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.

Separating the coherence transfer from chemical shift evolution in high-resolution pure shift COSY NMR.

Recent developments in data sampling and processing techniques have made it possible to acquire 2-dimensional NMR spectra of small molecules at digital resolutions in both dimensions approaching the intrinsic limitations of the equipment and sample on a realistic timescale. These developments offer the possibility of enormously increased effective resolution (peak dispersion) and the ability to effectively study samples where peak overlap was previously a limiting factor. Examples of such spectra have been produced for a number of 2-dimensional techniques including TOCSY and HSQC. In this paper, we investigate some of the problems in applying such techniques to COSY spectra and suggest a modification to the classic experiment that alleviates some of these problems.

Guanosine-5'-Monophosphate Polyamine Hybrid Hydrogels: Enhanced Gel Strength Probed by z-Spectroscopy.

The self-assembling tendencies of guanosine-5'-monophosphate (GMP) can be drastically increased using polyamines, with potential applications in the production of biocompatible smart materials, as well as for the design of antitumor drugs based on G-quadruplex stabilization. Results from scanning electron microscopy (SEM), wide angle X-ray scattering (WAXS), rheology, and nuclear magnetic resonance (NMR) z-spectroscopy studies are presented.

Exceedingly Fast Oxygen Atom Transfer to Olefins via a Catalytically Competent Nonheme Iron Species.

The reaction of [Fe(CF3 SO3 )2 (PyNMe3 )] with excess peracetic acid at -40 °C leads to the accumulation of a metastable compound that exists as a pair of electromeric species, [Fe(III) (OOAc)(PyNMe3 )](2+) and [Fe(V) (O)(OAc)(PyNMe3 )](2+) , in fast equilibrium. Stopped-flow UV/Vis analysis confirmed that oxygen atom transfer (OAT) from these electromeric species to olefinic substrates is exceedingly fast, forming epoxides with stereoretention. The impact of the electronic and steric properties of the substrate on the reaction rate could be elucidated, and the relative reactivities determined for the catalytic oxidations could be reproduced by kinetic studies. The observed fast reaction rates and high selectivities demonstrate that this metastable compound is a truly competent OAT intermediate of relevance for nonheme iron catalyzed epoxidations.

Synthesis and Structural Characterization of a Cyclen-Derived Molecular Cage.

Reaction of a tetrafunctionalized cyclen derivative containing four aldehyde groups with an appropriate diamine followed by reduction and demetalation highly efficiently affords a bis(cyclen)-derived molecular cage. Potentiometric investigations show that this compound forms dimetallic complexes with copper(II), with the two metal ions selectively coordinated to the cyclen units. X-ray crystallography indicates that these complexes could give rise to new cascade complexes after incorporation of anions between the metal centers.

From isolated 1H-pyrazole cryptand anion receptors to hybrid inorganic-organic 1D helical polymeric anion receptors.

We report a novel 1-D helical coordination polymer formed by protonated polyamine 1H-pyrazole cryptands interconnected by Cu(2+) metal ions that are able to encapsulate anionic species behaving as a multianion receptor. Switching from a monomeric receptor to a polymeric receptor is activated by metal ions and pH.

"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 .

Selective recognition of sulfate anions by a cyclopeptide-derived receptor in aqueous phosphate buffer.

A cyclopeptide-based anion receptor containing alternating 6-aminopicolinic acid and substituted (4R)-4-aminoproline subunits with appended ß-alanine residues binds sulfate anions in water. Importantly, appreciable sulfate binding is even observed in phosphate buffer, hence in the presence of anions of similar structure but with a different degree of protonation. The cause for the high selectivity of this receptor is related to the mode of action of the sulfate-binding protein.

Intermolecular binding modes in a novel [1 + 1] condensation 1H-pyrazole azamacrocycle: a solution and solid state study with evidence for CO2 fixation.

The synthesis of a novel cyclophane (L1) consisting of a 1H-pyrazole moiety linked through methylene groups to a 1,5,9,13-tetraazadecane chain is described. As far as we know, this is one of the first reported syntheses of a [1 + 1] condensation 1H-pyrazole azamacrocyclic ligand. The crystal structures of the complexes [Cu2(H(H(-1)L1))(H(-1)L1)](ClO4)3·3.75H2O (1) and ([Cu2(H(H(-1)L1))(0.5)(H(-1)L1)(1.5)]2(ClO4)3Br2·4.2H2O (2) show that Cu(2+) coordination leads to formation of 2:2 Cu(2+):L dinuclear dimeric complexes in which the 1H-pyrazole units lose a proton behaving as bis(monodentate) bridging ligands. Unlike previously reported complexes of [2 + 2] pyrazole azamacrocycles, the pyrazolate units in 1 are pointing outward from the macrocyclic cavity to bind the Cu(2+) ions. Inner coordination with formation of 1:1 Cu(2+):L complexes is however observed in [1 + 1] pyridine azamacrocycles as shown by the crystal structure here presented of the complex [CuL2](ClO4)2 (3). Crystals of [Cu3(H(-1)L1)2(CO3)(H2O)](ClO4)2·8H2O (4) grown by evaporating aqueous solution at pH 9 containing Cu(2+) and L1 in 3:2 molar ratio show the presence of a further Cu(2+) coordinated to the two free amine groups found in structures 1 and 2. The metal ion fills its coordination sphere capturing atmospheric CO2 as a η(1),η(2)-bidentate carbonate anion placed in the equatorial position and an axial water molecule. pH-metric data, UV-vis spectroscopic data, EPR measurements, and HR-ESI-MS data support that the outer coordination mode with formation of 2:2 dinuclear dimeric and 3:2 trinuclear complexes is preserved in aqueous solution.

Homo- and heterobinuclear Cu²âº and Zn²âº complexes of abiotic cyclic hexaazapyridinocyclophanes as SOD mimics.

The new receptor 3,7,11,15,19,23-hexaaza-1(2,6)-pyridinacyclotetracosaphane (L1) containing a complete sequence of propylenic chains has been synthesised. The acid-base behaviour and Cu²âº and Zn²âº coordination have been analysed by potentiometric measurements in 0.15 M NaClO4 for L1 and for the related compounds 3,7,11,14,18,22-hexaaza-1(2,6)-pyridinacyclotricosaphane (L2), 3,7,10,13,16,20-hexaaza-1(2,6)-pyridinacycloheneicosaphane (L3) and 3,7,10,12,15,19-hexaaza-1(2,6)-pyridinacycloicosaphane (L4). The crystal structure of [(CuH4L2)(H2O)(ClO4)](ClO4)5·3H2O shows an interesting combination of a metal ion coordinated by the pyridine nitrogen atom and the adjacent amine groups of the chain, and a perchlorate anion sitting at the middle of the site defined by the remaining four protonated ammonium groups of L1. Paramagnetic NMR data suggest that imidazole coordinates to the Cu²âº ions as a bridging ligand in a wide pH range. SOD activity for Cu²âº-Cu²âº and Cu²âº-Zn²âº complexes with L1-L4 have been measured by NBT assays at pH 7.4, obtaining some of the lowest values so far reported for SOD mimics. SOD activity has also been checked by chemiluminescence assays using polymorphonuclear leukocytes (PMNLs).

Zn(II)-coordination and fluorescence studies of a new polyazamacrocycle incorporating 1H-pyrazole and naphthalene units.

The synthesis and Zn(2+) coordination properties of a new macrocycle (L1) obtained by dipodal (2 + 2) condensation of the polyamine 3-(naphthalen-2-ylmethyl)pentane-1,5-diamine with 1H-pyrazole-3,5-dicarbaldehyde are reported. pH-metric studies show that L1 bears five measurable protonation steps in the 2.0-11.0 pH range. Fluorescence emission studies indicate that the removal of the first proton from the H(5)L1(5+) species leads to a significant decrease in the emission due to a photoinduced electron transfer process. Addition of Zn(2+) promotes a boat-like conformation that approaches both fluorophores and facilitates the formation of an excimer which reaches its highest emission for a 1 : 1 Zn(2+) : L1 molar ratio. Density functional theory calculations support the experimental data and suggest that the protective effect of the Zn(2+) ion along with hydrogen bonding between the 1H-pyrazole moiety and one of the tertiary nitrogen atoms is responsible for this behaviour.

Tritopic phenanthroline and pyridine tail-tied aza-scorpiands.

The synthesis of two new tritopic double-scorpiand receptors in which two equivalent 5-(2-aminoethyl)-2,5,8-triaza[9]-(2,6)-pyridinophane moieties have been linked with 2,6-dimethylpyridine (L1) or 2,9-dimethylphenanthroline (L2) units is reported for the first time. Their acid-base behaviour and Zn(2+) coordination chemistry have been studied by pH-metric titrations, molecular dynamic calculations, NMR, UV-Vis and steady-state fluorescence techniques. L1 and L2 behave, respectively, as hexaprotic and heptaprotic bases in the experimental conditions used (298.1 +/- 0.1 K, 0.15 mol dm(-3) NaCl, pH range under study 2.0-11.0). These ligands are able to form mono-, bi- and trinuclear Zn(2+) complexes depending on the Zn(2+)-receptor molar ratio. Interaction of L1 and L2 with pyrophosphate (PPi), tripolyphosphate (TPP) and adenosine 5'-triphosphate (ATP) has been followed by pH-metric titrations, (1)H and (31)P NMR techniques and molecular dynamic analysis. Finally, formation of mixed complexes Zn(2+)-L-PPi, Zn(2+)-L-TPP and Zn(2+)-L-ATP has been studied for both receptors by potentiometric titrations.

Synthesis and coordination properties of an azamacrocyclic Zn(II) chemosensor containing pendent methylnaphthyl groups.

The synthesis of a polyazamacrocycle constituted by two diethylenetriamine bridges functionalized at their central nitrogen with naphth-2-ylmethyl units and interconnected through 2,6-dimethylpyridine spacers (L1) is reported. The protonation behaviour of the new macrocycle in water and in water-ethanol 70/30 v/v mixed solvent has been examined by means of pH-metric, UV-Vis and steady-state fluorescence techniques. The fluorescence emission is slightly quenched following the deprotonation of the central tertiary amines and more deeply quenched upon deprotonation of the secondary amino groups. pH-Metric titrations show that in water-ethanol 70/30 v/v L1 forms stable mononuclear complexes with the divalent transition and post-transition metal ions Mn2+, Fe2+, Co2+, Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+. In the case of Cu2+, Zn2+, Hg2+ and Pb2+, formation of binuclear complexes has also been observed. Steady-state fluorescence emission studies show that while interaction with Cu2+ leads to quenching of the fluorescence emission above pH = 2, interaction with Zn2+, Cd2+, Hg2+ and Pb2+ give rise to enhancements of the fluorescence above pH ca. 5, which is particularly noticeable in the case of Zn2+.