Marcos D. García

Complexation and Extraction of PAHs to the Aqueous Phase with a Dinuclear PtII Diazapyrenium‐Based Metallacycle

New palladium and platinum metallacycles have been synthesized by reaction between a 2,7-diazapyrenium-based ligand and Pd(II) and Pt(II) complexes. The inclusion complexes between the metallacycles and polycyclic aromatic hydrocarbons (PAHs) in CD(3)NO(2) and D(2)O were studied by NMR spectroscopy. The structures of the inclusion complexes of the Pt metallacycle as host with pyrene, phenanthrene, and triphenylene were confirmed by single crystal X-ray crystallography. The association constants between the Pt metallacycle and the selected PAHs were determined in CH(3)CN following the characteristic charge-transfer band displayed in their UV/Vis absorption spectrum. Although in aqueous solution all the complexes showed a 1:1 stoichiometry, in CH(3)CN the Job plot indicated a 2:1 stoichiometry for complexes with triphenylene and benzo[a]pyrene. The estimated association constants in water correlate with the hydrophobicity of the PAH, indicating that hydrophobic forces play an important role in the complexation process.

Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4

We present the design, synthesis and biological activity of a library of substituted (biphenylcarbonyl)-tryptamine and (biphenylcarbonyl)-tetrahydro-beta-carboline compounds related to the natural product fascaplysin, as novel inhibitors of CDK4/cyclin D1. We show all these molecules, prepared using the Suzuki-Miyaura reaction, being selective inhibitors of CDK4 over CDK2. The most active compounds have a CDK4 IC(50) in the range 9-11 microM, three of them containing the para-biphenyl plus para-substituents supporting the existence of a pi-stacking pocket within the active site of CDK4.

Dimensional caging of polyiodides: cation-templated synthesis using bipyridinium salts

The potential of bipyridinium derivatives in the cation templated synthesis of polyiodides has been explored by applying the strategy of size-matching between cations and anions. Bipyridinium cations 1–4, bearing benzyl and functionalized benzyl pendants at nitrogen atoms, are able to template the selective formation of I42− and I3− species. Thanks to the supramolecular space compartmentation induced by the benzyl pendants, the formation of I42−and I3− is independent of the stoichiometry adopted in the crystallization procedure. Bipyridinium cation 5, bearing methyl pendants, is unable to induce space compartmentation and different polyiodides are obtained depending on the stoichiometry used in the crystallization process as the cation–anion size-matching alone does not control the polyiodide formation.

Self-assembly of new fluorescent Pd(II) and Pt(II) 2,7-diazapyrenium-based metallocycles and study of their inclusion complexes and [3]catenanes

New fluorescent square-shaped metallocycles were self-assembled from N-monoalkyl-2,7-diazapyrenium derivatives 1 and 4 and PdII/PtII complexes. Using ligand 1, the metal-directed self-assembly process produced a single metallocycle, while the non-symmetrical salt 4 produced mixtures of regioisomeric PdII and PtII metallocycles upon complexation with the corresponding square-planar cis-complexes. Due to the improved π-deficient character of 1 and 4 compared to related bipyridinium-based ligands, complexation and catenation of the obtained metallocycles with selected electron-rich aromatic substrates produced the corresponding 1 : 2 inclusion complexes and [3]catenanes in a highly efficient fashion. This is particularly relevant for metallocycles derived from ligand 4, as complexation and catenation occurs in a regioselective fashion, generating only the supramolecules with the appropriate parallel arrangement of the diazapyrenium subunits in order to maximize the host–guest π-stacking interactions. The potential of the new metallocycles for optical signalling applications is illustrated by analyzing their absorption and emission behaviour upon complexation and catenation.

Fascaplysin-inspired diindolyls as selective inhibitors of CDK4/cyclin D1

We present the design, synthesis and biological activity of a new series of substituted 3-(2-(1H-indol-1-yl)ethyl)-1H-indoles and 1,2-di(1H-indol-1-yl)alkanes as selective inhibitors of CDK4/cyclin D1. The compounds were designed to explore the relationship between the connection mode of the indolyl moieties and their CDK inhibitory activities. We found all the above-mentioned designed compounds to be selective inhibitors of CDK4/cyclin D1 compared to the closely related CDK2/cyclin A, with IC(50) for the best compounds 10m and 13a being 39 and 37microm, respectively.

Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-β-carbolines

The synthesis of a series of beta-carboline-based analogues of the natural product fascaplysin is presented; the compounds were produced using a novel photo-oxidation reaction of 1-benzyl-4,9-dihydro-3H-beta-carbolines as the key step.

Dimensional Matching of Polycyclic Aromatics with Rectangular Metallacycles: Insertion Modes Determined by [CH⋅⋅⋅π] Interactions

A family of Pd(II)/Pt(II) dinuclear receptors, designed to give a smooth increase in their cavity lengths (from 7.46-13.78 Å), is presented. Their inclusion complexes with a representative set of polycyclic aromatic substrates (naphthalene, carbazol, pyrene, and benzo[a]pyrene), were characterized and studied in aqueous solution and the solid state. By taking into account the dimensions of both receptors and substrates, an excellent complementarity was found between the size of the receptors and their ability to complex a given substrate. Furthermore, this dimensional matching results in specific binding modes depending on the ability of the guest to establish stabilizing [C-H···π] interactions with the host.

Synthesis of platinum(II) metallocycles using microwave-assisted heating.

An efficient microwave-assisted self-assembly of dinuclear platinum metallocycles is reported. The reactions proceed to afford the products with high purity and yields within 3-4 h. We have used this methodology to synthesize a new 14.75 Å × 14.75 Å molecular square. The solid-state structure showed a perfect alignment of the squares along the c axis.

Complexation and Catenation in Aqueous Media Using a Self-Assembled PdII Metallacyclic Receptor

A M2L2 rectangular-shaped metallacycle, obtained by metal-directed self-assembly of a 2-(pyridin-4-ylmethyl)-2,7-diazapyrenium salt and [(en)Pd(NO3)2 (en=ethylenediamine), has been investigated as a molecular receptor for a wide range of aromatic substrates in water. Complexation and catenation of the receptor with selected mono- and polycyclic aromatic substrates produced 1:1 inclusion complexes and [2]catenanes in a highly efficient fashion, as determined by NMR and UV/Vis spectroscopic techniques, as well as single-crystal X-ray crystallography. Furthermore, the thermodynamic and kinetic features of the complexation processes have been analyzed for selected model guests.

Diasterocontrol in the intramolecular meta-photocycloaddition of arenes and olefines

The intramolecular arene-olefin photoannulation reaction of diastereopure substrates and gave diastereopure and whose structures were determined by spectroscopic methods and confirmed by X-ray crystallography.