Exo- or endo-1H-pyrazole metal coordination modulated by the polyamine chain length in [1 + 1] condensation azamacrocycles. Binuclear complexes with remarkable SOD activity.

The Cu2+ complexes of three [1 + 1] azacyclophane macrocycles having the 1H-pyrazole ring as the spacer and the pentaamine 1,5,8,11,15-pentaazadecane (L1) or hexaamines 1,5,8,12,15,19-hexaazanonadecane (L2) and 1,5,9,13,17,21-hexaazaheneicosane (L3) as bridges show endo- coordination of the pyrazolate bridge giving rise to discrete monomeric species. Previously reported pyrazolacyclophanes evidenced, however, exo-coordination with the formation of dimeric species of 2 : 2, 3 : 2 or even 4 : 2 Cu2+ : L stoichiometry. The complexes have been characterized in solution using potentiometric studies, UV-Vis spectroscopy, paramagnetic NMR, cyclic voltammetry and mass spectrometry. The measurements show that all three ligands have as many protonation steps in water as secondary amines are in the bridge, while they are able to form both mono- and binuclear Cu2+ species. The crystal structures of the complexes [Cu(HL1)Br]Br(1+x)(ClO4)(1-x)·yH2O (1) and [Cu2(H-1L2)Cl(ClO4)](ClO4)·H2O·C2H5OH (2) have been solved by X-ray diffraction studies. In 1 the metal ion lies at one side of the macrocyclic cavity being coordinated by one nitrogen of the pyrazolate moiety and the three consecutive nitrogen atoms of the polyamine bridge. The other nitrogen of the pyrazole ring is hydrogen-bonded to an amine group. In 2 the two metal ions are interconnected by a pyrazolate bis(monodentate) moiety and complete their coordination spheres with three amines and either a bromide or a perchlorate anion, which occupy the axial positions of distorted square pyramid geometries. Paramagnetic NMR studies of the binuclear complexes confirm the coordination pattern observed in the crystal structures. Cyclic voltamperommetry data show potentials within the adequate range to exhibit superoxide dismutase (SOD) activity. The IC50 values calculated by McCord-Fridovich enzymatic assays show that the binuclear Cu2+ complexes of L2 and L3 have SOD activities that rank amongst the highest ones reported so far.

The Bioactivity of Xylene, Pyridine, and Pyrazole Aza Macrocycles against Three Representative Leishmania Species.

Due to the urgent need for finding effective and free of secondary effect treatments for every clinical form of Leishmaniasis, a series of synthetic xylene, pyridine and, pyrazole azamacrocycles were tested against three Leishmania species. A total of 14 compounds were tested against J774.2 macrophage cells which were models for host cells, and against promastigote and amastigote forms of each studied Leishmania parasite. Amongst these polyamines, one proved effective against L. donovani, another one for L. braziliensis and L. infantum, and another one was selective solely for L. infantum. These compounds showed leishmanicidal activity and reduced parasite infectivity and dividing ability. Action mechanism studies gave a hint that compounds were active against Leishmania due to their ability to alter parasite metabolic pathways and reduce (except Py33333) parasitic Fe-SOD activity.

Selective encapsulation of a chloride anion in a 1H-pyrazole Cu2+ metallocage.

A self-assembled metallobox from copper(ii) and two macrocycles containing 1H-pyrazole ligands has been prepared. The internal cavity of the box is able to selectively encapsulate a single chloride anion over any other halide anion.

Hybrid GMP-polyamine hydrogels as new biocompatible materials for drug encapsulation.

Here we present the preparation and characterization of new biocompatible materials for drug encapsulation. These new gels are based on positively charged [1+1] 1H-pyrazole-based azamacrocycles which minimise the electrostatic repulsions between the negatively charged GMP molecules. Rheological measurements confirm the electroneutral hydrogel structure as the most stable for all the GMP-polyamine systems. Nuclear magnetic resonance (NMR) was employed to investigate the kinetics of the hydrogel formation and cryo-scanning electron microscopy (cryo-SEM) was used to obtain information about the hydrogel morphology, which exhibited a non-homogeneous structure with a high degree of cross-linking. It is possible to introduce isoniazid, which is the most employed antibiotic for tuberculosis treatment, into the hydrogels without disrupting the hydrogel structure at appropriate concentrations for oral administration.

Influence of the chain length and metal : ligand ratio on the self-organization processes of Cu2+ complexes of [1 + 1] 1H-pyrazole azamacrocycles.

Three new [1 + 1] macrocycles formed by the reaction of 1H-3,5-bis(chloromethyl)pyrazole with the tosylated amines 1,4,7,10-tetraazadecane (L1), 1,4,8,11-tetraazaundecane (L2) and 1,5,10,14-tetraazatetradecane (L3) are described. Potentiometric studies and HR-ESI-Mass spectrometry show the formation of dimeric binuclear Cu2+ complexes whose organization depends on the type of hydrocarbon chains connecting the amine groups. Furthermore, trinuclear or/and tetranuclear complexes are formed depending also on the length of the polyaminic bridge and on the sequence of the hydrocarbon chains. The crystal structures of the [2 + 2] [Cu2(H(H-1L2))2](ClO4)4·4H2O (1) and [Cu2(H-1L2)2](ClO4)2 (2) complexes show in both of them two macrocycles self-assembled by the metal ions which interconnect their pyrazolate fragments that behave as bis(monodentate) ligands. While in 1 one central amine of each macrocycle binds to the axial position of a distorted square-pyramid and the other ones remain protonated, in 2 all the amine groups are involved in the coordination giving rise to a strongly distorted octahedral geometry. Paramagnetic 1H NMR measurements support that these structures also form in solution. Interestingly, tetranuclear complexes [Cu4(H-1L4)2(OH)2.08](ClO4)2.92Br0.54Cl0.46 (3) and [Pd2.39Cu1.61(H-1L4)2(OH)2](ClO4)2Cl1.33Br0.67·2.87H2O (4) have been isolated for the macrocycle containing the 1,5,9,13-tetraamine chain (L4). 3 has two binucleating units, one of them formed by the pyrazolate moieties and their neighbouring secondary amines and the other by the two central amines of both macrocycles. This latter Cu2+ coordination site is completed by two hydroxide anions as bridging ligands. 4 was obtained from a solution prepared to achieve full formation of the dimeric cage [Cu2(H-1(HL4))2]4+ by addition of K2PdCl4. The Pd2+ ion due to its softer acidic characteristics displaces the Cu2+ ions from the pyrazolate site. UV-vis spectroscopy suggests that the exchange is completed at room temperature after one hour.

Tripyridinophane Platform Containing Three Acetate Pendant Arms: An Attractive Structural Entry for the Development of Neutral Eu(III) and Tb(III) Complexes in Aqueous Solution.

We report a detailed characterization of Eu3+ and Tb3+ complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (H3tpptac). Tpptac3- displays an overall basicity (∑ log KiH) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln3+ (log KLnL = 17.5-18.7). These complexes are also thermodynamically stable at physiological pH (pEu = 18.6, pTb = 18.0). It should be noted that the pGd value of Gd-tpptac (18.4) is only slightly lower than that of commercially available MRI contrast agents such as Gd-dota (pGd = 19.2). Moreover, a very good selectivity for these ions over the endogenous cations (log KCuL = 14.4, log KZnL = 12.9, and log KCaL = 9.3) is observed. The X-ray structure of the terbium complex shows the metal coordinated by the nine N6O3 donor set of the ligand and one inner-sphere water molecule. DFT calculations result in two Eu-tpptac structures with similar bond energies (ΔE = 0.145 eV): one structure in which the water is coordinated to the metal ion and one structure in which the water molecule is farther away from the ion, bound to the ligand with an OH-π bond. By detailed luminescence experiments, we demonstrate that the europium complex in aqueous solution presents a hydration equilibrium between nine-coordinate, dehydrated [Eu-tpptac]0 and ten-coordinate, monohydrated [Eu-tpptac(H2O)]0 species. A similar trend is observed for the terbium complex. Despite the presence of this hydration equilibrium, the H3tpptac ligand sensitizes Eu3+ and Tb3+ luminescence efficiently in buffered water at physiological pH. Particularly, the terbium complex displays a long excited-state lifetime of 2.24 ms and an overall quantum yield of 33% with a brightness of 3600 M-1 cm-1. Such features of Ln3+ complexes of H3tpptac indicate that this platform appears to be particularly appealing for the further development of luminescent lanthanide labels.

"3 + 1 = 6 + 2" in Cu(II) coordination chemistry of 1H-pyrazole aza cryptands.

A polyazamacrocycle formed from two tris(2-aminoethyl)amine units connected by 1H-pyrazole units shows unique hexanuclear Cu(ii) complexes by combination of two binuclear Cu(ii) cryptand complexes through pyrazolate moieties belonging to both cryptands. The formation of these dimeric entities has been proven both in solution by potentiometric studies and mass spectroscopy and in the solid state by X-ray diffraction of crystals of three different batches of formulae [Cu6(H-3)2(H2O)2](TsO)6·22H2O (), [Cu6(H-3)2(NO3)2](NO3)4·2H2O () and [Cu6(H-3)2Cl2]Cl4·(C4H5N3O2)2·14.35H2O (). The hexanuclear unit in and can be viewed like three magnetically independent binuclear complexes with J = -366(3) cm(-1), g = 2.08(1) for and J = -360(3) cm(-1), g = 2.07(1) for .

Aryl-bis-(scorpiand)-aza receptors differentiate between nucleotide monophosphates by a combination of aromatic, hydrogen bond and electrostatic interactions.

Bis-polyaza pyridinophane scorpiands bind nucleotides in aqueous medium with 10-100 micromolar affinity, predominantly by electrostatic interactions between nucleotide phosphates and protonated aliphatic amines and assisted by aromatic stacking interactions. The pyridine-scorpiand receptor showed rare selectivity toward CMP with respect to other nucleotides, whereby two orders of magnitude affinity difference between CMP and UMP was the most appealing. The phenanthroline-scorpiand receptor revealed at pH 5 strong selectivity toward AMP with respect to other NMPs, based on the protonation of adenine heterocyclic N1. The results stress that the efficient recognition of small biomolecules within scorpiand-like receptors relies mostly on the electrostatic and H-bonding interactions despite the competitive interactions in the bulk solvent, thus supporting further optimisation of this versatile artificial moiety.

Fístulas enterourinarias, experiencia con quince pacientes en el Hospital Pablo Tobón Uribe, Medellín, Noviembre de 1989 – Febrero de 1997 / Enterourinary fistulas, experience with 15 patients in the Pablo Tobón Uribe Hospital, Medellín. November 1989 - February 1997

Estudio descriptivo de pacientes con fístulas enterourinarias (FEU). Se revisaron 15 pacientes que habían sido atendidos en el Hospital Pablo Tobón Uribe (HPTU) entre noviembre de 1989 y febrero de 1997. La edad varió entre 26 y 85 años, promedio de 57.6. El 53.4 por ciento fueron mujeres. Anatómicamente las fístulas fueron agrupadas así: siete colovesicales, seis rectovesicales, una ileovesical y una ureterocólica. Cinco de ellas fueron secundarias a diverticulitis, tres a lesión actínica, dos a cáncer de colon, dos a cáncer rectal postoperatorio, una por cáncer vesical y una postraumática. Para su diagnostico se realizo colon por enema a cinco pacientes, el cual fue positivo en todos, la cistoscopia se efectuó en cinco pacientes, el cual fue positivo en todos, la cistoscopia se efectuó en cinco pacientes, siendo positiva en cuatro de ellos...