Importance of platinum(II)-assisted platinum(IV) substitution for the oxidation of guanosine derivatives by platinum(IV) complexes

Guanosine derivatives with a nucleophilic group at the 5' position (G-5') are oxidized by the Pt (IV) complex Pt( d, l)(1,2-(NH 2) 2C 6H 10)Cl 4 ([Pt (IV)(dach)Cl 4]). The overall redox reaction is autocatalytic, consisting of the Pt (II)-catalyzed Pt (IV) substitution and two-electron transfer between Pt (IV) and the bound G-5'. In this paper, we extend the study to improve understanding of the redox reaction, particularly the substitution step. The [Pt (II)(NH 3) 2(CBDCA-O,O')] (CBDCA = cyclobutane-1,1-dicarboxylate) complex effectively accelerates the reactions of [Pt (IV)(dach)Cl 4] with 5'-dGMP and with cGMP, indicating that the Pt (II) complex does not need to be a Pt (IV) analogue to accelerate the substitution. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that the [Pt (IV)(dach)Cl 4]/[Pt (II)(NH 3) 2(CBDCA-O,O')]/cGMP reaction mixture contained two Pt (IV)cGMP adducts, [Pt (IV)(NH 3) 2(cGMP)(Cl)(CBDCA-O,O')] and [Pt (IV)(dach)(cGMP)Cl 3]. The LC/MS studies also indicated that the trans, cis-[Pt (IV)(dach)( (37)Cl) 2( (35)Cl) 2]/[Pt (II)(en)( (35)Cl) 2]/9-EtG mixture contained two Pt (IV)-9-EtG adducts, [Pt (IV)(en)(9-EtG)( (37)Cl)( (35)Cl) 2] and [Pt (IV)(dach)(9-EtG)( (37)Cl)( (35)Cl) 2]. These Pt (IV)G products are predicted by the Basolo-Pearson (BP) Pt (II)-catalyzed Pt (IV)-substitution scheme. The substitution can be envisioned as an oxidative addition reaction of the planar Pt (II) complex where the entering ligand G and the chloro ligand from the axial position of the Pt (IV) complex are added to Pt (II) in the axial positions. From the point of view of reactant Pt (IV), an axial chloro ligand is thought to be substituted by the entering ligand G. The Pt (IV) complexes without halo axial ligands such as trans, cis-[Pt(en)(OH) 2Cl 2], trans, cis-[Pt(en)(OCOCF 3) 2Cl 2], and cis, trans, cis-[Pt(NH 3)(C 6H 11NH 2)(OCOCH 3) 2Cl 2] ([Pt (IV)(a,cha)(OCOCH 3) 2Cl 2], satraplatin) did not react with 5'-dGMP. The bromo complex, [Pt (IV)(en)Br 4], showed a significantly faster substitution rate than the chloro complexes, [Pt (IV)(en)Cl 4] and [Pt (IV)(dach)Cl 4]. The results indicate that the axial halo ligands are essential for substitution and the Pt (IV) complexes with larger axial halo ligands have faster rates. When the Pt (IV) complexes with different carrier ligands were compared, the substitution rates increased in the order [Pt (IV)(dach)Cl 4] < [Pt (IV)(en)Cl 4] < [Pt (IV)(NH 3) 2Cl 4], which is in reverse order to the carrier ligand size. These axial and carrier ligand effects on the substitution rates are consistent with the BP mechanism. Larger axial halo ligands can form a better bridging ligand, which facilitates the electron-transfer process from the Pt (II) to Pt (IV) center. Smaller carrier ligands exert less steric hindrance for the bridge formation.     

Hydrogen bonding directs the H2O2 oxidation of platinum(II) to a cis-dihydroxo platinum(IV) complex

The use of ligands with proximate hydrogen bonding substituents in the oxidation of platinum(II) dimethyl complexes with H2O2 leads to the exclusive formation of an unusual cis-dihydroxo platinum(IV) complex, which can dehydrate to form a trinuclear metalla-azacrown complex.     

Two-electron oxidation of deoxyguanosine by a Ru(III) complex without involving oxygen molecules through disproportionation

Among the many mechanisms for the oxidation of guanine derivatives (G) assisted by transition metals, Ru(III) and Pt(IV) metal ions share basically the same principle. Both Ru(III)- and Pt(IV)-bound G have highly positively polarized C8-H's that are susceptible to deprotonation by OH(-), and both undergo two-electron redox reactions. The main difference is that, unlike Pt(IV), Ru(III) is thought to require O(2) to undergo such a reaction. In this study, however, we report that [Ru(III)(NH(3))(5)(dGuo)] (dGuo = deoxyguanosine) yields cyclic-5'-O-C8-dGuo (a two-electron G oxidized product, cyclic-dGuo) without O(2). In the presence of O(2), 8-oxo-dGuo and cyclic-dGuo were observed. Both [Ru(II)(NH(3))(5)(dGuo)] and cyclic-dGuo were produced from [Ru(III)(NH(3))(5)(dGuo)] accelerated by [OH(-)]. We propose that [Ru(III)(NH(3))(5)(dGuo)] disproportionates to [Ru(II)(NH(3))(5)(dGuo)] and [Ru(IV)(NH(3))(4)(NH(2)(-))(dGuo)], followed by a 5'-OH attack on C8 in [Ru(IV)(NH(3))(4)(NH(2)(-))(dGuo)] to initiate an intramolecular two-electron transfer from dGuo to Ru(IV), generating cyclic-dGuo and Ru(II) without involving O(2).     

Cyclometallated platinum(II) complexes: oxidation to, and C-H activation by, platinum(IV)

A series of cyclometallated phenylpyridine platinum(II) complexes have been synthesised with a systematic variation in both the phenylpyridine and the ancillary ligand. Oxidation of one of the cyclometallated species leads to a number of isomeric platinum(IV) complexes, all of which eventually isomerize to a single compound. The route to these new compounds has been demonstrated to involve an initial slow oxidation followed by a rapid C-H activation to give doubly cyclometallated complexes. The solid state structures of a number of both the platinum(II) and the platinum(IV) species have been solved; many of the structures exhibited extended interactions that result in complex three dimensional packing.     

Oxidatively induced reactions of a diimine platinum(IV) tetramethyl complex

The oxidation of the Pt(IV) tetramethyl complex [ArNCHCHNAr]PtMe₄ (Ar = 2,6-Me₂C₆H₃) has been investigated in acetonitrile and dichloromethane. Cyclic voltammetry demonstrates that the irreversible oxidation of [ArNCHCHNAr]PtMe₄ occurs at a slightly less positive oxidation potential than the irreversible oxidation of the analogous Pt(II) species [ArNCHCHNAr]PtMe₂. The product distribution arising from the oxidation depends strongly on the reaction conditions and includes cationic Pt(IV) species (acetonitrile, dichloromethane solvents) and Pt(II) species (dichloromethane only). Evidence is presented that suggests that homolytic cleavage of a weakened PtC bond in is involved in the oxidatively induced reactions.     

Synthesis of platinum nanoparticles by reaction of filamentous cyanobacteria with platinum(IV)-chloride complex

Interaction of cyanobacteria (Plectonema boryanum UTEX 485) with aqueous platinum(IV)-chloride (PtCl(4) degrees ) has been investigated at 25-100 degrees C for up to 28 days, and 180 degrees C for 1 day. The addition of PtCl(4) degrees to the cyanobacteria culture initially promoted the precipitation of Pt(II)-organic material as amorphous spherical nanoparticles (< or =0.3 microm) in solutions and dispersed nanoparticles within bacterial cells. The spherical Pt(II)-organic nanoparticles were connected into long beadlike chains by a continuous coating of organic material derived from the cyanobacterial cells, and aged to nanoparticles of crystalline platinum metal with increase in temperature and reaction time. The stepwise reduction for the formation of platinum nanoparticles in the presence of cyanobacteria was deduced to be Pt(IV) [PtCl(4) degrees ] --> Pt(II) [Pt(II)-organics] --> Pt(0). Spherical platinum-bearing nanoparticles were not present in abiotic PtCl(4) degrees experiments conducted under similar conditions and duration.     

Vibrational dynamics of deoxyguanosine 5'-monophosphate following UV excitation

The relaxation dynamics of the DNA nucleotide deoxyguanosine 5'-monophosphate (dGMP) following 266 nm photoexcitation has been studied by transient IR spectroscopy with femtosecond time resolution. The induced dynamics of the amide I (carbonyl) stretch, the asymmetric guanine ring stretch and the phosphate asymmetric stretch are monitored in the region 1000-1800 cm(-1). Excitation and subsequent rapid internal conversion to a "hot" ground state is reflected by depletion of the vibrational ground states of the amide I stretch and guanine ring stretch. However, the vibrational ground state of the phosphate is left unperturbed, indicating the absence of vibrational coupling between the guanine ring system and the phosphate group. The vibrational ground state of the amide I is repopulated in 2.5 ps (±0.2 ps) while it takes 3.7 ps (±0.5 ps) to repopulate the guanine ring vibration. This article discusses two possible relaxation pathways of dGMP, as well as the implications of the weak phosphate dynamics.     

Facile generation of platinum(IV) compounds with mixed labile moieties. Hydrogen peroxide oxidation of platinum(II) to platinum(IV) compounds

Hydrogen peroxide oxidation of platinum(II) compounds containing labile groups such as Cl, OH, and alkene moieties has been carried out and the products characterized. The reactions of [Pt^II (X)₂ (N–N)] (X = Cl, OH, X₂ = isopropylidenemalorate (ipm); N–N 2,2-dimethyl-1,3-propanediamine [(dmpda), N-isopropyl-1,3-propanediamine (ippda)] with hydrogen peroxide in an appropriate solvent at room temperature affords [Pt^IV (OH)(Y)(X)₂(N–N)] (Y = OH, OCH₃). The crystal structures of [Pt^IV(OH)(OCH₃)(Cl)₂(dmpda)]·2H₂O (P-1 bar, a = 6.339(2) Å , b = 9.861(1) Å, c = 11.561(1) Å, a = 92.078(9)°, β = 104.78(1)°, γ=100.54(1)°, V = 684.3(2) ų, Z = 2R = 0.0503) and [Pt^IV(OH)₂(ipm)(ippda)]·3H₂O (C 2/c, a = 27.275(6) Å, b=6.954(2) Å, c = 22.331(4) Å, β = 118.30(2)°, V = 3729(2) ų, Z = 8, R = 0.0345) have been solved and refined. The local geometry around the platinum(IV) atom approximates to a typical octahedral arrangement with two added groups (OH and OCH₃; OH and OH) in a transposition. The platinum(IV) compounds with potential labile moieties may be important intermediate species for further reactions.     

Unprecedented carbon-carbon bond formation induced by photoactivation of a platinum(IV)-diazido complex

UVA-induced photodecomposition of a Pt(IV)-diazido complex involves not only reduction to Pt(II) and N(2) release, but also O(2) evolution and formation of nitrene intermediates, whose trapping with (CH(3))(2)S gives rise to an unusual N,N'-bis(ethyl)sulfurousdiamide ligand in an apparently unprecedented process involving C-C bond formation.     

Preparation and reactivity of a monomeric octahedral platinum(IV) amido complex

Synthesis and isolation of the monomeric octahedral platinum(IV) amido complex (NCN)PtMe2NHPh have been accomplished upon deprotonation of the amine complex [(NCN)PtMe2(NH2Ph)][OTf]. The preliminary reactivity of the amido ligand has been explored.     

Kinetics of the homogeneous oxidation of hydrogen by platinum(II) and platinum(IV) chloro complexes in aqueous solution

The kinetics of the homogeneous oxidation of hydrogen in the Pt(II)–Pt(IV)–Cl^––H₂O system has been studied for the first time in conditions permitting to avoid the formation of Pt-black. It is shown that platinum (II) [Pt(II)Cl_i(H₂O)_4-i, where i=1, 2, 2], is active in the reaction, whereas the PtCl ₄ ^2– complex and platinum(IV) do not react with hydrogen.

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, Pt-, H₂ Pt^II–Pt^IV–Cl^––H₂O. (II) (Pt^IICl_i(H₂O)_4-i, i=1, 2, 3); PtCl ₄ ^2– (IV) .

     

Rearrangement of a (dithiolato)platinum(II) complex formed by reaction of cyclic disulfide 7,8-dithiabicyclo[4.2.1]nona-2,4-diene with a platinum(0) complex: oxidation of the rearranged (dithiolato)platinum(II) complex

Reaction of the title bicyclic disulfide 16 with [(Ph3P)2Pt(eta2-C2H4)] (2) yielded the corresponding (dithiolato)platinum(II) complex 17 by oxidative addition. The initial product 17 isomerized at room temperature in a [1,5]-sulfur rearrangement to give another (dithiolato)platinum(II) complex 18 in high isolated yield. Oxidation reactions of 18 with dimethyldioxirane (DMD) provided (sulfenato-thiolato)platinum(II) 23, (sulfinato-thiolato)platinum(II) 24, (sulfenato-sulfinato)platinum(II) 25, and (disulfinato)platinum(II) 26 complexes, the structures of which were elucidated by NMR spectroscopy and X-ray crystallography. The oxidation process took place regioselectively in the first step and chemoselectively in the second. The selectivities are discussed.     

Kinetics of oxidation of hypophosphite ion by platinum(IV) in an alkaline medium

Summary The kinetics of the oxidation of hypophosphite ion by platinum(IV) have been studied spectrophotometrically in alkaline medium at different temperatures. The rate increases as the pH increases and the empirical rate law applicable to the reaction is given by:-d[Pt^IV]/dt = k₃[Pt^IV][H₂PO^2–][OH^–]The rate constant is 2.17×10^–3 (l² mo^–2s^–1) at 40.5°. The energy and entropy of activation for the reaction are 104.2 kJ mol^–1 and 28.5 JK^–1mol^–1 respectively.     

Oxidation of guanosine derivatives by a platinum(IV) complex: internal electron transfer through cyclization

Many transition-metal complexes mediate DNA oxidation in the presence of oxidizing radiation, photosensitizers, or oxidants. The DNA oxidation products depend on the nature of the metal complex and the structure of the DNA. Earlier we reported trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum (trans-Pt(d,l)(1,2-(NH(2))(2)C(6)H(10))Cl(4), [Pt(IV)Cl(4)(dach)]; dach = diaminocyclohexane) oxidizes 2'-deoxyguanosine 5'-monophosphate (5'-dGMP) to 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-5'-dGMP) stoichiometrically. In this paper we report that [Pt(IV)Cl(4)(dach)] also oxidizes 2'-deoxyguanosine 3'-monophosphate (3'-dGMP) stoichiometrically. The final oxidation product is not 8-oxo-3'-dGMP, but cyclic (5'-O-C8)-3'-dGMP. The reaction was studied by high-performance liquid chromatography, (1)H and (31)P nuclear magnetic resonance, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The proposed mechanism involves Pt(IV) binding to N7 of 3'-dGMP followed by nucleophilic attack of a 5'-hydroxyl oxygen to C8 of G and an inner-sphere, 2e(-) transfer to produce cyclic (5'-O-C8)-3'-dGMP and [Pt(II)Cl(2)(dach)]. The same mechanism applies to 5'-d[GTTTT]-3', where the 5'-dG is oxidized to cyclic (5'-O-C8)-dG. The Pt(IV) complex binds to N7 of guanine in cGMP, 9-Mxan, 5'-d[TTGTT]-3', and 5'-d[TTTTG]-3', but no subsequent transfer of electrons occurs in these. The results indicate that a good nucleophilic group at the 5' position is required for the redox reaction between guanosine and the Pt(IV) complex.     

The edta complex of platinum(IV): a titrimetric and spectrophotometric study

Platinum in the form of hexachloroplatinate(IV) reacts slowly with EDTA in a 1:1 mole ratio. At the concentration level used (a few mg per 50–75 ml), favorable conditions were solution of pH 3–4.5, and 3–8-fold molar excess of EDTA. Complete reaction required heating at 100° for 1.5–2 h. The reaction rate was retarded by acetate ion, but not by nitrate or sulfate. Titrimetric determination of platinum was accomplished by addition of excess standard EDTA, buffering to pH 3–4.5, heating the mixture at 100° for 1.5 h, buffering to pH 5.3 with acetic acid-acetate, and back-titrating with zinc acetate to a xylenol orange end-point. Blank corrections were necessary to compensate for trace metal impurities in the water and/or reagents. Determinations of 0.4–3 mg of platinum per 50 ml were accurate to ± 1.3% standard deviation. Both titrimetric and spectrophotometric evidence ruled out the possibility of reduction of platinum(IV) by EDTA. Titrimetric methods showed the complex to be PtCl₄HY^3-, where Y is the deprotonated EDTA.     

Spectrophotometric studies on the platinum(IV)-prochlorperazine bismethanesulfonate complex

We have studied the formation of a platinum complex and developed a simple, rapid and sensitive spectrophotometric method for the determination of platinum in solution. The method is based on the complexation reaction of the chromogen, prochlorperazine bismethane-sulfonate (PCPMS), with platinum(IV) in phosphoric acid medium which forms a reddish brown 1 1 complex with an absorption maximum around 528 nm. The reaction is fast in the presence of copper(II) and goes to completion within 1 min. Beer's law is obeyed over the concentration range 0.3–7.2 g/ml of platinum(IV) with an optimal range of 1.2–6.6 g/ml. The molar absorptivity is 2.65 × 10⁴1 mol^–1 cm^–1 and the Sandell's sensitivity is 7.8 ng cm^–2. The stability constant, logK, of the complex is 4.96±0.1 at 25 ° C. The effects of time, temperature, concentrations of acids, PCPMS and copper(II), and the interference by various ions are investigated. The method has been successfully applied to the determination of platinum content in alloys and minerals.