Coordination Sphere Of Platinum Research Articles

Molecular Structure and Bonding in Platinum-Picoline Anticancer Complex: Density Functional Study

Density functional study has been performed for a new anticancer agent, cis-[PtCl2(NH3)(2-picoline)] (1), AMD473, now clinically tested. The molecular structure, natural charges, orbital occupancies, vibrational frequencies and metal-ligand stretching force constants were calculated using the modified Perdew-Wang functional (mPW1PW) with the combined D95V(d,p) and LANL2DZ basis set. For comparison, analogous calculations were performed for: cis-[PtCl2(NH3)(3-picoline)] (2), cis-[PtCl2(NH3)(pyridine)] (3) and cisplatin. The interesting structural feature of 1 is almost perpendicular orientation of the 2-picoline ligand with respect to the molecular plane. In the remaining complexes, 2 and 3, the tilt of the pyridine ring is smaller. The position of the methyl group in 1 introduces steric hindrance to an axial approach of the Pt metal. The natural bond analysis (NBO) has provided detailed insight into the electronic donor-acceptor interactions within the platinum coordination sphere. The results clearly indicate that the Pt-N(py) bond is stronger than Pt-NH3 bond, and the Pt-Cl bond trans to 2-picoline is weaker than the cis Pt-Cl bond. Thus, both the trans effect of the 2-picoline ligand and a steric hindrance of Pt in 1 can be of key importance in the different mode of binding of this drug to DNA, in comparison with cisplatin.

Platinum(IV) complex with adamantylamine as nonleaving amine group: synthesis, characterization, and in vitro antitumor activity against a panel of cisplatin-resistant cancer cell lines.

Procedure of the synthesis is described for new platinum(IV) drug LA-12 [(OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV)]. The X-ray diffraction analysis shows that the structure is created by molecules with octahedral arrangement of ligands around a platinum atom and contains one H(2)O molecule that is not a part of the coordination sphere of platinum. This new drug is more reactive with glutathione than cisplatin and is lacking cross-resistance with cisplatin as proven on the panel of cancer cell lines.

Novel apoptosis-inducing trans-platinum piperidine derivatives: synthesis and biological characterization.

The synthesis, chemical characterization, and interaction with cells of new sterically hindered trans- and cis-diaminedichloroplatinum(II) complexes are described. The amine ligands include monofunctional piperidine (pip) and piperazine (pz). The poor solubility of trans-diaminedichloroplatinum complexes was overcome by introducing the positively charged pz ligand, which allows retaining of the classic platinum coordination sphere. In vitro evaluation in OV-1063 and C-26 tumor cells revealed that replacing one NH3 of the inactive transplatin by an aromatic planar ligand (4-picoline, 4-pic) or by an aliphatic nonplanar heterocyclic ligand (pip) or replacing both NH3 groups with a 4-pic ligand and a pip or pz ligand significantly increases the cytotoxic activity of these complexes. The unsymmetric complexes trans-[PtCl2(4-pic)(pip)] and trans-[PtCl2(4-pic)(pz)]HCl were the most cytotoxic compounds against the cisplatin-sensitive tumor cell line C-26 (IC50 = 4.5 and 5.5 microM, respectively) and the cisplatin-sensitive tumor cell line OV-1063 (IC50 = 6.5 and 7.4 microM, respectively). In contrast, replacing one NH3 of the cis isomer by an aromatic planar ligand (4-pic) or by an aliphatic amine lowered their cytotoxiciy in comparison to cisplatin. Cell penetration and Pt-DNA adduct formation were also evaluated, and it was clearly shown that both trans-[PtCl2(4-pic)(pip)] and trans-[PtCl2(4-pic)(pz)]HCl penetrate efficiently the cellular membrane of the tumor cells and platinate the cellular DNA. When comparing cellular DNA platination, positively charged trans-[PtCl2(4-pic)(pz)]HCl was 7-fold higher than both cisplatin and its neutral analogue trans-[PtCl2(4-pic)(pip)]. Moreover, in contrast to cisplatin, in the cell lines used, cell death caused by both complexes appeared to be apoptotic according to several criteria including early phosphatidylserine exposure, activation of caspases, and characteristic morphological changes. Our results suggest that these novel mixed nonclassical trans-Pt(II) complexes are biologically and mechanistically distinct from known Pt complexes and deserve evaluation of their efficacy in tumor-bearing animals.

Sequential Deprotonation of Olefins in the Coordination Sphere of Platinum(II): Occurrence and Synthetic Aspects

The cationic platinum complexes [Pt(η2-alkene)X(tmeda)](ClO4) (1: X = Cl, alkene = propene, 1-butene, 1-hexene; X = NO2, alkene = (E)-2-butene, (Z)-2-butene; tmeda = N,N,N‘,N‘-tetramethylethylenediamine) smoothly react with triethylamine to undergo loss of one allylic proton of the alkene ligand and formation of the η1-allyl species [Pt(η1-allyl)X(tmeda)] (2). In the case of 1-butene and 1-hexene, the η1-allyl species containing a nonterminal olefinic function (X(tmeda)PtCH2CHCHR, R = Me, Pr) undergoes release of the X ligand and η1 → η3 rearrangement of the allyl to form [Pt(η3-allyl)(tmeda)]+ (3). The reaction is stereoselective, and the R substituent is always found syn to the central hydrogen of the allyl group; however, in solution, a partial isomerization of the syn into the anti form slowly takes place. In the case of propene and (E)- and (Z)-2-butene the terminal olefinic function of 2, [X(tmeda)PtCHRCHCH2], can displace the η2-alkene from a second molecule of 1 to form the η1:η2-allyl-bridged di...

The Kinetics of Substitution Reactions of Mixed Platinum(II)-Bis(nucleoside) Complexes in Aqueous Solution in the Presence of Thiourea; X-Ray Crystal Structure Determination ofcis-[Pt(NH3)2(adenosine-N7)2](ClO4)2⋅3.5 H2O

In aqueous solution, bis(nucleoside) complexes formed by the reaction of cis-[Pt(NH3)2(H2O)2]2+ with an excess of either adenosine (ado) or a mixture of adenosine and guanosine (guo) undergo a slow N7--> N1 linkage isomerisation in the adenine moiety. The isomerisation probably involves the breaking and reformation of Pt-nucleoside bonds, thus favouring the more stable N1 binding mode of the adenine base. Dynamic processes due to the presence of adenosine in the platinum coordination sphere are slow on the NMR time scale. The N7 binding mode of PtII in cis-[Pt(NH3)2(ado-N7)2](ClO4)2. 3.5H2O was confirmed by X-ray crystal structure analysis. In both of the crystallographically independent cations, the PtII coordination sphere is almost ideally square planar, with typical Pt-N bond lengths and angles. The most significant difference between the two cations lies in the sugar conformation of the coordinated nucleosides. In one cation, both have an anti (-ap) conformation, whilst in the other cation one has an anti (-ap) conformation and the other a syn (+sc) conformation stabilised by a relatively strong H-bond. Substitution of the nucleoside(s) by thiourea follows an associative mechanism with only a negligible contribution by the solvent path. For symmetric complexes, the order of lability of different binding modes is ado-N1 <guo-N7 < ado-N7 for substitution of the first nucleoside, whereas for the second nucleoside it is guo-N7 < ado-N1 < ado-N7. For asymmetric complexes, the concomitant cleavage of different PtII-nucleoside bonds can be explained by two parallel reaction pathways. The change in the PtII coordination sphere affects the lability of the coordinating nucleosides in a different manner. The ado-N1 binding mode renders all binding modes less labile, whereas the ado-N7 mode has the opposite effect, and the guo-N7 mode increases the lability of the ado-N1 mode but decreases that of the ado-N7 mode. The mixed-ligand complex with (ado-N7)(guo-N7) mode is far more susceptible to attack by thiourea than the symmetric (guo-N7)2 species. These two species can be considered as models for the two most abundant Cisplatin-DNA adducts.

Synthesis and characterization of [PtMe3L(H2O)]BF4·H2O (L=3-O-acetyl-1,2-O-isopropylidene-α-D-glucofuranose)

Reaction of [PtMe3(Me2CO)3]BF4 (1) with 3-O-acetyl-1,2;5,6-di-O-isopropylidene-α-D-glucofuranose in acetone affords [PtMe3L]BF4 (2) (L=3-O-acetyl-1,2-O-isopropylidene-α-D-glucofuranose). In wet methylene chloride, complex2 transforms to [PtMe3L(H2O)]BF4·H2O (3). Complex3 was characterized by microanalysis and NMR spectroscopy (1H,13C,195Pt). The X-ray structure analysis (monoclinic, P21, a=10.529(3) A, b=7.322(2) A, c=14.668(4) A, Z=2) reveals that 3-O-acetyl-1,2-O-isopropylidene-α-D-glucofuranose acts as a neutral bidentate ligand which is coordinated via two hydroxyl groups (κ2O5,6 coordination). The five-membered 1,3,2-dioxaplatina rings exhibit an envelope conformation. The coordination sphere of platinum is completed by H2O ligand.

Synthesis, structure and reactivity of N,O-metallacyclic (dicarbonyldiazene) platinum complexes

Reaction of cis-Pt(PR13)2Cl2 (R1=Me, Ph) with diacyl hydrazine R2OCNHNHCOR2 (R2=Me, Ph) in refluxing ethanol and NaHCO3 afforded platinum diazene diacyl complexes Pt(PR13)2(R2OCNNCOR2) (1, R1=R2=Ph; 3, R1=Me, R2=Ph; 4, R1=R2=Me). Reaction of Pt(PPh3)2(C2H4) with diazene dicarboxylates R2OCNNCOR2 (R2=OEt, OPri) resulted in the formation of Pt(PPh3)2(R2OCNNCOR2) (2, R2=OEt; 5, R2=OPri). Multinuclear NMR spectroscopy on 1–5 revealed that the dicarbonyl-substituted diazene ligand is coordinated asymmetrically, consistent with a five membered Pt–N–N–C–O ring. Compound 5 crystallises from THF–benzene as the solvate Pt(PPh3)2(PriO2CNNCO2Pri)·(C6H6)2; its X-ray crystal structure shows that the coordination sphere of platinum is essentially square planar and coplanar with the five membered Pt1–O1–C5–N2–N1 ring. The Pt1–O1 distance is 2.027(4) Åand the Pt1–N1 distance is 2.050(5) Å. The N1–N2 distance is 1.421(6) Åwhile the N2–C5 and C5–O1 distances are 1.273(7) and 1.314(7) Å, respectively. Complexes 1–5 show sensitivity towards chlorinated solvents (CH2Cl2, CHCl3) under photolysis conditions, forming the corresponding cis-platinum bis(phosphine) dichloride complexes; the same products are formed in a slower thermal reaction with 2 and 5. Complexes 2 and 5 react photochemically with ethylene in [2H8]THF yielding Pt(PPh3)2(C2H4) but 1, 3 and 4 are inert. Addition of an excess of dppe ligand to 2 and 5 resulted in the displacement of PPh3 and the formation of Pt(dppe)(EtO2CNNCO2Et) and Pt(dppe)(PriO2CNNCO2Pri) [dppe=1,2-bis(diphenylphosphino)ethane].

Synthesis, characterization, cytotoxic, and DNA binding studies of some platinum(II) complexes of 1,2-diamine and α-diimine with 2-pyridinecarboxylate anion

Seven new water-soluble cationic complexes of general formula [Pt(2-pyc)(NN)] + (where NN is 2NH 3, ethylenediamine (en), 1,2-diaminopropne (1,2-dap), 1,3-diaminopropane (1,3-dap), (±) trans-1,2-diaminocyclohaxane (dach), 2,2′-dipyridylamine (dpa) or 1,10-phenanthroline (phen), and 2-pyridinecarboxylate anion) have been prepared. These complexes have been characterized by conductance measurements, and by ultraviolet-visible, infrared (IR), and 1H nuclear magnetic resonance (NMR) spectroscopy. The COSY (correlated spectroscopy) spectra of [Pt(2-pyc)(dpa)] + and [Pt(2-pys)(dpa)] + further support the structures of the above complexes with three nitrogen and one oxygen donor atoms in the first coordination sphere of platinum(II) with 1,2-diamine or α-diimine and 2-pyridinecarboxylate anion behaving as bidentate ligands. One of the compounds, [Pt(2-pyc)(dpa)]Cl, also shows a birefringence property in water. These compounds inhibit the growth of P388 lymphocytic leukemia cells. [Pt(2-pyc)(dpa)] + shows I.D. 50 value comparable to cisplatin. However, six other complexes show higher I.D. 50 values than cisplatin. In addition, the inhibition studies also suggest that their target is DNA. Therefore, the interactions of four of the above complexes with calf thymus DNA have been studied by ultraviolet and fluorescence spectral methods. These studies suggest that [Pt(2-pyc)(NH 3) 2] + and [Pt(2-pyc)(1,2-dap) + bind to DNA by noncovalent interactions. On the other hand, [Pt(2-pyc)(dpa)] + and [Pt(2-pyc)(phen)] + bind to DNA by covalent monofunctional binding. The latter two complexes have also been interacted with PUCl9 DNA. The gel electrophoresis studies of these interactions suggest that these complexes bind to DNA, and this binding leads to a conformational change in DNA.

Synthesis and characterization of bifunctional trans-(Ph 3P) 2Pt(CO 2Me)(X) complexes

A series of trans-(Ph 3P) 2Pt(X)(Y) complexes (X = CO 2Me or CO; Y = CO 2Me, CO, OMe, OTf) has been prepared in order to determine the compatibility of electrophilic (CO, CO 2Me) and nucleophilic (OH, OMe) ligands in the same platinum coordination sphere. Dealkoxylation of CO 2Me complexes by trimethylsilyl triflate affords the corresponding cationic carbonyl derivatives, and represents a potentially useful metalloester deprotection method for controlling the formatioon of dimetalloester linkages. The crystal structure of [ trans-(Ph 3P) 2Pt(CO 2Me)(CO)]BF 4 has been determined, and reveals an unusual distortion of the PPtP angle perpendicular to the square planar coordination geometry. Attempted condensation reactions between trans-(Ph 3P) 2Pt(CO 2Me)(CO) + and trans-(Ph 3P) 2Pt(CO 2Me)(OH) did not yield a dimetalloester condensation product, presumably due to the steric bulk of the ancillary Ph 3P ligands.

Thermal dimerization of 1-substituted-3,4-dimethylphospholes within the coordination sphere of platinum(II)

The thermolyses of dihalobis (1 -substituted-3,4-dimethylphosphole)platinum(II) complexes were investigated in 1,1,2,2-tetrachloroethane solutions at 145 o C and in the crystalline state at 140 o C. Three types of species were formed: (1) [4+2] cycloaddition products, (2) [2+2] cycloaddition products, and (3) compounds that result from 1,5-hydrogen migration from a methyl group on one phosphole to the β-carbon of an adjacent phosphole (exomethylene). Kinetic studies suggest that the reaction mechanisms are the same in both the solid and solution states

(1,1-Cyclobutanedicarboxylato-O,O')bis(trimethylphosphine-P)platinum(II) monohydrate

The coordination around platinum is conventional square planar. The cyclobutane ring and the platinum coordination sphere are almost perpendicular to each other. The lattice contains water molecules though the crystals were grown from a cyclohexanol solution. Atom O(5) of the water molecule forms hydrogen bonds with the carboxylato O atoms O(4) and O(3'), respectively; the structure of the compound consists of one-dimensional polymeric chains

Unusual dehydrogenation of a diethylenetriamine ligand to a Schiff base ligand in the co-ordination sphere of platinum(IV)

Trans,mer-[(OH)2(dien)Pt(N-3-1 mec)](ClO4)2, (2), (dien = diethylenetriamine, C4H13N3; 1 mec = 1-methylcytosine, C5H7N3O) is, on warming in H2O, pH ca. 2–6, converted to several products, including the corresponding sym-fac, cis-isomer (4) and a PtII compound [(C4H11N3)Pt(N-3-1 mec)](ClO4)2, (3), which contains the tridentate Schiff base ligand NH2–CH2–CHN–CH2–CH2–NH2.

EXAFS studies of bimetallic [formula omitted] and [formula omitted] catalysts in the first stages of preparation, drying, and calcination

EXAFS (extended X-ray absorption fine structure) measurements have been applied to highly dispersed bimetallic Pt-(Re or Rh)/alumina catalysts in the first stages of their preparation, drying and calcination. In order to understand the role played by the second metal, different (Re or Rh) Pt ratios have been considered. In both systems, as early as the drying step, we observed a large substitution of chlorine by oxygen atoms in the first coordination sphere of platinum, ex H 2PtCl 6. These oxygens are attributed to the alumina carrier and the detailed analysis of the absorption signal, in particular for the PtRh case, leads to the conclusion that anchoring sites of different strength exist at the surface of the carrier. Their respective relations with the various metals loadings and atomic ratios are discussed.

Displacement reactions of cis-[Pt IICl(R′SCSO)(PR 3) 2] (R = Ph, C 6H 11; R′ = aryl) with nucleophiles. Formation with R′S − of an η 2-CS coordinated sulphine (R′S) 2CSO by reductive coupling [1

A cyclic process to synthesize sulphines in the coordination sphere of platinum has been tested by stepwise reactions. Step i: The Cl atoms in the metallo-sulphines cis-[Pt IICl(R′SCSO)(PR 3) 2] (R = Ph, C 6H 11; R′ = p-MeC 6H 4) were displaced by R″S − (R″ = p-MeC 6H]4, p-MeOC 6H 4) leading to the metallo-sulphines cis-[Pt II(SR″)(R′SCSO)(PR 3) 2], with only ( E)-( Z) isomerization being found and no scrambling between R′S and R″S groups. Step ii: These metallo-sulphines in the case of R = C 6H 11 were not detected, they are unstable because of the steric interaction between the bulky co-ligands and undergo immediate CS reductive coupling forming the η 2-CS coordinated sulphine compounds [Pt 0{P(C 6H 11) 3} 2{(R″S)(R′S)CSO}]. Step iii:These latter η 2-CS coordinated sulphines could be displaced by (E)-(R′S)ClCSO forming the highly unstable η 2-CS compound [Pt 0{P(C 6H 11) 3} 2{(E)-(R′S)-ClCSO}] which undergoes an immediate CCl oxidative addition and reforms the starting metallo-sulphine cis-[Pt IICl(R′SCSO){P(C 6H 11) 3} 2] ( Step iv).Two complications prevent this cyclic process becoming a catalytic cycle: ( i) slow cis-to- trans isomerization of the metallo-sulphines cis-[Pt IICl(R′SCSO){P(C 6H 11) 3} 2] and ( ii) decomposition during the sulphine displacement ( Step iii). Test reactions showed that the sulphine (R′S) 2CSO is formed faster via direct displacement in ( E)-(R′S)ClCSO by R″S − than by the cyclic process. When the bidentate ligand Et 2NCS − 2 is used as displacing ligand dissociation of one PR 3 group is initiated instead of CS reductive coupling, forming the metallo-sulphines [Pt III(S 2CNEt 2)(R′SCSO)(PR 3)].

Reactions of alkynyl- and alkenylplatinum(II) compounds. 1. Formation of alkoxycarbene ligands within the coordination sphere of platinum

Reactions of alkynyl- and alkenylplatinum(II) compounds. 1. Formation of alkoxycarbene ligands within the coordination sphere of platinum