Stereoisomeric Pt(IV) complexes with threonine

Stereoisomeric Pt(IV) complexes with threonine (ThrH = HOCH(CH₃)CH(NH₂)COOH, ??-amino-??-hydroxybutyric acid) were obtained. In the complexes trans-[Pt(S-ThrH)₂Cl₄] and trans-[Pt(R-ThrH)(S-ThrH)Cl₄], the ThrH molecules act as monodentate ligands coordinated through the NH₂ group. In the complexes cis- and trans-[Pt(S-Thr)₂Cl₂] and trans-[Pt(R-Thr)(S-Thr)Cl₂], the deprotonated ligands are coordinated in a bidentate fashion through the NH₂ and COO^?-groups (R,S is the absolute configuration of the asymmetric carbon atom). All the complexes were identified using elemental analysis, IR spectroscopy, and ¹⁹⁵Pt, ¹³C, and ¹H NMR spectroscopy. The complexes trans-[Pt(S-ThrH)₂Cl₄] · 3H₂O and cis-[Pt(S-Thr)₂Cl₂] · 2H₂O were additionally characterized by X-ray diffraction.     

HPLC Method for the Determination of the Purity of K[Pt(NH3)Cl3], a Precursor of the Platinum Complexes with Cytostatic Activity

K[Pt(NH₃)Cl₃], a valuable precursor for the preparation of platinum complexes with cytostatic activity, e.g. satraplatin, picoplatin, LA-12 and cycloplatam, is currently prepared from cis-[Pt(NH₃)₂Cl₂] or K₂[PtCl₄] and these are the usual impurities in the final product. A simple, selective and sensitive HPLC-UV analytical method for the determination of the purity of K[Pt(NH₃)Cl₃] and the quantification of the impurities has been developed and validated. The platinum complexes present in the final product were separated on a strong base ion exchange column by the gradient elution with detection at 213 nm. Intra-assay precisions for the platinum complexes respective to their ions ([PtCl₄]^2?, [Pt(NH₃)Cl₃]^? and cis-[Pt(NH₃)₂Cl₂]) were between 0.1 and 2.0% (relative standard deviation); intermediate precisions were between 1.4 and 2.0% and accuracies were between 98.6 and 101.4%. Limits of detection of [PtCl₄]^2?, [Pt(NH₃)Cl₃]^? and cis-[Pt(NH₃)₂Cl₂] were 6 µg · ml^?1, 13 mg · ml^?1 and 5 µg · ml^?1 respectively, limits of quantification of [PtCl₄]^2?, [Pt(NH₃)Cl₃]^? and cis-[Pt(NH₃)₂Cl₂] were 51 µg · ml^?1, 55 mg · ml^?1 and 20 µg · ml^?1 respectively.     

Dinuclear complexes with a μ-cyano ligand. Part XI(1). Synthesis and characterization of several derivatives ofcis-[Co(NH3)(en)2(H2O)]3+

Summary The new complex double saltscw-[Co(NH₃)(en)₂(H₂O)]₂ [M(CN)₄]₃ (en = ethylenediamine; M = Ni, Pd or Pt),cis-[Co(NH₃(en)₂(H₂O)]₂[FeNO(CN)₅]₃ andcis-[Co(NH₃)(en)₂(H₂O)][Co(CN)₆] have been synthesized and by anation in the solid state the corresponding new dinuclear complexes with a cyano bridgecis- ortrans-[(NH₃)(en)₂Co-NC-M(CN)₃]₂ [M(CN)₄] (M = Ni, Pd or Pt);cis-, trans-[(NH₃)(en)₂Co-NC-FeNO(CN)₄]₂[FeNO(CN)₅] andcis-[(NH₃)(en)₂Co-NC-Co(CN)₅ have been prepared. The complexes have been characterized by chemical analysis, t.g. measurements, and by i.r. and electronic spectroscopy. With [Ni(CN)₄][^2– and [Co(CN)in]₆ ^3– only thecis-isomer is produced; with [Pd(CN)₄]^2–, [Pt(CN)₄]^2– and [FeNO(CN)₅]^2– thetrans- isomer is the dominant species. The dinuclear complex derived from [Pt(CN)₄]^2– shows strong Pt-Pt interactions both in the solid state and in solution.     

Pt(II) stereoisomeric complexes with serine

There have been synthesized Pt(II) stereoisomeric complexes with hydroxy-α-amino acid serine (SerH = NH₂CH(CH₂OH)COOH is α-amino-β-hydroxypropionic acid): trans-[Pt(S-SerH)₂Cl₂], trans-[Pt(R-SerH)(S-SerH)Cl₂] with monodentately (through NH₂ group ) bound SerH and cis-, trans-[Pt(R-Ser)(S-Ser)], trans-[Pt(S-Ser)₂] with bidentately bound (through groups NH₂ and COO) ligands (R, S is the absolute configuration of asymmetric carbon atom). The successive phases in the synthesis of Pt(II) stereoisomeric complexes with serine were studied by ¹⁹⁵Pt NMR spectroscopy. To identificate the compounds synthesized the method of elemental analysis, IR and NMR (¹⁹⁵Pt, ¹³C, ¹H) spectroscopy were used. For trans-[Pt(R-Ser)(S-Ser)] the X-ray diffraction data were obtained.     

A kinetic analysis of oxidation of the antioxidant <Emphasis Type="Italic">N</Emphasis>-acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-cysteine (NAC) by Pt(IV) complexes

N-acetyl-l-cysteine (NAC) is an antioxidant and a supplement and has been demonstrated to have protective effects for a variety of toxic effects of heavy metals. Although previous works have shown that NAC can ameliorate the severe toxic effects of cisplatin, there is a lack of understanding of the interactions between NAC and Pt(IV)-based prodrugs. In this work, the oxidation of NAC by a cisplatin prodrug (cis-[Pt(NH₃)₂Cl₄]), by a prototype of Pt(IV) anticancer drug ormaplatin ([Pt(dach)Cl₄]) and by a model compound (trans-[PtCl₂(CN)₄]^2–) was characterized in detail. NAC was oxidized to NAC-disulfide as identified by mass spectrometric analysis. Time-resolved spectral and stopped-flow kinetic measurements were carried out over a wide pH range, demonstrating that the oxidation followed overall second-order kinetics. The observed second-order rate constants k′ versus pH profiles were established. A reaction mechanism was deduced, involving three parallel rate-determining steps; conceivable transition states were also proposed for these steps. Rate constants of the rate-determining steps, obtained from the simulations of rate equation to the k′–pH profiles, were largely correlated with the electron density on the sulfur atom in NAC. The Pt(IV) prodrugs can execute oxidative stress in the biological systems of the human body by direct oxidation of relevant molecules, similar to HOCl/OCl^? and chloroamines. Instead, the oxidative stress involved in the severe toxic effects of cisplatin is produced via a different mode. NAC could be a chemoprotecting agent also for the Pt(IV) anticancer drugs if recent drug delivery technologies are used.     

Influence of the chloride counterion on the redox reactivity of tetraammineplatinum(II) cation with octacyanotungstate(V) anion: Crystal structure of [Pt(NH3)4]2[W(CN)8]

The redox reaction between [Pt(NH₃)₄]²⁺ and [W(CN)₈]³⁻ in the presence of Cl⁻ anions in aqueous solution affords single crystals of [Pt^II(NH₃)₄]₂[W^IV(CN)₈] and [Pt^IV(NH₃)₄Cl₂]Cl₂. Trapped cyano ligands of [W(CN)₈]⁴⁻ rectangular antiprisms of D₂ point symmetry between parallel Pt(II) square planes show that the inner-sphere redox pathway is prohibited. The presence of Cl⁻ counterions enables the formation of [Pt(NH₃)₄Cl₂]Cl₂ as the product of the rare outer-sphere pathway of the oxidation of Pt(II) by [W(CN)₈]³⁻.     

Trifluoromethylselenato(0) and trifluoromethyltellurato(0) complexes of platinum(II)

The series of cis/trans-trifluoromethylselenato complexes [Pt(SeCF₃)_2 − xCl_x(PPh₃)₂] (x = 0, 1) was identified by NMR spectroscopic methods. While in acetonitrile solution spectra are dominated by the resonances of the cis derivatives, those of pure cis-[Pt(SeCF₃)₂(PPh₃)₂] indicate cis-trans-isomerisation in CH₂Cl₂ solution. In contrast, exchange reactions of cis-[PtCl₂(PPh₃)₂] and [NMe₄]TeCF₃ only gave evidence for cis isomers. Molecular structures of cis- and trans-[Pt(SeCF₃)₂(PPh₃)₂] and cis-[Pt(TeCF₃)₂(PPh₃)₂] are discussed in comparison with related compounds.     

The preparation of cis- and trans-[PtH(C6Cl5)(PEt3)2 and a study of the “hydride-donor capacity” of the complexes trans- [PtH(C6X5(PEt3)2] (X = F and Cl)

The preparations of cis- and trans-[PtH(C₆Cl₅)(PEt₃)₂] by thermal decomposition of cis- and trans-[Pt(OCHO)(C₆Cl₅)(PEt₃)₂], respectively, are reported. Also described are cis- and trans-[Pt(SnCl₃)(C₆Cl₅)(PEt₃)₂], obtained by treating SnCl₂ with cis- and trans-[PtCl(C₆,Cl₅)(PEt₃)₂], respectively. It is shown that while trans- [PtH(C₆Cl₅)(PEt₃)₂] does not form hydride-bridged complexes in the presence of trans-(PtH(MeOH)(PEt₃)₂]⁺, the corresponding complex trans-[PtH(C₆)(PEt₃)₂] reacts with the same solvento complex, in methanol, giving labile [(PEt₃)₂HPt(-μH)Pt(C₆F₅)(PEt₃)₂]⁺.     

Platinum(III) formation and stabilization as “platinum blues” with different types of ligands in the course of their interaction with PtCl4 2- and cis-Pt(NH3)2CI2

Studying the kinetics of PtCl₄ ^2- cis-[Pt(NH₃)₂(H₂O)₂]²⁺ and cis-Pt(NH₃)₂Cl₂ (cis-DDP) reactions with different types of ligands using spectrophotometric, Potentiometric and EPR methods, the conditions for Pt(III) formation as transient species and its further stabilization as “Platinum Blue” complexes were found. A general method for obtaining “Platinum Blue” species is suggested.     

The interaction of vinyl acetate and allyl acetate with chloro-bridged platinum(II) complexes [Pt2Cl4(PR3)2]: Crystal structure of cis-[PtCl2(PMe2Ph2)(CH2=CHOCOCH3)]

Five complexes of type cis-[PtCl₂(PR₃)Q] (PR₃ =PMe₃, PMe₂Ph, PEt₃; Q = CH₂ CHOCOCH₃ or CH₂=CHCH₂OCOCH₃) have been prepared. The crystal structure of cis-[PtCl₂[PME₂Ph)(CH₂=CHOCOCH₃)] is described. Crystals of cis-[PtCl₂(PME₂Ph)(CH₂-CHOCOCH₃)] are triclinic, with a 8.441(4), b 13.660(5), c 7.697(3) Å, a 101.61(3)°, β 111.85(3)° γ 95.22(3)°, pP1, Z = 2. The structure was determined from 2011 reflections I σ 3σ (I) and refined to R = 0.037. The CH₃COO grouping is syn to the cis-PMe₂Ph ligand, with bond lengths of PtCl (trans to P) 2.367(3), PtCl (trans to olefin) 2.314(3), PtP 2.264(2), and PtC of 2.147(12) and 2.168(11) Å. The complexes cis-[PtCl₂- (PR₃)Q] were studied by variable temperature ¹H and ³¹P NMR spectroscopy. Spectra of the vinyl acetate complexes were temperature dependent as a result of rotation about the platinum—olefin bond. The rotation was “frozen out” at ca. 240 K; for cis-[PtCl₂(PME₂Ph)(CH₂=CHOCOCH₃] ΔG≠ (rotation) 15.0 ± 0.2 kcal mol^-1. NMR parameters for the rotamers are reported. NMR studies of the interaction between chloro-bridged complexes of type [Pt₂Cl₂(PR₃)₂] (PR₃ = P-N-Pr₃ or PMe₂Ph) and vinyl acetate shows that even at low temperatures (213 K) equilibrium favours the bridged complex and the proportion of trans-[PtCl₂(PR₃)CH₂=CHOCOCH₃)] is very small e.g. 2%. The allyl acetate complexes cis-[PtCl₂(PR₃)(CH₂₌CHCH₂OCOCH₃)] showed only one rotamer over the range 333–213 K. Reversible dissociation of cis-[PtCl₂(PMe₂Ph)- (CH₂=CHCH₂OCOCH₃)] to [Pt₂Cl₄(PMe₂Ph)₂] + allyl acetate was studied at ambient temperature. At low temperatures e.g. 213–190 K addition of allyl acetate to a CDCl₃ solution of [Pt₂Cl₂(P-n-Pr₃)₂] reversibly gave some olefin complex trans-[PtCl₂(P-n-Pr₃)(CH₂=CHCH₂OCOCH₃)] and some O-bonded complex trans-[PtCl₂(P-n-Pr₃)(CH₂=CHCH₂OCOCH₃)].     

Cytotoxic properties of platinum(IV) and dinuclear platinum(II) complexes and their ligand substitution reactions with guanosine-5′-monophosphate

The substitution reaction of the Pt(IV) complex [PtCl₄(bipy)] with guanosine-5??-monophosphate (5??-GMP) was studied by UV?CVis spectrophotometry. This reaction was investigated under pseudo-first-order conditions at 37?°C in 25?mM Hepes buffer (pH?=?7.2) in the presence of 10?mM NaCl to prevent the hydrolysis of the complex. The substitution of chlorides in [{trans-Pt(NH₃)₂Cl}₂(??-1,2-bis(4-pyridyl)ethane)](ClO₄)₂ (Pt3) complex by 5??-GMP was followed by ¹H NMR spectroscopy under second-order conditions. Very similar values for the rate constants of both substitution steps were obtained. The Pt(IV) complexes, [PtCl₄(bipy)] and [PtCl₄(dach)], as well as dinuclaer Pt(II) [{trans-Pt(NH₃)₂Cl}₂(??-pyrazine)](ClO₄)₂ (Pt1), [{trans-Pt(NH₃)₂Cl}₂(??-4,4??-bipyridyl)](ClO₄)₂?·?DMF (Pt2) and [{trans-Pt(NH₃)₂Cl}₂(??-1,2-bis(4-pyridyl)ethane)](ClO₄)₂ (Pt3) complexes, displayed potent cytotoxic activity against human ovarium carcinoma cell line TOV21G and lower activity toward human colon carcinoma HCT116 cell line at the same concentrations. Our data indicate that these platinum complexes could be explored further, as potential therapeutic agents for ovarian cancer.     

Complexes of palladium,platinum and rhodium with 2,2′-biquinoline and 2-(2′-pyridyl)quinoline

Summary The reactions of 2,2-biquinoline(biq) with M(PhCN)₂X₂ (M=Pd; X=Cl or Br; M=Pt, X=Cl, Br or I), K₂PtCl₄ and RhCl₃·3H₂O and of 2-(2-pyridyl)quinoline (pq) with K₂PtCl₄ and RhCl₃·3H₂O have been investigated. The isolated complexescis-[Pd(biq)X₂] (X=Cl or Br),cis-[Pt(biq)Cl₂],cis-[Pt(biq)Cl₂]·H₂O,trans-[Pt(biq)₂Br₂]·5H₂O, [Pt₃(biq)₂I₆],mer-[Rh(biq)Cl₃-(H₂O)] andmer-[Rh(pq)Cl₃(H₂O)] have been characterized by elemental analyses, conductivity measurements, i.r., electronic, and¹H n.m.r. spectra. The reaction of pq with K₂PtCl₄ in 1M H₂SO₄ gave the salt 2-(2-pyridyl) quinolinium tetrachloroplatinate(II) pentahydrate, (pqH)₂[PtCl₄]·5H₂O; when the reaction was carried out in aqueous acetone,cis-[Pt(pq)Cl₂] was obtained. A new method for the synthesis ofcis-[Rh(biq)₂X₂]X (X=Cl or Br) is described; both compounds have been further characterized by¹H n.m.r.     

Aminobis(phenolate)s of imidomolybdenum(VI) and -tungsten(VI)

The reactions of trans-[MoO(ONO^Me)Cl₂] 1 (ONO^Me = methylamino-N,N-bis(2-methylene-4,6-dimethylphenolate) dianion) and trans-[MoO(ONO^tBu)Cl₂] 2 (ONO^tBu = methylamino-N,N-bis(2-methylene-4-methyl-6-tert-butylphenolate) dianion) with PhNCO afforded new imido molybdenum complexes trans-[Mo(NPh)(ONO^Me)Cl₂] 3 and trans-[Mo(NPh)(ONO^tBu)Cl₂] 4, respectively. As analogous oxotungsten starting materials did not show similar reactivity, corresponding imido tungsten complexes were prepared by the reaction between [W(NPh)Cl₄] with aminobis(phenol)s. These reactions yielded cis- and trans-isomers of dichloro complexes [W(NPh)(ONO^Me)Cl₂] 5 and [W(NPh)(ONO^tBu)Cl₂] 6, respectively. The molecular structures of 4, cis-6 and trans-6 were verified by X-ray crystallography. Organosubstituted imido tungsten(VI) complex cis-[W(NPh)(ONO^tBu)Me₂] 7 was prepared by the transmetallation reaction of 6 (either cis or trans isomer) with methyl magnesium iodide.     

Immobilization of Platinum(II) and Platinum(IV) Complexes on Oxidized Nanoporous Carbon Material and Evaluation of the Enthalpy of Adsorption

Physicochemical study of cis-[Pt(NH3)2Cl2] and cis-[Pt(NH₃)₂Cl₂(OH)₂] is carried out, and immobilization of platinum complexes on the nanoporous carbon substrate is investigated. The solubility of cis-[Pt(NH₃)₂Cl₂] in 1 M HCl solution is determined, and the average enthalpy of dissolution is calculated: Δ_solH° = 27.3 ± 0.9 kJ/mol. The batch capacity is determined experimentally for cis-[Pt(NH3)2Cl2] and cis- [Pt(NH₃)₂Cl₂(OH)₂] to be 32.9 mg/g (0.17 mg-equiv/g) and 47.6 mg/g (0.24 mg-equiv/g), respectively. Immobilization of platinum complexes on the oxidized carbon surface is found to take place due to interaction between carboxy groups and ammine groups of platinum complexes. The resulting heat capacity curves are used to calculate the enthalpies of adsorption for cis-[Pt(NH₃)₂Cl₂] and cis-[Pt(NH₃)₂Cl₂(OH)₂] on the oxidized carbon surface, equal to 24.46 and 27.46 kJ/mol, respectively.     

Kinetics of substitution reactions of transition metal complexes in 1,3-dioxolan-2-one + water and 4-methyl-1,3-dioxolan-2-one + water solvent mixtures

Summary Rate constants are reported and discussed for several substitutions of inorganic complexes in ethylene carbonate (1,3-dioxolan-2-one) + water and in propylene carbonate (4-methyl-1,3-dioxolan-2-one) + water solvent mixtures. The reactions include aquation ofcis- and oftrans-[Co(en)₂Cl₂]⁺, aquation oftrans-[Cr(OH₂)₄Cl₂]⁺, bromide substitution at [Pd(Et₄dien)Cl]⁺, thiourea substitution atcis-[Pt(4-NCpy)₂Cl₂], and aquation and cyanide attack at [Fe(X-phen)₃]²⁺ cations.     

Platinum-promoted cyclization reactions of amino olefins : II. Regio- and stereoselectivity in the cyclization reactions of C-methyl substituted pent-4-enylamines

The compounds 1-, 2- and 3-methylpent-4 enylamine cyclize, in a reaction medium containing [PtCl₄]^2-, to the corresponding cis- and trans-dimethylpyrrolidines showing marked regio and stereoselectivity effects. The following cyclization reactions are also reported: a) that of hex-4-enylamine which gives a mixture of 2-ethylpyrrolidine and 2-methylpiperidine, b) that of 2,2-dimethylpent-4-enylamine which produces 2,4,4-trimethylpyrrolidine and c) that of 2,2-dimethylhex-4-enylamine which results in the formation of 2-ethyl-4,4-dimethylpyrrolidine and 2-methyl-5,5-dimethylpiperidine.The X-ray crystal structures of trans-[PtCl₂(amine)(Et₃P)] (amine = cis-2, 4-dimethylpyrrolidine and cis-2,3-dimethylpyrrolidine) are reported.     

Experimental and quantum‐chemical studies of 1H, 13C and 15N NMR coordination shifts in Au(III), Pd(II) and Pt(II) chloride complexes with picolines

¹H, ¹³C and ¹⁵N NMR studies of gold(III), palladium(II) and platinum(II) chloride complexes with picolines, [Au(PIC)Cl₃], trans‐[Pd(PIC)₂Cl₂], trans/cis‐[Pt(PIC)₂Cl₂] and [Pt(PIC)₄]Cl₂, were performed. After complexation, the ¹H and ¹³C signals were shifted to higher frequency, whereas the ¹⁵N ones to lower (by ca 80–110 ppm), with respect to the free ligands. The ¹⁵N shielding phenomenon was enhanced in the series [Au(PIC)Cl₃] < trans‐[Pd(PIC)₂Cl₂] < cis‐[Pt(PIC)₂Cl₂] < trans‐[Pt(PIC)₂Cl₂]; it increased following the Pd(II) → Pt(II) replacement, but decreased upon the trans → cis‐transition. Experimental ¹H, ¹³C and ¹⁵N NMR chemical shifts were compared to those quantum‐chemically calculated by B3LYP/LanL2DZ + 6‐31G**//B3LYP/LanL2DZ + 6‐31G*. Copyright © 2008 John Wiley & Sons, Ltd.     

Mixed and partial oxidation states. Photoelectron spectroscopic evidence

X-ray photoelectron spectra of the single valence platinum complexes K₂[Pt(CN)₄] · 3H₂O(1),K₂[Pt(CN)₄]Cl_0.3 · n H₂O(2) and K₂[Pt(CN)₄]Cl₂ · 3H₂O(3) and the mixed valence compound [Pt^II(C₂H₅NH₂)₄]Cl₄ · [Pt^IV (C₂H₅NH₂)₄Cl₂] · 4H₂O(4) have been measured. It is found that one can distinguish clearly between mixed and single valence compounds by electron spectroscopy. The Pt spectrum of (4) is a superposition of a Pt^II and Pt_IV spectrum. The chemical shift between (1) and (3) is normal, however (2) shows an anomalous low binding energy for the Pt 4f electrons. The importance of using reliable reference peaks for obtaining absolute binding energies is emphasized.     

Influence de la nature du solvant sur le comportement photochimique de complexes trans- ET cis-[PtCl2(éthylène)(amine)]

Nature of the solvent plays a major role in the photochemical behaviour of cis- and trans-[PtCl₂(ethylene)(amine)] complexes. Dimeric compounds [Pt₂Cl₄-(amine)₂] are obtained on irradiation of these complexes in chloroform or diethyl ether. A non-stereospecific reaction of photosubstitution is observed in nitrile solvents. When methanol, dimethoxyethane or dimethylformamide are used as solvents, cis and trans complexes have a quite different photochemical behaviour, but in all of the cases, a photodegradation leading to ionic species [PtCl₃(ethylene)]^? H⁺ amine and [PtCl₃(amine)]^? H⁺ amine is the main reaction.     

Oxidative addition reactions of [Pt(CN)4]2−; A 13C and 195Pt NMR study

¹³C and ¹⁹⁵Pt NMR measurements show that complexes of the type trans-[Pt(CN)₄X₂]^2? are formed on addition of X₂ (X = Br, Cl, I) to M₂[Pt(CN)₄] (M = K or NBu₄) in aqueous and chloroform solution respectively. Addition of ICN to K₂[Pt(CN)₄] (60% ¹³CN^?) in aqueous solution results in the formation of potassium pentacyanoiodoplatinate(IV) with complete¹³CN^?/¹²CN^?scrambling. The reaction of equi-molar amounts of trans-[PtX₂(CN)₄]^2? (X = Br and Cl), which was previously claimed to result in complete transformation into trans-[PtBrCl(CN)₄]^2?, is instead shown to result in an approximately statistical redistribution of halogens. A progressive shift of δ_Pt to high field is observed on successive replacement of ¹²CN^? by ¹³CN^? in [Pt(CN)₄]^2?.