Trans Chelation Research Articles

Beyond Common Metal-Metal Bonds, κ3 -Bis(donor)ferrocenyl→Transition-Metal Interactions.

Ligands with 1,1'-bis(donor)ferrocene motif are capable of a wide range of binding modes, including the trans chelation mode in which there is a Fe-M interaction (κ3 -D,Fe,D), in the form of a dative Fe→TM bond (TM=transition metal). This Minireview will explore the nature of this Fe-TM interaction thorough select examples as well as how to characterize a Fe→TM dative bond using physical, computational, and spectroscopic techniques.

Reactivity of the [M(PS)2](+) building block (M = Re(III) and (99m)Tc(III); PS = phosphinothiolate) toward isopropylxanthate and pyridine-2-thiolate.

The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2-thiolate (PyS) toward the [M(PS)2](+) moiety (M = Re and (99m)Tc; PS = phosphinothiolate) were investigated. Synthesis and full characterization of [Re(PS2)2(i-Pr-Tiox)] (Re1), [Re(PSiso)2(i-Pr-Tiox)] (Re2), [Re(PS2)2(PyS)] (Re3), and [Re(PSiso)2(PyS)] (Re4), where PS2 = 2-(diphenylphosphino)ethanethiolate and PSiso = 2-(diisopropylphosphino)ethanethiolate, and the structural X-ray analysis of complex Re3 were carried out. (99m)Tc analogues of complexes Re2 ((99m)Tc2) and Re4 ((99m)Tc4) were obtained in high radiochemical yield following a simple one-pot procedure. The chemical identity of the radiolabeled compounds was confirmed by chromatographic comparison with the corresponding rhenium complexes and by dual radio/UV HPLC analysis combined with ESI(+)-MS of (99g/99m)Tc complexes prepared in carrier-added conditions. The two radiolabeled complexes were stable with regard to trans chelation with cysteine, glutathione, and ethylenediaminotetraacetic acid and in rat and human sera. This study highlights the substitution-inert metal-fragment behavior of the [M(PS)2](+) framework, which reacts with suitable bidentate coligands to form stable hexacoordinated asymmetrical complexes. This feature makes it a promising platform on which to develop a new class of Re/Tc complexes that are potentially useful in radiopharmaceutical applications.

A Versatile Diphosphine Ligand: cis and trans Chelation or Bridging, with Self Association through Hydrogen Bonding

The diphosphine ligand, N,N'-bis(2-diphenylphosphinoethyl)isophthalamide, dpipa, contains two amide groups and can form cis or trans chelate complexes or cis,cis or trans,trans bridged complexes. The amide groups are likely to be involved in intramolecular or intermolecular hydrogen bonding. This combination of properties of the ligand dpipa leads to very unusual structural properties of its complexes, which often exist as mixtures of monomers and dimers in solution. In the complex [Au2(μ-dpipa)2]Cl2, the ligands adopt the trans,trans bridging mode, with linear gold(I) centers, and the amide groups hydrogen bond to the chloride anions. In [Pt2Cl4(μ-dpipa)2], the ligands adopt the cis,cis bridging mode, with square planar platinum(II) centers, and the amide groups form intermolecular hydrogen bonds to the chloride ligands to form a supramolecular one-dimensional polymer. Both the monomeric and dimeric complexes [PtMe2(dpipa)] and [Pt2Me4(μ-dpipa)2] have cis-PtMe2 units with cis chelating or cis,cis bridging dpipa ligands respectively; each forms a supramolecular dimer through hydrogen bonding between amide groups and each contains an unusual NH···Pt interaction. An attempted oxidative addition reaction with methyl iodide gave the complex [PtIMe(dpipa)], which contains trans chelating dpipa, while a reaction with bromine gave a disordered complex with approximate composition [Pt2Me3Br5(μ-dpipa)2], which contains trans,trans bridging dpipa ligands.

Interaction between Platinum Complexes and the C-Terminal Motif of Human Copper Transporter 1

Human copper transporter 1 (hCTR1) facilitates the cellular uptake of cisplatin, and the extracellular N-terminal domain has been proven to coordinate to platinum drugs. It has been reported that the intracellular C-terminal motif is crucial for the function of hCTR1 in cisplatin influx. In this work, we conduct reactions of the intracellular motif with platinum drugs. The octapeptide from the C-terminal domain of hCTR1 is used, and the reactions are investigated using ultraviolet, high-performance liquid chromatography, electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy. Results show that the C8 peptide is highly reactive to cisplatin and oxaliplatin, and the -HCH sequence is the most favorable binding site of platinum agents. Cisplatin first binds to the cysteine residues in the reaction with the C8 peptide. The ammine ligand, even trans to a thiol ligand, can remain coordinated in platination adducts for a >12 h reaction. Intramolecular platinum migration was observed in the C8 peptide, and the ammine ligands remain coordinated to platinum during this process. This result indicates that hCTR1 can transfer cisplatin in the active form through a trans chelation process. These findings provide insight into the mechanism of the C-terminus of hCTR1 in the transfer of platinum drugs from the trimeric pore of hCTR1 to the cytoplasm.

Mono- and Dinuclear Ag(I), Au(I), and Au(III) Metallamacrocycles Containing N-Heterocyclic Dicarbene Ligands

Ag(I) dicarbene complexes [Ag(m)(L(n))m]X(m) (L(n) = Im(Me)(CH2)(n)Im(Me), Im(Me) = N-methylimidazol-N-yl-2-ylidene; n = 3, X = PF6, m = 2; n = 6-8, 10, X = AgBr2, m = 1, 2) were prepared by reacting Ag2O with 1 equiv of the corresponding bisimidazolium salt [H2L(n)]A2 (A = PF6, Br). The dibromoargentates react with 1 equiv of AgTfO to afford [Ag(m)(L(n))m](TfO)m (m = 1, 2). The room temperature transmetalation reaction of [Ag(m)(L(n))m][AgBr2]m (n = 3, 5, 6-8, 10) with [AuCl(SMe2)] and AgTfO (L(n):Au:TfO = 1:1:1) affords [Au2(μ-L(n))2](TfO)2 (n = 3, 5, 10), or mixtures of [Au(κ(2)-L(n))]TfO (main product for n = 7) and [Au2(μ-L(n))2](TfO)2 (main product for n = 6, 8). At room temperature, the equilibrium between [M2(μ-L(n))2](TfO)2 and [M(κ(2)-L(n))]TfO is fast for M = Ag, but slow for M = Au, in the NMR time scale. When n ≥ 7 and M = Ag or Au, the equilibrium is shifted toward the mononuclear complexes in the order 8 > 10 > 7, which proves that the (CH2)8 linker has the optimal length for trans chelation. Correspondingly, the high-temperature metalation of [H2L(n)]Br2 (n = 8, 10) with 1 equiv of [AuCl(SMe2)] and excess of NaAcO, affords [Au(κ(2)-L(n))]Br with a small amount of [Au2(μ-L(n))2]Br2. If AgTfO is added to the reaction mixture, [Au(κ(2)-L(8))]2[AgBr3] is isolated instead of the desired triflate, which can be obtained by reacting the mixture of [Au(κ(2)-L(8))]Br and [Au2(μ-L(8))2]Br2 with AgTfO. [Au(κ(2)-L(10))]TfO was isolated after thermal conversion of [Au2(μ-L(10))2](TfO)2. [Au(κ(2)-L(8))]TfO reacts with I2 to give trans-[AuI2(κ(2)-L(8))]TfO, which is the first Au(III) complex containing a trans-spanning bidentate ligand. We have determined the crystal structures of complexes [Ag2(μ-L(3))2](PF6)2, [Ag(κ(2)-L(7))]TfO, [Au2(μ-L(3))2](TfO)2, [Au(κ(2)-L(8))]Br, [Au(κ(2)-L(8))]2[AgBr3], and trans-[AuI2(κ(2)-L(8))]TfO.

Trans-bis[N-(2-hydroxyethyl)ethylenediamine-kappa2N,N']bis(isothiocyanato-kappaN)nickel(II).

The crystal structure of the title compound, [Ni(NCS)2(C4H12N2O)2], has two crystallographically independent half-mol­ecules in the asymmetric unit, with each Ni atom residing on a centre of symmetry. The two mol­ecules exhibit similar coordination geometry but display differences with regard to other structural features. Each NiII centre is octahedrally coordinated by two mutually trans chelating hydroxy­ethyl­ethyl­ene­di­amine ligands and two mutually trans iso­thio­cyanate ions. The two independent mol­ecules form chains through different types of non-covalent interactions. In the case of one of the mol­ecules, only NCS and free OH groups participate in hydrogen bonding, while in the chain based on the second mol­ecule, the NCS, NH, NH2 and free OH groups are involved in intermolecular hydrogen bonding. The two chains interact with one another through hydrogen bonding, forming planar sheets. The third packing direction is mediated only by van der Waals interactions.

The presence of lead decreases the availability of meso-2, 3-dimercaptosuccinic acid for analysis in the monobromobimane assay.

meso-2,3-Dimercaptosuccinic acid is a suitable chelating agent for routine pharmacotherapy of lead poisoning in children. Administration of meso-2,3-dimercaptosuccinic acid presumably permits complexation of lead in vivo, allowing excretion through urine or feces. Quantification of the lead is achieved independently from the analysis of meso-2,3-dimercaptosuccinic acid and metabolites from the monobromobimane assay. To date, no direct chemical characterization of the Pb species excreted in urine has been successful. Pharmacokinetic correlation of lead excretion with excretion of meso-2,3-dimercaptosuccinic acid and metabolites has been utilized as an indirect method to draw conclusions regarding the identity of the active chelating agent. In this study, we hypothesized that the Pb-coordinated thiols are not reactive with respect to monobromobimane, and thus, the active chelator contained in the lead complex escapes detection. We performed variations of the assay and found that (1) the fluorescence detector response for the meso-2,3-dimercaptosuccinic acid-monobromobimane adduct was clearly attenuated as a function of added Pb, (2) when meso-2, 3-dimercaptosuccinic acid and monobromobimane were mixed prior to the addition of lead, the lead had no effect on detector response, (3) the addition of dithiothreitol does not affect the ability of Pb to react with meso-2,3-dimercaptosuccinic acid and verifies that oxidation of meso-DMSA had not occurred, and (4) the addition of ethylenediaminetetraacetic acid to the assay reverses the result found in point 1, presumably through trans chelation of the Pb-DMSA complex. Indirect quantification of the Pb-DMSA complexes found in urine might be accomplished through modification of the standard monobromobimane assay for analysis of meso-2,3-dimercaptosuccinic acid.

Styrene-7,8-oxide exposure in the reinforced plastics industry

The dithioether, 1,12-bis(phenylthio)dodecane (dpd) reacts with tetrachloropalladate(II) and tetrachloroplatinate(II) in ethanol/dichloromethane to form trans-[M(dpd)Cl2] (M  Pd, Pt); trans-[Pd(dpd)Br2] has also been isolated. These are the first reported complexes which contain a trans-chelating bidentate ligand involving sulphur donors and is thus further evidence that bulky terminal substituents are not a prerequisite for trans chelation.

Retardation effect of trimethyl phosphite on chelate ring closure of 2,2′-bipyridine (bipy) in cis-[W(CO)4{P(OMe)3}(bipy)

In order to study the effect of a donor ligand on the chelate ring-closure reaction of a diimine ligand co-ordinated in monodentate fashion, cis-[W(CO)4{P(OMe)3}(bipy)] was synthesised from [W(CO)5{P(OMe)3}] and 2,2′-bipyridine (bipy) by using a newly developed method and characterized by means of IR and NMR spectroscopies. The complex was found to undergo neither cis→trans isomerization nor chelation thermally up to 150 °C. However the ring-closure reaction occurs photochemically. Thus irradiation of the complex yielded fac-[W(CO)3{P(OMe)3}(bipy)] which was also isolated and characterized. The extraordinary retardation effect of trimethyl phosphite on the ring-closure reaction of the 2,2′-bipyridine ligand is attributed to the reduction in substitution lability of the CO groups in the complex upon introduction of the phosphite donor ligand.

Synthesis and crystal structure of trans-bis(N,N-dibutyl-N′-naphthoylthioureato) platinum(II). First example of trans chelation of N,N-dialkyl-N′-acylthiourea ligands

N,N-Dibutyl-N′-naphthoylthiourea (HL1) reacted with [PtCl4]2– to yield a mixture of cis-(85%) and trans-[PtL12](15%); the crystal structure of the latter has been determined and represents the first example of trans chelation of N,N-dialkyl-N′-acylthiourea ligands.

Synthesis and Molecular Structure of trans-PdCl2{o-Ph2PC6H4CH2O-(CH2)3-2-C5H4N}. The First Transition Metal Complex Containing trans Coordinating Bidentate Pyridyl-phosphine Ligand

Abstract As the first example of a crystallographically confirmed transition metal complex with a bidentate hybrid ligand spanning trans positions, the square-planar palladium(II) complex containing the trans chelating pyridyl-phosphine bidentate hybrid ligand, bound through a pyridine and a phosphine, trans-PdCl2{o-Ph2PC6H4CH2O(CH2)3-2-C5H4N}, is prepared and the crystal structure was determined.

Synthesis, characterisation and structure of square-planar palladium(II) complexes with phosphine–pyridine hybrid ligands o-Ph2PC6H4CH2O(CH2)nC5H4N-2 (n= 1–3). Isolation of the first transition-metal complex with a trans-chelating bidentate PN ligand

The reaction of Na2[PdCl4] or [PdCl2(PhCN)2] with an equimolar amount of new bidentate hybrid ligands having a P and a N donor atom capable of trans chelation, o-Ph2PC6H4CH2O(CH2)nC5H4N-2 (n= 1–3), gave mainly the 1 : 1 complex [PdCl2{o-Ph2PC6H4CH2O(CH2)nC5H4N-2}]. Depending on the length of the backbone connecting the phosphino and the pyridyl groups, cis- or trans-co-ordinated complexes were mainly formed; when n= 1 the cis complex 1 was formed, but the ligands with longer bridges gave the trans complexes 2 and 3 respectively as the main products. From the reaction of the palladium(II) complex with o-Ph2PC6H4CH2O(CH2)nC5H4N-2 (n= 2 or 3) the trinuclear complexes [Pd3Cl6{o-Ph2PC6H4CH2O-(CH2)nC5H4N-2}2]4(n= 2) and 5(n= 3) were also obtained as minor products and the cis-chelated complexes analogous to 1 could not be isolated. The reaction of Na2[PdCl4] with 2 equivalents of o- Ph2PC6H4CH2O(CH2)3C5H4N-2 gave quantitatively the 1 : 2 complex trans-[PdCl2{o-Ph2PC6H4CH2O-(CH2)3C5H4N-2}2]7 in which the ligand is bound only through the P atom. This complex is in equilibrium with the trans 1 : 1 complex 3 in solution, dissociating one molecule of the ligand (Keq= 5.6 × 10–3 mol dm–3, 35 °C). On heating in CH2Cl2-tetrahydrofuran or diethyl ether, 3 partially isomerised to the dinuclear complex [Pd2Cl4{µ-o-Ph2PC6H4CH2O(CH2)3C5H4N-2}2]6, in which the hybrid ligands act as bridges. The crystal structures of 1, 3 and 6 were determined; 3 is the first example of a transition-metal complex with a trans-spanning chelate phosphine-pyridine hybrid ligand. The reaction of the ligand o-Ph2PC6H4CH2-O(CH2)3C5H4N-2 with K2[PtCl4], in contrast to the palladium complexes, always gave the 1 : 2 complex trans-[PtCl2{o-Ph2PC6H4CH2O(CH2)3C5H4N-2}2]8 in good yield regardless of the ligand: Pt ratio. It did not dissociate in solution and the trans-chelated complex analogous to 3 could not be isolated even from the reaction of K2[PtCl4] with an equimolar amount of the ligand o-Ph2PC6H4CH2O(CH2)3C5H4N-2.

Trans chelation in transition-metal complexes: synthesis and characterization of palladium(II) complexes of bis(diphenylarsino)alkanes

Preparation de Ph 2 As(CH 2 ) n AsPh 2 (n=6, 12, 16) et des complexes PdLX 2 (X=Cl, Br, I, CNS; n=6, 8, 10, 12, 16) et PdLCl 2 (n=7, 9, 11). Spectres RMN et IR

Platinum metal complexes of the methoxyphenylstibines Ph 3-nSb(o-MeOC 6H 4) n (n = 1, 2, 3,)o-Me 2SbC 6H 4OMe and of Me 2Sb(CH 2) 2O(CH 2) 2O(CH 2) 2SbMe 2

The stibine-ether Me 2Sb(o-C 6H 4OMe) (L) forms cis-[PdL 2Cl 2], cis-[PtL 2Cl 2], fac-[RhL 3Cl 3] and mer-[IrL 3Cl 3] which contain the ligand bonded only through antimony, and [RhL 2Cl 3] which contains one monodentate (Sb-coord) and one cheating (Sb- O) ligand. The latter complex reacts with CO to give [RhL 2(CO)Cl 3]. The Ph 3-nSb(o-C 6H 4OMe) n (n = 1, 2, 3) form only mer-[RhL 3Cl 3] and mer-[IrL 3Cl 3]. For Pd(II) and Pt(II) the [ML 2Cl 2] complexes are trans when L = Sb(o-C 6H 4OMe) 3, but cis with L = Ph 2Sb(o-C 6H 4OMe). The potentially tetradentate Me 2Sb(CH 2) 2O(CH 2) 2O(CH 2) 2SbMe (L′), behaves as a trans chelating bidentate in [PdL′Cl 2], and coordinates only via the antimony. The preparations of RhL′Cl 3, IrL′Cl 3, RuL′(CO)Cl 2 and (OsCl 4) 2L′·H 2O are described. Infrared, electronic and 1H NMR spectra are reported for all the complexes.

Trans-chelation in transition metal complexes: Synthesis and characterization of platinum(II) complexes of bis(disphenylarsino)alkanes

Cis and trans complexes of the type Pt(ligand)Cl 2 (ligand = Ph 2As(CH 2) nAsPh 2, n = 6–12, 16) have been synthesized, together with the bromo, iodo and thiocyanato derivatives for n = 10 and 12. The cis complexes are essentially dimeric. The complexes have been characterized by elemental analyses, infrared and proton NMR spectroscopy, solid state reflectance and visible/UV spectroscopy and vapor phase osmometry. Formation of the cis or trans isomer for the complexes Pt(ligand)Cl 2 is critically dependent on the choice of complex precursor: potassium tetrachloroplatinate(II) yields the cis isomer, whilst Zeise's salt gives the trans isomer. The bromo, iodo and thiocyanato derivatives prepared via an exchange reaction give cis complexes. Evidence is presented for the existence of PtNCS and PtSCN linkages both in the solid state and in solution for the thiocyanato derivatives. Product distribution and stereochemistry in all of the complexes are discussed in terms of the factors governing trans chelation.

Trans-chelation of the dithioehter, 1,12-bis(phenylthio)-dodecane to planar palladium(II)

The dithioether, 1,12-bis(phenylthio)dodecane (dpd) reacts with tetrachloropalladate(II) and tetrachloroplatinate(II) in ethanol/dichloromethane to form trans-[M(dpd)Cl 2] (M  Pd, Pt); trans-[Pd(dpd)Br 2] has also been isolated. These are the first reported complexes which contain a trans-chelating bidentate ligand involving sulphur donors and is thus further evidence that bulky terminal substituents are not a prerequisite for trans chelation.