DNA modification by cis-diaminoplatinum(ii) complexes with aminonitroxide ligands

The mixed-ligand complexes cis-Pt^II[R(CH₂)_nNH₂](NH₃)X₂, where R = 2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl, X₂ = ClI or Cl₂, n = 1 or 2, and binuclear complexes trans-3,4-bis[cis-ammine(iodochloro or dichloro)platinum(ii)amino]-2,2,6,6-tetramethylpiperidin-1-oxyls were synthesized. The reactivity of the aminonitroxide complexes toward DNA, the destabilizing effect of the adducts on DNA structure, and the distribution of the Pt adducts along the DNA duplex were studied. The platination activity of the complexes is affected by the natures of both the leaving ligands X and the carrying amino ligands. The decrease in the platination activity of the complexes with an increase in the amino ligand sizes is probably caused by steric hindrance. The complexes that effectively platinate isolated DNA and cause a moderate destabilizition of DNA duplex possess high antitumor activities.     

Conformations of N,N'-diphenyl-N-ethylthiourea and its related compounds in the solid state

The conformations of the related compounds RPhTUPh, RPhUPh and DRTUPh, DRUPh have been determined in the solid state by studying their v(N-H) vibrations and comparison with the conformations in solution. Only EPhTUPh in the solid state is observed to exhibit both cis and transv(N-H) bands. The coexistence of the cis and trans forms is suggested to take place with a balance between Ph-Ph interaction and hydrogen bond formation. In this balance the steric effect of the R group on the CS group plays an important role. For DRTUPh and DRUPh out-trans isomerism is discussed. The importance of hydrogen bond formation is emphasized as a factor determining conformations in the solid state.     

Reactivity of cyclopalladated compounds: VIII. Synthesis of cyclometallated compounds with an oxygen as the donor atom. Crystal and molecular structure of (8-methylquinoline-C,N)-(1-methoxynaphthalene-8-C,O)palladium(II)

Treatment of 1-methoxynaphthalene (MXNH) with n-butyllithium in a diethyl ether/n-hexane solution gives 1-methoxynaphthalene-8-lithium (MXNLi) in 30% yield as an insoluble material. This compound reacts with PdCl₂(SEt₂)₂ to give bis(1-methoxynaphthalene-8-C,O)palladium(II) (I)_and with PtCl₂(SEt₂)₂ to give cis- and trans-(1-methoxynaphthalene-8-C,O)(1-methoxynaphthalene-8-C)(diethylsulfide)platinum(II) (II), which are non-rigid molecules in solution. With the cyclopalladated dimers [{$\text{Pd(CN}$)Cl₂}₂], MXNLi gives the palladobicyclic compounds: ($\text{N∩C)P}$$\text{d(C∩O}$) (III). An X-ray diffraction study of compound IIIa where N∩N = 8-methylquinoline-C,N reveals the planarity of the molecule, shows that it has a cis configuration with respect to the PdC bonds, and confirms that the oxygen atom of MXN is bonded to palladium: PdO 2.236(4) Å. The geometry of IIIa is maintained in solution, whereas the corresponding compounds IIIb and IIIc in which N∩C is benzo[h]quinoline-9-C,N and N,N-dimethyl-1-naphthylamine-8-C,N, respectively, appear to be mixtures of cis and trans isomers in solution. With PMe₂Ph I and II give trans-Pd(MXN)₂(PMe₂Ph)₂ and cis-Pt(MNX)₂(PMe₂Ph)₂, respectively, in which the methoxynaphthalene is bound to the metals via the 8-carbon of the naphthalene ring. Only one phosphine ligand adds to compounds IIIb and IIIc with displacement of the O → Pd bond. One carbon monoxide ligand can be added to the platinum compound II to give Pt(MXN)₂(SEt₂)CO which in solution exists as two isomers in equilibrium.     

Coordination-driven synthesis of Ag(I) compounds based on a double emission ligand consisting of 1,3,4-oxadiazole and cyclotriphosphazene units

A new ligand (L) which consists of cyclotriphosphazene and 1,3,4-oxadiazole units is reported. Two new Ag(I) coordination compounds {[Ag(L)SO₃CF₃] _n (1) and Ag₂L₂(NO₃)₂ (2)} based on L and Ag(I) salts are obtained. Compound 1 features a 1-D chain, in which the ligand L adopts a divergent trans-conformation, whereas 2 is a discrete binuclear Ag(I) molecule in which L adopts convergent cis-conformation. Compounds 1 and 2 are fully characterized by ¹H-NMR, Infrared, elemental analysis, X-ray powder, and single-crystal diffraction. Luminescent properties of 1 and 2 are investigated.     

A series of hydridoplatinum(II) complexes stabilized with tribenzylphosphines: their preparation,and an empirical approach to the mutual influence of ligands

The preparation, IR and NMR spectra of 123 platinum hydrides of the general formula, trans-PtHX(PBz₃)₂ or trans-PtHL(PBz₃)₂BPh₄ (X = a uninegative anionic ligand, L = a neutral donor molecule, Bz = benzyl), are described. Neutral platinum hydrides have been synthesized by the reduction of trans-PtCl₂-(PBz₃)₂ with NaBH₄, by the Michaelis—Arbuzov rearrangement, or by metathesis. Cationic hydridoplatinum(II) complexes are obtained from the reaction of trans-PtHX(PBz₃)₂ (X = Cl or NO₃) with a donor molecule (L) in the presence of NaBPh₄, or by coordinating a donor molecule through use of PtH(PBz₃)₂BPh₄ · $\text{1}\text{2}$CH₂Cl₂. The observed trends in ν(PtH), τ(H), ¹J(PtH) and ¹J(PtP) in a series of the hydridobenzylphosphineplatinum(II) complexes are discussed in terms of “trans- or cis-influences”, defined as the ability of a ligand to weaken the bond trans or cis to itself. The data support the view that a donor atom trans to the hydridic ligand is important in determining the strength of the PtH bond in this series. Some remarks on the distinctive characteristics of some complexes, e.g., dissociation of coordinated cycloalkanone from platinum(II) or stereochemical non-rigidity of the sym-dimethylurea ligand, are included. Tricyclohexylphosphine analogs also have been prepared for comparison.     

14N NMR of amminecobalt(III) compounds

Directly detected ammine ¹⁴N NMR chemical shifts of 20 amminecobalt(III) compounds are reported. The coordination shifts, δ_CS = δ_coord ? δ_free, are in all cases negative and range from ?4.4 ppm for the trans ammine ligand in [Co(NH₃)₅(CH₃)]²⁺ to ?73.6 ppm for the trans ammine ligand in [Co(NH₃)₅(F)]²⁺. Among the ligands studied, the NO₂^? ligand is unique in that it exerts a significant cis influence. The regularity in trans or cis influences upon the ammine nitrogen chemical shifts provides a basis for assignments in cases where this cannot be deduced from intensity ratios. Copyright © 2003 John Wiley & Sons, Ltd.     

Electronic structure and vibrational spectra of cis-diammine(orotato)platinum(II), a potential cisplatin analogue: DFT and experimental study

Orotic acid (vitamin B₁₃) is a key intermediate in biosynthesis of the pyrimidine nucleotides in living organisms, moreover, it may serve as the biological carrier for some metal ions. cis-Diammine(orotato)platinum(II), cis-[Pt(C₅H₂N₂O₄)(NH₃)₂] can be considered as a new potential cisplatin analogue. The FT-Raman and FT-IR spectra of the title complex are reported, for the first time. The molecular structure, vibrational frequencies, and the theoretical infrared and Raman intensities have been calculated by the density functional mPW1PW91 method. The detailed vibrational assignment has been made on the basis of the calculated potential energy distribution. The theoretically predicted IR and Raman spectra show very good agreement with experiment. Natural bond orbital (NBO) analyses were performed for cisplatin, carboplatin and the title complex. The results provided new data on the nature of platinum–ligand bonding in these compounds. Strong intramolecular hydrogen bond between the orotate ligand and the coordinated ammonia group stabilizes the structure of the platinum(II) complex. Thus, it is suggested that the orotate ligand in the title complex is more inert to the substitution reactions than the chloride ligands in cisplatin.     

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.     

Hydridocyanoalkyl complexes of platinum(II). Insertion of olefins into the PtH bond

The preparation and spectroscopic properties are described of some platinum(II) complexes having a hydride ligand cis or trans to an sp³ carbon, viz. trans-PtH(YCN)(PPh₃)₂ and cis-PtH(YCN)(LL) with YCN = C₂H₄CN, n-C₃H₆CN, o-CH₂C₆H₄CN and LL = bis(diphenylphosphino)-ethene or -ethane. The complexes trans-PtH(YCN)(PPh₃)₂ can add a fifth ligand in solution; the resulting five-coordinate complex was observed by ³¹P NMR in the case of PtH(C₃H₆CN)(PPh₃)₃. Insertion of olefin (ethen, 1-cyanoethene, norbornadiene, allen) into the PtH bond of the trans-hydrido complexes occurs to give cis-dialkyl complexes, but the cis-hydrido complexes are unreactive. The mechanism of insertion is discussed in terms of the kinetics and the geometries of reactants and products.     

Synthesis of thecis andtrans isomers oftert-butylaminedichloro-(dimethyl sulphoxide)platinum(II) and X-ray structure analysis of thecis compound

Summary Treatment ofcis-dichlorobis(dimethyl sulphoxide)platinum(II) [1] with an excess oftert-butylamine in MeOH yieldstert-butylamine-trans-dichloro(dimethyl sulphoxide)-platinum(II) [(tr-5)], rather than thecis-diaminechloro-(dimethyl sulphoxide)platinum(II) cation expected by analogy with similar reactions reported in the literature. The correspondingcis isomer [(cis-5)] is prepared from the same reactants (and similarly from K₂PtCl₄ andtert-butylamine) in DMSO medium, in which the initially formedtrans compound partially isomerizes to the thermodynamically favouredcis complex. The molecular structure of (cis-5) is determined by X-ray analysis. The coordination around the Pt atom is square-planar, and the DMSO ligand is S-coordinated. The lengths of the Pt-Cl bondscis andtrans to the DMSO ligand are 2.296(11) and 2.321(10) Å, respectively, and are well within expected ranges. Interatomic distances within the amine and DMSO ligands are normal.     

Transition metal complexes with bidentate ligand 2, 11-Bis (diphenylphosphinomethyl)benzo[c]phenanthrene (1). X. Preparation and spectroscopic properties of cis-[PtCl2 (1)] trans- and cis-[PtH (PPh3) (1)] [BF4] and crystal and molecular structure of cis-[PtCl2 (1)] · CHCl3

It is shown that ligand 1 , designed to span trans-positions, under appropriate conditions also gives cis-mononuclear complexes of platinum (II). The structure of cis-[PtCl₂ (1) ] (2) has been determined by single-crystal X-ray diffraction. The major distortion from square planar coordination is the P-Pt-P angle of 104.8°. Values of valence angles within the bidentate ligand indicate that this part of the molecule is very strained. Two phenyl groups, one on each phosphorus, lie almost parallel to each other separated by ca. 3.2–3.3 Å. The ¹H-NMR. data for this compound show that the π-phenyl interactions observed in the solid state occur also in solution. The preparation and NMR.-spectroscopic properties of trans- and cis-[PtH(PPh₃) (1) ] [BF₄] are reported.     

Ruthenium Lewis Acid‐Catalyzed Asymmetric Diels–Alder Reactions: Reverse‐Face Selectivity for α,β‐Unsaturated Aldehydes and Ketones

Acrolein, methacrolein, methyl vinyl ketone, ethyl vinyl ketone, 3‐methyl‐3‐en‐2‐one, and divinyl ketone were coordinated to a cationic cyclopentadienyl ruthenium(II) Lewis acid incorporating the electron‐poor bidentate BIPHOP–F ligand. Analysis by NOESY and ROESY NMR techniques allowed the determination of conformations of enals and enones present in solution in CD₂Cl₂. The results were compared to solid‐state structures and to the facial selectivities of catalytic asymmetric Diels–Alder reactions with cyclopentadiene. X‐Ray structures of four Ru‐enal and Ru‐enone complexes show the α,β‐unsaturated C=O compounds to adopt an anti‐s‐trans conformation. In solution, enals assume both anti‐s‐trans and anti‐s‐cis conformations. An additional conformation, syn‐s‐trans, is present in enone complexes. Enantioface selectivity in the cycloaddition reactions differs for enals and enones. Reaction products indicate enals to react exclusively in the anti‐s‐trans conformation, whereas with enones, the major product results from the syn‐s‐trans conformation. The alkene in s‐cis conformations, while present in solution, is shielded and cannot undergo cycloaddition. A syn‐s‐trans conformation is found in the solid state of the bulky 6,6‐dimethyl cyclohexanone‐Ru(II) complex. The X‐ray structure of divinyl ketone is unique in that the Ru(II) center binds the enone via a η² bond to one of the alkene moieties. In solution, coordination to Ru–C=O oxygen is adopted. A comparison of facial preference is also made to the corresponding indenyl Lewis acids.     

Reactions of platinum complexes with 4,7-phenanthroline: crystal structures of mono- and binuclear platinum(II) complexes containing 4,7-phenanthroline

The reaction of a mixture of cis and trans-[PtCl₂(SMe₂)₂] with 4,7-phen (4,7-phen = 4,7-phenanthroline) in a molar ratio of 1 : 1 or 2 : 1 resulted in the formation of mono and binuclear complexes trans-[PtCl₂(SMe₂)(4,7-phen)] (1) and trans-[Pt₂Cl₄(SMe₂)₂(μ-4,7-phen)] (2), respectively. The products have been fully characterized by elemental analysis, ¹H, ¹³C{¹H}, HHCOSY, HSQC, HMBC, and DEPT-135 NMR spectroscopy. The crystal structure of 1 reveals that platinum has a slightly distorted square planar geometry. Both chlorides are trans with a deviation from linearity 177.66(3)°, while the N–Pt–S angle is 175.53(6)°. Similarly, the reaction of a mixture of cis and trans-[PtBr₂(SMe₂)₂] with 4,7-phen in a 1 : 1 or 2 : 1 mole ratio afforded the mono or binuclear complexes trans-[PtBr₂(SMe₂)(4,7-phen)] (3) and trans-[Pt₂Br₄(SMe₂)₂(μ-4,7-phen)] (4), respectively. The crystal structure of trans-[Pt₂Br₄(SMe₂)₂(μ-4,7-phen)].C₆H₆ reveals that 4,7-phen bridges between two platinum centers in a slightly distorted square planar arrangement of the platinum. In this structure, both bromides are trans, while the PtBr₂(SMe₂) moieties are syn to each other. NMR data of mono and binuclear complexes of platinum 1–4 show that the binuclear complexes exist in solution as a minor product, while the mononuclear complexes are major products.     

Kinetic characterization of the interactions of trans-dichloro-platinum(IV) anticancer prodrugs and a model compound with thiosulfate

Sodium thiosulfate has been utilized as a rescuing agent for relief of the toxic effects of cisplatin and carboplatin. In this work, we characterized the kinetics of reactions of the trans-dichloro-platinum(IV) complexes cis-[Pt(NH₃)₂Cl₄], ormaplatin [Pt(dach)Cl₄] and trans-[PtCl₂(CN)₄]^2? (anticancer prodrugs and a model compound) with thiosulfate at biologically important pH. An overall second-order rate law was established for the reduction of trans-[PtCl₂(CN)₄]^2? by thiosulfate, and varying the pH from 4.45 to 7.90 had virtually no influence on the reaction rate. In the reactions of thiosulfate with cis-[Pt(NH₃)₂Cl₄] and with [Pt(dach)Cl₄], the kinetic traces displayed a fast reduction step followed by a slow substitution involving the intermediate Pt(II) complexes. The reduction step also followed second-order kinetics. Reductions of cis-[Pt(NH₃)₂Cl₄] and [Pt(dach)Cl₄] by thiosulfate proceeded with similar rates, presumably due to their similar configurations, whereas the reduction of trans-[PtCl₂(CN)₄]^2? was about 1,000 times faster. A common reduction mechanism is suggested, and the transition state for the rate-determining step has been delineated. The activation parameters are consistent with transfer of Cl⁺ from the platinum(IV) center to the attacking thiosulfate in the rate-determining step.     

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.     

Calculations of microconstants and equilibrium formation constants for platinum(II) and palladium(II) halide complexes in solution

Distribution diagrams and formation functions for halide complexes [M(H₂O)_{4 ? n} Cl _n ]^{2 ? n} (M = Pt(II) or Pd(II)) and [PdCl_{4 ? n} Br _n ]^2? (n = 0?C4) in solution are analyzed in terms of the matrix model. Equilibrium constants for binding the first ligand $\left( {\bar K} \right)$ and corrections for the mutual influence between ligands (??) in the course of complex formation in solution are calculated. In examples analyzed, the substitution of chloride ion for water in the coordination sphere of platinum(II) and palladium(II) is an anti-cooperative process. The substitution of bromide ion for chloride ion in the coordination sphere of [PdCl₄]^2? is weakly cooperative. Quantum-chemical calculations show that platinum(II) and palladium(II) cis-bisaquadichloro complexes in the gas phase are thermodynamically less stable than trans-isomers. The cis-trans isomerization constants in the gas phase calculated by the DFT method and those found for solutions using the matrix model have the same order of magnitude.     

Mixed metal PtxMyLz complexes of L = 1-methyluracil and 1-methylthymine: Preparation and spectroscopic studies

The reactions of cis-(NH₃)₂PtL₂ (L = 1-MeT or 1-MeU, the anions of 1-methylthymine or 1-methyluracil respectively) in water with various salts of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) or Ag(I) have produced 14 new heteronuclear complexes of the general types: cis-[(NH₃)₂PtL₂ML₂Pt(NH₃)₂]X_n·mH₂O or cis-(NH₃)₂PtL₂MX_n·mH₂O, and also with silver(I) perchlorate a complex of stoichiometry cis-{(NH₃)₂Pt(1-MeU)₂}₂· 3AgClO₄·6H₂O. Comparisons are made with previously reported heteronuclear species derived from cis-(NH₃)₂PtL₂ and factors influencing the type of heteronuclear complex formed are discussed, particularly the versatility of binding patterns with Ag(I). A tetranuclear structure is suggested for the compound of stoichiometry cis-(NH₃)₂Pt(1-MeU)₂·FeSO₄·3H₂O involving iron(II) ions linked by sulphate bridges. The electronic spectra of the trinuclear complexes cis-[(NH₃)₂Pt(1-MeU)₂M(1-MeU)₂Pt(NH₃)₂] (NO₃)₂·mH₂O (M = Fe, Co or Ni) are reported. They show that the trans-MO₄Pt₂ geometry results in a very severely trans-elongated ligand field about the central metal ion, M. This conclusion is supported by the Mössbauer spectrum in the case of the iron(II) complex. The X- and Q-band EPR spectra of the Fe(III) analogue are also reported.     

PhP-PPh group bound to 1,8-positions of naphthalene: Preparation of cis isomer and synthesis of binuclear complex

A thermodynamically less stable cis isomer of 1,2-diphosphacycle was prepared from the corresponding trans isomer. Diphosphine, in which a PhP-PPh bond bridges the 1,8-positions of naphthalene, 1,2-diphenyl-1,2-dihydronaphtho[1,8-cd][1,2]diphosphole (1), was first prepared according to a previously reported method, and the trans isomer of 1 was irradiated in tetrahydrofuran with UV-vis light to reach equilibrium with cis-1 in a trans:cis ratio of 1:2. When a similar photochemical conversion was carried out using a saturated hexane solution of trans-1, cis-1 was precipitated in a good yield of 94%. The configuration of cis-1 was confirmed by X-ray analysis. Both cis- and trans-1 diphosphine ligands were used for the preparation of binuclear gold complexes. The crystal structure of (μ-cis-1)-[AuCl]₂ demonstrated that the two lone pairs of cis-1 are suitably directed for arrangement of the two gold centers in close proximity to each other. The two independent (μ-cis-1)-[AuCl]₂ molecules in the crystal were found to form a dimer through the multiple intermolecular interaction among the gold centers.     

Polymerization reactions in [Co(NH3)5(H2O)][CoX(CN)5] and cis-[Co(NH3)4(H2O)2][CoX(CN)5] (X = Cl,Br, I,No2 OR N3) double-complex salts

Polymerization reactions of [Co(NH₃)₅(H₂O)][CoX(CN)₅] and cis-[Co(NH₃)₄ (H₂O)₂][CoX(CN)₅] (X = Cl, Br, I, NO₂ or N₃] have been studied. The compounds undergo aging reactions in the solid state or in solution induced by the ligand X involving solvolytic processes affording polymeric materials with μ-cyano bridges. A mechanistic explanation of these reactions is given and a comparison between both series of compounds together with the parent compound [Co(NH₃)₆][Co(CN)₆] is discussed.     

Preparation,characterization and cytotoxic activity of new compounds trans-[PtCl2NH3(3-(hydroxymethyl)-pyridine)] and trans-[PtCl2NH3(4-(hydroxymethyl)-pyridine)]

We report the synthesis, characterization and cytotoxic assays of new trans-platinum compounds, trans-[PtCl₂NH₃(3-(hydroxymethyl)-pyridine)] and trans-[PtCl₂NH₃(4-(hydroxymethyl)-pyridine)]. In the present work, we found that the replacement of the ammine ligand in “classical” transplatinum with the two new ligands does not increase the cytotoxic activity, maybe because these complexes do not produce a stability of the intrastrand cross-links in DNA.