes
acetylmethionine, which reported that the release of the aliphatic chain occurred within 5.0 h of the reaction. Since the nucleophilicity of thiourea is higher than that of methionine, the release of bridge in 1,1/t,t dinuclear complexes should have occurred within the ca. 1500 min, time window used in the study. Substitution reactions with the sterically hindered nucleophiles DMTU and TMTU show a clear dependence on the steric bulkiness of the nucleophiles. The most sterically hindered nucleophile TMTU reacts significantly slower than the less hindered TU, which means the associative bond formation process in the trigonal-bipyramidal transition state is less favoured. The mode of activation remains associative in nature throughout the studied systems, since the activation enthalpy change, ∆H ≠, is positive and large, while activation entropy change, ∆S ≠ , is large and negative for all cases. 55-57 7.5 Conclusion In this study, the effect of increasing the alkanediamine chain length in the [{cis– Pt(NH3)2OH2}2–μ–NH2(CH2)nNH2] +4 complexes was investigated. It was found that the reactivity of the dinuclear Pt(II) complexes with S-donor nucleophiles decreased with elongation of the length of (CH2)n moiety between the Pt(II) centres. This is ascribed to the decrease in the in-space electrostatic interactions between the two Pt(II) centres, which becomes weaker as the chain–length is increased further. In addition, an increase in the σ-inductive effect through the introduction of the alkanediamine bridge results in accumulation of the electronic density at Pt(II) centre, which makes the metal centre less electrophilic. This results in higher pKa values of the coordinated aqua ligands and also slows down the substitution reaction on going from EnPt to DecPt by repelling the incoming thiourea nucleophiles. The results from the 1 H and 195 Pt NMR studies support the kinetic data clearly showing the two substitution processes, which involves an initial simultaneous displacement of the aqua ligands by thiourea followed by the release of the ammine trans to the bound sulphur to form the final product [{cis–Pt(TU)2NH3}2–µ–NH2(CH2)nNH2] +4. In addition, the results reveal that the alkanediamine linker remained interact during the reaction 28
with S-donor nucleophiles. This finding concurs with the results reported by Farrell and his group. 31(a), 33, 48 Compared to the dinuclear complexes containing the rigid aromatic linkers, viz. diazines 17, 18 and dipyridyl ligands 14 , whose results have been reported elsewhere in the earlier works by our group (Chapters 4, 5 & 6 of this study), it is demonstrated that the dinuclear complexes comprising of rigid aromatic linkers are relatively unstable and readily disintegrate to liberate the diamine bridge by sulphur donor nucleophiles. Taken together, the current results suggest that the cis-dinuclear complexes with α,ω- alkanediamine show high stability to strong S-donor nucleophiles that are present in human cells and play an important role in biological reactions. It can therefore be concluded that these compounds are likely to be more stable as anti-tumour drugs. The substitution process remains associative in nature, which is supported by the large negative ΔS ≠ values calculated from the temperature-dependent studies of the reactions. 29
- 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: Table S6.10: Average observed rate
- Page 350 and 351: Table S6.13: Average observed rate
- 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 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: Table S7.13: Average observed rate
- 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: Table S7.25: Average observed rate
- 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
with S-donor nucleophiles. This finding concurs with the results reported by Farrell and<br />
his group. 31(a), 33, 48<br />
Compared to the dinuclear complexes containing the rigid aromatic linkers, viz.<br />
diazines 17, 18 and dipyridyl ligands 14 , whose results have been reported elsewhere in the<br />
earlier works by our group (Chapters 4, 5 & 6 <strong>of</strong> this study), it is demonstrated that the<br />
dinuclear complexes comprising <strong>of</strong> rigid aromatic linkers are relatively unstable and<br />
readily disintegrate to liberate the diamine bridge by sulphur donor nucleophiles. Taken<br />
together, the current results suggest that the cis-dinuclear complexes with α,ω-<br />
alkanediamine show high stability to strong S-donor nucleophiles that are present in<br />
human cells and play an important role in biological reactions. It can therefore be<br />
concluded that these compounds are likely to be more stable as anti-tumour drugs. The<br />
substitution process remains associative in nature, which is supported by the large<br />
negative ΔS ≠ values calculated from the temperature-dependent studies <strong>of</strong> the reactions.<br />
29
Change language