195Pt NMR

The reactions of the [Pt(H20)4]2+ ion with various anionic ( Am ) ligands have been studied by means of 195Pt NMR spectroscopy.295 The formation of complexes of the type... 

Koch, K. R. Miller, J. Westra, A. N. On the liquid-liquid extraction of Pt(IV/II) from hydrochloric acid by N-Acyl(aroyl)-N, N -dialkylthioureas a multinuclear (1H, 13C and 195Pt) NMR speciation study of the extracted complexes. International Solvent Extraction Conference, Cape Town, South Africa, Mar. 17—21, 2002, 327-334. 

Fig. 8. The 195Pt-NMR spectra of a DMF solution of [Pt2(en)3(PRI)2(N02) (N03)](N03)2 0.5 H20 (11) at 5°C, acquired on a Bruker WM-250 spectrometer operating at 53.6 MHz. (a) Power spectrum of the Fourier transform of a 1 K FID accumulated with a 5-jjls pulse width, 100-kHz spectral width, and 2000 K transients, (b and c) Normal Fourier transforms of 1 K FIDs accumulated with 10-fis pulsewidths, 42-kHz spectral width, and 64 K transients per spectrum. All FIDs were treated with 400-Hz line broadening functions to suppress noise (58).

Fig. 11. The time course (0.43-23.6 h) of 195Pt-NMR spectra observed for the HH-HT isomerization after dissolution of HH-[Pt(2.0+)2(en)2(PRI)2](NO3)2 (9). The spectrum closest to the abscissa corresponds to the first run.

The advantage of these complexes is that each Pt complex is isolated in pure form, and the crystal structure is known. Based on 1H-and 195Pt-NMR spectroscopy, the antitumor active compounds were found to be disrupted as shown in Fig. 20, giving finally [Pt(NH3)2(H20)2]2+, which is the same hydrolysis product as ds-DDP and is responsible for the activity. Therefore, the subsequent reaction with DNA bases and the mechanism would be the same with those of cis-DDP. The antitumor inactive compounds are relatively stable and are disrupted only to dinuclear amidate-bridged compounds. No further decomposition to [Pt(NH3)2(H20)2]2+ occurs. 

Fig. 15. The stereoisomeric thiourea-platinum complexes shown in (a) display large 4/ptjC couplings for the a-carbon atom in that branch of the X.X-dialkyl substituent which is in a favourable W configuration with respect to the metal atom (thick bonds). The assignment of the (fortuitously overlapping) H and 195Pt NMR signals of all three stereoisomers was feasible by means of indirect detection of these couplings from a XH detected H/(13C)/195Pt correlation spectrum which is shown in (b) together with the one-dimensional and 195Pt NMR projections. Reproduced from Ref. 44 by permission of John Wiley Sons.

We wish to thank J. Champoux for additional checking of the synthesis and M. J. Doedee for recording 195Pt NMR spectra. V. Yu. K. is grateful to the Swedish Royal Academy of Sciences and the Academy of Sciences of Russia for financial support of his stay at the Lund University. 

The relative amounts of all these Pt species vary as a function of the pH and the chloride concentration. Only platinum species with a coordinated water molecule are regarded to be reactive, because, in contrast to coordinated chloride or hydroxide, this ligand can be easily substituted by other donor molecules. Hydroxo species are formed as indicated in Eqs. (3)-(7) (34, 35), with [ds-Pt(NH3)2(OH)2] as the stable end product in basic solution (36). It should be noted, however, that this species very easily dimerizes and trimerizes at higher concentrations, producing ions such as [cis-Pt(NH3)2]2(jU.-OH)2 and [cis-Pt(NH3)2]3(ju,-OH)3, as has been proved with, e.g., 195Pt NMR spectroscopy (36a, b). Very recently, accurate pAa values have been presented for the (de)hy-dronation equilibria (36b) the pKa values have been added to Eqs. (5)—(7). Miller and House (36c) have accurately determined the kinetic parameters for the several hydrolysis reactions. They concluded that acid hydrolysis of cis-Pt in vivo is unlikely to proceed beyond [cis-Pt(NH3)2Cl(H20)]+. 

In fact, the very recent 195Pt NMR results of Bancroft et al. (41) indicate that, in agreement with Miller and House (36c), most likely [cis-Pt(NH3)2Cl(H20)]+ is the predominant species that reacts with biomolecules (at least with DNA). Other Pt amine compounds that are antitumor active have different kinetics of the hydrolysis reactions, and usually react much slower. The second-generation drug CBDCA (Fig. 2) is known to hydrolyze (in a 1 mAf solution) with a half-life at 37°C of a few days (41a) (compared to only 1 hour for cis-Pt). 

Two features need to be noted. Firstly, platinum-195 chemical shifts are quite sensitive to temperature, and in order to obtain acceptably narrow lines the solution temperature should be kept constant over the data accumulation time. Secondly, solvent effects need to be considered. A study of cis- and fraraj-PtCl2(PBu )2 in 14 solvents shows a change in A<5(P) of only 0.83p.p.m., but a change in Av(PtP) of 84.2Hz between n-hexane and acetonitrile.1355 Further work on temperature, solvent, substituent, oxidation state and stereochemical effects on 31P and 195Pt NMR chemical shifts and complexes is needed, and further efforts to collect and correlate data will be very useful.1356-1358... 

In the absence of X-ray crystallographic data, 31P and 195Pt NMR spectroscopy is a useful method to investigate the nature of the products in the solution. In addition to earlier references to these topics, the Pople-Santry theory has been used to calculate the signs and relative magnitudes of the coupling constants for the type of phosphorus-bridged complexes covered in this section.1502... 

TABLE 7. I3C and 195Pt NMR spectra of platinum cyclopropenylidene and cyclopropenylium complexes351... 

Fluoride in pazufloxacin mesylate samples was determined by 19F NMR spectra (06MI61,62). Platina complexes of ofloxacin and levoflox-acin were characterized by 1H, 13C, and 195Pt NMR (09ICA2060). and 13C NMR spectra of quaternary derivative 175 of ofloxacin were determined in both acidic and alkaline solutions (08MI91). Mg complexes of ofloxacin [Mg(Oflo)2(H20)2-2H20] and levofloxacin [Mg (Levo)2(H20)2 2H20] were characterized by [H and 13C NMR spectra (06JIB1755). 

Careful analysis of 195Pt NMR spectra in a series of Pt-nucleobase compounds has allowed binding site determinations from chemical shifts127,144. ... 

Salvadori, R, Uccello-Barretta, G. and Lazzaroni, R. (1990) A new method for the enantiomeric excess determination of chiral trisubstituted allenes by 195Pt NMR of traKi-dichloro[(S)-a-methylbenzylamine](allene)platinum(II) complexes. /. Chem. Soc. Chem. Commun., 1121-1123. 

Uemura, T., Shimura, T., Nakanishi, H., Tomohiro, T., Nagawa, Y. and Okuno, H.Y. (1991) 13C and 195Pt NMR of anticancer platinum pyrimidine greens. Inorg. Chim. Acta, 181, 11-14. 

Some investigators suggest that supposedly inert anions interact with Ptn complexes [5]. The differences in pKa values for three anions in a single study were mentioned in the previous paragraph and appear in Table 1. The equilibrium constant for nitrate complexation to the m-diaqua complex has been found by 195Pt-NMR to be 0.17 M 1 [21], With this constant, at 0.2m N03 about 3% of the Pt is nitrate-bound and at 0.04m NO, less than 1%. These fractions amount to only 0.01 log units or less in equilibrium constants considered. Perchlorate was found not to bind to the m-diaqua complex [21], Thus the differences in pKa values for three salts of cis-Ai-aqua complex cannot be ascribed to binding by the anions to Pt11. 

A number of Pt-ssDNA adducts platinated at d(G pG ) sites have been studied utilizing H, 31P, 15N, and 195Pt-NMR spectroscopy [31][32] [38][56—58] [61—63][67—70] [87][91—97]. Both C2- and non-C2-symmetrical A2 ligands have been used, but most of the results were similar, and both... 

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