José M. Quintela

A new doubly interlocked [2]catenane.

The synthesis and the crystal structure of a doubly braided [2]catenane, a new molecular Solomon link, obtained by a 5-component-self-assembly process based on coordinative bonds, pi-donor/pi-acceptor interactions, and hydrogen bonding is reported.

Piperazine N-substituted naphthyridines, pyridothienopyrimidines and pyridothienotriazines: new antiprotozoals active against Philasterides dicentrarchi

New antiprotozoals active against Philasterides dicentrarchi, the causative agent of scuticociliatosis in farmed turbot and Black Sea bass-bream, have been synthesised and tested. The most active compounds posses a piperazine ring, generally N-bonded to the heterocycle, and are the 1,8-naphthyridines, 2f and 5o, the pyridothienopyrimidine (7), and the pyridothienotriazines, 8, 9, 12d, 12f, 12h, 12m and 12k. Pyridothienotriazine (12k) presents the same activity (Lethal Dose, LD=0.8/1.5 mg L(-1)) as the well-known antiparasitics niclosamide and oxyclozanide.

Synthesis, antihistaminic and cytotoxic activity of pyridothieno- and pyridodithienotriazines

Abstract The synthesis of pyrido[3′,2′:4,5]thieno[3,2- d ]-1,2,3-triazines 7a-n and 8a-c and pyrido[3′,2′:4,5]dithieno[3,2- d ]-1,2, 3-triazines 15 and 16a-c , and their inhibitory action on the release of histamine from rat mast cells under immunological and chemical stimulus are presented. Compounds 7b and 16a are strong inhibitors under all the conditions tested while 16c is a good inhibitor in all conditions except when it is preincubated with ovoalbumin. Compounds 7k, 7m and 7n are good inhibitors in the immunological experiments but are practically inactive under chemical stimulus. Compounds 6a and 15 show in vitro cytotoxic activity against several human and mouse tumoral cell lines with IC 50 values well under 1 mg/mL.

6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.

The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE(2) generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition.

Pyrazolopyrimidines : synthesis, effect on histamine release from rat peritoneal mast cells and cytotoxic activity

A series of 1H-pyrazolo[3,4-d]pyrimidines (3--6) substituted at positions 1 (R(1)=Ph, H, tert-butyl and ribosetribenzoate), 4 (R(2)=chlorine, nitrogen and oxygen nucleophiles), and 6 (dimethylamino) have been synthesized and their effect on the release of histamine from rat peritoneal mast cells measured. After chemical stimulation, (polymer 48/80), several compounds (i.e. 3b, 4a, 4b, 4d, 4g, 5a), produce inhibition two to three times higher (40--60%) than DSCG but this action is lower after preincubation. 4b (R(1)=Ph, R(2)=NHCH(2)Ph; 50--70% inhibition) and 5a (R(1)=H, R(2)=OMe; 50--55% inhibition) are the most active ones in both experiments. With ovoalbumin as stimulus, several pyrazolopyrimidines show inhibition similar to DSCG, the most active compounds being 6a--d (IC(50)=12--16 microM; R(1)=ribosetribenzoate, R(2)=methoxy and amino). Compounds 4e (R(1)=t-butyl, R(2)=OMe) and 4g (R(1)=t-butyl, R(2)=piperidino) are inducers of the release of histamine (60 and 150% increase). Compounds 4b and 4c showed cytotoxic activity (IC(50)=1 microg/mL) to HT-29 human colon cancer cells.

Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.

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.

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.

Access to iminosugars by aldol additions of metalated bis-lactim ethers to l-erythrose derivatives

Abstract Aldol additions of metalated bis-lactim ethers derived from cyclo -[Gly- d -Val] 3A – E* to mismatched l -erythrose-derivatives 4a and 4b have been studied. Reactions of titanium(IV) and tin(II) azaenolates with the lactol derivative 4b allow direct and moderate ( syn , syn )- or highly ( anti , anti )-selective access to polyhydroxy amino acids that have been efficiently transformed into 1-deoxy- d -gulonojirimycin or 1-deoxy- d -allonojirimycin.

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.