Search

A chiral, isomeric series of novel boron-rich Pt(II) metallointercalators ([PtL2(phen)](NO3)2: L = (x)-(1,y-closo-carboran-1-yl)pyrid-z-ylmethanol: x = R, S; y = 7, 12; z = 3, 4) wre prepared and fully characterized. By means of variable-temperature NMR spectroscopy, different combinations of Δ-head-to-tail, head-to-head, and Λ-head-to-tail rotamers were identified, and the free energies of activation for Pt-N bond rotation were determined for the pyrid-4-yl complexes with ΔG(‡)307 = 16.1 ± 0.3 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,7-carboranyl derivative and ΔG(‡)307 = 16.4 ± 0.5 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,12-carboranyl derivative. The corresponding 2:1 host-guest β-cyclodextrin (β-CD) adducts ([PtL2(phen)·2β-CD](NO3)2) were also prepared and fully characterized by high resolution electrospray ionization mass spectrometry and 2D-(1)H{(11)B} nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy NMR experiments. The interaction of the novel supramolecular adducts with calf thymus DNA was investigated by means of linear dichroism, ultraviolet-visible spectroscopy, thermal denaturation, and isothermal titration calorimetry experiments which revealed a bimodal binding regime with DNA intercalation favored at low [drug]/[DNA] ratios, while at higher drug loading, surface aggregation was observed. Furthermore, the data were also consistent with some degree of dissociation of the β-CD host-guest adducts upon DNA binding. When we used a single binding-site model, interpreted as a weighted average of all of the possible equilibrium interactions, the compounds showed high affinity for ct-DNA with K(assoc) ranging from (1.3 ± 0.1) × 10(5) M(-1) to (5.7 ± 0.4) × 10(5) M(-1). In general, the overall DNA-binding behavior was enthalpically driven with a minor or unfavorable entropic component, which is consistent with the thermodynamics of an intercalation-dominated process. A higher degree of DNA intercalation was observed for the R-isomer in the pyrid-3-yl compounds, and the opposite trend was observed in the case of pyrid-4-yl derivatives.

A series of novel platinum(II)-2,2':6',2' '-terpyridine (trpy) complexes containing (thioalkyl)dicarba-closo-dodecaborane(12) (closo-carborane) derivatives were prepared by treatment of the labile precursor species [Pt(MeCN)(trpy)](OTf)2 with R(CH2)nSH (R = closo-1,2-carborane, n = 0-3; R = closo-1,7-carborane, n = 1; R = closo-1,12-carborane, n = 1) in the presence of NEt3 to afford brightly colored complexes of the type [PtS(CH2)nR(trpy)]OTf. All products were characterized by means of multinuclear (1H, 13C, 11B, and 195Pt) 1D- and 2D-NMR spectroscopy, ESI-MS, and, for the 1,7-carborane derivative, X-ray crystallography. Preliminary in vitro cytotoxicity studies of selected complexes against human ovarian carcinoma cells are also reported.

The first examples of DNA metallointercalators containing a dicarba-closo-dodecaborane(12) (carborane) moiety are presented. Treatment of the labile platinum(II) complex [Pt(OTf)(terpy)](+) (terpy = 2,2':6',2' '-terpyridine) with the 1,2-carborane monothiol derivatives 1-HS(CH(2))(n)-1,2-C(2)B(10)H(11) (n = 0, 1) or the novel 1,7-carborane ligand, 1-HSCH(2)-1,7-C(2)B(10)H(11), affords the stable, brightly colored species [Pt(1-S(CH(2))(n)-1,Z-C(2)B(10)H(11))(terpy)](+) (Z = 2, n = 0, 1; Z = 7, n = 1) in good yield and purity. Preliminary DNA-binding experiments with calf-thymus DNA indicate an intercalative interaction by the platinum(II) complexes at high r(f) values.

Displacement of coordinated 1,5-cyclooctadiene or norbornadiene from suitable precursors has given a series of hapto1-C-bonded organoplatinum(II) complexes containing 1,4,7-trithiacyclononane (9S3), i.e. PtRR’(9S3) [R = R’ = Me(l), Et(2), CH2CMe3(3), CH2SiMe3(4), Ph(5); R = Me, R’ = CH2SiMe3(6); R = C1, R’ = CH2SiMe3(7)]. The dimethylpalladium(II) complex PdMe2(9S3)(8) has been obtained similarly from PdMe2(tetramethylethylenediamine), but Pd(CH2SiMe3)2(9S3)(9) could not be isolated in a pure state. Crystals of 5 are orthorhombic, space group Pbca, with a = 12.047(1) A, b = 17.660(2) A, c = 16.854(2) A, and Z = 8. The structure was solved by heavy-atom methods and refined by least squares analysis to R = 0.031 and R, = 0.046 for 2498 unique observed reflections. The platinum atom is bound to two sulfur atoms of bidentate 9S3 and to two cis-phenyl groups in an almost planar array. The macrocyclic thioether adopts an exodentate conformation such that the uncoordinated sulfur atom points away from the metal atom, in contrast to the more usual endodentate conformation found in PdX2(9S3) (X = C1, Br). At room temperature, the 9S3 CH2 resonances in the 1H and 13C{H} NMR spectra of 1-7 are broad; variable-temperature NMR studies of 2 and 4 suggest that this is caused by exchange of free and coordinated sulfur atoms. Complexes 3 and 4 react with halogens to give diorganoplatinum(IV) salts [PtXR2(9S3)]X [R = CH2SiMe3, X = I(l0), Br(11); R = CH2CMe3, X = I(13)], and 1 and 2 oxidatively add methyl or ethyl iodide to give triorganoplatinum(IV) salts [PtR2R’(9S3)]1 [R = R’ = Me(14); R = Et, R’ = Me(15); R = R’ = Et(16)]; in these products 9S3 is probably tridentate. The palladium(II) complex 8 likewise adds methyl iodide to give [PdMe3(9S3)]I(17), which can be converted into a nitrate salt [PdMe3(9S3)]N03(18). These compounds show no tendency to reductively eliminate ethane, and they are the first isolable organopalladium(IV) complexes that do not contain a nitrogen donor, thus demonstrating the ability of endodentate 9S3 to stabilize octahedral or pseudooctahedral geometries.

The preparation and characterization of novel platinum complexes with the 4,4'-dipyrazolylmethane (dpzm) ligand is described. Some proposed conformational isomers of the square-planar, dinuclear platinum(II) complexes α-[Cl 2 Pt(μ-dpzm) 2 PtCl 2 ]0.5dmf, β-[Cl 2 Pt(μ-dpzm) 2 PtCl 2 ], and γ-(Cl 2 Pt(dpzm) 2 PtCl 2 ]-2dmf

The preparation and characterization of a novel series of cationic sigma-phenylplatinum(II) complexes of the type trans-[Pt(sigma-C(6)H(5))(L)(2)A]OTf (A = picolinic acid, L = PPh(3) (4) and PMePh(2) (7); A = nicotinic acid, L = PPh(3) (5) and PMePh(2) (8); A = isonicotinic acid, L = PPh(3) (6), PMePh(2) (9), and PEt(3) (10)) are described. The pK(a) value for the carboxylic acid functionality in selected complexes was found to follow the order 7 (pK(a) = 5.23 +/- 0.09)8 (4.85 +/- 0.10)9 (3.51 +/- 0.08)6 (3.26 +/- 0.07) approximately 10 (3.21 +/- 0.08) by means of potentiometric titration experiments in 50% (v/v) EtOH/H(2)O solution at 295 K. The X-ray crystal structures of 9 and 10 were also determined. The asymmetric unit of each of 9 and 10 comprises a univalent complex cation, a triflate anion, and a solvent CH(2)Cl(2) molecule of crystallization. Centrosymmetrically related pairs of complex cations in 9 associate via the familiar carboxylic acid dimer motif, whereas with 10, the carboxylic acid dimer motif is absent. Instead, the carboxylic acid residue forms both donor and acceptor interactions to the triflate anion and CH(2)Cl(2) solvent of crystallization, respectively, to afford a 10-membered ring structure. Possible reasons for the observed differences in the solid-state structures of 9 and 10 are presented.

The first metallacycles formed by oxidative addition of tin-sulfur, tin-selenium, tin-tellurium, and germanium-tellurium bonds to platinum(II) are reported. In particular, the ring compounds [(R(2)SnE)(3)], where R = Me, Ph and E = Se, Te, and the new compound [(Me(2)GeTe)(3)], react with [PtMe(2)(bu(2)bpy)] (bu(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine) to give the new organoplatinum(IV) metallacycles [PtMe(2)(R(2)SnE)(2)(bu(2)bpy)] and [PtMe(2)(Me(2)GeTe)(2)(bu(2)bpy)], respectively. The tin-containing metallacycles complexes can undergo exchange of either the R(2)Sn or the E groups by reaction with [(R'(2)SnE)(3)] or [(R(2)SnE')(3)], respectively, to give the corresponding new metallacycles of general formula [PtMe(2)(R(2)SnE-R'(2)SnE)(bu(2)bpy)] or [PtMe(2)(R(2)SnE-R(2)SnE')(bu(2)bpy)]. The isostructural series of complexes [PtMe(2)(Ph(2)SnE)(2)(bu(2)bpy)] with E = S, Se, and Te have been characterized by X-ray structure determinations. It is shown that (119)Sn NMR is a useful method of structure determination for these metallacyclic compounds.