The preparation and characterization of trans-platinum(IV) complexes with unusually high cytotoxicity

The physical and biological properties have been determined for three Pt(IV) complexes with trans amine ligands: trans,trans,trans-[PtCl(2)(OH)(2)(dimethylamine)(isopropylamine)] (1(IV)), trans,trans,trans-[PtCl(2)(OH)(2)(dimethylamine)(methylamine)] (2(IV)) and trans,trans,trans-[PtCl(2)(OH)(2)(isopropylamine)(methylamine)] (3(IV)). The crystal structures of 2(IV) and 3(IV) reveal substantial strain resulting from repulsion between the amine ligands and the chlorido and hydroxido ligands. All three complexes have reduction potentials in the range -666 to -770 mV, values usually associated with high resistance to reduction and low cytotoxicity. However, the complexes all demonstrate surprisingly high cytotoxicity with values and trends that closely follow those seen for the Pt(II) congeners of these complexes. These results are consistent with more rapid reduction of the Pt(IV) complexes than would be expected based on the reduction potentials, perhaps associated with the trans arrangement of the chlorido ligands.     

Monte Carlo and event-driven dynamics of Brownian particles with orientational degrees of freedom

Recently, a simple scaling argument was introduced that allows us to map, with some precautions, Brownian and Monte Carlo dynamics for spherical particles. Here, we extend the scaling to study systems that have orientational degrees of freedom and carefully asses its validity over a wide region of temperature and density. Our work allows us to devise a Brownian Monte Carlo algorithm that produces, to a good approximation, physically meaningful trajectories with a minimum programming effort, although at the expense of some sampling efficiency.     

Metallatriangles and metallasquares: the diversity behind structurally characterized examples and the crucial role of ligand symmetry

Reports on spontaneous self-assembly processes between metal fragments and organic ligands frequently tend to ignore the fact that the product isolated and structurally characterized in most cases is only one out of a more or less large series of feasible ones. This is true even for rings containing as few as three or four metal ions. Here we shall review metallatriangles and metallasquares containing predominantly cis-square-planar metal entities and a range of bidentate bridging ligands. The most significant features contributing to the number of possible stereoisomers appear to be ligand symmetry and flexibility, viz. rotation of two halves of a ligand about a single bond, or rotation of the whole ligand about the metal-donor atom bonds. With low-symmetry bidentate ligands the number of isomers increases dramatically with ring size as a consequence of an increase in possible connectivity patterns, hence linkage isomers, and an increase in possible rotamer states of the bridging ligands. In this tutorial review it is demonstrated how complexity increases as the symmetry of the bridging ligands is lowered from D(∞h) and D(2h) to C(∞v), C(2v), C(2h) and C(s). Special attention will be paid to cyclic tri- and tetranuclear complexes of substituted pyrimidine ligands (C(2v) and C(s) symmetries) as well as the flexible 2,2'-bipyrazine, which can adopt states of either C(2v) or C(2h) symmetry. Uses of these complexes and ways to reduce the number of isomers will be pointed out.     

Nitrogen/gold codoping of the TiO2(101) anatase surface. A theoretical study based on DFT calculations

The interaction between implanted nitrogen atoms, adsorbed gold atoms, and oxygen vacancies at the anatase TiO(2)(101) surface is investigated by means of periodic density functional theory calculations. Substitutional and interstitial configurations for the N-doping have been considered, as well as several adsorption sites for Au adatoms and different types of vacancies. Our total energy calculations suggest that a synergetic effect takes place between the nitrogen doping on one hand and the adsorption of gold and vacancy formation on the other hand. Thus, while pre-implanted nitrogen increases the adsorption energy for gold and decreases the energy required for the formation of an oxygen vacancy, pre-adsorbed gold or the presence of oxygen vacancies favors the nitrogen doping of anatase. The analysis of the electronic structure and electron densities shows that a charge transfer takes place between implanted-N, adsorbed Au and oxygen vacancies. Moreover, it is predicted that the creation of vacancies on the anatase surface modified with both implanted nitrogen and supported gold atoms produces migration of substitutional N impurities from bulk to surface sites. In any case, the most stable configurations are those where N, Au and vacancies are close to each other.     

Quantitative comparison of molecular electrostatic potential distributions from several semiempirical and ab initio wave functions

A quantitative comparative analysis of molecular electrostatic potential (MEP) distributions generated from different wave functions was carried out. Wave functions were computed by using MNDO, AMl, STO-3G, 3-21G, 4-31G, 6-31G, 4-31G*, 6-31G*, and 6-31G** methods. Ten different compounds, which include usual atoms and groups of biomolecules, such as hydroxyl, carbonyl, amine, amide, imine, double and triple bonds, and heteroaromatic rings, were studied. For each compound, MEP values in the points of a common 3-D grid were computed; thereafter, the similarity between each pair of MEP distributions generated by different methods was assessed. Similarities were measured using the Spearman rank correlation coefficient. A similarity matrix was obtained for each compound. Similarity matrices were averaged and a hierarchical cluster analysis was carried out to classify the different quantum chemical methods. In the compounds studied, the main conclusion is the negligible difference between the pattern of MEP distributions generated from all split valence basis sets (with and without polarization functions). © 1993 John Wiley & Sons, Inc.     

PtII Coordination to N1 of 9‐Methylguanine: Why it Facilitates Binding of Additional Metal Ions to the Purine Ring

The preparation and X‐ray crystal structure analysis of {trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂]} ? {3 K₂[Pt(CN)₄]} ? 6 H₂O ( 3 a ) (with 9‐MeG being the anion of 9‐methylguanine, 9‐MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9‐MeGH‐N7)]²⁺ ( 1 ; dien=diethylenetriamine) with trans‐[Pt(MeNH₂)₂(H₂O)₂]²⁺ at pH 9.6, 60 °C, and subsequent removal of the [(dien)Pt^II] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)₄]^2?. Cocrystallization of K₂[Pt(CN)₄] with trans‐[Pt(MeNH₂)₂(9‐MeG‐N1)₂] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pK_a values of trans‐[Pt(MeNH₂)₂(9‐MeGH‐N1)₂]²⁺ (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K⁺ to the guaninato ligands. DFT calculations confirm that K⁺ binding to the sugar edge of guanine for a N1‐platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid‐state structure of 3 a . The linkage isomer of 3 a , trans‐[Pt(MeNH₂)₂(9‐MeG‐N7)₂] ( 6 a ) has likewise been isolated, and its acid–base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9‐MeG in 3 a has been studied in detail for [(NH₃)₃Pt^II], trans‐[(NH₃)₂Pt^II], and [(en)Pd^II] (en=ethylenediamine) by using ¹H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans‐[(Me₂NH₂)Pt^II] cross‐linking N1 positions and trans‐[(NH₃)₂Pt^II] cross‐linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence.     

Exploring the Reactivity of α‐Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]‐Wittig Rearrangement and the Mechanistic Proposal Revisited

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α‐lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]‐Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α‐lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups. The more favored rearrangements are found for substrates with electron‐poor aryl groups that favor the anionic pathway.