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Efficient intercalation of a luminescent Ir(III) complex exclusively made of polypyridine ligands in natural and synthetic biopolymers is reported for the first time. The emission of the complex is largely enhanced in the presence of [poly(dA-dT)(2)] and strongly quenched in the presence of [poly(dG-dC)(2)]. By comparing the emission decays in DNA and in synthetic polynucleotides, it is proposed that the emission quenching of the title compound by guanine residues in DNA is no longer effective over a distance of four dA-dT base pairs., (© 2011 American Chemical Society)

A comparative investigation of the noncovalent interaction of the platinum(II) polypyridine complexes [Pt(dipy)(n-Rpy)2]2+ and [Pt(4,4'-Me2dipy)(2-Rpy)2]2+ (dipy = 2,2'-dipyridine; Me = CH3; n = 2-4; R = H or CH3) with double-helical DNA (calf thymus) and RNA [poly(A).poly(U)] has been conducted. With the exception of [Pt(dipy)(2-Mepy)2]2+, all of the complexes interact strongly, by intercalation, with both nucleic acids giving rise to large changes in the electronic spectra and induced circular dichroism signals; in addition, viscosity experiments on rodlike DNA and RNA show that both biopolymers elongate upon interaction with the complexes. The binding constant values, KB, determined at 25 degrees C, indicate that, at 0.101 M ionic strength, the affinity for poly(A).poly(U) is strongly dependent on the complexes nature, while for DNA it is leveled off. [Pt(dipy)(2-Mepy)2]2+ binds to DNA but does not interact appreciably with poly(A).poly(U).

The interaction mechanisms responsible for the binding between metal complexes and biopolymers in aqueous solution, as well as the consequent aggregation process of biopolymers themselves, involve many factors, from geometrical aspects and hydrophobic contributions, as examples, to the electrostatic potential. In this paper aqueous solutions of a polynucleotide, polyadenylic acid (PolyA), which mimics the helix arrangement of RNA or single-stranded DNA but has a simpler structure, are used as a model system. The role of the electrostatic interactions in the binding process between some platinum(II) complexes and PolyA and in the aggregation among PolyA molecules is investigated, by means of elastic and quasielastic light scattering and electrophoretic mobility. The results show that the presence of large, planar aromatic moiety in the dicationic platinum(II) complexes is essential for the binding with PolyA and suggest that the consequent lowering of the local electrostatic barrier between PolyA molecules can be involved in triggering the aggregation process.

The interaction with DNA of the platinum(II) square planar complexes [Pt(N-N)(py)(2)](2+) (N-N = 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz), benzodipyrido[b:3,2-h:2'3'-f]phenazine (bdppz)) has been investigated by means of absorption, circular and linear dichroism spectroscopy, DNA melting, and viscosity. In the presence of excess [DNA] all the complexes intercalate to the double helix. For those with the most extended phenanthrolines the binding mode depends on the [DNA]/[complex] ratio (q); at low q values the substances bind externally to DNA probably self-aggregating along the double helix. When the DNA concentration is large enough, the aggregate breaks up and the complex intercalates within the nucleobases. The complexes self-aggregate, without added DNA, in the presence of a large salt concentration.

Novel platinum(II) square planar coordination complexes, in which two heteroaromatic ligands are held by the metal in an unusual L-shaped geometry orthogonal to each other, have been synthesized, and their interaction with DNA was investigated with absorption and linear dichroism spectroscopy. As a rule, the ligand that is coplanar with the coordination square of Pt is found to be oriented perpendicular relative to the DNA helix axis when bound, suggestive of its intercalation between the base pairs of DNA. However, when this coplanar ligand is replaced by two pyridines, the opposite ligand, orthogonal to the coordination square, is instead preferentially intercalated. This behavior shows that these new complexes do indeed show some properties of true ambintercalators, i.e., compounds that can bind by intercalation of either of two distinct aromatic moieties.

The kinetics of substitution, by thiourea, of ethylenediamine (en) or N,N'-dimethylethylenediamine (Me(2)en) coordinated to palladium(II) in the complexes [Pd(4,4'-R(2)bpy)(en)](PF(6))(2) (bpy = 2,2'-bipyridine; R = H or Me), [Pd(en)(2)](PF(6))(2) and [Pd(Me(2)en)(2)](PF(6))(2) have been studied at 25 degrees C, pH 7 and various ionic strength values, in the presence of calf thymus DNA. The rate of the reaction in water depends on ionic strength, pH, and nucleophile concentration; at fixed pH and ionic strength the k(obsd) values are correlated to the square of the thiourea concentration. This rate law is not altered by the presence of DNA, but the rate of reaction is influenced, depending on the nature of ancillary ligand, L-L, bound to palladium. DNA inhibits the substitution process when L-L is bpy or 4,4'-Me(2)bpy and catalyzes the same reaction when L-L is en or Me(2)en. These opposite kinetic effects can be related to the noncovalent interactions of the various complexes with the DNA double helix. Inhibition of the reactivity of the complexes [Pd(4,4'-R(2)bpy)(en)](2+) is due to protection of the reaction center from nucleophile attack by DNA. Acceleration of the reaction when L-L is en or Me(2)en is related to the dependence of the rate of reaction on pH. If, due to the higher activity of water under the electric field of phosphate groups, hydronium ion concentration on DNA surface is higher than in the bulk solution, the enzyme-like dependence of the rate of reaction on [DNA] is due to progressive accumulation of the complexes around the double helix. Regardless of the complexes' nature, the rate constant values obtained in DNA at pH 7 correspond to values determined in water at pH 5. This pH value on the DNA surface, lower by about two units with respect to the bulk solution, is in good agreement with theoretical predictions. Acceleration of ethylenediamine substitution has been observed for all of the complexes studied in the presence of sodium polyvinylsulfonate.

The kinetics of substitution of pyridine or 2-methylpyridine, by iodide or thiourea, in the complexes [Pt(4'-R'terpy)(2-Rpy)](BF4)2 (R' = o-tolyl or H; R = H or CH3) has been studied, at 25 degrees C, pH 7, and various ionic strength values, in the presence of and without calf thymus DNA. The reactions occur in one observable step, and plots of kobsd against nucleophile concentration give straight lines with zero intercepts. DNA inhibits all the reactions studied without altering the rate law; the second-order rate constants k2 decrease systematically on increasing DNA concentration and are larger at higher ionic strength values. Partitioning of the ionic reactants in solution on electrostatic grounds can account for this kinetic effect in the reaction with iodide. Iodide is kept off the double helix proximity while the dicationic complexes concentrate on it. The inhibiting effect observed for the uncharged reagent thiourea can be related to the specific binding mode of the complexes to DNA. The complexes studied are effective intercalators to double helix, and this type of interaction, which prevents attack of thiourea at platinum, decreases their actual concentration in solution. The inhibiting effect is larger for [Pt(terpy)(py)]2+ that is a better intercalator. Likewise, the decrease in the rate of substitution of 2-Rpy, at a given [DNA] on decreasing ionic strength, is due to the influence of ionic strength on the complex-DNA interactions.

The interaction of the platinum(II) polypyridine complexes [Pt(bipy)(2)](2+), [Pt(quaterpy)](2+), [Pt(terpy)(n-Rpy)](2+) and [Pt(bipy)(py)(2)](2+) (bipy = 2,2'-bipyridine; terpy = 2,2':6',2' '-terpyridine; quaterpy = 2,2':6',2' ':6' ',2' "-quaterpyridine; n-R = H, 2-CH(3), or 4-CH(3) ) with double-helix DNA has been studied with a variety of experimental techniques. Induced circular dichroism, strong hypochromism and red shifts of the absorption maxima of the complexes, increase in melting temperature and viscosity of DNA, and inhibition of the reaction of the complexes with thiourea in the presence of DNA, characterize the processes. Intercalation, implying the whole molecule or part of it, is the suggested binding mode. The binding constants, K(B), determined spectrophotometrically at 25 degrees C, pH 7, and I = 0.15 M, using the McGhee-von Hippel approach, increase in the order [Pt(bipy)(py)(2)](2+)< [Pt(terpy)(py)](2+)< [Pt(quaterpy)](2+), on increasing aromatic planar surface extension. The steric interference with double helix of the methyl group in [Pt(terpy)(2-Mepy)](2+) destabilizes the interaction by reducing the stacking surface.

The interaction of the complexes [Pt(bipy)(4-Rpy)(2)](2+) and [Pt(4,4'-Ph(2)bipy)(4-Rpy)(2)](2+) (Ph = phenyl; bipy = 2,2'-bipyridine; R = H, CN, CH(3), NH(2)) with DNA has been studied with a series of techniques. The processes give rise to (i) lengthening of rodlike DNA and unwinding of closed circular DNA and (ii) an increase in the DNA melting temperature comparable with that observed for known intercalators. In addition, the reaction of the complexes [Pt(bipy)(py)(2)](2+) and [Pt(4,4'-Ph(2)bipy)(py)(2)](2+) is inhibited by the presence of DNA. These results have been interpreted by assuming that the substances intercalate in spite of the presence of ligands out of plane. The crystal structure determined for [Pt(4,4'-Ph(2)bipy)(3,5-Me(2)py)(2)](2+) by X-ray analysis shows that also one of the phenyl rings is twisted with respect to the square plane. Binding constants, K(B), determined spectrophotometrically at 25 degrees C and pH 7 using the McGhee-von Hippel approach, increase for both series of complexes on increasing pK(a) of coordinated pyridines and are larger for those with 4,4'-Ph(2)bipy. The increasing affinity for DNA on increasing electron density of the interacting moiety is accounted for by assuming that London dispersion forces play a major role in the processes.