No abstract

Modifications of natural DNA and synthetic oligodeoxyribonucleotide duplexes in a cell-free medium by analogs of antitumor cisplatin containing enantiomeric amine ligands, such as cis-[PtCl(2)(RR-DAB)] and cis-[PtCl(2)(SS-DAB)] (DAB = 2,3-diaminobutane), were studied by various methods of molecular biophysics and biophysical chemistry. These methods include DNA binding studies by pulse polarography and atomic absorption spectrophotometry, mapping of DNA adducts using transcription assay, interstrand cross-linking assay using gel electrophoresis under denaturing conditions, differential scanning calorimetry, chemical probing, and bending and unwinding studies of the duplexes containing single, site-specific cross-link. The major differences resulting from the modification of DNA by the two enantiomers are the thermodynamical destabilization and conformational distortions induced in DNA by the 1,2-d(GpG) intrastrand cross-link. It has been suggested that these differences are associated with a different biological activity of the two enantiomers observed previously. In addition, the results of the present work are also consistent with the view that formation of hydrogen bonds between the carbonyl oxygen of the guanine residues and the "quasi equatorial" hydrogen of the cis amine in the 1, 2-d(GpG) intrastrand cross-link plays an important role in determining the character of the distortion induced in DNA by this lesion.

The ground state geometry of the platinum(ii) complexes [Pt(N-N)(L)X,] (N-N = bidentate N-donor ligand; L, X = monodentate ligands) becomes five-coordinate trigonal-bipyramidal whenever a strong n-accepting ligand (L) is present in the coordination sphere, in absence of it even a rigid phenanthroline acts as monodentate ligand and the complex is four-coordinate.

Mono-and bisnitrile platinum complexes, [PtC13(NCR)]-and cis-and trans-[PtC12(NCR)2] (R = Bu', Me and Ph), hydrolyze to amidate amide and mixed amide-nitrile complexes. The amide ligands generally adopt the enol tautomeric form and coordinate to platinum through nitrogen. The presence of two amides cis to one another plays a critical role in favoring the association of platinum units in dimers. For example, molecules of cis-[PtCl2{HN=C-(OH)Bu'jz]2, 7b, comprise two monomeric units, placed face to face, with a Pt-Pt distance of 3.165(1) A and four interplanar N-H...Cl hydrogen bonds. Although hydrogen bonding interactions would place the dimer in the eclipsed conformation, the compound adopts the staggered conformation which minimizes interligand steric interactions allowing a closer approach of the two platinum subunits. The driving force to shortening the intermetallic distance stems from a direct intermetallic bonding interaction. Addition of two extra amides to axial sites of 7b gave [PtClz{HN= C(OH)BU')~{H~NC(=O)BU']]~, 7c. The axial amides differ from the equatorial ones, in both tautomeric form (keto instead of enol) and donor atom (oxygen instead of nitrogen). In spite of a very long Pt-0 distance [3.229(5) A] the axial coordination causes a considerable lengthening of the intermetallic distance (0.23 A) and, furthermore, conversion from the staggered to the eclipsed conformation. The solution chemistry of both 7b and 7c is in accord with their dimeric structure. A fast rate of proton exchange, between the hydroxyl group of the amide ligands and water present in the solvent, was observed whenever two amide ligands are cis to one another. Such an exchange process could be favored by the hydrogen bonding interaction of the two cis amides with a molecule of water. Mixed amide nitrile complexes have also been prepared; one trans-[PtC12{HN=C(OH)Buf}(NCBu')] proved to be the complex previously formulated as a platinum(1V) dichlorobisamidate derivative having the two amidate ligands in different tautomeric forms. The structure of 7b-CzH4C12 and 7c have been solved by single-crystal X-ray diffraction. 7b crystallizes as 1 ,Zdichloroethane solvate (1:l) in the space group P i (no 2) with a = 11.292(3), b = 13.618(3), c = 14.069(4) A, a = 62.12(2), p = 83.58(2), y = 76.47(2)', V = 1859(1) A3, Z = 2. 7c crystallizes in the space group P i (no 2) with a = 10.279(1), b = 10.772(1), c = 11.099(3) A, CY = 90.66(1), fl = 89.58(1), y = 114.27(1)', V = 1120(1) A3, Z = 1.

In recent years a number of chelating ligands. when combined with a n-acid such as an alkene, have been found to stabilize five-coordination in palladium(I1) and platinum(I1) chemistry. The complexes have invariably a trigonal bipyramidal geometry with the bidentate ligand and the alkene in the equatorial plane. The n-acceptor capacity of the alkene and a small bite of the chelate ligand (between 70 and 85') are both required for accommodating them in the equatorial plane where the d:electron concentrations (which in the square planar d X complexes are located above and below the coordination plane) are also confined. Two monodentate ligands, in place of one chelate. do not stabilize the five-coordination since for entropic reasons the dissociation of one of them is strongly favored. A great bulk of the chelate ligand is also found to stabilize five-coordination since interligand steric interactions are smaller in the trigonal plane of a five-coordinate complex than in the square-plane of a four-coordinate species. Moreover the same steric factors that destabilize four-versus five-coordination can also destabilize fourversus three-coordination, and T-shaped ML, species appear to provide a low energy path for the interconversion between four-and five-coordinate complexes. The alkene is strongly bound to the metal. the metal-carbon bond distances are shorter, and the bending back of the alkene substituents is greater than those found in four-coordinate compounds. The activation energy for alkene rotation is also greater in five-coordinate species, and in a number of cases atropisomers are generated. The chelate dinitrogen ligand also lying in the equatorial plane is. on the other hand, loosely bound to the metal, and dissociation of one end of this ligand Comments Inorg. Chem. appears to be the preliminary step in all substitution processes involving the alkene. the axial ligands. and the bidentate ligand itself. These processes should therefore occur through a mechanism analogous to that operating in four-coordinate complexes. The dissociation of one end of the bidentate ligand also provides a low energy path to proton exchange and inversion of configuration at coordinated nitrogens. Other aspects related to the conformation of the alkene and of the chelate ligand as well as to the preparation and reactivity of this class of compounds are discussed.

The cation [ Pt(q2-C,H,)CI(tmen)] + (1) (tmen = N,N,N',N'-tetramethylethylenediamine) reacts with water and alcohol under basic conditions t o give nucleophilic addition of hydroxide and alkoxide anions to ethylene and formation of [Pt(CH,CH,OH)CI( tmen)] (4) and [Pt(CH,CH,OR)Cl(tmen)] [R = M e (2) or Et (3)] respectively. Compound (4), either in solution or in the solid, undergoes a condensation reaction with formation of [ (trnen)CIPt(CH,CH,OCH,CH,) PtCl(tmen)] (5). Compound (1 ) reacts also with excess of acetate in water t o give the ester complex [ Pt{CH,-CH,OC(O) Me}CI(tmen)] (6). Compound (6), in the solid state, slowly dissociates to acetate anion and cation ( I ) , redissolution in chloroform restoring the original species. Compounds (3)-(6), dissolved in methanol, are transformed into (2).

No abstract

The evolution in basic medium ([RO-] = 1 M in methanol, R = H or Me) of five-coordinate platinum(II) compounds, [PtCl2(eta2-C2H4)(N-N)], 2a-c, (N-N = N,N,N',N'-tetramethyl-1,2-ethanediamine, a; 2,2'-bipyridyl, b; 1,10-phenanthroline, c) leads to the formation of [PtCl(eta1-CH2CH2-OCH3)(N-N)], 5a-c. The analogous compound 5d (N-N = 2,9-dimethyl-1,10-phenanthroline, d) can also be prepared, but not via transformation of the five-coordinate species 2d in basic medium where it is quite stable. 5d can instead be prepared by reaction of d with a strongly basic methanol solution of Zeise's anion [PtCl3(eta2-C2H4)](-), 1. In such a medium the di-anionic trans-[PtCl2(OR)(eta1-CH2CH2-OCH3)](2-) species (1") reacts with to form exclusively 5d. Hydrolysis of with acids bearing weakly coordinating anions leads to [PtCl(eta2-C2H4)(N-N)]+, 3a-c, as stable cations; upon the same treatment 5d does not generate 3d, but it reacts with HCl to give 2d in almost quantitative yield. Cationic complexes 3b, 3c, here reported for the first time, were reacted with some nucleophiles and their behaviour compared with that of the already known 3a. In 3b, 3c the metal centre competes with the coordinated ethene for binding to nucleophiles; therefore the acetylacetonate anion can either add to the olefin (affording compounds 6b, 6c ) or to the metal ion replacing the ethene ligand (yielding compounds 7b, 7c). Under similar conditions, 3a gives exclusively 6a. Secondary amines readily add to ethene in 3b, 3c, affording the addition products 8b, 8c, which undergo a ready cyclization to an azaplatinacyclobutane ring (9b, 9c). The remarkable ease of the four-membered ring formation has been related to the high electrophilic character of the metal core in 3b, 3c.