Synthesis,characterization and some reactions of trans-[Co(NH3)4(CH3NH2)Br]2+ and trans-[Co(NH3)4(CH3NH2)(NO3)]2+ complexes

The preparation of trans-[Co(NH₃)₄(CH₃NH₂)Br]²⁺ and trans-[Co(NH₃)₄(CH₃NH₂)-(NO₃)]²⁺ complexes is described. The UV-VIS spectra of the complexes indicate a decrease of the ligand field compared to the parent pentaammines. Infrared spectra match with the pattern of the corresponding pentaammines. The catalyzed (by Hg²⁺) aquation of the trans-bromomethylamine complex go under retention of the stereochemical configuration. The base hydrolysis (studied at 25°C) products show trans to cis rearrangement for both complexes. ¹H NMR spectroscopy is used for identification of the stereochemical configuration of the compounds.     

Synthesis,spectroscopic characterization and X-ray crystallographic studies of trans-[PtCl2(PEt3)(PySOR)] complexes,where PySOR = (2-methylsulphinyl)-pyridine and (2-n-propylsulphinyl)pyridine

Alkylsulphinylpyridine ligands containing three potential donor centres: N, S and O atoms and two complexes of general formula trans-[PtCl₂(PEt₃)PySOR)] (R = Me and ⁿ Pr) were prepared and characterized by elemental analysis, i.r. spectroscopy, ¹H- and ³¹P-n.m.r. and X-ray crystallography. The ambidentate ligands act in both situations as monodentate ligands, bonded to the metal exclusively through the nitrogen atom. The crystal structures revealed the occurrence of discrete molecules and, in both complexes, the Pt atoms are coordinated in square planar arrangements by two chloride ions, in a trans configuration, by the pyridine nitrogen atom, and by the phosphine P atom. The oxygen atoms do not take part in the complexation scheme.     

Structural Characterization of trans-[Cr(NH3)4(H2O)Cl]Cl2 and trans-[Cr(NH3)4Cl2]l

Trans-[Cr(NH₃)₄(H₂O)Cl]Cl₂ (A) crystallizes in the monoclinic space group P2₁/m (No. 11) with a = 6.556(1), b = 10.630(5), c = 6.729(2) Å and β = 96.15(3)°. Trans-[Cr(NH₃)₄Cl₂]I (B) has monoclinic C2/m (No. 12) space group and a = 9.877(2), b = 8.497(2), c = 6.047(2) Å and β = 108.98(2)°. Both unit cells contain two formula units. Cr? Cl, Cr? O(H₂O) and three independent Cr? N(NH₃) distances for A are 2.98(1), 2.023(2), 2.067(2), 2.086(3) and 2.064(3) °. Cr? Cl and Cr? N(NH₃) bonds in B are 2.325(1) and 2.071(2) °. All octahedral angles are close to 90 and 180°. Both structures were refined to very low R values. Water molecule from trans-[Cr(NH₃)₄(H₂O)Cl]²⁺ is hydrogen bonded to both ionic chlorides. Cation and two anions form the motive which repeats itself in the crystal. Cations and anions of the second structure are distributed in layers. Each cation and anion have coordination number eight.     

Kinetics and mechanism for reduction of the anticancer prodrug trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2)(NH3)] (JM335) by thiols

The reduction of the platinum(IV) prodrug trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2)(NH3)] (JM335) by L-cysteine, DL-penicillamine, DL-homocysteine, N-acetyl-L-cysteine, 2-mercaptopropanoic acid, 2-mercaptosuccinic acid, and glutathione has been investigated at 25 degrees C in a 1.0 M aqueous perchlorate medium with 6.8 < or = pH < or = 11.2 using stopped-flow spectrophotometry. The stoichiometry of Pt(IV):thiol is 1:2, and the redox reactions follow the second-order rate law -d[Pt(IV)]/dt = k[Pt(IV)][RSH]tot, where k denotes the pH-dependent second-order rate constant and [RSH]tot the total concentration of thiol. The pH dependence of k is ascribed to parallel reductions of JM335 by the various protolytic species of the thiols, the relative contributions of which change with pH. Electron transfer from thiol (RSH) or thiolate (RS-) to JM335 is suggested to take place as a reductive elimination process through an attack by sulfur at one of the mutually trans chloride ligands, yielding trans-[Pt(OH)2(c-C6H11NH2)(NH3)] and RSSR as the reaction products, as confirmed by 1H NMR. Second-order rate constants for the reduction of JM335 by the various protolytic species of the thiols span more than 3 orders of magnitude. Reduction with RS- is approximately 30-2000 times faster than with RSH. The linear correlation log(kRS) = (0.52 +/- 0.06)-pKRSH--(2.8 +/- 0.5) is observed, where kRS denotes the second-order rate constant for reduction of JM335 by a particular thiolate RS- and KRSH is the acid dissociation constant for the corresponding thiol RSH. The slope of the linear correlation indicates that the reactivity of the various thiolate species is governed by their proton basicity, and no significant steric effects are observed. The half-life for reduction of JM335 by 6 mM glutathione (40-fold excess) at physiologically relevant conditions of 37 degrees C and pH 7.30 is 23 s. This implies that JM335, in clinical use, is likely to undergo in vivo reduction by intracellular reducing agents such as glutathione prior to binding to DNA. Reduction results in the immediate formation of a highly reactive platinum(II) species, i.e., the bishydroxo complex in rapid protolytic equilibrium with its aqua form.     

Synthesis, characterization, and reactivity of trans-[PtCl(R'R'SO)(A)2]NO3 (R'R'SO = Me2SO, MeBzSO, MePhSO; A= NH3, py, pic). Crystal structure of trans-[PtCl(Me2SO)(py)2]+

Trans complexes such as trans-[PtCl(2)(NH(3))(2)] have historically been considered therapeutically inactive. The use of planar ligands such as pyridine greatly enhances the cytotoxicity of the trans geometry. The complexes trans-[PtCl(R'R'SO)(A)(2)]NO(3) (R'R'SO = substituted sulfoxides such as dimethyl (Me(2)SO), methyl benzyl (MeBzSO), and methyl phenyl sulfoxide (MePhSO) and A = NH(3), pyridine (py) and 4-methylpyridine or picoline (pic)) were prepared for comparison of the chemical reactivity between ammine and pyridine ligands. The X-ray crystal structure determination for trans-[PtCl(Me(2)SO)(py)(2)]NO(3) confirmed the geometry with S-bound Me(2)SO. The crystals are orthorhombic, space group P2(1)2(1)2(1), with cell dimensions a = 7.888(2) A, b = 14.740(3) A, c =15.626(5) A, and Z = 4. The geometry around the platinum atom is square planar with l(Pt-Cl) = 2.304(4) A, l(Pt-S) = 2.218(5) A, and l(Pt-N) = 2.03(1) and 2.02(1) A. Bond angles are normal with Cl-Pt-S = 177.9(2) degrees, Cl-Pt-N(1) = 88.0(4) degrees, Cl-Pt-N(2) = 89.3(5) degrees, S-Pt-N(1) = 93.8(4) degrees, S-Pt-N(2) = 88.9(4) degrees, and N(1)-Pt-N(2) = 177.2(6) degrees. The intensity data were collected with Mo Kalpha radiation with lambda = 0.710 69 A. Refinement was by full-matrix least-squares methods to a final R value of 3.80%. Unlike trans-[PtCl(2)(NH(3))(2)], trans-[PtCl(2)(A)(2)] (A = py or pic) complexes do not react with Me(2)SO. The solvolytic products of cis-[PtCl(2)(A)(2)] (A = py or pic) were characterized. Studies of displacement of the sulfoxide by chloride were performed using HPLC. The sulfoxide was displaced faster for the pyridine complex relative to the ammine complex. Chemical studies comparing the reactivity of trans-[PtCl(R'R'SO)(amine)(2)]NO(3) with a model nucleotide, guanosine 5'-monophosphate (GMP), showed that the reaction gave two principal products: the species [Pt(R'R'SO)(amine)(2)(N7-GMP)], which reacts with a second equivalent of GMP, forming [Pt(amine)(2)(N7-GMP)(2)]. The reaction pathways were different, however, for the pyridine complexes in comparison to the NH(3) species, with sulfoxide displacement again being significantly faster for the pyridine case.     

Synthesis, structure, and properties of [RuNO(NH3)4OH][PtCl4] and [RuNO(NH3)4OH][PdCl4]

Double complex [RuNO(NH₃)₄OH][PtCl₄] (I) and [RuNO(NH₃)₄OH][PdCl₄] (II) salts have been prepared and explored with TGA, IR spectroscopy, powder and single crystals X-ray diffraction. Crystal phases of I and II are isostructural (space group Cmc2₁) and have the following crystal chemical characteristics: a = 8.106 Å, b = 18.190(3) Å, c = 8.097 Å, V = 1194.0 ų, Z = 4, ρ_calc = 3.077 g/cm³ (I), and a = 8.116 Å, b = 18.135 Å, c = 8.062 Å, V = 1186.5 ų, Z = 4, ρ_calc = 2.600 g/cm³ (II). The product of thermal decomposition of I in inert and hydrogen atmospheres is a substitution solid solution Pt_0.5Ru_0.5 with the parameter of the FCC unit cell a = 3.856(3) Å. Thermolysis of II affords two-phase mixtures of limited solid solutions of the metals featuring Ru-based HCP and Pd-based FCC cells. __________ Translated from Zhurnal Strukturnoi Khimii, Vol. 48, No.1, pp.114–121, January–February, 2007.     

Cucurbituril binding of trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ and the effect on the reaction with cysteine

The effect of encapsulation by cucurbiturils Q[7] and Q[8] on the rate of reaction of the anti-cancer dinuclear platinum complex trans-[{PtCl(NH3)2}2(micro-NH2(CH2)8NH2)]2+ with the model biological nucleophiles glutathione and cysteine has been examined by NMR spectroscopy. It was expected that the octamethylene linking chain would fold inside the cucurbituril host and hence position the reactive platinum centres close to the cucurbituril portals, and thereby, confer resistance to degradation by biological nucleophiles. The upfield shifts of the resonances from the methylene protons in the linking ligand observed in 1H NMR spectra of the platinum complex upon addition of either Q[7] or Q[8] indicate that the cucurbituril is positioned over the linking ligand, with the Pt(II) centres projecting out of the portal. Furthermore, the relative changes in chemical shift of the methylene resonances suggest that the octamethylene linking chain folds within the cucurbituril cavity, particularly in Q[8]. Simple molecular models, based on the observed relative changes in chemical shift, could be constructed that were consistent with the proposed folding of the linking ligand within the cucurbituril cavity. Encapsulation by Q[7] was found to reduce the rate of reaction of the platinum complex with glutathione. Encapsulation by Q[7] and Q[8] was also found to reduce the rate of reaction of the platinum complex with cysteine, with Q[8] slowing the reaction to a greater extent than Q[7], consistent with the inferred encapsulation geometries. Encapsulation of dinuclear platinum complexes within the cucurbituril cavity may provide a novel way of reducing the reactivity and degradation of these promising chemotherapeutic agents with blood plasma proteins.     

First characterization of the ammine-ammonium complex [(NH4(NH3)4)2(mu-NH3)2]2+ in the crystal structure of [NH4(NH3)4][B(C6H5)4].NH3 and the [NH4(NH3)4]+ complex in [NH4(NH3)4][Ca(NH3)7]As3S6.2NH3 and [NH4(NH3)4][Ba(NH3)8]As3S6.NH3

The compound [NH4(NH3)4][B(C6H5)4].NH3 (1) was prepared by the reaction of NaB(C(6)H(5))(4) with a proton-charged ion-exchange resin in liquid ammonia. [NH(4)(NH(3))(4)][Ca(NH(3))(7)]As(3)S(6).2NH(3) (2) and [NH4(NH3)4][Ba(NH3)8]As3S6.NH3 (3) were synthesized by reduction of As(4)S(4) with Ca and Ba in liquid ammonia. All ammoniates were characterized by low-temperature single-crystal X-ray structure analysis. They were found to contain the ammine-ammonium complex with the maximal possible number of coordinating ammonia molecules, the [NH4(NH3)4]+ ion. 1 contains a special dimer, the [(NH4(NH3)4)2(mu-NH3)2]2+ ion, which is formed by two[NH4(NH3)4]+ ions linked by two ammonia molecules. The H(3)N-H...N hydrogen bonds in all three compounds range from 1.82 to 2.20 A (DHA = Donor-H...Acceptor angles: 156-178 degrees). In 2 and 3, additional H(2)N-H...S bonds to the thioanions are observed, ranging between 2.49 and 3.00 A (DHA angles: 120-175 degrees). Two parallel phenyl rings of the [B(C(6)H(5))(4)](-) anion in 1 form a pi...pi hydrogen bond (C...C distance, 3.38 A; DHA angles, 82 degrees), leading to a dimeric [B(C6H5)4]2(2-) ion.     

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.     

[CrBr2(NH3)4][CrBr4(NH3)2], a new chromium(III) complex

Green single crystals of trans‐tetraamminedibromidochromium(III) trans‐diamminetetrabromidochromate(III), [CrBr₂(NH₃)₄][CrBr₄(NH₃)₂], are found to contain two symmetry‐independent sixfold coordinated Cr^III cations on centres of inversion. The structure is composed of octahedral trans‐[CrBr₂(NH₃)₄]⁺ cations and octahedral trans‐[CrBr₄(NH₃)₂]⁻ anions, and adopts a distorted CsCl‐type lattice. The cations and anions are linked by N—H...Br interactions. This is the first example in which both ions are mixed ammine–bromide Cr^III complexes.     

Reaction of trans-[RuNO(NH3)4(OH)]Cl2 with nitric acid and synthesis of ammine(nitrato)nitrosoruthenium complexes

The reaction of trans-[RuNO(NH₃)₄(OH)]Cl₂ with nitric acid has been studied. Reaction products have been identified by IR spectroscopy, NMR, mass spectrometry, powder and single-crystal X-ray diffraction, and chemical analysis. Synthesis methods have been developed for amminenitrosoruthenium complexes containing outer-sphere and coordinated nitrate ions: trans-[RuNO(NH₃)₄(H₂O)](NO₃)₃ (I), trans-[RuNO(NH₃)₄(NO₃)](NO₃)₂ (II), and fac-[RuNO(NH₃)₂(NO₃)₃] (III). Complex II has two polymorphs: monoclinic and tetragonal. The latter has been studied by X-ray crystallography.     

Speciation of nitrogen - [N(3-)] and [N(2)(2-)] - in binary compounds

The nitrogen content of the binary compounds SrN = Sr(4)[N](2)[N(2)], Sr[N(2)], and Ba[N(2)] (prepared by high-pressure syntheses) was determined analytically by using the carrier gas hot extraction method. For handling of the air- and moisture-sensitive samples, a transfer chamber was constructed to protect the compounds against decomposition before being analyzed. Additionally, it was necessary to develop a method allowing controlled and variable heating of the electrode furnace to get analytical results with high precision and accuracy. By means of a suitable temperature program it was possible not only to verify the existence but also to quantify the two different nitrogen species ([N(3-)] and [N(2)(2-)]), and thus confirm the results of recent neutron diffraction studies.     

Synthesis, characterization and Stat3 inhibitory properties of the prototypical platinum(IV) anticancer drug, [PtCl3(NO2)(NH3)2] (CPA-7)

This paper describes a reinvestigation of the literature concerning the synthesis and structural characterization of the platinum(IV)-based anticancer drug known as CPA-7 and believed to be the compound fac-[PtCl3(NO2)(NH 3)2]. CPA-7 has previously been extensively investigated for its ability to control tumor cell growth by inhibition of Stat3 signaling, but very little information is available concerning its synthesis or spectroscopic properties. A reproducible synthetic route is shown to produce an active material which is characterized by IR and (1)H, (14)N, (15)N, and (195)Pt NMR spectroscopy, and single crystal X-ray crystallography. The freshly prepared drug is obtained as a single isomer which may in fact be fac- or mer-[PtCl3(NO2)(NH3)2], but recrystallization resulted in a disordered crystal containing approximately equal amounts of the two geometric isomers.     

Mechanistic Study on the Monofunctional Binding of Hydrolysis Products of Non-planar Heterocyclic Complexes Trans-[PtCl_2NH_3（piperidine）] and Trans-[PtCl_2（piperidine）_2] to DNA Purine Bases

The monofunctional substitution reactions between trans-[PtCl(H2O)(NH3)(pip)]+,trans-[Pt(H2O)2(NH3)(pip)]2+,trans-[PtCl(H2O)(pip)2]+,trans-[Pt(H2O)2(pip)2]2+ (pip = piperidine) and adenine/guanine nucleotides are explored by using B3LYP hybrid functional and IEF-PCM salvation models. For the trans-[Pt(H2O)2(NH3)(pip)]2+ and trans-[PtCl(H2O)(NH3)(pip)]+ complexes,the computed barrier heights in aqueous solution are 13.5/13.5 and 11.6/11.6 kcal/mol from trans-Pt-chloroaqua complex to trans/cis-monoadduct for adenine and guanine,and the corresponding values are 20.7/20.7 and 18.8/18.8 kcal/mol from trans-Pt-diaqua complex to trans/cis-monoadduct for adenine and guanine,respectively. For trans-[PtCl(H2O)(pip)2]+ and trans-[Pt(H2O)2(pip)2]2+,the corresponding values are 21.5/21.3 and 19.4/19.4 kcal/mol,and 26.0/26.0 and 20.7/20.8 kal/mol for adenine and guanine,respectively. Our calculations demonstrate that the barrier heights of chloroaqua are lower than the corresponding values of diaqua for adenine and guanine. In addition,the free energies of activation for guanine in aqueous solution are all smaller than that for adenine,which predicts a preference of 1.9 kcal/mol when trans-[PtCl(H2O)(NH3)(pip)]+ and trans-[Pt(H2O)2(NH3)(pip)]2+ are the active agents and ～1.9 and ～ 5.3 kcal/mol when trans-[PtCl(H2O)(pip)2]+ and trans-[Pt(H2O)2(pip)2]2+ are the active agents,respectively. For the reaction of trans-Pt-chloroaqua (or diaqua) to cis-monoadduct,we obtain the same transition-state structure as from the reaction of trans-Pt-chloroaqua (or diaqua) to trans-monoadduct,which seems that the trans-Pt-chloroaqua (or diaqua) complex can generate trans-or cis-monoadduct via the same transition-state.     

Theoretical Study of the Mechanism of Nucleophilic Addition of Oximes to trans-[PtCl4(NCCH3)2]

The mechanism of nucleophilic addition of oximes to organic nitriles coordinated to platinum was studied by ab initio methods of quantum chemistry using trans-[PtCl₄(NCCH₃)₂] as an example. It was shown that in the absence of acidic or basic catalysis, the reaction proceeds through the formation of an orientation complex and a 4-membered cyclic transition state, whose decomposition yields the product of oxime addition to the CN bond. To compare and elucidate the reasons for nitrile activation in these complexes, the mechanism of hypothetical addition of formaldoxime to noncoordinated acetonitrile was studied. Calculated values of activation energy and energy effects of the reactions allow one to interpret the activation of nitriles during complexation in terms of the activated-complex model.