Tuning Reactivity of Platinum(II) Complexes
Tuning Reactivity of Platinum(II) Complexes Tuning Reactivity of Platinum(II) Complexes
Against this background, several reports have indicated that bulky planar ligands such as pyridine and substituted pyridines attached next to the metal centre in Pt(II) complexes, e.g. cis-[PtCl(NH3)2(2-methylpyridine)] + and cis-[Pt(NH3)2Cl(4- methylpyridine] +, 21 could reduce the rate of reaction between the metal complexes and bio-molecules containing –SH groups due to steric hindrance around the Pt(II) ion, 6,22 . In recent reports, Jaganyi and his group 23 have studied the importance of introducing electron-donating methyl groups at 2,3-, 2,6- and 2,5-positions of the pyrazine bridging moiety (and in Chapter 4 of this study) and noted that increased steric hindrance and σ- inductive effect decreased the positive charge on the metal centre, slowing down reactivity of the Pt(II) complexes. In addition, recent studies 24–26 have established that there is a strong interaction between the two Pt(II) centres of dinuclear complexes, which proportionately weakens as the chain-length and flexibility of the linker is increased. The other factors which influence reactivity of multinuclear Pt(II) complexes include hydrogen-bonding capacity, charge at the metal centre and the linker, and the geometry of the leaving group relative to the linker. 27–29 It was systematically demonstrated in this work (Chapters 4 & 5) that the cis-dinuclear Pt(II) complexes bridged by the diazine ligands are degraded by thiourea, resulting in the loss of the integrity of the dinuclear structure and eventually releases the linker, in contrast to what was reported by Farrell and co-workers. 30 This is because of the strong trans influence of the sulphur atom that weakens the am(m)ine nitrogen–platinum bond, making it susceptible to further substitution reactions. 31 Pyridine has extensively been used as a ligand for the synthesis of new platinum coordination compounds because of its ability to connect metal centres by forming metal-to-ligand bonds. To try and shed some light with respect to the degradation of the bridging ligand that has been observed in a number of studies, 21,32–34 sp 3 hybridized sulphur spacer groups at the 4-position of the pyridine unit were investigated. In this study we report the kinetic and thermodynamic data for the substitution of the aqua ligand of the dinuclear Pt(II) complexes of the type [{cis-Pt(NH3)2H2O}2L] +4 (L = 4,4’-bis(pyridine)sulphides or 1,2-bis(4-pyridyl)ethane) (Scheme 6.1), by thioureas (TU, DMTU and TMTU) and ionic (Br ¯, I ¯ and SCN ¯) nucleophiles. The pKa values have also 3
een determined for the two aqua ligands and together with the DFT calculations interpreted in terms of the ability to stabilize the transition state of the reaction. NH3 Pt1 NH3 NH 3 N 1 H 2 O NH 3 Pt H 2 O S Pt1 N 2 N CH 3 Pt4 H 2 O 2+ Pt 2 4+ NH 3 NH 3 NH 3 NH 3 H 2 O Pt NH 3 H 2 O Pt 4 N NH 3 NH 3 S N Pt N S H O 2 NH 3 N Pt Scheme 6.1: Structures of the investigated dinuclear Pt(II) complexes. Included for 6.2 Experimental 6.2.1 Materials comparison of pKa and computation data purposes is the mononuclear complex Pt4. The numbering system adopted for the Pt centres is indicated on the structure of Pt1 Cisplatin (cis-(PtCl2(NH3)2, 99%) was purchased from Strem Chemicals. Methanol (Saarchem) was distilled over magnesium before use. 35 The nucleophiles thiourea (TU, 99%), 1,3-dimethyl-2-thiourea (DMTU, 99%), 1,1,3,3-tetramethyl-2-thiourea (TMTU, 98%), sodium bromide (NaBr, 99%), sodium iodide (NaI, 99%), sodium thiocyanide (NaSCN, 99%) and the ligands: 4-mercaptopyridine (95%), 4,4’-dipyridyldisulphide (dpss, 98%), 1,2-bis(4-pyridyl)ethane (bpe, 99%), dipyridinium hydrochloride (98%), 4- bromopyridine hydrochloride (99%), sodium perchlorate monohydrate (NaClO4.H2O, 98%) and perchloric acid (HClO4, 70%) were obtained from Aldrich and used without further purification. Silver perchlorate (AgClO4, 99.9%) from Aldrich was stored under nitrogen and used as supplied. Ultrapure water (Modulab Systems) was used in all experiments. Pt2 Pt3 H 2 O NH 3 NH 3 4+ 4+
- 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 258 and 259: Table S5.5: Average observed rate c
- 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 264 and 265: Table S5.9: Average observed rate c
- 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 270 and 271: Table S5.17: Average observed rate
- 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 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 288 and 289: Table S5.28: Average observed rate
- Page 290 and 291: Table S5.29: Average observed rate
- 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 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: Table S6.10: Average observed rate
- Page 350 and 351: Table S6.13: Average observed rate
een determined for the two aqua ligands and together with the DFT calculations<br />
interpreted in terms <strong>of</strong> the ability to stabilize the transition state <strong>of</strong> the reaction.<br />
NH3 Pt1 NH3 NH 3<br />
N 1<br />
H 2 O<br />
NH 3<br />
Pt<br />
H 2 O<br />
S<br />
Pt1<br />
N 2<br />
N CH 3<br />
Pt4<br />
H 2 O<br />
2+<br />
Pt 2<br />
4+<br />
NH 3<br />
NH 3<br />
NH 3<br />
NH 3<br />
H 2 O<br />
Pt<br />
NH 3<br />
H 2 O<br />
Pt<br />
4<br />
N<br />
NH 3<br />
NH 3<br />
S N Pt<br />
N S<br />
H O 2<br />
NH 3<br />
N Pt<br />
Scheme 6.1: Structures <strong>of</strong> the investigated dinuclear Pt(<strong>II</strong>) complexes. Included for<br />
6.2 Experimental<br />
6.2.1 Materials<br />
comparison <strong>of</strong> pKa and computation data purposes is the mononuclear<br />
complex Pt4. The numbering system adopted for the Pt centres is<br />
indicated on the structure <strong>of</strong> Pt1<br />
Cisplatin (cis-(PtCl2(NH3)2, 99%) was purchased from Strem Chemicals. Methanol<br />
(Saarchem) was distilled over magnesium before use. 35 The nucleophiles thiourea (TU,<br />
99%), 1,3-dimethyl-2-thiourea (DMTU, 99%), 1,1,3,3-tetramethyl-2-thiourea (TMTU,<br />
98%), sodium bromide (NaBr, 99%), sodium iodide (NaI, 99%), sodium thiocyanide<br />
(NaSCN, 99%) and the ligands: 4-mercaptopyridine (95%), 4,4’-dipyridyldisulphide<br />
(dpss, 98%), 1,2-bis(4-pyridyl)ethane (bpe, 99%), dipyridinium hydrochloride (98%), 4-<br />
bromopyridine hydrochloride (99%), sodium perchlorate monohydrate (NaClO4.H2O,<br />
98%) and perchloric acid (HClO4, 70%) were obtained from Aldrich and used without<br />
further purification. Silver perchlorate (AgClO4, 99.9%) from Aldrich was stored under<br />
nitrogen and used as supplied. Ultrapure water (Modulab Systems) was used in all<br />
experiments.<br />
Pt2<br />
Pt3<br />
H 2 O<br />
NH 3<br />
NH 3<br />
4+<br />
4+
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