Atmospheric pressure plasma polymers for tuned QCM detection of protein adhesion.

Our efforts have been concentrated in preparing plasma polymeric thin layers at atmospheric pressure grown on Quartz Crystal Microbalance-QCM electrodes for which the non-specific absorption of proteins can be efficiently modulated, tuned and used for QCM biosensing and quantification. Plasma polymerization reaction at atmospheric pressure has been used as a simple and viable method for the preparation of QCM bioactive surfaces, featuring variable protein binding properties. Polyethyleneglycol (ppEG), polystyrene (ppST) and poly(ethyleneglycol-styrene) (ppST-EG) thin-layers have been grown on QCM electrodes. These layers were characterized by Atomic Force Microscopy (AFM), Contact angle measurements, Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS). The plasma ppST QCM electrodes present a higher adsorption of Concanavalin A (ConA) and Bovine Serum Albumin (BSA) proteins when compared with the commercial coated polystyrene (ppST) ones. The minimum adsorption was found for ppEG, surface, known by their protein anti-fouling properties. The amount of adsorbed proteins can be tuned by the introduction of PEG precursors in the plasma discharge during the preparation of ppST polymers.

4-Ammonio-benzamidinium dichloride.

The crystal structure of the title compound, C(7)H(11)N(3) (2+)·2Cl(-), has been determined as part of a project focusing on the ability of the benzamidine system to form strong hydrogen bonds in aqueous media. It is commonly used as a ligand in affinity chromatography for purification and immobilization of enzymes. A twofold rotation axis runs along the axis of the cation. The orientation of the amidinium group with respect to the benzene ring is indicated by the N-C-C-C torsion angle of 40.2 (1)°. In the crystal structure, cations and anions are linked via hydrogen bonds. The chloride anion is surrounded by four ammonium cations in a tetra-hedral environment. The aromatic rings of the amidinium cations are π-stacked, with a centroid-centroid distance of 4.178 (1) Å.

A two-dimensional network of R(2)(2)(16) and R(4)(2)(8) rings in trans-bis(4-aminopyridine-kappaN(1))bis(benzoato-kappa(2)O,O')copper(II) benzene 0.75-solvate.

The structure of the title supramolecular complex, [Cu(C(7)H(5)O(2))(2)(C(5)H(6)N(2))(2)].0.75C(6)H(6), has been determined. The Cu(2+) ion lies on an inversion centre and is coordinated by four O atoms of two opposing benzoate molecules and two pyridine N atoms of two opposing aminopyridine molecules. The partially occupied benzene site lies across a twofold rotation axis. The crystal structure is dominated by two-dimensional networks containing two different hydrogen-bonded rings [R(2)(2)(16) and R(4)(2)(8)].

Hydrogen bonding in calcium-trifluoromethanesulfonate-1,3-di-4-pyridylurea-methanol (1/2/2/4).

The structure of the supramolecular complex calcium-trifluoromethanesulfonate-1,3-di-4-pyridylurea-methanol (1/2/2/4), Ca(2+) x 2CF(3)SO(3)(-) x 2C(11)H(10)N(4)O x 4CH(4)O, is presented. The Ca(2+) ion lies on an inversion centre and is octahedrally coordinated by four methanol molecules and two trifluoromethanesulfonate counter-ions. The molecular packing is dominated by hydrogen-bonded sheets in the (110) plane which contain R(4)(4)(32) rings; in these rings, significant pi-pi interactions are observed between inversion-related 1,3-di-4-pyridylurea molecules.

Carbonic anhydrase inhibitors. Synthesis of topically effective intraocular pressure lowering agents derived from 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide.

Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.

Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide.

Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.

Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-alpha-Demethylase Ihibitors.

Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3-0.5 mug/mL. The mechanism of antifungal action of these coordination compounds is probably connected to an inhibition of lanosterol-14-alpha-demethylase, a metallo-enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes.

Synthesis and antifungal activity of metal complexes containing dichloro-tetramorpholino-cyclophosphazatriene.

Metal complexes of dichloro-tetramorpholino-cyclophosphazatriene containing divalent cations such as Ni(II), Co(II), and Mn(II) have been prepared and characterised by standard physico-chemical procedures (elemental chemical analysis, IR and UV-VIS spectra, conductimetric measurement). The newly synthesised compounds possessed antifungal activity against Aspergillus and Candida spp., some of them showing effects comparable to ketoconazole (with minimum inhibitory concentrations in the range of 2- 30 mug/mL) but being generally less active as compared to the azole. Best activity was detected against C. albicans, and worst activity against A. niger. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis, and interaction with lanosterol-14-alpha-demethylase (CYP51A1), since reduced amounts of ergosterol were evidenced by means of HPLC in cultures of the sensitive strain A. niger treated with some of these inhibitors.

1,3,4-thiadiazole derivatives. Part 9. Synthesis and biological activity of metal complexes of 5-(2-aminoethyl)-2-amino-1,3,4-thiadiazole.

Metal complexes of the title ligand (L) containing Co(II), Ni(II) and Cu(II) were prepared and characterized by elemental analysis, IR, electronic spectroscopy and conductimetry. The new derivatives, possessing the following formulae, CuL(2)(OH)(2), NiL(2)Cl(2), and [Co(2)LCl(4)](n) showed in vitro antifungal activity against Aspergillus and Candida spp.

Complexes With Biologically Active Ligands. Part 7 Synthesis and Fungitoxic Activity of Metal Complexes Containing 1,3,5-tris-(8-Hydroxyquinolino)- Trichlorocyclo-Triphosphazatriene.

Complexes containing 1,3,5-tris-(8-hydroxyquinolino)-trichlorocyclotriphosphazatriene, a new cyclophosphazene ligand, and Co(II), Cu(II) and Ni(II) were prepared. The new complexes, having the general formula [MLCl(2)], [ML(2)]Cl(2), (M=Cu, Co, Ni); [NiLAc], [NiL(2)Ac]Ac and [ML(3)]X(3) (M=Ni, Co, X=Cl, Ac) were characterised by elemental analysis, electronic-, IR spectroscopy, and electrical conductivity measurements. Some of them inhibited the growth of several fungi species (Aspergillus and Candida spp.).