EQUILIBRIUM AMONG HEMATOPORPHYRIN DERIVATIVE COMPONENTSs—II. EFFECT OF ESTERASE ACTIVITY

Photofrin II is the hematoporphyrin-derivative fraction enriched in covalently-linked oligomers, characterized by a high degree of folding. Interaction with hydrophobic structures, such as biomolecules and cell structures, results in a modification of the equilibria among the different species, as a consequence of an unfolding effect exerted towards the electrostatic aggregates. The effect of esterase activity was evaluated, taking into account the nature suggested for the covalent linkage of the oligomers (ether and/or ester). The study was performed in Photofrin II aqueous solution by means of absorption and fluorescence spectral analysis. The results showed that the esterase is active only towards the unfold oligomers: that is, in Photofrin II solution supplemented with albumin. In these conditions, spectral analysis revealed the presence of a monomerization process, which is clearly evident during the first four hours of incubation. The monomerization effect induced by the enzyme was also proven by both equilibrium-dialysis measurements and zinc ion complexation. Zinc ion complexes with high affinity for monomeric species, giving rise to a very distinct emission band at 580 nm. The amount of ester linkage shown in the oligomers through enzyme hydrolysis appeared to be less than might have been expected, owing to the inhibiting effect of the monomer produced on the enzyme. The results are a step toward clarifying the intracellular and intratissue turnover of the drug observed after administration.     

A macrocyclic ligand as receptor and Zn(II)-complex receptor for anions in water: binding properties and crystal structures

Binding properties of 24,29-dimethyl-6,7,15,16-tetraoxotetracyclo[19.5.5.0(5,8).0(14,17)]-1,4,9,13,18,21,24,29-octaazaenatriaconta-Δ(5,8),Δ(14,17)-diene ligand L towards Zn(II) and anions, such as the halide series and inorganic oxoanions (phosphate (Pi), sulfate, pyrophosphate (PPi), and others), were investigated in aqueous solution; in addition, the Zn(II)/L system was tested as a metal-ion-based receptor for the halide series. Ligand L is a cryptand receptor incorporating two squaramide functions in an over-structured chain that connects two opposite nitrogen atoms of the Me(2)[12]aneN(4) polyaza macrocyclic base. It binds Zn(II) to form mononuclear species in which the metal ion, coordinated by the Me(2)[12]aneN(4) moiety, lodges inside the three-dimensional cavity. Zn(II)-containing species are able to bind chloride and fluoride at the physiologically important pH value of 7.4; the anion is coordinated to the metal center but the squaramide units play the key role in stabilizing the anion through a hydrogen-bonding network; two crystal structures reported here clearly show this aspect. Free L is able to bind fluoride, chloride, bromide, sulfate, Pi, and PPi in aqueous solution. The halides are bound at acidic pH, whereas the oxoanions are bound in a wide range of pH values ranging from acidic to basic. The cryptand cavity, abundant in hydrogen-bonding sites at all pH values, allows excellent selectivity towards Pi to be achieved mainly at physiological pH 7.4. By joining amine and squaramide moieties and using this preorganized topology, it was possible, with preservation of the solubility of the receptor, to achieve a very wide pH range in which oxoanions can be bound. The good selectivity towards Pi allows its discrimination in a manner not easily obtainable with nonmetallic systems in aqueous environment.     

Sodium β-Diketonate Glyme Adducts as Precursors for Fluoride Phases: Synthesis,Characterization and Functional Validation

Very few sodium complexes are available as precursors for the syntheses of sodium-based nanostructured materials. Herein, the diglyme, triglyme, and tetraglyme (CH₃O(CH₂CH₂O)_nCH₃, n = 2–4) adducts of sodium hexafluoroacetylacetonate were synthesized in a single-step reaction and characterized by IR spectroscopy, ¹H, and ¹³C NMR. Single-crystal X-ray diffraction studies provide evidence of the formation of the ionic oligomeric structure [Na₄(hfa)₆]²⁻•2[Na(diglyme₂]⁺ when the diglyme is coordinated, while a mononuclear seven-coordinated complex Na(hfa)•tetraglyme is formed with the tetraglyme. Reaction with the monoglyme (CH₃OCH₂CH₂OCH₃) does not occur, and the unadducted polymeric structure [Na(hfa)]_n forms, while the triglyme gives rise to a liquid adduct, Na(hfa)•triglyme•H₂O. Thermal analysis data reveal great potentialities for their applications as precursors in metalorganic chemical vapor deposition (MOCVD) and sol-gel processes. As a proof-of-concept, the Na(hfa)•tetraglyme adduct was successfully applied to both the low-pressure MOCVD and the sol-gel/spin-coating synthesis of NaF films.     

Microstructured cocultures of cardiac myocytes and fibroblasts: a two-dimensional in vitro model of cardiac tissue.

Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-microm-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.     

Synthesis of 3-substituted-2,3,4,5-tetrahydro-1H-naphth[1,2-d]-imidazole-2,4,5-triones and 1-Substituted-2,3,4,9-tetrahydro-1H-naphth[2,3-d]imidazole-2,4,9-triones

Tricyclic compounds with an imidazolinone ring fused to 1,2- and 1,4-naphtoquinones were synthesized by a reaction of 4-amino-1,2-naphthoquinone and 2-amino-1,4-naphthoquinone with electrophilic symmetric and non symmetric diazenes.     

Synthesis, characterization and application of Ni(tta)2.tmeda to MOCVD of nickel oxide thin films

A novel nickel beta-diketonate adduct, Ni(tta)2.tmeda, has been synthesized using 2-thenoyltrifluoroacetone as the beta-diketonate and N,N,N,'N'-tetramethylethylendiamine as the Lewis base. It has been characterized by elemental analyses, IR, 1H NMR, 13C NMR spectroscopy and single-crystal X-ray diffraction studies. Physical and thermal properties of Ni(tta)2.tmeda precursor have been also extensively investigated. Its efficacy as a metal-organic chemical vapour deposition (MOCVD) precursor for the growth of nickel oxide films has been fully tested by applying it to the deposition of NiO films on quartz substrate. NiO thin films have been characterized by X-ray diffraction (XRD), scanning electron microscopy and UV spectroscopy.